bluuebunny/crossref_metadata_2025 huggingface dataset:
Anticytokine autoantibodies leading to infection: early recognition, diagnosis and treatment options
Authors: Barcenas-Morales Gabriela , Cortes-Acevedo Paulina , Doffinger Rainer
Published: May 2019

Purpose of review

The current review gives a concise and updated overview of the relative new field of anticytokine autoantibodies (ACAA) and associated infections with a focus on recent findings regarding clinical manifestions, diagnostic and treatments.

Recent findings

Several recent case reports of unusual presentations of patients with neutralizing autoantibodies to IFN-γ and granulocyt macrophage colony-stimulating factor and expand the spectrum of clinical manifestations and suggest that anticytokine-mediated acquired immunodeficiency causing susceptibility to infection may be underdiagnosed. There is an expanding geographical distribution of antigranulocyt macrophage colony-stimulating factor associated Cryptococcus gattii infection. The spectrum of identified infections in patients with neutralizing antibodies to IFN-γ has a strong endemic component. Rituximab or cyclophophamide in addition to antimycobacterials could be a treatment options in refractory cases. NF-κB2 deficiency may be associated with a complex pattern of high titre neutralizing ACAA similar to autoimmune polyglandular syndrome type I and Thymoma. New technique for the detection of anticytokine antibodies are presented. Quantiferon testing, which is widely available for TB-diagnostic, may be repurposed to detect anti-IFN-γ autoantibodies. We propose that this test could be as well used to show if they are neutralizing.

ACAA are an emerging cause of acquired immunodeficiency which is likely underdiagnosed. Recent case reports document expanding spectra of clinical manifestations. NF-κB2 deficiency may be associated with a complex anti cytokine autoantibody pattern.
Balancing Deliberate Practice and Reflection
Authors: Diederich Emily , Lineberry Matthew , Blomquist Michael , Schott Vanessa , Reilly Chelsi , Murray Megan , Nazaran Pooneh , Rourk Meghan , Werner Rachel , Broski Julie
Published: May 2019

Introduction

A key question in simulation-based education is how to maximize learning within time and resource limits, including how best to balance hands-on practice versus reflective debriefing. Several instructional design frameworks suggest setting the balance according to the type of learning objective(s); however, broad professional activities such as team-based cardiopulmonary resuscitation include several interrelated component skills. This study experimentally manipulated hands-on practice versus reflective debriefing for cardiopulmonary resuscitation skills, hypothesizing that the former best supports learning taskwork (eg, compression quality), whereas the latter best supports learning teamwork.

Methods

The study was a randomized comparison trial with a pretest and posttest. Twenty-six teams of 5 to 6 first-year residents underwent either “drill” practice of key resuscitation phases, designed to maximize deliberate practice opportunities for individual and team skills, or “scrimmage” practice, designed to maximize full-scenario rehearsals and reflective debriefs. Key taskwork and teamwork behaviors were coded, and compression quality was collected and analyzed from an accelerometer.

Results

Most performance parameters improved considerably from a pretest to posttest for both taskwork (eg, percent correct compression depth 62%–81%, P = 0.01) and teamwork (eg, role leadership, 47%–70%, P = 0.00). Only 2 parameters improved differently by condition, favoring “drill” training: checking “Do Not Actively Resuscitate” wristband (odds ratio = 14.75, P = 0.03) and use of compression adjuncts (estimated marginal means = 75% versus 67%, P = 0.03).

Conclusions

Consistent with the notion that component skills in resuscitation do not clearly and exclusively constitute “taskwork” versus “teamwork,” both instructional designs led to similar improvements despite differences in the balance between hands-on practice versus reflection.
The efficiency of migration and profile control with emulsion systems in class III reservoirs
Authors: Fu Cheng , Zhu Tingting , Huang Bin , Dai Tingge , Wang Ying , Zhang Wei , Liu Xiangbin
Published: May 2019

In order to reveal the migration law and profile control efficiency of the emulsion system in the core of class III reservoir (the permeability less than 100 mD), the influence of the size and distribution of the droplets, the effect of the migration law and the adjustment of the interlayer contradiction to class III reservoir are studied in this paper. By measuring the droplet distribution in the emulsion system, we found that the average droplet diameter decreases with the increase in water cut. But, the droplet distribution is the most uniform when the water cut is 50%, which is the transition point of the emulsion. Through the core seepage test, the pressure is measured when the emulsion system is flowing through the core. It can be seen that the emulsion flowing is related to the resistance coefficient, the viscosity of the chemical agent and the core permeability; that is, the greater the resistance coefficient, the greater the viscosity of the chemical agent, the smaller the core permeability is and the higher the level of the emulsion is. The matching chart between different emulsion systems and layers with different permeability of class III reservoir was established. The effect of profile control with different permeability contrasts was predicted according to the matching chart. The emulsification has a positive effect on the enhancement of recovery when the permeability contrast is small, but a negative effect when the permeability contrast is larger. The study of the emulsion migration and profile control efficiency in class III reservoir are of great significance for understanding the emulsification in class III reservoirs.
Facile fabrication and characterization on alginate microfibres with grooved structure via microfluidic spinning
Authors: Zhang Xiaolin , Weng Lin , Liu Qingsheng , Li Dawei , Deng Bingyao
Published: May 2019

