Miracle-dz/UniFAR-FTUs huggingface dataset:
Haematopoietic development and leukaemia in Down syndrome

Children with constitutional trisomy 21 (cT21, Down Syndrome, DS) are at a higher risk for both myeloid and B‐lymphoid leukaemias. The myeloid leukaemias are often preceded by a transient neonatal pre‐leukaemic syndrome, Transient Abnormal Myelopoiesis (TAM). TAM is caused by cooperation between cT21 and acquired somatic N‐terminal truncating mutations in the key haematopoietic transcription factor GATA1. These mutations, which are not leukaemogenic in the absence of cT21, are found in almost one‐third of neonates with DS. Analysis of primary human fetal liver haematopoietic cells and of human embryonic stem cells demonstrates that cT21 itself substantially alters human fetal haematopoietic development. Consequently, many haematopoietic developmental defects are observed in neonates with DS even in the absence of TAM. Although studies in mouse models have suggested a pathogenic role of deregulated expression of several chromosome 21‐encoded genes, their role in human leukaemogenesis remains unclear. As cT21 exists in all embryonic cells, the molecular basis of cT21‐associated leukaemias probably reflects a complex interaction between deregulated gene expression in haematopoietic cells and the fetal haematopoietic microenvironment in DS.
Centers for Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines.

fective clinical management of STDs represent an important combined strategy necessary to improve reproductive and sexual health and to improve HIV prevention efforts. This is especially relevant to women, adolescents, and infants, because untreated infections frequently result in severe, long-term complications, including facilitation of HIV infection, tubal infertility, adverse pregnancy outcomes, and cancer. For >20 years, the publication of national guidelines by the Centers for Disease Control and Prevention
High sensitive C-reactive protein in acute ischemic stroke and its short term Prognostic significance : A study from rural hospital

1 Professor, Department of Medicine, Adichunchanagiri Institute of Medical Sciences, Balagangadharanatha Nagar, Nagamangala, Mandya -571448, India. 2 Associate Professor, Department of Medicine, Adichunchanagiri Institute of Medical Sciences, Balagangadharanatha Nagar, Nagamangala, Mandya -571448, India. 3 3rd Year Resident Department of Medicine, Adichunchanagiri Institute of Medical Sciences, Balagangadharanatha Nagar, Nagamangala, Mandya571448, India.
Probiotics‐impregnated bedding covers for house dust mite allergic rhinitis: A pilot randomized clinical trial

Upper Airways Research Laboratory, Ghent University, Ghent, Belgium Laboratory of Immunoregulation, VIB Inflammation Research Center, Ghent, Belgium Ghent University, Ghent, Belgium BekaertDeslee Innovation bvba, Waregem, Belgium Chrisal NV, Lommel, Belgium Devan Chemicals NV, Ronse, Belgium Department of Internal Medicine, Ghent University, Ghent, Belgium Clinical Immunology Research Lab, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
Organ-specific gene expression in the rhesus monkey eye following intravenous non-viral gene transfer.

