bluuebunny/crossref_metadata_2025 huggingface dataset:
High‐fidelity detection and sorting of nanoscale vesicles in viral disease and cancer
Authors: Morales‐Kastresana Aizea , Musich Thomas A. , Welsh Joshua A. , Telford William , Demberg Thorsten , Wood James C. S. , Bigos Marty , Ross Carley D. , Kachynski Aliaksander , Dean Alan , Felton Edward J. , Van Dyke Jonathan , Tigges John , Toxavidis Vasilis , Parks David R. , Overton W. Roy , Kesarwala Aparna H. , Freeman Gordon J. , Rosner Ariel , Perfetto Stephen P. , Pasquet Lise , Terabe Masaki , McKinnon Katherine , Kapoor Veena , Trepel Jane B. , Puri Anu , Kobayashi Hisataka , Yung Bryant , Chen Xiaoyuan , Guion Peter , Choyke Peter , Knox Susan J. , Ghiran Ionita , Robert‐Guroff Marjorie , Berzofsky Jay A. , Jones Jennifer C.
Published: June 2019

Biological nanoparticles, including viruses and extracellular vesicles (EVs), are of interest to many fields of medicine as biomarkers and mediators of or treatments for disease. However, exosomes and small viruses fall below the detection limits of conventional flow cytometers due to the overlap of particle‐associated scattered light signals with the detection of background instrument noise from diffusely scattered light. To identify, sort, and study distinct subsets of EVs and other nanoparticles, as individual particles, we developed nanoscale Fluorescence Analysis and Cytometric Sorting (nanoFACS) methods to maximise information and material that can be obtained with high speed, high resolution flow cytometers. This nanoFACS method requires analysis of the instrument background noise (herein defined as the “reference noise”). With these methods, we demonstrate detection of tumour cell‐derived EVs with specific tumour antigens using both fluorescence and scattered light parameters. We further validated the performance of nanoFACS by sorting two distinct HIV strains to >95% purity and confirmed the viability (infectivity) and molecular specificity (specific cell tropism) of biological nanomaterials sorted with nanoFACS. This nanoFACS method provides a unique way to analyse and sort functional EV‐ and viral‐subsets with preservation of vesicular structure, surface protein specificity and RNA cargo activity.
Severe influenza pneumonitis in children with inherited TLR3 deficiency
Authors: Lim Hye Kyung , Huang Sarah X.L. , Chen Jie , Kerner Gaspard , Gilliaux Olivier , Bastard Paul , Dobbs Kerry , Hernandez Nicholas , Goudin Nicolas , Hasek Mary L. , García Reino Eduardo Javier , Lafaille Fabien G. , Lorenzo Lazaro , Luthra Priya , Kochetkov Tatiana , Bigio Benedetta , Boucherit Soraya , Rozenberg Flore , Vedrinne Catherine , Keller Michael D. , Itan Yuval , García-Sastre Adolfo , Celard Marie , Orange Jordan S. , Ciancanelli Michael J. , Meyts Isabelle , Zhang Qian , Abel Laurent , Notarangelo Luigi D. , Snoeck Hans-Willem , Casanova Jean-Laurent , Zhang Shen-Ying
Published: June 2019

Autosomal recessive IRF7 and IRF9 deficiencies impair type I and III IFN immunity and underlie severe influenza pneumonitis. We report three unrelated children with influenza A virus (IAV) infection manifesting as acute respiratory distress syndrome (IAV-ARDS), heterozygous for rare TLR3 variants (P554S in two patients and P680L in the third) causing autosomal dominant (AD) TLR3 deficiency. AD TLR3 deficiency can underlie herpes simplex virus-1 (HSV-1) encephalitis (HSE) by impairing cortical neuron-intrinsic type I IFN immunity to HSV-1. TLR3-mutated leukocytes produce normal levels of IFNs in response to IAV. In contrast, TLR3-mutated fibroblasts produce lower levels of IFN-β and -λ, and display enhanced viral susceptibility, upon IAV infection. Moreover, the patients’ iPSC-derived pulmonary epithelial cells (PECs) are susceptible to IAV. Treatment with IFN-α2b or IFN-λ1 rescues this phenotype. AD TLR3 deficiency may thus underlie IAV-ARDS by impairing TLR3-dependent, type I and/or III IFN–mediated, PEC-intrinsic immunity. Its clinical penetrance is incomplete for both IAV-ARDS and HSE, consistent with their typically sporadic nature.
Bayesian optimization in ab initio nuclear physics
Authors: Ekström A , Forssén C , Dimitrakakis C , Dubhashi D , Johansson H T , Muhammad A S , Salomonsson H , Schliep A
Published: June 2019

Theoretical models of the strong nuclear interaction contain unknown coupling constants (parameters) that must be determined using a pool of calibration data. In cases where the models are complex, leading to time consuming calculations, it is particularly challenging to systematically search the corresponding parameter domain for the best fit to the data. In this paper, we explore the prospect of applying Bayesian optimization to constrain the coupling constants in chiral effective field theory descriptions of the nuclear interaction. We find that Bayesian optimization performs rather well with low-dimensional parameter domains and foresee that it can be particularly useful for optimization of a smaller set of coupling constants. A specific example could be the determination of leading three-nucleon forces using data from finite nuclei or three-nucleon scattering experiments.
Stereotactical fields applied in proton spot scanning mode with range shifter and collimating aperture
Authors: Bäumer C , Fuentes C , Janson M , Matic A , Timmermann B , Wulff J
Published: June 2019

