Miracle-dz/UniFAR-FTUs huggingface dataset:
Indexing glomerular filtration rate to suit children.

UNLABELLED In order to be able to compare individuals of differing size, glomerular filtration rate (GFR) is conventionally indexed to body surface area (BSA). This does not, however, suit children because they naturally have a relatively high BSA simply because of their small size. The aim of the study was to identify an appropriate simple whole-body variable based on height and weight suitable for indexing GFR that would be simultaneously appropriate for both children and adults. METHODS A database of 532 routine clinical GFR measurements, each based on 3 venous blood samples obtained between 2 and 4 h after injection of (51)Cr-ethylenediaminetetraacetic acid, was analyzed to give GFR and, using only the half-time of the slope of the clearance curve, the quotient GFR to extracellular fluid volume (ECV). BSA was obtained from the Haycock formula, which is based on height and weight raised to indices to give units of area. Both GFR and GFR/ECV were corrected for the 1-compartment assumption using previously published empiric correction formulas. ECV was obtained by dividing GFR by GFR/ECV. An equation analogous to Haycock's was derived in which the indices of height and weight were varied to give an iterative best fit to ECV instead of BSA. RESULTS GFR, ECV, and BSA increase as functions of age until about age 13 y, corresponding to a BSA of about 1.35 m(2), which was taken as the cutoff point between children and adults. As humans grow, their ratio of height to effective radius changes as a nonlinear function of surface area. Humans must therefore change shape as they grow. Moreover, the ECV-to-weight ratio decreases as a function of body size, suggesting that humans also change body composition as they grow. The new equation, giving an iterative best fit to ECV, was ECV = weight(0.6469) x height(0.7236) x 0.02154. ECV, either measured or estimated from the new equation, corresponding to a BSA of 1.73 m(2), was 12.9 L. Expressed as values normalized to the corresponding average adult values, the new equation and the second-order polynomial fit to ECV were superimposed as they increased as functions of BSA or weight. In contrast, normalized BSA and normalized weight were respectively larger and smaller than normalized ECV in children. GFR indexed to the new equation correlated more closely with GFR indexed to ECV than did GFR indexed to BSA and, along with GFR/ECV, showed a greater fall as a function of age than did GFR/BSA. CONCLUSION When required in absolute units rather than as a rate of turnover of ECV, GFR is appropriately indexed to indices of height and weight as defined by this new equation, which avoids disadvantages to children from indexing to BSA. This unmasks higher values of filtration function in children than have hitherto been recognized.
Isolation and characterization of a novel thermophile; Bacillus haynesii, applied for the green synthesis of ZnO nanoparticles

Abstract The establishment of a benign system for the nanoparticle (NPs) synthesis, is a key in nanotechnology for the environmental and health care industries. Therefore, enrichment of novel biological systems for the green synthesis is in significant demand, to lift up these compounds in the biomedical industries. The present work, reports the green synthesis of ZnO NPs, employing a novel thermophile, identified as Bacillus haynesii (GeneBank: MG822851) isolated from the leaf of date palm plant (Phoenix dactylifera), as an eco-friendly nanobiofactory. Physiochemical characterization of ZnO NPs (50 ± 5 nm in size), was achieved by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), diffuse reflectance UV-Visible spectroscopy (DR UV-Vis spectroscopy), Thermogravimetry analysis (TGA), scanning electron microscopy (SEM) and transmissiom electron microscopy (TEM). The morphogenesis and antimicrobial activity of synthesized ZnO NPs, was studied by evaluating the minimum inhibitory/bactericidal concentration (MIC&MBC) against Escherchia coli (8 and 16 mg/mL) and Staphylococcus aureus (4 and 8 mg/mL), respectively. The present study encourages the use of B. haynesii for the green synthesis of ZnO NP. To the best of our knowledge, this is the first report on the study of thermophilic, B. haynesii for green synthesis of NPs in general and ZnO NPs in particular.
ARE RECURRENT FALLERS DEPRESSED?