Alginate microfibres were fabricated by a simple microfluidic spinning device consisting of a coaxial flow. The inner profile and spinnability of polymer were analysed by rheology study, including the analysis of viscosity, storage modulus and loss modulus. The effect of spinning parameters on the morphological structure of fibres was studied by SEM, while the crystal structure and chemical group were characterized by FTIR and XRD, respectively. Furthermore, the width and depth of grooves on the fibres was investigated by AFM image analysis and the formation mechanism of grooves was finally analysed. It was illustrated that the fibre diameter increased with an increase in the core flow rate, whereas on the contrary of sheath flow rate. Fibre diameter exhibited an increasing tendency as the concentration of alginate solution increased, and the minimum spinning concentration of alginate solution was 1% with the finest diameter being around 25 µm. Importantly, the grooved structure was obtained by adjusting the concentration of solutions and flow rates, the depth of groove increased from 278.37 ± 2.23 µm to 727.52 ± 3.52 µm as the concentration varied from 1 to 2%. Alginate fibres, with topological structure, are candidates for wound dressing or the engineering tissue scaffolds.
Oil adsorption does not structurally or functionally alter whale baleen
Authors: Werth Alexander J. , Blakeney Shemar M. , Cothren Adrian I.
Published: May 2019

Mysticete whales filter small prey from seawater using baleen, a unique keratinous oral tissue that grows from the palate, from which it hangs in hundreds of serial plates. Laboratory experiments testing effects of oils on material strength and flexibility, particle capture and tissue architecture of baleen from four mysticete species (bowhead,Balaena mysticetus; North Atlantic right,Eubalaena glacialis; fin,Balaenoptera physalus; humpback,Megaptera novaeangliae) indicate that baleen is hydrophilic and oleophobic, shedding rather than adsorbing oil. Oils of different weights and viscosities were tested, including six petroleum-based oils and two fish or plankton oils of common whale prey. No notable differences were found by oil type or whale species. Baleen did not adsorb oil; oil was readily rinsed from baleen by flowing water, especially from moving fringes. Microscopic examination shows minimal wrinkling or peeling of baleen's cortical keratin layers, probably due to oil repelling infiltrated water. Combined results cast doubt on fears of baleen fouling by oil; filter porosity is not appreciably affected, but oil ingestion risks remain. Particle capture studies suggest potentially greater danger to mysticetes from plastic pollution than oil.
A hollow mesoporous carbon from metal-organic framework for robust adsorbability of ibuprofen drug in water
Authors: Van Tran Thuan , Cam Nguyen Duyen Thi , Le Hanh T. N. , Nguyen Oanh T. K. , Nguyen Vinh Huu , Nguyen Thuong Thi , Bach Long Giang , Nguyen Trinh Duy
Published: May 2019

Herein, we described a tunable method for synthesis of novel hollow mesoporous carbon (MPC) via direct pyrolysis (800
o
C) of MIL-53 (Fe) as a self-sacrificed template. The structural characterization revealed a hollow, amorphous, defective and mesoporous MPC along with high surface area (approx. 200 m
2
g
−1
). For the experiments of ibuprofen adsorption onto MPC, effects of contact time, MPC dosage, ionic strength, concentration and temperature were systematically investigated. The optimal conditions consisted of pH = 3, concentration 10 mg l
−1
and dose of 0.1 g l
−1
for the highest ibuprofen removal efficiency up to 88.3% after 4 h. Moreover, adsorption behaviour, whereby chemisorption and monolayer controlled the uptake of ibuprofen over MPC, were assumed. Adsorption mechanisms including H-bonding, π–π interaction, metal–oxygen, electrostatic attraction were rigorously proposed. In comparison to several studies, the MPC nanocomposite in this work obtained the outstanding maximum adsorption capacity (206.5 mg g
−1
) and good reusability (5 cycles); thus, it can be used as a feasible alternative for decontamination of ibuprofen anti-inflammatory drug from water.
Electrochemical characterization of manganese oxides as a water oxidation catalyst in proton exchange membrane electrolysers
Authors: Hayashi Toru , Bonnet-Mercier Nadège , Yamaguchi Akira , Suetsugu Kazumasa , Nakamura Ryuhei
Published: May 2019

The performance of four polymorphs of manganese (Mn) dioxides as the catalyst for the oxygen evolution reaction (OER) in proton exchange membrane (PEM) electrolysers was examined. The comparison of the activity between Mn oxides/carbon (Mn/C), iridium oxide/carbon (Ir/C) and platinum/carbon (Pt/C) under the same condition in PEM electrolysers showed that the γ-MnO
2
/C exhibited a voltage efficiency for water electrolysis comparable to the case with Pt/C, while lower than the case with the benchmark Ir/C OER catalyst. The rapid decrease in the voltage efficiency was observed for a PEM electrolyser with the Mn/C, as indicated by the voltage shift from 1.7 to 1.9 V under the galvanostatic condition. The rapid deactivation was also observed when Pt/C was used, indicating that the instability of PEM electrolysis with Mn/C is probably due to the oxidative decomposition of carbon supports. The OER activity of the four types of Mn oxides was also evaluated at acidic pH in a three-electrode system. It was found that the OER activity trends of the Mn oxides evaluated in an acidic aqueous electrolyte were distinct from those in PEM electrolysers, demonstrating the importance of the evaluation of OER catalysts in a real device condition for future development of noble-metal-free PEM electrolysers.
UV
185+254 nm
photolysis of typical thiol collectors: decomposition efficiency, mineralization and formation of sulfur byproducts
Authors: Fu Pingfeng , Li Gen , Wu Xiaoting , Lin Xiaofeng , Lei Bolan
Published: May 2019

