bluuebunny/crossref_metadata_2025 huggingface dataset:
In response to Luteijn et al.: Concerns regarding cGAMP uptake assay and evidence that SLC19A1 is not the major cGAMP importer in human PBMCs
Authors: Ritchie Christopher , Cordova Anthony F. , Li Lingyin
Published: October 2019

We previously reported that SLC19A1 is an importer of the immunotransmitter 2’3’-cyclic-GMP-AMP (cGAMP)1 by performing a genome wide screen in U937 cells. Soon after, Lutejin et al. reported similar findings by conducting a screen in THP-1 cells2. While the conclusions of these two studies largely overlap, we arrived at significantly different conclusions regarding how broadly SLC19A1 is used by different cell types. Our study suggests that in addition to SLC19A1, many cultured and primary cell types use alternative, unidentified transporters to import cGAMP and other cyclic dinucleotides (CDNs). This conclusion was based on our findings that inhibition of SLC19A1 did not significantly reduce extracellular cGAMP signaling in multiple cell types, including primary CD14+peripheral blood mononuclear cells (PBMCs) from most donors. In contrast, Luteijn et al. concluded that SLC19A1 is the major CDN importer in humans, largely based on their use of a radiolabeled [32P] cGAMP uptake assay. Using this assay, they showed that inhibition of SLC19A1 abolishes [32P] uptake in total PBMCs. However, they did not test whether inhibition of SLC19A1 affects extracellular cGAMP signaling in these cells. Here, we highlight an important issue with the [32P] cGAMP uptake assay used by Luteijn et al. and demonstrate that measuring extracellular cGAMP signaling through the STING pathway is currently the best method for evaluating cGAMP import. We also show that inhibition of SLC19A1 has no effect on extracellular cGAMP signaling in total PBMCs, confirming that this cell type relies on other transport mechanisms for cGAMP import.
Erosion of the Epigenetic Landscape and Loss of Cellular Identity as a Cause of Aging in Mammals
Authors: Yang Jae-Hyun , Griffin Patrick T. , Vera Daniel L. , Apostolides John K. , Hayano Motoshi , Meer Margarita V. , Salfati Elias L. , Su Qiao , Munding Elizabeth M. , Blanchette Marco , Bhakta Mital , Dou Zhixun , Xu Caiyue , Pippin Jeffrey W. , Creswell Michael L. , O’Connell Brendan L. , Green Richard E. , Garcia Benjamin A. , Berger Shelley L. , Oberdoerffer Philipp , Shankland Stuart J. , Gladyshev Vadim N. , Rajman Luis A. , Pfenning Andreas R. , Sinclair David A.
Published: October 2019

All living things experience entropy, manifested as a loss of inherited genetic and epigenetic information over time. As budding yeast cells age, epigenetic changes result in a loss of cell identity and sterility, both hallmarks of yeast aging. In mammals, epigenetic information is also lost over time, but what causes it to be lost and whether it is a cause or a consequence of aging is not known. Here we show that the transient induction of genomic instability, in the form of a low number of non-mutagenic DNA breaks, accelerates many of the chromatin and tissue changes seen during aging, including the erosion of the epigenetic landscape, a loss of cellular identity, advancement of the DNA methylation clock and cellular senescence. These data support a model in which a loss of epigenetic information is a cause of aging in mammals.

One Sentence Summary

The act of repairing DNA breaks induces chromatin reorganization and a loss of cell identity that may contribute to mammalian aging
Correlation between Serum Kisspeptin and Spermatogenic Function in Men
Authors: Yu Hongling , Liu Jin , Han Yilong , Chen Chao , Meng Fanwei
Published: October 2019

Kisspeptin along with its receptor GPR54 or KISS1R regulates the secretion of hormones involved in the hypothalamic-pituitary-testicular axis, which is one of the contributing factors of adolescent spermatogenesis. This study aimed to investigate the correlation between serum kisspeptin concentration and spermatogenic function, and its predictive value in azoospermia. We retrospectively analyzed data of 196 males who visited the Reproductive Medicine Center of Qilu Hospital of Shandong University from June–November 2018; 20 were fertile and 176 were infertile. The following semen tests were performed: serum kisspeptin level by enzyme immunoassay; and levels of follicle-stimulating and luteinizing hormones, and testosterone by chemiluminescence assay. Percutaneous testicular sperm aspiration was performed on males with azoospermia. Subjects were divided into 5 groups: azoospermia (group A: 22 men with obstructive azoospermia; group B: 54 men with non-obstructive azoospermia), oligospermia (group C: 56 men), infertility with normal semen concentration (group D: 44 men), and fertility with normal semen concentration (group E: 20 men). Kisspeptin levels in the fertile group were higher than those in the infertile group. Levels of serum hormones, testosterone, and kisspeptin correlated with sperm concentration, with the strongest correlation between kisspeptin and sperm concentration (correlation coefficient=0.692). Levels of kisspeptin in obstructive and non-obstructive azoospermia groups were analyzed using Receiver-Operating-Curve analysis. A serum kisspeptin level ≥80.655 was classified as obstructive azoospermia; otherwise, the classification was non-obstructive azoospermia. Serum kisspeptin levels in the fertility group were significantly higher than that in the infertility group; this suggests kisspeptin may be associated with male fertility. Moreover, kisspeptin had a stronger correlation with sperm concentration than the hormones. A serum kisspeptin level of 80.655 can be used to differentiate obstructive and non-obstructive azoospermia.
Genome-wide variations analysis of special waxy sorghum cultivar Hongyingzi for brewing Moutai liquor
Authors: Wang Can , Zhou Lingbo , Gao Xu , Ding Yanqing , Cheng Bin , Zhang Guobing , Cao Ning , Xu Yan , Shao Mingbo , Zhang Liyi
Published: October 2019

