bluuebunny/crossref_metadata_2025_split huggingface dataset:
Invasive Infections with Nontyphoidal
Salmonella
in Sub-Saharan Africa
Authors: Mahon Barbara E. , Fields Patricia I. 
Published: June 2016

ABSTRACT

Invasive nontyphoidal
Salmonella
(NTS) infections in Africa cause an enormous burden of illness. These infections are often devastating, with mortality estimated at 20%, even with appropriate antimicrobial therapy. Two major groups—young children and HIV-infected adults—suffer the great majority of these infections. In children, younger age itself, as well as malaria, malnutrition, and HIV infection, are prominent risk factors. In adults, HIV infection is by far the most important risk factor. The most common serotypes in invasive infections are
Salmonella enterica
serotypes Typhimurium and Enteritidis. In recent years, a specific strain of
Salmonella
Typhimurium, multilocus sequence type 313, has caused epidemics of invasive disease. Little is known about risk factors for exposure to NTS, making the design of rational interventions to decrease exposure difficult. Antimicrobial therapy is critically important for treatment of invasive NTS infections. Thus, the emergence and spread of resistance to agents commonly used for treatment of invasive NTS infection, now including third-generation cephalosporins, is an ominous development. Already, many invasive NTS infections are essentially untreatable in many health care facilities in sub-Saharan Africa. Several candidate vaccines are in early development and, if safe and effective, could be promising. Interventions to prevent exposure to NTS (e.g., improved sanitation), to prevent the occurrence of disease if exposure does occur (e.g., vaccination, malaria control), and to prevent severe disease and death in those who become ill (e.g., preserving antimicrobial effectiveness) are all important in reducing the toll of invasive NTS disease in sub-Saharan Africa.
Zika Virus Disease
Authors: Slenczka Werner 
Published: June 2016

ABSTRACT

The history of Zika virus disease serves as a paradigm of a typical emerging viral infection. Zika virus disease, a mosquito-borne flavivirus, was first isolated in 1947 in the Zika forest of Uganda. The same virus was also isolated from jungle-dwelling mosquitoes (
Aedes
[
Stegomyia
]
africanus
). In many areas of Africa and South Asia human infections with Zika virus were detected by both serology and virus isolation. About 80% of infections are asymptomatic, and in 20% a mostly mild disease with fever, rash, arthralgia, and conjunctivitis may occur. Fetal infections with malformations were not recorded in Africa or Asia. Zika virus was imported to northern Brazil possibly during the world soccer championship that was hosted by Brazil in June through July 2014. A cluster of severe fetal malformations with microcephaly and ocular defects was noted in 2015 in the northeast of Brazil, and intrauterine infections with Zika virus were confirmed. The dramatic change in Zika virus pathogenicity upon its introduction to Brazil has remained an enigma.
Dynamic links among rock damage, erosion, and strain during orogenesis
Authors: Roy S.G. , Koons P.O. , Upton P. , Tucker G.E. 
Published: June 2016

Abstract
We provide model evidence for a previously unexplored positive feedback between tectonic strain and fluvial erosion by considering rock erodibility as a function of shear damage. Plastic shear strain permanently damages the upper crust within planar shear zones, providing a greater ease for detachment and transport by fluvial processes. The subsequent rapid erosion of exposed shear zones reforms the topographic stress field in a way that encourages continued accommodation of strain, a positive feedback response that becomes more prominent with greater shear damage. Based on model results and natural examples, rock strength heterogeneity plays a major role in the evolution of drainage network patterns and the capability for valley-scale strain localization in active orogens.
Diagnostic utility of CSF α-synuclein species in Parkinson's disease: protocol for a systematic review and meta-analysis
Authors: Eusebi Paolo , Giannandrea David , Biscetti Leonardo , Abraha Iosief , Chiasserini Davide , Orso Massimiliano , Calabresi Paolo , Parnetti Lucilla 
Published: June 2016

