Miracle-dz/UniFAR-FTUs huggingface dataset:
Tuberculosis peer educators: personal experiences of working with socially excluded communities in London.

SETTING Peer education is a relatively unexplored intervention for tuberculosis (TB) control, particularly among socially excluded communities. In London, peer educators are used to raise awareness of TB and promote uptake of radiological screening among people using homeless and/or drug and alcohol treatment services. OBJECTIVE To understand the motivation and personal impact of being a peer educator on people with experience of anti-tuberculosis treatment, homelessness and addiction. DESIGN In-depth semi-structured interviews with peer educators were recorded and transcribed, and then analysed using a grounded theory approach to identify themes. Reflexivity and thick description were used to support transparency of findings. RESULTS Becoming a peer educator supports individuals in making sense of past experiences and renewing their sense of self. The role places value on personal experience and the communication approach this supports. The project environment is an important motivator, providing the peer with structure, social support and respect. CONCLUSION Being a peer educator with experience of homelessness and addiction can be beneficial and empowering and help long-term recovery. Peers are an underused resource for strengthening TB control among socially excluded populations. There is a need for further research into the contribution of peers to TB control, including analyses of economic effectiveness.
Motor Experience Influences Object Knowledge

An object’s perceived readiness-for-action (e.g., its size, the degree of rotation from its canonical position, the user’s viewpoint) can influence semantic knowledge retrieval. Yet, the organization of object knowledge may also be affected by body-specific sensorimotor experiences. Here, we investigated whether people’s history of performing motor actions with their hands influences the knowledge they store and retrieve about graspable objects. We compared object representations between healthy right- and left-handers (Experiment 1), and between unilateral stroke patients, whose motor experience was changed by impairment of either their right or left hand (Experiment 2). Participants saw pictures of graspable everyday items with the handles oriented toward either the left or right hand, and they generated the type of grasp they would employ (i.e., clench or pinch) when using each object, responding orally. In both experiments, hand dominance and object orientation interacted to predict response times. In Experiment 1, judgments were fastest when objects were oriented toward the right hand in right-handers, but not in left-handers. In Experiment 2, judgments were fastest when objects were oriented toward the left hand in patients who had lost the use of their right hand, even though these patients were right-handed prior to brain injury. Results suggest that at least some aspects of object knowledge are determined by motor experience, and can be changed by new patterns of motor experience. People with different bodily characteristics, who interact with objects in systematically different ways, form correspondingly different neurocognitive representations of the same common objects.
Effects of new beta-type Ti-40Nb implant materials, brain-derived neurotrophic factor, acetylcholine and nicotine on human mesenchymal stem cells of osteoporotic and non osteoporotic donors

Introduction Treatment of osteoporotic fractures is still challenging and an urgent need exists for new materials, better adapted to osteoporotic bone by adjusted Young’s modulus, appropriate surface modification and pharmaceuticals. Materials and methods Titanium-40-niobium alloys, mechanically ground or additionally etched and titanium-6-aluminium-4-vanadium were analyzed in combination with brain-derived neurotrophic factor, acetylcholine and nicotine to determine their effects on human mesenchymal stem cells in vitro over 21 days using lactate dehydrogenase and alkaline phosphatase assays, live cell imaging and immunofluorescence microscopy. Results Cell number of human mesenchymal stem cells of osteoporotic donors was increased after 14 d in presence of ground titanium-40-niobium or titanium-6-aluminium-4-vanadium, together with brain-derived neurotrophic factor. Cell number of human mesenchymal stem cells of non osteoporotic donors increased after 21 d in presence of titanium-6-aluminium-4-vanadium without pharmaceuticals. No significant increase was measured for ground or etched titanium-40-niobium after 21 d. Osteoblast differentiation of osteoporotic donors was significantly higher than in non osteoporotic donors after 21 d in presence of etched, ground titanium-40-niobium or titanium-6-aluminium-4-vanadium accompanied by all pharmaceuticals tested. In presence of all alloys tested brain-derived neurotrophic factor, acetylcholine and nicotine increased differentiation of cells of osteoporotic donors and accelerated it in non osteoporotic donors. Conclusion We conclude that ground titanium-40-niobium and brain-derived neurotrophic factor might be most suitable for subsequent in vivo testing.
Racioethnic Differences in Human Posterior Scleral and Optic Nerve Stump Deformation