The decomposition of toxic flotation reagents upon UV
185+254 nm
irradiation was attractive due to operational simplicity and no dosage of oxidants. In this work, the degradation of typical thiol collectors (potassium ethyl xanthate (PEX), sodium diethyl dithiocarbamate (SDD),
O
-isopropyl-
N
-ethyl thionocarbamate (IET) and dianilino dithiophoshoric acid (DDA)) was investigated by UV
185+254 nm
photolysis. The degradation efficiencies and mineralization extents of collectors were assessed. The formation of CS
2
and H
2
S byproducts was studied, and the mechanisms of collector degradation were proposed under UV
185+254 nm
irradiation. The PEX, SDD and IET were decomposed with nearly 100% removal upon 75 min of UV
185+254 nm
irradiation. The decomposition rate constants decreased in the order SDD > PEX > IET ≫ DDA, and the DDA was the refractory collector. After 120 min of UV
185+254 nm
irradiation, 15−45% of carbon and 25−75% of sulfur of collectors were completely mineralized, and the mineralization extent decreased in the order PEX > SDD > IET > DDA. The percentage of gaseous sulfur (CS
2
and H
2
S) ranged from 0.48 to 4.85% for four collectors, showing the fraction of emitted sulfur byproducts was small. The aqueous CS
2
concentration increased in the first 10−20 min, and was decreased to a low level of 0.05–0.1 mg l
−1
at 120 min. Two mechanisms, i.e. direct UV
254 nm
photolysis and indirect oxidation with free radicals, were responsible for collector decomposition in the UV
185+254 nm
photolysis.
Taxonomy and conservation of grassland earless dragons: new species and an assessment of the first possible extinction of a reptile on mainland Australia
Authors: Melville Jane , Chaplin Kirilee , Hutchinson Mark , Sumner Joanna , Gruber Bernd , MacDonald Anna J. , Sarre Stephen D.
Published: May 2019

Taxonomic research is of fundamental importance in conservation management of threatened species, providing an understanding of species diversity on which management plans are based. The grassland earless dragon lizards (Agamidae:
Tympanocryptis
) of southeastern Australia have long been of conservation concern but there have been ongoing taxonomic uncertainties. We provide a comprehensive taxonomic review of this group, integrating multiple lines of evidence, including phylogeography (mtDNA), phylogenomics (SNPs), external morphology and micro X-ray CT scans. Based on these data we assign the lectotype of
T. lineata
to the Canberra region, restrict the distribution of
T. pinguicolla
to Victoria and name two new species:
T. osbornei
sp. nov. (Cooma) and
T. mccartneyi
sp. nov. (Bathurst). Our results have significant conservation implications. Of particular concern is
T. pinguicolla
, with the last confident sighting in 1969, raising the possibility of the first extinction of a reptile on mainland Australia. However, our results are equivocal as to whether
T. pinguicolla
is extant or extinct, emphasizing the immediate imperative for continued surveys to locate any remaining populations of
T. pinguicolla
. We also highlight the need for a full revision of conservation management plans for all the grassland earless dragons.
In silico
simulation of a clinical trial with anti-CTLA-4 and anti-PD-L1 immunotherapies in metastatic breast cancer using a systems pharmacology model
Authors: Wang Hanwen , Milberg Oleg , Bartelink Imke H. , Vicini Paolo , Wang Bing , Narwal Rajesh , Roskos Lorin , Santa-Maria Cesar A. , Popel Aleksander S.
Published: May 2019

The low response rate of immune checkpoint blockade in breast cancer has highlighted the need for predictive biomarkers to identify responders. While a number of clinical trials are ongoing, testing all possible combinations is not feasible. In this study, a quantitative systems pharmacology model is built to integrate immune–cancer cell interactions in patients with breast cancer, including central, peripheral, tumour-draining lymph node (TDLN) and tumour compartments. The model can describe the immune suppression and evasion in both TDLN and the tumour microenvironment due to checkpoint expression, and mimic the tumour response to checkpoint blockade therapy. We investigate the relationship between the tumour response to checkpoint blockade therapy and composite tumour burden, PD-L1 expression and antigen intensity, including their individual and combined effects on the immune system, using model-based simulations. The proposed model demonstrates the potential to make predictions of tumour response of individual patients given sufficient clinical measurements, and provides a platform that can be further adapted to other types of immunotherapy and their combination with molecular-targeted therapies. The patient predictions demonstrate how this systems pharmacology model can be used to individualize immunotherapy treatments. When appropriately validated, these approaches may contribute to optimization of breast cancer treatment.
Original plant traceability of
Dendrobium
species using multi-spectroscopy fusion and mathematical models
Authors: Wang Ye , Zuo Zhi-Tian , Huang Heng-Yu , Wang Yuan-Zhong
Published: May 2019

Dendrobium
is the largest genus of orchids most of which have excellent medicinal properties. Fresh stems of some species have been consumed in daily life by Asians for thousands of years. However, there are differences in flavour and clinical efficacy among different species. Therefore, it is necessary for a detector to establish an effective and rapid method controlling botanical origins of these crude materials. In our study, three spectroscopies including mid-infrared (MIR) (transmission and reflection mode) and near-infrared (NIR) spectra were investigated for authentication of 12
Dendrobium
species. Generally, two fusion strategies, reflection MIR and NIR spectra, were combined with three mathematical models (random forest, support vector machine with grid search (SVM-GS) and partial least-squares discrimination analysis (PLS-DA)) for discrimination analysis. In conclusion, a low-level fusion strategy comprising two spectra after pretreated by the second derivative and multiplicative scatter correction was recommended for discrimination analysis because of its excellent performance in three models. Compared with MIR spectra, NIR spectra were more responsible for the discrimination according to a bi-plot analysis of PLS-DA. Moreover, SVM-GS and PLS-DA were suitable for accurate discrimination (100% accuracy rates) of calibration and validation sets. The protocol combined with low-level fusion strategy and chemometrics provides a rapid and effective reference for control of botanical origins in crude
Dendrobium
materials.
Enhanced effective codon numbers to understand codon usage bias
Authors: Smith Reginald
Published: May 2019