IntroductionThe diagnostic criteria currently used for Parkinson's disease (PD) are mainly based on clinical motor symptoms. For these reasons many biomarkers are under investigation to support the diagnosis at the early stage. The neuropathological hallmark of PD is represented by Lewy bodies (LBs), which are intracytoplasmic inclusions in substantia nigra neurons. The major component of LBs, α-synuclein (α-syn), has been implicated in the pathogenesis of PD and in other ‘synucleinopathies’ such as multisystem atrophy (MSA) and dementia with LBs (DLBs). Several studies have investigated this presynaptic protein as a potential biomarker of PD. The aim of our meta-analysis is to determine the ability of cerebrospinal fluid (CSF) concentrations of total α-syn, oligomeric α-syn and phosphorylated α-syn to discriminate patients with PD from healthy participants, non-degenerative neurological controls and patients suffering from parkinsonism and or synucleinopathies.Methods and analysisThis systematic review protocol has been developed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses Protocol (PRISMA-P) 2015 statement and was registered on PROSPERO (CRD42016013217). We will search Cochrane Library, Web of Science, MEDLINE (via PubMed) and EMBASE from inception, using appropriate search strategies. Two independent reviewers will screen titles, abstracts and full-text articles, and will complete data abstraction. We will include studies that involved patients with PD, DLB, MSA, progressive supranuclear palsy, corticobasal disease and vascular PD, and in which at least one between total α-syn, oligomeric α-syn and phosphorylated α-syn was measured in CSF. To evaluate the risk of bias and applicability of primary diagnostic accuracy studies, we will use QUADAS-2.Ethics and disseminationOur study will not include confidential data, and no intervention will be involved, so ethical approval is not required. The results of the study will be reported in international peer-reviewed journals.
Is selective prenatal iron prophylaxis better than routine prophylaxis: final results of a trial (PROFEG) in Maputo, Mozambique
Authors: Hemminki Elina , Nwaru Bright I , Salomé Graca , Parkkali Saara , Abacassamo Fatima , Augusto Orvalho , Cliff Julie , Regushevskaya Elena , Dgedge Martinho , Sousa Cesar , Chilundo Baltazar 
Published: June 2016

ObjectiveTo compare routine versus selective (ie, screening and treatment for anaemia) prenatal iron prophylaxis in a malaria-endemic and HIV-prevalent setting, an extended analysis including previously missing data.DesignA pragmatic randomised controlled clinical trial.Setting2 health centres in Maputo, Mozambique.ParticipantsPregnant women (≥18 years old; non-high-risk pregnancy) were randomly allocated to routine iron (n=2184) and selective iron (n=2142) groups.InterventionsIn the routine group, women received 60 mg ferrous sulfate plus 400 μg folic acid daily. In the selective group, women received 1 mg of folic acid daily and haemoglobin (Hb) screening at each visit; with low Hb (cut-off 9 g/dL) treatment (120 mg+800 μg of folic acid daily) for a month.Outcome measuresPrimary outcomes: preterm birth, low birth weight; secondary outcomes: self-reported malaria, labour complications, caesarean section, perinatal death, woman's death. Nurses collected pregnancy data. Birth data were abstracted from hospital records for 52% of women and traced using various methods and linked with probabilistic matching for 24%. Women's deaths were collected from death registers.ResultsBirth data were available for 3301 (76%) of the women. Outcomes were similar in the two groups: preterm births (27.1% in the selective vs 25.3% in the routine group), low birthweight infants (11.0% vs 11.7%), perinatal deaths (2.4% vs 2.4%) and caesarean sections (4.0% vs 4.5%). Women's deaths during pregnancy or <42 days postpartum were more common in the selective group (0.8% among the two best matched women) than in the routine group (0.4%). Extra deaths could not be explained by the cause of death, Hb level or HIV status at recruitment.ConclusionsBirth outcomes were similar in the two iron groups. There might have been more women's deaths in the selective iron group, but it is unclear whether this was due to the intervention, other factors or chance finding.Trial registration numberNCT00488579.
Randomized controlled trial of vertebroplasty versus kyphoplasty in the treatment of vertebral compression fractures
Authors: Evans Avery J , Kip Kevin E , Brinjikji Waleed , Layton Kennith F , Jensen Mary L , Gaughen John R , Kallmes David F 
Published: June 2016

