Miracle-dz/UniFAR-FTUs huggingface dataset:
Controversies in oncology: are genomic tests quantifying homologous recombination repair deficiency (HRD) useful for treatment decision making?

Mechanisms that protect DNA are crucial to preserve the genome integrity from injuries produced by environmental agents or those spontaneously generated during DNA metabolism.1 DNA single-strand breaks (SSBs) are repaired by mismatch repair (MMR), base excision repair (BER) and nucleotide excision repair (NER). 1 Non-homologous end joining (NHEJ) or homologous recombination repair (HRR) processes double-strand breaks (DSBs). 1 While NHEJ solves DSBs in a potentially inaccurate way, HRR is an error-free pathway that restores the genomic sequence of the broken DNA ends by using the sister chromatid as template for repair.1 Several proteins are involved in the HRR pathway: some of them act as sensors of DSBs such as γH2AX, ATM and ATR, leading to the activation of signal mediator proteins (ie, BRCA1, BRCA2 and PALB2). The final event of the HRR pathway is the loading of a small nuclear protein called RAD51 onto single-stranded DNA, where it promotes strand invasion and replication fork stabilisation (figure 1). 2 Tumours with HRR deficiency (HRD) were described for the first time in cancers that harbour germline mutations of the tumour suppressors BRCA1 and BRCA2 (BRCA1/2 ). 3 Nonetheless, genetic and epigenetic events can also result in inactivation of other HRR components, leading to HRD in sporadic cancers.3 Figure 1 Homologous recombination pathway. Adapted from De Picciotto et al. 50 HRD is harboured by approximately 13% and 15% of ovarian and triple negative breast cancers (TNBC), respectively, and it is attributable to germline BRCA1/2 ( gBRCA1/2 ) mutations.4 5 Furthermore, 50% and 40% of ovarian and TNBC, respectively, are characterised by harbouring HRD in the absence of gBRCA1/2 mutations.4 6 Also, 10%–12% of advanced prostate cancer harbour germline or somatic BRCA2 inactivation and up to 25% contain a DNA repair defect.7 As HRR is required for the repair of DSBs …
The Role of Digital Engagement in the Self-Management of Type 2 Diabetes

ABSTRACT Mobile tablet devices and applications have the potential to help type 2 diabetes patients in the self-management of their disease. However, users must be equipped with an appropriate level of digital literacy in order to use the tools and technologies effectively. This study reports from an exploratory mobile health (mHealth) pilot program that was conducted at a large, local clinic in Canberra, Australia. The research team provided digital training and support opportunities to participants as part of the longitudinal study. The aim of the research project was to examine the diverse range of participant digital literacy and how it impacted on self-management and the adoption of mHealth. Mid-study results from online surveys conducted at 2 and 5 months after enrolling 28 participants in the pilot program revealed that digital engagement is crucial to the patients’ participation in mHealth activities. Support, by way of digital training, was essential to the patients’ sustainable use of the devices and applications for health care.
Identification and cloning of a novel heterogeneous nuclear ribonucleoprotein C-like protein that functions as a transcriptional activator of the hepatitis B virus enhancer II

Liver specificity of hepatitis B virus (HBV) replication has been attributed to the action of its second enhancer (EII). We report here the characterization of EII and the subsequent isolation of a novel liver-specific DNA-binding protein which binds to and activates EII. The cDNA clone of the protein, designated E2BP, was isolated from a lambda gt11 expression library constructed from the hepatoma cell line HuH-6 which was screened with a binding site probe derived from EII. Sequence analysis of E2BP revealed 86.6% homology with a rat heterogeneous nuclear ribonucleoprotein C protein sequence, while conformational studies suggest a helix-loop-helix motif as a DNA-binding site. Cloned E2BP expressed in human fibroblasts by transient transfection displayed EII binding and activating characteristics similar to those of native E2BP in hepatocytes.
Correlation of the One‐Minute Apgar Score and the pH Value of Umbilical Arterial Blood