ileptic seizure, although in this particular case, the potential confounds of hypoxia and metabolic disturbances in contributing to the seizure and the elevation in CSF-tau cannot be excluded. There is clinical evidence of secondary damage caused by seizures from several studies. A longitudinal MRI study examined 24 patients with mild temporal lobe epilepsy and demonstrated that hippocampal volume loss of 9% on average was seen during the 3.5-year follow-up and that the volume loss was correlated with the number of generalized seizures. Another study found that the duration of poorly controlled epilepsy was associated with ongoing cognitive deterioration. These findings also strongly support that extra attention should be paid to patients with repeated seizures that may result in irreversible sequelae. By contrast, it was previously demonstrated that CSF-tau levels from six patients with chronic epilepsy were all within the normal range, suggesting that well-controlled epilepsy has a favorable long-term outcome, although it is not clear to what extent intense epileptic seizure could raise CSF-tau levels. Therefore, CSF-tau may be a potential marker for patients with repeated seizures, helping to decide about choice of early and radical intervention to sustain cognitive function, although a large number of patients with different types of epilepsy will need to be studied to draw firm conclusions.
MicroRNA-203 promotes the progression of non-small cell lung cancer via surviving.

PURPOSE MicroRNAs are involved in the occurrence and progression of tumors. Previous studies have confirmed that microRNA-203 serves as an oncogene. The specific role of microRNA-203 in non-small cell lung cancer (NSCLC) is rarely reported. This study aimed to explore the regulatory effect of microRNA-203 on NSCLC and its underlying mechanism. METHODS MicroRNA-203 expression in 96 pairs of NSCLC tissues and paracancer tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Correlation between microRNA-203 expression and prognosis of NSCLC was further analyzed. Proliferative, migratory and invasive abilities of NSCLC cells after transfection with si-microRNA-203 or si-negative control (NC) were assessed by cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), colony formation and Transwell assay, respectively. Rescue experiments were conducted to investigate the interaction between microRNA-203 and survivin in regulating NSCLC progression. RESULTS MicroRNA-203 was highly expressed in NSCLC tissues than in paracancer tissues. Correlation analyses showed that microRNA-203 expression was positively correlated to tumor stage, lymph node metastasis and distant metastasis, whereas it was not correlated to age and sex of NSCLC patients. MicroRNA-203 knockdown inhibited proliferative, migratory and invasive abilities of NSCLC cells. Rescue experiments confirmed that microRNA-203 promotes the progression of NSCLC via targeting survivin. CONCLUSIONS MicroRNA-203 is highly expressed in NSCLC, and is closely related to tumor stage, lymph node metastasis, distant metastasis and poor prognosis of NSCLC patients. It is concluded that microRNA-203 promotes the progression of NSCLC via regulating survivin expression.
The Large-Scale Organization of Gestures and Words in the Middle Temporal Gyrus

The middle temporal gyrus (MTG) has been shown to be recruited during the processing of words, but also during the observation of actions. Here we investigated how information related to words and gestures is organized along the MTG. To this aim, we measured the BOLD response in the MTG to video clips of gestures and spoken words in 17 healthy human adults (male and female). Gestures consisted of videos of an actress performing object-use pantomimes (iconic representations of object-directed actions; e.g., playing guitar), emblems (conventional gestures, e.g., thumb up), and meaningless gestures. Word stimuli (verbs, nouns) consisted of video clips of the same actress pronouncing words. We found a stronger response to meaningful compared with meaningless gestures along the whole left and large portions of the right MTG. Importantly, we observed a gradient, with posterior regions responding more strongly to gestures (pantomimes and emblems) than words and anterior regions showing a stronger response to words than gestures. In an intermediate region in the left hemisphere, the response was significantly higher to words and emblems (i.e., items with a greater arbitrariness of the sign-to-meaning mapping) than to pantomimes. These results show that the large-scale organization of information in the MTG is driven by the input modality and may also reflect the arbitrariness of the relationship between sign and meaning. SIGNIFICANCE STATEMENT Here we investigated the organizing principle of information in the middle temporal gyrus, taking into consideration the input-modality and the arbitrariness of the relationship between a sign and its meaning. We compared the middle temporal gyrus response during the processing of pantomimes, emblems, and spoken words. We found that posterior regions responded more strongly to pantomimes and emblems than to words, whereas anterior regions responded more strongly to words than to pantomimes and emblems. In an intermediate region, only in the left hemisphere, words and emblems evoked a stronger response than pantomimes. Our results identify two organizing principles of neural representation: the modality of communication (gestural or verbal) and the (arbitrariness of the) relationship between sign and meanings.
Effect of Learning to Use a Mobility Aid on Gait and Cognitive Demands in People with Mild to Moderate Alzheimer's Disease: Part I - Cane.