Purpose The purpose of this study was to quantify the biomechanical response of human posterior ocular tissues from donors of various racioethnic groups to better understand how differences in these properties may play a role in the racioethnic health disparities known to exist in glaucoma. Methods Sequential digital image correlation (S-DIC) was used to measure the pressure-induced surface deformations of 23 normal human posterior poles from three racioethnic groups: African descent (AD), European descent (ED), and Hispanic ethnicity (HIS). Regional in-plane principal strains were compared across three zones: the optic nerve stump (ONS), the peripapillary (PP) sclera, and non-PP sclera. Results The PP scleral tensile strains were found to be lower for ED eyes compared with AD and HIS eyes at 15 mm Hg (P = 0.024 and 0.039, respectively). The mean compressive strains were significantly higher for AD eyes compared with ED eyes at 15 mm Hg (P = 0.018). We also found that the relationship between tensile strain and pressure was significant for those of ED and HIS eyes (P < 0.001 and P = 0.004, respectively), whereas it was not significant for those of AD (P = 0.392). Conclusions Our results suggest that, assuming glaucomatous nerve loss is caused by mechanical strains in the vicinity of the optic nerve head, the mechanism of increased glaucoma prevalence may be different in those of AD versus HIS. Our ONS strain analysis also suggested that it may be important to account for ONS geometry and material properties in future scleral biomechanical analysis.
Anti-Inflammatory Activity and Structure-Activity Relationships of Brominated Indoles from a Marine Mollusc

Marine molluscs are rich in biologically active natural products that provide new potential sources of anti-inflammatory agents. Here we used bioassay guided fractionation of extracts from the muricid Dicathais orbita to identify brominated indoles with anti-inflammatory activity, based on the inhibition of nitric oxide (NO) and tumour necrosis factor α (TNFα) in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages and prostaglandin E2 (PGE2) in calcium ionophore-stimulated 3T3 ccl-92 fibroblasts. Muricid brominated indoles were then compared to a range of synthetic indoles to determine structure-activity relationships. Both hypobranchial gland and egg extracts inhibited the production of NO significantly with IC50 of 30.8 and 40 μg/mL, respectively. The hypobranchial gland extract also inhibited the production of TNFα and PGE2 with IC50 of 43.03 µg/mL and 34.24 µg/mL, respectively. The purified mono-brominated indole and isatin compounds showed significant inhibitory activity against NO, TNFα, and PGE2, and were more active than dimer indoles and non-brominated isatin. The position of the bromine atom on the isatin benzene ring significantly affected the activity, with 5Br > 6Br > 7Br. The mode of action for the active hypobranchial gland extract, 6-bromoindole, and 6-bromoisatin was further tested by the assessment of the translocation of nuclear factor kappa B (NFκB) in LPS-stimulated RAW264.7 mouse macrophage. The extract (40 µg/mL) significantly inhibited the translocation of NFκB in the LPS-stimulated RAW264.7 macrophages by 48.2%, whereas 40 µg/mL of 6-bromoindole and 6-bromoistain caused a 60.7% and 63.7% reduction in NFκB, respectively. These results identify simple brominated indoles as useful anti-inflammatory drug leads and support the development of extracts from the Australian muricid D. orbita, as a new potential natural remedy for the treatment of inflammation.
Chk1 and DNA-PK mediate TPEN-induced DNA damage in a ROS dependent manner in human colon cancer cells

