bluuebunny/crossref_metadata_2025 huggingface dataset:
The environmental stress sensitivities of pathogenic Candida species, including Candida auris, and implications for their spread in the hospital setting
Authors: Heaney Helen , Laing Juliette , Paterson Linda , Walker Alan W , Gow Neil A R , Johnson Elizabeth M , MacCallum Donna M , Brown Alistair J P
Published: December 2019

Candida auris is an emerging pathogenic yeast of significant clinical concern because of its frequent intrinsic resistance to fluconazole and often other antifungal drugs and the high mortality rates associated with systemic infections. Furthermore, C. auris has a propensity for persistence and transmission in health care environments. The reasons for this efficient transmission are not well understood, and therefore we tested whether enhanced resistance to environmental stresses might contribute to the ability of C. auris to spread in health care environments. We compared C. auris to other pathogenic Candida species with respect to their resistance to individual stresses and combinations of stresses. Stress resistance was examined using in vitro assays on laboratory media and also on hospital linen. In general, the 17 C. auris isolates examined displayed similar degrees of resistance to oxidative, nitrosative, cationic and cell wall stresses as clinical isolates of C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. krusei, C. guilliermondii, C. lusitaniae and C. kefyr. All of the C. auris isolates examined were more sensitive to low pH (pH 2, but not pH 4) compared to C. albicans, but were more resistant to high pH (pH 13). C. auris was also sensitive to low pH, when tested on contaminated hospital linen. Most C. auris isolates were relatively thermotolerant, displaying significant growth at 47°C. Furthermore, C. auris was relatively resistant to certain combinations of combinatorial stress (e.g., pH 13 plus 47°C). Significantly, C. auris was sensitive to the stress combinations imposed by hospital laundering protocol (pH > 12 plus heat shock at >80°C), suggesting that current laundering procedures are sufficient to limit the transmission of this fungal pathogen via hospital linen.
The impact of (n,γ) reaction rate uncertainties on the predicted abundances of i-process elements with 32 ≤ Z ≤ 48 in the metal-poor star HD94028
Authors: McKay John E , Denissenkov Pavel A , Herwig Falk , Perdikakis Georgios , Schatz Hendrik
Published: December 2019

Several anomalous elemental abundance ratios have been observed in the metal-poor star HD94028. We assume that its high [As/Ge] ratio is a product of a weak intermediate (i) neutron-capture process. Given that observational errors are usually smaller than predicted nuclear physics uncertainties, we have first set-up a benchmark one-zone i-process nucleosynthesis simulation results of which provide the best fit to the observed abundances. We have then performed Monte Carlo simulations in which 113 relevant (n,γ) reaction rates of unstable species were randomly varied within Hauser–Feshbach model uncertainty ranges for each reaction to estimate the impact on the predicted stellar abundances. One of the interesting results of these simulations is a double-peaked distribution of the As abundance, which is caused by the variation of the 75Ga (n,γ) cross-section. This variation strongly anticorrelates with the predicted As abundance, confirming the necessity for improved theoretical or experimental bounds on this cross-section. The 66Ni (n,γ) reaction is found to behave as a major bottleneck for the i-process nucleosynthesis. Our analysis finds the Pearson product–moment correlation coefficient rP > 0.2 for all of the i-process elements with 32 ≤ Z ≤ 42, with significant changes in their predicted abundances showing up when the rate of this reaction is reduced to its theoretically constrained lower bound. Our results are applicable to any other stellar nucleosynthesis site with the similar i-process conditions, such as Sakurai’s object (V4334 Sagittarii) or rapidly accreting white dwarfs.
Fundamental physics with blazar spectra: a critical appraisal
Authors: Galanti Giorgio , Tavecchio Fabrizio , Landoni Marco
Published: December 2019

Very-high-energy (VHE) BL Lacertae (BL Lac) spectra extending above $10 \, \rm TeV$ provide a unique opportunity for testing physics beyond the standard model of elementary particle and alternative blazar emission models. We consider the hadron beam scenario, the conversion of photons to axion-like particles (ALPs) and the Lorentz invariance violation (LIV) by analysing their consequences and induced modifications to BL Lac spectra. In particular, we consider how different processes can provide similar spectral features (e.g. hard tails) and we discuss the ways they can be disentangled. We use data from High-Energy Gamma-Ray Astronomy (HEGRA) of a high state of Markarian 501 and the High-Energy Stereoscopic System (H.E.S.S.) spectrum of the extreme BL Lac (EHBL) 1ES 0229+200. In addition, we consider two hypothetical EHBLs similar to 1ES 0229+200 located at redshifts z = 0.3 and z = 0.5. We observe that both the hadron beam and the photon–ALP oscillations predict a hard tail extending to energies larger than those possible in the standard scenario. Photon–ALP interaction predicts a peak in the spectra of distant BL Lacs at about $20\rm {-}30 \, \rm TeV$, while LIV produces a strong peak in all BL Lac spectra around $\sim 100 \, \rm TeV$. The peculiar feature of the photon–ALP conversion model is the production of oscillations in the spectral energy distribution, so that its detection/absence can be exploited to distinguish between the considered models. The above-mentioned features of the three models might be detected by the upcoming Cherenkov Telescope Array. Thus, future observations of BL Lac spectra could eventually shed light on new physics and alternative blazar emission models, driving fundamental research towards a specific direction.
Baryons in the Cosmic Web of IllustrisTNG – II. The connection among galaxies, haloes, their formation time, and their location in the Cosmic Web
Authors: Martizzi Davide , Vogelsberger Mark , Torrey Paul , Pillepich Annalisa , Hansen Steen H , Marinacci Federico , Hernquist Lars
Published: December 2019