Some clinical indications require small fields with sharp lateral dose gradients, which is technically challenging in proton beam therapy. This holds especially true for low-range fields applied with the spot scanning technique, where large beam profiles entering from the beam-line or the insertion of range shifting blocks lead to large lateral gradients. We regard the latter case and solve it by shifting the range shifting block far upstream in conjunction with a collimating aperture close to the patient. The experiments of the current work are based on a commercial proton therapy treatment head designed for several delivery modes. In a research environment of the spot-scanning delivery mode a range shifter is inserted downstream of the scanning magnets in a slot which is usually employed only in a scattering delivery mode. This configuration is motivated by equations assuming a simple model of proton transport. In the experiments lateral dose planes are acquired with a scintillation screen and radiochromic films. Dose distributions are calculated with the Monte Carlo dose engine of the RayStation treatment planning system. We demonstrate that proton fields with 80%–20% lateral dose fall-off values between 1.4 mm and 4.0 mm can be achieved for water equivalent depths between 0 cm and 10 cm. The simulated lateral dose profiles agree with the experimental dose profiles. The sharpening of the field edges is set off by a broadening of the proton spots towards the center of the fields. This limits the clinical application mainly to small fields for which the distal and proximal conformality is of minor importance.
An assessment of indoor radon level in a suburb of Ghana
Authors: Kitson-Mills Doris , Sovoe Simon , Opoku-Ntim Irene , Kyei Kofi Adesi , Marnotey Stephen , Anim-Sampong Samuel , Kwabeng Michael Addo , Otoo Francis , Baiden Frank
Published: June 2019

Radiation and radioactive isotopes form part of our natural environment. Elevated levels of these radioactive isotopes in the environment can pose a threat to our health. A greater proportion of the natural radiation is from the radioactive gas radon. Although it cannot be detected by human senses, radon and its progenies are of health concern as it can cause lung cancer when inhaled over a period of time. This study sought to provide baseline indoor radon data, the life time risk of lung cancer and its interpretation within a suburb of Ghana. Solid State Nuclear Track Detector (LR-115 type II) was deployed in 82 homes within a suburb for a period of three months (September 2017- January 2018). Indoor radon concentration (IRC) for the suburb was within the range of 4.1–176.3 Bq m−3. With mean 57 ± 39 Bq m−3. The mean radon exposure to the dwellers was recorded as 0.12 ± 0.08 WLMy−1 resulting in 0.7 ± 0.5 mSvy−1 effective dose to the lung with an excess lifetime cancer risk of 0.39 ± 0.26%. There was a positive correlation between indoor radon concentration and the building type and the association was significant with a P value of 0.047.
Chronic Binge Alcohol-Associated Differential Brain Region Modulation of Growth Factor Signaling Pathways and Neuroinflammation in Simian Immunodeficiency Virus-Infected Male Macaques
Authors: Maxi John K , Mercante Don , Foret Brittany , Oberhelman Sarah , Ferguson Tekeda F , Bagby Gregory J , Nelson Steve , Amedee Angela M , Edwards Scott , Simon Liz , Molina Patricia E
Published: June 2019

In chronic alcohol-administered, SIV-infected macaques, differential brain region susceptibility to inflammatory, viral, neurotropic, and alcohol insults was associated with neurocognitive impairment. In the prefrontal cortex, suppression of growth factor signaling may be an important neuropathological mechanism, while inflammatory processes play a more important role in the caudate and hippocampus.
Reorganization of Sound Location Processing in the Auditory Cortex of Blind Humans
Authors: van der Heijden Kiki , Formisano Elia , Valente Giancarlo , Zhan Minye , Kupers Ron , de Gelder Beatrice
Published: June 2019

Auditory spatial tasks induce functional activation in the occipital—visual—cortex of early blind humans. Less is known about the effects of blindness on auditory spatial processing in the temporal—auditory—cortex. Here, we investigated spatial (azimuth) processing in congenitally and early blind humans with a phase-encoding functional magnetic resonance imaging (fMRI) paradigm. Our results show that functional activation in response to sounds in general—independent of sound location—was stronger in the occipital cortex but reduced in the medial temporal cortex of blind participants in comparison with sighted participants. Additionally, activation patterns for binaural spatial processing were different for sighted and blind participants in planum temporale. Finally, fMRI responses in the auditory cortex of blind individuals carried less information on sound azimuth position than those in sighted individuals, as assessed with a 2-channel, opponent coding model for the cortical representation of sound azimuth. These results indicate that early visual deprivation results in reorganization of binaural spatial processing in the auditory cortex and that blind individuals may rely on alternative mechanisms for processing azimuth position.
Six vs Eight Weeks of Antibiotics for Small Mycobacterium ulcerans Lesions in Australian Patients
Authors: O’Brien Daniel P , Friedman N Deborah , Cowan Raquel , Walton Aaron , Athan Eugene
Published: June 2019

Background

Antibiotics are highly effective in curing Mycobacterium ulcerans lesions, but are associated with significant toxicity. In those not undergoing surgery, we compared 6 weeks with the currently recommended 8 weeks of combination antibiotic therapy for small M. ulcerans lesions.