Abstracts

Hongyingzi is a special waxy sorghum (Sorghum bicolorL. Moench) cultivar for brewing Moutai liquor. For an overall understanding of the whole genome of Hongyingzi, we performed whole-genome resequencing technology with 56.10 X depth to reveal its comprehensive variations. Compared with the BTx623 reference genome, 2.48% of genome sequences were altered in the Hongyingzi genome. Among these alterations, there were 1885774 single nucleotide polymorphisms (SNPs), 309381 small fragments insertions and deletions (Indels), 31966 structural variations (SVs), and 217273 copy number variations (CNVs). These alterations conferred 29614 genes variations. It was also predicted that 35 genes variations were related to the multidrug and toxic efflux (MATE) transporter, chalcone synthase (CHS), ATPase isoform 10 (AHA10) transporter, dihydroflavonol-4-reductase (DFR), the laccase 15 (LAC15), flavonol 3′-hydroxylase (F3′H), flavanone 3-hydroxylase (F3H),O-methyltransferase (OMT), flavonoid 3′5′ hydroxylase (F3′5′H), UDP-glucose:sterol-glucosyltransferase (SGT), flavonol synthase (FLS), and chalcone isomerase (CHI) involved in the tannin synthesis. These results would provide theoretical supports for the molecular markers developments and gene function studies related to the liquor-making traits, and the genetic improvement of waxy sorghum based on the genome editing technology.
Optimal fertigation for high yield and fruit quality of greenhouse strawberry
Authors: Yong Wu , Li Li , Minzan Li , Man Zhang , Hong Sun , Sygrimis Nikolaos
Published: October 2019

Nitrogen (N), phosphorus (P), potassium (K), and water are four crucial factors that have significant effects on strawberry yield and fruit quality. A quadratic regression orthogonal rotation combination experiment that involved 36 treatments with five levels of the four variables (N, P, and K fertilizers and water) was executed to optimize the fertilization and water combination for high yield and quality. SSC/TA ratio (the ratio of soluble solid content to titratable acid) was selected as the index of quality. Results showed that the N fertilizer was the most important factor, followed by water and P fertilizer, and the N fertilizer had a significant effect on yield and SSC/TA ratio. By contrast, the K fertilizer had a significant effect only on yield. N×K fertilizer interaction had a significant effect on yield, whereas the other interactions among the four factors had no significant effects on yield and SSC/TA ratio. The effects of the four factors on the yield and SSC/TA ratio were ranked as N fertilizer > water > K fertilizer > P fertilizer and N fertilizer > P fertilizer > water > K fertilizer, respectively. The yield and SSC/TA ratio increased and then decreased when NPK fertilizer and water increased. The optimal fertilizer and water combination was 22.28–24.61 g/plant Ca (NO3)2⋅4H2O, 1.75–2.03 g/plant NaH2PO4, 12.41–13.91 g/plant K2SO4, and 12.00– 13.05 L/plant water for yields of more than 110 g/plant and optimal SSC/TA ratio of 8.5–14.
Activation of phospholipase C β by Gβγ and Gαqinvolves C-terminal rearrangement to release auto-inhibition
Authors: Fisher Isaac , Jenkins Meredith , Tall Greg , Burke John E , Smrcka Alan V.
Published: October 2019

Phospholipase C (PLC) enzymes hydrolyse phosphoinositide lipids to inositol phosphates and diacylglycerol. Direct activation of PLCβ by Gαqand/or Gβγ subunits mediates signalling by Gq and some Gi coupled G protein-coupled receptors (GPCRs), respectively. PLCβ isoforms contain a unique C-terminal extension, consisting of proximal and distal C-terminal domains (CTD) separated by a flexible linker. The structure of PLCβ3 bound to Gαqis known, however, for both Gαqand Gβγ, the mechanism for PLCβ activation on membranes is unknown. We examined PLCβ2 dynamics on membranes using hydrogen deuterium exchange mass spectrometry (HDX-MS). Gβγ caused a robust increase in dynamics of the distal C-terminal domain (CTD). Gαqshowed decreased deuterium incorporation at the Gαqbinding site on PLCβ.In vitroGβγ-dependent activation of PLC is inhibited by the distal CTD. The results suggest that disruption of auto-inhibitory interactions with the CTD, respectively, leads to increased PLCβ hydrolase activity.
Elevated Expression of a Functional Suf Pathway in theE.coliBL21(DE3) Cell Line Enhances Recombinant Production of an Iron-Sulfur Cluster Containing Protein
Authors: Corless Elliot I. , Mettert Erin L. , Kiley Patricia J. , Antony Edwin
Published: October 2019