BACKGROUND People with Alzheimer's disease (AD) exhibit balance and walking impairments that increase falls risk. Prescription of a mobility aid is done to improve stability, yet also requires increased cognitive resources. Single-point canes require unique motor sequencing for safe use. The effect of learning to use a single-point cane has not been evaluated in people with AD. OBJECTIVES In people with AD and healthy adult controls: 1) examine changes in gait while using a cane under various walking conditions; and 2) determine the cognitive and gait costs associated with concurrent cane walking while multi-tasking. METHODS Seventeen participants with AD (age 82.1±5.6 years) and 25 healthy controls (age 70.8±14.1 years) walked using a single-point cane in a straight (6 meter) and a complex (Figure of 8) path under three conditions: single-task (no aid), dual-task (walking with aid), and multi-task (walking with aid while counting backwards by ones). Velocity and stride time variability were recorded with accelerometers. RESULTS Gait velocity significantly slowed for both groups in all conditions and stride time variability was greater in the AD group. Overall, multi-tasking produced a decrease in gait and cognitive demands for both groups, with more people with AD self-prioritizing the cognitive task over the gait task. CONCLUSION Learning to use a cane demands cognitive resources that lead to detrimental changes in velocity and stride time variability. This was most pronounced in people with mild to moderate AD. Future research needs to investigate the effects of mobility aid training on gait performance.
Expression of DNA Damage Response Markers in Early-Onset or Familial Gastric Cancers

Background: Early-onset or familial gastric cancer (GC) is known to have clinicopathologic profiles different from those of sporadic GC. We aimed to compare DNA damage response marker expression between early-onset or familial GC and sporadic GC. Methods: GC samples were obtained from patients who underwent gastrectomy for GC at Seoul National University Hospital. Immunohistochemical analyses of various DNA damage response markers, including BRCA1, BRCA2, MRE11, RAD51C, and γH2AX, were performed using 54 early-onset GC, 59 familial GC, and 337 sporadic GC tissue microarray samples. Correlations between marker expression and clinicopathologic features were evaluated by univariate and multivariate analyses, and overall survival was analyzed. Results: The rate of γH2AX positivity was significantly higher (p < 0.001) in early-onset or familial GC than in sporadic GC. In contrast, the rates of MRE11 negativity and RAD51C negativity were significantly higher in sporadic GC than in early-onset or familial GC. BRCA1 negativity was associated with decreased overall survival in sporadic GC (p = 0.002), and MRE11 negativity was associated with decreased overall survival in sporadic GC (p = 0.012). Conclusion: Our results show significant differences in DNA damage response marker expression between early-onset or familial GC and sporadic GC.
Index-Based Dietary Patterns and the Risk of Prostate Cancer among Iranian Men

Background and objective: The second most common cancer in men after lung cancer is prostate cancer (PC). Previous studies assessed the association between food items or food groups and the risk of PC, but diet quality indices are unique approaches to study any relations between diet and disease. Our objective was to investigate the effect of healthy eating index (HEI-2010) and Mediterranean-Style Dietary Pattern Score (MSDPS) on PC risk. Methods: In this case-control study, we recruited 97 patients with MS and 205 control subjects . Dietary intake was evaluted using a valid and reliable food frequency questionnaire. The HEI and MSDPS were calculated. Logistic regression was used to evaluate the relationship between HEI and MSDP scores and PC risk after adjusting the confounders. Results: In comparison to controls, cases had lower score on HEI (61 vs. 70.07; P< 0.001), and higher score on MSDP (26.20 vs. 24.49; P= 0.44). After comparing the highest and the lowest tertile of HEI, we observed a significant decreasing trend in the risk of PC (p for trend<0.001). Conclusion: Our findings suggested that a high quality diet, according to HEI, may decrease the risk of PC.
In Situ Accessibility of Small-Subunit rRNA of Members of the Domains Bacteria, Archaea, and Eucarya to Cy3-Labeled Oligonucleotide Probes