Methods

Mycobacterium ulcerans cases from an observational cohort at Barwon Health, Victoria, treated with antibiotics alone from 1 October 2010 to 31 March 2018 were included. The 6-week antibiotic group received ≥28 days and ≤42 days and the 8-week antibiotic group received ≥56 days of antibiotic therapy, respectively. Only World Health Organization category 1 lesions were included.

Results

207 patients were included; 53 (25.6%) in the 6-week group and 154 (74.4%) in the 8-week group. The median age of patients was 53 years (interquartile range [IQR], 33–69 years) and 100 (48.3%) were female. Lesions were ≤900 mm2 in size in 79.7% of patients and 93.2% were ulcerative. Fifty-three patients (100%) achieved treatment cure in the 6-week group compared with 153 (99.4%) in the 8-week group (P = .56). No patients died or were lost to follow-up during the study. Median time to heal was 70 days (IQR, 60–96 days) in the 6-week group and 128 days (IQR, 95–173 days) in the 8-week group (P < .001). Two (3.8%) patients in the 6-week group experienced a paradoxical reaction compared with 39 (25.3%) patients in the 8-week group (P = .001).

Conclusions

For selected small M. ulcerans lesions, 6 weeks may be as effective as 8 weeks of combined antibiotic therapy in curing lesions without surgery.
Chromatin-dependent regulation of secondary metabolite biosynthesis in fungi: is the picture complete?
Authors: Collemare Jérôme , Seidl Michael F
Published: June 2019

Fungal secondary metabolites are small molecules that exhibit diverse biological activities exploited in medicine, industry and agriculture. Their biosynthesis is governed by co-expressed genes that often co-localize in gene clusters. Most of these secondary metabolite gene clusters are inactive under laboratory conditions, which is due to a tight transcriptional regulation. Modifications of chromatin, the complex of DNA and histone proteins influencing DNA accessibility, play an important role in this regulation. However, tinkering with well-characterised chemical and genetic modifications that affect chromatin alters the expression of only few biosynthetic gene clusters, and thus the regulation of the vast majority of biosynthetic pathways remains enigmatic. In the past, attempts to activate silent gene clusters in fungi mainly focused on histone acetylation and methylation, while in other eukaryotes many other post-translational modifications are involved in transcription regulation. Thus, how chromatin regulates the expression of gene clusters remains a largely unexplored research field. In this review, we argue that focusing on only few well-characterised chromatin modifications is significantly hampering our understanding of the chromatin-based regulation of biosynthetic gene clusters. Research on underexplored chromatin modifications and on the interplay between different modifications is timely to fully explore the largely untapped reservoir of fungal secondary metabolites.
The whole is more than the sum of the parts: establishing an enabling health system environment for reducing acute child malnutrition in a rural South African district
Authors: Schneider Helen , van der Merwe Maria , Marutla Beauty , Cupido Joseph , Kauchali Shuaib
Published: June 2019

There is a gap in understanding of how national commitments to child nutrition are translated into sub-national implementation. This article is a mixed methods case study of a rural South African health district which achieved accelerated declines in morbidity and mortality from severe acute malnutrition (SAM) in young children, following a district health system strengthening (HSS) initiative centred on real-time death reporting, analysis and response. Drawing on routine audit data, the declining trends in under-five admissions and in-hospital mortality for SAM over a 5-year period are presented, comparing the district with two others in the same province. Adapting Gillespie et al.’s typology of ‘enabling environments’ for Maternal and Child Nutrition, and based on 41 in-depth interviews and a follow-up workshop, the article then presents an analysis of how an enabling local health system environment for maternal-child health was established, creating the conditions for achievement of the SAM outcomes. Embedded in supportive policy and processes at national and provincial levels, the district HSS interventions and the manner in which they were implemented produced three kinds of system-level change: knowledge and use of evidence by providers and managers (‘ways of thinking’), leadership, participation and coordination (‘ways of governing’) and inputs and capacity (‘ways of resourcing’). These processes mainstreamed responsibility, deepened accountability and triggered new service delivery and organizational practices and mindsets. The article concludes that it is possible to foster enabling district environments for the prevention and management of acute malnutrition, emphasizing the multilevel and simultaneous nature of system actions, where action on system ‘software’ complements the ‘hardware’ of HSS interventions, and where the whole is more than the sum of the parts.
Comparative spallation performance of silicone versus Tygon extracorporeal circulation tubing
Authors: Ippoliti Francesco , Piscioneri Fernando , Sartini Patrizio , Peruzzi Mariangela , Domenico Marina Di , Dannhauser David , Rossi Domenico , Causa Filippo , Netti Paolo Antonio , Miraldi Fabio , Greco Ernesto , Marullo Antonino , Iaccarino Alessandra , Cavarretta Elena , Zoccai Giuseppe Biondi , Sciarretta Sebastiano , Frati Giacomo
Published: June 2019

OBJECTIVES

Reports ranged from mixed to marginal tubing wear and spallation effects as a complication of roller pumps in cardiopulmonary bypass (CPB). Because the rollers constantly compress part of the tubing, we sought to determine whether circuit materials behave differently under a 3-h simulation of CPB.

METHODS

Two different tubing materials (silicone and Tygon) were tested with a customized experimental circuit, designed to allow in vitro simulation of CPB with priming volumes, pressures, revolutions per minute and temperatures equivalent to the clinical scenario. Samples were analysed with optical and field-emission scanning electron microscopy. We collected 200-ml fluid samples at 4 different times: before starting the CPB (T0), when the predicted revolutions per minute corresponded to about 2 min of CPB (T1), at 90 min (T2) and at 180 min (T3). At the end of CPB, we harvested 2 samples of tubing. Lastly, optical investigations and field-emission scanning electron microscopy observations were used for qualitative and quantitative analysis of circulating fragments.

