Miracle-dz/UniFAR-FTUs huggingface dataset:
Replication Study: Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia

In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Fung et al., 2015), that described how we intended to replicate selected experiments from the paper "Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia" (Dawson et al., 2011). Here, we report the results of those experiments. We found treatment of MLL-fusion leukaemia cells (MV4;11 cell line) with the BET bromodomain inhibitor I-BET151 resulted in selective growth inhibition, whereas treatment of leukaemia cells harboring a different oncogenic driver (K-562 cell line) did not result in selective growth inhibition; this is similar to the findings reported in the original study (Figure 2A and Supplementary Figure 11A,B; Dawson et al., 2011). Further, I-BET151 resulted in a statistically significant decrease in BCL2 expression in MV4;11 cells, but not in K-562 cells; again this is similar to the findings reported in the original study (Figure 3D; Dawson et al., 2011). We did not find a statistically significant difference in survival when testing I-BET151 efficacy in a disseminated xenograft MLL mouse model, whereas the original study reported increased survival in I-BET151 treated mice compared to vehicle control (Figure 4B,D; Dawson et al., 2011). Differences between the original study and this replication attempt, such as different conditioning regimens and I-BET151 doses, are factors that might have influenced the outcome. We also found I-BET151 treatment resulted in a lower median disease burden compared to vehicle control in all tissues analyzed, similar to the example reported in the original study (Supplementary Figure 16A; Dawson et al., 2011). Finally, we report meta-analyses for each result. DOI: http://dx.doi. org/10.7554/eLife.25306. 001
Divine targets: youth at the centre of Catholic and Pentecostal responses to HIV and AIDS in Brazil

This study explored the focus on youth in Catholic and Evangelical Pentecostal discussions about and responses to HIV and AIDS in Brazil. Key informant, oral history and in-depth interviews revealed a disconnect between young people's views of themselves as leaders in their religious institutions' responses to HIV and other social problems, and adult religious leaders' views of young people as vulnerable and in need of being ‘saved’. Religious leaders presented young people as institutional commodities, emphasizing their symbolic value as signs of the health and future of their churches. We explore the unofficial exchange between religious institutions and young people, who benefited from the leadership opportunities and communities provided by their churches and youth groups. We discuss the political economy of youth in religious institutions' responses to HIV and AIDS within the context of Brazil's high levels of religious mobility as well as the broader, global commodification of spirituality and religion.
Clinical and virological implications of A1846T and C1913A/G mutations of hepatitis B virus genome in severe liver diseases

Abstract Objective: Mutations occurring within different genes of hepatitis B virus (HBV) genome may have different clinical implications. This study aimed to observe the clinical and virological implications of the A1846T and C1913A/G mutations of HBV genome in the development and treatment outcome of severe liver diseases, which has not been previously determined. Materials and methods: A total of 438 cases of patients with liver diseases were retrospectively reviewed, including 146 with mild chronic hepatitis B infection (CHB-M), 146 with severe chronic hepatitis B infection (CHB-S), and 146 with acute-on-chronic liver failure (ACLF). Partial or full-length HBV genome was directly sequenced. Replicons containing A1846T, C1913A or other mutant sequences, or the wild-type counterparts were constructed respectively, and then transfected into HepG2 cells for phenotype analysis. Results: There was significant difference in the detection rates of A1846T (30.82%, 40.41% and 55.48%, respectively) and C1913A/G (15.52%, 28.77%, and 35.62%, respectively) among patients with CHB-M, those with CHB-S, and those with ACLF (p < .01). A1846T was significantly associated with the mortality of ACLF patients within six months after the disease onset (OR 1.704, p = .041). In vitro experiment revealed that A1846T mutant resulted in 3.20-fold and 1.85-fold increase of replication capacity and promoter activity, respectively compared with wild type counterpart (p < .001), while C1913A led to a significant decrease of core protein expression (p < .05). Conclusion: Occurrence of A1846T and C1913A is positively associated with clinical presentations of severe liver disease. A1846T mutation is significantly associated with poor prognosis of ACLF.
5-HT2A Agonists: A Novel Therapy for Functional Neurological Disorders?