BackgroundWe present the results of a randomized controlled trial evaluating the efficacy of vertebroplasty versus kyphoplasty in treating vertebral body compression fractures.MethodsPatients with vertebral body compression fractures were randomly assigned to treatment with kyphoplasty or vertebroplasty. Primary endpoints were pain (0–10 scale) and disability assessed using the Roland–Morris Disability Questionnaire (RMDQ). Outcomes were assessed at 3 days, 1 month, 6 months, and 1 year following the procedure.Results115 subjects were enrolled in the trial with 59 (51.3%) randomly assigned to kyphoplasty and 56 (48.7%) assigned to vertebroplasty. Mean (SD) pain scores at baseline, 3 days, 30 days, and 1 year for kyphoplasty versus vertebroplasty were 7.4 (1.9) vs 7.9 (2.0), 4.1 (2.8) vs 3.7 (3.0), 3.4 (2.5) vs 3.6 (2.9), and 3.0 (2.8) vs 2.3 (2.6), respectively (p>0.05 at all time points). Mean (SD) RMDQ scores at baseline, 3 days, 30 days, 180 days, and 1 year were 17.3 (6.6) vs 16.3 (7.4), 11.8 (7.9) vs 10.9 (8.2), 8.6 (7.2) vs 8.8 (8.5), 7.9 (7.4) vs 7.3 (7.7), 7.5 (7.2) vs 6.7 (8.0), respectively (p>0.05 at all time points). For baseline to 12-month assessment in average pain and RMDQ scores, the standardized effect size between kyphoplasty and vertebroplasty was small at −0.36 (95% CI −1.02 to 0.31) and −0.04 (95% CI −1.68 to 1.60), respectively.ConclusionsOur study indicates that vertebroplasty and kyphoplasty appear to be equally effective in substantially reducing pain and disability in patients with vertebral body compression fractures.Trial registration numberNCT00279877.
The 750 GeV diphoton excess in unified SU(2)L ×SU(2)R ×SU(4) models from noncommutative geometry
Authors: Aydemir Ufuk , Minic Djordje , Sun Chen , Takeuchi Tatsu 
Published: June 2016

We discuss a possible interpretation of the 750 GeV diphoton resonance, recently reported at the large hadron collider (LHC), within a class of [Formula: see text] models with gauge coupling unification. The unification is imposed by the underlying noncommutative geometry (NCG), which in these models is extended to a left–right symmetric completion of the Standard Model (SM). Within such unified [Formula: see text] models the Higgs content is restrictively determined from the underlying NCG, instead of being arbitrarily selected. We show that the observed cross-sections involving the 750 GeV diphoton resonance could be realized through a SM singlet scalar field accompanied by colored scalars, present in these unified models. In view of this result, we discuss the underlying rigidity of these models in the NCG framework and the wider implications of the NCG approach for physics beyond the SM.
SURFACE ROUGHNESS STUDY ON MICROCHANNELS OF CO2 LASER FABRICATING PMMA-BASED MICROFLUIDIC CHIP
Authors: CHEN XUEYE , LI TIECHUAN , FU BAODING 
Published: June 2016

A novel method named soak sacrificial layer ultrasonic method (SSLUM) has been presented for optimizing the surface roughness of the microchannels of polymethyl methacrylate (PMMA)-based microfluidic chips. CO2 laser was used for ablative microchannels on the PMMA sheet, and the effects of key parameters including laser power, laser ablation speed and solution concentration on the surface roughness of microchannels were estimated and optimized by SSLUM. The experimental observation demonstrates that the surface roughness results mainly from the residues on the channel wall, which are produced by the bubbles movement and bursting. The research results show that the surface roughness can be improved effectively by using SSLUM. In our experiment, the best value was Ra [Formula: see text] 110[Formula: see text]nm with laser power 12[Formula: see text]W, laser ablation speed 10[Formula: see text]mm/s, the solution concentration 75%, and the time of ultrasonic vibration 25[Formula: see text]min. SSLUM is proven to be an effective, simple and rapid method for optimizing the surface roughness of microchannels of microfluidic chips.
A generalization of Turaev’s virtual string cobracket and self-intersections of virtual strings
Authors: Cahn Patricia 
Published: June 2016

