Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of p53 expression in cancer cells alters cell cycle response after inhibition of exportin-1 but does not prevent cell death

ABSTRACT The tumor suppressor protein p53 is central to the cellular stress response and may be a predictive biomarker for cancer treatments. Upon stress, wildtype p53 accumulates in the nucleus where it enforces cellular responses, including cell cycle arrest and cell death. p53 is so dominant in its effects, that p53 enforcement – or – restoration therapy is being studied for anti-cancer therapy. Two mechanistically distinct small molecules that act via p53 are the selective inhibitor of nuclear export, selinexor, and MDM2 inhibitor, nutlin-3a. Here, individual cells are studied to define cell cycle response signatures, which captures the variability of responses and includes the impact of loss of p53 expression on cell fates. The individual responses are then used to build the population level response. Matched cell lines with and without p53 expression indicate that while loss-of-function results in altered cell cycle signatures to selinexor treatment, it does not diminish overall cell loss. On the contrary, response to single-agent nutlin-3a shows a strong p53-dependence. Upon treatment with both selinexor and nutlin-3a there are combination effects in at least some cell lines – even when p53 is absent. Collectively, the findings indicate that p53 does act downstream of selinexor and nutlin-3a, and that p53 expression is dispensable for selinexor to cause cell death, but nutlin-3a response is more p53-dependent. Thus, TP53 disruption and lack of expression may not predict poor cell response to selinexor, and selinexor’s mechanism of action potentially provides for strong efficacy regardless of p53 function.
Droplet Digital PCR with EvaGreen Assay: Confirmational Analysis of Structural Variants

DNA structural variants can be analyzed by droplet digital PCR (ddPCR), a water‐oil microfluidics and fluorescence technology to quantify target nucleic acids with extreme precision and sensitivity. Traditional ddPCR uses expensive fluorescent oligonucleotide probes that require extensive optimization. Here we describe a variation of ddPCR using a DNA‐binding dye (EvaGreen), whose properties allow target products to be effectively quantified at a significantly lower cost. © 2018 by John Wiley & Sons, Inc.
Comparison of central corneal thickness measurement with Sirius Topographer and Nidek Axial Length Scan

1. Neena J, Rachel J, Praveen V, Murthy GV; Rapid Assessment of Avoidable Blindness India Study Group. Rapid assessment of avoidable blindness in India. PLoS One 2008;3:e2867. 2. Murthy GV, Gupta SK, Bachani D, Jose R, John N. Current estimates of blindness in India. Br J Ophthalmol 2005; 89:257‐60. 3. Dandona L, Dandona R, John RK. Estimation of blindness in India from 2000 through 2020: Implications for the blindness control policy. Natl Med J India 2001;14:327‐34. 4. Vemparala R, Gupta P. National Programme for Control of Cite this article as: Saluja G, Takkar B, Agarwal E, Sharma B, Khokhar S. Planning a new intraocular lens library in the Indian scenario. Indian J Ophthalmol 2018;66:1227-8.
Antibiotic Stewardship: The Health of the World Depends on It

What words would you fear more, “You have cancer” or “You have a urinary tract infection (UTI)”? I believe most people would fear the words “You have cancer” because many types of cancer are untreatable and are associated with death. Unfortunately, due the escalating rates of antibiotic resistance the world is entering an era of “untreatable” UTIs where just like cancer, a UTI can also be associated with death. Pharmacists need to have an awareness of the global rates of antibiotic resistance because every multidrug-resistant organism (MDRO) is just a plane ride away. Dr. Marc Sprenger, director of the World Health Organization (WHO) Antimicrobial Resistance Secretariat stated, “Some of the world’s most common—and potentially most dangerous— infections are proving drug-resistant, and most worrying of all, pathogens don’t respect national borders. ” Consider the following four scenarios and the impact it might have on your antibiotic decisions for a hospitalized patients.
Finding flies in the mushroom soup: Host specificity of fungus‐associated communities revisited with a novel molecular method