ABSTRACT: The one-minute Apgar score, proven useful for rapid assessment of the neonate, is often poorly correlated with other indicators of intrauterine well-being. Fetal asphyxia is directly associated with neonatal acidosis. A low Apgar score in the face of normal pH and base deficit does not, therefore, indicate an asphyxiated infant. We performed a study at Vanderbilt University Hospital to ascertain the feasibility of combining the pH value of umbilical arterial blood with the one-minute Apgar score for neonatal assessment. The pH values and Apgar scores were obtained on 172 singleton neonates. When the Apgar score was <7, over one half (56%) of the neonates had a normal pH value. Of this group 46% had undergone intubation and nasopharyngeal suctioning, procedures known to be associated with lowered Apgar scores. We recommend, therefore, that neonates with a one-minute Apgar score of <7 be further evaluated with umbilical arterial blood gas studies to ascertain the prsence of acidosis and to differentiate between metabolic and respiratory acidosis. More precise confirmation of the diagnosis of fetal distress and neonatal asphyxia, for both treatment and medicolegal purposes, is possible with this information.
Essential Oils from Different Plant Parts of Eucalyptus cinerea F. Muell. ex Benth. (Myrtaceae) as a Source of 1,8-Cineole and Their Bioactivities

Eucalyptus cinerea, known as silver dollar tree, has few descriptions in traditional medicine. Chemical composition and antimicrobial properties of the essential oils of leaves, flowers and fruits, collected seasonally, were determined by GC/MS and disk diffusion/MIC, respectively. 1,8-Cineole was the main compound, particularly in fresh leaves—Spring (74.98%), dried leaves—Spring (85.32%), flowers—Winter (78.76%) and fruits—Winter (80.97%). Other compounds were found in the aerial parts in all seasons: α-pinene (2.41% to 10.13%), limonene (1.46% to 4.43%), α-terpineol (1.73% to 11.72%), and α-terpinyl acetate (3.04% to 20.44%). The essential oils showed antimicrobial activities against bacteria and yeasts, with the best results being found for the dried autumn and winter leaves oils (MIC < 0.39 mg/mL) against Streptococcus pyogenes. For the other tested microorganisms the following MIC results were found: Staphylococcus aureus— Dried leaves oil from summer (0.78 mg/mL), Pseudomonas aeruginosa—Flowers oil from autumn and fruits oil from winter (1.56 mg/mL) and Candida albicans—Flowers oil from autumn and fruits oils from winter and spring (0.78 mg/mL).
Malaria Prevalence, Indoor Residual Spraying, and Insecticide-Treated Net Usage in Sub-Saharan Africa

This paper examines the extent to which bed net usage is responsive to changes in malaria prevalence and whether indoor residual spraying crowds out bed net usage. We show that malaria prevalence increases the probability of sleeping under an insecticide treated net but the implied elasticities are below one. For children under five, a one percentage point increase in malaria prevalence increases the probability of sleeping under a bed net by 0.41 percentage point. We find that indoor residual spraying does not crowd out bed net usage. Instead, children under five who live in houses that were recently sprayed are 3.1 percentage points more likely to sleep under a bed net.
Evaluation of Linear and Nonlinear Site Effects for the MW 6.3, 2009 L’Aquila Earthquake

