bluuebunny/crossref_metadata_2025 huggingface dataset:
FDG PET/CT in a Case of Bilateral Tuberculous Epididymo-orchitis
Authors: Ran Pengcheng , Liang Xiang , Zhang Yu , Sun Pengtao , Dong Aisheng
Published: May 2019

Isolated genital tuberculosis is rare. We present a case of bilateral tuberculous epididymo-orchitis showing high FDG uptake on FDG PET/CT. In addition, the patient had a prostatic FDG-avid lesion, consistent with tuberculous prostatitis. This case indicates tuberculous epididymo-orchitis, especially in tuberculosis-endemic regions, should be considered as a differential diagnosis in patients with hypermetabolic epididymal or testicular lesions, including benign and malignant tumors, bacterial epididymo-orchitis, abscess, idiopathic granulomatous orchitis, and sarcoidosis.
18F-FACBC PET/MRI in Diagnostic Assessment and Neurosurgery of Gliomas
Authors: Karlberg Anna , Berntsen Erik Magnus , Johansen Håkon , Skjulsvik Anne Jarstein , Reinertsen Ingerid , Dai Hong Yan , Xiao Yiming , Rivaz Hassan , Borghammer Per , Solheim Ole , Eikenes Live
Published: May 2019

Purpose

This pilot study aimed to evaluate the amino acid tracer 18F-FACBC with simultaneous PET/MRI in diagnostic assessment and neurosurgery of gliomas.

Materials and Methods

Eleven patients with suspected primary or recurrent low- or high-grade glioma received an 18F-FACBC PET/MRI examination before surgery. PET and MRI were used for diagnostic assessment, and for guiding tumor resection and histopathological tissue sampling. PET uptake, tumor-to-background ratios (TBRs), time-activity curves, as well as PET and MRI tumor volumes were evaluated. The sensitivities of lesion detection and to detect glioma tissue were calculated for PET, MRI, and combined PET/MRI with histopathology (biopsies for final diagnosis and additional image-localized biopsies) as reference.

Results

Overall sensitivity for lesion detection was 54.5% (95% confidence interval [CI], 23.4–83.3) for PET, 45.5% (95% CI, 16.7–76.6) for contrast-enhanced MRI (MRICE), and 100% (95% CI, 71.5–100.0) for combined PET/MRI, with a significant difference between MRICE and combined PET/MRI (P = 0.031). TBRs increased with tumor grade (P = 0.004) and were stable from 10 minutes post injection. PET tumor volumes enclosed most of the MRICE volumes (>98%) and were generally larger (1.5–2.8 times) than the MRICE volumes. Based on image-localized biopsies, combined PET/MRI demonstrated higher concurrence with malignant findings at histopathology (89.5%) than MRICE (26.3%).

Conclusions

Low- versus high-grade glioma differentiation may be possible with 18F-FACBC using TBR. 18F-FACBC PET/MRI outperformed MRICE in lesion detection and in detection of glioma tissue. More research is required to evaluate 18F-FACBC properties, especially in grade II and III tumors, and for different subtypes of gliomas.
Predictive Value of 16α-[18F]-Fluoro-17β-Estradiol PET as a Biomarker of Progestin Therapy Resistance in Patients With Atypical Endometrial Hyperplasia and Low-Grade Endometrial Cancer
Authors: Yamada Shizuka , Tsuyoshi Hideaki , Tsujikawa Tetsuya , Okazawa Hidehiko , Yoshida Yoshio
Published: May 2019

For early-stage endometrial cancer patients who wish to preserve fertility, progestin treatment is effective. However, repeated endometrial curettage to evaluate treatment response may cause infertility. The clinical courses of 3 patients who were treated with fertility-sparing progestin treatment and underwent serial 18F-FES PET before and after treatment are presented. The SUVmean decreased greatly in patients with pathologically complete response (44.2%, 46.2%), whereas there was only a small change (22.5%) in the patient with pathologically stable disease who finally underwent hysterectomy. 18F-FES PET can be a noninvasive method to evaluate response to fertility-sparing progestin treatment.
A Critical Assessment of the Linear No-Threshold Hypothesis
Authors: Siegel Jeffry A. , Brooks Antone L. , Fisher Darrell R. , Zanzonico Pat B. , Doss Mohan , O'Connor Michael K. , Silberstein Edward B. , Welsh James S. , Greenspan Bennett S.
Published: May 2019

The Society of Nuclear Medicine and Molecular Imaging convened a task group to examine the evidence for the risk of carcinogenesis from low-dose radiation exposure and to assess evidence in the scientific literature related to the overall validity of the linear no-threshold (LNT) hypothesis and its applicability for use in risk assessment and radiation protection. In the low-dose and dose-rate region, the group concluded that the LNT hypothesis is invalid as it is not supported by the available scientific evidence and, instead, is actually refuted by published epidemiology and radiation biology. The task group concluded that the evidence does not support the use of LNT either for risk assessment or radiation protection in the low-dose and dose-rate region.
Thyroid Cancer Brain Metastasis
Authors: Osborne Joseph R. , Kondraciuk Jessica D. , Rice Samuel L. , Zhou Xiaosun , Knezevic Andrea , Spratt Daniel E. , Sabra Mona , Larson Steven M. , Grewal Ravinder K.
Published: May 2019

Purpose

Brain metastases (BMs) in patients with differentiated thyroid cancer (DTC) are rare but associated with poor prognosis. We examined risk factors for overall survival (OS) in this population and explored the pattern of genomic alterations.

