bluuebunny/crossref_metadata_2025 huggingface dataset:
Antifungal activity and killing kinetics of anidulafungin, caspofungin and amphotericin B against Candida auris
Authors: Dudiuk Catiana , Berrio Indira , Leonardelli Florencia , Morales-Lopez Soraya , Theill Laura , Macedo Daiana , Yesid-Rodriguez José , Salcedo Soraya , Marin Adriana , Gamarra Soledad , Garcia-Effron Guillermo
Published: May 2019

Background

Candida auris is an emerging MDR pathogen. It shows reduced susceptibility to azole drugs and, in some strains, high amphotericin B MICs have been described. For these reasons, echinocandins were proposed as first-line treatment for C. auris infections. However, information on how echinocandins and amphotericin B act against this species is lacking.

Objectives

Our aim was to establish the killing kinetics of anidulafungin, caspofungin and amphotericin B against C. auris by time–kill methodology and to determine if these antifungals behave as fungicidal or fungistatic agents against this species.

Methods

The susceptibility of 50 C. auris strains was studied. Nine strains were selected (based on echinocandin MICs) to be further studied. Minimal fungicidal concentrations, in vitro dose–response and time–kill patterns were determined.

Results

Echinocandins showed lower MIC values than amphotericin B (geometric mean of 0.12 and 0.94 mg/L, respectively). Anidulafungin and caspofungin showed no fungicidal activity at any concentration (maximum log decreases in cfu/mL between 1.34 and 2.22). On the other hand, amphotericin B showed fungicidal activity, but at high concentrations (≥2.00 mg/L). In addition, the tested polyene was faster than echinocandins at killing 50% of the initial inoculum (0.92 versus >8.00 h, respectively).

Conclusions

Amphotericin B was the only agent regarded as fungicidal against C. auris. Moreover, C. auris should be considered tolerant to caspofungin and anidulafungin considering that their MFC:MIC ratios were mostly ≥32 and that after 6 h of incubation the starting inoculum was not reduced in >90%.
Safety and efficacy of rifabutin among HIV/TB-coinfected children on lopinavir/ritonavir-based ART
Authors: Rawizza Holly E , Darin Kristin M , Oladokun Regina , Brown Biobele , Ogunbosi Babatunde , David Nkiruka , Akanmu Sulaimon , Olaitan Oluremi , Chang Charlotte , Scarsi Kimberly K , Okonkwo Prosper , Kanki Phyllis J
Published: May 2019

Background

TB is the leading cause of death among HIV-infected children, yet treatment options for those who require PI-based ART are suboptimal. Rifabutin is the preferred rifamycin for adults on PI-based ART; only one study has evaluated its use among children on PIs and two of six children developed treatment-limiting neutropenia.

Methods

Since 2009, rifabutin has been available for HIV/TB-coinfected children requiring PI-based ART in the Harvard/APIN programme in Nigeria. We retrospectively analysed laboratory and clinical toxicities at baseline and during rifabutin therapy, and examined HIV/TB outcomes.

Results

Between 2009 and 2015, 48 children received rifabutin-containing TB therapy with PI (lopinavir/ritonavir)-based ART: 50% were female with a median (IQR) baseline age of 1.7 (0.9–5.0) years and a median (IQR) CD4+ cell percentage of 15% (9%–25%); 52% were ART experienced. Eighty-five percent completed the 6 month rifabutin course with resolution of TB symptoms and 79% were retained in care at 12 months. Adverse events (grade 1–4) were more common at baseline (27%) than during rifabutin treatment (15%) (P = 0.006). Absolute neutrophil count was lower during rifabutin compared with baseline (median = 1762 versus 2976 cells/mm3, respectively), but only one instance (2%) of grade 3 neutropenia occurred during rifabutin treatment.

Conclusions

With clinical and laboratory monitoring, our data suggest that rifabutin is a safe option for TB therapy among children on PI-based ART. By contrast with the only other study of this combination in children, severe neutropenia was rare. Furthermore, outcomes from this cohort suggest that rifabutin is effective, and a novel option for children who require PI-based ART. Additional study of rifabutin plus PIs in children is urgently needed.
Toll-like receptor 7 regulates osteoclastogenesis in rheumatoid arthritis
Authors: Kim Kyoung-Woon , Kim Bo-Mi , Won Ji-Yeon , Lee Kyung-Ann , Kim Hae-Rim , Lee Sang-Heon
Published: May 2019

This study aimed to determine the regulatory role of toll-like receptor 7 (TLR7) in receptor activator of nuclear factor kappa-B ligand (RANKL) production and osteoclast differentiation in rheumatoid arthritis (RA). In confocal microscopy, the co-expression of TLR7, CD55 and RANKL was determined in RA synovial fibroblasts. After RA synovial fibroblasts were treated with imiquimod, the RANKL gene expression and protein production were determined by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Osteoclastogenesis from peripheral blood CD14+ monocytes which were cultured with imiquimod was assessed by determining the numbers of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. The signal pathways mediating the TLR7-induced RANKL expression and osteoclastogenesis were analysed after inhibition of intracellular signal molecules and their phosphorylation. Imiquimod stimulated the expression of TLR7 and RANKL and production of RANKL in RA synovial fibroblasts, increasing the phosphorylation of TRAF6, IRF7, mitogen-activated protein kinases (MAPK), c-Jun and NFATc1. When CD14+ monocytes were cultured with imiquimod or co-cultured with imiquimod-pre-treated RA synovial fibroblasts, they were differentiated into TRAP+ multinucleated osteoclasts in the absence of RANKL. TLR7 activation-induced osteoclastogenesis in RA through direct induction of osteoclast differentiation from its precursors and up-regulation of RANKL production in RA synovial fibroblasts. Thus, the blockage of TLR7 pathway could be a promising therapeutic strategy for preventing bone destruction in RA.
Effects of Two Cultivated Brassica spp. on the Development and Performance of Diadegma semiclausum (Hymenoptera: Ichneumonidae) and Cotesia vestalis (Hymenoptera: Braconidae) Parasitizing Plutella xylostella (Lepidoptera: Plutellidae) in Kenya
Authors: Kahuthia-Gathu Ruth , Othim Stephen T O
Published: May 2019

