Miracle-dz/UniFAR-FTUs huggingface dataset:
Blood pressure and the global burden of disease 2000. Part 1: Estimates of blood pressure levels

Objective To provide global estimates of blood pressure by age and sex for adults aged ≥ 30 years, by WHO subregion. Design and methods Data were obtained from studies identified in a literature review of population-based surveys. These were complemented by data from MONICA and INTERSALT studies. Estimates of the shape of the age–systolic blood pressure (SBP) association were made from survey data utilizing parametric and non-parametric analyses. A linear sex-specific association of SBP with age was demonstrated from 30 to 70 years in females and 20 to 70 years for males in each subregion. Mean age- and sex-specific estimates of SBP were estimated for each WHO subregion separately, based on study and country-weighted SBP data. Results Analyses were based on data from about 230 surveys and over 660 000 participants. Age-specific mean SBP values ranged from 114 to 164 mmHg for females, and 117–153 mmHg for males. Females typically had lower SBP levels than males in the 30–44-year age groups, but in all subregions, SBP levels rose more steeply with age for females than males. Therefore, SBP levels in those aged ≥ 60 years tended to be higher in females. Subregions with consistently high mean SBP levels included parts of eastern Europe and Africa. Mean SBP levels were lowest in south-east Asia and parts of the western Pacific. Conclusions These global estimates of blood pressure by age, sex and subregion show considerable variation in estimated levels. The lack of data in developing countries is substantial, and this is an important limitation given the role of blood pressure in increasing cardiovascular disease levels.
Direct Allorecognition Promotes Activation of Bystander Dendritic Cells and Licenses Them for Th1 Priming: A Functional Link Between Direct and Indirect Allosensitization

T‐cell sensitization to indirectly presented alloantigens (indirect pathway of allorecognition) plays a critical role in chronic rejection. The usual very efficient priming of such self‐restricted, T helper type 1 (Th1)‐deviated CD4+ T cells obviously conflicts with the fact that allogeneic MHC molecules are poorly immunogenic per se. The aim of the present study is to elucidate whether direct allosensitization induces production of inflammatory mediators that may affect recruitment and activation of immature bystander (host) dendritic cells (DC). These potential mechanisms were studied in vitro by conducting primary allogeneic mixed leucocyte reactions (MLR), mimicking the priming phase in secondary lymphoid organs, and secondary MLR, mimicking the effector phase within the graft. Primary, and particularly secondary, MLR supernatants were found to contain high levels of monocyte/immature DC‐recruiting CC chemokines and pro‐inflammatory cytokines. Exposure of immature DC to primary or secondary MLR supernatants was found to upregulate CD40 expression and further enhanced lipopolysaccharide‐induced interleukin‐12 (IL‐12) p70 production. Secondary MLR supernatants additionally induced upregulation of CD86 and deviated allogeneic T‐cell responses towards Th1 (enhanced interferon‐γ production without concomitant induction of detectable IL‐4 or IL‐10 production). These findings indicate that direct allorecognition may act as a Th1‐deviating adjuvant for indirect allosensitization.
Commentary on the clinical and preclinical dosage limits of interstitially administered magnetic fluids for therapeutic hyperthermia based on current practice and efficacy models

Abstract We offer a critique of what constitutes a suitable dosage limit, in both clinical and preclinical studies, for interstitially administered magnetic nanoparticles in order to enable therapeutic hyperthermia under the action of an externally applied alternating magnetic field. We approach this first from the perspective of the currently approved clinical dosages of magnetic nanoparticles in the fields of MRI contrast enhancement, sentinel node detection, iron replacement therapy and magnetic thermoablation. We compare this to a simple analytical model of the achievable hyperthermia temperature rise in both humans and animals based on the interstitially administered dose, the heating and dispersion characteristics of the injected fluid, and the strength and frequency of the applied magnetic field. We show that under appropriately chosen conditions a therapeutic temperature rise is achievable in clinically relevant situations. We also show that in such cases it may paradoxically be harder to achieve the same therapeutic temperature rise in a preclinical model. We comment on the implications for the evidence-based translation of hyperthermia based interventions from the laboratory to the clinic.
Tumor‐promoting phenotype of CD90hi prostate cancer‐associated fibroblasts