An effective strategy for the seismic risk mitigation needs the use of advanced seismological methodologies for a realistic estimate of the seismic hazard and, consequently, to reduce earthquake damage through a preventive evaluation of vulnerability and actions for structure safety. Prediction of earthquakes and their related effects (expressed in terms of ground shaking) can be performed either by a probabilistic approach or by using modelling tools based, on one hand, on the theoretical knowledge of the physics of the seismic source and of wave propagation and, on the other hand, on the rich database of geological, tectonic, historical information already available. Strong earthquakes are very rare phenomena and it is therefore statistically very difficult to assemble a representative database of recorded strong motion signals that could be analyzed to define ground motion parameters suitable for seismic hazard estimations. That is, the probabilistic estimation of the seismic hazard is a very gross approximation, and often a severe underestimation, of reality. A realistic and reliable estimate of the expected ground motion can be performed by using the Neo-Deterministic Seismic Hazard Analysis (NDSHA), an innovative modelling technique that takes into account source, propagation and local site effects (for a recent review see Panza et al., 2011). This is done using basic principles of physics about wave generation and propagation in complex media, and does not require to resort to convolutive approaches, that have been proven to be quite unreliable, mainly when dealing with complex geological structures, the most interesting from the practical point of view. The NDSHA approach has been used, among others, in the framework of the UNESCOIUGS-IGCP project 414 "Seismic Ground Motion in Large Urban Areas", to evaluate ground motion of a group of Large Urban Areas and Megacities in the world representative of a broad spectrum of seismic hazard severity (Panza et al., 2004). A MW 6.3 earthquake struck on 6 April 2009, at 01.32 GMT, the Abruzzo region (central Italy). The L’Aquila town, located few km northeast to the main shock epicentre, and several villages located nearby, suffered heavy damages and the casualties were about 300. The damage level generally corresponded to intensity ≤ VIII MCS, with few maximum values ≥
The role of sex, executive functioning, and perceptions of safety on urban adolescent substance use

Abstract Background: Perceptions of safety within one’s activity space (commonly frequented locations) reduces risk for adolescent substance use. Less is known about urban adolescents’ neuropsychological vulnerabilities to substance use and how these may interact with activity space risk. Questions regarding how male and female adolescents respond to these interactions have yet to be sufficiently studied. Method: To examine these interactions, we conducted a moderated moderation analysis with a sample of 194 adolescents to determine whether executive functioning moderated the influence of activity space risk on substance use, and if this moderation varied by sex. Results: Results indicate that adolescents with low levels of executive functioning were more sensitive to dangerous activity spaces and had more substance use compared to adolescents with higher levels of executive functioning. Males were more vulnerable to substance use when they felt unsafe in their activity spaces; whereas for females, their perceptions of activity space risk was not associated with substance use. Conclusion: For these adolescents, executive functioning’s moderation of the effect of activity space risk on substance use, is conditional on sex. Understanding the interaction of executive functioning, activity space, and sex could be useful for contextually sensitive substance use interventions with urban youth.
After a Stroke

The benefits of exercise and rehabilitation after stroke are well-known. A regimen of exercise after stroke helps to improve strength and balance. These benefits have both short-term and long-term effects: people function much better in the long run if they have had a focused, challenging course of rehabilitation. The lead author of an article published in this issue of Neurology®, Dr. Julie Bernhardt, had reported in 2017 on the benefits of beginning exercise within 7 days after stroke.1 In the article appearing in this issue, “Fatal and Nonfatal Events Within 14 Days After Early, Intensive Mobilization Poststroke,”2 Dr. Julie Bernhardt and her colleagues tried to answer a simple question: Are there any concerns that arise if a person recovering from a stroke begins an exercise regimen that starts within 24 hours after the stroke?
A Temporal Transcriptional Map of Human Natural Killer Cell Differentiation

Natural killer cell repertoires are functionally diversified as a result of differentiation, homeostatic receptor-ligand interactions and adaptive responses to viral infections. However, the regulatory gene-circuits that define the manifold cell states and drive NK cell differentiation have not been clearly resolved. Here, we performed single-cell RNA sequencing of 26,506 cells derived from sorted phenotypically-defined human NK cell subsets to delineate a tightly coordinated differentiation process from a small population of CD56bright precursors to adaptive NKG2C+ CD56dim NK cells. RNA velocity analysis identified a clear directionality in the transition from CD56bright to CD56dim NK cells, which was dominated by genes involved in transcription and translation as well as acquisition of NK cell effector function. Gene expression trends mapped to pseudotime, defined by increasing entropy, identified three distinct transcriptional checkpoints, reflecting important changes in regulatory gene-circuits. The CD56bright NK cell population dominated pseudotime with two distinct checkpoints separating precursors from intermediate states that gradually took on transcriptional signatures similar to CD56dim NK cells. The final checkpoint occurred during late terminal differentiation of CD56dim NK cells and was associated with unique divergent gene-expression trends. Furthermore, we utilized this single-cell RNA sequencing resource to decipher the regulation of genes involved in lysosomal biogenesis and found a coordinated gradual increase in the RAB4 and BLOC1S gene families with differentiation into CD56dim NK cells. These results identify important gene programs driving functional diversification and specialization during NK cell differentiation and hold potential to guide new strategies for NK cell-based cancer immunotherapy.
PLAG1 activation in lipoblastoma coinciding with low-level amplification of a derivative chromosome 8 with a deletion del(8)(q13q21.2)