ABSTRACT Low accessibility of the rRNA is together with cell wall impermeability and low cellular ribosome content a frequent reason for failure of whole-cell fluorescence hybridization with fluorescently labeled oligonucleotide probes. In this study we compare accessibility data for the 16S rRNA of Escherichia coli (gamma Proteobacteria, Bacteria) with the phylogenetically distantly related organisms Pirellula sp. strain 1 (Planctomycetes, Bacteria) and Metallosphaera sedula (Crenarchaeota, Archaea) and the 18S rRNA accessibility of Saccharomyces cerevisiae (Eucarya). For a total of 537 Cy3-labeled probes, the signal intensities of hybridized cells were quantified under standardized conditions by flow cytometry. The relative probe-conferred fluorescence intensities are shown on color-coded small-subunit rRNA secondary-structure models. For Pirellula sp. , most of the probes belong to class II and III (72% of the whole data set), whereas most of the probes targeting sites on M. sedula were grouped into class V and VI (46% of the whole data set). For E. coli, 45% of all probes of the data set belong to class III and IV. A consensus model for the accessibility of the small-subunit rRNA to oligonucleotide probes is proposed which uses 60 homolog target sites of the three prokaryotic 16S rRNA molecules. In general, open regions were localized around helices 13 and 14 including target positions 285 to 338, whereas helix 22 (positions 585 to 656) and the 3′ half of helix 47 (positions 1320 to 1345) were generally inaccessible. Finally, the 16S rRNA consensus model was compared to data on the in situ accessibility of the 18S rRNA of S. cerevisiae.
Comparison of TACE combined with and without iodine-125 seeds implantation therapy for advanced stage hepatocellular carcinoma: a systematic review and meta-analysis.

PURPOSE Hepatocellular carcinoma (HCC) has the second-highest cancer-related mortality in patients worldwide. Recently, TACE plus Iodine-125 (125I) seed strand endovascular implantation (ISEI) was shown to be feasible in advanced HCC patients. The aim of this study was to evaluate the efficacy and safety of this combined therapy for the treatment of advanced stage HCC by meta-analysis. METHODS A systematic search in PubMed, EMBASE and Cochrane Library Databases was conducted until April 1st 2018. Outcomes included overall survival (OS), objective response rate (ORR) of primary liver tumor, and procedure-related complications. All statistical analyses were performed using Review Manager 5.3 and Stata 12.0. RESULTS Nine eligible studies on 1059 advanced HCC patients were included. The results showed that TACE plus ISEI had significantly improved the 6-month OS (OR, 5.01: 95%CI, 3.19~7.86: P<0. 01) and 1-year OS (OR, 4.97: 95%CI, 3.12~7.92: P<0.01) compared to TACE alone. CONCLUSION The safety and efficacy of TACE plus ISEI is superior to TACE alone for advanced HCC.
Microhomologies are prevalent at Cas9-induced larger deletions

Abstract The CRISPR system is widely used in genome editing for biomedical research. Here, using either dual paired Cas9D10A nickases or paired Cas9 nuclease we characterize unintended larger deletions at on-target sites that frequently evade common genotyping practices. We found that unintended larger deletions are prevalent at multiple distinct loci on different chromosomes, in cultured cells and mouse embryos alike. We observed a high frequency of microhomologies at larger deletion breakpoint junctions, suggesting the involvement of microhomology-mediated end joining in their generation. In populations of edited cells, the distribution of larger deletion sizes is dependent on proximity to sgRNAs and cannot be predicted by microhomology sequences alone.
A Bird’s-Eye View of the Multiple Biochemical Mechanisms that Propel Pathology of Alzheimer’s Disease: Recent Advances and Mechanistic Perspectives on How to Halt the Disease Progression Targeting Multiple Pathways