Methods

Single-institution, retrospective review of all patients with DTC from January 2000 to November 2016 identified 79 patients for analysis. Multiple prognostic factors, including age, gender, distal metastasis (DM), diagnosis time, DM sites, BM diagnosis time, BM number and size, genomic sequencing data, craniectomy, external beam radiation therapy, and kinase inhibitor therapies, were evaluated. Univariate and multivariate analyses were performed.

Results

Median survival after BM was 18 months. One- and 3-year survival rates were 63% and 33%, respectively. Univariate analysis identified 4 covariates correlated with prolonged survival: time between DTC diagnosis and BM for less than 3 years (P = 0.01), time from initial DM diagnosis to BM for 22 months or less (P = 0.03), 3 BM sites or fewer (P = 0.002), and craniectomy (P = 0.05). Multivariate model revealed 3 variables associated with OS: DTC diagnosis to BM time of less than 3 years (P = 0.04), craniectomy (P = 0.06), and patients with fewer than 3 BM sites (P = 0.06). The majority of patients with BM had a telomerase reverse transcriptase promoter mutation, However, mutational status was not an independent predictor of survival.

Conclusions

For BM from DTC, time interval between DTC diagnosis and BM, number of BM sites, and craniectomy were independently associated with OS. Further studies are needed to define the role of genomic mutations in advanced cancer.
Renal Pelvis Involvement of Immunoglobulin G4–Related Disease Mimicking Malignancy on 18F-FDG PET/CT
Authors: Jiang Yuanyuan , Hou Guozhu , Cheng Wuying
Published: May 2019

A 70-year-old woman with bilateral submandibular gland enlargement was referred to our hospital. Submandibular gland biopsy indicated immunoglobulin G4 (IgG4)–related disease (IgG4-RD) involvement. Contrast-enhanced CT was undergone for evaluation of IgG4-RD and revealed a mass located at the left renal pelvis. 18F-FDG PET/CT showed bilateral FDG-avid submandibular gland and a hypermetabolic mass in the left renal pelvis. The lesions were decreased in both size and metabolism on follow-up PET/CT 2 months after treatment with prednisone. This case illustrated a rare site for IgG4-RD, and the renal pelvis involvement should be considered into differential diagnosis in patients with IgG4-RD history.
Bone Pseudometastasis on 18F-FDG PET in Japanese Patients With Esophageal Cancer
Authors: Okuyama Chio , Higashi Tatsuya , Ishizu Koichi , Nakamoto Ryusuke , Takahashi Masaaki , Kusano Kuninori , Kagawa Shinya , Yamauchi Hiroshi
Published: May 2019

Purpose of the Report

False-positive bone lesions mimicking bone metastases (bone pseudometastasis) on 18F-FDG PET/CT have often been reported in patients with esophageal cancer. We aimed to evaluate the prevalence and features of these lesions in Japanese patients with esophageal cancer.

Methods

In this retrospective study, we analyzed 83 FDG PET/CT studies for initial staging of esophageal cancer, and extracted patients with 1 or more localized high uptake sites with no subsequent progression, which were therefore judged to be bone pseudometastasis. The FDG PET/CT imaging features of the bone pseudometastasis were evaluated, and other available imaging and clinical features reviewed.

Results

Of the 83 patients, 7 had bone pseudometastasis. All 7 were males diagnosed with squamous cell cancer, of which 5 had T1a tumors. Bone pseudometastasis showed normal or ill-defined hyperdense (nonosteolytic) sites compared with the surrounding area on the CT. Additionally, accumulation in the upper vertebral levels of each case was contiguously high compared with the lumbar spines (we named this finding “contiguous accumulation”). On MRI, these findings were visualized as low signals on T1-weighted imaging (T1WI) and T2WI images but were unclear on fat-suppressed T2WI images.

Conclusions

Among all PET/CT performed for staging of esophageal cancer, 8.3% demonstrated bone pseudometastasis characterized by heterogeneous distribution with severe fatty degeneration of bone marrow accompanied by contiguous accumulation. Caution is required during diagnoses of bone lesions in esophageal cancer patients in Japan to prevent inappropriate therapeutic choices.
Endoscopic Magnetic Compression Anastomosis For Small Bowel Bypass in a High Operative Risk Setting
Authors: Lebares Carter C. , Graves Claire E. , Lin Matthew Y. , Fidelman Nicholas , Cello John , Harrison Michael R. , Rogers Stanley
Published: May 2019

The endoscopic enteroenteral bypass could revolutionize the treatment of small bowel obstruction (SBO) in inoperable patients. We describe the technique of endoscopic delivery of a magnetic compression anastomosis device and the creation of an enteroenteral anastomosis in a patient with recurrent acute on chronic SBOs and prohibitively high operative risk. In this novel procedure, a magnetic compression anastomosis device is delivered on either side of the obstruction using a hybrid endoscopic/fluorographic technique, effectively bypassing the obstruction and relieving symptoms. The anastomosis was endoscopically evaluated at regular intervals postprocedure. By 7 days, healthy villi were visible through the mated magnetic rings. By 10 days, the anastomosis was widely patent. The rings passed through the ileostomy and were evacuated, and the patient’s symptoms completely resolved. The anastomosis remained widely patent at 1 year. In summary, this case demonstrates the benefit of magnetic compression anastomosis in a patient with SBO and high operative risk.
Endoscopic Ultrasound-guided Celiac Plexus Neurolysis to Alleviate Intractable Pain Caused by Advanced Pancreatic Cancer
Authors: Lou Songmei
Published: May 2019