Lipoblastoma is a benign uncommon soft-tissue-tumor resembling fetal adipose tissue affecting mainly children under three years of age. In lipoblastoma, the typical cytogenetic changes are clonal rearrangements involving chromosomal region 8q11→q13. The oncogene PLAG1 (pleomorphic adenoma gene 1) is located within this chromosomal region on band 8q12. Recent reports have demonstrated that in lipoblastoma, the PLAG1 gene is activated by ‘promoter-swapping’. Herein, we demonstrate that in lipoblastoma, the PLAG1 gene may also be activated by low-level amplification. We report on a lipoblastoma with the karyotype 48∼50,XX,del(8)(q13q21.2),+del(8)(q13q21.2)×4[cp12]. Subsequent FISH analysis on uncultured tumor cells confirmed this result and demonstrated a low-level amplification of the chromosomal region 8pter→8q13 and 8q21.2→8qter. A partial monosomy was seen for the chromosomal region 8q13→8q21.2. No other gains or losses were observed by CGH analysis. RT-PCR analysis showed that the PLAG1 gene is activated in the tumor sample of the lipoblastoma analyzed, in contrast to normal fatty tissue without PLAG1 expression. In conclusion, our results demonstrate that low-level amplification is a further mechanism of PLAG1 activation in lipoblastomas.
Research Commentary - The New Organizing Logic of Digital Innovation: An Agenda for Information Systems Research

In this essay, we argue that pervasive digitization gives birth to a new type of product architecture: the layered modular architecture. The layered modular architecture extends the modular architecture of physical products by incorporating four loosely coupled layers of devices, networks, services, and contents created by digital technology. We posit that this new architecture instigates profound changes in the ways that firms organize for innovation in the future. We develop (1) a conceptual framework to describe the emerging organizing logic of digital innovation and (2) an information systems research agenda for digital strategy and the creation and management of corporate information technology infrastructures.
Iodide benzamides for the in-vivo detection of melanoma and metastases

The aim of this work was to synthesize, label and evaluate in vivo [131I]N-(2-diethylaminoethyl)-3-iodo-4-methoxybenzamide ([131I]IMBA) as a radiotracer for B16-F0 melanoma cells, in C57 mice bearing a subcutaneous melanoma tumour and experimentally induced lung metastases. The average radio-iodination yield achieved, after labelling and Sep-Pak purification, was 65%, with a radiochemical purity of ≥96%. Biodistribution studies using [131I]IMBA (2.2 GBq/μmol) showed high specific tumour uptake, with low non-target tissue background, due to a rapid renal clearance from the animal body (corporal retention was 19.7±7.1% of the injected dose at 6 h and 4.00±2.4% of the injected dose at 24 h). The very high targeting efficiency of this radiopharmaceutical was also confirmed by images in which primary subcutaneous tumour and induced lung metastases were clearly visualized. In addition, a clear correlation was found between the uptake of radioactivity in the lungs (percentage of the injected dose per gram of tissue) and the number of metastases carried by them.
Does the Quality of the Working Alliance Predict Treatment Outcome in Online Psychotherapy for Traumatized Patients?