Previously we defined an operation [Formula: see text] that generalizes Turaev’s cobracket for loops on a surface. We showed that, in contrast to the cobracket, this operation gives a formula for the minimum number of self-intersections of a loop in a given free homotopy class. In this paper, we consider the corresponding question for virtual strings, and conjecture that [Formula: see text] gives a formula for the minimum number of self-intersection points of a virtual string in a given virtual homotopy class. To support the conjecture, we show that [Formula: see text] gives a bound on the minimal self-intersection number of a virtual string which is stronger than a bound given by Turaev’s virtual string cobracket. We also use Turaev’s based matrices to describe a large set of strings [Formula: see text] such that [Formula: see text] gives a formula for the minimal self-intersection number [Formula: see text]. Finally, we compare the bound given by [Formula: see text] to a bound given by Turaev’s based matrix invariant [Formula: see text], and construct an example that shows the bound on the minimal self-intersection number given by [Formula: see text] is sometimes stronger than the bound [Formula: see text].
Theranostic Agents for Photodynamic Therapy of Prostate Cancer by Targeting Prostate-Specific Membrane Antigen
Authors: Wang Xinning , Tsui Brian , Ramamurthy Gopolakrishnan , Zhang Ping , Meyers Joseph , Kenney Malcolm E. , Kiechle Jonathan , Ponsky Lee , Basilion James P. 
Published: June 2016

AbstractProstatectomy has been the mainstay treatment for men with localized prostate cancer. Surgery, however, often can result in major side effects, which are caused from damage and removal of nerves and muscles surrounding the prostate. A technology that can help surgeons more precisely identify and remove prostate cancer resulting in a more complete prostatectomy is needed. Prostate-specific membrane antigen (PSMA), a type II membrane antigen highly expressed in prostate cancer, has been an attractive target for imaging and therapy. The objective of this study is to develop low molecular weight PSMA-targeted photodynamic therapy (PDT) agents, which would provide image guidance for prostate tumor resection and allow for subsequent PDT to eliminate unresectable or remaining cancer cells. On the basis of our highly negatively charged, urea-based PSMA ligand PSMA-1, we synthesized two PSMA-targeting PDT conjugates named PSMA-1-Pc413 and PSMA-1-IR700. In in vitro cellular uptake experiments and in vivo animal imaging experiments, the two conjugates demonstrated selective and specific uptake in PSMA-positive PC3pip cells/tumors, but not in PSMA-negative PC3flu cells/tumors. Further in vivo photodynamic treatment proved that the two PSMA-1–PDT conjugates can effectively inhibit PC3pip tumor progression. The two PSMA-1–PDT conjugates reported here may have the potential to aid in the detection and resection of prostate cancers. It may also allow for the identification of unresectable cancer tissue and PDT ablation of such tissue after surgical resection with potentially less damage to surrounding tissues. Mol Cancer Ther; 15(8); 1834–44. ©2016 AACR.
Acridine Derivatives as Inhibitors of the IRE1α–XBP1 Pathway Are Cytotoxic to Human Multiple Myeloma
Authors: Jiang Dadi , Tam Arvin B. , Alagappan Muthuraman , Hay Michael P. , Gupta Aparna , Kozak Margaret M. , Solow-Cordero David E. , Lum Pek Y. , Denko Nicholas C. , Giaccia Amato J. , Le Quynh-Thu , Niwa Maho , Koong Albert C. 
Published: June 2016

Abstract
Using a luciferase reporter–based high-throughput chemical library screen and topological data analysis, we identified N-acridine-9-yl-N',N'-dimethylpropane-1,3-diamine (DAPA) as an inhibitor of the inositol requiring kinase 1α (IRE1α)–X-box binding protein-1 (XBP1) pathway of the unfolded protein response. We designed a collection of analogues based on the structure of DAPA to explore structure–activity relationships and identified N9-(3-(dimethylamino)propyl)-N3,N3,N6,N6-tetramethylacridine-3,6,9-triamine (3,6-DMAD), with 3,6-dimethylamino substitution on the chromophore, as a potent inhibitor. 3,6-DMAD inhibited both IRE1α oligomerization and in vitro endoribonuclease (RNase) activity, whereas the other analogues only blocked IRE1α oligomerization. Consistent with the inhibition of IRE1α-mediated XBP1 splicing, which is critical for multiple myeloma cell survival, these analogues were cytotoxic to multiple myeloma cell lines. Furthermore, 3,6-DMAD inhibited XBP1 splicing in vivo and the growth of multiple myeloma tumor xenografts. Our study not only confirmed the utilization of topological data analysis in drug discovery but also identified a class of compounds with a unique mechanism of action as potent IRE1α–XBP1 inhibitors in the treatment of multiple myeloma. Mol Cancer Ther; 15(9); 2055–65. ©2016 AACR.
A New Anti-CXCR4 Antibody That Blocks the CXCR4/SDF-1 Axis and Mobilizes Effector Cells
Authors: Broussas Matthieu , Boute Nicolas , Akla Barbara , Berger Sven , Beau-Larvor Charlotte , Champion Thierry , Robert Alain , Beck Alain , Haeuw Jean-François , Goetsch Liliane , Bailly Christian , Dumontet Charles , Matthes Thomas , Corvaia Nathalie , Klinguer-Hamour Christine 
Published: June 2016

