bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug Susceptibility Profiling and Genetic Determinants of Drug Resistance in Mycobacterium kansasii
Authors: Bakuła Zofia , Modrzejewska Magdalena , Pennings Lian , Proboszcz Małgorzata , Safianowska Aleksandra , Bielecki Jacek , van Ingen Jakko , Jagielski Tomasz 
Published: February 2018

ABSTRACT

Very few studies have examined drug susceptibility of
Mycobacterium kansasii
, and they involve a limited number of strains. The purpose of this study was to determine drug susceptibility profiles of
M. kansasii
isolates representing a spectrum of species genotypes (subtypes) with two different methodologies, i.e., broth microdilution and Etest assays. To confirm drug resistance, drug target genes were sequenced. A collection of 85
M. kansasii
isolates, including representatives of eight different subtypes (I to VI, I/II, and IIB) from eight countries, was used. Drug susceptibility against 13 and 8 antimycobacterial agents was tested by using broth microdilution and Etest, respectively. For drug-resistant or high-MIC isolates, eight structural genes (
rrl
,
katG
,
inhA
,
embB
,
rrs
,
rpsL
,
gyrA
, and
gyrB
) and one regulatory region (
embCA
) were PCR amplified and sequenced in the search for resistance-associated mutations. All isolates tested were susceptible to rifampin (RIF), amikacin (AMK), co-trimoxazole (SXT), rifabutin (RFB), moxifloxacin (MXF), and linezolid (LZD) according to the microdilution method. Resistance to ethambutol (EMB), ciprofloxacin (CIP), and clarithromycin (CLR) was found in 83 (97.7%), 17 (20%), and 1 (1.2%) isolate, respectively. The calculated concordance between the Etest and dilution method was 22.6% for AMK, 4.8% for streptomycin (STR), 3.2% for CLR, and 1.6% for RIF. For EMB, INH, and SXT, not even a single MIC value determined by one method equaled that by the second method. The only mutations disclosed were A2266C transversion at the
rrl
gene (CLR-resistant strain) and A128G transition at the
rpsL
gene (strain with STR MIC of >64 mg/liter). In conclusion, eight drugs, including RIF, CLR, AMK, SXT, RFB, MXF, LZD, and ethionamide (ETO), showed high
in vitro
activity against
M. kansasii
isolates. Discrepancies of the results between the reference microdilution method and Etest preclude the use of the latter for drug susceptibility determination in
M. kansasii
. Drug resistance in
M. kansasii
may have different genetic determinants than resistance to the same drugs in
M. tuberculosis
.
High Genetic Plasticity in Multidrug-Resistant Sequence Type 3-IncHI2 Plasmids Revealed by Sequence Comparison and Phylogenetic Analysis
Authors: Fang Liang-Xing , Li Xing-Ping , Deng Guo-Hui , Li Shu-Min , Yang Run-Shi , Wu Zuo-Wei , Liao Xiao-Ping , Sun Jian , Liu Ya-Hong 
Published: February 2018

ABSTRACT

We report a novel fusion plasmid, pP2-3T, cointegrating sequence type 3 (ST3)-IncHI2 with an IncFII plasmid backbone mediating multidrug resistance (MDR) and virulence. Phylogenetic analysis and comparative genomics revealed that pP2-3T and other MDR ST3-IncHI2 plasmids clustered together, representing a unique IncHI2 lineage that exhibited high conservation in backbones of plasmids but possessed highly genetic plasticity in various regions by acquiring numerous antibiotic resistance genes and fusing with other plasmids. Surveillance studies should be performed to monitor multiresistance IncHI2 plasmids among
Enterobacteriaceae
.
Establishment and Validation of Galleria mellonella as a Novel Model Organism To Study Mycobacterium abscessus Infection, Pathogenesis, and Treatment
Authors: Meir Michal , Grosfeld Tatyana , Barkan Daniel 
Published: February 2018