Codon usage bias is a well recognized phenomenon but the relative influence of its major causes: G+C content, mutational biases, and selection, are often difficult to disentangle. This paper presents methods to calculate modified effective codon numbers that allow the investigation of the sources of codon bias and how genes or organisms have their codon biases shaped. In particular, it demonstrates that variation in codon usage bias across organisms is likely driven more by likely mutational forces while the variation in codon usage bias within genomes is likely driven by codon selectional forces.

Author summary

A new method of disaggregating codon bias influences is described where I show how that different values of the effective codon number, following Wright’s Nc, can be used as ratios to demonstrate the similar or different causes of codon biases across genes or organisms. By calculating ratios of the different types of effective codon numbers, one can easily compare organisms or different genes while controlling for gene G+C content or codon nucleotide G+C content. The driving forces determining the variations in codon usage bias across or within organisms thus become much clearer.
Changes in the expression of mitochondrial morphology-related genes during the differentiation of murine embryonic stem cells
Authors: Lee Jeong Eon , Seo Bong Jong , Han Min Ji , Hong Yean Ju , Hong Kwonho , Song Hyuk , Lee Jeong Woong , Do Jeong Tae
Published: May 2019

During embryonic development, cells undergo changes in gene expression, signaling pathway activation/inactivation, metabolism, and intracellular organelle structures, which are mediated by mitochondria. Mitochondria continuously switch their morphology between elongated tubular and fragmented globular via mitochondrial fusion and fission. Mitochondrial fusion is mediated by proteins encoded byMfn1, Mfn2, andOpa1, whereas mitochondrial fission is mediated by proteins encoded byFis1andDmn1L. Here, we investigated the expression patterns of mitochondria-related genes during the differentiation of mouse embryonic stem cells (ESCs) in response to leukemia inhibitory factor (LIF) withdrawal. The expression ofMfn2andDnm1Lwas, as expected, increased and decreased, respectively. By comparing gene expression and mitochondrial morphology, we proposed an index that could precisely represent mitochondrial changes during the differentiation of pluripotent stem cells by analyzing the expression ratios of three fusion- and two fission-related genes. Surprisingly, increasedMfn2/Dnm1Lratio was correlated with elongation of mitochondria during the differentiation of ESCs. Moreover, application of this index to other specialized cell types revealed that neural stems cells (NSCs) and mouse embryonic fibroblasts (MEFs) showed increasedMfn2/Dnm1Lratio compared to ESCs. Thus, we suggest that theMfn2/Dnm1Lratio could reflect changes in mitochondrial morphology according to the extent of differentiation.
Antibiotic transport kinetics in Gram-negative bacteria revealed via single-cell uptake analysis and mathematical modelling
Authors: Cama Jehangir , Voliotis Margaritis , Metz Jeremy , Smith Ashley , Iannucci Jari , Keyser Ulrich F. , Tsaneva-Atanasova Krasimira , Pagliara Stefano
Published: May 2019

The double-membrane cell envelope of Gram-negative bacteria is a formidable barrier to intracellular antibiotic accumulation. A quantitative understanding of antibiotic transport in these cells is crucial for drug development, but this has proved elusive due to the complexity of the problem and a dearth of suitable investigative techniques. Here we combine microfluidics and time-lapse auto-fluorescence microscopy to quantify antibiotic uptake label-free in hundreds of individual Escherichia coli cells. By manipulating the microenvironment, we showed that drug (ofloxacin) accumulation is higher in growing versus non-growing cells. Using genetic knockouts, we provide the first direct evidence that growth phase is more important for drug accumulation than the presence or absence of individual transport pathways. We use our experimental results to inform a mathematical model that predicts drug accumulation kinetics in subcellular compartments. These novel experimental and theoretical results pave the way for the rational design of new Gram-negative antibiotics.
Differential chromatin accessibility in developing projection neurons is correlated with transcriptional regulation of cell fate
Authors: Heavner Whitney E. , Ji Shaoyi , Notwell James H. , Dyer Ethan S. , Tseng Alex M. , Birgmeier Johannes , Yoo Boyoung , Bejerano Gill , McConnell Susan K.
Published: May 2019

We are only just beginning to catalog the vast diversity of cell types in the cerebral cortex. Such categorization is a first step toward understanding how diversification relates to function. All cortical projection neurons arise from a uniform pool of progenitor cells that lines the ventricles of the forebrain. It is still unclear how these progenitor cells generate the more than fifty unique types of mature cortical projection neurons defined by their distinct gene expression profiles. Here we compare gene expression and chromatin accessibility of two subclasses of projection neurons with divergent morphological and functional features as they develop in the mouse brain between embryonic day 13 and postnatal day 5 in order to identify transcriptional networks that diversity neuron cell fate. We find groups of transcription factors whose expression is correlated with chromatin accessibility, transcription factor binding motifs, and lncRNAs that define each subclass and validate the function of a family of novel candidate genes in vitro. Our multidimensional approach reveals that subclass-specific chromatin accessibility is significantly correlated with gene expression, providing a resource for generating new specific genetic drivers and revealing regions of the genome that are particularly susceptible to harmful genetic mutations by virtue of their correlation with important developmental genes.
Opposing functions for retromer and Rab11 in extracellular vesicle cargo traffic at presynaptic terminals
Authors: Walsh Rylie B. , Becalska Agata N. , Zunitch Matthew J. , Lemos Tania , Dresselhaus Erica C. , Lee So Min , Wang ShiYu , Isaac Berith , Yeh Anna , Koles Kate , Rodal Avital A.
Published: May 2019