Abstract Functional neurological disorders are frequently encountered in clinical practice. They have a poor prognosis and treatment options are limited. Their etiology is unknown, but leading theories propose a disturbance of somatic self-representation: the mind perceives dysfunction of a body region despite intact motor and sensory pathways. Central to this model is the concept of an abnormal top-down cognitive influence upon sensorimotor function. There is growing interest in the use of 5-HT2A agonists in the management of neuropsychiatric conditions. Recent studies have shown that these agents induce changes in neural activity that disrupt hierarchical brain dynamics and modulate networks subserving self-related processing. Converging evidence suggests they may hold unique therapeutic potential in functional neurological disorders. This is of importance given the considerable personal and societal burden of this condition and we argue a clinical trial to test this hypothesis is warranted.
Effects of kanamycin administration to poultry on the interspecies transmission of drug-resistant Salmonella.

Three experiments were conducted to assess the relationship between antibiotic administration to poultry and the transmission of drug-resistant Salmonella through a simulated food chain. Poults were inoculated per os with either multiply drug-resistant Escherichia coli and drug-sensitive S. typhimurium or with multiply drug-resistant S. typhimurium. One-half of the poults inoculated with drug-sensitive S. typhimurium and all poults given drug-resistant S. typhimurium received kanamycin in their drinking water. Liver tissue from these poults was incorporated into diets fed to rats, half of which were treated with kanamycin. Antibiotic administration to the poults was associated with a significantly (P less than .05) higher frequency of transmission of drug-resistant S. typhimurium to the rats through the simulated food chain. S. typhimurium was isolated only from rats treated with kanamycin. The highest frequency of isolation of drug-resistant S. typhimurium from rats (40%) was observed in kanamycin-treated rats fed a diet containing liver from kanamycin-treated poults. Results of this experiment indicate that antibiotic administration can increase the frequency of transmission of drug-resistant Salmonella through the food chain.
Building IoT Services for Aging in Place Using Standard-Based IoT Platforms and Heterogeneous IoT Products

An aging population and human longevity is a global trend. Many developed countries are struggling with the yearly increasing healthcare cost that dominantly affects their economy. At the same time, people living with old adults suffering from a progressive brain disorder such as Alzheimer’s disease are enduring even more stress and depression than those patients while caring for them. Accordingly, seniors’ ability to live independently and comfortably in their current home for as long as possible has been crucial to reduce the societal cost for caregiving and thus give family members peace of mind, called ‘aging in place’ (AIP). In this paper we present a way of building AIP services using standard-based IoT platforms and heterogeneous IoT products. An AIP service platform is designed and created by combining previous standard-based IoT platforms in a collaborative way. A service composition tool is also created that allows people to create AIP services in an efficient way. To show practical usability of our proposed system, we choose a service scenario for medication compliance and implement a prototype service which could give old adults medication reminder appropriately at the right time (i.e., when it is time to need to take pills) through light and speaker at home but also wrist band and smartphone even outside the home.
Gating of remote effects on lightness Dipartimento

In various versions of the dungeon illusion (P. Bressan, 2001), we show that grouping between targets and contextual disks determines whether remote luminances affect target lightness or not. In the dungeon illusion, target disks surrounded by contextual disks contrast with them rather than with the immediate background. We formally establish the existence of this illusion and show that it reverses when the luminance of the targets is either lower (double decrement) or higher (double increment) than the luminances of both the background and the contextual disks rather than in between them. On the basis of the double-anchoring theory of lightness (P. Bressan, 2006a), we predict and show that grouping gates the effects of remote luminances in such a way that they go in opposite directions in the double-decrement and double-increment inverted-dungeon illusions. Our results support the double-anchoring theory and demonstrate that luminances that are far away from the targets are irrelevant in some conditions but critical in others.
Connexin-dependent intercellular stress signaling in tissue homeostasis and tumor development.

