Miracle-dz/UniFAR-FTUs huggingface dataset:
Sphere-Forming Culture for Expanding Genetically Distinct Patient-Derived Glioma Stem Cells by Cellular Growth Rate Screening

Diffusely infiltrating gliomas (DIGs) are difficult to completely resect and are associated with a high rate of tumor relapse and progression from low- to high-grade glioma. In particular, optimized short-term culture-enriching patient-derived glioma stem cells (GSCs) are essential for customizing the therapeutic strategy based on clinically feasible in vitro drug screening for a wide range of DIGs, owing to the high inter-tumoral heterogeneity. Herein, we constructed a novel high-throughput culture condition screening platform called ‘GFSCAN’, which evaluated the cellular growth rates of GSCs for each DIG sample in 132 serum-free combinations, using 13 previously reported growth factors closely associated with glioma aggressiveness. In total, 72 patient-derived GSCs with available genomic profiles were tested in GFSCAN to explore the association between cellular growth rates in specific growth factor combinations and genomic/molecular backgrounds, including isocitrate dehydrogenase 1 (IDH1) mutation, chromosome arm 1p and 19q co-deletion, ATRX chromatin remodeler alteration, and transcriptional subtype. GSCs were clustered according to the dependency on epidermal growth factor and basic fibroblast growth factor (E&F), and isocitrate dehydrogenase 1 (IDH1) wild-type GSCs showed higher E&F dependencies than IDH1 mutant GSCs. More importantly, we elucidated optimal combinations for IDH1 mutant glioblastoma and lower grade glioma GSCs with low dependencies on E&F, which could be an aid in clinical decision-making for these DIGs. Thus, we demonstrated the utility of GFSCAN in personalizing in vitro cultivation to nominate personalized therapeutic options, in a clinically relevant time frame, for individual DIG patients, where standard clinical options have been exhausted.
Complex Systems Model of Dynamic Mechanisms of Early Childhood Caries Development

Early childhood caries (ECC) is a largely preventable condition that occurs when children develop caries in their primary teeth before the age of six. National trends of ECC indicate that prevalence is decreasing, but disparities between various sociodemographic groups may be increasing, despite intervention efforts. Dynamic mechanisms in caries development are hypothesized to be responsible for the observed population distributions of disease. Agent-based models (ABMs) have been utilized to explore similar hypotheses in many areas of health research. Therefore, we developed an ABM of ECC development mechanisms and examined population outcomes of hypothetical preventive intervention scenarios. We found that risk-based targeting had minimal impact on population averages or disparities and was largely due to the strength of the dynamic mechanisms among those considered to be at high caries risk. Universally increasing intervention access reduced population caries prevalence, but increased disparities between different groups of caries risk profiles. We show that population distributions of ECC can emerge as a result of dynamic mechanisms that have been shown to drive disease development. Understanding the effectiveness of a proposed intervention in relation to the hypothesized mechanism(s) that contributes to the outcome of interest is critical to future efforts to address population disparities in ECC.
The Metabolization Profile of the CYP2D6 Gene in Amerindian Populations: A Review

Background: the CYP2D6 gene is clinically important and is known to have a number of variants. This gene has four distinct metabolization profiles that are determined by the different allelic forms present in the individual. The relative frequency of these profiles varies considerably among human populations around the world. Populations from more isolated regions, such as Native Americans, are still relatively poorly studied, however. Even so, recent advances in genotyping techniques and increasing interest in the study of these populations has led to a progressive increase in publication rates. Given this, the review presented here compiled the principal papers published on the CYP2D6 gene in Amerindian populations to determine the metabolic profile of this group. Methods: a systematic literature review was conducted in three scientific publication platforms (Google Scholar, Science Direct, and Pubmed). The search was run using the keywords “CYP2D6 Amerindians” and “CYP2D6 native Americans”. Results: a total of 13 original papers met the inclusion criteria established for this study. All the papers presented frequencies of the different CYP2D6 alleles in Amerindian populations. Seven of the papers focused specifically on Amerindian populations from Mexico, while the others included populations from Argentina, Chile, Costa Rica, Mexico, Paraguay, Peru, and the United States. The results of the papers reviewed here showed that the extensive metabolization profile was the most prevalent in all Amerindian populations studied to date, followed by the intermediate, slow, and ultra-rapid, in that order. Conclusion: the metabolization profiles of the Amerindian populations reviewed in the present study do not diverge in any major way from those of other populations from around the world. Given the paucity of the data available on Amerindian populations, further research is required to better characterize the metabolization profile of these populations to ensure the development of adequate therapeutic strategies.
Differential Effects of Awareness and Task Relevance on Early and Late ERPs in a No-Report Visual Oddball Paradigm