The connections among galaxies, the dark matter haloes where they form and the properties of the large-scale Cosmic Web still need to be completely disentangled. We use the cosmological hydrodynamical simulation TNG100 of the IllustrisTNG suite to quantify the effects played by the large-scale density field and the Cosmic Web morphology on the relation between halo mass and galaxy stellar mass. We select objects with total dynamical mass in the range ${\ge}6.3\times 10^{10} \,h ^{-1}\, \mathrm{ M}_{\odot }$ up to a few $10^{14}\, h^{-1} \, \mathrm{ M}_{\odot }$ between redshift z = 4 and redshift z = 0. A Cosmic Web class (knot, filament, sheet, void) is assigned to each region of the volume using a density field deformation tensor-based method. We find that galaxy stellar mass strongly correlates with total dynamical mass and formation time, and more weakly with large-scale overdensity and Cosmic Web class. The latter two quantities correlate with each other, but are not entirely degenerate. Furthermore, we find that at fixed halo mass, galaxies with stellar mass lower than the median value are more likely to be found in voids and sheets, whereas galaxies with stellar mass higher than the median are more likely to be found in filaments and knots. Finally, we find that the dependence on environment is stronger for satellites than for centrals, and discuss the physical implications of these results.
Self-induced dust traps around snow lines in protoplanetary discs
Authors: Vericel Arnaud , Gonzalez Jean-François
Published: December 2019

Dust particles need to grow efficiently from micrometre sizes to thousands of kilometres to form planets. With the growth of millimetre to metre sizes being hindered by a number of barriers, the recent discovery that dust evolution is able to create ‘self-induced’ dust traps shows promises. The condensation and sublimation of volatile species at certain locations, called snow lines, are also thought to be important parts of planet formation scenarios. Given that dust sticking properties change across a snow line, this raises the question: how do snow lines affect the self-induced dust trap formation mechanism? The question is particularly relevant with the multiple observations of the carbon monoxide (CO) snow line in protoplanetary discs, since its effect on dust growth and dynamics is yet to be understood. In this paper, we present the effects of snow lines in general on the formation of self-induced dust traps in a parameter study, and then focus on the CO snow line. We find that for a range of parameters, a dust trap forms at the snow line where the dust accumulates and slowly grows, as found for the water snow line in a previous work. We also find that, depending on the grains’ sticking properties on either side of the CO snow line, it could be either a starting or braking point for dust growth and drift. This could provide clues to understand the link between dust distributions and snow lines in protoplanetary disc observations.
Expression quantitative trait loci in ABC transporters are associated with survival in 5-FU treated colorectal cancer patients
Authors: Vymetalkova Veronika , Rosa Fabio , Susova Simona , Bendova Petra , Levy Miroslav , Buchler Tomas , Kral Jan , Bartu Linda , Vodickova Ludmila , Hughes David J , Soucek Pavel , Naccarati Alessio , Kumar Rajiv , Vodicka Pavel , Pardini Barbara
Published: December 2019

The chemotherapeutic efficacy in colorectal cancer (CRC) is limited due to the inter-individual variability in drug response and the development of tumour resistance. ATP-binding cassette (ABC) transporters are crucial in the development of resistance by the efflux of anticancer agents from cancer cells. In this study, we identified 14 single nucleotide polymorphisms (SNPs) in 11 ABC transporter genes acting as an expression of quantitative trait loci (eQTLs), i.e. whose variation influence the expression of many downstream genes. These SNPs were genotyped in a case–control study comprising 1098 cases and 1442 healthy controls and analysed in relation to CRC development risk and patient survival. Considering a strict correction for multiple tests, we did not observe any significant association between SNPs and CRC risk. The rs3819720 polymorphism in the ABCB3/TAP2 gene was statistically significantly associated with shorter overall survival (OS) in the codominant, and dominant models [GA vs. GG, hazard ratio (HR) = 1.48; P = 0.002; AA vs. GG, HR = 1.70; P = 0.004 and GA + AA vs. GG, HR = 1.52; P = 0.0006]. Additionally, GA carriers of the same SNP displayed worse OS after receiving 5-FU based chemotherapy. The variant allele of rs3819720 polymorphism statistically significantly affected the expression of 36 downstream genes. Screening for eQTL polymorphisms in relevant genes such as ABC transporters that can regulate the expression of several other genes may help to identify the genetic background involved in the individual response to the treatment of CRC patients.
New perspectives in cancer biology from a study of canonical and non-canonical functions of base excision repair proteins with a focus on early steps
Authors: Malfatti Matilde Clarissa , Antoniali Giulia , Codrich Marta , Burra Silvia , Mangiapane Giovanna , Dalla Emiliano , Tell Gianluca
Published: December 2019