PURPOSE The transfer of exogenous genes to the entire retina and other ocular structures is possible with a vascular route of gene delivery using a non-viral gene transfer method. The present studies examine the extent to which either beta-galactosidase or luciferase expression plasmids are targeted to the retina in the adult rhesus monkey following intravenous administration. In addition, these studies examine the pattern of organ expression of the transgene in the rhesus monkey depending on whether the plasmid is under the influence of a widely expressed promoter, the SV40 promoter, or an ocular-specific promoter, the opsin promoter. METHODS The plasmid DNA with either the SV40 or opsin promoter is encapsulated in the interior of 85 nm pegylated immunoliposomes (PILs), which are targeted across the blood-retinal barrier and into ocular cells with a monoclonal antibody to the human insulin receptor. Following a single intravenous injection of the PIL carrying the transgene, the animals were sacrificed 2, 7, or 14 days later for the measurement of beta-galactosidase or luciferase gene expression in the monkey eye and peripheral organs. RESULTS Histochemistry showed expression of the beta-galactosidase gene throughout the entire primate retina including the photoreceptor cells with either an SV40 or a bovine opsin promoter. Whereas the SV40 promoter enables gene expression in other organs of the primate (brain, liver, spleen), the opsin promoter restricted trans-gene expression to the primate eye, as there was no gene expressed in other organs. The retinal luciferase activity at 2 days after administration was 9.6+/-0.4 pg luciferase/mg protein, and at 14 days after administration was still comparable to maximal levels of luciferase gene expression in the mouse or rat. Confocal microscopy with antibodies to the insulin receptor and to beta-galactosidase demonstrated co-localization in the retina, with high expression of the trans-gene and the insulin receptor in the inner segments of the photoreceptor cells. CONCLUSIONS The PIL non-viral gene transfer technology makes possible adult transgenics in 24 h. Ectopic expression of exogenous genes in organs other than the target organ is made possible with the use of organ specific promoters, and gene expression in the primate is restricted to the eye when the trans-gene is under the influence of the opsin promoter. Plasmid-based gene expression is still in the therapeutic range for 2-3 weeks after a single intravenous administration. Exogenous genes are expressed throughout the entire primate retina following the delivery of the gene to the eye via a trans-vascular route.
Mobile mental health: Review of the emerging field and proof of concept study

Background The ubiquitous nature of mobile phones and their increasing functionality make them an ideal medium for the delivery of large-scale public health information and interventions. While mobile phones have been used to this end in behavioural and physical health settings, their role in monitoring and managing mental health is in its infancy. Aims The purpose of this paper is (1) to provide an overview of the field of mobile mental health and (2) by way of illustration, describe an initial proof of concept study carried out to assess the potential utility and effectiveness of a newly developed mobile phone and web-based program in the management of mild-to-moderate stress, anxiety and depression. Methods Over 6 weeks, participants were given access to “myCompass”: an interactive self-help program, which includes real-time self-monitoring with short message service prompts and brief online modules grounded in cognitive behavioural therapy. Results Preliminary analyses found that participants' symptoms of stress, anxiety, depression and overall psychological distress were significantly reduced after using myCompass. Improvements were also found in functional impairment and self-efficacy. Conclusions These preliminary results support the feasibility of implementing mobile phone-based interventions with the potential of improving psychological wellbeing.
Regulation of Type 1 Fimbriae by Unlinked FimB- and FimE-Like Recombinases in Uropathogenic Escherichia coli Strain CFT073

ABSTRACT Genomic DNA sequence analysis of the uropathogenic Escherichia coli strain CFT073 revealed that besides the fimB and fimE recombinase genes that control the type 1 pilus fim phase switch, there are three additional fimB- and fimE-like genes: ipuA, ipuB, and ipbA. Alignment of the predicted amino acid sequences showed that the five recombinases range in sequence similarity from 63 to 70%. An epidemiological survey indicates that ipuA and ipuB are present and linked next to the dsdCXA locus in 24 of 67 uropathogenic E. coli strains but are found in only 1 of 15 normal human fecal isolates. The ipbA sequence located next to the betABIT locus was found in 42 of 67 uropathogenic isolates and 8 of 15 of the commensal strains. We show that two of these recombinases, those encoded by ipuA and ipbA, can function at the type 1 pilus fim switch. In a CFT073 deletion mutant lacking all five recombinase genes, recombinant ipuA or ipbA provided in trans inverted the fim element from the off state to the on state. When a fim OFF CFT073 ΔfimBE mutant was used to infect the urinary tracts of mice, a switch to the fim on state was detected within 24 h in bacteria recovered from urine, the bladder, and the kidneys. A fim OFF CFT073 ΔfimBE ipuB ipbA mutant also demonstrated the ability to switch from the fim off state to the on state during mouse infection. CFT073 recombinase mutants derived from isolates in either the fim on or off state showed a reciprocal relationship for motility. Switches from a nonmotile to a motile phenotype and from a fim on to off genotype were observed in fim ON CFT073 ΔfimBE ipuAB ipbA mutants when ipuA or fimB was provided in trans. Together these results indicate that ipuA has fimB-like on-to-off and off-to-on fim switching activity and that ipbA has the ability to switch fim from the off to the on orientation.
Genomic profiling reveals distinctive molecular relapse patterns in IDH1/2 wild‐type glioblastoma