To date it is poorly understood how and when deviance processing interacts with awareness and task relevance. Furthermore, an important issue in the study of consciousness is the prevalent confound of conscious perception with the requirement of reporting it. This study addresses these topics using a no-report inattentional blindness paradigm with a visual oddball sequence of geometrical shapes presented to male and female human participants. To date it is poorly understood how and when deviance processing interacts with awareness and task relevance. Furthermore, an important issue in the study of consciousness is the prevalent confound of conscious perception with the requirement of reporting it. This study addresses these topics using a no-report inattentional blindness paradigm with a visual oddball sequence of geometrical shapes presented to male and female human participants. Electrophysiological responses were obtained in three physically identical Phases A–C that differed only with respect to the instructions: (A) participants were uninformed about the shapes and attended an unrelated foreground task (inattentional blind), (B) were informed about the shapes but still attended the foreground task, and (C) attended the shapes. Conscious processing of shapes was indexed by the visual awareness negativity but not a P3. Deviance processing was associated with the visual mismatch negativity independently of consciousness and task relevance. The oddball P3, however, only emerged when the stimuli were task relevant, and was absent for consciously perceived but task irrelevant stimuli. The P3 thus does not represent a reliable marker of stimulus awareness. This result pattern supports the view of hierarchical predictive processing, where lower levels display automatic deviance processing, whereas higher levels require attention and task relevance. SIGNIFICANCE STATEMENT To react to potentially important changes in our environment it is fundamental to detect deviations from regularities of sensory input. It has yet to be understood how awareness and task relevance of this input interact with deviance processing. We investigated the role of awareness in deviance detection while at the same time circumventing the confound of awareness and report by means of a no-report paradigm. Our results suggest that early processes are elicited automatically, whereas, contrary to prominent theories, late processes do not depend on awareness but on task-based attention.
Bevacizumab for NF2‐associated vestibular schwannomas of childhood and adolescence

Seventeen children at six institutions with neurofibromatosis type 2 (NF2)‐related vestibular schwannomas received bevacizumab. Eight of the 13 patients with initial hearing loss (61%) showed objective hearing improvement within six months of treatment. No patients showed hearing deterioration during therapy; however, only two patients showed objective radiological response. Seven of eight patients had tumor progression or worsening hearing loss upon cessation of treatment. Bevacizumab was well tolerated with no patients discontinuing therapy. Bevacizumab appears to postpone hearing loss in childhood NF2‐associated vestibular schwannomas, but responses are not durable, suggesting that either longer maintenance therapy or new strategies are required.
Identification of Two Novel Peanut Genotypes Resistant to Aflatoxin Production and Their SNP Markers Associated with Resistance

