bluuebunny/crossref_metadata_2025 huggingface dataset:
Preoperative plasma fibrinogen level and transfusion in cardiac surgery: a biphasic correlation
Authors: Charbonneau Hélène , Pasquie Marie , Mayeur Nicolas
Published: July 2020

Coagulopathic bleeding is a serious complication of cardiac surgery. A very low preoperative plasma fibrinogen level (PFL) has been previously described as a risk factor for red blood cell (RBC) transfusion in the perioperative setting. Nevertheless, contradictory results have been published concerning preoperative fibrinogen infusion to decrease RBC transfusion. These results highlight the need for a better description of the relation between preoperative PFL and RBC transfusion. In this single-centre retrospective study, we showed that both high and low PFLs are associated with an increase in RBC transfusion. A pro-inflammatory preoperative status could be involved in the association between high PFL and the increase in RBC transfusion. This non-linear relation between PFL and RBC transfusion could explain the difficulty of decreasing postoperative bleeding using only an algorithm aimed at increasing preoperative PFL.
Enhanced efficacy of endonuclease inhibitor baloxavir acid against orthobunyaviruses when used in combination with ribavirin
Authors: ter Horst Sebastiaan , Fernandez-Garcia Yaiza , Bassetto Marcella , Günther Stephan , Brancale Andrea , Neyts Johan , Rocha-Pereira Joana
Published: July 2020

Objectives

Baloxavir acid is an endonuclease inhibitor approved for use against influenza. We evaluated whether this compound also targets the endonuclease domain of orthobunyaviruses and therefore could potentially be used against orthobunyavirus infections.

Methods

We performed a thermal shift assay and a fluorescence resonance energy transfer (FRET)-based nuclease monitoring assay using the La Crosse virus (LACV) endonuclease and baloxavir acid to prove their interaction and identify an inhibitory effect. Their interaction was further studied in a docking simulation using Glide SP. We show that baloxavir acid inhibits the viral replication of Bunyamwera virus (BUNV)–mCherry in vitro using high-content imaging and virus yield assay. Lastly, we investigated the use of baloxavir acid in combination with ribavirin in vitro by implementing the Zero Interaction Potency response surface model.

Results

We show that baloxavir acid augments LACV enzyme’s melting temperature with ΔTm 9.5 ± 0.4°C and inhibited substrate cleavage with IC50 0.39 ± 0.03 μM. Moreover, our docking simulation suggests that baloxavir acid is able to establish an efficient binding with the LACV endonuclease. In the cell-based assay, we observed that baloxavir acid and ribavirin inhibited BUNV–mCherry with an EC50 of 0.7 ± 0.2 μM and 26.6 ± 8.9 μM, respectively. When used in combination, we found a maximum synergistic effect of 8.64.

Conclusions

The influenza endonuclease inhibitor baloxavir acid is able to bind to and interfere with the endonuclease domain of orthobunyaviruses and yields a more potent antiviral effect than ribavirin against BUNV–mCherry. The combination of both compounds results in a more potent antiviral effect, suggesting that these molecules could potentially be combined to treat orthobunyavirus-infected patients.
A heat transfer tube wear reliability analysis method based on first-order reliability method
Authors: Chen Xiao , He Xing , Tang Lichen , Li Yuebing , Zhou Mingjue , Jin Weiya , Gao Zengliang
Published: July 2020

The heat transfer tube is one of the most essential components of the nuclear power plant as the boundary between the first and second circuit pressures. The wear between the heat transfer tube and the support plate or the anti-vibration strip is one of the essential reasons for its failure. Based on a heat transfer tube wear analysis method, combined with the reliability analysis theory, the calculation scheme of tube wear failure probability is proposed in this paper. In the analysis and calculation process, the key factors affecting the reliability are determined, including the baffle thickness B and the aperture difference Ce. In the manufacturing process, these key factors can be controlled, which is instructive for engineering practice.
A fuzzy-based framework to support multicriteria design of mechatronic systems
Authors: Mohebbi Abolfazl , Achiche Sofiane , Baron Luc
Published: July 2020