Cellular stress responses determine tissue development, homeostasis and pathogenesis. Paracrine signaling, exchange of mechanical stimuli and intercellular transfer of small metabolites via connexin-built gap junctional channels are involved in the cellular stress detection and propagation of stress stimuli in multicellular networks. Cellular stress responses are also regulated through the activity of unpaired connexons (hemichannels) and via the intracellular interference of connexins with the cell cycle and pro-apoptotic machinery. Therefore, connexins are considered as multidirectional transmitters of the "outside-in" and "inside-out" stress signaling that are crucial for tissue homeostasis, regeneration and pathology. In particular, the disturbance of connexin function during the multi-stage process of tumor development leads to abnormal reactions of tumor cells to stress stimuli. In this review, we outline the current knowledge on the multidirectional role of connexins in the detection of stress signals. We also discuss the role of connexin-mediated intercellular transmittance of stress signals in tumour promotion, progression and metastatic cascade. HIGHLIGHTS 1. Connexins and gap junctions protect cells from the microenvironmental stress and are involved in propagation and intracellular processing of stress signals. 2. The quality and quantity of stress stimuli, which may lead to cell adaptation or death by apoptosis, is determined by intrinsic properties of connexins and the cell phenotype. 3. Connexin deficiency increases the resistance of tumor cells to the "outside-in" stress signaling. 4. The connexin-mediated "inside-out" stress signaling participates in tumor cell invasion during the metastatic cascade.
A systematic review of treatment modalities for primary basal cell carcinomas.

OBJECTIVE To systematically review the literature for studies reporting on recurrence rates of basal cell carcinomas (BCCs) after different therapies. DESIGN We reviewed all studies published in English, French, German, Dutch, Spanish, or Italian between 1970 and 1997 that prospectively examined recurrence rates for at least 50 patients with primary BCCs observed for at least 5 years after treatment with Mohs micrographic surgery, surgical excision, curettage and electrodesiccation, cryosurgery, radiotherapy, immunotherapy with interferon or fluorouracil, or photodynamic therapy. SETTING Department of Dermatology, University Hospital Maastricht, Maastricht, the reference center for dermatologic oncology and Mohs micrographic surgery in the Netherlands. MAIN OUTCOME MEASURES The recurrence rates after different therapies for BCCs, resulting in the development of guidelines for the treatment of these disorders. RESULTS Of 298 studies found in several electronic databases, only 18 met the requirements and could be used for analysis. Tumors treated with Mohs micrographic surgery show the lowest recurrence rates after 5 years, followed in order by those treated with surgical excision, cryosurgery, and curettage and electrodesiccation. CONCLUSIONS Recurrence rates for different therapies could not be compared because of a lack of uniformity in the method of reporting, so evidence-based guidelines could not be developed. We surmise that Mohs micrographic surgery should be used mainly for larger, morphea-type BCCs located in danger zones. For smaller BCCs of the nodular and superficial types, surgical excision remains the first treatment of choice. Other treatment modalities can be used in patients in whom surgery is contraindicated. Immunotherapy and photodynamic therapy are still investigative.
Genetic Population Structure of Dastarcus helophoroides (Coleoptera: Bothrideridae) From Different Long-Horned Beetle Hosts Based on Complete Sequences of Mitochondrial COI

Abstract Dastarcus helophoroides (Fairmaire) (Coleoptera: Bothrideridae) is an important natural enemy of long-horned beetles in China, Japan, and Korea. In this study, the genetic sequence of cytochrome oxidase subunit I was used to investigate the genetics and relationships within and among D. helophoroides populations collected from five different geographic locations. We used principal component analysis, heatmap, and Venn diagram results to determine the relationship between haplotypes and populations. In total, 26 haplotypes with 51 nucleotide polymorphic sites were defined, and low genetic diversity was found among the different populations. Significant genetic variations were observed mainly within populations, and no correlation was found between genetic distribution and geographical distance. Low pairwise fixation index values (–0.01424 to 0.04896) and high gene flows show that there was high gene exchange between populations. The codistributed haplotype DH01 was suggested to be the most ancestral haplotype, and other haplotypes were thought to have evolved from it through several mutations. In four of the populations, both common haplotypes (DH01, DH03, and DH22) and unique haplotypes were found. Low genetic diversity among different populations is related to a relatively high flight capacity, host movement, and human-aided dispersal of D. helophoroides. The high gene exchange and typically weak population genetic structure among five populations, especially among populations of Anoplophora glabripennis (Motschulsky), Monochamus alternatus (Hope), and Massicus raddei (Blessig), may suggest that these populations cross naturally in the field.
Action Anticipation: Reading the Intentions of Humans and Robots