Background The provision of online counseling and online therapy is steadily increasing. The results of a number of controlled trials investigating the efficacy of online approaches indicate that some of these new treatment alternatives might indeed be effective. Yet, little is known about how the therapeutic relationship (or working alliance) evolves over the Internet and whether it influences treatment outcome as it does in traditional face-to-face therapy. The working alliance has been defined as the extent to which a patient and a therapist work collaboratively and purposefully and connect emotionally. Objective The aim of the study was to investigate the quality and predictive relevance of the therapeutic alliance for patients receiving a short-term, Internet-based, cognitive-behavioral therapy program for posttraumatic stress reactions. Methods After rigorous screening for exclusion criteria of high dissociative tendencies, risk of psychosis, and suicidal tendencies, 48 patients, who had experienced a traumatic event in the past, were included in the online treatment study. The short form of the Working Alliance Inventory (WAI-S) was administered at the fourth treatment session. The relevance of the therapeutic relationship for treatment outcome was assessed in terms of residual gain from pretreatment assessment to the end of treatment. The revised Impact of Event Scale (IES-R) and the depression and anxiety subscales of the Brief Symptom Inventory (BSI) were used to assess treatment outcome. Results A total of 48 participants were included in the analysis. Overall, high alliance scores were found. In contrast to previous studies of conventional face-to-face therapy, there was only a low to modest association (.13 to .33) between the quality of the therapeutic relationship and treatment outcome. Conclusion High alliance scores indicate that it was possible to establish a stable and positive therapeutic relationship online. However, the therapeutic relationship was found to be a less relevant predictor of the therapy outcome than in face-to-face approaches. We discuss whether this finding can be attributed to methodological reasons such as the restricted range of alliance ratings obtained or the time of administration of the WAI-S, or whether the therapeutic relationship might be less relevant to the treatment outcome of online therapy approaches.
(Re)introducing embodied practical understanding to the sociology of sustainable consumption

In this article, we argue that the sociology of sustainable consumption has had a strong focus on practical understandings embedded in material entities and thereby also on the role of the material for the reproduction and change of sustainable consumption practices. Consequently, the role of social relations and practical understandings embodied in humans has been downplayed. We give two possible explanations to this rather one-sided focus; first, a general focus within social sciences on rethinking the role of the material in the wake of the cultural turn and second, engagement with science and technology studies. In this article, we use Bourdieu’s theoretical framework and his concept of habitus to (re)introduce embodied practical understandings to the sociology of sustainable consumption. By showing interconnections between the perspective focusing on practical understandings embodied in systems of dispositions and the perspective focusing on practical understandings embedded in systems of material entities, the article provides a basis for applying both perspectives to better understand the complexity of sustainable consumption practices and how they reproduce and change. Accordingly, we encourage more studies focusing on how sustainable consumption practices reproduce and transmit through social interaction.
A Nonparametric Procedure for Defining a New Humoral Immunologic Profile in a Pilot Study on HIV Infected Patients

This work aims at identifying a set of humoral immunologic parameters that improve prediction of the activation process in HIV patients. Starting from the well-known impact of humoral immunity in HIV infection, there is still a lack of knowledge in defining the role of the modulation of functional activity and titers of serum antibodies from early stage of infection to the development of AIDS. We propose an integrated approach that combines humoral and clinical parameters in defining the host immunity, implementing algorithms associated with virus control. A number of humoral parameters were simultaneously evaluated in a whole range of serum samples from HIV-positive patients. This issue has been afforded accounting for estimation problems typically related to “feasibility” studies where small sample size in each group and large number of parameters are jointly estimated. We used nonparametric statistical procedures to identify biomarkers in our study which included 42 subjects stratified on five different stages of HIV infection, i.e., Elite Controllers (EC), Long Term Non Progressors (LTNP), HAART, AIDS and Acute Infection (AI). The main goal of the paper is to illustrate a novel profiling method for helping to design a further confirmatory study. A set of seventeen different HIV-specific blood humoral factors were analyzed in all subjects, i.e. IgG and IgA to gp120IIIB, to gp120Bal, to whole gp41, to P1 and T20 gp41 epitopes of the MPER-HR2 region, to QARILAV gp41 epitope of the HR1 region and to CCR5; neutralization activity against five different virus strains and ADCC were also evaluated. Patients were selected on the basis of CD4 cell counts, HIV/RNA and clinical status. The Classification and Regression Trees (CART) approach has been used to uncover specific patterns of humoral parameters in different stages of HIV disease. Virus neutralization of primary virus strains and antibodies to gp41 were required to classify patients, suggesting that clinical profiles strongly rely on functional activity against HIV.