Structural and spectroscopic analysis of iron-sulfur [Fe-S] cluster-containing proteins is often limited by the occupancy and yield of recombinantly produced proteins. Here we report thatEscherichia coliBL21(DE3), a strain routinely used to overexpress [Fe-S] cluster-containing proteins, has a nonfunctional Suf pathway, one of twoE. coli[Fe-S] cluster biogenesis pathways. We confirmed that BL21(DE3) and commercially available derivatives carry a deletion that results in an inframe fusion ofsufAandsufBgenes within thesufABCDSEoperon. We show that this fusion protein accumulates in cells but is - inactive in [Fe-S] biogenesis. Restoration of an intact Suf pathway combined with enhanced suf operon expression led to a remarkable (~3-fold) increase in the production of the [4Fe-4S] cluster-containing BchL protein, a key component of the dark-operative protochlorophyllide oxido-reductase complex. These results show that this engineered ‘SufFeScient’ derivative of BL21(DE3) is suitable for enhanced large-scale synthesis of an [Fe-S] cluster-containing protein.

IMPORTANCE

Large quantities of recombinantly overexpressed iron-sulfur cluster-containing proteins are necessary for their in-depth biochemical characterization. Commercially availableE. colistrain BL21(DE3) and its derivatives have a mutation that inactivates the function of one of the two native pathways (Suf pathway) responsible for cluster biogenesis. Correction of the mutation, combined with sequence changes that increase Suf expression can increase yield and cluster occupancy of [Fe-S] cluster-containing enzymes, facilitating the biochemical analysis of this fascinating group of proteins.
PhISCS: a combinatorial approach for subperfect tumor phylogeny reconstruction via integrative use of single-cell and bulk sequencing data
Authors: Malikic Salem , Mehrabadi Farid Rashidi , Ciccolella Simone , Rahman Md. Khaledur , Ricketts Camir , Haghshenas Ehsan , Seidman Daniel , Hach Faraz , Hajirasouliha Iman , Sahinalp S. Cenk
Published: October 2019

Available computational methods for tumor phylogeny inference via single-cell sequencing (SCS) data typically aim to identify the most likely perfect phylogeny tree satisfying the infinite sites assumption (ISA). However, the limitations of SCS technologies including frequent allele dropout and variable sequence coverage may prohibit a perfect phylogeny. In addition, ISA violations are commonly observed in tumor phylogenies due to the loss of heterozygosity, deletions, and convergent evolution. In order to address such limitations, we introduce the optimal subperfect phylogeny problem which asks to integrate SCS data with matching bulk sequencing data by minimizing a linear combination of potential false negatives (due to allele dropout or variance in sequence coverage), false positives (due to read errors) among mutation calls, and the number of mutations that violate ISA (real or because of incorrect copy number estimation). We then describe a combinatorial formulation to solve this problem which ensures that several lineage constraints imposed by the use of variant allele frequencies (VAFs, derived from bulk sequence data) are satisfied. We express our formulation both in the form of an integer linear program (ILP) and—as a first in tumor phylogeny reconstruction—a Boolean constraint satisfaction problem (CSP) and solve them by leveraging state-of-the-art ILP/CSP solvers. The resulting method, which we name PhISCS, is the first to integrate SCS and bulk sequencing data while accounting for ISA violating mutations. In contrast to the alternative methods, typically based on probabilistic approaches, PhISCS provides a guarantee of optimality in reported solutions. Using simulated and real data sets, we demonstrate that PhISCS is more general and accurate than all available approaches.
SiCloneFit: Bayesian inference of population structure, genotype, and phylogeny of tumor clones from single-cell genome sequencing data
Authors: Zafar Hamim , Navin Nicholas , Chen Ken , Nakhleh Luay
Published: October 2019

Accumulation and selection of somatic mutations in a Darwinian framework result in intra-tumor heterogeneity (ITH) that poses significant challenges to the diagnosis and clinical therapy of cancer. Identification of the tumor cell populations (clones) and reconstruction of their evolutionary relationship can elucidate this heterogeneity. Recently developed single-cell DNA sequencing (SCS) technologies promise to resolve ITH to a single-cell level. However, technical errors in SCS data sets, including false-positives (FP) and false-negatives (FN) due to allelic dropout, and cell doublets, significantly complicate these tasks. Here, we propose a nonparametric Bayesian method that reconstructs the clonal populations as clusters of single cells, genotypes of each clone, and the evolutionary relationship between the clones. It employs a tree-structured Chinese restaurant process as the prior on the number and composition of clonal populations. The evolution of the clonal populations is modeled by a clonal phylogeny and a finite-site model of evolution to account for potential mutation recurrence and losses. We probabilistically account for FP and FN errors, and cell doublets are modeled by employing a Beta-binomial distribution. We develop a Gibbs sampling algorithm comprising partial reversible-jump and partial Metropolis-Hastings updates to explore the joint posterior space of all parameters. The performance of our method on synthetic and experimental data sets suggests that joint reconstruction of tumor clones and clonal phylogeny under a finite-site model of evolution leads to more accurate inferences. Our method is the first to enable this joint reconstruction in a fully Bayesian framework, thus providing measures of support of the inferences it makes.
Development of flight and foraging behaviour in a juvenile seabird with extreme soaring capacities
Authors: Corbeau Alexandre , Prudor Aurélien , Kato Akiko , Weimerskirch Henri
Published: October 2019

The early life of animals is a period of high mortality, when foraging capacities are assumed to be improved progressively. In birds, this critical period involves the improvement of the flight. How do young birds gain these capacities has rarely been studied in natural conditions especially in seabirds that spend most of their life at sea.