Humans have the fascinating capacity of processing nonverbal visual cues to understand and anticipate the actions of other humans. This “intention reading” ability is underpinned by shared motor repertoires and action models, which we use to interpret the intentions of others as if they were our own. We investigate how different cues contribute to the legibility of human actions during interpersonal interactions. Our first contribution is a publicly available dataset with recordings of human body motion and eye gaze, acquired in an experimental scenario with an actor interacting with three subjects. From these data, we conducted a human study to analyze the importance of different nonverbal cues for action perception. As our second contribution, we used motion/gaze recordings to build a computational model describing the interaction between two persons. As a third contribution, we embedded this model in the controller of an iCub humanoid robot and conducted a second human study, in the same scenario with the robot as an actor, to validate the model's “intention reading” capability. Our results show that it is possible to model (nonverbal) signals exchanged by humans during interaction, and how to incorporate such a mechanism in robotic systems with the twin goal of being able to “read” human action intentionsand acting in a way that is legible by humans.
Nanocrystal: a novel approach to overcome skin barriers for improved topical drug delivery

ABSTRACT Introduction: Skin is an important route of drug delivery for the treatment of various dermatological conditions. The advent of nanotechnology is paving the roadmaps for topical drug delivery by providing sustained release as well as maintaining a localized effect, outweighing the toxicity concern. Area covered: This review highlighted the morphology of skin, its barrier nature as well as drug penetration pathways after topical application of formulations. The existing methods to improve topical drug delivery, by infringing or permeating the skin barriers, are discussed. This context concretes the foundation to accentuate the need for the development of nanocrystal-based topical formulation. The mechanism of drug release, immediate as well as sustained release, after topical administration of drug nanocrystals is also elaborated. The special emphasis is given on the breakthrough achieved, in topical drug delivery using drug nanocrystals, so far in the plethora of literature, patents, and products, under clinical trial as well as in the market. Expert opinion: The current research on nanocrystals for topical drug delivery is highlighting the breakthroughs achieved so far. The output of these research envisages that topical nanocrystals based formulations can be a novel strategy for the drugs which are facing solubility, bioavailability and toxicity concerns.
In vivo nuclear magnetic resonance spectroscopy of chicken embryos from two broiler strains of varying fat content.

In vivo nuclear magnetic resonance (NMR) imaging and spectroscopy techniques were used to monitor changes in P- and H-containing molecules in embryos of two broiler strains (30 and 31) differing genetically in fat content and ranging in age from 0 to 20 days of incubation. Chemical analysis showed that Strain 30 has more carcass fat than Strain 31 at market age (7 wk). Proton (1H) and 31P spectra were obtained on four eggs per strain at Days 0, 2, 4, 6, 8, 11, 12, 14, 16, 17, 19, and 20 of incubation. Fat:water, phosphomonoester (PME):phosphodiester (PDE), and adenosine triphosphate (ATP):PDE ratios were calculated. Chicks were hatched, grown to market weight (2,000 g for females and 2,300 g for males at 7 wk), and the whole intact carcasses were analyzed for crude fat. Hydrogen-1 NMR spectroscopy studies of incubated eggs indicated no significant difference (P > .05) in the fat:water ratio between the two strains. The difference in the PME:PDE ratios between the two strains as obtained by 31P-NMR spectroscopy over all days of incubation analyzed was not significant (P > .05); however, there was a significant difference in this ratio between the two strains at Days 4, 6, and 11. Up to Day 16, Strain 30 had a slightly, but not significantly (P > .05), higher ATP:PDE ratio as shown on 31P-NMR spectra, whereas after Day 17 the ATP:PDE ratio was significantly higher (P < .01) for Strain 31. Strain 31 birds had a significantly lower (P < .05) crude fat content. There was a significant difference (P < .05) in 7-wk carcass fat content between sexes, males having significantly (P < .01) less fat than females, which was correlated with a significantly higher (P < .01) ATP:PDE ratio in male embryos. It might be possible to use ATP:PDE ratios obtained during embryonic development by 31P-NMR to select strains of birds for low fat content at market weight and to distinguish between sexes during late embryonic development.
POPE—a tool to aid high-throughput phylogenetic analysis