Fruiting bodies of fungi constitute an important resource for thousands of other taxa. The structure of these diverse assemblages has traditionally been studied with labour‐intensive methods involving cultivation and morphology‐based species identification, to which molecular information might offer convenient complements. To overcome challenges in DNA extraction and PCR associated with the complex chemical properties of fruiting bodies, we developed a pipeline applicable for extracting amplifiable total DNA from soft fungal samples of any size. Our protocol purifies DNA in two sequential steps: (a) initial salt–isopropanol extraction of all nucleic acids in the sample is followed by (b) an extra clean‐up step using solid‐phase reversible immobilization (SPRI) magnetic beads. The protocol proved highly efficient, with practically all of our samples—regardless of biomass or other properties—being successfully PCR‐amplified using metabarcoding primers and subsequently sequenced. As a proof of concept, we apply our methods to address a topical ecological question: is host specificity a major characteristic of fungus‐associated communities, that is, do different fungus species harbour different communities of associated organisms? Based on an analysis of 312 fungal fruiting bodies representing 10 species in five genera from three orders, we show that molecular methods are suitable for studying this rich natural microcosm. Comparing to previous knowledge based on rearing and morphology‐based identifications, we find a species‐rich assemblage characterized by a low degree of host specialization. Our method opens up new horizons for molecular analyses of fungus‐associated interaction webs and communities.
Impact of root canal preparation performed by ProTaper Next or Reciproc on the quality of life of patients: a randomized clinical trial

AIM To compare the impact of the two different root canal preparation systems on the quality of life of patients and correlate postoperative pain with the impact on quality of life. METHODOLOGY A randomized clinical trial was conducted with 58 patients allocated into two groups based on the root canal preparation system employed: ProTaper Next (PN) or Reciproc (R). Data collection involved the administration of a questionnaire addressing demographic and clinical characteristics, the OHIP-14 (quality of life) and a visual analog scale (pain). The latter two were the outcomes of interest and were administered in the first 24 h after root canal treatment. The data were submitted to descriptive analysis, bivariate analysis, Poisson univariate and multiple regression, and Spearman's correlation test, with a 5% significance level. RESULTS A greater frequency of impact after treatment was found for the items 'uncomfortable to eat food' and 'felt self-conscious'. No significant difference between groups was found regarding the severity of impact for total OHIP-14 score or any of the domain scores. CONCLUSIONS The two root canal preparation systems exerted a similar impact on quality of life. Postoperative pain was correlated with impact on quality of life, affecting chewing function, self-consciousness and stress. Thus, it is important for dentists to provide care capable of preventing or treating the negative consequences of such therapy.
Detection of novel germline mutations in six breast cancer predisposition genes by targeted next‐generation sequencing

In this study, a customized amplicon‐based target sequencing panel was designed to enrich the whole exon regions of six genes associated with the risk of breast cancer. Targeted next‐generation sequencing (NGS) was performed for 146 breast cancer patients (BC), 71 healthy women with a family history of breast cancer (high risk), and 55 healthy women without a family history of cancer (control). Sixteen possible disease‐causing mutations on four genes were identified in 20 samples. The percentages of possible disease‐causing mutation carriers in the BC group (8.9%) and in the high‐risk group (8.5%) were higher than that in the control group (1.8%). The BRCA1 possible disease‐causing mutation group had a higher prevalence in family history and triple‐negative breast cancer, while the BRCA2 possible disease‐causing mutation group was younger and more likely to develop axillary lymph node metastasis (P < 0.05). Among the 146 patients, 47 with a family history of breast cancer were also sequenced with another 14 moderate‐risk genes. Three additional possible disease‐causing mutations were found on PALB2, CHEK2, and PMS2 genes, respectively. The results demonstrate that the six‐gene targeted NGS panel may provide an approach to assess the genetic risk of breast cancer and predict the clinical prognosis of breast cancer patients.
Prevalence of proximal ascending aorta and target organ damage in hypertensive patients: the multicentric ARGO-SIIA project (Aortic RemodellinG in hypertensiOn of the Italian Society of Hypertension)