Cancer‐associated stroma contributes to the malignant behavior of adenocarcinomas of the prostate and other organs. CD90 is a marker of mesenchymal stem cells (MSCs) and its expression is higher in prostate cancer stroma compared to normal tissue. Cultured prostate cancer‐associated fibroblasts (CAFs) expressing high versus low levels of CD90 were analyzed for an MSC‐like or tumor‐promoting phenotype.
Molecular Characterization of the Gene Encoding the DNA Gyrase A Subunit of Streptococcus pneumoniae

ABSTRACT The gene encoding the DNA gyrase A subunit of Streptococcus pneumoniae was cloned and sequenced. The gyrA gene codes for a protein of 822 amino acids homologous to the gyrase A subunit of eubacteria. Translation of the gene in an Escherichia coli expression system revealed a 92-kDa polypeptide. A sequence-directed DNA curvature was identified in the promoter region of gyrA. The bend center was mapped and located between the −35 and −10 regions of the promoter. Primer extension analysis showed that gyrA transcription initiates 6 bp downstream of an extended −10 promoter. The possible implications of the bent DNA region as a regulatory element in the transcription of gyrAare discussed.
Dysphagia in the Elderly: Preliminary Evidence of Prevalence, Risk Factors, and Socioemotional Effects

Objectives: Epidemiological studies of dysphagia in the elderly are rare. A non-treatment-seeking, elderly cohort was surveyed to provide preliminary evidence regarding the prevalence, risks, and socioemotional effects of swallowing disorders. Methods: Using a prospective, cross-sectional survey design, we interviewed 117 seniors living independently in Utah and Kentucky (39 men and 78 women; mean age, 76.1 years; SD, 8.5 years; range, 65 to 94 years) regarding 4 primary areas related to swallowing disorders: Lifetime and current prevalence, symptoms and signs, risk and protective factors, and socioemotional consequences. Results: The lifetime prevalence of a swallowing disorder was 38%, and 33% of the participants reported a current problem. Most seniors with dysphagia described a sudden onset with chronic problems that had persisted for at least 4 weeks. Stepwise logistic regression identified 3 primary symptoms uniquely associated with a history of swallowing disorders: Taking a longer time to eat (odds ratio [OR], 9.5; 95% confidence interval [CI], 2.3 to 40.2); coughing, throat clearing, or choking before, during, or after eating (OR, 3.4; 95% CI, 1.1 to 10.2); and a sensation of food stuck in the throat (OR, 5.2; 95% CI, 1.8 to 10.0). Stroke (p = .02), esophageal reflux (p = .003), chronic obstructive pulmonary disease (p = .05), and chronic pain (p = .03) were medical conditions associated with a history of dysphagia. Furthermore, dysphagia produced numerous adverse socioemotional effects. Conclusions: This study provides preliminary evidence to suggest that chronic swallowing disorders are common among the elderly, and highlights the need for larger epidemiological studies of these disorders.
PUFs as Promising Tools for Security in Internet of Things

The article has presented an overview on the promise of PUFs in providing much needed security in IoTs. We have discussed a security violation in the authentication of a commercial-lighting-based IoT, and argued that the use of PUFs as a hardware security primitive can provide a low-cost but secured mechanisThe article has presented an overview on the promise of PUFs in providing much needed security in IoTs. We have discussed a security violation in the authentication of a commercial-lighting-based IoT, and argued that the use of PUFs as a hardware security primitive can provide a low-cost but secured mechanism to subvert such attacks. However, there are several challenges which need to be considered: starting from making the PUF primitives secured against machine learning but yet lightweight, to develop protocols using them to prevent such machine-learning-based attacks. Case studies for a lightweight construction of PUFs (called LSPUF), attacks on it, and a protocol on PUFs, called SPUF, have been detailed to highlight these challenging constraints of PUF-based designs. Finally, a proof-of-concept testbed has been presented using commercially available tools to show how PUFs can be used to interact with other IoT nodes to provide overall security.m to subvert such attacks. However, there are several challenges which need to be considered: starting from making the PUF primitives secured against machine learning but yet lightweight, to develop protocols using them to prevent such machine-learning-based attacks. Case studies for a lightweight construction of PUFs (called LSPUF), attacks on it, and a protocol on PUFs, called SPUF, have been detailed to highlight these challenging constraints of PUF-based designs. Finally, a proof-of-concept testbed has been presented using commercially available tools to show how PUFs can be used to interact with other IoT nodes to provide overall security.
Addressing challenges in obtaining high coverage when model checking Android applications