RESULTS

T2 and T3 fluid samples showed more particles than T1 samples. Significant differences in terms of particle numbers were detected: silicone tubing released more fragments per millilitre than Tygon tubing, with both materials releasing particles from 5 to 500 µm. Silicone tubing was associated with a time-dependent increase in small particles released (P = 0.04), whereas this did not apply to large particles or to Tygon tubing. Yet, bootstrap estimates suggested that silicone tubing was associated with the release of more small particles whereas Tygon tubing released more large particles (both P < 0.01). Unlike silicone, Tygon samples taken from the portion of the circuit not subjected to the action of the roller pump did not show any erosion on their surfaces. Samples of both materials taken from the portion subjected to the compression of the roller pump showed signs of significant deterioration.

CONCLUSIONS

Silicone showed a worse spallation performance than Tygon, thus appearing less safe for more complex surgery of prolonged duration or for patients with a prior cerebral ischaemic event. Additional risk and cost-effectiveness comparisons to determine the potential benefits of one type of tubing material over the other are warranted to further expand our findings.
Updated good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT) in adults and children in the UK
Authors: Chapman Ann L N , Patel Sanjay , Horner Carolyne , Green Helen , Guleri Achyut , Hedderwick Sara , Snape Susan , Statham Julie , Wilson Elizabeth , Gilchrist Mark , Seaton R Andrew
Published: June 2019

UK good practice recommendations for outpatient parenteral antimicrobial therapy (OPAT) were published in 2012 and 2015 for adult and paediatric patients, respectively. Here we update the initial good practice recommendations in a combined document based on a further review of the OPAT literature and an extensive consultation process. As with the previous good practice recommendations, these updated recommendations are intended to provide pragmatic guidance for new and established OPAT services across a range of settings and to act as a set of quality indicators for service evaluation and quality improvement.
Genetic parameters for hair characteristics and core body temperature in a multibreed Brahman–Angus herd1
Authors: Sarlo Davila Kaitlyn M , Hamblen Heather , Hansen Peter J , Dikmen Serdal , Oltenacu Pascal A , Mateescu Raluca G
Published: June 2019

Thermal stress in hot humid conditions limits cattle production. The objectives for this study were to estimate genetic parameters for hair characteristics and core body temperature under low and high temperature humidity index (THI) conditions. Hair samples were collected and measured for length and diameter. Core body temperature was measured as vaginal temperature every 15 min over a 5-d period using an iButton temperature measuring device implanted in a blank CIDR in 336 heifers from the University of Florida multibreed herd (ranging from 100% Angus to 100% Brahman). Restricted maximum likelihood procedures were used to estimate heritabilities from multiple bivariate animal models using the WOMBAT program. Estimates of heritability for hair diameter, undercoat length, topcoat length, body temperature under low THI conditions, and body temperature under high THI conditions were 0.50, 0.67, 0.42, 0.32, and 0.26, respectively. The genetic parameters estimated in this study indicate a large, exploitable genetic variance which can be selected upon to improve tolerance in cattle. Breed effects for differing compositions of Brahman and Angus were also estimated. As Brahman breed composition increased by 25% undercoat length, topcoat length, body temperature under low THI conditions, and body temperature under high THI conditions decreased by 1.32 mm, 2.94 mm, 0.11 °C, and 0.14 °C, respectively. Under both low and high THI conditions, cattle with 25% Brahman breed composition or greater maintained a significantly lower body temperature than the 100% Angus breed group. The incorporation of Brahman germplasm is recommended for herds that often experience heat stress conditions in order to increase resilience to heat stress.
Risk factor for wound complications following wide resection of soft tissue sarcoma in the adductor compartment of the thigh
Authors: Kito Munehisa , Ae Keisuke , Koyanagi Hirotaka , Gokita Tabu , Furuoka Hideto , Okamoto Masanori , Tanaka Atsushi , Suzuki Shuichiro , Takazawa Akira , Aoki Kaoru , Yoshimura Yasuo
Published: June 2019

Background

The purpose of this study was to investigate deep-seated soft tissue sarcoma (STS) occurring in the adductor compartment of the thigh that underwent wide resection and to clarify the high-risk group for wound complications.

Patients and methods

From 2000 to 2017, we reviewed 104 cases of deep-seated STS occurring in the adductor compartment of the thigh that were treated at four specialized facilities with expertise in sarcoma treatment.

Results

Wound complications occurred in 40 cases (38.5%), of which 23 cases (22.1%) were cases with major wound complications (MWC). In univariate analysis, BMI (P < 0.01), maximum tumor diameter (P < 0.01), operation time (P < 0.01), amount of intraoperative bleeding (P < 0.01), and intraoperative intervention to the femoral artery and vein (P < 0.01) were significantly associated with wound complications. In multivariate analysis, the associated parameters were BMI (P < 0.01), maximum tumor diameter (P = 0.02), and intraoperative intervention to the femoral artery and vein (P = 0.01). When limited to cases with MWC, univariate analysis showed that maximum tumor diameter (P < 0.01), diabetes mellitus (P = 0.03), operation time (P < 0.01), amount of intraoperative bleeding (P < 0.01), and intraoperative intervention to the femoral artery and vein (P = 0.02) were significantly associated parameters. In multivariate analysis, maximum tumor diameter (P = 0.02) and amount of intraoperative bleeding (P = 0.04) were associated parameters.