ABSTRACT Recently, we showed that the metal chelator TPEN targets colon cancer cells through redox cycling of copper. Here, we studied the DNA damage potential of TPEN and deciphered the role of Chk1, ATM and DNA-PK in TPEN-induced toxicity in 3 human colon cancer cell lines, HCT116, SW480 and HT29. We also investigated the role of reactive oxygen species (ROS) in TPEN-induced DNA damage. TPEN reduced cell viability in a dose- and time-dependent manner. Cytotoxicity was associated with significant DNA damage and higher expression of γ-H2AX protein and activation of ATM/ATR signaling pathway. Cell death by TPEN was dependent on ROS generation as evidenced by the reversal of cell viability, and DNA damage and the abrogation of γ-H2AX levels in the presence of antioxidants. Treatment with antioxidants, however, failed to reverse cytotoxicity at high TPEN concentrations (10µM). TPEN-induced cell death was also dependent on the redox cycling of copper since the copper chelator neocuproine inhibited DNA damage and reduced pChk1, γ-H2AX, and ATM protein expression. Cell death by low TPEN concentrations, involved ATM/ATR signaling in all 3 cell lines, since pre-incubation with specific inhibitors of ATM and DNA-PK led to the recovery of cells from TPEN-induced DNA damage. In addition, siRNA silencing of Chk1, DNA-PK and ATM abrogated the expression of γ-H2AX and reversed cell death, suggesting that Chk1 and DNA-PK mediate TPEN-induced cytotoxicity in colon cancer cells. This study shows for the first time the involvement of Chk1, DNA-PK and ATM in TPEN-induced DNA damage and confirms our previous findings that ROS generation and the redox cycling of copper in response to TPEN are the main mechanisms by which this compound induces cell death in human colon cancer cells. Inhibition of ATM or DNA-PK did not reverse cytotoxicity at high TPEN concentrations that cause excessive levels of ROS and irreversible cellular damage.
The neuroendocrine phenotype, genomic profile and therapeutic sensitivity of GEPNET cell lines

Experimental models of neuroendocrine tumour disease are scarce, and no comprehensive characterisation of existing gastroenteropancreatic neuroendocrine tumour (GEPNET) cell lines has been reported. In this study, we aimed to define the molecular characteristics and therapeutic sensitivity of these cell lines. We therefore performed immunophenotyping, copy number profiling, whole-exome sequencing and a large-scale inhibitor screening of seven GEPNET cell lines. Four cell lines, GOT1, P-STS, BON-1 and QGP-1, displayed a neuroendocrine phenotype while three others, KRJ-I, L-STS and H-STS, did not. Instead, these three cell lines were identified as lymphoblastoid. Characterisation of remaining authentic GEPNET cell lines by copy number profiling showed that GOT1, among other chromosomal alterations, harboured losses on chromosome 18 encompassing the SMAD4 gene, while P-STS had a loss on 11q. BON-1 had a homozygous loss of CDKN2A and CDKN2B, and QGP-1 harboured amplifications of MDM2 and HMGA2. Whole-exome sequencing revealed both disease-characteristic mutations (e.g. ATRX mutation in QGP-1) and, for patient tumours, rare genetic events (e.g. TP53 mutation in P-STS, BON-1 and QGP-1). A large-scale inhibitor screening showed that cell lines from pancreatic NETs to a greater extent, when compared to small intestinal NETs, were sensitive to inhibitors of MEK. Similarly, neuroendocrine NET cells originating from the small intestine were considerably more sensitive to a group of HDAC inhibitors. Taken together, our results provide a comprehensive characterisation of GEPNET cell lines, demonstrate their relevance as neuroendocrine tumour models and explore their therapeutic sensitivity to a broad range of inhibitors.
The Obligate Human Pathogen, Neisseria gonorrhoeae, Is Polyploid

We show using several methodologies that the Gram-negative, diplococcal-bacterium Neisseria gonorrhoeae has more than one complete genome copy per cell. Gene dosage measurements demonstrated that only a single replication initiation event per chromosome occurs per round of cell division, and that there is a single origin of replication. The region containing the origin does not encode any genes previously associated with bacterial origins of replication. Quantitative PCR results showed that there are on average three genome copies per coccal cell unit. These findings allow a model for gonococcal DNA replication and cell division to be proposed, in which a minimum of two chromosomal copies exist per coccal unit within a monococcal or diplococcal cell, and these chromosomes replicate in unison to produce four chromosomal copies during cell division. Immune evasion via antigenic variation is an important mechanism that allows these organisms to continually infect a high risk population of people. We propose that polyploidy may be necessary for the high frequency gene conversion system that mediates pilin antigenic variation and the propagation of N. gonorrhoeae within its human hosts.
Sympathetic neurovascular regulation during pregnancy: A longitudinal case series study

What is the main observation in this case? The main observation of this case report is that during pregnancy there is a progressive sympatho‐excitation in basal conditions and under stress, which is offset by a concurrent reduction in neurovascular transduction. Strong correlations between autonomic nervous system activity and sex hormones (oestrogen and progesterone), vasopressin and aldosterone were found. What insights does it reveal? Our findings suggest that hormonal surges might be associated with central sympathetic activation.
DeepRoad: GAN-based Metamorphic Autonomous Driving System Testing