Alterations of DNA repair enzymes and consequential triggering of aberrant DNA damage response (DDR) pathways are thought to play a pivotal role in genomic instabilities associated with cancer development, and are further thought to be important predictive biomarkers for therapy using the synthetic lethality paradigm. However, novel unpredicted perspectives are emerging from the identification of several non-canonical roles of DNA repair enzymes, particularly in gene expression regulation, by different molecular mechanisms, such as (i) non-coding RNA regulation of tumour suppressors, (ii) epigenetic and transcriptional regulation of genes involved in genotoxic responses and (iii) paracrine effects of secreted DNA repair enzymes triggering the cell senescence phenotype. The base excision repair (BER) pathway, canonically involved in the repair of non-distorting DNA lesions generated by oxidative stress, ionising radiation, alkylation damage and spontaneous or enzymatic deamination of nucleotide bases, represents a paradigm for the multifaceted roles of complex DDR in human cells. This review will focus on what is known about the canonical and non-canonical functions of BER enzymes related to cancer development, highlighting novel opportunities to understand the biology of cancer and representing future perspectives for designing new anticancer strategies. We will specifically focus on APE1 as an example of a pleiotropic and multifunctional BER protein.
A nucleobase-binding pocket in a viral RNA-dependent RNA polymerase contributes to elongation complex stability
Authors: Shi Wei , Ye Han-Qing , Deng Cheng-Lin , Li Rui , Zhang Bo , Gong Peng
Published: December 2019

The enterovirus 71 (EV71) 3Dpol is an RNA-dependent RNA polymerase (RdRP) that plays the central role in the viral genome replication, and is an important target in antiviral studies. Here, we report a crystal structure of EV71 3Dpol elongation complex (EC) at 1.8 Å resolution. The structure reveals that the 5′-end guanosine of the downstream RNA template interacts with a fingers domain pocket, with the base sandwiched by H44 and R277 side chains through hydrophobic stacking interactions, and these interactions are still maintained after one in-crystal translocation event induced by nucleotide incorporation, implying that the pocket could regulate the functional properties of the polymerase by interacting with RNA. When mutated, residue R277 showed an impact on virus proliferation in virological studies with residue H44 having a synergistic effect. In vitro biochemical data further suggest that mutations at these two sites affect RNA binding, EC stability, but not polymerase catalytic rate (kcat) and apparent NTP affinity (KM,NTP). We propose that, although rarely captured by crystallography, similar surface pocket interaction with nucleobase may commonly exist in nucleic acid motor enzymes to facilitate their processivity. Potential applications in antiviral drug and vaccine development are also discussed.
Identification of α-Tomatine 23-Hydroxylase Involved in the Detoxification of a Bitter Glycoalkaloid
Authors: Nakayasu Masaru , Akiyama Ryota , Kobayashi Midori , Lee Hyoung Jae , Kawasaki Takashi , Watanabe Bunta , Urakawa Shingo , Kato Junpei , Sugimoto Yukihiro , Iijima Yoko , Saito Kazuki , Muranaka Toshiya , Umemoto Naoyuki , Mizutani Masaharu
Published: December 2019

Tomato plants (Solanum lycopersicum) contain steroidal glycoalkaloid α-tomatine, which functions as a chemical barrier to pathogens and predators. α-Tomatine accumulates in all tissues and at particularly high levels in leaves and immature green fruits. The compound is toxic and causes a bitter taste, but its presence decreases through metabolic conversion to nontoxic esculeoside A during fruit ripening. This study identifies the gene encoding a 23-hydroxylase of α-tomatine, which is a key to this process. Some 2-oxoglutarate-dependent dioxygenases were selected as candidates for the metabolic enzyme, and Solyc02g062460, designated Sl23DOX, was found to encode α-tomatine 23-hydroxylase. Biochemical analysis of the recombinant Sl23DOX protein demonstrated that it catalyzes the 23-hydroxylation of α-tomatine and the product spontaneously isomerizes to neorickiioside B, which is an intermediate in α-tomatine metabolism that appears during ripening. Leaves of transgenic tomato plants overexpressing Sl23DOX accumulated not only neorickiioside B but also another intermediate, lycoperoside C (23-O-acetylated neorickiioside B). Furthermore, the ripe fruits of Sl23DOX-silenced transgenic tomato plants contained lower levels of esculeoside A but substantially accumulated α-tomatine. Thus, Sl23DOX functions as α-tomatine 23-hydroxylase during the metabolic processing of toxic α-tomatine in tomato fruit ripening and is a key enzyme in the domestication of cultivated tomatoes.
Interplay between Fluid Extraction Mechanisms and Antigorite Dehydration Reactions (Val Malenco, Italian Alps)
Authors: Clément Maxime , Padrόn-Navarta José Alberto , Tommasi Andréa
Published: December 2019