The diamondback moth (DBM), Plutella xylostella L., is the most destructive pest affecting vegetable production in Kenya and around the world. Parasitoids have shown promising results in lowering the pest populations and damage caused by DBM. However, variations in host plant quality have been reported to have bottom-up effects up to the third and fourth trophic levels. We assessed the effects of two cultivated Brassica varieties (cabbage, Brassica oleracea var. capitata L. cultivar ‘Gloria F1’ and kale, B. oleracea var. acephala L. cultivar ‘Thousand headed’) on the development and performance of the specialist pest P. xylostella and two exotic parasitoids Diadegma semiclausum (Hellen) and Cotesia vestalis (Haliday). The exposed larval period of DBM took about 1.5 d longer on kale than cabbage and the total immature development time of both females and males was significantly longer on kale than cabbage. Higher pupal weight and higher fecundity were recorded on DBM fed on kale. Development time of D. semiclausum and C. vestalis was not affected by the host crop as was the parasitism rate of D. semiclausum. Heavier male pupae and larger adults of D. semiclausum, as well as more fecund adults of C. vestalis, were obtained from hosts fed on cabbage. Larger adults of C. vestalis were obtained from herbivores fed on kale. These results show potentially positive effects of host plant allelochemicals that are detrimental to herbivores while promoting parasitoid development and performance, which can be harnessed for the control of DBM.
Developing a Quality of Cancer Survivorship Care Framework: Implications for Clinical Care, Research, and Policy
Authors: Nekhlyudov Larissa , Mollica Michelle A , Jacobsen Paul B , Mayer Deborah K , Shulman Lawrence N , Geiger Ann M
Published: May 2019

There are now close to 17 million cancer survivors in the United States, and this number is expected to continue to grow. One decade ago the Institute of Medicine report, From Cancer Patient to Cancer Survivor: Lost in Transition, outlined 10 recommendations aiming to provide coordinated, comprehensive care for cancer survivors. Although there has been noteworthy progress made since the release of the report, gaps remain in research, clinical practice, and policy. Specifically, the recommendation calling for the development of quality measures in cancer survivorship care has yet to be fulfilled. In this commentary, we describe the development of a comprehensive, evidence-based cancer survivorship care quality framework and propose the next steps to systematically apply it in clinical settings, research, and policy.
Contrasting Epidemiology and Clinicopathology of Female Breast Cancer in Asians vs the US Population
Authors: Lin Ching-Hung , Yap Yoon Sim , Lee Kyung-Hun , Im Seock-Ah , Naito Yoichi , Yeo Winnie , Ueno Takayuki , Kwong Ava , Li Huiping , Huang Shu-Min , Leung Roland , Han Wonshik , Tan Benita , Hu Fu-Chang , Huang Chiun-Sheng , Cheng Ann-Lii , Lu Yen-Shen ,   The Asian Breast Cancer Cooperative Group
Published: May 2019

Background

The incidence of breast cancer among younger East Asian women has been increasing rapidly over recent decades. This international collaborative study systemically compared the differences in age-specific incidences and pathological characteristics of breast cancer in East Asian women and women of predominantly European ancestry.

Methods

We excerpted analytic data from six national cancer registries (979 675 cases) and eight hospitals (18 008 cases) in East Asian countries and/or regions and, for comparisons, from the US Surveillance, Epidemiology, and End Results program database. Linear regression analyses of age-specific incidences of female breast cancer and logistic regression analyses of age-specific pathological characteristics of breast cancer were performed. All statistical tests were two-sided.

Results

Unlike female colorectal cancer, the age-specific incidences of breast cancer among East Asian women aged 59 years and younger increased disproportionally over recent decades relative to rates in US contemporaries. For years 2010–2014, the estimated age-specific probability of estrogen receptor positivity increased with age in American patients, whereas that of triple-negative breast cancer (TNBC) declined with age. No similar trends were evident in East Asian patients; their probability of estrogen receptor positivity at age 40–49 years was statistically significantly higher (odd ratio [OR] = 1.50, 95% confidence interval [CI] = 1.36 to 1.67, P < .001) and of TNBC was statistically significantly lower (OR = 0.79, 95% CI = 0.71 to 0.88, P < .001), whereas the probability of ER positivity at age 50–59 years was statistically significantly lower (OR = 0.88, 95% CI = 0.828 to 0.95, P < .001). Subgroup analyses of US Surveillance, Epidemiology, and End Results data showed similarly distinct patterns between East Asian American and white American patients.