While Deep Neural Networks (DNNs) have established the fundamentals of DNN-based autonomous driving systems, they may exhibit erroneous behaviors and cause fatal accidents. To resolve the safety issues of autonomous driving systems, a recent set of testing techniques have been designed to automatically generate test cases, e.g., new input images transformed from the original ones. Unfortunately, many such generated input images often render inferior authenticity, lacking accurate semantic information of the driving scenes and hence compromising the resulting efficacy and reliability. In this paper, we propose DeepRoad, an unsupervised framework to automatically generate large amounts of accurate driving scenes to test the consistency of DNN-based autonomous driving systems across different scenes. In particular, DeepRoad delivers driving scenes with various weather conditions (including those with rather extreme conditions) by applying the Generative Adversarial Networks (GANs) along with the corresponding real-world weather scenes. Moreover, we have implemented DeepRoad to test three well-recognized DNN-based autonomous driving systems. Experimental results demonstrate that DeepRoad can detect thousands of behavioral inconsistencies in these systems.
Assessment of risk and prophylaxis for deep vein thrombosis and pulmonary embolism in medically ill patients during their early days of hospital stay at a tertiary care center in a developing country

Aim Deep vein thrombosis (DVT) and pulmonary thromboembolism (PE) are important causes of morbidity and mortality in medically ill patients. This study was done to assess risk factors and prophylaxis given for DVT and PE in newly admitted medically ill patients during the first two weeks of their hospital stay at a tertiary care center hospital in India. Methods All patients within one week of their admission in intensive care unit (ICU) and wards were enrolled in the study after an informed written consent. Patients who had DVT prophylaxis within the past month or any contraindications for DVT prophylaxis were excluded. A structured proforma was designed and effective risk stratification for DVT was done. Patients were followed for up to two weeks to record any changes in the risk categories and document any signs of PE or DVT if present. Any prophylaxis given for DVT or PE was noted. Results Seventy-five percent of patients had the highest risk for DVT and PE. Only 12.5% had DVT prophylaxis within the first two days of admission. Within two weeks of admission, 30.8% of patients were discharged, and 16.2% died. 72.6% of the patients still in the wards belonged to the highest risk category. Clinical signs and symptoms of DVT and PE were present in 25.8% and 9.8% of patients, respectively after the second week of admission. 86% of symptomatic patients belonged to the highest risk category initially and none of them received any prophylaxis. 21.6% of the highest risk category patients died within two weeks of their admission. A statistically significant correlation was found between mortality and risk score of the patients for DVT and between lack of prophylaxis and mortality (p < 0.05). Conclusion A significant risk for DVT and PE exists in medically ill patients, but only a small proportion of the patients are given prophylaxis. This study underlines the need to aggressively implement DVT risk stratification strategy in medical patients and provide prophylaxis unless contraindicated.
Cutaneous fungal microbiome: Malassezia yeasts in seborrheic dermatitis scalp in a randomized, comparative and therapeutic trial

ABSTRACT Malassezia spp in skin microbiome scalp has been implicated in seborrheic dermatitis pathogenesis. Thus, treatment based in antifungal combined to topical keratolitic agents have been indicated as well as oral isotretinoin as it reduces the sebum production, glandular's size and possesses anti-inflammatory properties. This randomized, comparative and therapeutic trial aimed toper form the genotypic identification of Malassezia species before and after low-dose oral isotretinoin or topical antifungal treatments for moderate to severe seborrhea and/or seborrheic dermatitis on scalp. Scales and sebum of the scalp were seeded in the middle of modified Dixon and incubated at 32°C. For genotypic identification polymerase chain reaction primers for the ITS and D1/D2 ribossomal DNA were used and followed by samples sequencing. The procedure was conducted before and after therapeutic and randomized intervention for moderate to severe seborrhea/seborrheic dermatitis on the scalp, including oral isotretinoin, 10 mg, every other day and anti-seborrheic shampoo (piroctone olamine), over six months. The M. globosa and M. restricta were the most frequent species isolated on the scalp before and after both treatments. Other non-Malassezia species were also identified. The Malassezia spp. were maintained in the scalp after both treatments that were equally effective for the control of seborrhea/seborrheic dermatitis clinical signs.
Autism Spectrum Disorder: From Pensieve to Crystal Ball