Neuronal extracellular vesicles (EVs) play important roles in intercellular communication and pathogenic protein propagation in neurological disease. However, it remains unclear how cargoes are selectively packaged into neuronal EVs. Here, we show that loss of the endosomal retromer complex leads to accumulation of EV cargoes Amyloid Precursor Protein (APP) and Synaptotagmin-4 (Syt4) atDrosophilamotor neuron presynaptic terminals, resulting in increased release of these cargoes in EVs. By systematically exploring known retromer-dependent trafficking mechanisms, we show that EV regulation is separable from several previously identified roles of neuronal retromer, and depends on the ESCPE-1 complex. Conversely, loss of the recycling endosome regulatorrab11leads to reduced EV cargo levels, and suppresses cargo accumulation in retromer mutants. Thus, EV traffic reflects a balance between Rab11-mediated loading and retromer-dependent removal from EV precursor compartments. Our data shed light on previous studies implicating Rab11 and retromer in competing pathways in Alzheimer’s Disease, and suggest that misregulated EV traffic may be an underlying defect.
Linking nutrient stoichiometry to Zika virus transmission in a mosquito
Authors: Paige Andrew S. , Bellamy Shawna K. , Alto Barry W. , Dean Catherine L. , Yee Donald A.
Published: May 2019

Food quality and quantity serve as the basis for cycling of key chemical elements in trophic interactions, yet the role of nutrient stoichiometry in shaping host-parasite interactions is under appreciated. Most of the emergent mosquito-borne viruses affecting human health are transmitted by mosquitoes that inhabit container systems during their immature stages, where allochthonous input of detritus serves as the basal nutrients. Quantity and type of detritus (animal and plant) were manipulated in microcosms containing newly hatched Aedes aegypti mosquito larvae. Adult mosquitoes derived from these microcosms were allowed to ingest Zika virus infected blood and then tested for disseminated infection, transmission, and total nutrients (percent carbon, percent nitrogen, ratio of carbon to nitrogen). Treatments lacking high quality animal (insect) detritus significantly delayed development. Survivorship to adulthood was closely associated with the amount of insect detritus present. Insect detritus was positively correlated with percent nitrogen, which affected Zika virus infection. Disseminated infection and transmission decreased with increasing insect detritus and percent nitrogen. We provide the first definitive evidence linking nutrient stoichiometry to arbovirus infection and transmission in a mosquito using a model system of invasive Ae. aegypti and emergent Zika virus.
High resolution nonlinear registration with simultaneous modelling of intensities
Authors: Andersson Jesper L. R. , Jenkinson Mark , Smith Stephen
Published: May 2019

This paper describes and evaluates FMRIB’s nonlinear image registration tool (FNIRT), that is part of the FMRIB software library (FSL). It is a small deformation framework using sum of squared differences (SSD) as its cost function and Gauss-Newton for minimisation. The framework uses a joint shape and intensity model that attempts to explain the observed differences between two images in terms of having different shape and/or contrast, being differently affected by intensity bias-fields etc. Thus the estimation of the warps will be relatively unaffected by intensity differences that would otherwise violate the assumptions behind the SSD cost function. It uses a projection onto a manifold defined by a specified range of allowed Jacobian determinants to ensure that the warps are diffeomorphic. The utility of the model is demonstrated on a variety of simulated and experimental data with good results. FNIRT is also quantitatively evaluated using previously published datasets consisting of scans from multiple subjects, all with anatomically defined brain regions that are manually outlined. In this evaluation FNIRT performs well in comparison to previously published results with other registration algorithms.
Predicting failures of Molteno and Baerveldt glaucoma drainage devices using machine learning models
Authors: Morrison Paul , Dixon Maxwell , Sheybani Arsham , Rahmani Bahareh
Published: May 2019

The purpose of this retrospective study is to measure machine learning models’ ability to predict glaucoma drainage device failure based on demographic information and preoperative measurements. The medical records of sixty-two patients were used. Potential predictors included the patient’s race, age, sex, preoperative intraocular pressure, preoperative visual acuity, number of intraocular pressure-lowering medications, and number and type of previous ophthalmic surgeries. Failure was defined as final intraocular pressure greater than 18 mm Hg, reduction in intraocular pressure less than 20% from baseline, or need for reoperation unrelated to normal implant maintenance. Five classifiers were compared: logistic regression, artificial neural network, random forest, decision tree, and support vector machine. Recursive feature elimination was used to shrink the number of predictors and grid search was used to choose hyperparameters. To prevent leakage, nested cross-validation was used throughout. Overall, the best classifier was logistic regression.
Plasticity in zwitterionic drugs: the bending properties of Pregabalin and Gabapentin and their hydrates
Authors: Khandavilli U. B. Rao , Lusi Matteo , Frawley Patrick J.
Published: May 2019

The investigation of mechanical properties in molecular crystals is emerging as a novel area of interest in crystal engineering. Indeed, good mechanical properties are required to manufacture pharmaceutical and technologically relevant substances into usable products. In such endeavour, bendable single crystals help to correlate microscopic structure to macroscopic properties for potential design. The hydrate forms of two anticonvulsant zwitterionic drugs, Pregabalin and Gabapentin, are two examples of crystalline materials that show macroscopic plasticity. The direct comparison of these structures with those of their anhydrous counterparts, which are brittle, suggests that the presence of water is critical for plasticity. In contrast, structural features such as molecular packing and anisotropic distribution of strong and weak interactions seem less important.
Jagdish N. Sheth: reflections of an accidental scholar
Authors: Sheth Jagdish
Published: May 2019

Purpose

The aim of this paper is to demonstrate that scholarship is all about challenging the prevailing wisdom by offering an alternative perspective or explanation. Hopefully, the author’s journey of more than 50 years will inspire others to be eclectic and become deep generalists.