Conclusions

For patients with risk factors for wound complications, control of bleeding are crucial when resecting deep-seated STS in the adductor compartment of the thigh. In cases with large tumors, surgeons should be especially cautious of cases requiring interventions that surround the femoral artery and vein in order to attain an appropriate surgical margin.
Laparoscopic anatomical segment 3 segmentectomy for hepatocellular carcinoma accompanied by hypoplasia of the right hepatic lobe
Authors: Yamane Hisoka , Yoshida Sachiko , Yoshida Toshihiko , Nishi Masayasu , Yamagishi Takashi , Goto Hironobu , Otsubo Dai , Furutani Akinobu , Matsumoto Taku , Fujino Yasuhiro , Tominaga Masahiro
Published: June 2019

We report a case of laparoscopic anatomical segment 3 segmentectomy for hepatocellular carcinoma (HCC) accompanied by hypoplasia of the right hepatic lobe. An 80-year-old man was admitted with a suspicion of HCC diagnosed by computed tomography during follow-up for thyroid cancer. Dynamic computed tomography showed 40-mm HCC in segment 3 and hypoplasia of the right hepatic lobe with the Chilaiditi sign. We performed laparoscopic anatomical segment 3 segmentectomy. There were no postoperative complications, and the patient was discharged 6 days postoperatively. This procedure can be performed safely and is technically feasible, but special attention should be paid to anatomical alterations to avoid fatal surgical complications.
Sulfated plant peptide hormones
Authors: Kaufmann Christine , Sauter Margret
Published: June 2019

Sulfated peptides are plant hormones that are active at nanomolar concentrations. The sulfation at one or more tyrosine residues is catalysed by tyrosylprotein sulfotransferase (TPST), which is encoded by a single-copy gene. The sulfate group is provided by the co-substrate 3´-phosphoadenosine 5´-phosphosulfate (PAPS), which links synthesis of sulfated signaling peptides to sulfur metabolism. The precursor proteins share a conserved DY-motif that is implicated in specifying tyrosine sulfation. Several sulfated peptides undergo additional modification such as hydroxylation of proline and glycosylation of hydroxyproline. The modifications render the secreted signaling molecules active and stable. Several sulfated signaling peptides have been shown to be perceived by leucine-rich repeat receptor-like kinases (LRR-RLKs) but have signaling pathways that, for the most part, are yet to be elucidated. Sulfated peptide hormones regulate growth and a wide variety of developmental processes, and intricately modulate immunity to pathogens. While basic research on sulfated peptides has made steady progress, their potential in agricultural and pharmaceutical applications has yet to be explored.
Genotypic variation and nitrogen stress effects on root anatomy in maize are node specific
Authors: Yang Jennifer T , Schneider Hannah M , Brown Kathleen M , Lynch Jonathan P
Published: June 2019

Root phenotypes that improve nitrogen acquisition are avenues for crop improvement. Root anatomy affects resource capture, metabolic cost, hydraulic conductance, anchorage, and soil penetration. Cereal root phenotyping has centered on primary, seminal, and early nodal roots, yet critical nitrogen uptake occurs when the nodal root system is well developed. This study examined root anatomy across nodes in field-grown maize (Zea mays L.) hybrid and inbred lines under high and low nitrogen regimes. Genotypes with high nitrogen use efficiency (NUE) had larger root diameter and less cortical aerenchyma across nodes under stress than genotypes with lower NUE. Anatomical phenes displayed slightly hyperallometric relationships to shoot biomass. Anatomical plasticity varied across genotypes; most genotypes decreased root diameter under stress when averaged across nodes. Cortex, stele, total metaxylem vessel areas, and cortical cell file and metaxylem vessel numbers scaled strongly with root diameter across nodes. Within nodes, metaxylem vessel size and cortical cell size were correlated, and root anatomical phenotypes in the first and second nodes were not representative of subsequent nodes. Node, genotype, and nitrogen treatment affect root anatomy. Understanding nodal variation in root phenes will enable the development of plants that are adapted to low nitrogen conditions.
Untimely Developments: Genre Drag and Gish Jen’s Mona in the Promised Land
Authors: Lee Wendy Allison
Published: June 2019

Through a reinterpretation of Gish Jen’s novel Mona in the Promised Land (1996), this essay makes the case for the queer possibilities immanent to the most conservative “family values” Asian American genre—the bildungsroman organized around intergenerational conflict. In a decade obsessed with the question of what shifting racial and ethnic demographics meant for the national future, Mona’s content tempted 1990s readers to interpret its vision of the 1960s as a timely meditation on the present. Read in such a way, the novel resolves anxieties about demographic change by reproducing the “timeless” values of family and nation. However, Mona’s form tells a different story. Rather than using the historical past as a mere backdrop to tell a timely story about national progress, Mona is reflexive in its preoccupation with its relationship to the past. Jen’s novel shows us what a coming-of-age story looks like when it does not assimilate its subject into national time. Instead, Mona draws “untimely comparisons” between past US imperial formations that are the present’s condition of possibility. I examine how the novel disrupts the bildungroman’s formal and ideological relationship to national futurity by evoking the past as a drag on progress and the novel as enacting a formal corollary to queer drag performance. I read Mona as a novel of untimely development that reinvents the coming-of-age narrative so that the Asian American subject becomes not a figure that exemplifies a certain future subject or nation but instead one that generatively obstructs national fantasies of progress.
Exogenous RNAi mechanisms contribute to transcriptome adaptation by phased siRNA clusters in Paramecium
Authors: Karunanithi Sivarajan , Oruganti Vidya , Marker Simone , Rodriguez-Viana Angela M , Drews Franziska , Pirritano Marcello , Nordström Karl , Simon Martin , Schulz Marcel H
Published: June 2019