This study aimed to analyze the clinical safety and effectiveness of endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) in alleviating intractable abdominal pain caused by advanced pancreatic cancer. A total of 58 patients with inoperable pancreatic cancer who underwent EUS-CPN from May 2015 to December 2017 were enrolled. Pain levels before and after EUS-CPN were assessed and compared using the Visual Analogue Scale. The preoperative Visual Analogue Scale score was 8.2±2.3, which decreased significantly to 3.6±1.5 at 2 days after EUS-CPN and to 2.2±0.8 after 1 month. The response rate was 79.3%. No patient experienced serious complications; 14 patients experienced mild, transient side effects (self-limiting diarrhea, reflex hypotension, and worsening of abdominal pain) that resolved within 48 hours. For pancreatic cancer patients, EUS-CPN can effectively control pain with minimal adverse effects.
Area Under Trough Concentrations of Tacrolimus as a Predictor of Progressive Renal Impairment After Liver Transplantation
Authors: Rodríguez-Perálvarez Manuel , Guerrero Marta , De Luca Laura , Gros Beatriz , Thorburn Douglas , Patch David , Aumente María D. , Westbrook Rachel , Fernández Rocío , Amado Víctor , Aguilar Patricia , Montero Jose Luis , O’Beirne James , Briceño Javier , Tsochatzis Emmanuel , De la Mata Manuel
Published: May 2019

Background.

Tacrolimus minimization is usually restricted to patients with pretransplant renal impairment, and this strategy could result into worse renal outcomes after liver transplantation (LT).

Methods.

A consecutive cohort of 455 LT patients receiving tacrolimus-based immunosuppression was studied (2008–2013). Cumulative exposure to tacrolimus was calculated as the area under curve of trough concentrations (AUCtc). Patients were stratified as tacrolimus minimization, conventional, or high exposure, according to the thresholds based in the COMMIT consensus. Estimated glomerular filtration rates (eGFR) were assessed by the Modification of Diet in Renal Disease formula (MDRD-4) up to 5 years after LT.

Results.

Seventy patients (15.4%) had pretransplant eGFR < 60 mL/min, which was associated with increased mortality rates, particularly within the first 5 years post-LT (31.4% versus 17.5%; Breslow P = 0.010). After LT, there was an abrupt eGFR decline within the first 3 months (median 18.6 mL/min; P < 0.001), further decreasing up to 12 months (additional 3 mL/min), without any improvement thereafter. According to AUCtc, 33.7% of patients received tacrolimus minimization, 44.8% conventional exposure, and 21.5% high exposure. Conventional/high exposure to tacrolimus resulted in a more pronounced eGFR decline within the first 3 months when compared with minimization (23.3 mL/min versus 9.5 mL/min; P < 0.001). This gap was even higher in patients with initially preserved renal function. Tacrolimus AUCtc was an independent predictor of eGFR decline within the first 3 months after controlling for potential confounders.

Conclusions.

AUCtc is a surrogate of cumulative exposure to tacrolimus and may be helpful for routine dose adjustments. Tacrolimus minimization should be universally attempted after LT to preserve renal function.
Changes of T-cell Immunity Over a Lifetime
Authors: Nian Yeqi , Minami Koichiro , Maenesono Ryoichi , Iske Jasper , Yang Jinrui , Azuma Haruhito , ElKhal Abdala , Tullius Stefan G.
Published: May 2019

T-cell immunity undergoes a complex and continuous remodeling with aging. Understanding those dynamics is essential in refining immunosuppression. Aging is linked to phenotypic and metabolic changes in T-cell immunity, many resulting into impaired function and compromised effectiveness. Those changes may impact clinical immunosuppression with evidences suggesting age-specific efficacies of some (CNI and mammalian target of rapamycin inhibitors) but not necessarily all immunosuppressants. Metabolic changes of T cells with aging have only recently been appreciated and may provide novel ways of immunosuppression. Here, we provide an update on changes of T-cell immunity in aging.
Decreasing Incontinence-Associated Dermatitis in the Surgical Intensive Care Unit
Authors: Gates Brandon P. , Vess Joy , Long Mary Arnold , Johnson Emily
Published: May 2019

PURPOSE:

The purpose of this quality improvement (QI) project was to determine if use of an algorithm focusing on skin care in patients with fecal and urinary incontinence reduces the rate of hospital-acquired incontinence-associated dermatitis (IAD) over a period of 4 months.

PARTICIPANTS AND SETTING:

The QI setting was an 18-bed surgical intensive care unit (SICU) in an acute care urban hospital located in the southeastern United States. Two hundred eleven patients participated in this pre/postintervention QI project.

APPROACH:

The algorithm for skin care used evidence-based bundled interventions for patients with fecal and urinary incontinence. The project comprised education of the SICU nursing staff in January 2018 and implementation of the algorithm from February 5, 2018, to June 5, 2018. Weekly chart reviews were conducted to determine algorithm compliance, documentation of fecal and urinary incontinence, and accuracy of IAD documentation. Descriptive statistics were used to determine the rate of hospital-acquired IAD, algorithm compliance, and average length of time from admission to the onset of hospital-acquired IAD.