Design/methodology/approach

It is an autobiographical evaluation of an accidental scholar. It emphasizes that an educator is more than a scientist or a priest or a public servant. It is all of them. Educators are in the business of making ordinary people extraordinary. They are diamond cutters who are entrusted by society with its rough diamonds to get their brilliance out and make them useful to themselves, the society and the community.

Findings

Over 50 years, marketing has evolved and adapted to the external environment, including technology revolution, changing demographics, global competition and geopolitics. This provides enormous opportunity for the next generation of scholars to establish their own identity in managerial marketing, consumer behavior or marketing analytics.

Practical implications

While publishing in the top journals is both necessary and desirable in the early stages of an academic career, it is also important to make an impact on practitioners by publishing professional books.

Social implications

According to Peter Drucker, there are only two functions of business: innovation and marketing. While innovation is admired by everyone, marketing can also become a positive force for a better world.

Originality/value

Lessons learnt over time from different encounters and circumstances in research, teaching and service are important to document. In the end, according to the author, they are all academic entrepreneurs.
Ruby Roy Dholakia: autobiographical reflections of a female marketing academic
Authors: Dholakia Ruby Roy
Published: May 2019

Purpose

In a very personal reflection, this paper aims to trace the academic trajectory of a female marketing academic in a very male-dominated discipline. It also highlights the struggle balancing work and family, as well as protecting an immigrant identity in a foreign culture.

Design/methodology/approach

Given the period and unique conditions of the author’s academic journey, this highly personal retrospective account is based on recall of significant events that have shaped my singular experience. It attempts to capture the experience of an immigrant female novice navigating not only a foreign culture but also a very male-dominant discipline.

Findings

While times have changed and gender barriers are lower today, challenges remain. In addition, the set of choices faced by women with partners in the same discipline differ significantly and complicate the family-work balance decisions. There is no one set of path that can be followed.

Practical implications

While there is a professional cost to deviating from the mainstream, pursuing alternatives to the dominant topics is vital to advancing the health and relevance of the marketing discipline. The relationships between marketing and development have been an important topic for me; however, these macromarketing topics continue to be neglected. Given the current socio-economic-political conditions globally, perhaps future marketing scholars will devote greater attention to these topics.

Originality/value

This is purely the author’s personal reflection of a journey that began accidentally. It also occurred in the 1970s when women were rare in the business world, particularly business academia. It offers a retrospective comparison to male peers who, aside from their individual talents and history (Belk, 2017; Firat, 2014; Holbrook, 2017), were achieving their professional goals at a similar period. It also provides some historical context that can be compared to experiences of other female pioneers in marketing academia and marketing practice (Bolton, 2017; Tadajewski and Maclaran, 2013; Zeithaml, 2017).
Focal skeletal FDG uptake indicates poor prognosis in cHL regardless of extent and first‐line chemotherapy
Authors: Pedersen Mette A. , Gormsen Lars C. , Kamper Peter , Wassberg Cecilia , Andersen Maja D. , d'Amore Alexander L. , Barrington Sally F. , Johnson Peter , Hamilton‐Dutoit Stephen , Amini Rose‐Marie , Enblad Gunilla , Molin Daniel , d'Amore Francesco
Published: May 2019

18F‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography/computed tomography (FDG‐PET/CT) is used for staging classical Hodgkin lymphoma (cHL) with high sensitivity for skeletal involvement. However, it is unclear whether a single bone lesion carries the same adverse prognosis as multifocal lesions and if this is affected by type of chemotherapy [ABVD (adriamycin, bleomycin, vincristine, dacarbazine) versus BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone)]. We reviewed the clinico‐pathological and outcome data from 209 patients with newly diagnosed cHL staged by FDG‐PET/CT. Patterns of skeletal/bone marrow uptake (BMU) were divided into ‘low’ and ‘high’ diffuse BMU (i.e. without focal lesions), and unifocal or multifocal lesions. Additional separate survival analysis was performed, taking type of chemotherapy into account. Forty patients (19·2%) had skeletal lesions (20 unifocal, 20 multifocal). The 3‐year progression‐free‐survival (PFS) was 80% for patients with ‘low BMU’, 87% for ‘high BMU’, 69% for ‘unifocal’ and 51% for ‘multifocal’ lesions; median follow‐up was 38 months. The presence of bone lesions, both uni‐ and multifocal, was associated with significantly inferior PFS (log rank P = 0·0001), independent of chemotherapy type. Thus, increased diffuse BMU should not be considered as a risk factor in cHL, whereas unifocal or multifocal bone lesions should be regarded as important predictors of adverse outcome, irrespective of the chemotherapy regimen used.
Second allogeneic stem cell transplantation in patients with acute lymphoblastic leukaemia: a study on behalf of the Acute Leukaemia Working Party of the European Society for Blood and Marrow Transplantation
Authors: Nagler Arnon , Labopin Myriam , Dholaria Bhagirathbhai , Finke Jürgen , Brecht Arne , Schanz Urs , Niittyvuopio Riitta , Neubauer Andreas , Bornhäuser Martin , Santarone Stella , Beelen Dietrich , Shimoni Avichai , Rösler Wolf , Giebel Sebastian , Savani Bipin N. , Mohty Mohamad
Published: May 2019

Although second allogeneic haematopoietic cell transplantation (allo‐HCT2) is a therapeutic option for patients relapsing after first HCT (allo‐HCT1), there is limited data on allo‐HCT2 in patients with acute lymphoblastic leukaemia (ALL).