Aflatoxin B1 (AFB1) and aflatoxin B2 (AFB2) are the most common aflatoxins produced by Aspergillus flavus in peanuts, with high carcinogenicity and teratogenicity. Identification of DNA markers associated with resistance to aflatoxin production is likely to offer breeders efficient tools to develop resistant cultivars through molecular breeding. In this study, seeds of 99 accessions of a Chinese peanut mini-mini core collection were investigated for their reaction to aflatoxin production by a laboratory kernel inoculation assay. Two resistant accessions (Zh.h0551 and Zh.h2150) were identified, with their aflatoxin content being 8.11%–18.90% of the susceptible control. The 99 peanut accessions were also genotyped by restriction site-associated DNA sequencing (RAD-Seq) for a genome-wide association study (GWAS). A total of 60 SNP (single nucleotide polymorphism) markers associated with aflatoxin production were detected, and they explained 16.87%–31.70% of phenotypic variation (PVE), with SNP02686 and SNP19994 possessing 31.70% and 28.91% PVE, respectively. Aflatoxin contents of accessions with “AG” (existed in Zh.h0551 and Zh.h2150) and “GG” genotypes of either SNP19994 or SNP02686 were significantly lower than that of “AA” genotypes in the mean value of a three-year assay. The resistant accessions and molecular markers identified in this study are likely to be helpful for deployment in aflatoxin resistance breeding in peanuts.
Recent Progress of Stem Cell Therapy in Cancer Treatment: Molecular Mechanisms and Potential Applications

The insufficient and unspecific target of traditional therapeutic approaches in cancer treatment often leads to therapy resistance and cancer recurrence. Over the past decades, accumulating discoveries about stem cell biology have provided new potential approaches to cure cancer patients. Stem cells possess unique biological actions, including self-renewal, directional migration, differentiation, and modulatory effects on other cells, which can be utilized as regenerative medicine, therapeutic carriers, drug targeting, and generation of immune cells. In this review, we emphasize the mechanisms underlying the use of various types of stem cells in cancer treatment. In addition, we summarize recent progress in the clinical applications of stem cells, as well as common risks of this therapy. We finally give general directions for future studies, aiming to improve overall outcomes in the fight against cancer.
JNK/p66Shc/ITCH Signaling Pathway Mediates Angiotensin II-induced Ferritin Degradation and Labile Iron Pool Increase

Angiotensin II (Ang II) induces deleterious changes in cellular iron metabolism and increases the generation of reactive oxygen species. This leads to an impairment of neuronal and vascular function. However, the mechanism underpinning Ang II-induced changes in iron metabolism is not known. We hypothesized that Ang II-induced ferritin degradation and an increase in the labile iron pool are mediated by the c-Jun N-terminal kinase (JNK)/p66Shc/ITCH signaling pathway. We show that Ang II treatment induced ferritin degradation in an endothelial cell lines derived from the bovine stem pulmonary artery (CPAE), human umbilical vein endothelial cells (HUVEC), and HT22 neuronal cells. Ferritin degradation was accompanied by an increase in the labile iron pool, as determined by changes in calcein fluorescence. The JNK inhibitor SP600125 abolished Ang II-induced ferritin degradation. Furthermore, the effect of Ang II on ferritin levels was completely abolished in cells transfected with vectors encoding catalytically inactive variants of JNK1 or JNK2. CPAE cells expressing inactive ITCHor p66Shc (substrates of JNK kinases) were completely resistant to Ang II-induced ferritin degradation. These observations suggest that Ang II-induced ferritin degradation and, hence, elevation of the levels of highly reactive iron, are mediated by the JNK/p66Shc/ITCH signaling pathway.
The Dynamics of Respiratory Microbiota during Mechanical Ventilation in Patients with Pneumonia

Bacterial pneumonia is a major cause of mechanical ventilation in intensive care units. We hypothesized that the presence of particular microbiota in endotracheal tube aspirates during the course of intubation was associated with clinical outcomes such as extubation failure or 28-day mortality. Sixty mechanically ventilated ICU (intensive care unit) patients (41 patients with pneumonia and 19 patients without pneumonia) were included, and tracheal aspirates were obtained on days 1, 3, and 7. Gene sequencing of 16S rRNA was used to measure the composition of the respiratory microbiome. A total of 216 endotracheal aspirates were obtained from 60 patients. A total of 22 patients were successfully extubatedwithin3 weeks, and 12 patients died within 28days. Microbiota profiles differed significantly between the pneumonia group and the non-pneumonia group (Adonis, p < 0.01). While α diversity (Shannon index) significantly decreased between day 1 and day 7 in the successful extubation group, it did not decrease in the failed extubation group among intubated patients with pneumonia. There was a significant difference in the change of βdiversity between the successful extubation group and the failed extubation group for Bray-Curtis distances (p < 0.001). At the genus level, Rothia, Streptococcus, and Prevotella correlated with the change of β diversity. A low relative abundance of Streptococci at the time of intubation was strongly associated with 28-day mortality. The dynamics of respiratory microbiome were associated with clinical outcomes such as extubation failure and mortality. Further large prospective studies are needed to test the predictive value of endotracheal aspirates in intubated patients.
Association between Helicobacter pylori infection and Guillain‐Barré Syndrome: A meta‐analysis