We investigate the feedback between antigorite dehydration reactions and fluid extraction mechanisms through the analysis of field-scale structures and microtextures formed by antigorite dehydration reactions producing olivine and talc in the Bergell intrusion contact aureole at Alpe Zocca (Malenco Unit, Northern Italy). The reactions, which resulted in the replacement of serpentinites by metaperidotites, occurred under quasi-static conditions. The main reaction front, which defines the equilibrium isograd, is an ∼150 m wide zone composed of variably reacted rocks with an irregular distribution at scales ranging from a few centimeters to a few meters. Veins composed of the prograde mineral assemblage occur downstream (<100 m) of this front. They are often surrounded by centimeter- to decimeter-scale dehydration reaction zones that propagate into the serpentinite wall-rock. Olivine in the metaperidotites and partially reacted serpentinites has a crystallographic preferred orientation (CPO) correlated with the antigorite CPO, with [010]Ol axes parallel to [001]Atg. This CPO is accompanied by a shape-preferred orientation (SPO) that marks the foliation in both rock types. Olivine crystals in Ol–Tlc dehydration veins also have SPO and CPO that define a jackstraw texture within the plane of the vein. They are elongated parallel to [001] within the vein plane and have their [010]Ol axes normal to the vein. We interpret the olivine–talc assemblage in the veins as resulting from dehydration reactions at lower temperature than the equilibrium conditions owing to fluid extraction from the wall-rock into the veins. The jackstraw texture indicates fast kinetics, with the crystal orientation controlled by anisotropic growth under a fluid pressure gradient. We interpret the foliated metaperidotites as formed at near equilibrium conditions, with pervasive fluid extraction from the metaperidotite by viscous metamorphic compaction. Olivine CPO in these rocks may result from topotaxy, oriented growth in the presence of an anisotropic (foliation-controlled) fluid flow, and/or solid reorientation of the anisometric olivine crystals accommodated by the deformation of the weaker talc (± chlorite) matrix during compaction.
Pelagic occurrences of the ice amphipod Apherusa glacialis throughout the Arctic
Authors: Kunisch Erin H , Bluhm Bodil A , Daase Malin , Gradinger Rolf , Hop Haakon , Melnikov Igor A , Varpe Øystein , Berge Jørgen
Published: December 2019

Apherusa glacialis is a common, sea ice-associated amphipod found throughout the Arctic Ocean and has long been considered permanently associated with the sea ice habitat. However, pelagic occurrences of A. glacialis have also been reported. It was recently suggested that A. glacialis overwinters at depth within the Atlantic-water inflow near Svalbard, to avoid being exported out of the Arctic Ocean through the Fram Strait. This study collated pelagic occurrence records over a 71-year period and found that A. glacialis was consistently found away from its presumed sea ice habitat on a pan-Arctic scale, in different depths and water masses. In the Svalbard region, A. glacialis was found in Atlantic Water both in winter and summer. Additionally, we analyzed A. glacialis size distributions throughout the year, collected mostly from sea ice, in order to elucidate potential life cycle strategies. The majority of young-of-the-year A. glacialis was found in the sea ice habitat during spring, supporting previous findings. Data on size distributions and sex ratios suggest a semelparous lifestyle. A synchronous seasonal vertical migration was not evident, but our data imply a more complex life history than previously assumed. We provide evidence that A. glacialis can no longer be regarded as an autochthonous sympagic species.
Long-Term Functional Outcomes Among Childhood Survivors of Cancer Who Have a History of Osteonecrosis
Authors: DeFeo Brian M , Kaste Sue C , Li Zhenghong , Brinkman Tara M , Neel Michael D , Srivastava Deo Kumar , Hudson Melissa M , Robison Leslie L , Karol Seth E , Ness Kirsten K
Published: December 2019

Background

Glucocorticoids used to treat childhood leukemia and lymphoma can result in osteonecrosis, leading to physical dysfunction and pain. Improving survival rates warrants research into long-term outcomes among this population.

Objective

The objective of this study was to compare the physical function and quality of life (QOL) of survivors of childhood cancer who had an osteonecrosis history with that of survivors who had no osteonecrosis history and with that of people who were healthy (controls).

Design

This was a cross-sectional study.

Methods

This study included St Jude Lifetime Cohort Study participants who were ≥ 10 years from the diagnosis of childhood leukemia or lymphoma and ≥ 18 years old; 135 had osteonecrosis (52.5% men; mean age = 27.7 [SD = 6.08] years) and 1560 had no osteonecrosis history (52.4% men; mean age = 33.3 [SD = 8.54] years). This study also included 272 people who were from the community and who were healthy (community controls) (47.7% men; mean age = 35.1 [SD = 10.46] years). The participants completed functional assessments and questionnaires about QOL.

Results

Survivors with osteonecrosis scored lower than other survivors and controls for dorsiflexion strength (mean score = 16.50 [SD = 7.91] vs 24.17 [SD = 8.61] N·m/kg) and scored lower than controls for flexibility with the sit-and-reach test (20.61 [SD = 9.70] vs 23.96 [SD = 10.73] cm), function on the Physical Performance Test (mean score = 22.73 [SD = 2.05] vs 23.58 [SD = 0.88]), and mobility on the Timed “Up & Go” Test (5.66 [SD = 2.25] vs 5.12 [SD = 1.28] seconds). Survivors with hip osteonecrosis requiring surgery scored lower than survivors without osteonecrosis for dorsiflexion strength (13.75 [SD = 8.82] vs 18.48 [SD = 9.04] N·m/kg), flexibility (15.79 [SD = 8.93] vs 20.37 [SD = 10.14] cm), and endurance on the 6-minute walk test (523.50 [SD = 103.00] vs 572.10 [SD = 102.40] m).

Limitations

Because some eligible survivors declined to participate, possible selection bias was a limitation of this study.

Conclusions

Survivors of childhood leukemia and lymphoma with and without osteonecrosis demonstrated impaired physical performance and reported reduced QOL compared with controls, with those requiring surgery for osteonecrosis most at risk for impairments. It may be beneficial to provide strengthening, flexibility, and endurance interventions for patients who have pediatric cancer and osteonecrosis for long-term function.
Birth characteristics of children who used early intervention and special education services in New York City
Authors: Romo Matthew L , McVeigh Katharine H , Jordan Phoebe , Stingone Jeanette A , Chan Pui Ying , Askew George L
Published: December 2019

Background

Early intervention (EI) and special education (SE) are beneficial for children with developmental disabilities and/or delays and their families, yet there are disparities in service use. We sought to identify the birth characteristics that predict EI/SE service use patterns.