Extensive research has characterized distinct exogenous RNAi pathways interfering in gene expression during vegetative growth of the unicellular model ciliate Paramecium. However, role of RNAi in endogenous transcriptome regulation, and environmental adaptation is unknown. Here, we describe the first genome-wide profiling of endogenous sRNAs in context of different transcriptomic states (serotypes). We developed a pipeline to identify, and characterize 2602 siRNA producing clusters (SRCs). Our data show no evidence that SRCs produce miRNAs, and in contrast to other species, no preference for strand specificity of siRNAs. Interestingly, most SRCs overlap coding genes and a separate group show siRNA phasing along the entire open reading frame, suggesting that the mRNA transcript serves as a source for siRNAs. Integrative analysis of siRNA abundance and gene expression levels revealed surprisingly that mRNA and siRNA show negative as well as positive associations. Two RNA-dependent RNA Polymerase mutants, RDR1 and RDR2, show a drastic loss of siRNAs especially in phased SRCs accompanied with increased mRNA levels. Importantly, most SRCs depend on both RDRs, reminiscent to primary siRNAs in the RNAi against exogenous RNA, indicating mechanistic overlaps between exogenous and endogenous RNAi contributing to flexible transcriptome adaptation.
Cholera outbreak during a scientific conference at a Nairobi hotel, Kenya 2017
Authors: Mwenda Valerian , Niyomwungere Alexis , Oyugi Elvis , Githuku Jane , Obonyo Mark , Gura Zeinab
Published: June 2019

Background

Cholera globally affects 1.3–4.0 million people and causes 21 000–143 000 deaths annually. In June 2017, a cluster of diarrhoeal illness occurred among participants of an international scientific conference at a hotel in Nairobi, Kenya. Culture confirmed Vibrio cholerae, serotype Ogawa. We investigated to assess magnitude, identify likely exposures and suggest control measures.

Methods

We carried out a retrospective cohort study utilizing a structured questionnaire administered by telephone, email and internet-based survey. We calculated food-specific attack rates, risk ratios and in a nested-case control analysis, performed logistic regression to identify exposures independently associated with the outbreak.

Results

We interviewed 249 out of 456 conference attendees (response rate=54.6%). Mean age of respondents was 37.8 years, ±8.3 years, 131 (52.6%) were male. Of all the respondents, 137 (55.0%) were cases. Median incubation time was 35 (11–59) hours. Eating chicken (adjusted OR 2.49, 95% CI, 1.22–5.06) and having eaten lunch on Tuesday (adjusted OR 2.34, 95% CI 1.09–5.05) were independently associated with illness; drinking soda was protective (adjusted OR 0.17, 95% CI 0.07–0.42).

Conclusion

Point source outbreak, associated with chicken eaten at lunch on Tuesday 20th June 2017 occurred. We recommend better collaboration between the food and health sectors in food-borne outbreak investigations.
Towards therapeutic drug monitoring of TNF inhibitors for children with juvenile idiopathic arthritis: a scoping review
Authors: Verstegen Ruud H J , McMillan Rhona , Feldman Brian M , Ito Shinya , Laxer Ronald M
Published: June 2019

Objectives

Before a clinician decides whether treatment with TNF inhibition in children with JIA has failed, one should ensure adequate systemic exposure has been achieved. Therapeutic drug monitoring might allow for improved treatment outcome with lower treatment-associated costs. However, this requires understanding of the pharmacokinetic (PK) characteristics, and the pharmacokinetic/pharmacodynamic (PK/PD) relationship for children with JIA. We performed a scoping review to summarize the available literature and identify areas for future research.

Methods

A systematic search was conducted of the Medline, EMBASE, Web of Science and Cochrane databases as well as the clinicaltrials.gov registry. In total, 3959 records were screened and 130 publications were selected for full text assessment.

Results

Twenty publications were included and divided into three categories: PK (n = 9), PK/PD (n = 3) and anti-drug antibodies (n = 13). Industry involvement was significant in 14 publications. Although data are limited, systemic exposure to TNF inhibitors is generally lower in younger children but meta-analysis is not possible. The PK/PD relationship has had limited study but there is partial evidence for infliximab. Anti-drug antibodies are common, and are related to impaired clinical outcome with adalimumab and infliximab therapy.

