Miracle-dz/UniFAR-FTUs huggingface dataset:
The cerebral cavernous malformation disease causing gene KRIT1 participates in intestinal epithelial barrier maintenance and regulation

Epithelial barrier maintenance and regulation requires an intact perijunctional actomyosin ring underneath the cell‐cell junctions. By searching for known factors affecting the actin cytoskeleton, we identified Krev interaction trapped protein 1 (KRIT1) as a major regulator for epithelial barrier function through multiple mechanisms. KRIT1 is expressed in both small intestinal and colonic epithelium, and KRIT1 knockdown in differentiated Caco‐2 intestinal epithelium decreases epithelial barrier function and increases cation selectivity. KRIT1 knockdown abolished Rho‐associated protein kinase‐induced and myosin II motor inhibitor–induced barrier loss by limiting both small and large molecule permeability but did not affect myosin light chain kinase–induced increases in epithelial barrier function. These data suggest that KRIT1 participates in Rho‐associated protein kinase‐ and myosin II motor–dependent (but not myosin light chain kinase–dependent) epithelial barrier regulation. KRIT1 knockdown exacerbated low‐dose TNF‐induced barrier loss, along with increased cleaved casρase‐3 production. Both events are blocked by pan‐caspase inhibition, indicating that KRIT1 regulates TNF‐induced barrier loss through limiting epithelial apoptosis. These data indicate that KRIT1 controls epithelial barrier maintenance and regulation through multiple pathways, suggesting that KRIT1 mutation in cerebral cavernous malformation disease may alter epithelial function and affect human health. —Wang, Y. , Li, Y. , Zou, J., Polster, S. P., Lightle, R. , Moore, T. , Dimaano, M. , He, T. ‐C. , Weber, C. R. , Awad, I. A. , Shen, L. The cerebral cavernous malformation disease causing gene KRITl participates in intestinal epithelial barrier maintenance and regulation. FASEB J. 33, 2132–2143 (2019). www.fasebj. org
Serum level of interleukin 36 in patients with multiple sclerosis

ABSTRACT Introduction: Multiple sclerosis is a chronic autoimmune demyelinating disorder of central nervous system with unknown origin. In MS disease, T cells are pointed to myelin antigens and it leads to myelin loss and axonal degeneration. Cytokines are important regulators of immune system and has critical roles in MS pathogenesis. Interleukin 36, a member of interleukin 1 family, has been shown having important roles in some autoimmune disorders due to its proinflammatory actions and its role in host immunity. Methods and materials: In the current study, 49 relapsing remitting multiple sclerosis patients and 41 healthy individuals were recruited. IL36 measurement was performed using enzyme-linked immunosorbent assay technique. Results: Mean age of RRMS patient and control group were 31.84 ± 6.89 and 34.27 ± 8.83 years, respectively. Serum level of IL36 were 61.91 ± 16.29 in MS patients and 42.26 ± 17.54 in healthy group (P < 0.001). Conclusion: in this study for the first time, significantly higher serum level of IL36 was determined in RRMS patients comparing healthy individuals. This data may suggest important roles of this cytokine in MS pathogenesis.
Improving the Accuracy, Quality, and Signal-To-Noise Ratio of MRI Parametric Mapping Using Rician Bias Correction and Parametric-Contrast-Matched Principal Component Analysis (PCM-PCA)