Methods

We conducted a retrospective cohort study using linked administrative data from five sources for all children born in 1998 to New York City resident mothers. Multinomial regression was used to identify birth characteristics that predicted predominant patterns of service use.

Results

Children with service use patterns characterized by late or limited/no EI use were more likely to be first-born children and have Black or Latina mothers. Children born with a gestational age ≤31 weeks were more likely to enter services early. Early term gestational age was associated with patterns of service use common to children with pervasive developmental delay, and maternal obesity was associated with the initiation of speech therapy at the time of entry into school.

Conclusions

Maternal racial disparities existed for patterns of EI/SE service use. Specific birth characteristics, such as parity and gestational age, may be useful to better identify children who are at risk for suboptimal EI use.
MRI inflammation of facet and costovertebral joints is associated with restricted spinal mobility and worsened functional status
Authors: Chui Eva Tsz Fung , Tsang Helen Hoi Lun , Lee Kam Ho , Lau Chak Sing , Wong Ching Han , Chung Ho Yin
Published: December 2019

Objective

To investigate the association of spinal inflammation on MRI in patients with various clinical, functional and radiological outcomes in patients with axial spondyloarthritis (SpA).

Methods

Three hundred and ninety-seven participants with axial SpA and back pain were recruited from 10 rheumatology centres. Clinical, biochemical and radiological parameters were collected and participants underwent MRI of the spine. MRI features including inflammatory lesions of facet joints and costovertebral joints, corner inflammatory lesions, and spondylitis were assessed. BASFI, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Global Index, BASMI and modified Stoke Ankylosing Spondylitis Spinal Score were measured. Multivariate linear regression models were used to determine the associations between MRI parameters and various clinical, functional and radiological outcomes.

Results

BASMI and BASFI correlated well with inflammatory features in spinal MRI. Multivariate analysis showed that lumbar facet joint inflammation was independently associated with BASMI (regression coefficient (β) = 0.12, P < 0.001), lumbar spinal flexion (β = 0.13, P = 0.00), lateral spinal flexion (β = 0.09, P = 0.04), tragus-to-wall distance (β = 0.16, P < 0.001) and BASFI (β = 0.14, P = 0.01). Costovertebral joint inflammation was also associated with BASMI (β = 0.08, P = 0.05).

Conclusion

Inflammatory lesions of facet and costovertebral joints in MRI are associated with restriction in spinal mobility and functional impairment. These important yet commonly overlooked lesions should be reviewed in clinical practice in patients with SpA.
Toxicokinetics of cis- and trans-Permethrin: Influence of Isomer, Maturation, and Sex
Authors: Pang Jing , Mortuza Tanzir , White Catherine A , Muralidhara Srinavasa , Cummings Brian S , Bruckner James V
Published: December 2019

Permethrin exposure of children and adults is widespread in many populations, but knowledge of its relative toxicokinetics (TK) and health risks in immature age groups is lacking. Studies were conducted in rats to determine the influence of immaturity and sex (on plasma and target organ dosimetry of each of the insecticide’s 2 isomers, cis- and trans-permethrin [CIS and TRANS]). Postnatal day 15, 21, and 90 (adult), Sprague Dawley rats were orally administered a graduated series of doses of CIS and TRANS in corn oil. Serial sacrifices were conducted over 24 h to obtain plasma, brain, liver, skeletal muscle, and fat profiles of CIS and TRANS. Levels of TRANS decreased relatively rapidly, despite administration of relatively high doses. Concentrations of each isomer in plasma, brain, and other tissues monitored were inversely proportional to the animals’ age. The youngest pups exhibited 4-fold higher plasma and brain area under the curves than did adults. Little difference was observed in the TK of CIS or TRANS between adult male and female rats, other than higher initial plasma and liver CIS levels in females. Elevated exposure of the immature brain appears to be instrumental in increased susceptibility to the acute neurotoxicity of high-dose permethrin (Cantalamessa [1993]), but it remains to be established whether age-dependent TK is relevant to long-term, low-level risks.
Evaluating Quantitative Trait Locus Resistance in Tomato to Multiple Xanthomonas spp.
Authors: Bernal Eduardo , Liabeuf Debora , Francis David M.
Published: December 2019

Bacterial spot of tomato is a foliar disease caused by four Xanthomonas species. Identifying genetic resistance in wild tomatoes and subsequent breeding of varieties has been a strategy to reduce the loss from this disease because control using pesticides has been ineffective. Three independent sources of resistance have been identified with quantitative trait loci (QTL) mapping to the centromeric region on chromosome 11. These sources are derived from Hawaii 7998 (QTL-11A), PI 114490 (QTL-11B), and LA2533 (QTL-11C). To determine which QTL introgression from chromosome 11 provides the greatest resistance to multiple species, we developed near-isogenic lines (NILs) using marker-assisted backcrossing. In parallel, we developed an NIL that contains Rx-4/Xv3, which provides major gene resistance to Xanthomonas perforans. Additionally, we combined Rx-4/Xv3 resistance with QTL-11A. These sources of resistance were independently introduced into the susceptible parent, OH88119. During a 3-year period from 2016 to 2018, we evaluated backcross-derived families and NILs from each source in independent field trials inoculated with X. perforans, X. euvesicatoria, or X. gardneri. Our results suggest that both QTL-11C and QTL-11A combined with Rx-4/Xv3 provide effective genetic resistance against multiple Xanthomonas species. In addition, we provide evidence for additive to dominant genetic action for the QTL introgressions.
Care of the Post-CABG Patient
Authors: Collins David , Goldberg Sheldon
Published: December 2019