Conclusions

Contrasting age-specific incidences and pathological characteristics of breast cancer between East Asian and American women, as well as between East Asian Americans and white Americans, suggests racial differences in the biology.
Multiple intestinal intussusceptions caused by highly impaired gastrointestinal motility in a patient with chronic cannabis consumption
Authors: Prokopchuk Olga , Neumann Philipp-Alexander , Hüser Norbert , Friess Helmut , Wilhelm Dirk
Published: May 2019

Since the therapeutic use of cannabis and its derivatives is currently rising, the adverse effects of cannabis and cannabinoids are of special interest. However little is known about the possible effects of long-term use of cannabis on the gastrointestinal motility. Herewith we describe the case of a patient with a rare severe form of intestinal intussusception following long-term cannabis consumption. The case shall raise awareness of possible life threatening complications of the use of cannabis and its derivates.
Response of Sulfolobus solfataricus Dpo4 polymerase in vitro to a DNA G-quadruplex
Authors: Berroyer Alexandra , Alvarado Gloria , Larson Erik D
Published: May 2019

Repetitive DNA sequences support the formation of structures that can interrupt replication and repair, leading to breaks and mutagenesis. One particularly stable structure is G-quadruplex (G4) DNA, which is four-stranded and formed from tandemly repetitive guanine bases. When folded within a template, G4 interferes with DNA synthesis. Similar to non-duplex structures, DNA base lesions can also halt an advancing replication fork, but the Y-family polymerases solve this problem by bypassing the damage. In order to better understand how guanine-rich DNA is replicated, we have investigated the activity of the model Y-family polymerase, Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4), on guanine-rich templates in vitro. We find that Dpo4 progression on templates containing either a single GC-rich hairpin or a G4 DNA structure is greatly reduced and synthesis stalls at the structure. Human polymerase eta (hPol eta) showed the same pattern of stalling at G4; however, and in contrast to Klenow, hPol eta and Dpo4 partially synthesise into the guanine repeat. Substitution of the nucleotide selectivity residue in Dpo4 with alanine permitted ribonucleotide incorporation on unstructured templates, but this further reduced the ability of Dpo4 to synthesise across from the guanine repeats. The advancement of Dpo4 on G4 templates was highest when the reaction was supplied with only deoxycytidine triphosphate, suggesting that high-fidelity synthesis is favoured over misincorporation. Our results are consistent with a model where the Y-family polymerases pause upon encountering G4 structures but have an ability to negotiate some synthesis through tetrad-associated guanines. This suggests that the Y-family polymerases reduce mutagenesis by catalysing the accurate replication of repetitive DNA sequences, but most likely in concert with additional replication and structure resolution activities.
Chromatin condensation fluctuations rather than steady-state predict chromatin accessibility
Authors: Audugé Nicolas , Padilla-Parra Sergi , Tramier Marc , Borghi Nicolas , Coppey-Moisan Maïté
Published: May 2019

Chromatin accessibility to protein factors is critical for genome activities. However, the dynamic properties of chromatin higher-order structures that regulate its accessibility are poorly understood. Here, we took advantage of the microenvironment sensitivity of the fluorescence lifetime of EGFP-H4 histone incorporated in chromatin to map in the nucleus of live cells the dynamics of chromatin condensation and its direct interaction with a tail acetylation recognition domain (the double bromodomain module of human TAFII250, dBD). We reveal chromatin condensation fluctuations supported by mechanisms fundamentally distinct from that of condensation. Fluctuations are spontaneous, yet their amplitudes are affected by their sub-nuclear localization and by distinct and competing mechanisms dependent on histone acetylation, ATP and both. Moreover, we show that accessibility of acetylated histone H4 to dBD is not restricted by chromatin condensation nor predicted by acetylation, rather, it is predicted by chromatin condensation fluctuations.
EPIC-TABSAT: analysis tool for targeted bisulfite sequencing experiments and array-based methylation studies
Authors: Krainer Julie , Weinhäusel Andreas , Hanak Karel , Pulverer Walter , Özen Seza , Vierlinger Klemens , Pabinger Stephan
Published: May 2019

DNA methylation is one of the major epigenetic modifications and has frequently demonstrated its suitability as diagnostic and prognostic biomarker. In addition to chip and sequencing based epigenome wide methylation profiling methods, targeted bisulfite sequencing (TBS) has been established as a cost-effective approach for routine diagnostics and target validation applications. Yet, an easy-to-use tool for the analysis of TBS data in combination with array-based methylation results has been missing. Consequently, we have developed EPIC-TABSAT, a user-friendly web-based application for the analysis of targeted sequencing data that additionally allows the integration of array-based methylation results. The tool can handle multiple targets as well as multiple sequencing files in parallel and covers the complete data analysis workflow from calculation of quality metrics to methylation calling and interactive result presentation. The graphical user interface offers an unprecedented way to interpret TBS data alone or in combination with array-based methylation studies. Together with the computation of target-specific epialleles it is useful in validation, research, and routine diagnostic environments. EPIC-TABSAT is freely accessible to all users at https://tabsat.ait.ac.at/.
NAPS update: network analysis of molecular dynamics data and protein–nucleic acid complexes
Authors: Chakrabarty Broto , Naganathan Varun , Garg Kanak , Agarwal Yash , Parekh Nita
Published: May 2019