MRI parametric mapping, including T2 mapping, can quantitatively characterize tissue properties and is an important MRI procedure in biomedical research and studies of diseases [1-3]. However, the accuracy, quality, and signal-to-noise ratio (SNR) of MRI parametric mapping may be negatively impacted by Rician noise in multi-contrast MRI data [4]. As such, it is important to develop a post-processing method to minimize the negative impact of Rician noise. In this study, we report a new parametric-contrast-matched principal component analysis (PCM-PCA) denoising method that involves 1) identifying voxels with similar T2 decay characteristics and 2) using the principal component analysis (PCA) to denoise multi-contrast MRI data along the echo time (TE) dimension. We additionally evaluated the effects of integrating Rician bias correction and the new PCM-PCA method. In this study, we mathematically added Rician noise at various levels to human brain MRI data and performed different combinations of denoising and Rician bias correction on the magnitude-valued images. We found that MRI denoising using the PCM-PCA method resulted in improved image quality, SNR, and accuracy of the measured T2 relaxation time constants. Additionally, we found that for data with low SNR (e.g., 1.5 or lower), Rician bias correction further improved image quality and T2 mapping accuracy. In summary, our experimental results demonstrated that the new PCM-PCA denoising method and Rician bias correction adequately improve multi-contrast MRI quality and T2 parametric mapping accuracy.
Impact of an Inpatient Palliative Care Consultation in Terminally Ill Cancer Patients

Abstract: Limited data are available to guide the timing of palliative care involvement in the treatment of cancer. We describe the referral patterns of inpatient palliative care consultations(IPCC) in advanced cancer patients in a tertiary care center. Methods: A retrospective review was performed of IPCC for cancer patients from January 1, 2014, to December 31, 2014. Descriptive statistics are reported. Results: IPCCs were requested for 245 cancer inpatients, of which 130 were male (53.1%) and 115 (46.9%) were female; 128 (52.2%) were Caucasian, 114 (46.5%) were African American, and 3 (1.2%) were another race. Of the 245 patients, 79 (32.2%) were newly diagnosed during the current admission, and the remaining 146 (67.8%) had been diagnosed previously. Fifty-seven (23.3%) patients were admitted to the intensive care unit (ICU) during hospitalization. Of the 39 patients (15.9%) who died during their hospital stay, 34 (87.0%) had an ICU stay during the hospitalization or died in the ICU. The most common malignancies were lung (71; 29.0%), pancreatic-biliary (33; 13.4%), lymphoma and leukemia (22; 8.9%), hepatocellular (18; 7.3%), head and neck (16; 6.5%), and upper gastrointestinal tract(GI) (16; 6.5%). Conclusions: Our data show that 15.9% of terminally ill cancer patients with IPCC died in the hospital, the majority of whom died in the ICU. This was likely due to delays in the initiation of outpatient palliative care consultation, leading to an increased strain on tertiary referral centers. Our study highlights a racial disparity in the rate of IPCC in African Americans, compared to historical data.
Evaluation of Genotype MTBDRplus and MTBDRsl Assays for Rapid Detection of Drug Resistance in Extensively Drug-Resistant Mycobacterium tuberculosis Isolates in Pakistan

Pakistan ranks 5th among the world's highest tuberculosis (TB) burden countries alongside the 6th among countries with the highest burden of drug-resistant TB, including multi-drug resistant (MDR)-TB. Methods for rapid and reliable drug susceptibility testing (DST) are prerequisite for the prompt institution of effective anti-TB treatment. The aim of this study was to evaluate the efficiency of Genotype MTBDRplus and MTBDRsl assays for the detection of MDR and (pre-) extensively drug-resistant (XDR-TB) isolates in Pakistan. The study included 47 pre-XDR and 6 XDR-TB isolates, recovered from 53 patients from Pakistan. Conventional DST was performed using the standard 1% proportion method on the Löwenstein-Jensen medium. For molecular determination of drug resistance, GenoType MTBDRplus and GenoType MTBDRsl assays (Hain Lifescience, Germany) were used. To evaluate discrepancies between conventional and molecular DST results, mutation profiling was performed by amplifying and sequencing seven genetic loci, i.e., katG, inhA, and mabA-inhA promoter, rpoB, gyrA, embB, rrs. The sensitivity of Genotype MTBDRplus was 71.7% for isoniazid (INH) and 79.2% for rifampicin (RIF). Sequence analysis revealed non-synonymous mutations in 93.3 and 27.3% of isolates phenotypically resistant to INH and RIF, respectively, albeit susceptible when tested by GenoType MTBDRplus. GenoType MTBDRsl had a sensitivity of 73.6, 64.7, 20, 25, and 100% for the detection of fluoroquinolones, ethambutol, kanamycin, amikacin, and capreomycin resistance, respectively. Upon sequencing, mutations were detected in 20, 77.8%, and all isolates phenotypically resistant to aminoglycosides, ethambutol, and fluoroquinolones, respectively, yet declared as susceptible with GenoType MTBDRsl. Low sensitivities seriously impede the large-scale application of the Genotype MTBDRplus and MTBDRsl assays. Unless further optimized, the currently available line-probe assays should rather be auxiliary to the conventional, phenotype-based methods in the detection of MDR- and XDR-TB in Pakistan.
miRNA-based therapeutic potential of stem cell-derived extracellular vesicles: a safe cell-free treatment to ameliorate radiation-induced brain injury