An estimated 400,000 coronary artery bypass graft operations are performed annually in the United States. Saphenous vein grafts are the most commonly used conduits; however, graft failure is common. In contrast, left internal mammary artery grafts have more favorable long-term patency rates. Guidelines recommend aggressive secondary prevention. In the 2 decades following surgery, 16% of patients require repeat revascularization, and percutaneous coronary intervention accounts for 98% of procedures performed. Post-coronary artery bypass graft patients presenting with symptoms of acute coronary syndrome or progressive heart failure should undergo early coronary angiography given the high likelihood that such a presentation represents graft failure. Percutaneous coronary intervention in degenerated saphenous vein grafts is associated with embolization that may cause the “no-reflow phenomenon,” which can be avoided with the use of embolic protection devices. Hybrid revascularization procedures are a promising emerging strategy to avoid the placement of vein grafts.
Sodium-glucose cotransporter 2 inhibitors and type 2 diabetes: clinical pearls for in-hospital initiation, in-hospital management, and postdischarge
Authors: Mazer C. David , Arnaout Amel , Connelly Kim A. , Gilbert Jeremy D. , Glazer Stephen A. , Verma Subodh , Goldenberg Ronald M.
Published: December 2019

Purpose of review

The aim of this article is to provide practical recommendations on safe initiation of sodium-glucose cotransporter 2 (SGLT2) inhibitors to in-patients as well as management of those who are already on SGLT2 inhibitors.

Recent findings

Robust data from stable outpatient cohorts indicate that the SGLT2 inhibitors are associated with clinically meaningful reductions in major adverse cardiovascular events, lower rates of hospitalization for heart failure, and a reduction in major kidney outcomes There is however a lack of information on how to initiate and manage SGLT2 inhibitors in an acute in-patient setting.

SGLT2 inhibitors may be cautiously appropriate for in-patients if all the criteria for safe use are met but good clinical judgment must prevail. Temporary withholding of SGLT2 inhibitors is appropriate in hospitalized patients during a period of stress and/or insulinopenia.
Hacking teamwork in health care: Addressing adverse effects of ad hoc team composition in critical care medicine
Authors: McLeod Poppy L. , Cunningham Quinn W. , DiazGranados Deborah , Dodoiu Gabi , Kaplan Seth , Keyton Joann , Larson Nicole , LeNoble Chelsea , Marsch Stephan U. , O’Neill Thomas A. , Parker Sarah Henrickson , Semmer Norbert K. , Shuffler Marissa , Su Lillian , Tschan Franziska , Waller Mary , Wang Yumei
Published: December 2019

Background

The continued need for improved teamwork in all areas of health care is widely recognized. The present article reports on the application of a hackathon to the teamwork problems specifically associated with ad hoc team formation in rapid response teams.

Purposes

Hackathons—problem-solving events pioneered in computer science—are on the rise in health care management. The focus of these events tends to be on medical technologies, however, with calls for improvements in management practices as general recommendations. The hackathon reported here contributes to health care management practice by addressing improvements in teamwork as the focal problem.

Methodology

The hackathon event took place over 2.5 days in conjunction with an academic conference focused on group research. Three teams comprised of practicing healthcare professionals, academic researchers and students developed solutions to problems of ad hoc team formation in rapid response teams.

Findings

The event fulfilled several goals. The teams produced three distinct, yet complementary solutions that were backed by both field-based experience and solid research evidence. The event provided the opportunity for two-way translation of research and practice through direct collaboration among key stakeholders. The hackathon produced long term effects through establishing or strengthening collaborations, dissemination of the ideas through presentations, workshops, and publications, and changes in participantsâ work practices.

Practice Implication

The event demonstrated that hackathons, classically focused on technology, can also offer a spur to innovation around organizational processes. The article provides advice for organizing other hackathons focused on similar topics. The solutions offered by the participants in the event yields the clear insight that multipronged solutions for emergency-oriented teamwork are needed. The hackathon highlighted the scaled of collaboration and effort needed to tackle the many complexities in health care that impact outcomes for providers, patients, and health organizations.
Impact of number of medications and age on adherence to antihypertensive medications
Authors: Kim Seung Jae , Kwon Oh Deog , Han Eunice Bormee , Lee Cheol Min , Oh Seung-Won , Joh Hee-Kyung , Oh Bumjo , Kwon Hyuktae , Cho BeLong , Choi Ho Chun
Published: December 2019

This study tried to investigate the effects of number of medications and age on antihypertensive medication adherence in a real-world setting using a nationwide representative cohort.