ABSTRACT

Treatment of
Mycobacterium abscessus
infections is extremely challenging due to its intrinsic resistance to most antibiotics, and research of pathogenesis is limited due to a lack of a practical
in vivo
model of infection. The objective of this study was to establish a simple
in vivo
model for
M. abscessus
infection, virulence, and drug testing in
Galleria mellonella
larvae. We inoculated larvae with
M. abscessus
bacteria and assessed histopathology, CFU count, and mortality with and without antibiotic treatment. We also constructed a luminescent, recombinant
M. abscessus
mutant, mDB158, and imaged infected larvae using the IVIS
in vivo
imaging system.
M. abscessus
proliferated and induced granuloma-like responses in infected larvae, leading to larval mortality. The
G. mellonella
model was further validated successfully by demonstration of the expected favorable antimicrobial effect of treatment with meropenem and the superiority of combination treatment (meropenem and tigecycline) over that with single agents. We then used IVIS imaging of larvae infected with luminescent
M. abscessus
, allowing live real-time assessment of bacterial load. We used this method to compare the antimicrobial effects of various antibiotics (meropenem, amikacin, linezolid, levofloxacin, etc.) on bacterial proliferation and larval survival. Meropenem and amikacin had the most favorable effects, correlating well with common clinical practice guidelines. These findings suggest
G. mellonella
to be an excellent
in vivo
model for research of
M. abscessus
infection, pathogenesis, and treatment. Luminescent
M. abscessus
and IVIS imaging further facilitates this model. Results obtained in this model clearly substantiated common clinical practice, thus validating the model as a predictor of treatment efficacy and outcome.
Comparative Genomics Shows That Mycobacterium ulcerans Migration and Expansion Preceded the Rise of Buruli Ulcer in Southeastern Australia
Authors: Buultjens Andrew H. , Vandelannoote Koen , Meehan Conor J. , Eddyani Miriam , de Jong Bouke C. , Fyfe Janet A. M. , Globan Maria , Tobias Nicholas J. , Porter Jessica L. , Tomita Takehiro , Tay Ee Laine , Seemann Torsten , Howden Benjamin P. , Johnson Paul D. R. , Stinear Timothy P. 
Published: February 2018

ABSTRACT

Since 2000, cases of the neglected tropical disease Buruli ulcer, caused by infection with
Mycobacterium ulcerans
, have increased 100-fold around Melbourne (population 4.4 million), the capital of Victoria, in temperate southeastern Australia. The reasons for this increase are unclear. Here, we used whole-genome sequence comparisons of 178
M. ulcerans
isolates obtained primarily from human clinical specimens, spanning 70 years, to model the population dynamics of this pathogen from this region. Using phylogeographic and advanced Bayesian phylogenetic approaches, we found that there has been a migration of the pathogen from the east end of the state, beginning in the 1980s, 300 km west to the major human population center around Melbourne. This move was then followed by a significant increase in
M. ulcerans
population size. These analyses inform our thinking around Buruli ulcer transmission and control, indicating that
M. ulcerans
is introduced to a new environment and then expands, rather than it being from the awakening of a quiescent pathogen reservoir.

IMPORTANCE
Buruli ulcer is a destructive skin and soft tissue infection caused by
Mycobacterium ulcerans
and is characterized by progressive skin ulceration, which can lead to permanent disfigurement and long-term disability. Despite the majority of disease burden occurring in regions of West and central Africa, Buruli ulcer is also becoming increasingly common in southeastern Australia. Major impediments to controlling disease spread are incomplete understandings of the environmental reservoirs and modes of transmission of
M. ulcerans
. The significance of our research is that we used genomics to assess the population structure of this pathogen at the Australian continental scale. We have then reconstructed a historical bacterial spread and modeled demographic dynamics to reveal bacterial population expansion across southeastern Australia. These findings provide explanations for the observed epidemiological trends with Buruli ulcer and suggest possible management to control disease spread.
Neutrophils from Both Susceptible and Resistant Mice Efficiently Kill Opsonized Listeria monocytogenes
Authors: Pitts Michelle G. , Combs Travis A. , D'Orazio Sarah E. F. 
Published: February 2018

ABSTRACTInbred mouse strains differ in their susceptibility to infection with the facultative intracellular bacteriumListeria monocytogenes, largely due to delayed or deficient innate immune responses. Previous antibody depletion studies suggested that neutrophils (polymorphonuclear leukocytes [PMN]) were particularly important for clearance in the liver, but the ability of PMN from susceptible and resistant mice to directly killL. monocytogeneshas not been examined. In this study, we showed that PMN infiltrated the livers of BALB/c/By/J (BALB/c) and C57BL/6 (B6) mice in similar numbers and that both cell types readily migrated toward leukotriene B4 in anin vitrochemotaxis assay. However, CFU burdens in the liver were significantly higher in BALB/c mice than in other strains, suggesting that PMN in the BALB/c liver might not be able to clearL. monocytogenesas efficiently as B6 PMN. Unprimed PMN harvested from either BALB/c or B6 bone marrow killedL. monocytogenesdirectlyex vivo, and pretreatment with autologous serum significantly enhanced killing efficiency for both.L. monocytogeneswere internalized within 10 min and rapidly triggered intracellular production of reactive oxygen species in a dose-dependent manner. However, PMN from gp91phox-deficient mice also readily killedL. monocytogenes, which suggested that nonoxidative killing mechanisms may be sufficient for bacterial clearance. Together, these results indicate that there is not an intrinsic defect in the ability of PMN from susceptible BALB/c mice to killL. monocytogenesand further suggest that if PMN function is impaired in BALB/c mice, it is likely due to locally produced modulating factors present in the liver during infection.
Dysbiosis of Inferior Turbinate Microbiota Is Associated with High Total IgE Levels in Patients with Allergic Rhinitis
Authors: Hyun Dong-Wook , Min Hyun Jin , Kim Min-Soo , Whon Tae Woong , Shin Na-Ri , Kim Pil Soo , Kim Hyun Sik , Lee June Young , Kang Woorim , Choi Augustine M. K. , Yoon Joo-Heon , Bae Jin-Woo 
Published: February 2018