Abstract Purpose: This review compiles what is known about extracellular vesicles (EVs), their bioactive cargo, and how they might be used to treat radiation-induced brain injury. Radiotherapy (RT) is effective in cancer treatment, but can cause substantial damage to normal central nervous system tissue. Stem cell therapy has been shown to be effective in treating cognitive dysfunction arising from RT, but there remain safety concerns when grafting foreign stem cells into the brain (i.e. immunogenicity, teratoma). These limitations prompted the search for cell-free alternatives, and pointed to EVs that have been shown to have similar ameliorating effects in other tissues and injury models. Conclusions: EVs are nano-scale and lipid-bound vesicles that readily pass the blood–brain barrier. Arguably the most important bioactive cargo within EVs are RNAs, in particular microRNAs (miRNA). A single miRNA can modulate entire gene networks and signalling within the recipient cell. Determining functionally relevant miRNA could lead to therapeutic treatments where synthetically-derived EVs are used as delivery vectors for miRNA. Stem cell-derived EVs can be effective in treating brain injury including radiation-induced cognitive deficits. Of particular interest are systemic modes of administration which obviate the need for invasive procedures.
Targeting self-regulation and academic functioning among preschoolers with behavior problems: Are there incremental benefits to including cognitive training as part of a classroom curriculum?

ABSTRACT The purpose of this study was to examine the additional benefit of an adaptive Cogmed working memory training (CWMT) to a social-emotional/self-regulation classroom curriculum for preschoolers with externalizing behavior problems (EBP). Participants for this study included 49 children (71% boys, Mage = 4.52) with at-risk or clinically elevated levels of EBP. Children participated in an 8-week summer treatment program for Pre-Kindergarteners (STP-PreK), where they were randomly assigned to either adaptive CWMT (n = 24), or nonadaptive CWMT (n = 25). Multiple repeated measures analyses were conducted to examine the impact of adaptive versus nonadaptive CWMT on pre and posttreatment parent-/teacher-reported behavioral functioning, parent-/teacher reported and child task performance of executive functioning, and standardized academic achievement measures. Repeated measures analyses found that children in both groups improved on all measures (d’s = .23-.86). However, there were no significant time X condition effects for parent or teacher-reported behavior, reported or observed executive functioning, or standardized academic measures. These findings suggest that CWMT does not appear to provide any incremental benefits to children’s executive functioning, behavior, or academics when implemented within a comprehensive behavioral modification intervention.
Par3 interacts with Prickle3 to generate apical PCP complexes in the vertebrate neural plate

Vertebrate neural tube formation depends on the coordinated orientation of cells in the tissue known as planar cell polarity (PCP). In the Xenopus neural plate, PCP is marked by the enrichment of the conserved proteins Prickle3 and Vangl2 at anterior cell boundaries. Here we show that the apical determinant Par3 is also planar polarized in the neuroepithelium, suggesting a role for Par3 in PCP. Consistent with this hypothesis, interference with Par3 activity inhibited asymmetric distribution of PCP junctional complexes and caused neural tube defects. Importantly, Par3 physically associated with Prickle3 and promoted its apical localization, whereas overexpression of a Prickle3-binding Par3 fragment disrupted PCP in the neural plate. We also adapted proximity biotinylation assay for use in Xenopus embryos and show that Par3 functions by enhancing the formation of the anterior apical PCP complex. These findings describe a mechanistic link between the apical localization of PCP components and morphogenetic movements underlying neurulation.
LncRNA SNHG17 promotes gastric cancer progression by epigenetically silencing of p15 and p57