We obtained data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) of Korea, which is a sample of 2.2% (N = 1,048,061) of total population (N = 46,605,433). Patients aged 20 years or older (N = 150,550) who took antihypertensive medications for at least 1 year were selected. Medication possession ratio (MPR) was used for measuring adherence. The subjects were divided into 5 subgroups according to total number of medications: 1–2, 3–4, 5–6, 7–8, and 9 or more. The mean age and the mean number of medications were 60.3 ± 12.6 years and 4.1 ± 2.2, respectively. The mean MPR was 80.4 ± 23.9%, and 66.9% (N = 100,645) of total subjects were adherent (MPR ≥ 80%). The overall tendency of antihypertensive medication adherence according to the total number of medications displayed an inverted U-shape with a peak at 3–4 drugs. Adherence consistently increased as the age increased until age 69 and started to decrease from age 70. The proportion of adherent patients (MPR ≥ 80%) according to the total number of medications also showed an inverted U-shape with a peak at 3–4 drugs. When the same number of drugs was taken, the proportion of adherent patients according to age featured an inverted U- shape with a peak at 60 to 69 years. Patients taking 9 or more total drugs had the overall odds ratio (95% CI) of non-adherence (MPR < 80%) with 1.17 (1.11–1.24) compared with those taking 1 to 8 total drugs and the odds ratios in the age subgroups of 40 to 49, 50 to 59, 60 to 69 years were 1.57 (1.31–1.87), 1.21 (1.08–1.36), and 1.14 (1.04–1.25), respectively (P < .05).

Association between age, total number of medications, and antihypertensive adherence displayed an inverted U-shape with a peak at 3 to 4 total medications and at age 60 to 69 years. When the total number of drugs was 9 or more, adherence decreased prominently, regardless of age.
A very rare presentation of lung cancer
Authors: Afrăsânie Vlad-Adrian , Adavidoaiei Anca Maria , Zamisnicu Iuliana Hunea , Funingănă Ionut Gabriel , Marinca Mihai Vasile , Gafton Bogdan , Clement Dana Elena , Păduraru Marius-Ionut , Demşa Irina , Miron Lucian , Alexa-Stratulat Teodora
Published: December 2019

Rationale:

Acrometastases of the hand are an unusual sign of lung cancer onset and may often be mistaken for other benign disorders, thus delaying diagnosis and treatment.

Patient concerns:

A 58-year-old man presented at the Rheumatology Clinic with a lump in the distal phalanx of the right index finger associated with intense pain, swelling, rib pain, and hemoptysis.

Diagnoses:

Given the clinical manifestations, an x-ray of the right hand was performed, and it revealed an osteolytic lesion in the distal phalanx of the right index finger. The subsequent CT of the thorax and abdomen showed a lung tumor, osteolytic lesions in the ribs, sternum, and the thoracic spine.

Interventions:

Amputation of the phalanx was decided on account of intense pain refractory to NSAIDs and opioids. Pathology assessment established the diagnosis of bone metastases secondary to lung adenocarcinoma. The patient underwent 6 cycles of first-line palliative chemotherapy with cisplatin and gemcitabine with partial response according to the RECIST 1.1. criteria. EGFR and ALK testing were not available at the time. A year later, the patient presented with progressive disease, which lead to 6 more cycles of chemotherapy with docetaxel. The disease progressed during chemotherapy and the patient was switched to erlotinib.

Outcomes:

After 7 months of anti-EGFR treatment, the patient passed away due to disease progression, thus having an overall survival of 25 months.

Lessons:

On rare occasions, acrometastases of the hand may be the first manifestation of a lung cancer and, as such, they must be taken into consideration in the differential diagnosis of rheumatologic disorders. They are a poor prognosis marker, but some cases like this one can have a better survival than reported in the literature, most likely due to that particular cancer's biology.
Reactive arthritis induced by active extra-articular tuberculosis
Authors: Endo Yushiro , Kawashiri Shin-ya , Koga Tomohiro , Okamoto Momoko , Tsuji Sosuke , Takatani Ayuko , Shimizu Toshimasa , Sumiyoshi Remi , Igawa Takashi , Iwamoto Naoki , Ichinose Kunihiro , Tamai Mami , Nakamura Hideki , Origuchi Tomoki , Kawakami Atsushi
Published: December 2019

Rationale:

Rare cases of reactive arthritis induced by active extra-articular tuberculosis (Poncet disease) have been reported. Complete response to antitubercular treatment and evidence of active extra-articular tuberculosis are the most important clinical features of Poncet disease. We report the case of successfully treated a patient with reactive arthritis induced by active extra-articular tuberculosis with a TNF inhibitor after sufficient antitubercular treatment.

Patient concerns:

A 56-year-old Japanese man was admitted to our department with polyarthralgia, low back pain, and high fever. The results of rheumatoid factor, anti-citrullinated protein antibody, human leukocyte antigen B27, and the assays for the detection of infections (with an exception of T-SPOT.TB) were all negative. Fluoro-deoxy-D-glucose–positron emission tomography with CT (PET/CT) showed moderate uptake in the right cervical, right supraclavicular, mediastinal, and abdominal lymph nodes. As magnetic resonance imaging and power Doppler ultrasonography showed peripheral inflammation (tendinitis, tenosynovitis, ligamentitis, and enthesitis in the limbs).

Diagnosis:

A diagnosis of tuberculous lymphadenitis was eventually established on the basis of lymph node biopsy results. There was no evidence of a bacterial infection including acid-fast bacteria in his joints, and the symptoms of polyarthralgia and low back pain were improved but not completely resolved with NSAID therapy; in addition, a diagnosis of reactive arthritis induced by active extraarticular tuberculosis was made.

Interventions:

The patient experienced persistent peripheral inflammation despite antitubercular treatment for more than nine months and was then successfully treated with a tumor necrosis factor inhibitor (adalimumab 40 mg every 2 weeks).