ABSTRACT

Abnormalities in the human microbiota are associated with the etiology of allergic diseases. Although disease site-specific microbiota may be associated with disease pathophysiology, the role of the nasal microbiota is unclear. We sought to characterize the microbiota of the site of allergic rhinitis, the inferior turbinate, in subjects with allergic rhinitis (
n
= 20) and healthy controls (
n
= 12) and to examine the relationship of mucosal microbiota with disease occurrence, sensitized allergen number, and allergen-specific and total IgE levels. Microbial dysbiosis correlated significantly with total IgE levels representing combined allergic responses but not with disease occurrence, the number of sensitized allergens, or house dust mite allergen-specific IgE levels. Compared to the populations in individuals with low total IgE levels (group IgE
low
), low microbial biodiversity with a high relative abundance of
Firmicutes
phylum (
Staphylococcus aureus
) and a low relative abundance of
Actinobacteria
phylum (
Propionibacterium acnes
) was observed in individuals with high total serum IgE levels (group IgE
high
). Phylogeny-based microbial functional potential predicted by the 16S rRNA gene indicated an increase in signal transduction-related genes and a decrease in energy metabolism-related genes in group IgE
high
as shown in the microbial features with atopic and/or inflammatory diseases. Thus, dysbiosis of the inferior turbinate mucosa microbiota, particularly an increase in
S. aureus
and a decrease in
P. acnes
, is linked to high total IgE levels in allergic rhinitis, suggesting that inferior turbinate microbiota may be affected by accumulated allergic responses against sensitized allergens and that site-specific microbial alterations play a potential role in disease pathophysiology.
Persistent Pandemic Lineages of Uropathogenic Escherichia coli in a College Community from 1999 to 2017
Authors: Yamaji Reina , Rubin Julia , Thys Erika , Friedman Cindy R. , Riley Lee W. 
Published: February 2018

ABSTRACT

The incidence of drug-resistant community-acquired urinary tract infections (CA-UTI) continues to increase worldwide. In 1999 to 2000, a single lineage of uropathogenic
Escherichia coli
(UPEC) sequence type 69 (ST69) caused 51% of trimethoprim-sulfamethoxazole-resistant UTI in a Northern California university community. We compared the clonal distributions of UPEC and its impact on antimicrobial resistance prevalence in the same community during two periods separated by 17 years. We analyzed
E. coli
isolates from urine samples from patients with symptoms of UTI who visited a health service between September 2016 and May 2017 and compared them to UPEC isolates collected similarly between October 1999 and March 2000. Isolates were tested for antimicrobial drug susceptibility and genotyped by multilocus sequence typing. In 1999 to 2000, strains belonging to ST95, ST127, ST73, ST69, ST131, and ST10 caused 125 (56%) of 225 UTI cases, while the same STs caused 148 (64%) of 233 UTI cases in 2016 to 2017. The frequencies of ampicillin resistance and ciprofloxacin resistance rose from 24.4% to 41.6% (
P
< 0.001) and from 0.9% to 5.1% (
P
< 0.003), respectively. The six STs accounted for 78.6% and 72.7% of these increases, respectively. Prevalence of drug-resistant UTI in this community appears to be largely influenced by a small set of dominant UPEC STs circulating in the same community 17 years apart. Further research to determine the origin and reasons for persistence of these dominant genotypes is necessary to combat antimicrobial-resistant CA-UTI.
The epidemiology of childhood blindness and severe visual impairment in Indonesia
Authors: Muhit Mohammad , Karim Tasneem , Islam Johurul , Hardianto Denny , Muhiddin Habibah Setyawati , Purwanta Setia A , Suhardjo Suhardjo , Widyandana Doni , Khandaker Gulam 
Published: February 2018