Aim: The aim of this study was to assess the prevalence of ascending aortic dilatation and to evaluate the possible association between proximal aorta dilatation and structural or functional markers of cardiac organ damage in hypertensive patients. Background: Dilatation of the sinus of valsalva (SoV) is a common finding in clinical practice and it is associated with an increased cardiovascular risk in hypertensive patients: less is known about the dilatation prevalence of the subsequent portion, the proper ascending aorta and its relationship with cardiovascular organ damage. Methods: This multicentric study included 582 hypertensive and 104 normotensive control individuals. All individuals underwent clinical evaluation and two-dimensional transthoracic echocardiography focused on the evaluation of the aorta. Aortic diameters at three levels were measured: SoV, sinotubular junction and ascending aorta. Results: The prevalence of ascending aorta dilatation was 13%. Patients with ascending aorta dilatation were on average 10 years older than hypertensive patients without aortic dilatation and control individuals. Left ventricular mass was significantly increased (P < 0.0001) in patients with ascending aorta dilatation with (113.29 ± 3 g/m2) or without (109.16 ± 3 g/m2) SoV dilatation compared with patients with isolated SoV dilatation (98.80 ± 21.8 g/m2) or normal aorta (96.04 ± 26.5 g/m2), with left ventricular hypertrophy (LVH) being twice as common in this group compared with the latter (60 vs. 28%, P < 0.0001). Conclusion: Prevalence of ascending aorta dilatation in hypertensive patients reaches 13%. Hypertensive individuals with enlarged ascending aorta showed significantly increased left ventricular mass, a well known sign of hypertension related cardiac damage and could thus represent a subset of hypertensive patients at an increased cardiovascular risk.
Mobile Quantitative Colocalization Analysis of Fluorescence Microscopy Images

Understanding the nature of fluorescently‐labelled molecules requires proper quantification of their colocalization. We developed a new approach to enable quantification of colocalization of markers in fluorescence microscopy images using mobile computers. It consists of three interacting components: desktop computer – cloud – mobile device. After an image is opened on a desktop computer, it is then saved to the cloud and becomes available to a mobile device. Functionality of the desktop and mobile software consists of the same steps and therefore allows using any of the platforms when performing analysis. Changes of the state of the image between devices are synchronized via the cloud, so that nothing is lost when switching them. All interactions are performed seamlessly in the background and do not require any input from the researchers’ side. This approach augments access to analytical imaging by allowing to work in completely new ways with superior levels of control, simplicity, and convenience. © 2018 by John Wiley & Sons, Inc.
Peptide Nucleic Acid Probe-Based Analysis as a New Detection Method for Clarithromycin Resistance in Helicobacter pylori

Background/Aims Helicobacter pylori eradication rates are decreasing because of increases in clarithromycin resistance. Thus, finding an easy and accurate method of detecting clarithromycin resistance is important. Methods We evaluated 70 H. pylori isolates from Korean patients. Dual-labeled peptide nucleic acid (PNA) probes were designed to detect resistance associated with point mutations in 23S ribosomal ribonucleic acid gene domain V (A2142G, A2143G, and T2182C). Data were analyzed by probe-based fluorescence melting curve analysis based on probe-target dissociation temperatures and compared with Sanger sequencing. Results Among 70 H. pylori isolates, 0, 16, and 58 isolates contained A2142G, A2143G, and T2182C mutations, respectively. PNA probe-based analysis exhibited 100.0% positive predictive values for A2142G and A2143G and a 98.3% positive predictive value for T2182C. PNA probe-based analysis results correlated with 98.6% of Sanger sequencing results (κ-value=0.990; standard error, 0.010). Conclusions H. pylori clarithromycin resistance can be easily and accurately assessed by dual-labeled PNA probe-based melting curve analysis if probes are used based on the appropriate resistance-related mutations. This method is fast, simple, accurate, and adaptable for clinical samples. It may help clinicians choose a precise eradication regimen.
Elimination of Mitochondrial DNA from Mammalian Cells