Designing a mechatronic system is a complex task since it deals with a high number of system components with multidisciplinary nature in the presence of interacting design objectives. Currently, the sequential design is widely used by designers in industries that deal with different domains and their corresponding design objectives separately leading to a functional but not necessarily an optimal result. Consequently, the need for a systematic and multiobjective design methodology arises. A new conceptual design approach based on a multicriteria profile for mechatronic systems has been previously presented by the authors, which uses a series of nonlinear fuzzy-based aggregation functions to facilitate decision-making for design evaluation in the presence of interacting criteria. Choquet fuzzy integrals are one of the most expressive and reliable preference models used in decision theory for multicriteria decision-making. They perform a weighted aggregation by the means of fuzzy measures assigning a weight to any coalition of criteria. This enables the designers to model importance and also interactions among criteria, thus covering an important range of possible decision outcomes. However, specification of the fuzzy measures involves many parameters and is very difficult when only relying on the designer's intuition. In this paper, we discuss three different methods of fuzzy measure identification tailored for a mechatronic design process and exemplified by a case study of designing a vision-guided quadrotor drone. The results obtained from each method are discussed in the end.
Effect of neoadjuvant chemotherapy on health-related quality of life in patients with muscle-invasive bladder cancer: results from JCOG0209, a randomized phase III study
Authors: Kitamura Hiroshi , Hinotsu Shiro , Tsukamoto Taiji , Shibata Taro , Mizusawa Junki , Kobayashi Takashi , Miyake Makito , Nishiyama Naotaka , Kojima Takahiro , Nishiyama Hiroyuki ,   Urologic Oncology Study Group of the Japan Clinical Oncology Group
Published: July 2020

Background

Although neoadjuvant chemotherapy provides survival benefits in muscle-invasive bladder cancer, the impact of neoadjuvant chemotherapy on health-related quality of life has not been investigated by a randomized trial. The purpose of this study is to compare health-related quality of life in patients with muscle-invasive bladder cancer who received neoadjuvant chemotherapy followed by radical cystectomy or radical cystectomy alone based on patient-reported outcome data.

Methods

Patients were randomized to receive two cycles of neoadjuvant methotrexate, doxorubicin, vinblastine, and cisplatin followed by radical cystectomy or radical cystectomy alone. Health-related quality of life was measured using the Functional Assessment of Cancer Therapy-Bladder (version 4) questionnaire before the protocol treatments, after neoadjuvant chemotherapy, after radical cystectomy and 1 year after registration.

Results

A total of 99 patients were analysed. No statistically significant differences in postoperative health-related quality of life were found between the arms. In the neoadjuvant chemotherapy arm, the scores after neoadjuvant chemotherapy were significantly lower than the baseline scores in physical well-being, functional well-being, Functional Assessment of Cancer Therapy-General total, weight loss, diarrhoea, appetite, body appearance, embarrassment by ostomy appliance and total Functional Assessment of Cancer Therapy-Bladder. However, there was no difference in scores for these domains, except for embarrassment by ostomy appliance, between the two arms after radical cystectomy and 1 year after registration.

Conclusions

Although health-related quality of life declined during neoadjuvant chemotherapy, no negative effect of neoadjuvant chemotherapy on health-related quality of life was apparent after radical cystectomy. These data support the view that neoadjuvant chemotherapy can be considered as a standard of care for patients with muscle-invasive bladder cancer regarding health-related quality of life.
Pedicled jejunal flap reconstruction for partial duodenectomy: a report of two cases
Authors: Takei Ryohei , Hashimoto Masashi , Zaimoku Ryosuke , Terakawa Hirohumi , Terada Itsuro , Tsukioka Yuji , Kiriyama Masato
Published: July 2020

Conventional jejunal reconstruction procedures for large duodenal defects include jejunal serosal patch repair and duodenojejunostomy and have some risks of postoperative complications. The pedicled jejunal flap is used for reconstruction following laryngopharyngectomy, esophagectomy and other gastrointestinal surgeries. We report two cases of successful closure of duodenal defects after partial duodenectomies by pedicled jejunal flap reconstruction. Case 1: A 72-year-old man was diagnosed with gastrointestinal stromal tumor by esophagogastroduodenoscopy (EGD), endoscopic ultrasound-guided fine needle aspiration biopsy and computed tomography (CT). Case 2: A 63-year-old woman was diagnosed with early duodenal cancer using EGD and CT. Partial duodenectomy and pedicled jejunal flap reconstruction were performed in both patients. A part of the jejunum was formed into a pedicled flap to fit the duodenal defect and duodenojejunal anastomosis was performed. The patients did not report any postoperative gastrointestinal symptoms or abnormal findings during follow-up EGD or upper gastrointestinal radiography.
AGN dichotomy beyond radio loudness: a Gaussian mixture model analysis
Authors: Beaklini Pedro P B , Quadros Allan V C , de Avellar Marcio G B , Dantas Maria L L , Cançado André L F
Published: July 2020