Network theory is now a method of choice to gain insights in understanding protein structure, folding and function. In combination with molecular dynamics (MD) simulations, it is an invaluable tool with widespread applications such as analyzing subtle conformational changes and flexibility regions in proteins, dynamic correlation analysis across distant regions for allosteric communications, in drug design to reveal alternative binding pockets for drugs, etc. Updated version of NAPS now facilitates network analysis of the complete repertoire of these biomolecules, i.e., proteins, protein–protein/nucleic acid complexes, MD trajectories, and RNA. Various options provided for analysis of MD trajectories include individual network construction and analysis of intermediate time-steps, comparative analysis of these networks, construction and analysis of average network of the ensemble of trajectories and dynamic cross-correlations. For protein–nucleic acid complexes, networks of the whole complex as well as that of the interface can be constructed and analyzed. For analysis of proteins, protein–protein complexes and MD trajectories, network construction based on inter-residue interaction energies with realistic edge-weights obtained from standard force fields is provided to capture the atomistic details. Updated version of NAPS also provides improved visualization features, interactive plots and bulk execution. URL: http://bioinf.iiit.ac.in/NAPS/
DaReUS-Loop: a web server to model multiple loops in homology models
Authors: Karami Yasaman , Rey Julien , Postic Guillaume , Murail Samuel , Tufféry Pierre , de Vries Sjoerd J
Published: May 2019

Loop regions in protein structures often have crucial roles, and they are much more variable in sequence and structure than other regions. In homology modeling, this leads to larger deviations from the homologous templates, and loop modeling of homology models remains an open problem. To address this issue, we have previously developed the DaReUS-Loop protocol, leading to significant improvement over existing methods. Here, a DaReUS-Loop web server is presented, providing an automated platform for modeling or remodeling loops in the context of homology models. This is the first web server accepting a protein with up to 20 loop regions, and modeling them all in parallel. It also provides a prediction confidence level that corresponds to the expected accuracy of the loops. DaReUS-Loop facilitates the analysis of the results through its interactive graphical interface and is freely available at http://bioserv.rpbs.univ-paris-diderot.fr/services/DaReUS-Loop/.
Fido-SNP: the first webserver for scoring the impact of single nucleotide variants in the dog genome
Authors: Capriotti Emidio , Montanucci Ludovica , Profiti Giuseppe , Rossi Ivan , Giannuzzi Diana , Aresu Luca , Fariselli Piero
Published: May 2019

As the amount of genomic variation data increases, tools that are able to score the functional impact of single nucleotide variants become more and more necessary. While there are several prediction servers available for interpreting the effects of variants in the human genome, only few have been developed for other species, and none were specifically designed for species of veterinary interest such as the dog. Here, we present Fido-SNP the first predictor able to discriminate between Pathogenic and Benign single-nucleotide variants in the dog genome. Fido-SNP is a binary classifier based on the Gradient Boosting algorithm. It is able to classify and score the impact of variants in both coding and non-coding regions based on sequence features within seconds. When validated on a previously unseen set of annotated variants from the OMIA database, Fido-SNP reaches 88% overall accuracy, 0.77 Matthews correlation coefficient and 0.91 Area Under the ROC Curve.
RAD51 and mitotic function of mus81 are essential for recovery from low-dose of camptothecin in the absence of the WRN exonuclease
Authors: Aiello Francesca Antonella , Palma Anita , Malacaria Eva , Zheng Li , Campbell Judith L , Shen Binghui , Franchitto Annapaola , Pichierri Pietro
Published: May 2019

Stabilization of stalled replication forks prevents excessive fork reversal or degradation, which can undermine genome integrity. The WRN protein is unique among the other human RecQ family members to possess exonuclease activity. However, the biological role of the WRN exonuclease is poorly defined. Recently, the WRN exonuclease has been linked to protection of stalled forks from degradation. Alternative processing of perturbed forks has been associated to chemoresistance of BRCA-deficient cancer cells. Thus, we used WRN exonuclease-deficiency as a model to investigate the fate of perturbed forks undergoing degradation, but in a BRCA wild-type condition. We find that, upon treatment with clinically-relevant nanomolar doses of the Topoisomerase I inhibitor camptothecin, loss of WRN exonuclease stimulates fork inactivation and accumulation of parental gaps, which engages RAD51. Such mechanism affects reinforcement of CHK1 phosphorylation and causes persistence of RAD51 during recovery from treatment. Notably, in WRN exonuclease-deficient cells, persistence of RAD51 correlates with elevated mitotic phosphorylation of MUS81 at Ser87, which is essential to prevent excessive mitotic abnormalities. Altogether, these findings indicate that aberrant fork degradation, in the presence of a wild-type RAD51 axis, stimulates RAD51-mediated post-replicative repair and engagement of the MUS81 complex to limit genome instability and cell death.
A new normalization for Nanostring nCounter gene expression data
Authors: Molania Ramyar , Gagnon-Bartsch Johann A , Dobrovic Alexander , Speed Terence P
Published: May 2019