OUTCOMES:

Seventy-nine individuals with incontinence were included in the 3-month preintervention period and 132 individuals with incontinence in the 3-month postintervention period. We observed a 24% reduction in the rate of hospital-acquired IAD following implementation of the algorithm (29% vs 5%). The average length of time from admission to the onset of hospital-acquired IAD increased from 15 days in February 2018 to 25 days in May 2018.

IMPLICATIONS FOR PRACTICE:

Our experience with this QI project suggest that IAD can be identified and managed at the bedside by first clinical nursing staff without expertise in skin assessment and wound care.
A probabilistic census-travel model to predict introduction sites of exotic plant, animal and human pathogens
Authors: Gottwald Tim , Luo Weiqi , Posny Drew , Riley Tim , Louws Frank
Published: May 2019

International travel offers an extensive network for new and recurring human-mediated introductions of exotic infectious pathogens and biota, freeing geographical constraints. We present a predictive census-travel model that integrates international travel with endpoint census data and epidemiological characteristics to predict points of introduction. Population demographics, inbound and outbound travel patterns, and quantification of source strength by country are combined to estimate and rank risk of introduction at user-scalable land parcel areas (e.g. state, county, zip code, census tract, gridded landscapes (1 mi2, 5 km2, etc.)). This risk ranking by parcel can be used to develop pathogen surveillance programmes, and has been incorporated in multiple US state/federal surveillance protocols. The census-travel model is versatile and independent of pathosystems, and applies a risk algorithm to generate risk maps for plant, human and animal contagions at different spatial scales. An interactive, user-friendly interface is available online (https://epi-models.shinyapps.io/Census_Travel/) to provide ease-of-use for regulatory agencies for early detection of high-risk exotics. The interface allows users to parametrize and run the model without knowledge of background code and underpinning data.

This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’. This theme issue is linked with the earlier issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’.
Perfect counterfactuals for epidemic simulations
Authors: Kaminsky Joshua , Keegan Lindsay T. , Metcalf C. Jessica E. , Lessler Justin
Published: May 2019

Simulation studies are often used to predict the expected impact of control measures in infectious disease outbreaks. Typically, two independent sets of simulations are conducted, one with the intervention, and one without, and epidemic sizes (or some related metric) are compared to estimate the effect of the intervention. Since it is possible that controlled epidemics are larger than uncontrolled ones if there is substantial stochastic variation between epidemics, uncertainty intervals from this approach can include a negative effect even for an effective intervention. To more precisely estimate the number of cases an intervention will prevent within a single epidemic, here we develop a ‘single-world’ approach to matching simulations of controlled epidemics to their exact uncontrolled counterfactual. Our method borrows concepts from percolation approaches, prunes out possible epidemic histories and creates potential epidemic graphs (i.e. a mathematical representation of all consistent epidemics) that can be ‘realized’ to create perfectly matched controlled and uncontrolled epidemics. We present an implementation of this method for a common class of compartmental models (e.g. SIR models), and its application in a simple SIR model. Results illustrate how, at the cost of some computation time, this method substantially narrows confidence intervals and avoids nonsensical inferences.

This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’. This theme issue is linked with the earlier issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’.
Using models to provide rapid programme support for California's efforts to suppress Huanglongbing disease of citrus
Authors: McRoberts Neil , Figuera Sara Garcia , Olkowski Sandra , McGuire Brianna , Luo Weiqi , Posny Drew , Gottwald Tim
Published: May 2019

We describe a series of operational questions posed during the state-wide response in California to the arrival of the invasive citrus disease Huanglongbing. The response is coordinated by an elected committee from the citrus industry and operates in collaboration with the California Department of Food and Agriculture, which gives it regulatory authority to enforce the removal of infected trees. The paper reviews how surveillance for disease and resource allocation between detection and delimitation have been addressed, based on epidemiological principles. In addition, we describe how epidemiological analyses have been used to support rule-making to enact costly but beneficial regulations and we highlight two recurring themes in the programme support work: (i) data are often insufficient for quantitative analyses of questions and (ii) modellers and decision-makers alike may be forced to accept the need to make decisions on the basis of simple or incomplete analyses that are subject to considerable uncertainty.

This article is part of the theme issue ‘Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control’. This theme issue is linked with the earlier issue ‘Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes’.
Sequence similarity searches for morphine biosynthesis enzymes in bacteria yield putative targets for understanding associations between infection and opiate administration
Authors: Zhan Shing Hei , French Leon
Published: May 2019

Exploiting the immunosuppressive, analgesic and highly addictive properties of morphine could increase the success of a bacterial pathogen. Therefore, we performed sequence similarity searches for two morphine biosynthesis demethylases in bacteria. For thebaine 6-O-demethylase and codeine O-demethylase, we found strong alignments to three (

Pseudomonas aeruginosa
,
Klebsiella pneumoniae

and

Acinetobacter baumannii

) of the six ESKAPE pathogens (

Enterococcus faecalis

,

Staphylococcus aureus

,

K. pneumoniae

,

A. baumannii

,

P. aeruginosa

and

Enterobacter

species) that are commonly associated with drug resistance and nosocomial infections. Expression of the aligned sequence found in