Summary: POPE (Phylogeny, Ortholog and Paralog Extractor) provides an integrated platform for automatic ortholog identification. Intermediate steps can be visualized, modified and analyzed in order to assess and improve the underlying quality of orthology and paralogy assignments. Availability: POPE is available for download from the website: http://www.well.ox.ac.uk/~tota/pope. Contact: tota@well.ox.ac.uk
Characterization of the discriminative stimulus effects of 3,4-methylenedioxypyrovalerone in male Sprague-Dawley rats

Recreational use of 3,4-methylenedioxypyrovalerone (MDPV) in the early 2000s prompted numerous scientific investigations of its behavioral and neurochemical effects. The purpose of this study was to further characterize the interoceptive stimulus effects of MDPV using a validated in-vivo drug-detection assay. Male Sprague-Dawley rats were trained to discriminate 0.3 mg/kg MDPV from saline under a fixed ratio 20 (FR 20) schedule of food reinforcement. After stimulus control was established with MDPV (∼35 training sessions), substitution tests were commenced with drugs from several chemical classes, including drugs with predominantly dopaminergic actions [MDPV, D-amphetamine, (+)-methamphetamine, (−)-cocaine], drugs with predominantly serotonergic actions [(+)-lysergic acid diethylamide, (+)-fenfluramine], and drugs with both serotonergic and dopaminergic actions (3,4-methylenedioxymethamphetamine, 4-methylmethcathinone). Full substitution for the 0.3 mg/kg MDPV cue was observed with D-amphetamine, (+)-methamphetamine, and (−)-cocaine. Surprisingly, the 5-HT releaser (+)-fenfluramine fully substituted in half the subjects, but completely suppressed responding in the remaining subjects. 3,4-Methylenedioxymethamphetamine, 4-methylmethcathinone, and (+)-lysergic acid diethylamide failed to fully substitute for MDPV. These results indicate that the MDPV cue is similar to cues produced by drugs with predominantly dopamine-increasing effects and perhaps serotonin-releasing effects among individual subjects. Given these findings, further research is warranted to directly assess the contributions of dopamine and serotonin receptor isoforms to the discriminative stimulus functions of MDPV.
Self-emulsifying tablets of Ibuprofen: Design, optimization and evaluation

Self-emulsifying tablets were formulated with the objective of enhancing the bioavailability of nonsteroidal anti-inflammatory drug, ibuprofen. Isotropic mixture of oil, surfactant was used to design the formulations. Goat fat and tween60 admixture was employed to formulate Self-emulsifying tablets (SETs). Different formulations were developed with varying composition of oil and surfactant by melt granulation technique and optimized. Resultant SETs were evaluated for weight variation, liquefaction time and drug content. The dissolution studies of ibuprofen from the SETs were determined in simulated gastric fluid without pepsin. Weight uniformity and absolute drug content was observed within the range in case of formulations made of admixtures of high proportion of tween60 and low content of goat fat. Liquefaction time determined was high but there was an every chance of reduction in liquefaction time due to gastric motility. Maximum drug release was shown for the formulations having high amount of tween60 and low content of goat fat. Dissolution studies revealed remarkable increase in release of the drug as compared to the standard drug. Results obtained indicated that ibuprofen could be conveniently administered in the form of SETs containing goat fat and tween60 admixtures.