Current dynamic analysis tools for Android applications do not get good code coverage since they can only explore a subset of the behaviors of the applications and do not have full control over the environment in which they execute. In this work we use model checking to systematically explore application paths while reducing the analysis size using state matching and backtracking. In particular, we extend the Java PathFinder (JPF) model checking environment for Android. We describe the difficulties one needs to overcome to make this a reality as well as our current approaches to handling these issues. We obtain significantly higher coverage using shorter event sequences on a representative sample of Android apps, when compared to Dynodroid and Sapienz, the current state-of-the-art dynamic analysis tools for Android applications.
Synaptic organization of enkephalinlike‐immunoreactive amacrine cells in the goldfish retina

Immunoelectron microscopy was used to examine the synaptic organization of enkephalinlike‐immunoreactive amacrine cells in the goldfish retina. Enkephalin‐immunostained processes sometimes contained dense‐cored vesicles (115–145 nm) in addition to a generally homogeneous population of small, round, clear synaptic vesicles. A total of 194 synaptic relationships were observed that involved the immunostained processes of enkephalin‐amacrine cells. The large majority of these were observed in sublayer 5 of the inner plexiform layer. In greater than 95% of the synaptic relationships, the enkephalin‐immunostained profile served as the presynaptic element. In 58.8% of these relationships, enkephalin processes synapsed onto amacrine cell processes, while 30.4% of their synapses were onto processes that lacked synaptic vesicles. They also occasionally formed synaptic contacts (6.7%) onto the somas of cells located either in the inner nuclear or in the ganglion cell layers. Enkephalin profiles received synaptic input only from amacrine cells (4.1%), while no direct synaptic interaction was observed between enkephalin processes and bipolar cells. However, in sublayer 1, enkephalin profiles were found to synapse onto amacrine cell processes that were presynaptic to bipolar cell terminals. In the proximal inner plexiform layer, enkephalin processes were presynaptic to amacrine cell processes that as a group surrounded and sometimes provided synaptic input to extremely large and round bipolar cell endings.
Prevalence and diversity of IncX plasmids carrying fluoroquinolone and β-lactam resistance genes in Escherichia coli originating from diverse sources and geographical areas.

OBJECTIVES To describe the prevalence and diversity of IncX plasmids with antibiotic resistance genes in Enterobacteriaceae and to identify the most disseminated lineages of the plasmid family. METHODS IncX plasmids were screened in 1894 Enterobacteriaceae isolates resistant to cefotaxime (2 mg/L) or with reduced susceptibility to ciprofloxacin (0.05 mg/L) obtained from various sources in five continents using PCR. IncX plasmid-harbouring isolates were identified using MALDI-TOF or biochemical tests, and screened for antibiotic resistance genes using PCR and sequencing; their clonality was determined by PFGE. Horizontal transfer of plasmids was tested using transformation and conjugation. IncX plasmids were characterized by S1-nuclease and PFGE, RFLP and hybridization. RESULTS A total of 164 Escherichia coli isolates (8.7%, n = 1894) carried at least one IncX subgroup. Seven isolates harboured two distinct subgroups. IncX1 subgroup was found in 93 isolates, followed by IncX2 (35 isolates), IncX4 (28) and IncX3 (15). IncX4 plasmids were not transferred horizontally as single plasmids and therefore excluded from further analysis. The most disseminated lineages of IncX plasmids included IncX1 harbouring qnrS1 and blaTEM-1,-135 found in 36 E. coli from different sources in Europe and Australia and IncX2 carrying qnrS1 and tet(A) detected in nine E. coli from wildlife in Europe. IncX3 plasmids harboured predominantly blaSHV-12 and qnrS1 or qnrB7. CONCLUSIONS IncX plasmids were widely distributed in E. coli from wildlife in Europe and were predominantly associated with fluoroquinolone resistance genes. Plasmids showing indistinguishable restriction profiles were identified in E. coli from different sources and countries suggesting wide dissemination of certain plasmid lineages.
Histological and functional recovery in patients with multifocal atrophic gastritis after eradication of Helicobacter pylori infection.