P. aeruginosa

(NP_252880.1/PA4191) is upregulated in isolates obtained from cystic fibrosis patients. Our findings provide putative mechanistic targets for understanding the role of morphine in pathogenicity.
Emergence and divergence of major lineages of Shiga-toxin-producing Escherichia coli in Australia
Authors: Ingle Danielle J. , Gonçalves da Silva Anders , Valcanis Mary , Ballard Susan A. , Seemann Torsten , Jennison Amy V. , Bastian Ivan , Wise Rolf , Kirk Martyn D. , Howden Benjamin P. , Williamson Deborah A.
Published: May 2019

Shiga-toxin-producing

Escherichia coli

(STEC) infection is an important global cause of foodborne disease. To date however, genomics-based studies of STEC have been predominately focused upon STEC collected in the Northern Hemisphere. Here, we demonstrate the population structure of 485 STEC isolates in Australia, and show that several clonal groups (CGs) common to Australia were infrequently detected in a representative selection of contemporary STEC genomes from around the globe. Further, phylogenetic analysis demonstrated that lineage II of the global O157:H7 STEC was most prevalent in Australia, and was characterized by a frameshift mutation in flgF, resulting in the H-non-motile phenotype. Strong concordance between in silico and phenotypic serotyping was observed, along with concordance between in silico and conventional detection of stx genes. These data represent the most comprehensive STEC analysis from the Southern Hemisphere, and provide a framework for future national genomics-based surveillance of STEC in Australia.
Global phylogenomics of multidrug-resistant Salmonella enterica serotype Kentucky ST198
Authors: Hawkey Jane , Le Hello Simon , Doublet Benoît , Granier Sophie A. , Hendriksen Rene S. , Fricke W. Florian , Ceyssens Pieter-Jan , Gomart Camille , Billman-Jacobe Helen , Holt Kathryn E. , Weill François-Xavier
Published: May 2019

Salmonella enterica

serotype Kentucky can be a common causative agent of salmonellosis, usually associated with consumption of contaminated poultry. Antimicrobial resistance (AMR) to multiple drugs, including ciprofloxacin, is an emerging problem within this serotype. We used whole-genome sequencing (WGS) to investigate the phylogenetic structure and AMR content of 121 S.
e
nterica serotype Kentucky sequence type 198 isolates from five continents. Population structure was inferred using phylogenomic analysis and whole genomes were compared to investigate changes in gene content, with a focus on acquired AMR genes. Our analysis showed that multidrug-resistant (MDR) S.
enterica serotype Kentucky isolates belonged to a single lineage, which we estimate emerged circa 1989 following the acquisition of the AMR-associated

Salmonella

genomic island (SGI) 1 (variant SGI1-K) conferring resistance to ampicillin, streptomycin, gentamicin, sulfamethoxazole and tetracycline. Phylogeographical analysis indicates this clone emerged in Egypt before disseminating into Northern, Southern and Western Africa, then to the Middle East, Asia and the European Union. The MDR clone has since accumulated various substitution mutations in the quinolone-resistance-determining regions (QRDRs) of DNA gyrase (gyrA) and DNA topoisomerase IV (parC), such that most strains carry three QRDR mutations which together confer resistance to ciprofloxacin. The majority of AMR genes in the
S. e
nterica
serotype Kentucky genomes were carried either on plasmids or SGI structures. Remarkably, each genome of the MDR clone carried a different SGI1-K derivative structure; this variation could be attributed to IS26-mediated insertions and deletions, which appear to have hampered previous attempts to trace the clone’s evolution using sub-WGS resolution approaches. Several different AMR plasmids were also identified, encoding resistance to chloramphenicol, third-generation cephalosporins, carbapenems and/or azithromycin. These results indicate that most MDR
S. e
nterica
serotype Kentucky circulating globally result from the clonal expansion of a single lineage that acquired chromosomal AMR genes 30 years ago, and has continued to diversify and accumulate additional resistances to last-line oral antimicrobials. This article contains data hosted by Microreact.
A Kuramoto model of self-other integration across interpersonal synchronization strategies
Authors: Heggli O.A. , Cabral J. , Konvalinka I. , Vuust P. , Kringelbach M.L.
Published: May 2019

Human social behaviour is complex, and the biological and neural mechanisms underpinning it remain debated1,2. A particularly interesting social phenomenon is our ability and tendency to fall into synchrony with other humans3,4. Our ability to coordinate actions and goals relies on the ability to distinguish between and integrate self and other, which when impaired can lead to devastating consequences. Interpersonal synchronization has been a widely used framework for studying action coordination and self-other integration, showing that in simple interactions, such as joint finger tapping, complex interpersonal dynamics emerge. Here we propose a computational model of self-other integration via within- and between-person action-perception links, implemented as a simple Kuramoto model with four oscillators. The model abstracts each member of a dyad as a unit consisting of two connected oscillators, representing intrinsic processes of perception and action. By fitting this model to data from two separate experiments we show that interpersonal synchronization strategies rely on the relationship between within- and between-unit coupling. Specifically, mutual adaptation exhibits a higher between-unit coupling than within-unit coupling; leading-following requires that the follower unit has a low within-unit coupling; and leading-leading occurs when two units jointly exhibit a low between-unit coupling. These findings are consistent with the theory of interpersonal synchronization emerging through self-other integration mediated by processes of action-perception coupling4. Hence, our results show that chaotic human behaviour occurring on a millisecond scale can be modelled using coupled oscillators.
Microbial evolution reshapes soil carbon feedbacks to climate change
Authors: Abs Elsa , Saleska Scott R. , Ferriere Regis
Published: May 2019