BackgroundThe magnitude of blindness among children in Indonesia is unknown. In this study, we aimed to define the magnitude and aetiology of childhood blindness in two parts of Indonesia.MethodChildren aged 0–15 years, identified through key informant method and from special schools and community-based rehabilitation programme in Sumba and Yogyakarta, were assessed following WHO protocol and definitions for ophthalmological assessment and classification of visual impairment and blindness among children.ResultsOut of 195 children assessed, 113 had blindness/severe visual impairment (BL/SVI), 48 had visual impairment (VI) and 34 had no VI. 43.4% children with BL/SVI were female.The main anatomical site of BL/SVI was lens (n=35, 31.0%), followed by retina (n=13, 11.5%) and cornea (n=9, 8.0%). Among the known aetiologies, childhood factors predominated (n=14, 12.4%), followed by hereditary diseases (n=12, 10.6%) where parental consanguinity was found among 33.3% (n=4) of them. Overall, 77.8% (n=88) had avoidable causes of BL/SVI: 69.0% (n=78) treatable and 8.8% (n=10) preventable causes.The estimated prevalence of BL/SVI was 0.25 (95% CI 0.19 to 0.32) and 0.23 (95% CI 0.18 to 0.29) per 1000 children in Sumba and Yogyakarta, respectively. The estimated prevalence of cataract was 0.07 per 1000 children (95% CI 0.04 to 0.12) in Sumba and 0.05 per 1000 children (95% CI 0.03 to 0.09) in Yogyakarta. Based on our conservative estimates, there are 17 241 children with BL/SVI in Indonesia; 4270 are blind due to cataract.ConclusionThe magnitude of childhood BL/SVI in Sumba and Yogyakarta is high. Our study suggests that a large proportion of childhood BL/SVI in Indonesia is avoidable.
Search for PeVatrons at the Galactic Center using a radio air-shower array at the South Pole
Authors: Balagopal V. A. , Haungs A. , Huege T. , Schröder F. G. 
Published: February 2018

AbstractThe South Pole, which hosts the IceCube Neutrino Observatory, has a complete and around-the-clock exposure to the Galactic Center. Hence, it is an ideal location to search for gamma rays of PeV energy coming from the Galactic Center. However, it is hard to detect air showers initiated by these gamma rays using cosmic-ray particle detectors due to the low elevation of the Galactic Center. The use of antennas to measure the radio footprint of these air showers will help in this case, and would allow for a 24/7 operation time. So far, only air showers with energies well above $$10^{16}$$

10
16

eV have been detected with the radio technique. Thus, the energy threshold has to be lowered for the detection of gamma-ray showers of PeV energy. This can be achieved by optimizing the frequency band in order to obtain a higher level of signal-to-noise ratio. With such an approach, PeV gamma-ray showers with high inclination can be measured at the South Pole.
Updated checklist and distribution of the diaptomid copepods (Copepoda, Calanoida, Diaptomidae) of China
Authors: Li Huiming , Dumont Henri J. , Han Bo-Ping , Lin Qiuqi 
Published: February 2018

We present an updated checklist of the Diaptomidae of China, based on a literature review and on original field data from all over China during 2012-2016. A total of 19 genera and 56 species have been recorded.Neutrodiaptomushas the highest species richness (10 species), followed byArctodiaptomus(9 species). Only one species each ofEudiaptomus,Mixodiaptomus,Eodiaptomus,Dentodiaptomus,Dolodiaptomus,Allodiaptomus,Karstodiaptomus,MetadiaptomusandParadiaptomuswas found. The taxonomic status of 16 species was revised: one wrongly attributed genus,Argyrodiaptomus, was corrected toSinodiaptomus. First records for China includeArctodiaptomus parvispineusand one new cave-dwelling genus,Karstodiaptomus, is added. One Latin name from Shen & Sung’s book (1979) is corrected. Remarks on nomenclature and taxonomic issues are supplemented with information on the geographical distribution of the various species within China.
Behind the Mask: Hybrid Identity Work of Indian Women Managers in Corporate South Africa
Authors: Carrim Nasima M. H. 
Published: February 2018