Neurons consume the highest amount of oxygen, depend on oxidative metabolism for energy, and survive for the lifetime of an individual. Therefore, neurons are vulnerable to death caused by oxidative-stress, accumulation of damaged and dysfunctional proteins and organelles. There is an exponential increase in the number of patients diagnosed with neurodegenerative diseases such as Alzheimer’s (AD) as the number of elderly increases exponentially. Development of AD pathology is a complex phenomenon characterized by neuronal death, accumulation of extracellular amyloid-β plaques and neurofibrillary tangles, and most importantly loss of memory and cognition. These pathologies are most likely caused by mechanisms including oxidative stress, mitochondrial dysfunction/stress, accumulation of misfolded proteins, and defective organelles due to impaired proteasome and autophagy mechanisms. Currently, there are no effective treatments to halt the progression of this disease. In order to treat this complex disease with multiple biochemical pathways involved, a complex treatment regimen targeting different mechanisms should be investigated. Furthermore, as AD is a progressive disease-causing morbidity over many years, any chemo-modulator for treatment must be used over long period of time. Therefore, treatments must be safe and non-interfering with other processes. Ideally, a treatment like medicinal food or a supplement that can be taken regularly without any side effect capable of reducing oxidative stress, stabilizing mitochondria, activating autophagy or proteasome, and increasing energy levels of neurons would be the best solution. This review summarizes progress in research on different mechanisms of AD development and some of the potential therapeutic development strategies targeting the aforementioned pathologies.
Beneficial effects of inducible nitric oxide synthase inhibitor on reperfusion injury in the pig liver.

BACKGROUND Although inhibition of endothelial nitric oxide synthase (eNOS) has been reported to aggravate hepatic ischemia-reperfusion (I/R) injury, the role of inducible nitric oxide synthase (iNOS) has been still unknown. We investigated the role of NO produced by iNOS, and evaluated the effect of an iNOS inhibitor on prolonged warm I/R injury in the pig liver. METHODS Pigs were subjected to 120 min of hepatic warm I/R under the extracorporeal circulation. We investigated the time course of changes in serum and hepatic microdialysate NO2- + NO3- (NOx) and the cellular distribution of eNOS and iNOS by immunohistochemistry, including a double-immunofluorescence technique in combination with confocal laser scanning microscopy. The effect of iNOS inhibitor was also investigated. RESULTS Hepatic I/R induced new nitric oxide production in serum and hepatic microdialysate NOx after reperfusion and severe hepatic damage in the centrilobular region where nitrotyrosine was strongly expressed. Diffuse eNOS expression in sinusoidal endothelium did not differ before and after reperfusion. In contrast, strong iNOS expression in Kupffer cells and neutrophils appeared strongly in the centrilobular region after reperfusion. Pigs with intraportal administration of N(G)-nitro-L-arginine (10 mg/kg) died during the period of ischemia or early in the period of reperfusion with a high mortality rate (80.0%). Intraportal administration of aminoguanidine hemisulfate (10 mg/kg) significantly suppressed nitric oxide production and serum aspartate aminotransferase after reperfusion, inhibited nitrotyrosine expression, and attenuated hepatic damage. CONCLUSIONS These results indicate that hepatic I/R injury is triggered by centrilobular iNOS expression; and attenuated by inhibition of iNOS.
A Review on Dietary Intervention in Obesity Associated Colon Cancer

Background: Colorectal cancer (CRC) is one of the major causes of morbidity and mortality. According to National Cancer Registry, the incidence of colorectal cancer in Peninsular Malaysia increases with age. The incidence is highest among Chinese population but lower among Indians and Malays. Many reviews have suggested that obesity may be associated with a higher risk (>50%) of colorectal cancer. Methods: This study collects a comprehensive data from the literature review available from respective journals on dietary intervention and the chemo-protective mechanisms of a few natural resources in obesity -associated colon cancer based on previous and current studies. Results: In obesity-associated colon cancer, the genes of interest and pathways that are mainly involved include NFκB, P13K/Akt, and MAPK pathways, and FTO, leptin, Cyclin D, MMPs, and STAT3 genes. Dietary modification is one of the alternative steps in early prevention of colon cancer. It has been proposed that the components: present in certain foods may have the ability to protect against many diseases including the prevention of cancer. Conclusion: There are many factors that lead to obesity-associated colon cancer and the mechanisms behind it is still undergoing intensive research. This review aims to scrutinize research as well as reviews that have been previously reported on obesity associated colorectal cancer and the beneficial effects of including antioxidants-rich foods such as vegetables and fruits in the diet to reduce the risk of obesity associated colorectal cancer.