We retrospectively studied 245 patients receiving allo‐HCT2 as a salvage treatment for relapse following allo‐HCT1 between the 2000 and 2017. The median age at allo‐HCT2 was 34·6 years (range: 18–74). One hundred and one patients (41%) received sibling donor and 144 (59%) unrelated donor allo‐HCT2. Acute graft‐versus‐host disease (GVHD) grade II–IV and III–IV occurred in 33% and 17% of the patients, respectively. The incidence of 2‐year total and extensive chronic GVHD was 38% and 19%, respectively. The 2‐ and 5‐year cumulative incidence of non‐relapse mortality, relapse incidence, leukaemia‐free survival, overall survival and GVHD‐free, relapse‐free survival (GRFS) were 24% and 26%, 56% and 62%, 20% and 12%, 30% and 14% and 12% & 7%, respectively. In multivariate analysis, factors associated with overall survival were age, time from allo‐HCT1 to relapse, conditioning for allo‐HCT1, Karnofsky score at allo‐HCT2 and donor type for allo‐HCT2. In conclusion, outcomes of allo‐HCT2 in ALL patients were poor, with only 14% overall survival and 7% GRFS at 5 years with very high relapse incidence.
Prediction of Human Pharmacokinetics of Antibody–Drug Conjugates From Nonclinical Data
Authors: Li Chunze , Zhang Cindy , Deng Rong , Leipold Douglas , Li Dongwei , Latifi Brandon , Gao Yuying , Zhang Crystal , Li Zao , Miles Dale , Chen Shang‐Chiung , Samineni Divya , Wang Bei , Agarwal Priya , Lu Dan , Prabhu Saileta , Girish Sandhya , Kamath Amrita V.
Published: May 2019

Prediction of human pharmacokinetics (PK) based on preclinical information for antibody–drug conjugates (ADCs) provide important insight into first‐in‐human (FIH) study design. This retrospective analysis was conducted to identify an appropriate scaling method to predict human PK for ADCs from animal PK data in the linear range. Different methods for projecting human clearance (CL) from animal PK data for 11 ADCs exhibiting linear PK over the tested dose ranges were examined: multiple species allometric scaling (CL vs. body weight), allometric scaling with correction factors, allometric scaling based on rule of exponent, and scaling from only cynomolgus monkey PK data. Two analytes of interest for ADCs, namely total antibody and conjugate (measured as conjugated drug or conjugated antibody), were assessed. Percentage prediction errors (PEs) and residual sum of squares (RSS) were compared across methods. Human CL was best estimated using cynomolgus monkey PK data alone and an allometric scaling exponent of 1.0 for CL. This was consistently observed for both conjugate and total antibody analytes. Other scaling methods either underestimated or overestimated human CL, or produced larger average absolute PEs and RSS. Human concentration‐time profiles were also reasonably predicted from the cynomolgus monkey data using species‐invariant time method with a fixed exponent of 1.0 for CL and 1.0 for volume of distribution. In conclusion, results from this retrospective analysis of 11 ADCs indicate that allometric scaling of CL with an exponent of 1.0 using cynomolgus monkey PK data alone can successfully project human PK profiles of an ADC within linear range.
Reinduktion zielgerichteter Therapie beim metastasierten Melanom
Authors: Reschke Robin , Simon Jan‐Christoph , Ziemer Mirjana
Published: May 2019

Die Reinduktion bzw. Rechallenge zielgerichteter Therapie bei Patienten mit BRAFV600‐mutierten Melanomen gewinnt zunehmend an Bedeutung. Die erneute Gabe von zielgerichteter Therapie erfolgt nach einer Medikamentenpause bei Nebenwirkungen, nach Bestrahlung oder Operation, nach Tumorprogress unter zwischengeschalteter Immun‐ oder Chemotherapie oder nach erneutem Progress ohne zwischengeschaltete Therapie. Bisher sind nur wenige Daten zu den Ergebnissen einer Rechallenge publiziert. Diese sind in der folgenden Arbeit präsentiert.

Alle Arbeiten mit einer Gesamtpatientenzahl von 238 Patienten konnten zeigen, dass auch bei Patienten, die zuvor unter zielgerichteter Therapie einen Progress erlitten hatten, ein erneutes Ansprechen nach Wiedereinleitung möglich ist. Dieses variiert von stabiler Erkrankung, über partielles Ansprechen bis hin zu einzelnen Fällen mit kompletter Remission. Die Daten zeigen Ansprechraten auf eine Rechallenge von 47 %, wobei eine Krankheitskontrolle bei 67 % der Patienten erreicht werden konnte. Das mittlere progressionsfreie Überleben lag bei 6,4 Monaten. Das Ansprechen fiel allerdings kürzer aus als bei der erstmaligen zielgerichteten Therapie (mittleres progressionsfreies Überleben 9,2 Monate). Die Reinduktion zielgerichteter Therapie bietet somit eine weitere Option in der Behandlung bereits ausgiebig behandelter Krankheitszustände. Es bleibt zu klären, ob die Art der zwischengeschalteten Therapie einen Einfluss auf das erneute Ansprechen hat.
Trichophyton mentagrophytes – ein neuer Genotyp des zoophilen Dermatophyten verursacht sexuell übertragbare Infektionen
Authors: Kupsch Christiane , Czaika Viktor‐Alexander , Deutsch Cornelia , Gräser Yvonne
Published: May 2019