Long noncoding RNAs (lncRNA) are attractive biomarkers and therapeutic targets because of their disease‐ and stage‐restricted expression. Small nucleolar RNA host gene 17 (SNHG17) belongs to a large family of noncoding genes hosting small RNAs, with its expression pattern and biological function not clarified in gastric cancer (GC). Thus, we conducted this study to investigate the functional significance and the underlying mechanisms of SNHG17 in GC progression. Our results showed that SNHG17 expression was upregulated in GC tissues and cells, and its high expression was significantly correlated with increased invasion depth, lymphatic metastasis, and advanced TNM stage. The expression of plasma SNHG17 was also found upregulated in patients with GC compared with healthy controls, with a moderate accuracy for diagnosis of GC (area under the receiver operating characteristic curve = 0.748; 95% CI, 0.666–0.830). Gain‐ and loss‐of‐function of SNHG17 revealed that SNHG17 promoted GC cell proliferation, cell cycle progression, invasion, and migration and inhibited apoptosis. Mechanistic investigations showed that SNHG17 was associated with polycomb repressive complex 2 and that this association was required for epigenetic repression of cyclin‐dependent protein kinase inhibitors, including p15 and p57, thus contributing to the regulation of GC cell cycle and proliferation. Furthermore, rescue experiments indicated that SNHG17 functioned as an oncogene via activating enhancer of zeste homolog 2 in GC cells. Our study provides a new perspective for SNHG17 acting as a noncoding oncogene in GC tumorigenesis, and it may serve as a novel early diagnostic marker and potential target for the treatment of GC.
Safety of gadobutrol: results of a non-interventional study of 3710 patients, including 404 children

Background The safety of gadolinium-based contrast agents is a hot topic in radiology. Purpose To evaluate the safety profile of gadobutrol during routine use. Material and Methods Prospective, non-interventional study in 80 centers in Germany. The primary outcome was the number of adverse drug reactions (ADR) following gadobutrol administration. Results A total of 3710 patients were included in the analysis, including 404 children (10.9%). A total of 6026 magnetic resonance imaging examinations of organs/organ systems and 872 magnetic resonance angiography examinations were performed. A total of 22 (0.59%) patients experienced at least one ADR. Nausea and vomiting were the most frequent ADRs, experienced by nine (0.24%) and three (0.08%) patients, respectively. One serious ADR was recorded (anaphylactoid reaction). No deaths were reported. Conclusion This non-interventional study in 3710 patients confirmed gadobutrol as a safe and reliable contrast agent in adults and children.
Effects of Quantity and Size of Buttons of In-Vehicle Touch Screen on Drivers’ Eye Glance Behavior

ABSTRACT This article investigates the effects of the quantity and size of touch screen buttons and the task-interleaving strategies on drives’ eye glance behavior. An experiment was conducted on a fixed-base driving simulator with 20 participants. The participants were asked to perform a button search-and-press task on an in-vehicle touch screen while driving. A full-factorial within-subject design was used with three button quantities (4, 8, and 15) and three button sizes (14 mm, 24 mm, and 33 mm). Although a normal distribution was often assumed for the eye glance data in previous studies, our results show that the total eyes-off-road time (TEORT) and glance durations are generally not normally distributed (positively skewed) even after a log transformation. The results show that the number of buttons has an increasing effect on task completion time, TEORT, and long (2+ s) glances. However, in general, no such differences were found for button sizes. Further analysis shows that long glances were strongly associated with drivers completing the task with a single glance. It seems to suggest that a major cause of long glances is that drivers are reluctant to switch the task back to driving at subtask boundaries that are probably associated with the high cost of interruption. These findings confirm the importance of task resumability for in-vehicle user interfaces and have implications that careful task analysis needs to be conducted in the context of multitasking. Certain subtask combinations, such as a visual search followed by pressing the search target, may discourage task interleaving and ultimately compromise driving safety.
Effects of an Empowerment Program on Resilience and Posttraumatic Growth Levels of Cancer Survivors: A Randomized Controlled Feasibility Trial.