Microbial decomposition of soil organic matter is a key component of the global carbon cycle. As Earth’s climate changes, the response of microbes and microbial enzymes to rising temperatures will largely determine the soil carbon feedback to atmospheric CO2. However, while increasing attention focuses on physiological and ecological mechanisms of microbial responses, the role of evolutionary adaptation has been little studied. To address this gap, we developed an ecosystem-evolutionary model of a soil microbe-enzyme system under warming. Constraining the model with observations from five contrasting sites reveals evolutionary aggravation of soil carbon loss to be the most likely outcome; however, temperature-dependent increases in mortality could cause an evolutionary buffering effect instead. We generally predict a strong latitudinal pattern, from small evolutionary effects at low latitude to large evolutionary effects at high latitudes. Accounting for evolutionary mechanisms will likely be critical for improving projections of Earth system responses to climate change.
Increasing plant group productivity through latent genetic variation for cooperation
Authors: Wuest Samuel E. , Pires Nuno D. , Luo Shan , Vasseur Francois , Messier Julie , Grossniklaus Ueli , Niklaus Pascal A.
Published: May 2019

Historic yield advances in the major crops have to a large part been achieved by selection for improved productivity of groups of plant individuals such as high-density stands. Research suggests that such improved group productivity depends on “cooperative” traits (e.g. erect leaves, short stems) that – while beneficial to the group – decrease individual fitness under competition. This poses a problem for some traditional breeding approaches, especially when selection occurs at the level of individuals, because “selfish” traits will be selected for and reduce yields in high-density monocultures. One approach therefore has been to select individuals based on ideotypes with traits expected to promote group productivity. However, this approach is limited to architectural and physiological traits whose effects on growth and competition are relatively easy to anticipate.

Here, we developed a general and simple method for the discovery of alleles promoting cooperation in plant stands. Our method is based on the game-theoretical premise that alleles increasing cooperation incur a cost to the individual but benefit the monoculture group. Testing the approach using the model plant Arabidopsis thaliana, we found a major effect locus where the rarer allele was associated with increased cooperation and productivity in high-density stands. The allele likely affects a pleiotropic gene, since we find that it is also associated with reduced root competition but higher resistance against disease. Thus, even though cooperation is considered evolutionarily unstable, conflicting selective forces acting on a pleiotropic gene might maintain latent genetic variation for it in nature. Such variation, once identified in a crop, could be rapidly leveraged in modern breeding programs and provide efficient routes to increase yields.
Caffeine-dependent changes of sleep-wake regulation: evidence for adaptation after repeated intake
Authors: Weibel Janine , Lin Yu-Shiuan , Landolt Hans-Peter , Garbazza Corrado , Kolodyazhniy Vitaliy , Kistler Joshua , Rehm Sophia , Rentsch Katharina , Borgwardt Stefan , Cajochen Christian , Reichert Carolin
Published: May 2019

To enhance wakefulness, daily consumption of caffeine in the morning and afternoon is highly common. However, it is unknown whether such a regular intake pattern affects timing and quality of wakefulness, as regulated by an interplay of circadian and sleep-homeostatic mechanisms. Thus, we investigated the effects of daily caffeine intake and its withdrawal on circadian rhythms and wake-promotion in 20 male young habitual caffeine consumers. We applied a double-blind, within-subject design with a caffeine (150 mg, 3 x daily), a placebo, and a withdrawal condition each lasting ten days. Starting on day nine of treatment, salivary melatonin and cortisol, evening nap sleep, as well as sleepiness and vigilance performance throughout day and night were quantified during 43 h under controlled laboratory conditions. Neither the time course of melatonin (i.e., onset, amplitude, or area under the curve) nor the time course of cortisol were significantly affected by caffeine intake or its withdrawal. During withdrawal, however, volunteers reported increased sleepiness, showed more attentional lapses, as well as polysomnography-derived markers of elevated sleep propensity in the late evening compared to both, placebo and caffeine conditions. Thus, the typical timing of habitual caffeine intake in humans may not necessarily shift circadian phase nor lead to clear-cut benefits in alertness. The time-of-day independent effects of caffeine withdrawal suggest an adaptation to the substance, presumably in the homeostatic aspect of sleep-wake regulation.
Divergent paths to seizure-like events
Authors: Codadu Neela K. , Graham Robert , Burman Richard J. , Jackson-Taylor R. Thomas , Raimondo Joseph V. , Trevelyan Andrew. J. , Parrish R. Ryley
Published: May 2019

Aim

Much debate exists about how the brain transitions into an epileptic seizure. One source of confusion is that there are likely to be critical differences between experimental seizure models. To address this, we compared the evolving activity patterns in two, widely used, in vitro models of epileptic discharges.

Methods

We compared brain slices, prepared in the same way from young adult mice, that were bathed either in 0 Mg2+, or 100µM 4AP, artificial cerebrospinal fluid.

Results

We find that while local field potential recordings of epileptiform discharges in the two models appear broadly similar, patch-clamp analysis reveals an important difference in the relative degree of glutamatergic involvement. 4AP affects parvalbumin-expressing interneurons more than other cortical populations, destabilizing their resting state and inducing spontaneous bursting behavior. Consequently, the most prominent pattern of transient discharge (“interictal event”) in this model is almost purely GABAergic, although the transition to seizure-like events (SLEs) involves pyramidal recruitment. In contrast, interictal discharges in 0 Mg2+ are only maintained by a very large glutamatergic component that also involves transient discharges of the interneurons. Seizure-like events in 0 Mg2+ have significantly higher power in the high gamma frequency band (60-120Hz) than these events do in 4AP, and are greatly delayed in onset by diazepam, unlike 4AP events.