The Nanostring nCounter gene expression assay uses molecular barcodes and single molecule imaging to detect and count hundreds of unique transcripts in a single reaction. These counts need to be normalized to adjust for the amount of sample, variations in assay efficiency and other factors. Most users adopt the normalization approach described in the nSolver analysis software, which involves background correction based on the observed values of negative control probes, a within-sample normalization using the observed values of positive control probes and normalization across samples using reference (housekeeping) genes. Here we present a new normalization method, Removing Unwanted Variation-III (RUV-III), which makes vital use of technical replicates and suitable control genes. We also propose an approach using pseudo-replicates when technical replicates are not available. The effectiveness of RUV-III is illustrated on four different datasets. We also offer suggestions on the design and analysis of studies involving this technology.
HIV Coinfection Predicts Failure of Ledipasvir/Sofosbuvir in Treatment-Naïve Noncirrhotic Patients With HCV Genotype 1
Authors: Berenguer Juan , Calleja José Luis , Montes María Luisa , Gil Ángela , Moreno Ana , Bañares Rafael , Aldámiz-Echevarría Teresa , Albillos Agustín , Téllez María Jesús , Olveira Antonio , Domínguez Lourdes , Fernández Inmaculada , García-Samaniego Javier , Polo Benjamín A , Álvarez Beatriz , Ryan Pablo , Barrio José , Devesa María J , Benítez Laura , Santos Ignacio , Buey Luisa García , Sanz José , Poves Elvira , Losa Juan E , Fernández-Rodríguez Conrado , Jarrín Inmaculada , Calvo María J , González-García Juan
Published: May 2019

Background

The efficacy of licensed direct-acting antiviral (DAA) regimens is assumed to be the same for hepatitis C virus (HCV)–monoinfected patients (HCV-Mono) and HIV/HCV-coinfected patients (HCV-Co). However, the high sustained viral response (SVR) rates of DAA regimens and the small number of HIV-infected patients included in registration trials have made it difficult to identify predictors of treatment failure, including the presence of HIV.

Methods

We compared treatment outcomes for ledipasvir/sofosbuvir (LDV/SOF) against HCV G1 in treatment-naïve HCV-Mono and HCV-Co without cirrhosis in a prospective registry of individuals receiving DAAs for HCV.

Results

Up to September 2017, a total of 17 269 patients were registered, and 1358 patients (1055 HCV-Mono/303 HCV-Co) met the inclusion criteria. Significant differences between HCV-Mono and HCV-Co were observed for age, gender, and G1 subtype distribution. Among HCV-Co, 99.0% were receiving antiretroviral therapy. SVR rates for LDV/SOF at 8 weeks did not differ significantly between HCV-Mono and HCV-Co (96.9% vs 94.0%; P = .199). However, the SVR rate for LDV/SOF at 12 weeks was significantly higher for HCV-Mono than HCV-Co (97.2% vs 91.8%; P = .001). A multivariable logistic regression model including age, sex, liver stiffness, G1 subtype, HCV-RNA, HIV, and treatment duration showed the factors associated with treatment failure to be male sex (adjusted odds ratio [aOR], 2.49; 95% confidence interval [CI], 1.27–4.91; P = .008) and HIV infection (aOR, 2.23; 95% CI, 1.13–4.38; P = .020).

Conclusions

The results of this large prospective study analyzing outcomes for LDV/SOF against HCV G1 in treatment-naïve noncirrhotic patients suggest that HIV infection is a predictor of treatment failure in patients with chronic hepatitis C.
Treatment Duration and Associated Outcomes for Skin and Soft Tissue Infections in Patients With Obesity or Heart Failure
Authors: Ihm Claudia , Sutton Jesse D , Timbrook Tristan T , Spivak Emily S
Published: May 2019

Background

Although existing literature supports durations of 5–7 days for skin and soft tissue infections (SSTIs), longer durations are commonly used. Obesity and heart failure (HF) have been associated with increased risk for treatment failure of SSTIs; however, whether prolonged antibiotic durations reduce the risk of treatment failure is unknown. We evaluated practice patterns for SSTIs in patients with obesity and/or HF and whether short antibiotic durations (≤8 days) were associated with treatment failure.

Methods

We performed a single-center, retrospective cohort study of inpatients between January 1, 2006, and December 30, 2016, with SSTIs based on International Classification of Diseases (ICD) coding, and obesity and/or HF. Charts were manually reviewed to collect demographic, clinical, treatment, and outcome data. Propensity score matching was used to estimate the risk of treatment failure between the 2 groups. Secondary outcomes included length of stay, 30-day readmission, and Clostridium difficile infection rates.

Results

A total of 207 patients were included. Forty-nine (23.7%) received a short antibiotic duration and 158 (76.3%) a long duration. The median duration of therapy (interquartile range [IQR]) was 7 (7–8) days in the short group and 14 (10–15) days in the long group. In the propensity score–matched cohort, 28 (28.6%) treatment failures occurred in the long group, as compared with 5 (10.2%) in the short group (P = .02), as well as a shorter length of stay (IQR) in the short- vs long-duration group (2 [2–3] vs 3 [2–5] days, respectively; P = .002). There was no difference in other secondary outcomes.