Since the discovery of quasi-stellar objects (QSOs), also known as quasars, they have been traditionally subdivided as radio-loud and radio-quiet sources. Whether such division is a misleading effect from a highly heterogeneous single population of objects, or real has yet to be answered. Such dichotomy has been evidenced by observations of the flux ratio between the optical and radio emissions (usually B band and 5 GHz). Evidence of two populations in quasars and samples of a wide diversity of active galactic nuclei (AGNs) has been accumulated over the years. Other quantities beyond radio loudness also seem to show the signature of the existence of two different populations of AGNs. To verify the existence of a dichotomy through different parameters, we employed a soft clustering scheme, based on the Gaussian mixture model (GMM), to classify these objects simultaneously using the following parameters: black hole mass, colour, and R loudness index, as well as the usual radio and B-band luminosity. To investigate whether different kinds of AGNs manifest any population dichotomy, we applied GMM to four independent catalogues composed of both optical and radio information. Our results indicate the persistence of a dichotomy in all data sets, although the discriminating power differs for different choices of parameters. Although the radio loudness parameter alone does not seem to be enough to display the dichotomy, the evidence of two populations of AGNs could persist even if we consider other parameters. Our research suggests that the dichotomy is not a misleading effect but real.
Dynamical effects of the ambipolar diffusion in a protoplanetary disc
Authors: Gholipour Mahmoud
Published: July 2020

Several recent simulation works in the non-ideal magnetohydrodynamic (MHD) formalism have shown the importance of ambipolar diffusion (AD) within the protoplanetary discs (PPDs) at large radii. In this study, we model the time evolution of a polytropic PPD in the presence of the AD. In this regard, the non-ideal MHD equations are investigated in the outer region of a PPD where the magnetic field evolution is dominated by the AD. The self-similar solution technique is used for a polytropic fluid including the self-gravity and viscosity. The ambipolar diffusivity and its derivative are crucial for the formulation of this study. Hence, this variable is scaled by an important factor, that is the Elsasser number. The self-similar equations are derived, and the semi-analytical and numerical solutions are presented for the isothermal and polytropic cases. The analytical approach enables us to know the asymptotic behaviour of the physical variables in a PPD, such as the angular momentum and magnetic field. Furthermore, the coupling/decoupling of magnetic field with the angular momentum was discussed analytically to find a corresponding model for the angular momentum loss at large radii of a PPD. Regarding this approach, we found that the magnetic braking induced by the AD at large radii has a high potential to loss the angular momentum even if the turbulent viscosity is not efficient. Also, the sign and values of vertical velocity strongly depends on the sign and values of radial field in the polytropic case.
The 300-pc scale ALMA view of [C i] 3P1–3P0, CO J = 1–0, and 609-μm dust continuum in a luminous infrared galaxy
Authors: Saito T , Michiyama T , Liu D , Ao Y , Iono D , Nakanishi K , Schinnerer E , Tadaki K , Ueda J , Yamashita T
Published: July 2020

We present high-quality Atacama Large Millimeter/submillimeter Array (ALMA) Band 8 observations of the [C i] 3P1–3P0 line and 609-μm dust continuum emission towards the nearby luminous infrared galaxy (LIRG) IRAS F18293-3413, as well as matched resolution (300-pc scale) Band 3 CO J = 1–0 data, which allow us to assess the use of the [C i] 3P1–3P0 line as a total gas mass estimator. We find that the [C i] line basically traces structures detected in CO (and dust) and a mean (median) [C i]/CO luminosity ($L^{\prime }_{\rm [C\, {\small I}]}$/$L^{\prime }_{\rm CO}$) ratio of 0.17 (0.16) with a scatter of 0.04. However, a pixel-by-pixel comparison revealed that there is a radial $L^{\prime }_{\rm [C\, {\small I}]}$/$L^{\prime }_{\rm CO}$ gradient and a superlinear $L^{\prime }_{\rm CO}$ versus $L^{\prime }_{\rm [C\, {\small I}]}$ relation (slope = 1.54 ± 0.02) at this spatial scale, which can be explained by radial excitation and/or line opacity gradients. Based on the molecular gas masses converted from the dust continuum emission, we found that the CO-to-H2 and [C i]-to-H2 conversion factors are relatively flat across the molecular gas disc with a median value of 3.5$^{+1.9}_{-1.3}$ and 20.7$^{+9.2}_{-4.9}$ M⊙ (K km s−1 pc2)−1, respectively. A non-LTE calculation yields that typical molecular gas properties seen in nearby (U)LIRGs ($n_{\rm H_2}$ = 103−4 cm−3, Tkin ∼ 50 K, and $X_{\rm C\, {\small I}}$ = (0.8–2.3) × 10−5) can naturally reproduce the derived [C i]-to-H2 conversion factor. However, we caution that a careful treatment of the physical gas properties is required in order to measure H2 gas mass distributions in galaxies using a single [C i] line. Otherwise, a single [C i] line is not a good molecular gas estimator in a spatially resolved manner.
Alternative linker histone permits fast paced nuclear divisions in early Drosophila embryo
Authors: Henn László , Szabó Anikó , Imre László , Román Ádám , Ábrahám Andrea , Vedelek Balázs , Nánási Péter , Boros Imre M
Published: July 2020