We used detailed GPS and body acceleration data on 37 great frigatebirds (Fregata minor), to test the hypothesis that juveniles starting their first flights have lower flying capacities than adults, but that these capacities will improve during a long learning period, before independence from parents, specific to this seabird that can spend months on the wing at sea.

We found that most flight components improved over time to tend towards those of adults, especially the travel speed, range, duration and maximum altitude of trips. However, unexpectedly, juveniles had higher ascent rates, soaring and gliding capacities above the sea than adults. Moreover, energy expenditure of juveniles was similar to adults during low cost travelling movements and during active foraging, but juveniles spent more time foraging actively than adults.

Our results suggest that flight tactics based on long‐distance effortless movements specific to this family are acquired during a long period, but soaring and gliding capacities are already inherited by juveniles and possibly favoured by morphological adaptations specific to juveniles. These adaptations might explain the extreme dispersive capacities of juveniles.
Fungal connections between plants and biocrusts facilitate plants but have little effect on biocrusts
Authors: Dettweiler‐Robinson Eva , Sinsabaugh Robert L. , Rudgers Jennifer A.
Published: October 2019

Species interactions may couple the resource dynamics of different primary producers and may enhance productivity by reducing loss from the system. In low‐resource systems, this biotic control may be especially important for maintaining productivity. In drylands, the activities of vascular plants and biological soil crusts can be decoupled in space because biocrusts grow on the soil surface but plant roots are underground, and decoupled in time due to biocrusts activating with smaller precipitation events than plants. Soil fungi are hypothesized to functionally couple the plants and biocrusts by transporting nutrients. We studied whether disrupting fungi between biocrusts and plants reduces nitrogen transfer and retention and decreases primary production as predicted by the fungal loop hypothesis. Additionally, we compared varying precipitation regimes that can drive different timing and depth of biological activities.

We used field mesocosms in which the potential for fungal connections between biocrusts and roots remained intact or were impeded by mesh. We imposed a precipitation regime of small, frequent or large, infrequent rain events. We used15N to track fungal‐mediated nitrogen (N) transfer. We quantified microbial carbon use efficiency and plant and biocrust production and N content.

Fungal connections with biocrusts benefitted plant biomass and nutrient retention under favourable (large, infrequent) precipitation regimes but not under stressful (small, frequent) regimes, demonstrating context dependency in the fungal loop. Translocation of a15N tracer from biocrusts to roots was marginally lower when fungal connections were impeded than intact. Under large, infrequent rains, when fungal connections were intact, the C:N of leaves converged towards the C:N of biocrusts, suggesting higher N retention in the plant, and plant above‐ground biomass was greater relative to the fungal connections‐impeded treatment. Carbon use efficiency in both biocrust and rooting zone soil was less C‐limited when connections were intact than impeded, again only in the large, infrequent precipitation regime.

Synthesis. Although we did not find evidence of a reciprocal transfer of C and N between plants and biocrusts, plant production was benefited by fungal connections with biocrusts under favourable conditions.
Propagule composition regulates the success of an invasive seaweed across a heterogeneous seascape
Authors: Bulleri Fabio , Marzinelli Ezequiel M. , Voerman Sofie E. , Gribben Paul E.
Published: October 2019

Propagule pressure is acknowledged as a key determinant of invasion success. Nonetheless, the role of morphological or physiological attributes of propagules (i.e. their quality) in regulating invader establishment has been little explored. In particular, no study has investigated how the presence of propagules differing in quality within an inoculum influences establishment across heterogeneous landscapes.

We experimentally tested the hypothesis that the quality (+Fronds+Rhizoids; +Fronds−Rhizoids; −Fronds+Rhizoids) and the diversity (1, 2 and 3 fragment types) of vegetative fragments of the seaweed Caulerpa taxifolia determine their establishment success across seascapes consisting of bare sediments and patches of the seagrass Zostera muelleri exposed to different disturbance intensities (control, seagrass canopy clipping and total removal).

After 6 weeks, seaweed biomass, stolon and frond length, frond and rhizoid number were generally greater in unvegetated habitats (bare sediments and total seagrass removal) than full or reduced seagrass canopies. The type and the diversity of types of fragments inoculated had significant effects on the final biomass and morphological features of C. taxifolia only in vegetated habitats. In control plots, inocula of fragments retaining both fronds and rhizoids achieved higher biomass, developed longer stolons and more fronds. In canopy clipping plots, mixed inocula of +Fronds+Rhizoids and −Fronds+Rhizoids fragments had the greatest biomass and stolon length.