Helicobacter pylori (H pylori) is a Gram‐negative bacterium, considered to trigger autoimmune gastrointestinal disorders. This pathogen has also been linked to the autoimmune sequelae in extra‐gastrointestinal diseases and peripheral neuropathies. Guillain‐Barré syndrome (GBS) is a serious autoimmune demyelinating disorder of peripheral nerves, usually with a post‐infectious onset. About 30% of cases of GBS attributed to by Campylobacter jejuni, so, H pylori, could be also involved. Growing evidence suggests the likely involvement of H pylori infection in the development of GBS. The aim of the current study was to therefore estimate the prevalence of H pylori antibodies in GBS.
Basement Membrane Changes in Ischemic Stroke

Ischemic stroke, the most common type of stroke, causes high rate of long-term disability and significant economic burden. Current therapeutic options for ischemic stroke include thrombolysis and thrombectomy, which only help <10% of patients due to the relatively narrow therapeutic windows. Additionally, these treatments are associated with severe complications, such as secondary hemorrhage. One important pathology of ischemic stroke is blood-brain barrier (BBB) breakdown. The BBB is a physical barrier that separates the central nervous system and systemic circulation. By preventing the entry of blood components and toxic macromolecules into the brain, the BBB maintains the homeostasis of the central nervous system. Accumulating evidence suggests that BBB disruption is a common pathology in a variety of neurological disorders, including stroke. More importantly, BBB breakdown also plays a causal role in some diseases. For example, it has been shown that BBB disruption induces secondary brain injury and actively contributes to the pathogenesis of ischemic stroke. Over the past century, we have made substantial progress on the cellular constituents of the BBB, including endothelial cells (ECs), pericytes, and astrocytes. The noncellular component of the BBB, the basement membrane (BM), on the other hand, is understudied and its importance in BBB function has just started to be elucidated. Here, we first introduce the structure and function of the BM in detail. Next, we summarize how the BM and its individual components change in ischemic stroke. Furthermore, we discuss potential therapeutic targets at the BBB and critical questions that need future research with a focus on the BM. Our goals are to provide a comprehensive review on BM alterations in ischemic stroke, stimulate novel hypotheses in the field, and promote the development of innovative therapies for ischemic stroke.
Effect of Standardized Skin Care Guidelines on Skin Dryness among Elderly People at Ismailia City

Background: Aged Nursing home residents suffer from a wide range of skin problems. Skin dryness is the most prevalent skin problems in this group. Aim of the study: The present study aimed to evaluate the effect standardized skin care guidelines on dry skin among elderly people at Ismailia City. Design: A quasi-experimental design was utilized to conduct this study. Setting: The study was conducted in all nursing homes for elderly at Ismailia city. Sample: A purposive sample of 105 Nursing home elderly residents who fulfilled the study inclusion criteria. Tools: Two tools were used in the present study; the first tool was a structured interview questionnaire consisted of three parts; the second tool was the clinical scoring systems of EEMCO guidance. Results: The results revealed statistically significant improvements in total scores of dry skin knowledge and skin care practices. There were statistically significant improvements of overall dry skin score (ODS) and in all dry skin specified symptoms (scaling, roughness, redness, and cracks fissures (SRRC)) at post skin care guidelines. Conclusion: Standardized skin care guidelines are effective in reducing skin dryness in aged nursing home residents. Recommendations: Standardized skin care guidelines should be implemented in the study settings on a long term basis to test its sustainability, and in similar settings to confirm its effectiveness and for further improvements.
The Paradox Between Integration and Perceived Discrimination Among American Muslims