In most animals, the start of embryogenesis requires specific histones. In Drosophila linker histone variant BigH1 is present in early embryos. To uncover the specific role of this alternative linker histone at early embryogenesis, we established fly lines in which domains of BigH1 have been replaced partially or completely with that of H1. Analysis of the resulting Drosophila lines revealed that at normal temperature somatic H1 can substitute the alternative linker histone, but at low temperature the globular and C-terminal domains of BigH1 are essential for embryogenesis. In the presence of BigH1 nucleosome stability increases and core histone incorporation into nucleosomes is more rapid, while nucleosome spacing is unchanged. Chromatin formation in the presence of BigH1 permits the fast-paced nuclear divisions of the early embryo. We propose a model which explains how this specific linker histone ensures the rapid nucleosome reassembly required during quick replication cycles at the start of embryogenesis.
The chromatin-binding protein PHF6 functions as an E3 ubiquitin ligase of H2BK120 via H2BK12Ac recognition for activation of trophectodermal genes
Authors: Oh Sungryong , Boo Kyungjin , Kim Jaebeom , Baek Seon Ah , Jeon Yoon , You Junghyun , Lee Ho , Choi Hee-Jung , Park Daechan , Lee Ji Min , Baek Sung Hee
Published: July 2020

Epigenetic regulation is important for establishing lineage-specific gene expression during early development. Although signaling pathways have been well-studied for regulation of trophectoderm reprogramming, epigenetic regulation of trophectodermal genes with histone modification dynamics have been poorly understood. Here, we identify that plant homeodomain finger protein 6 (PHF6) is a key epigenetic regulator for activation of trophectodermal genes using RNA-sequencing and ChIP assays. PHF6 acts as an E3 ubiquitin ligase for ubiquitination of H2BK120 (H2BK120ub) via its extended plant homeodomain 1 (PHD1), while the extended PHD2 of PHF6 recognizes acetylation of H2BK12 (H2BK12Ac). Intriguingly, the recognition of H2BK12Ac by PHF6 is important for exerting its E3 ubiquitin ligase activity for H2BK120ub. Together, our data provide evidence that PHF6 is crucial for epigenetic regulation of trophectodermal gene expression by linking H2BK12Ac to H2BK120ub modification.
Pentatricopeptide repeats of protein-only RNase P use a distinct mode to recognize conserved bases and structural elements of pre-tRNA
Authors: Teramoto Takamasa , Kaitany Kipchumba J , Kakuta Yoshimitsu , Kimura Makoto , Fierke Carol A , Hall Traci M Tanaka
Published: July 2020

Pentatricopeptide repeat (PPR) motifs are α-helical structures known for their modular recognition of single-stranded RNA sequences with each motif in a tandem array binding to a single nucleotide. Protein-only RNase P 1 (PRORP1) in Arabidopsis thaliana is an endoribonuclease that uses its PPR domain to recognize precursor tRNAs (pre-tRNAs) as it catalyzes removal of the 5′-leader sequence from pre-tRNAs with its NYN metallonuclease domain. To gain insight into the mechanism by which PRORP1 recognizes tRNA, we determined a crystal structure of the PPR domain in complex with yeast tRNAPhe at 2.85 Å resolution. The PPR domain of PRORP1 bound to the structurally conserved elbow of tRNA and recognized conserved structural features of tRNAs using mechanisms that are different from the established single-stranded RNA recognition mode of PPR motifs. The PRORP1 PPR domain-tRNAPhe structure revealed a conformational change of the PPR domain upon tRNA binding and moreover demonstrated the need for pronounced overall flexibility in the PRORP1 enzyme conformation for substrate recognition and catalysis. The PRORP1 PPR motifs have evolved strategies for protein-tRNA interaction analogous to tRNA recognition by the RNA component of ribonucleoprotein RNase P and other catalytic RNAs, indicating convergence on a common solution for tRNA substrate recognition.
Self-assembly of metalla[3]catenanes, Borromean rings and ring-in-ring complexes using a simple π-donor unit
Authors: Lu Ye , Liu Dong , Lin Yue-Jian , Li Zhen-Hua , Jin Guo-Xin
Published: July 2020