Synthesis. Assessing how propagules differing in quality perform in different habitats might be not sufficient to draw a comprehensive picture of invasion risk, as their establishment can be modulated by both negative and positive interactions among them. Propagule composition should be, therefore, considered as a further dimension of propagule pressure. Our results also suggest that the relevance of specific propagule traits for invader establishment decreases from intact to degraded habitats. Considering propagule size in terms of amount of competent propagules, rather than an absolute measure, would refine our ability of predicting invasion risk across habitats differing in biotic or abiotic conditions.
Suppletive Stem Distribution: A Diachronic Perspective
Authors: Kim Ronald I.
Published: October 2019

Suppletion is typically conceived of in diachronic terms as a discontinuous phenomenon, by which two or more originally distinct lexical items come to share slots in a single paradigm. However, it has long been known that regular sound change acting undisturbed over long periods of time can in fact give rise to what in synchronic terms must be considered suppletive stem relationships. It is proposed, on the basis of examples from ancient and modern Indo‐European languages, that instances of suppletion with a morphosyntactically unmotivated distribution are more likely to have arisen by the accretion of sound change than those which neatly contrast morphosyntactic categories such as singular vs. plural, which typically result from merger of two or more lexemes. Supporting this view is the phonological origin of several well‐known cases of morphomic alternations, which can serve as a gateway for the introduction of suppletive stems. However, this hypothesis is to be understood only as a general tendency, since the distribution of stems in phonological suppletion may be altered by irregular morphological developments.
EnTAP: Bringing faster and smarter functional annotation to non‐model eukaryotic transcriptomes
Authors: Hart Alexander J. , Ginzburg Samuel , Xu Muyang (Sam) , Fisher Cera R. , Rahmatpour Nasim , Mitton Jeffry B. , Paul Robin , Wegrzyn Jill L.
Published: October 2019

EnTAP (Eukaryotic Non‐Model Transcriptome Annotation Pipeline) was designed to improve the accuracy, speed, and flexibility of functional gene annotation for de novo assembled transcriptomes in non‐model eukaryotes. This software package addresses the fragmentation and related assembly issues that result in inflated transcript estimates and poor annotation rates of protein‐coding transcripts. Following filters applied through assessment of true expression and frame selection, open‐source tools are leveraged to functionally annotate the reduced set of translated proteins. Downstream features include fast similarity search across five repositories, protein domain assignment, orthologous gene family assessment, and Gene Ontology (GO) term assignment. The final annotation integrates across multiple databases and selects an optimal assignment from a combination of weighted metrics describing similarity search score, taxonomic relationship, and informativeness. Researchers have the option to include additional filters to identify and remove contaminants, identify associated pathways, and prepare the transcripts for enrichment analysis. This fully featured pipeline is easy to install, configure, and runs significantly faster than comparable annotation packages. EnTAP is optimized to generate extensive functional information for the gene space of organisms with limited or poorly characterized genomic resources.
Fetal alcohol spectrum disorder: a systematic review of the cost of and savings from prevention in the United States and Canada
Authors: Greenmyer Jacob R. , Popova Svetlana , Klug Marilyn G. , Burd Larry
Published: October 2019

Background and aims

Fetal alcohol spectrum disorder (FASD) is a preventable condition that imposes a significant financial burden on societies. Funding of FASD prevention is a small portion of the total expenditures associated with FASD. This paper aimed to review the literature on the costs of and savings from prevention of FASD and present a model for the United States and Canada of projected savings based on expansion of existing evidence‐based prevention models.

Methods

A systematic review of published literature on the cost of FASD prevention was conducted and experts in the field were interviewed. Studies that reported the cost of primary prevention of FASD were eligible for further consideration.

Results

Applying evidenced‐based prevention programs to women at highest risk to have a future child with FASD greatly reduces the cost of prevention. In the United States, one case of FASD can be prevented for as little as USD $20 200 – 47 615. Cost of prevention is considerably less expensive than cost of care for a case of FASD.

Conclusion

Expansion of risk‐based prevention strategies for fetal alcohol spectrum disorder in the United States and Canada would be an economically efficient and worthwhile investment for society.
Association between atrial fibrillation and hip fractures and the implications for hip fracture patients: a systematic review
Authors: Abu‐Assi Rabieh , Campbell Jed , Bacchi Stephen , Gill Tiffany K. , George Daniel , Chehade Mellick
Published: October 2019

Background

Atrial fibrillation (AF) and hip fractures are both prevalent in the elderly population. The aim of this study was to systematically review the literature regarding the association between AF and hip fractures, and the impact of AF on hip fracture prognosis.

Methods

The literature search was performed using PubMed, MEDLINE, Embase and Scopus. Inclusion was based upon the application of eligibility criteria in duplicate prior to data extraction with a standardized form.

Results

A total of 42 studies met the inclusion criteria. AF prevalence was found to vary between 6.5% and 35% in cohorts. Large studies with broad inclusion criteria found the prevalence of AF in hip fracture patients to be approximately 12–15%. There were conflicting results as to whether patients with AF have an increased rate of hip fractures, as compared to patients without AF. Several studies demonstrated that hip fracture patients with AF have increased rates of mortality, both as an inpatient and following discharge, and increased readmission rates.

Conclusion

AF and hip fractures frequently coexist, and there is evidence to suggest AF is associated with increased readmission and mortality rates in hip fracture patients. Elements of the relationship between AF and hip fractures remain uncertain and further prospective studies on AF and hip fracture cohorts may clarify this relationship. Interventional studies targeting hip fracture patients with AF may be beneficial.
Ambient theatre temperature and cement setting time in total knee arthroplasty
Authors: Elliott Ross , Regazzola Gianmarco , Bruce Warwick J. M.
Published: October 2019

Background

Polymethylmethacrylate cement is used in total knee arthroplasty and plays a significant role in the success of the procedure. Temperature variation is known to influence cement setting time in vitro. Our aim is to evaluate the relationship between ambient theatre temperature and cement setting time in vivo.