Conclusions

The majority of patients with obesity or HF received a longer antibiotic course for SSTIs; however, a longer antibiotic course was not associated with lower treatment failure rates. Higher failure rates in the long-duration group may be reflective of clinical decisions made in the face of diagnostic uncertainty and warrant further evaluation.
Religious Origins and Modern Legal Norms: A Dialectical Account
Authors: Mauldin Joshua T
Published: May 2019

A significant amount of scholarship in the field of law and religion involves tracing the sources of contemporary legal and political norms to historical religious traditions. But the relationship between historical religious traditions and modern legal norms is often implicit and undertheorized. This article examines three examples of leading scholars who trace the influence of religious ideas to legal norms in strikingly different ways. Highlighting the work of Martha Nussbaum, Jeremy Waldron, and Samuel Moyn helps bring to rational articulation the normative decisions that are made in attempts to trace historical religious traditions to the contemporary norms that shape modern legal systems.
Endoscopic Fluorescence-Guided Resection Increases Radicality in Glioblastoma Surgery
Authors: Bettag Christoph , Hussein Abdelhalim , Behme Daniel , Maragkou Theoni , Rohde Veit , Mielke Dorothee
Published: May 2019

BACKGROUND

Several studies have proven the benefit of a greater extent of resection on progression-free survival and overall survival in glioblastoma (GBM). Possible reasons for incomplete tumor resection might be wrong interpretation of fading fluorescence or overseen fluorescent tumor tissue by a lacking line of sight between tumor tissue and the microscope.

OBJECTIVE

To evaluate if an endoscope being capable of inducing fluorescence might overcome some limitations of microscopic fluorescence-guided (FG) resection.

METHODS

5-Aminolevulinic acid (20 mg/kg) was given 4 h before surgery. Microsurgical resection of all fluorescent tissue was performed. Then, the resection cavity was scanned with the endoscope. Fluorescent tissue, not being visualized by the microscope, was additionally removed and histopathologically examined separately. Neuronavigation was used for defining the sites of additional tumor resection. All patients underwent magnetic resonance imaging within 48 h after surgery.

RESULTS

Twenty patients with GBM were operated using microscopic and endoscopic FG resection. In all patients, additional fluorescent tissue was detected with the endoscope. This tissue was completely resected in 19 patients (95%). Eloquent localization precluded complete resection in the remaining patient. In 19 patients (95%), histopathological examination confirmed tumor in the additionally resected tissue. In 19 patients (95%), complete resection was confirmed. In all patients, endoscopic FG resection reached beyond the borders of contrast-enhancing tumor.

CONCLUSION

Endoscopic FG resection of GBM allows increasing the complete resection rate substantially and therefore is a useful adjunct to microscopic FG resection.
Understanding further education as a context for public health intervention: qualitative findings from a study process evaluation
Authors: Langford R , Willmott M , Fletcher A
Published: May 2019

Background

Over 1.2 million 16–18 year-olds are enrolled in further education (FE—advanced secondary education) in England. Life course transitions provide opportunities to change, establish or reinforce health behaviours. FE presents an opportunity for public health improvement, yet few interventions target this setting. Using a smoking prevention intervention, we explore how young people were viewed in FE and how this affected intervention acceptability.

Methods

Eleven student and five staff focus groups were conducted in three intervention institutions (two colleges, one school sixth-form), as part of the process evaluation of a smoking prevention feasibility study. FE managers in intervention and control institutions were also interviewed (n = 5). Data were analysed using thematic analysis.

Results

In both colleges and the sixth-form, students were viewed as emergent adults and treated differently from ‘school-children’, in practice if not in policy. Colleges permitted smoking in designated areas; in the school sixth-form smoking was unofficially tolerated but concealed from younger students. Using staff to deliver anti-smoking messages reintroduced an unwanted power dynamic which disrupted perceptions of students as young adults.

Conclusions

FE is an important setting for young people’s health. Understanding the culture and context of FE is critical in designing acceptable and effective public health interventions.
Effectiveness of public procurement of innovation versus supply-side innovation measures in manufacturing and service sectors
Authors: Radicic Dragana
Published: May 2019

Most quantitative evaluations report positive but small effects of supply-side innovation measures. Although the literature suggests that demand-side measures, in particular, public procurement of innovation, might be more effective in stimulating innovation than supply-side measures, empirical evidence on this proposition is scarce. To empirically test this proposition, we utilize the Eurobarometer 2014 survey to estimate the effects from public procurement of innovation as well as from the supply-side innovation measures on product and process innovations in manufacturing and service firms in the USA and Europe. Our findings suggest that the treatment effects of public procurement of innovation are indeed larger than the effects of supply-side public support on product innovation in both manufacturing and service sectors. This finding also holds for process innovation, but only in the service sector. In contrast, in manufacturing firms, the estimated effects on process innovation are only positive and significant in firms receiving public support.
The transcriptional activity of a temperature-sensitive transcription factor module is associated with pollen shedding time in pine
Authors: Niu Shi-Hui , Liu Shuang-Wei , Ma Jing-Jing , Han Fang-Xu , Li Yue , Li Wei
Published: May 2019

It has long been known that the pollen shedding time in pine trees is correlated with temperature, but the molecular basis for this has remained largely unknown. To better understand the mechanisms driving temperature response and to identify the hub regulators of pollen shedding time regulation in Pinus tabuliformis Carr., we identified a set of temperature-sensitive genes by carrying out a comparative transcriptome analysis using six early pollen shedding trees (EPs) and six late pollen shedding trees (LPs) during mid-winter and at three consecutive time points in early spring. We carried out a weighted gene co-expression network analysis and constructed a transcription factor (TF) collaborative network, merging the common but differentially expressed TFs of the EPs and LPs into a joint network. We found five hub genes in the core TF module whose expression was rapidly induced by low temperatures. The transcriptional activity of this TF module was strongly associated with pollen shedding time, and likely to produce the fine balance between cold hardiness and growth activity in early spring. We confirmed the key role of temperature in regulating flowering time and identified a transcription factor module associated with pollen shedding time in P. tabuliformis. This suggests that repression of growth activity by repressors is the main mechanism balancing growth and cold hardiness in pine trees in early spring. Our results provide new insights into the molecular mechanisms regulating seasonal flowering time in pines.
Epidemiology and distribution of Plasmodium vivax malaria in Sudan
Authors: Elgoraish Amanda G , Elzaki Salah Eldin G , Ahmed Rania TagElsir , Ahmed Arwa Ibrahim , Fadlalmula Huda A , Abdalgader Mohamed Shymaa , Abdallah Nusiba I , Abdelgadir Osman , Ageep Tellal B , El-Sayed Badria B
Published: May 2019