Abstract
The type IV C-X-C-motif chemokine receptor (CXCR4) is expressed in a large variety of human cancers, including hematologic malignancies, and this receptor and its ligand, stromal cell–derived factor-1 (SDF-1), play a crucial role in cancer progression. We generated a humanized immunoglobulin G1 mAb, hz515H7, which binds human CXCR4, efficiently competes for SDF-1 binding, and induces a conformational change in CXCR4 homodimers. Furthermore, it inhibits both CXCR4 receptor–mediated G-protein activation and β-arrestin-2 recruitment following CXCR4 activation. The binding of the hz515H7 antibody to CXCR4 inhibits the SDF-1–induced signaling pathway, resulting in reduced phosphorylation of downstream effectors, such as Akt, Erk1/2, p38, and GSK3β. Hz515H7 also strongly inhibits cell migration and proliferation and, while preserving normal blood cells, induces both antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against neoplastic cells. In mouse xenograft models, hz515H7 displays antitumor activities with multiple hematologic tumor cell lines, with its Fc-mediated effector functions proving essential in this context. Furthermore, hz515H7 binds to primary tumor cells from acute myeloid leukemia and multiple myeloma patients. Collectively, our results demonstrate two major mechanisms of action, making hz515H7 unique in this regard. Its potential as a best-in-class molecule is currently under investigation in a phase I clinical trial. Mol Cancer Ther; 15(8); 1890–9. ©2016 AACR.
Factors Associated With Noncompletion During the Run-In Period Before Randomization and Influence on the Estimated Benefit of LCZ696 in the PARADIGM-HF Trial
Authors: Desai Akshay S. , Solomon Scott , Claggett Brian , McMurray John J.V. , Rouleau Jean , Swedberg Karl , Zile Michael , Lefkowitz Martin , Shi Victor , Packer Milton 
Published: June 2016

Background—
The 8442 patients randomized in the Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, in which sacubitril/valsartan (LCZ696) reduced both death and HF hospitalization more than enalapril, were a subset of 10 521 patients entering sequential, single-blind run-in periods (enalapril 10 mg twice daily for 2 weeks followed by LCZ696 200 mg twice daily for 4 to 6 weeks) to ensure short-term tolerability of the 2 study medications. We identified the predictors of run-in noncompletion and estimated the implications of noncompletion for the overall study result.

Methods and Results—
Patient factors associated with run-in noncompletion were defined in multivariable logistic regression models. The effectiveness of LCZ696 in a broader cohort approximating the full run-in population was estimated by weighting randomized patients according to the inverse probability of run-in completion; 2079 (19.8%) subjects discontinued the study during the run-in period, including 1102 (10.5%) during the enalapril phase and 977 (9.3%) during the LCZ696 phase. In multivariable models, lower systolic blood pressure, lower estimated glomerular filtration rate, higher N-terminal pro–B-type natriuretic peptide, and ischemic cause of heart failure were associated with higher risk for run-in noncompletion. Repeat analysis of the effect of randomized treatment giving greater weight to randomized patients resembling those who did not complete the run-in did not alter the hazard ratio favoring LCZ696 over enalapril for the primary end point of cardiovascular death or heart failure hospitalization, or the additional key end points of cardiovascular death and all-cause mortality.

Conclusions—
Patients with lower blood pressure, lower glomerular filtration rate, and more severe heart failure were at higher risk for noncompletion during the run-in period of PARADIGM-HF. Weighted analysis of key study outcomes accounting for the effect of run-in noncompletion did not alter the benefit of LCZ696 over enalapril.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01035255.