Methods

Theatre temperature and cement setting time were prospectively recorded during 683 total knee arthroplasties over 8 years using a single cement and vacuum mixing system (Simplex with tobramycin). Setting time was defined as the time until a scalpel blade could not indent the cement surface.

Results

Mean temperature was 18.92°C (SD 1.16) and setting time 13.08 min (SD 1.92). A moderate inverse relationship exists between ambient temperature and setting time (Pearson's R = −0.423); however, potential setting times within a given temperature range varied considerably (<19°C: 8–19.1 min, 19–20°C: 7–18 min and >20°C: 7.5–16 min), suggesting that temperature alone cannot reliably predict setting time.

Conclusion

Our data support the current understanding of bone cement properties in vivo and suggest that surgeons should be mindful in regards to unpredictable cement setting time and optimal theatre environment.
Aspiration and sclerotherapy of hydroceles and spermatoceles/epididymal cysts with 100% alcohol
Authors: Low Li Sian , Nair Shiva M. , Davies Adam J. W. , Akapita Teresa , Holmes Michael A.
Published: October 2019

Objective

To evaluate the efficacy of aspiration and sclerotherapy with 100% alcohol for the primary treatment of benign scrotal cysts.

Methods

From March 2014 to March 2018, 114 patients were identified who underwent their first aspiration and sclerotherapy procedure (80 hydroceles and 34 spermatoceles/epididymal cysts). The procedure was carried out in the outpatient clinic with local anaesthesia. A 16‐gauge IV catheter is used to puncture the sac under aseptic conditions. The volume of alcohol instilled was 10% of the aspirated volume (maximum of 50 mL). Patients were then observed in the waiting room and completed a questionnaire. Urology clinic follow up was scheduled at 6 weeks.

Results

At follow up, 54 patients (67.5%) with hydroceles and 25 patients (73.5%) with spermatoceles/epididymal cysts had resolution after a single procedure. A second procedure was offered if fluid collection persisted, of which 71% of patients with hydroceles and 100% of patients with spermatoceles/epididymal cysts had a successful outcome. At a median of 31 months post‐initial procedure, the overall success rate, after at most two procedures, was 80% for hydroceles and 85% for spermatoceles/epididymal cysts. The complication rate was low (6%). Almost all patients were happy to undergo the procedure again, if needed. Persistence following aspiration and sclerotherapy were more likely to occur in younger patients (45.4 versus 61.2 years, P = 0.001). Persistence was not related to the volume of fluid aspirated.

Conclusion

Aspiration and sclerotherapy with alcohol is a reliable, safe and effective technique for treatment of benign scrotal cysts.
The added benefit of transvaginal sonography in the clinical staging of cervical carcinoma
Authors: Goldberg Yael , Siegler Yoav , Segev Yakir , Mandel Rachel , Siegler Efraim , Auslander Ron , Lavie Ofer
Published: October 2019

Introduction

Patients diagnosed with cervical cancer face several treatment options, depending on the physical examination and the imaging modality results. Transvaginal sonography (TVS) was proposed as an imaging option to determine local spread of cervical tumors, along with magnetic resonance imaging, also by recently released International Federation of Gynecology and Obstetrics recommendations. We examined whether combined data from physical examination, high‐detail TVS, and positron emission tomography with 18F‐labeled fluoro‐2‐deoxyglucose and computed tomography (18F‐FDG PET/CT) may contribute to triage efficiency of cervical cancer patients.

Material and methods

This is a retrospective study of consecutive women diagnosed with cervical cancer at the Carmel Health Center, Haifa, Israel, during 2010‐2015. Inclusion criteria were histology of cervical cancer and the availability of three modalities—a thorough physical examination, a high‐detail TVS, and positron emission tomography (PET) with 18F‐FDG and computed tomography (18F‐FDG PET/CT). End points were the possibility to predict local invasion to the parametrium and distant lymph node metastasis at the time of triage to surgery or chemoradiation.

Results

Seventy‐three patients with cervical cancer were evaluated. TVS correctly predicted no involvement of the parametrium for the 25 who had a postoperative pathological report. TVS measurement of tumor dimension was also matched by the pathological report in these cases. Only three patients were referred for adjuvant therapy according to postoperative pathology criteria. Among 43 women treated with a combination of chemotherapy and radiotherapy due to advanced disease, and with complete data, at least two modalities were congruent with chemoradiation for 33 (77%). Three patients (7%) were referred to chemoradiation due to TVS result alone.

Conclusions

The combination of high‐detail TVS, directed to predict tumor dimensions and local spread, performed by a trained operator, combined with 18F‐FDG PET/CT and physical examination, can assist in selecting optimal treatment for cervical cancer patients, thus avoiding unnecessary operations.
Rationalizing the management of pregnancies of unknown location: Diagnostic accuracy of human chorionic gonadotropin ratio‐based decision tree compared with the risk prediction model M4
Authors: Nadim Batool , Leonardi Mathew , Infante Fernando , Lattouf Ihab , Reid Shannon , Condous George
Published: October 2019

Introduction

The objective was to compare the diagnostic accuracy of the decision tree analysis prediction model P1, which incorporates the human chorionic gonadotropin (hCG) ratio (hCG 48 hours/hCG 0 hour), and risk prediction model M4 in the management of women with pregnancy of unknown location (PUL).