Hintergrund

Ein erst kürzlich in zwei Studien beschriebener neuer Genotyp des zoophilen Dermatophyten Trichophyton (T.) mentagrophytes wurde von drei Patienten mit Südostasienaufenthalt und von einem Patienten nach dem Aufenthalt in Ägypten isoliert. Im Gegensatz zu diesen Publikationen haben wir hier eine Anzahl von Fällen in der Dimension eines Epidemieausbruchs beobachtet.

Patienten und Methodik

An der Charité – Universitätsmedizin Berlin wurden zwischen Januar 2016 und Juli 2017 43 Patienten beobachtet, die überwiegend an hoch entzündlichen, schmerzhaften und hartnäckigen Infektionen der Pubogenitalregion litten. Die mykologische Untersuchung erfolgte mittels Pilzkultur und Sequenzierung der ITS‐Region (Internal Transcribed Spacer) der ribosomalen DNA. Drei weitere genomische Regionen wurden stichprobenartig sequenziert.

Ergebnisse

In 37 der Fälle wurde der neue Genotyp der Spezies T. mentagrophytes (hier T. mentagrophytes VII genannt) als Verursacher isoliert. Die Sequenzierungen ergaben identische Sequenzen für alle Isolate. Die meisten der infizierten Patienten hatten keine Reiseanamnese, nur zwei Patienten berichteten von Tierkontakt.

Schlussfolgerungen

Der neue Genotyp lässt sich phylogenetisch in vier verschiedenen DNA‐Markern der zoophilen Spezies T. mentagrophytes zuordnen. Während die Übertragung von zoophilen Dermatophyten von Mensch zu Mensch in der Regel selten ist, erfolgt die Übertragung hier scheinbar sehr effektiv über sexuellen Kontakt.
Multiple papillary fibroelastomas attached to left ventricular side and aortic side of the aortic valve: A report of new case and literature review
Authors: Tsugu Toshimitsu , Nagatomo Yuji , Endo Jin , Kawakami Takashi , Murata Mitsushige , Yamazaki Masataka , Shimizu Hideyuki , Fukuda Keiichi , Mitamura Hideo , Lancellotti Patrizio
Published: May 2019

The aortic valve (AV) is the most commonly affected site in multiple papillary fibroelastomas, but the frequency of embolism caused by the attachment side of the AV has not been elucidated. According to the review of the previous literature, 16 cases have been found attached to the AV. Of these, 6 of these have been found to be attached on the aortic side and 4 on the left ventricular side, 1 was bilateral, and 5 cases were unknown. Of the cases found on the aortic side, embolism occurred in 3 of them, and of the left ventricular side cases, embolism occurred in 2 of them. The frequency of embolism is equivalent even if papillary fibroelastoma attached to either side of the AV.
Googling the requester: Identity‐questing and discrimination in public service provision
Authors: Michener Gregory , Velasco Rafael B. , Contreras Evelyn , Rodrigues Karina F.
Published: May 2019

Innovating upon previous field experiments and theories of identity‐based discrimination, we test whether public officials are using searches (“identity‐questing”) to profile citizens and acting on latent biases. Pairs of “institutional” and “noninstitutional” requesters send lower and moderate burden freedom of information (FOI) requests—providing no identity cues apart from undistinctive names, e‐mails, and ID numbers—to nearly 700 of Brazil's largest municipalities. Results show institutional requesters receive one‐fifth more responses than noninstitutional comparators. For moderate versus lower burden requests, noninstitutional requesters are 11% less likely to receive a compliant response than their institutional comparators. The only plausible explanation for these results is identity‐questing, a phenomenon that has far‐reaching policy implications. Most of the world's FOI laws, for example, contain vague ID obligations, which translate incoherently from laws to regulation and practice. Results enjoin public service providers to protect the identities of citizens by default or upon request.
Inadvertently high dialysate magnesium causing weakness and nausea in hemodialysis patients
Authors: Chakurkar Vipul V. , Gade Pritam S. , Godbole Anil V. , Wadia Farrokh F. , Lobo Valentine A.
Published: May 2019

As maintenance hemodialysis patients are exposed to large quantities of dialysis water, any contamination of it might be reflected in plasma levels. We present a series of cases due to such a contamination. Six maintenance hemodialysis patients dialyzing at the same peripheral hemodialysis facility presented to us over a short period of time with symptoms mimicking inadequate dialysis. Their blood urea and creatinine levels were not very high, but all the patients had hypermagnesemia [serum Mg levels = 1.8 (±0.3) mmol/L]. Except for one patient who had cardiac arrest at presentation, all patients improved after undergoing hemodialysis at our center [serum Mg at discharge = 0.86 (±0.01) mmol/L]. The origin of hypermagnesemia was traced to dialysis water contamination with magnesium due to inadequate maintenance of the water treatment system. Corrective measures improved the quality of water, and no further cases were reported from that center. Proper maintenance and periodic checks of the quality of water are central to the outcomes of maintenance hemodialysis patients.