BACKGROUND/AIMS To assess the effect of Helicobacter pylori eradication on gastric histology and physiology in patients with multifocal atrophic gastritis over 1-year period. PATIENTS Fourteen consecutive patients with histological evidence of chronic gastritis and Helicobacter pylori infection diagnosed by histology and serology entered this study. Patients with pernicious anaemia, gastric ulcer or carcinoma, duodenal ulcer, reflux oesophagitis and regular intake of nonsteroidal anti-inflammatory drugs were excluded. METHODS Patients underwent triple anti-Helicobacter treatment for one week, which resulted successful in all subjects on the basis of negative CLO test and histology as well as 50% decrease in IgG antibodies after 4 weeks and 6 months of treatment, respectively. Histological and functional investigations were performed at baseline, 6 and 12 months after Helicobacter pylori eradication. Histological assessment of inflammatory cell infiltrates was performed on multiple biopsy specimens of the corpus and fundus. Functional tests were 24-hour continuous gastric pH-metry, fasting serum gastrin assay and pepsinogen I levels. RESULTS There was a progressive significant improvement (p < 0.01-0.001) in acute and chronic inflammatory cell infiltrates in the gastric mucosa throughout the 12-month period. Functional recovery with increase in gastric acidity (p < 0.01) and decrease in gastrin and pepsinogen I levels (p < 0.001) was more evident at the 6-month than at the 12-month checkpoint after Helicobacter pylori eradication (p = NS for gastric pH and p < 0.02 for the other two variables) between 6 and 12 months. CONCLUSIONS Eradication of Helicobacter pylori infection significantly improves the inflammatory status of oxyntic mucosa and this promotes an almost complete functional recovery. However, the non-parallel behaviour of gastric acidity, which was maximal at 6-month checkpoint, and histological parameters which continued to improve throughout the entire 12-month observation period, seems to indicate that removal of acid-inhibitory substances induced by Helicobacter pylori infection was also responsible for the more rapid recovery of gastric secretory function.
Alginate microencapsulation of human mesenchymal stem cells as a strategy to enhance paracrine‐mediated vascular recovery after hindlimb ischaemia

Stem cell‐based therapies hold great promise as a clinically viable approach for vascular regeneration. Preclinical studies have been very encouraging and early clinical trials have suggested favourable outcomes. However, significant challenges remain in terms of optimizing cell retention and maintenance of the paracrine effects of implanted cells. To address these issues, we have proposed the use of a cellular encapsulation approach to enhance vascular regeneration. We contained human mesenchymal stem cells (hMSCs) in biocompatible alginate microcapsules for therapeutic treatment in the setting of murine hindlimb ischaemia. This approach supported the paracrine pro‐angiogenic activity of hMSCs, prevented incorporation of hMSCs into the host tissue and markedly enhanced their therapeutic effect. While injection of non‐encapsulated hMSCs resulted in a 22 ± 10% increase in vascular density and no increase in perfusion, treatment with encapsulated hMSCs resulted in a 70 ± 8% increase in vascular density and 21 ± 7% increase in perfusion. The described cellular encapsulation strategy may help to better define the mechanisms responsible for the beneficial effects of cell‐based therapies and provide a therapeutic strategy for inducing vascular growth in the adult. As hMSCs are relatively easy to isolate from patients, and alginate is biocompatible and already used in clinical applications, therapeutic cell encapsulation for vascular repair represents a highly translatable platform for cell‐based therapy in humans. Copyright © 2012 John Wiley & Sons, Ltd.
The potential of the human CD38-specific antibody daratumumab to improve the antimyeloma effect of novel multidrug therapies including patients refractory to lenalidomide or bortezomib.