Material and methods

A retrospective diagnostic accuracy study was performed on PUL data collected between August 2011 and September 2018. Women with a PUL were prospectively managed according to the P1 prediction model, which utilizes the hCG ratio and, if necessary, a day (D) 7 hCG. We compared the performance of P1 with the M4 model, a logistic regression mathematical model using initial hCG and hCG ratio, to classify PULs as low risk (failed PUL [failed] or intrauterine pregnancy) or high risk (ectopic pregnancy or persistent PUL). The reference standard was defined as the final PUL outcome.

Results

Transvaginal ultrasound was done in 3847 consecutive women for early pregnancy complications, 437 (11.3%) of whom were classified as PUL. Final analysis comprised 413 cases with complete data. Final PUL clinical outcomes were: 247 (59.8%) failed PUL, 94 (22.7%) intrauterine pregnancy, 49 (11.8%) ectopic pregnancy and 23 (5.5%) persistent PUL. The sensitivity of P1 and M4 in predicting high‐risk PUL were 81.9% (95% confidence interval [CI] 71.1‐90.0) and 80.6% (95% CI 69.5‐88.9), respectively. The specificities were 74.5% (95% CI 69.5‐79.1) and 75.6% (95% CI 70.7‐80.1), respectively.

Conclusions

P1 and M4 performed similarly with respect to diagnostic accuracy in predicting PUL outcome. P1 needs to be externally validated.
Histological changes in refractory Helicobacter pylori infection and its relationship with increased levels of resistance to antibiotics and therapeutic regimens: one‐year follow‐up
Authors: Bayati Saeed , Alebouyeh Masoud , Amirmozafari Nour , Ebrahimi Daryani Nasser , Talebi Maliheh , Zali Mohammad Reza
Published: October 2019

Eradication failure of Helicobacter pylori infection could play a causal role in progression of gastric disorders. In this study, infection with H. pylori was followed in gastric biopsies of symptomatic adult patients at two phases during 1‐year period. Analyses were done to show association of therapeutic regimens with the refractory infection, changes in sequence types (STs) and minimum inhibitory concentration (MIC) values, and progression of histopathological changes. Infection with H. pylori was confirmed in 32.3% (57/170) of the patients. Persistent infection with H. pylori was confirmed in 14 out of the 25 patients (56%) who participated at the second phase of the study. A difference between primary and secondary resistance rates to clarithromycin (49% vs 64.3%), metronidazole (76.36% vs 100%), and ciprofloxacin (45% vs 57.1%) was detected. Although the re‐emerged strains in patients with refractory infection did not show alteration in STs, their MIC50 values showed twofold increases for clarithromycin and ciprofloxacin. While ciprofloxacin containing regimens were more successful, failure of metronidazole containing regimens was detected in 77% of the patients. Consequently, inappropriate medication has an impact on refractory H. pylori infection, which could cause to a rise in resistance levels to antibiotics and progression of pathological disorders.
Exome sequencing of 22 genes using tissue from patients with biliary tract cancer
Authors: Høgdall Dan , Larsen Ole F. , Linnemann Dorte , Svenstrup Poulsen Tim , Høgdall Estrid V.
Published: October 2019

Biliary tract cancers (BTC) are a rare heterogeneous disease group with a dismal prognosis and limited treatment options. The mutational landscape consists of genetic aberrations both shared by and characteristic for anatomical location. Here, we present exome sequencing data on 22 genes from a phase 2 trial using a clinically validated panel used in patients with colorectal cancer. A total of 56 patients were included in a one‐armed phase 2 trial investigating the treatment combination of capecitabine, gemcitabine, oxaliplatin, and cetuximab. Tissue DNA yield and quality allowed analysis of 30 patients on our panel including 22 genes. ARID1A (33%) and TP53 (33%) were found to be most frequently mutated followed by KRAS mutations found in 20% of the patients. Mutational aberrations in ARID1A were found more prevalent than expected, whereas TP53 and KRAS were in concordance with earlier reported data. Mutation in CTNNB1 was significantly associated with poor prognosis. Our panel is clinically validated and suitable for a high volume of samples to detect mutations in patients with BTC. However, it is reasonable to assume that the clinical utility could be optimized in this patient group by extending the panel to include BTC specific mutations with potential therapeutic consequences such as IDH1/2, FGFR fusions, ERBB3, and BRCA1/2.
The first report on epidemiology of oropharyngeal Kingella kingae carriage in Scandinavian children: K. kingae carriage is very common in children attending day care facilities in Western Norway
Authors: Lillebo Kristine , Breistein Rebecca Irene , Aamas Jon Vangdal , Kommedal Oyvind
Published: October 2019

Kingella kingae colonizes the upper airways in children and has been recognized as the most common causative agent of osteoarticular infections (OAI) in children below 4 years of age. This is the first Scandinavian study to investigate oropharyngeal K. kingae carriage in healthy children. From June 2015 to August 2016, we recruited 198 healthy children aged 11–14 months from routine consultations at health promotion centers in Hordaland County, Norway for a cross‐sectional study. After their parents had provided informed consent; demographic data were registered, and an oropharyngeal swab was collected. The oropharyngeal swab was analyzed with a real‐time PCR assay specific to K. kingae targeting the RTX toxin locus. Results showed an asymptomatic carriage rate of 12.6%. A striking and highly significant difference was observed between the children that had started attending day care facilities as compared with children still being at home (33.33% vs 8.5%; p < 0.001). K. kingae is prevalent in young children in Norway. This study emphasize that K. kingae should be considered an important etiological agent in OAI. Transmission seems to be facilitated in day care facilities. The correlation between oropharyngeal carriage and OAI needs to be further explored.
Gene expression profiling in the hippocampus of adolescent rats after chronic alcohol administration
Authors: Choi Mi Ran , Han Jasmin Sanghyun , Chai Young Gyu , Jin Yeung‐Bae , Lee Sang‐Rae , Kim Dai‐Jin
Published: October 2019