Background

Plasmodium vivax malaria has been recognised as an important cause of morbidity in several African countries. The prevalence was previously estimated as 2–5% in eastern Sudan. These estimates are observed to be rising and spreading continuously. The present study was undertaken to investigate the situation of distribution and epidemiology of P. vivax malaria in Sudan.

Methods

Cross-sectional malaria surveys carried out in hospitals and health centres covered 21 sites in 10 states. Data and blood samples were collected from 1226 clinically investigated suspected malaria cases of both genders and all ages. Microscopically detected malaria parasites were confirmed by PCR.

Results

The overall prevalence of P. vivax among the malaria cases was 26.6%. The prevalence showed significant variations between the states (p<0.001), which could be explained by differences in population movement, the presence of refugees and proximity to endemic neighbouring countries. It also varied significantly with residence status (p<0.001), reflecting the stability of transmission.

Conclusion

Although malaria in Sudan is still largely attributed to Plasmodium falciparum, P. vivax has been rising with worrying proportions and spreading to new areas. The emergence and marked increase of P. vivax poses new challenges to malaria treatment and control in Sudan.
Chitin-Binding Protein ofVerticillium nonalfalfaeDisguises Fungus from Plant Chitinases and Suppresses Chitin-Triggered Host Immunity
Authors: Volk Helena , Marton Kristina , Flajšman Marko , Radišek Sebastjan , Tian Hui , Hein Ingo , Podlipnik Črtomir , Thomma Bart P. H. J. , Košmelj Katarina , Javornik Branka , Berne Sabina
Published: May 2019

During fungal infections, plant cells secrete chitinases, which digest chitin in the fungal cell walls. The recognition of released chitin oligomers via lysin motif (LysM)-containing immune host receptors results in the activation of defense signaling pathways. We report here that Verticillium nonalfalfae, a hemibiotrophic xylem-invading fungus, prevents these digestion and recognition processes by secreting a carbohydrate-binding motif 18 (CBM18)-chitin-binding protein, VnaChtBP, which is transcriptionally activated specifically during the parasitic life stages. VnaChtBP is encoded by the Vna8.213 gene, which is highly conserved within the species, suggesting high evolutionary stability and importance for the fungal lifestyle. In a pathogenicity assay, however, Vna8.213 knockout mutants exhibited wilting symptoms similar to the wild-type fungus, suggesting that Vna8.213 activity is functionally redundant during fungal infection of hop. In a binding assay, recombinant VnaChtBP bound chitin and chitin oligomers in vitro with submicromolar affinity and protected fungal hyphae from degradation by plant chitinases. Moreover, the chitin-triggered production of reactive oxygen species from hop suspension cells was abolished in the presence of VnaChtBP, indicating that VnaChtBP also acts as a suppressor of chitin-triggered immunity. Using a yeast-two-hybrid assay, circular dichroism, homology modeling, and molecular docking, we demonstrated that VnaChtBP forms dimers in the absence of ligands and that this interaction is stabilized by the binding of chitin hexamers with a similar preference in the two binding sites. Our data suggest that, in addition to chitin-binding LysM (CBM50) and Avr4 (CBM14) fungal effectors, structurally unrelated CBM18 effectors have convergently evolved to prevent hydrolysis of the fungal cell wall against plant chitinases and to interfere with chitin-triggered host immunity.
Sensitivity of the Colletotrichum acutatum Species Complex From Apple Trees in Brazil to Dithiocarbamates, Methyl Benzimidazole Carbamates, and Quinone Outside Inhibitor Fungicides
Authors: Moreira Rafaele R. , Hamada Natasha A. , Peres Natalia A. , De Mio Louise L. May
Published: May 2019

Glomerella leaf spot (GLS) and bitter rot (BR) on apples are often caused by Colletotrichum acutatum in Paraná State, Brazil. GLS control is difficult because of its rapid development, with an incubation period of only 2 days under favorable conditions. Therefore, producers use successive fungicide applications every season; however, failure to control GLS has been commonly reported. The objectives of this study were to determine the sensitivity of isolates of the C. acutatum species complex obtained from apple orchards in Brazil to mancozeb, thiophanate-methyl, and azoxystrobin fungicides. Isolates from the different parts of the plant (leaves, flowers, buds, and twigs) and cultivars (Gala and Eva) showed different levels of sensitivity to mancozeb, thiophanate-methyl, and azoxystrobin. For mancozeb, the frequencies of isolates were 25% highly resistant, 50% low-resistance, and 25% sensitive. For thiophanate-methyl, the frequencies of isolates were 72.2% highly resistant, 11.1% resistant, and 16.7% moderately resistant. For azoxystrobin, the frequencies of isolates were 11.1% highly resistant, 5.6% resistant, and 83.3% sensitive. Interestingly, no mutations in the β-tubulin and cytochrome b genes were observed in any of the isolates resistant to thiophanate-methyl and azoxystrobin fungicides.
A Microsatellite Analysis Used to Identify Global Pathways of Movement of Phytophthora cinnamomi and the Likely Sources of Wildland Infestations in California and Mexico
Authors: Socorro Serrano María , Osmundson Todd , Almaraz-Sánchez Alejandra , Croucher Peter J. P. , Swiecki Tedmund , Alvarado-Rosales Dionicio , Garbelotto Matteo
Published: May 2019