Conclusion

The current knowledge about the PK and PK/PD of TNF inhibitors in the treatment of children with JIA is limited, which prevents the introduction of TDM. Re-analysis of available data from previous trials, incorporation of pharmacologic assessments into existing biorepository studies as well as new prospective PK and PK/PD trials are required to obtain this knowledge.
Trust law in Chinese courts: judicial decisions as data (2001–2017)
Authors: Qu Jian
Published: June 2019

Trust law was transplanted into China nearly two decades ago, but how has it been applied by the Chinese courts? The answer may be found in relevant judgments. This study collected accessible Chinese court decisions related to trusts, and, relying on this, the citation practice of Trust Law in courts can be analyzed chronologically, and intensively applied articles can be singled out. Thus, this study intends to use these judicial documents, as data and as individual cases, to examine the role that the Chinese Trust Law has played in the judicial field since its enactment in 2001.
Accurate estimation of cell composition in bulk expression through robust integration of single-cell information
Authors: Jew Brandon , Alvarez Marcus , Rahmani Elior , Miao Zong , Ko Arthur , Sul Jae Hoon , Pietiläinen Kirsi H. , Pajukanta Päivi , Halperin Eran
Published: June 2019

We present Bisque, a tool for estimating cell type proportions in bulk expression. Bisque implements a regression-based approach that utilizes single-cell RNA-seq (scRNA-seq) data to generate a reference expression profile and learn gene-specific bulk expression transformations to robustly decompose RNA-seq data. These transformations significantly improve decomposition performance compared to existing methods when there is significant technical variation in the generation of the reference profile and observed bulk expression. Importantly, compared to existing methods, our approach is extremely efficient, making it suitable for the analysis of large genomic datasets that are becoming ubiquitous. When applied to subcutaneous adipose and dorsolateral prefrontal cortex expression datasets with both bulk RNA-seq and single-nucleus RNA-seq (snRNA-seq) data, Bisque was able to replicate previously reported associations between cell type proportions and measured phenotypes across abundant and rare cell types. Bisque requires a single-cell reference dataset that reflects physiological cell type composition and can further leverage datasets that includes both bulk and single cell measurements over the same samples for improved accuracy. We further propose an additional mode of operation that merely requires a set of known marker genes. Bisque is available as an R package at: https://github.com/cozygene/bisque.
Primary human chondrocytes respond to compression with plasma membrane receptors and by microtubule activation: a phosphoproteomic study
Authors: Zignego Donald L. , Hilmer Jonathan K. , Bothner Brian , Schell William J. , June Ronald K.
Published: June 2019

Chondrocytes are responsible for maintaining the cartilage that helps joints like the knee and hip bear load and move smoothly. These cells typically respond to physiological compression with pathways consistent with matrix synthesis, and chondrocyte mechanotransduction is essential for tissue and joint homeostasis. In osteoarthritis (OA), chondrocyte mechanotransduction appears to be dysregulated, yet many pathways and mechanisms of osteoarthritic chondrocyte mechanotransduction remain poorly understood. The objective of this study is to document the phosphoproteomic responses of primary osteoarthritic chondrocytes to physiological sinusoidal compression. Here we show that OA chondrocytes respond to physiological compression by first activating proteins consistent with cytoskeletal remodeling and decreased transcription, and then later activating proteins for transcription. These results show that several microtubule-related proteins respond to compression, as well as proteins related to calcium signaling, which has previously been extensively shown in chondrocytes. Our results demonstrate that compression is a relevant physiological stimulus for osteoarthritic chondrocytes. We anticipate these data to be a starting point for more sophisticated analysis of both normal and osteoarthritic chondrocyte mechanotransduction. For example, finding differences in compression-induced phosphoproteins between normal and OA cells may lead to druggable targets to restore homeostasis to diseased joints.
Inherited duplications ofPPP2R3Bpromote naevi and melanoma via a novelC21orf91-driven proliferative phenotype
Authors: Polubothu Satyamaanasa , Al-Olabi Lara , Lionarons Daniël A , Harland Mark , Thomas Anna C , Horswell Stuart , Hunt Lilian , Wlodarchak Nathan , Aguilera Paula , Brand Sarah , Bryant Dale , Beales Philip , Carrera Cristina , Chen Hui , Elgar Greg , Harwood Catherine A , Howell Michael , Jenkins Dagan , Larue Lionel , Loughlin Sam , MacDonald Jeff , Malvehy Josep , Barberan Sara Martin , Martins da Silva Vanessa , Molina Miriam , Morrogh Deborah , Moulding Dale , Nsengimana Jérémie , Pittman Alan , Puig-Butillé Juan-Anton , Parmar Kiran , Sebire Neil J , Scherer Stephen , Stadnik Paulina , Stanier Philip , Tell Gemma , Waelchli Regula , Zarrei Mehdi , Zecchin Davide , Puig Susana , Bataille Véronique , Xing Yongna , Healy Eugene , Moore Gudrun E , Di Wei-Li , Newton-Bishop Julia , Downward Julian , Kinsler Veronica A
Published: June 2019

The majority of the heredity of melanoma remains unexplained, however inherited copy number changes have not yet been systematically studied. The genetic environment is highly relevant to treatment stratification, and new gene discovery is therefore desirable. Using an unbiased whole genome screening approach for copy number we identify here a novel melanoma predisposing factor, familial duplications of genePPP2R3B, encoding a regulatory unit of critical phosphatase PP2A. Significant correlation between expression ofPPP2R3Bin tumour tissue and survival in a large melanoma cohort was confirmed, and associated with a non-immunological expression profile. Mechanistically, construction and extensive characterization of a stable, inducible cellular model forPPP2R3Boverexpression revealed induction of pigment cell switching towards proliferation and away from migration. Importantly, this was independent of the known microphthalmia-associated transcription factor(MITF)-controlled pigment cell phenotype switch, and was instead driven by uncharacterised geneC21orf91. Bioinformatic studies point toC21orf91as a novel target ofMITF,and therefore a potential hub in the control of phenotype switching in melanoma. This study identifies novel germline copy number variants inPPP2R3Bpredisposing to melanocytic neoplasia, and uncovers a new potential therapeutic targetC21orf91in the control of pigment cell proliferation.
Autonomous drones are a viable tool for acoustic bat surveys
Authors: August Tom , Moore Tom
Published: June 2019