Molecular changes associated with the progression of glioblastoma after standard radiochemotherapy remain poorly understood. We compared genomic profiles of 27 paired primary and recurrent IDH1/2 wild‐type glioblastomas by genome‐wide array‐based comparative genomic hybridization. By bioinformatic analysis, primary and recurrent tumor profiles were normalized and segmented, chromosomal gains and losses identified taking the tumor cell content into account, and difference profiles deduced. Seven of 27 (26%) pairs lacked DNA copy number differences between primary and recurrent tumors (equal pairs). The recurrent tumors in 9/27 (33%) pairs contained all chromosomal imbalances of the primary tumors plus additional ones, suggesting a sequential acquisition of and/or selection for aberrations during progression (sequential pairs). In 11/27 (41%) pairs, the profiles of primary and recurrent tumors were divergent, i.e., the recurrent tumors contained additional aberrations but had lost others, suggesting a polyclonal composition of the primary tumors and considerable clonal evolution (discrepant pairs). Losses on 9p21.3 harboring the CDKN2A/B locus were significantly more common in primary tumors from sequential and discrepant (nonequal) pairs. Nonequal pairs showed ten regions of recurrent genomic differences between primary and recurrent tumors harboring 46 candidate genes associated with tumor recurrence. In particular, copy numbers of genes encoding apoptosis regulators were frequently changed at progression. In summary, approximately 25% of IDH1/2 wild‐type glioblastoma pairs have stable genomic imbalances. In contrast, approximately 75% of IDH1/2 wild‐type glioblastomas undergo further genomic aberrations and alter their clonal composition upon recurrence impacting their genomic profile, a process possibly facilitated by 9p21.3 loss in the primary tumor. © 2014 Wiley Periodicals, Inc.
Evaluation of rapid cell division in non‐uniform cell cycles

To better understand the mechanisms of development of harmful algal blooms (HABs), accurate estimates of species‐specific in situ growth rates are needed. HABs are caused by rapid cell division by the causative microorganisms. To accurately estimate the in situ growth rates of harmful algae having non‐uniform and/or irregular cell cycles, we modified a standard equation based on the cell cycle, and calculated the in situ growth rate to describe the process of bloom development in nature. Sampling of a developing bloom of Heterosigma akashiwo in Pohang Bay, Korea, was conducted every 3 h from 15:00 on August 2 to 07:00 on August 4, 2006. The amount of H. akashiwo DNA was measured using flow cytometry following tyramide signal amplification‐fluorescence in situ hybridization. On August 2, the percentage of G1 phase cells decreased from 15:00 to 19:00 then increased until 22:00; it then decreased until 07:00 on August 3, followed by an increase to 10:00. This indicates the ability of the cells in nature to undergo more than one round of division per day. During the following night two rounds of division did not occur. The in situ growth rates estimated using the modified equation ranged from 0.31 to 0.53 d−1. We conclude that the use of this equation enables more accurate estimates of bloom formation by rapidly dividing cells.
Enabling Patient Control of Personal Electronic Health Records Through Distributed Ledger Technology

The rise of distributed ledger technology, initiated and exemplified by the Bitcoin blockchain, is having an increasing impact on information technology environments in which there is an emphasis on trust and security. Management of electronic health records, where both conformation to legislative regulations and maintenance of public trust are paramount, is an area where the impact of these new technologies may be particularly beneficial. We present a system that enables fine-grained personalized control of third-party access to patients' electronic health records, allowing individuals to specify when and how their records are accessed for research purposes. The use of the smart contract based Ethereum blockchain technology to implement this system allows it to operate in a verifiably secure, trustless, and openly auditable environment, features crucial to health information systems moving forward.
Challenges Facing Nurses While Participating in Continuing Professional Development: A Case of Western Kenya