The genetic structure of a sample of isolates of the oomycete plant pathogen Phytophthora cinnamomi from natural and agricultural outbreaks and the long-distance movement of individual genotypes were studied using four microsatellite markers to genotype 159 isolates of Californian, Mexican, and worldwide origins. Allelic profiles identified 75 multilocus genotypes. A STRUCTURE analysis placed them in three groups characterized by different geographic and host ranges, different genic and genotypic diversity, and different reproductive modes. When relationships among genotypes were visualized on a minimum spanning network (MSN), genotypes belonging to the same STRUCTURE group were contiguous, with rare exceptions. A putatively ancestral group 1 had high genic diversity, included all A1 mating type isolates and all Papuan isolates in the sample, was rarely isolated from natural settings in California and Mexico, and was positioned at the center of the MSN. Putatively younger groups 2 and 3 had lower genic diversity, were both neighbors to group 1 but formed two distinct peripherical sectors of the MSN, and were equally present in agricultural commodities and natural settings in Mexico and California. A few genotypes, especially in groups 2 and 3, were isolated multiple times in different locations and settings. The presence of identical genotypes from the same hosts in different continents indicated that long-distance human-mediated movement of P. cinnamomi had occurred. The presence of identical genotypes at high frequencies in neighboring wildlands and agricultural settings suggest that specific commodities may have been the source of recent wild infestations caused by novel invasive genotypes.
The influence of visual experience and cognitive goals on spatial representations of nociceptive stimuli
Authors: Vanderclausen Camille , Manfron Louise , De Volder Anne , Legrain Valéry
Published: May 2019

Localizing pain is an important process as it allows detecting which part of the body is being hurt and identifying in its surrounding which stimulus is producing the damage. Nociceptive inputs should therefore be mapped according to both somatotopic (“which limb is stimulated?”) and spatiotopic representations (“where is the stimulated limb?”). Since the limbs constantly move in space, the brain has to realign the different spatial representations, for instance when the hands are crossed and the left/right hand is in the right/left part of space, in order to adequately guide actions towards the threatening object. Such ability is thought to be dependent on past sensory experience and contextual factors. This was tested by comparing performances of early blind and normally sighted participants during nociceptive temporal order judgment tasks. The instructions prioritized either anatomy (left/right hands) or the external space (left/right hemispaces). As compared to an uncrossed hands posture, sighted participants’ performances were decreased when the hands were crossed, whatever the instructions. Early blind participants’ performances were affected by crossing the hands only during spatial instruction, but not during anatomical instruction. These results indicate that nociceptive stimuli are automatically coded according to both somatotopic and spatiotopic representations, but the integration of the different spatial reference frames would depend on early visual experience and ongoing cognitive goals, illustrating the plasticity and the flexibility of the nociceptive system.
Photoreceptor inputs to pupil control
Authors: Spitschan Manuel
Published: May 2019

The size of the pupil depends on light level. Watson & Yellott (2012) developed a unified formula to predict pupil size from luminance, field diameter, age, and number of eyes. Luminance reflects input from the L and M cones in the retina but ignores the contribution of intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin, which are known to control the size of the pupil. We discuss the role of melanopsin in controlling pupil size by reanalysing an extant data set. We confirm that melanopsin-weighted quantities, in conjunction with Watson & Yellott’s formula, adequately model intensity-dependent pupil size. We discuss the contributions of other photoreceptors into pupil control.
Auditory cortical alpha desynchronization prioritizes the representation of memory items during a retention period
Authors: Kraft Nadine , Demarchi Gianpaolo , Weisz Nathan
Published: May 2019

Maintaining information in working memory normally happens in dynamic environments, with a multitude of distracting events. This is particularly evident in the auditory system, for example, when trying to memorize a telephone number during ongoing background noise. How relevant to-be-memorized information is protected against the adverse influence of a temporally predictable distractor was the main goal of the present study. For this purpose we adapted a Sternberg task variant established in the visual modality, with either a strong or a weak distracting sound presented at a fixed time during the retention period. Our behavioral analysis confirmed a small, albeit significant deterioration of memory performance in the strong distractor condition. We used a time-generalized decoding approach applied to magnetoencephalography (MEG) data to investigate the extent of memory probe-related information prior to the anticipated distractor onset and found a relative decrease for the strong distractor condition. This effect was paralleled by a pre-distractor alpha power decrease in the left superior temporal gyrus (STG), a cortical region putatively holding memory content relevant information. Based on gating frameworks of alpha oscillations, these results could be interpreted as a failed inhibition of an anticipated strong (more salient) distractor. However, in a critical analysis we found that reduced alpha power in the left STG was associated with relatively increased memory probe-related information. Our results therefore support the view of alpha power reductions in relevant sensory (here auditory) cortical areas to be a mechanism by which to-be-remembered information is prioritized during working memory retention periods.