Conclusions

The 0 Mg2+ and 4AP models display fundamentally different levels of glutamatergic drive, demonstrating how ostensibly similar pathological discharges can arise from different sources. We contend that similar interpretative issues will also be relevant to clinical practice.
Regulation of theErythrobacter litoralisDSM 8509 general stress response by visible light
Authors: Fiebig Aretha , Varesio Lydia M. , Navarreto Xiomarie Alejandro , Crosson Sean
Published: May 2019

Extracytoplasmic function (ECF) sigma factors are a major class of environmentally-responsive transcriptional regulators. InAlphaproteobacteriathe ECF sigma factor, σEcfG, activates general stress response (GSR) transcription and protects cells from multiple stressors. A phosphorylation-dependent protein partner switching mechanism, involving HWE/HisKA_2-family histidine kinases, underlies σEcfGactivation. The identity of these sensor kinases and the signals that regulate them remain largely uncharacterized. We have developed the aerobic anoxygenic photoheterotrophic (AAP) bacterium,Erythrobacter litoralisDSM 8509, as a comparative genetic model to investigate GSR regulation. Using this system, we sought to define the contribution of visible light and a photosensory HWE kinase, LovK, to GSR transcription. We identified three HWE kinases that collectively regulate GSR:gsrKandlovKare activators, whilegsrPis a repressor. GSR transcription is higher in the dark than light, and the opposing activities ofgsrKandgsrPare sufficient to achieve light-dependent differential transcription. In the absence ofgsrKandgsrP,lovKalone is sufficient to regulate GSR transcription in response to light. This regulation requires a photochemically active LOV domain in LovK. Our studies establish a role for visible light and HWE kinases in light-dependent regulation of GSR transcription inE. litoralis, an AAP species.

GRAPHICAL ABSTRACT

ABBREVIATED SUMMARY

General stress response (GSR) systems protect bacteria from a diverse range of physical and chemical stressors. We have developedErythrobacter litoralisas a new genetic model to study GSR inAlphaproteobacteriaand show that three HWE-family histidine kinases collectively regulate GSR transcription via σEcfG. Visible light is a GSR regulatory signal inE. litoralis, and LovK is a blue-light photosensor kinase that functions as a dark activated GSR regulator.
Creatine transporter knockout mice (Slc6a8) show increases in serotonin-related proteins and are resilient to learned helplessness
Authors: Abdulla Zuhair I. , Pennington Jordan L. , Gutierrez Arnold , Skelton Matthew R.
Published: May 2019

Approximately 20% of adults in the U.S. will experience an affective disorder during their life. While it is well established that serotonin (5-HT) is a crucial factor in mood, impaired cellular bioenergetics are also implicated. Creatine (Cr), through the Cr/Phospho-Cr (PCr) shuttle, maintains high ATP concentrations in the neuron. This system may be implicated in the etiology of affective disorders, as reduced Cr, PCr, and ATP are often seen in the brains of affected patients. To address this issue, Cr transporter (Crt) deficient male mice (Slc6a8−/y) and female mice heterozygous for Crt expression (Slc6a8+/−) were used to evaluate how a Cr deficient system would alter affective-like behaviors. Slc6a8−/y and Slc6a8+/− mice had more escapes and faster escape latencies in learned helplessness, indicating a potential resilience to behavioral despair. Elevated zero maze and tail-suspension test performance matched that of wildtype mice, however. Slc6a8−/y mice have increased 5-hydroxyindoleacetic acid content in the hippocampus and striatum and increased monoamine oxidase protein and tryptophan hydroxylase-2 protein content in the hippocampus, while serotonin levels are unchanged. This indicates an increase in 5-HT turnover. Our results indicate that Cr plays a complex role in affective disorders and 5-HT neurotransmission, warranting further investigation.
Simple rules govern the diversity of bacterial nicotianamine-like metallophores
Authors: Laffont Clémentine , Brutesco Catherine , Hajjar Christine , Cullia Gregorio , Fanelli Roberto , Ouerdane Laurent , Cavelier Florine , Arnoux Pascal
Published: May 2019

In metal-scarce environments, some pathogenic bacteria produce opine-type metallophores mainly to face the host’s nutritional immunity. This is the case of staphylopine, pseudopaline and yersinopine, identified inStaphylococcus aureus,Pseudomonas aeruginosaandYersinia pestisrespectively. These metallophores are synthesized by two (CntLM) or three enzymes (CntKLM), CntM catalyzing the last step of biosynthesis using diverse substrates (pyruvate or α-ketoglutarate), pathway intermediates (xNA or yNA) and cofactors (NADH or NADPH), depending on the species. Here, we explored substrate specificity of CntM by combining bioinformatics and structural analysis with chemical synthesis and enzymatic studies. We found that NAD(P)H selectivity was mainly due to the amino acid at position 33 (S. aureusnumbering) which ensures a preferential binding to NADPH when it is an arginine. Moreover, whereas CntM fromP. aeruginosapreferentially uses yNA over xNA, the staphylococcal enzyme is not stereospecific. Most importantly, selectivity towards α-ketoacids is largely governed by a single residue at position 150 of CntM (S. aureusnumbering): an aspartate at this position ensures selectivity towards pyruvate whereas an alanine leads to the consumption of both pyruvate and α-ketoglutarate. Modifying this residue inP. aeruginosaled to a complete reversal of selectivity. Thus, opine-type metallophore diversity is mainly mediated by the absence/presence of acntKgene encoding a histidine racemase, and the presence of an aspartate/alanine at position 150 of CntM. These two simple rules predict the production of a fourth metallophore byPaenibacillus mucilaginosus, which was confirmedin vitroand called bacillopaline.
BiocPkgTools: Toolkit for Mining the Bioconductor Package Ecosystem
Authors: Su Shian , Carey Vincent J. , Shepherd Lori , Ritchie Matthew , Morgan Martin T. , Davis Sean
Published: May 2019