Background: The context of work for nurses is rapidly changing due to changes in care, innovative technologies, and emergence of new knowledge. Participation in Continuing Professional Development (CPD) in many countries in Africa remains low. Objective: The objective of the study was to explore the challenges facing Nurses while participating in CPD in Western Kenya. Methods: A descriptive cross- sectional study design was employed where 235 stratified and randomly selected nurses and four CPD Coordinators from four County Hospitals in Western Kenya were selected. The Key informants and the respondents for Focus Group Discussions were selected purposively. Data for this research was collected using a semi-structured questionnaire, interview schedules and Focus Group Discussion guide. Data analysis was done using statistical package for social sciences (SPSS V. 20). Data was summarized using frequencies; means and standard deviation. The data obtained was presented using percentage distributions, bar graphs and frequencies. Qualitative data was analysed thematically. Results: Majority of the nurses reported staff shortage 199 (85.8%), lack of time due to heavy workload 179 (77.2%) and lack of finance 137 (59.1%). Other challenges included: lack of information on availability of CPD (35.8%), family commitment (28.9%), lack of interest (15.1%) and distance (27.2%). Findings from FGDs showed similar results; staff shortage and heavy workload were cited as major challenges hindering nurse’s participation in CPDs. Key informants reported, lack of written policies for CPD, lack of available guidelines for CPD and lack of coordination with other CPD coordinators either at County level or at National level. Conclusion and Recommendations: The main challenges highlighted by nurses were:-staff shortages, lack of time due to heavy workload, lack of finances, night shift and lack of information on the availability of CPD. Key informants highlighted:- lack of written policies for CPD, lack of available guidelines for CPD, lack of coordination with other CPD coordinators. The study recommends employing more nurses, formulating policies affecting CPD and providing financial support to help support CPD activities. Coordinators should organize favorable time and space for CPD activities while ensuring equal opportunities are offered for participation and there is need for coordination with other CPD coordinators either at County level or at National level.
Arthralgias, bodily aches and pains and somatic complaints in midlife women: etiology, pathophysiology and differential diagnosis

Somatic symptoms characterized by arthralgias, bodily aches and pains, musculoskeletal pain and joint pain have been investigated in a number of menopause and depression studies. Although depression is one of the most common causes of bodily aches and pains, and arthralgias, these same symptoms are also commonly associated with a natural menopause, surgical menopause and menopause induced by chemotherapy in breast cancer treatment. Somatic symptoms in the absence of definitive medical diagnoses result in these patients receiving various diagnoses and labels –‘medically unexplained symptoms’, ‘worried well’, as well as various Diagnostic and Statistical Manual of Mental Disorders (4th edition) somatoform diagnoses. Osteoarthritis and joint pain increase in prevalence from premenopausal- to menopausal-aged women with hormonal change implicated in their etiology. The current research on the relationships among menopause, depression, nociceptive mechanisms, perception and pain in the distressed midlife patient is discussed. The amelioration and management of pain symptoms in the menopausal and postmenopausal woman, with or without comorbid depression, have been elusive and difficult problems for clinicians. Familiarity with the differential diagnosis, pathophysiology and evidence-based treatment for such patients is crucial to their proper care.
Fracture Patterns and Mechanisms in Pedestrian Motor‐Vehicle Trauma: The Ipsilateral Dyad

Summary Pedestrians struck by motor vehicles have the highest mortality and morbidity rates of all motor-vehicle traumas. Fracture patterns and mechanisms were reviewed in a retrospective study of 115 consecutive patients. The most common fracture was tibia-fibula (39 patients), followed by pelvic (35 patients) and femur fractures (31 patients). A majority (90%) of long-bone fractures were the result of a direct-blow mechanism, and pelvic fractures were caused usually by lateral-compressive forces. Unstable pelvic and femur fractures both correlated with mortality (p <0.05), whereas tibia-fibula fractures (open or closed) did not. The triad of head, pelvis, and knee injuries traditionally associated with pedestrian motor-vehicle accident (MVA) victims was not found to occur with any statistical significance in this study group. Several characteristic fracture patterns were discovered: femur fractures associated with an accompanying pelvic fracture, and the ipsilateral dyad, an upper- and lower-extremity fracture on the same side, were found to occur with statistical significance (p <0.05). A lower extremity fracture warrants particularly close attention to the examination of the corresponding upper extremity, and a femur fracture should alert the clinician to the possibility of pelvic injury. The ipsilateral dyad has not been described previously in the literature and should be appreciated by physicians evaluating and treating pedestrian MVA victims.
The phosphatidylinositol 3-kinase inhibitor, PX-866, is a potent inhibitor of cancer cell motility and growth in three-dimensional cultures