In South Korea, the average age of onset of alcohol drinking is 13.3 years and half of adolescents drink alcohol more than once a month; 8.45% of the Korean adolescent population become future high‐risk alcohol drinkers. Chronic alcohol abuse causes physical and psychiatric health problems such as alcohol addiction, liver disease, stroke and cognitive impairments. This study aimed to investigate the effect of alcohol on gene expression and their function in the hippocampus of adolescent rats. After chronic alcohol administration in male (control, n = 6; alcohol, n = 6) Sprague‐Dawley rats for 6 weeks, we analysed up‐ or down‐regulated genes using RNA‐sequencing technology. We found 83 genes more than 1.5‐fold up‐ or down‐regulated in the alcohol‐treated group. Among them, genes (Dnai1, Cfap206 and Dnah1) associated with cilium movement were up‐regulated in the alcohol‐treated group. Mlf1, related to cell cycle arrest, was also up‐regulated in the alcohol‐treated group. On the other hand, genes (Smad3 and Plk5) involved in negative regulation of cell proliferation were down‐regulated in the hippocampus by chronic alcohol administration. In addition, expression levels of genes associated with oxidative stress (Krt8 and Car3) and migration (Vim) were changed by chronic alcohol administration. These results pave a path for a better understanding of the neuromolecular mechanisms mediated by chronic alcohol exposure in the hippocampus of adolescents and negative pathology due to chronic alcohol abuse.
Pharmaceutical care for adult asthma patients: A controlled intervention one‐year follow‐up study
Authors: Khdour Maher R. , Elyan Sabrin O. , Hallak Hussein O. , Jarab Anan S. , Mukattash Tareq L. , Astal Amr
Published: October 2019

Asthma is a clinical problem with social, psychological and economic burdens. To improve patient disease management, different education programmes have been developed. Challenges in asthma management may be partially attributed to non‐adherence or improper use of inhalers. This study aimed to implement and assess hospital‐based pharmaceutical care services for asthmatic patients. A 12‐month, single‐centre, randomized, controlled study was initiated in asthmatic adult patients who had been divided into either a control or intervention group. Patients in the control group received the usual care, and patients in the intervention group received patient counselling per study protocol that covered asthma knowledge, control, adherence to treatment and inhalation techniques. The main variables compared measurements at baseline with those at 6 and 12 months. A total of 192 patients completed the study protocol: 90 in the control group and 102 in the intervention group. The control group included 90 patients, and the intervention group included 102 patients. Over the course of the 12‐month follow‐up period, a significant difference was observed between intervention and control groups with respect to asthma control (38.2% vs 10.0%; P < .001), mean correct inhalation technique (confidence interval [CI]: 8.1, 7.8‐8.5 vs CI: 6.1; 5.6‐6.6; P = .01) and good medication adherence (60.7% vs 50.0%, P = .02). There were 34% and 25% decreases in emergency room visits and hospital admissions, respectively, in the intervention group compared to the control group. This study emphasizes the importance of patient counselling in asthma management and the significant contribution that the pharmacist's intervention can have on asthma control.
Childhood maltreatment and polygenic risk in bipolar disorders
Authors: Aas Monica , Bellivier Frank , Bettella Francesco , Henry Chantal , Gard Sebastien , Kahn Jean‐Pierre , Lagerberg Trine V. , Aminoff Sofie R. , Melle Ingrid , Leboyer Marion , Jamain Stéphane , Andreassen Ole A. , Etain Bruno
Published: October 2019

Background

Childhood maltreatment is a well‐known risk factor for developing a more severe and complex form of bipolar disorders (BD). However, knowledge is scarce about the interactions between childhood maltreatment and underlying genetic vulnerability on the clinical expression of BD.

Method

We assigned a BD‐polygenic risk score (BD‐PRS), calculated from the Psychiatric Genomics Consortium, to each individual in a sample of 402 cases with BD. The lifetime clinical expression of BD was characterized using structured interviews and patients completed the Childhood Trauma Questionnaire (CTQ) to assess the severity of childhood maltreatment.

Results

Cases who reported more severe childhood maltreatment had a lower BD‐PRS (rho = −0.12, P = .01), especially when considering emotional abuse (rho = −0.16, P = .001). An interaction between BD‐PRS and childhood maltreatment was observed for the risk of rapid cycling (P = .01). No further interactions between BD‐PRS and childhood maltreatment were observed for other clinical characteristics (age at onset, suicide attempts, number of mood episodes, mixed features, substance use disorders and psychotic symptoms).

Conclusion

Our study is the first to show that less genetic risk may be needed to develop a more unstable form of BD when exposed to childhood maltreatment. Our study supports childhood trauma as an independent risk factor for BD.