Acoustic surveys of bats are currently limited by the detection range of ultrasound microphones. This makes it difficult to survey bats at height, over water, or in other hard to reach locations. Drones, also known as UAVs or UASs, are becoming more affordable and feature rich, resulting in more uptake in conservation, primarily for aerial imagery. In this paper we address current limitations to acoustic bat surveys by developing three autonomous drones for surveying bats; a plane, quadcopter and boat. All three are capable of moving autonomously from one waypoint to another while carrying a bat detector to record bats and are all low cost (under US$950) with large operational ranges that make them suited to aerial transect work.

Initial testing highlighted ultrasound noise generated by the drones as a major issue for recording bats from these systems. This was mitigated through iterative design of the microphone placement and the vehicles themselves. Subsequent testing in real world settings, in the presence of bats, demonstrated that bats could be recorded under autonomous navigation and that the ultrasound interference could be reduced to a negligible level.

Autonomous drones offer an exciting new tool in the tool box of bat workers and researchers. They allow us to study areas previously inaccessible on foot, as well as at heights that have previously been inaccessible. We also discuss current limitations to this technology, including legal considerations, hidden costs and potential impacts on bat behaviour.
Identifying Combinations of Cancer Drivers in Individual Patients
Authors: Klein Michael I. , Cannataro Vincent L. , Townsend Jeffrey P. , Stern David F. , Zhao Hongyu
Published: June 2019

Identifying the subset of genetic alterations present in individual tumors that are essential and collectively sufficient for cancer initiation and progression would advance the development of effective personalized treatments. We present CRSO for inferring the combinations of alterations, i.e., rules, that cooperate to drive tumor formation in individual patients. CRSO prioritizes rules by integrating patient-specific passenger probabilities for individual alterations along with information about the recurrence of particular combinations throughout the population. We present examples in glioma, liver cancer and melanoma of significant differences in patient outcomes based on rule assignments that are not identifiable by consideration of individual alterations.
Nascent chromatin occupancy profiling reveals locus- and factor-specific chromatin maturation dynamics behind the DNA replication fork
Authors: Gutiérrez Mónica P. , MacAlpine Heather K. , MacAlpine David M.
Published: June 2019

Proper regulation and maintenance of the epigenome is necessary to preserve genome function. However, in every cell division, the epigenetic state is disassembled and then reassembled in the wake of the DNA replication fork. Chromatin restoration on nascent DNA is a complex and regulated process that includes nucleosome assembly and remodeling, deposition of histone variants, and the re-establishment of transcription factor binding. To study the genome-wide dynamics of chromatin restoration behind the DNA replication fork, we developed nascent chromatin occupancy profiles (NCOPs) to comprehensively profile nascent and mature chromatin at nucleotide resolution. Although nascent chromatin is inherently less organized than mature chromatin, we identified locus-specific differences in the kinetics of chromatin maturation that were predicted by the epigenetic landscape, including the histone variant H2AZ, which marked loci with rapid maturation kinetics. The chromatin maturation at origins of DNA replication was dependent on whether the origin underwent initiation or was passively replicated from distal-originating replication forks, suggesting distinct chromatin assembly mechanisms surrounding activated and disassembled prereplicative complexes. Finally, we identified sites that were only occupied transiently by DNA-binding factors following passage of the replication fork, which may provide a mechanism for perturbations of the DNA replication program to shape the regulatory landscape of the genome.
RFID-based tracking and monitoring approach of real-time data in production workshop
Authors: Li Xixing , Du Baigang , Li Yibing , Zhuang Kejia
Published: June 2019

Purpose

In practical workshop production process, there are many production emergencies, e.g. new manufacturing tasks, facilities failure and tasks change. On one hand, it results in poor timeliness and reliability of real-time production data collection, acquisition and transmission; on the other hand, it increases the difficulty of real-time data tracking and monitoring. This paper aims to develop a novel RFID-based tracking and monitoring approach of real-time data in production workshop (TMrfid) to solve them.

Design/methodology/approach

At first, a three-layer model of real-time data based on RFID has been constructed, which contains RFID-based integrated acquisition center; “RFID & Cloud-service-rules”-based calculation and analysis center; and “RFID & Ontology-knowledge-base”-based monitoring and scheduling center. Then, a targeted analysis and evaluation method of TMrfid with feasibility, quality and performance has been proposed. Finally, a prototype platform of a textile machinery manufacturing enterprise has been built to verify the effective of TMrfid.

Findings

The effectiveness of TMrfid is verified by applying two groups of actual experimental data from the case enterprise, the results show that TMrfid can promote the efficiency, reliability and feasibility of tacking and monitoring of real-time data in production workshop.

Originality/value

RFID-based tracking and monitoring approach of real-time data in production workshop has been developed to solve the data information transmission and sharing problem. Three analysis and evaluation approaches have been introduced to solve the un-standardized evaluation problem of RFID application. A prototype platform of a textile machinery manufacturing enterprise has been constructed.