BACKGROUND Psychosocial empowerment of cancer survivors can help improve their psychological resilience and enhance their posttraumatic growth. However, there is a lack of research exploring the effects of such empowerment programs on resilience and posttraumatic growth of cancer survivors. OBJECTIVE The aim of this study was to assess the feasibility of a randomized controlled trial on the effectiveness of an integrated empowerment program on cancer survivors. METHODS We conducted a randomized controlled trial with 89 adult cancer survivors (>25 years old) from 2 oncology hospitals. Using a table of random numbers, they were assigned randomly to the experimental group (n = 45), which participated in 10 sessions of a structured empowerment program, and the control group (n = 44), which received only routine care and no further intervention. Data were collected from patients using the Posttraumatic Growth Inventory and the Resilience Scale for Adults. RESULTS Posttraumatic growth and resilience levels significantly improved in the intervention group compared with the control group both at the end of and a month after the program. CONCLUSION This study's empowerment program is effective in improving posttraumatic growth and resilience levels of cancer survivors who are prone to trauma. IMPLICATIONS FOR PRACTICE By enhancing resilience and posttraumatic growth of cancer survivors, the empowerment program may help restore life, and thus its application can contribute to the psychosocial well-being of cancer survivors. Nurses with training and experience can integrate this kind of program into clinical settings.
Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma.

The introduction of novel agents has led to major improvements in clinical outcomes for patients with multiple myeloma. To shorten evaluation times for new treatments, health agencies are currently examining minimal residual disease (MRD) as a surrogate end point in clinical trials. We assessed the prognostic value of MRD, measured during maintenance therapy by next-generation sequencing (NGS). MRD negativity was defined as the absence of tumor plasma cell within 1 000 000 bone marrow cells (<10-6). Data were analyzed from a recent clinical trial that evaluated the role of transplantation in newly diagnosed myeloma patients treated with lenalidomide, bortezomib, and dexamethasone (RVD). MRD negativity was achieved at least once during maintenance in 127 patients (25%). At the start of maintenance therapy, MRD was a strong prognostic factor for both progression-free survival (adjusted hazard ratio, 0.22; 95% confidence interval, 0.15-0.34; P < .001) and overall survival (adjusted hazard ratio, 0.24; 95% confidence interval, 0.11-0.54; P = .001). Patients who were MRD negative had a higher probability of prolonged progression-free survival than patients with detectable residual disease, regardless of treatment group (RVD vs transplant), cytogenetic risk profile, or International Staging System disease stage at diagnosis. These results were similar after completion of maintenance therapy. Our findings confirm the value of MRD status, as determined by NGS, as a prognostic biomarker in multiple myeloma, and suggest that this approach could be used to adapt treatment strategies in future clinical trials.
Roles of microRNAs in preeclampsia

Preeclampsia (PE) is a complex disorder that is characterized by hypertension and proteinuria after the 20th week of pregnancy, and it causes most neonatal morbidity and perinatal mortality. Most studies suggest that placental dysfunction is the main cause of PE. However, genetic factors, immune factors, and systemic inflammation are also related to the pathophysiology of this syndrome. Thus far, the exact pathogenesis of PE is not yet fully understood, and intense research efforts are focused on PE to elucidate the pathophysiological mechanisms. MicroRNAs (miRNAs) refer to small single‐stranded and noncoding molecules that can negatively regulate gene expression, and miRNA regulatory networks play an important role in diverse pathological processes. Many studies have confirmed deregulated miRNA in pregnant patients with PE, and the function and mechanism of these differentially expressed miRNA are gradually being revealed. In this review, we summarize the current research about miRNA involved in PE, including placenta‐specific miRNA, their predictive value, and their function in the development of PE. This review will provide fundamental evidence of miRNA in PE, and further studies are necessary to explore the roles of miRNA in the early diagnosis and treatment of PE.