Abstract In the next decade, professionals in communication sciences and disorders will encounter a wealth of needs, opportunities, and challenges in research and practice related to autism spectrum disorder. What lies ahead will reflect both transformations of and continuities with past perspectives (psychodynamic, biological, and learning theory). Among our largest challenges as individuals and as a discipline will be to determine the most important needs to address and the most productive opportunities to seize. Interprofessional collaboration, community engagement, and partnerships among researchers, practitioners, and community stakeholder are all strategies that can better guide our selection of priorities.
On the Relation Between SIM and IND-RoR Security Models for PAKEs

Password-based Authenticated Key-Exchange (PAKE) protocols allow users, who need only to share a password, to compute a high-entropy shared session key despite passwords being taken from a dictionary. Security models for PAKE protocols aim to capture the desired security properties that such protocols must satisfy when executed in the presence of an active adversary. They are usually classified into i) indistinguishabilitybased (IND-based) or ii) simulation-based (SIM-based). The relation between these two security notions is unclear and mentioned as a gap in the literature. In this work, we prove that SIM-BMP security from Boyko et al. (EUROCRYPT 2000) implies IND-RoR security from Abdalla et al. (PKC 2005) and that IND-RoR security is equivalent to a slightly modified version of SIM-BMP security. We also investigate whether IND-RoR security implies (unmodified) SIM-BMP security.
Role of immune factors in angiotensin II-induced hypertension and renal damage in Dahl salt-sensitive rats.

The present study assessed the importance of immunity in angiotensin (ANG) II (5 ng·kg-1·min-1 iv)-mediated hypertension in Dahl salt-sensitive (SS) rats and SS rats deficient in T and B lymphocytes (SSRag1-/-) fed a 0.4% NaCl diet. Baseline mean arterial blood pressure (MAP) was not different between groups. ANG II infusion significantly increased MAP in both groups, although MAP increased more rapidly in SS rats, and the maximal MAP achieved was significantly greater in SS than SSRag1-/- rats (190 ± 3 vs. 177 ± 3 mmHg) after 12 days. Renal damage, as assessed by albumin excretion rate, was significantly increased after 12 days of ANG lI infusion in SS (from 32 ± 4 to 81 ± 9 mg/day) and SSRag1-/- (from 12 ± 2 to 51 ± 8 mg/day) rats; albumin excretion rate was significantly different between SS and SSRag1-/- rats at all points measured. After 9 days of recovery from ANG II, MAP was decreased to a greater extent in SSRag1-/- than SS rats (143 ± 5 vs. 157 ± 8 mmHg) compared with the peak MAP during ANG II infusion. At this same time point, albumin excretion rate was significantly lower in SSRag1-/- than SS rats (42 ± 8 vs. 66 ± 7 mg/day). Further studies demonstrated an increase in CD45+ total leukocytes, CD11b/c+ macrophages/monocytes, and CD3+ T cells in kidneys of ANG II- compared with vehicle-treated SS rats. The present data suggest that infiltrating T cells in the kidney exacerbate renal damage in ANG II-induced hypertension in SS rats maintained on a 0.4% NaCl diet, similar to results observed with a salt stimulus in SS rats.
Interpreting focus

Although it is widely agreed, if often only tacitly, that there is a close connection between focus and presupposition, recent research has tended to shy away from the null hypothesis, which is that focus is systematically associated with presupposition along the following lines: The Background-Presupposition Rule (BPR) Whenever focusing gives rise to a background λx. φ(x), there is a presupposition to the effect that λx. φ(x) holds of some individual. This paper aims to show, first, that the evidence in favour of the BPR is in fact rather good, and attempts to clarify its role in the interpretation of focus particles like ‘only’ and ‘too’, arguing that unlike the former the latter is focus-sensitive in an idiosyncratic way, adding its own interpretative constraints to those of the BPR. The last part of the paper discusses various objections that have been raised against the BPR, taking a closer look at the peculiarities of ‘nobody’ and ‘somebody’, and comparing the interpretative effects of focusing with those of it-clefts.