Muslim Americans are increasingly integrated into American life, displaying high socioeconomic status, political participation, and adherence to American values. However, they are evaluated more negatively than many other racial, ethnic, and religious minorities and are frequent targets of discrimination. This article examines the mismatch between the integration of Muslims and their poor reception. Drawing on theories of cultural fluency and cognitive dissonance, we argue that cultural integration can exacerbate, rather than mitigate, perceived discrimination because integrated individuals are socialized to expect fair treatment and can recognize and decode even subtle forms of discrimination due to high levels of cultural and language fluency. Using three nationally representative surveys and an opt-in, online study of American Muslims between 2007 and 2017, we find that integrated Muslims are consistently more likely than their counterparts to report individual- and group-level societal and political discrimination. The paradox between adopting the host culture and feeling marginalized poses a challenge to the assumption that integration naturally leads to a sense of belonging among minorities, with important implications for liberal democracies.
The Bright sides of Dark Liquidity

Modern financial markets have experienced fragmentation in lit (displayed) order books as well as an increase in the use of dark (non-displayed) liquidity. Recent dark pool proliferation has raised regulatory and academic concerns about market quality implication. We empirically study the liquidity commonalities in lit and dark venues. We find that compared with lit venues, dark venues proportionally contribute more liquidity to the aggregate market. This is because dark pools facilitate trades that otherwise might not easily have occurred in lit venues when the limit order queue builds up. We also find that the spread of the trades subsquent to dark trades tends to be narrow. This is consistent with the order flow competition between venues in that dark trade might give market makers a signal of uninformed liquidity demand to narrow the spread. Based on the recent dark volume cap regulation under MiFID II, we provide causal evidence that dark trading cap brings a negative impact on transaction cost. JEL classification: G10, G14, G15
NONLINEAR DYNAMICS AND STABILITY OF THIN FILMS WITH INSOLUBLE SURFACTANTS

In the present work the dynamics of a surfactant coated free film, laterally bounded by a solid frame, is studied by means of an evolutionary system consisting of three coupled non-linear Partial Differential Equations (PDE) for the film thickness, lateral velocity and insoluble surfactant concentration. A linear stability analysis is implemented numerically by the method of the differential Gauss elimination. It is found that the film is more stable with the increase of the surfactant concentration (related to the Marangoni number) with respect to antisymmetrical disturbances applied to its shape at different combinations of the Reynolds number, the Weber number, the Hamaker constant and the wetting angle. These results are approximately confirmed by the results of the non-linear stability analysis, from which the evolution of the film thickness, lateral velocity and surfactant concentration is found.
Kuwait child nutrition knowledge questionnaire: validity, reliability and use to assess Kuwaiti schoolchildren’s knowledge before and after a nutrition knowledge intervention

Background: Little is known about the nutritional knowledge of children in Kuwait and school-based nutrition interventions are scarce. No validated tool to assess the nutrition knowledge of schoolchildren in Kuwait is available. Aim: This study determined the validity and reliability of a nutrition knowledge questionnaire in Kuwaiti primary-school children, and measured children’s nutrition knowledge before and after a nutrition awareness intervention. Methods: The questionnaire included five questions to measure nutritional knowledge. The face and content validity were assessed by nutrition and paediatric experts. To assess questionnaire reliability and nutrition knowledge, 642 schoolchildren (8–12 years) were assigned to an intervention, control or reliability group. Each group completed the questionnaire twice, one or two weeks apart. Students in the intervention group attended a nutrition knowledge presentation before completing the questionnaire the second time. Independent and paired samples t-tests were used to assess score differences between and within the intervention and control groups for changes in nutrition knowledge. Pearson correlation coefficients were used to measure score consistency in the reliability group. Results: Overall, the questionnaire had good content validity and moderate to strong reliability (r = 0.44, P < 0.001). Students in the intervention group had significantly higher mean nutritional knowledge scores after the intervention (from 3.65 (SD 1.03) to 4.20 (SD 1.02); P = 0.17). Control group scores were mostly unchanged.