e18571 Background: Multiple myeloma (MM) represents an incurable malignancy of antibody-producing clonal plasma cells. Over the past decade significant progress has been made in MM treatment using novel immunomodulating agents such as lenalidomide (LEN) and bortezomib (BORT). Daratumumab (DARA) is a first-in-class human therapeutic CD38-specific antibody with a broad mechanism of action. DARA mediates MM cell death primarily via ADCC (antibody dependent cellular cytotoxicity), CDC (complement dependent cytotoxicity) and apoptosis. We are currently exploring the possibility to further improve MM therapy by combining novel MM therapeutics with DARA. Our initial in vitro work already showed significantly improved MM cell killing by combining DARA with LEN treatment. METHODS In ex vivo assays, which allow us to address killing of MM cells in bone marrow aspirates isolated from MM patients, we now investigated whether the addition of DARA to the LEN+BORT combination significantly exceeds the effectiveness of LEN+BORT treatment alone. DARA was also combined with two recently introduced triple combination therapies: LEN, BORT, dexamethasone (RVD) and melphalan, prednisone, BORT (MPV). RESULTS we demonstrate that the addition of DARA to the LEN+BORT combination significantly exceeds the effectiveness of LEN+BORT treatment alone (P<0.001). Strikingly, killing was most improved in treatment of patient samples which showed poor responses to the LEN-BORT combination. Notably, 5 of these samples were derived from patients who were refractory to BORT and/or LEN. In these samples DARA increased MM cell killing up to 50%. Furthemore, when DARA was combined with novel triple agent regimens RVD and MPV, it almost doubled MM cell killing especially in the low-dose range of these novel cocktails. CONCLUSIONS Our results illustrate that treatment of MM with DARA in combination with novel multidrug therapies bears great promise.
The cobZ Gene of Methanosarcina mazei Gö1 Encodes the Nonorthologous Replacement of the α-Ribazole-5′-Phosphate Phosphatase (CobC) Enzyme of Salmonella enterica

ABSTRACT Open reading frame (ORF) Mm2058 of the methanogenic archaeon Methanosarcina mazei strain Gö1 was shown in vivo and in vitro to encode the nonorthologous replacement of the α-ribazole-phosphate phosphatase (CobC; EC 3.1.3.73) enzyme of Salmonella enterica serovar Typhimurium LT2. Bioinformatics analysis of sequences available in databases tentatively identified ORF Mm2058, which was cloned under the control of an inducible promoter and was used to support growth of an S. enterica strain under conditions that demanded CobC-like activity. The Mm2058 protein was expressed with a decahistidine tag at its N terminus and was purified to homogeneity using nickel affinity chromatography. High-performance liquid chromatography followed by electrospray ionization mass spectrometry showed that the Mm2058 protein had phosphatase activity that converted α-ribazole-5′-phosphate to α-ribazole, as reported for the bacterial CobC enzyme. On the basis of the data reported here, we refer to ORF Mm2058 as cobZ. We tested the prediction by Rodionov et al. (D. A. Rodionov, A. G. Vitreschak, A. A. Mironov, and M. S. Gelfand, J. Biol. Chem. 278:41148-41159, 2003) that ORF HSL01294 (also called Vng1577) encoded the nonorthologous replacement of the bacterial CobC enzyme in the extremely halophilic archaeon Halobacterium sp. strain NRC-1. A strain of the latter carrying an in-frame deletion of ORF Vng1577 was not a cobalamin auxotroph, suggesting that either there is redundancy of this function in Halobacterium or the gene was misannotated.
Sevoflurane postconditioning affects post‐ischaemic myocardial mitochondrial ATP‐sensitive potassium channel function and apoptosis in ageing rats

This study investigated the effect of sevoflurane postconditioning on post‐ischaemic cardiac function, infarct size, myocardial mitochondrial ATP‐sensitive potassium channel (mitoKATP) function and apoptosis in ageing rats to determine the possible mechanism underlying the cardioprotective property of sevoflurane. Ageing rat hearts were isolated and attached to a Langendorff apparatus. The hearts were then exposed or not to sevoflurane postconditioning in the presence or absence of 100 μmol/L 5‐hydroxydecanoate (5‐HD), a selective mitoKATP inhibitor. The infarct size was measured by triphenyltetrazolium chloride (TTC) staining. Mitochondrial morphology was observed by electron microscopy and scored using FlaMeng semiquantitative analysis. In addition, the expression levels of Bax, Bcl‐2, and cytochrome‐C (Cyt‐C) were determined by Western blot analysis at the end of reperfusion. Sevoflurane postconditioning increased coronary flow, improved functional recovery, reduced Bax/Bcl‐2 and Cyt‐C phosphorylation levels, and decreased mitochondrial lesion severity and the extent of apoptosis. The protective effects of sevoflurane postconditioning were prevented by the mitoKATP inhibitor 5‐HD. Sevoflurane postconditioning significantly protected the function of ageing hearts that were subjected to ischaemia and reperfusion, and these protective effects were mediated by mitoKATP opening.