To cope with DNA damage, mitochondria developed a pathway by which severely damaged or unrepairable mitochondrial DNA (mtDNA) molecules are abandoned and degraded, and new molecules are resynthesized using intact templates, if available. In this unit, we describe a method that harnesses this pathway to completely eliminate mtDNA from mammalian cells by transiently overexpressing the Y147A mutant of human uracil‐N‐glycosylase (mUNG1). We also provide an alternate protocol for mtDNA depletion using combined treatment with ethidium bromide (EtBr) and dideoxycytidine (ddC). Support protocols detail approaches for (1) genotyping ρ° cells of human, mouse, and rat origin by PCR; (2) quantitation of mtDNA by quantitative PCR (qPCR); and (3) preparation of calibrator plasmids for mtDNA quantitation. © 2018 by John Wiley & Sons, Inc.
Why is measuring communication difficult? A critical review of current speech pathology concepts and measures

ABSTRACT Human society is organised through communicative interactions between co-present people. Speech pathology (SP) assessment and intervention strategies aim to access these sites of communication in order to facilitate participation in life situations for people with communication disorders. Surprisingly, however, there is no explicit theory of communication underpinning SP practice and research. As a result, the conceptual and practical basis for rigorous, empirical measurement of communication remains limited, which is a significant challenge for professional practice and research. This critical review discusses the prevailing ways that co-present communication has been conceptualised and measured in SP. In particular, we examine how models of health have informed current ideas and measurement practices. We argue that although patently valuable for SP, they are largely incommensurate with the realities of co-present communication. Drawing on current empirical research in Sociology and Linguistics, we specify the properties of real-time co-present communication and discuss their relationship to current SP concepts and measurement practices. We conclude by suggesting directions for conceptual development and empirical research that will draw SP assessment and intervention strategies closer to real-time co-present communication.
The terpenoid backbone biosynthesis pathway directly affects the biosynthesis of alarm pheromone in the aphid

The terpenoid backbone biosynthesis pathway is responsible for the synthesis of different backbones for terpenoids; (E)‐β‐farnesene (EβF), a sesquiterpene, is the major component of aphid alarm pheromone. Our previous studies eliminated the possibility of host plants and endosymbionts as the sources of EβF, and we thus speculate that the terpenoid pathway might affect the biosynthesis of EβF in aphids. First, the transcriptional responses of four genes encoding farnesyl diphosphate synthase (FPPS), geranylgeranyl diphosphate synthase (GGPPS) and decaprenyl diphosphate synthase in the cotton aphid Aphis gossypii to simulated stimulation were analysed using quantitative real‐time PCR, showing an immediate decrease in the transcript abundances of the four genes. Next, RNA‐interference‐mediated gene knockdown was performed, indicating that fpps knockdown caused a significant cost in terms of body size and fecundity. Finally, an association analysis of gene knockdown with the amount of EβF was conducted, revealing that the concentration of EβF per milligram of aphid was drastically decreased in response to fpps knockdown, whereas ggpps knockdown significantly raised the concentration of EβF. Our data support a peculiar mode of biosynthesis and storage of the aphid alarm pheromone that relies directly on the terpenoid backbone biosynthesis pathway in the aphid.
Region Convolutional Features for Multi-Label Remote Sensing Image Retrieval

Conventional remote sensing image retrieval (RSIR) systems usually perform single-label retrieval where each image is annotated by a single label representing the most significant semantic content of the image. This assumption, however, ignores the complexity of remote sensing images, where an image might have multiple classes (i.e., multiple labels), thus resulting in worse retrieval performance. We therefore propose a novel multi-label RSIR approach with fully convolutional networks (FCN). In our approach, we first train a FCN model using a pixel-wise labeled dataset,and the trained FCN is then used to predict the segmentation maps of each image in the considered archive. We finally extract region convolutional features of each image based on its segmentation map.The region features can be either used to perform region-based retrieval or further post-processed to obtain a feature vector for similarity measure. The experimental results show that our approach achieves state-of-the-art performance in contrast to conventional single-label and recent multi-label RSIR approaches.
Abbreviated dignity therapy for adults with advanced-stage cancer and their family caregivers: Qualitative analysis of a pilot study