Outcomes:

Finally, the patient responded to the treatment and has been in remission for over 4 months as of this writing.

Lessons:

In patients who present with symptoms associated with spondyloarthritis, it is important to distinguish between classic reactive arthritis and reactive arthritis induced by extra-articular tuberculosis infection. Introduction of biological agents should be carefully considered in settings where reactive arthritis induced by active extra-articular tuberculosis shows progression to chronicity despite sufficient antitubercular treatment.
The effect and safety of acupuncture on patients with functional constipation
Authors: Xu Mingmin , Zhang Wei , Wang Lu , Feng Xiumei , Li Ying
Published: December 2019

Background:

Functional constipation (FC) is a prevalent clinical disease that affects a considerable proportion of the population of all ages. Persistent FC significantly reduces quality of life and influences physical and emotional well-being, as well as consumes many substantial healthcare resources. Acupuncture originates from Traditional Chinese Medicine (TCM), and emerging evidence of several randomized controlled trials (RCTs) published suggest that acupuncture has positive effects for FC. Since 2019, several new results of high quality RCTs about acupuncture treatment for FC have been published. Thus a systematic review will be designed to appraise the effectiveness and safety of acupuncture for improvement of FC in patients based on high quality RCTs.

Methods:

We carried out a rigorous literature search in English and Chinese electronic database from inception to present. Two reviewers will identify relevant studies, extract and manage trial information, and then assess the risk of bias in included studies by the Cochrane risk of bias assessment tool. Only high quality RCTs will be included. Data will be synthesized by either fixed-effects or random-effects model regarding to a heterogeneity test. The primary outcome measurement will be the change from baseline in mean complete spontaneous bowel movements and stool form. The secondary outcomes involved disappearance rate of symptoms, proportion of responders, mean transit time, health-related quality of life, and safety of intervention. Meta-analysis will be performed by using Cochrane's RevMan software.

Results:

This systematic review will summarize high quality clinical evidence to assess and appraise the effectiveness and safety of acupuncture treatment for FC patient.

Expected conclusion:

This systematic review and meta-analysis will provide evidence to determine whether acupuncture treatment is an effective and safe therapy for the prevention and treatment of FC compared with medication treatment.
Manipulation for treatment of degenerative lumbar spondylolisthesis
Authors: Sun Kai , Liang Long , Yin He , Yu Jie , Feng Minshan , Zhan Jiawen , Jin Zhefeng , Yin Xunlu , Wei Xu , Zhu Liguo
Published: December 2019

Background:

Degenerative lumbar spondylolisthesis (DLS) is one of the common orthopedic diseases which causes low back pain in patients, which seriously affects people's daily life and work. As a method of conservative treatment of this disease, manipulation is widely used in clinical practice. We will summarize the current published evidence of manipulation in the treatment of DLS, and evaluate the effectiveness and safety of manipulation through systematic review and meta-analysis, so as to provide more reliable evidence for future clinical practice.

Methods:

We will conduct a comprehensive search of the following 9 databases until January 2019: PubMed, Embase, Cochrane Library, ClinicalTrials.gov, Web of Science, Chinese National Knowledge Infrastructure, Chinese Science and Technique Journals Database, Wan Fang Database, and Chinese Biomedical Database. The 2 researchers will independently search, screen, extract data, and evaluate the quality of the literatures. The primary outcomes include clinical effectiveness, Japanese Orthopaedic Association scores, and the secondary outcomes include visual analog scale scores, symptom scores, and adverse events. Bias risk tools provided by Cochrane Collaboration will be used for literature quality assessment, and RevMan 5.3 software will be used for meta-analysis.

Results:

The results of this study will systematically evaluate the effectiveness and safety of manipulation intervention for people with DLS, especially in improving lumbar function scores and pain scores.

Conclusion:

The systematic review of this study will summarize the current published evidence of manipulation for the treatment of DLS, which can further guide the promotion and application of it.

Ethics and dissemination:

This study does not require ethical approval and the results will be published in a peer-reviewed journal.

PROSPERO registration number:

CRD42019139933.
Multiple sites of soft-tissue metastases secondary to lung cancer
Authors: Zhu Xingxing , Chen Jialu , Yang Fanfan , Tang Congsheng
Published: December 2019

Rationale:

The prognosis of lung cancer is dismal, which has resulted in lung carcinoma being one of the leading causes of cancer-related deaths worldwide. Non-small cell lung cancer accounts for approximately 80% of all types of lung carcinoma. The skeletal system and central nervous system are the most common distal metastatic sites in patients with lung cancer, while cutaneous and soft tissues metastasis is rare.

Patient concerns:

We report a case of concomitant metastasis in the nasal tip and suspected buttocks metastasis secondary to lung cancer, who complained of repeated cough and white sputum for 6 months.

Diagnose:

Primary lung cancer was diagnosed by bronchoscopy and biopsy, lesion on nasal tip was confirmed by biopsy. Furthermore, PET-CT scan identified the untouchable buttocks lesion that could have been easily missed.

Interventions:

This patient refused systemic treatments, but he chose traditional Chinese medicine at home.

Outcomes:

He died 6 months after the diagnosis.

Lessons:

The possibility of metastasis of primary cancers should be considered when encountering soft-tissue neoplasm lesions, and a biopsy of the suspicious cutaneous lesions could likely aid in the histological identification of the primary cancer. PET-CT scan could be an effective supplementary tool for the diagnosis and evaluation of cancers.