Motivation

The Bioconductor project, a large collection of open source software for the comprehension of large-scale biological data, continues to grow with new packages added each week, motivating the development of software tools focused on exposing package metadata to developers and users. The resulting BiocPkgTools package facilitates access to extensive metadata in computable form covering the Bioconductor package ecosystem, facilitating downstream applications such as custom reporting, data and text mining of Bioconductor package text descriptions, graph analytics over package dependencies, and custom search approaches.

Results

The BiocPkgTools package has been incorporated into the Bioconductor project, installs using standard procedures, and runs on any system supporting R. It provides functions to load detailed package metadata, longitudinal package download statistics, package dependencies, and Bioconductor build reports, all in “tidy data” form. BiocPkgTools can convert from tidy data structures to graph structures, enabling graphbased analytics and visualization. An end-user-friendly graphical package explorer aids in task-centric package discovery. Full documentation and example use cases are included.

Availability

The BiocPkgTools software and complete documentation are available from Bioconductor (https://bioconductor.org/packages/BiocPkgTools).
Inferred microbial networks lack replicability: consequences for next-generation biomonitoring
Authors: Pauvert Charlie , Vallance Jessica , Delière Laurent , Bohan David A. , Buée Marc , Vacher Corinne
Published: May 2019

Plant-associated microbial interaction networks protect plants against disease. There is, therefore, a need to monitor in real time their responses to environmental changes to predict disease risk and adjust crop protection strategies. Next-Generation Biomonitoring (NGB) proposes to reconstruct automatically these networks from metabarcoding data, to complement ecological community properties commonly used for ecosystem health assessment. This study aimed to evaluate the benefits and shortcomings of community-level and network-level properties for biomonitoring. We specifically investigated whether microbial networks inferred from metabarcoding data show robust responses to agricultural practices, using the grapevine microbiota as a study system. Our results demonstrate a strong footprint of the agricultural practice on the metabarcoding data, when analyzed at the community level. The richness, diversity and evenness of fungal communities were significantly higher in organic than conventional plots. The cropping system also affected the composition of grapevine foliar fungal communities significantly. Contrary to our expectations, microbial networks were less sensitive to changes in agricultural practices than microbial communities, confirming that NGB should not only consider network-level properties but also community-level properties. Moreover, we found that microbial networks lacked replicability within a cropping system but that consensus networks, built from several network replicates, could generate relevant hypotheses of microbial interactions. As things stand, community-level properties appear to be a more reliable and statistically powerful monitoring option than network-level properties. Future developments, especially in network inference methods, are likely to challenge our findings and help to improve the monitoring of the ecosystem services provided by the plant microbiota.
Spatiotemporal limits of optogenetic manipulations in cortical circuits
Authors: Li Nuo , Chen Susu , Guo Zengcai V. , Chen Han , Huo Yan , Inagaki Hidehiko K. , Davis Courtney , Hansel David , Guo Caiying , Svoboda Karel
Published: May 2019

Neuronal inactivation is commonly used to assess the involvement of groups of neurons in specific brain functions. Optogenetic tools allow manipulations of genetically and spatially defined neuronal populations with excellent temporal resolution. However, the targeted neurons are coupled with other neural populations over multiple length scales. As a result, the effects of localized optogenetic manipulations are not limited to the targeted neurons, but produces spatially extended excitation and inhibition with rich dynamics. Here we benchmarked several optogenetic silencers in transgenic mice and with viral gene transduction, with the goal to inactivate excitatory neurons in small regions of neocortex. We analyzed the effects of the perturbations in vivo using electrophysiology. Channelrhodopsin activation of GABAergic neurons produced more effective photoinhibition of pyramidal neurons than direct photoinhibition using light-gated ion pumps. We made transgenic mice expressing the light-dependent chloride channel GtACR under the control of Cre-recombinase. Activation of GtACR produced the most potent photoinhibition. For all methods, localized photostimuli produced photoinhibition that extended substantially beyond the spread of light in tissue, although different methods had slightly different resolution limits (radius of inactivation, 0.5 mm to 1 mm). The spatial profile of photoinhibition was likely shaped by strong coupling between cortical neurons. Over some range of photostimulation, circuits produced the “paradoxical effect”, where excitation of inhibitory neurons reduced activity in these neurons, together with pyramidal neurons, a signature of inhibition-stabilized neural networks. The offset of optogenetic inactivation was followed by rebound excitation in a light dose-dependent manner, which can be mitigated by slowly varying photostimuli, but at the expense of time resolution. Our data offer guidance for the design of in vivo optogenetics experiments and suggest how these experiments can reveal operating principles of neural circuits.