Abstract
There is a dearth of research on how women managers engage in hybrid identity work during their career transitions, and the aim of this study was to fill this gap. Interviews were conducted with 13 Indian women managers in senior and top managerial positions, and the data obtained were analysed using thematic analysis. The narratives indicate that previously disadvantaged groups (Indian women in this case) are caught between subscribing to cultural values and concurrently conforming to organisational norms. Participants’ answers to the question: “Who am I as an Indian female manager?” reveal that during their career ascendency these women engage in a tremendous amount of hybrid identity work and rework related to their self-concept of being an “ideal” Indian female and simultaneously being a “perfect” manager. Nevertheless, in their career transitions to managerial positions, these women are selective in the hybrid identity work they engage in.
Slavery in Third-Millennium Mesopotamia
Authors: Verderame Lorenzo 
Published: February 2018

Abstract
Third-millennium Mesopotamia has provided an impressive quantity of sources for the study of ancient slavery, among them a collection of standards (the so-called Laws of Ur-Namma). Despite the volume of documents, Mesopotamian slavery remains elusive in its general traits. This is partly due to the nature of the sources, but also to the approaches and interpretations of modern scholars. Slavery in ancient Mesopotamia has been the focus of several studies in the 1960s and 1970s that interpreted the sources using comparative approaches and Marxist analyses. Since then, the topic has seldom been revisited. In this article, I present the status quaestionis with an overview of the available sources and related studies, together with a sketch of the different types of bonded and forced labor in the Neo-Sumerian period (21st cent. BCE).
A Grid-Refinement-Based Approach for Modeling the Convective Boundary Layer in the Gray Zone: Algorithm Implementation and Testing
Authors: Zhou Bowen , Xue Ming , Zhu Kefeng 
Published: February 2018

Abstract
A grid-refinement-based method is implemented in a community atmospheric model to improve the representation of convective boundary layer (CBL) turbulence on gray-zone [i.e., ~O(1) km] grids. At this resolution, CBL convection is partially resolved and partially subgrid scale (SGS), such that neither traditional mesoscale planetary boundary layer (PBL) schemes nor SGS closures for large-eddy simulations (LESs) are appropriate. The proposed method utilizes two-way interactive nesting to refine the horizontal resolution of the unstable surface layer of the daytime CBL. SGS turbulent mixing in the fine nest and coarse parent grids are parameterized by an LES turbulence closure and a PBL scheme, respectively. The method does not rely on predetermined empirical functions to introduce grid (scale) dependency and in theory works with any PBL scheme. Compared to the stand-alone gray-zone simulation, the proposed approach shows improvements in terms of higher-order statistics, the timing of the onset of resolved convection, and the convective structures. A deficiency of the method exists when the nest domain is limited to the surface layer; the convective structures become gradually contaminated by spurious convection on the parent gray-zone grid. A deeper nest domain alleviates the issue at increased computational costs.
Risk Factors for Intraoperative and Postoperative Cerebrospinal Fluid Leaks in Endoscopic Transsphenoidal Sellar Surgery
Authors: Patel Priyesh N. , Stafford Alicia M. , Patrinely James R. , Smith Derek K. , Turner Justin H. , Russell Paul T. , Weaver Kyle D. , Chambless Lola B. , Chandra Rakesh K. 
Published: February 2018

ObjectiveTo determine the factors associated with intra‐ and postoperative cerebrospinal fluid (CSF) leaks in setting of endoscopic transsphenoidal sellar surgery.Study DesignRetrospective cohort.SettingTertiary referral center.Subjects and MethodsThis study included 806 patients who underwent endoscopic transsphenoidal sellar surgery between 2004 and 2016. The associations between CSF leaks (intra‐ and postoperative) and patient demographics, medical history, tumor characteristics, and intraoperative repair techniques were analyzed.ResultsIn sum, 205 (25.4%) patients had a CSF leak: 188 (23.3%) intraoperative leaks and 38 (4.7%) postoperative leaks. Twenty‐one (2.6%) patients had postoperative leaks after having repair of an intraoperative leak; 55% of patients with a postoperative leak had an intraoperative leak repaired. On multivariate analysis, body mass index (BMI), hydrocephalus, suprasellar extension, and craniopharyngioma significantly predicted intraoperative CSF leaks, while only BMI and hydrocephalus predicted postoperative CSF leaks. Patients having septal flap repairs of CSF leaks had a higher postoperative leak rate relative to other repair techniques (odds ratio, 6.37; P =. 013). Rigid reconstruction did not correlate with leaks.ConclusionFor this large cohort of patients undergoing endoscopic transsphenoidal sellar surgery, BMI and hydrocephalus were identified as predictors of postoperative CSF leaks, including those occurring after repair of intraoperative leak. These variables may put stress on the surgical repair of sellar defects, and consideration of these risk factors may help counsel patients and guide perioperative decision making in regard to repair strategies and CSF diversion techniques.