Abstract Objective Dignity therapy (DT) is designed to address psychological and existential challenges that terminally ill individuals face. DT guides patients in developing a written legacy project in which they record and share important memories and messages with those they will leave behind. DT has been demonstrated to ease existential concerns for adults with advanced-stage cancer; however, lack of institutional resources limits wide implementation of DT in clinical practice. This study explores qualitative outcomes of an abbreviated, less resource-intensive version of DT among participants with advanced-stage cancer and their legacy project recipients. Method Qualitative methods were used to analyze postintervention interviews with 11 participants and their legacy recipients as well as the created legacy projects. Direct content analysis was used to assess feedback from the interviews about benefits, barriers, and recommendations regarding abbreviated DT. The legacy projects were coded for expression of core values. Result Findings suggest that abbreviated DT effectively promotes (1) self-expression, (2) connection with loved ones, (3) sense of purpose, and (4) continuity of self. Participants observed that leading the development of their legacy projects promoted independent reflection, autonomy, and opportunities for family interaction when reviewing and discussing the projects. Consistent with traditional DT, participants expressed “family” as the most common core value in their legacy projects. Expression of “autonomy” was also a notable finding. Significance of results Abbreviated DT reduces resource barriers to conducting traditional DT while promoting similar benefits for participants and recipients, making it a promising adaptation warranting further research. The importance that patients place on family and autonomy should be honored as much as possible by those caring for adults with advanced-stage cancer.
Antioxidation and Melanogenesis Inhibition of Various Dendrobium tosaense Extracts

This study investigated the polyphenol content, antioxidant activity, and inhibition ability of mushroom tyrosinase and melanogenesis of Dendrobium tosaense (DT) extract. Ground DT was extracted using deionized water (W) or 50% ethanol (50E) at room temperature (RT) or 50 °C (50T) for 20 min. The 50T + 50E extract exhibited the highest total phenol content 47.0 ± 4.0 mg gallic acid equivalent/g DT extract, the highest level of 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) free-radical scavenging 66.0 ± 3.0 mg Trolox equivalent/g DT extract, and the highest reducing power 12.00 ± 0.50 mg vitamin C equivalent/g DT extract. The RT + W extract had the highest total flavonoid content 110.0 ± 3.0 mg quercetin equivalent/g DT extract. The RT + 50E extract had the lowest half maximal inhibitory concentration 1.30 ± 0.00 mg/mL for 2,2-diphenyl-1-picrylhydrazyl free-radical scavenging, and the lowest half maximal inhibitory concentration 6.40 ± 0.30 mg/mL for mushroom tyrosinase inhibition activity. DT extracts, especially RT + W and 50T + W, exhibited potent inhibitory effects on melanogenesis of B16/F10 cells. These results demonstrated the application potential of DT extract for skincare.
Immunotherapy for melanoma

Immunotherapy for the treatment of advanced melanoma has become a primary treatment in the clinic. Current therapies include systemic cytokines, immune checkpoint inhibitors, and localized intratumoral therapies. Checkpoint inhibitors block natural pathways that dampen or inhibit an immune response to stimulus. These pathways include programmed cell death 1 receptor/programmed death-ligand 1 and cytotoxic T lymphocyte antigen-4. Systemic immunotherapies have proven to be effective in clinical trials both as monotherapy and in combination therapy. Oncolytic viruses are used to treat tumor locally and induce an effective immune response. Although some immune-mediated adverse events have been shown to occur with immunotherapy and may cause disease through systemic immune activation, most symptoms are mild to moderate. Overall immunotherapy in advanced melanoma has provided effective and durable responses to treat patients with advanced melanoma.