The phosphatidylinositol 3-kinase (PI3K) pathway is activated in many human tumors and mediates processes such as cell proliferation, survival, adhesion, and motility. The natural product, wortmannin, has been widely used to study the functional consequences of PI3K inhibition in both normal and transformed cells in culture but is not a suitable cancer chemotherapeutic agent due to stability and toxicity issues. PX-866, an improved wortmannin analogue, displays significant antitumor activity in xenograft models. Here, we directly compare PX-866 and wortmannin in human cancer cell lines cultured in monolayer or as three-dimensional spheroids. Both PI3K inhibitors failed to inhibit monolayer cell growth at concentrations up to 100 nmol/L but strongly suppressed spheroid growth at low nanomolar concentrations, with PX-866 showing greater potency than wortmannin. Relative to wortmannin, PX-866 treatment results in a more sustained loss of Akt phosphorylation, suggesting that the increased potency of PX-866 is related to a more durable inhibition of PI3K signaling. PX-866 and wortmannin both inhibit spheroid growth without causing cytotoxicity, similar to known cytostatic agents, such as rapamycin. PX-866 also inhibits cancer cell motility at subnanomolar concentrations. These findings suggest that the antitumor activities of PX-866 stem from prolonged inhibition of the PI3K pathway and inhibition of cell motility. In addition, we propose that the use of three-dimensional tumor models is more predictive of in vivo growth inhibition by PI3K inhibitors in cancer cell lines lacking phosphatase and tensin homologue activity or expression. [Mol Cancer Ther 2007;6(9):2505–14]
Signal transduction pathways that function in both development and innate immunity

C. elegans is developing in importance as a model for innate immunity. Several signaling pathways are known to be required for immune responses to a diverse range of pathogens, including the insulin signaling, p38 MAP kinase and transforming growth factor‐β pathways. These pathways also have roles during development, which can complicate the analysis of their functions in immunity. Recent studies have suggested that immunity in C. elegans is integrated across the organism by both paracrine and neuronal communication, showing the complexity of the immune system in this organism. Developmental Dynamics 239:1330–1336, 2010. © 2010 Wiley‐Liss, Inc.
A method for interleaved acquisition of a vascular input function for dynamic contrast‐enhanced MRI in experimental rat tumours

Dynamic contrast‐enhanced MRI is widely used for the evaluation of the response of experimental rodent tumours to antitumour therapy, particularly for the newly developing antiangiogenic and antivascular agents. However, standard models require a time‐course for the plasma concentration of contrast agent (usually referred to as the arterial input function) to calculate the transfer constant Ktrans from the dynamic time‐course data. Ideally, the plasma concentration time‐course should be measured during each experiment to obtain the most accurate measure of Ktrans. This is technically difficult in rodents, so assumed values are generally used. A method is presented here using interleaved acquisitions from a tail coil to obtain the plasma concentration simultaneously with DCE‐MRI data obtained from a solenoid coil around the tumour. The SNR of the resulting vascular input function data is high compared with methods using a volume coil to acquire plasma concentrations from the aorta and vena cava. Copyright © 2004 John Wiley & Sons, Ltd.
L2 stable four-channel control architecture for bilateral teleoperation with time delay

Passivity theory is very useful for stability analysis of bilateral teleoperation. Many researchers use passivity-based stabilization method such as scattering theory or wave variables. However, passivity-based stabilization is too conservative to design a high performance teleoperation system. High performance means that human operators can feel high-accuracy reaction force from environments. In this paper, we analyze l2 stability of some bilateral control systems with communication delay using small gain theorem. This theorem is renowned as a stable condition of multi-input multi-output feedback systems. And a novel control architecture which satisfies h stable condition of the theorem is proposed. The proposed control system has four communication channels. The validity of the proposed control system is shown by experimental results.