Despite extensive research and several stunning breakthroughs in the synthesis of interlocked molecular species, [3]catenanes, Borromean rings and ring-in-ring complexes are exceedingly rare and their targeted synthesis remains a formidable challenge. Herein, a series of Cp*Rh-based homogeneous and heterogeneous interlocked structures have been prepared by coordination-driven self-assembly, not only including metalla[2]catenanes and molecular Borromean rings, but also linear metalla[3]catenanes and ring-in-ring complexes. The interlocked structures are all based on bithiophenyl groups. The bithiophenyl groups effectively enhance the strength of the inter-ring interactions and play a crucial role in the formation of these interlocked structures. By taking advantage of the strong interaction between π-donor (D) and π-acceptor (A) groups, the electron-deficient methylviologen cation was introduced into a cationic metallarectangle based on bithiophenyl groups. Taking inspiration from these results, a cationic metallarectangle based on A units was threaded into a metallarectangle based on D units, leading to a heterogeneous D–A ring-in-ring structure.
Multiple market moralities: identifying distinct patterns in how consumers evaluate the fairness of price changes
Authors: McDonnell Erin Metz , Stoltz Dustin S , Taylor Marshall A
Published: July 2020

The default position in economic psychology is that consumers evaluate the fairness of firms' pricing strategies based on a widely shared schema of market morality, operationalized by analysing the average response within a respondent pool to a given price-change scenario. Conversely, drawing on economic and cultural sociology, we argue that there are multiple, distinctive schemas that pattern consumers’ moral evaluation of market pricing practices. We identify distinctive moral schemas by replicating and reanalysing scenarios from the foundational study of the fairness in pricing field (Kahneman et al., 1986) with a new online survey of American adults. Using correlational class analysis, we find respondents orient to one of four different configurations of moral judgement about price-change fairness: dual-entitlement principles, free-market proponents (and opponents), retail-labour domain specificity and procedural (un)fairness. This research gives analysts new tools for more precisely specifying variation in consumer moral sentiment and raises new questions about the causes, consequences and contours of multiple market moralities.
Mainstreaming Dissidence: Confronting Binary Gender in Social Work's Grand Challenges
Authors: Kroehle Kel , Shelton Jama , Clark Emilie , Seelman Kristie
Published: July 2020

To genuinely embody its commitment to anti-oppression, social work must call on a critical gender framework in its response to the Grand Challenges for Social Work. Such an approach demands that social workers move beyond reactivity to thoroughly interrogate the binary gender system upholding the gendered injustices this special issue calls us to confront. This includes a consideration of the ways a binary gender system is ideologically linked to and acts together with constructs of whiteness, nationhood, citizenship, and ability. The present article seeks to complicate the lens such that gender is not a proxy for White cisgender womanhood but rather a call to unravel webs of normative thinking. Guided by transfeminist theory, the authors examine three grand challenges—climate change, technology, and advancing long and productive lives—in an effort to detail the current and historical function of the binary gender system as a tool for the subjugation of trans and nonbinary people and to explore social work’s role in building freer and more equitable futures.
On the Effect of Asymmetrical Trait Inheritance on Models of Trait Evolution
Authors: Duchen Pablo , Alfaro Michael L , Rolland Jonathan , Salamin Nicolas , Silvestro Daniele
Published: July 2020

Current phylogenetic comparative methods modeling quantitative trait evolution generally assume that, during speciation, phenotypes are inherited identically between the two daughter species. This, however, neglects the fact that species consist of a set of individuals, each bearing its own trait value. Indeed, because descendent populations after speciation are samples of a parent population, we can expect their mean phenotypes to randomly differ from one another potentially generating a “jump” of mean phenotypes due to asymmetrical trait inheritance at cladogenesis. Here, we aim to clarify the effect of asymmetrical trait inheritance at speciation on macroevolutionary analyses, focusing on model testing and parameter estimation using some of the most common models of quantitative trait evolution. We developed an individual-based simulation framework in which the evolution of phenotypes is determined by trait changes at the individual level accumulating across generations, and cladogenesis occurs then by separation of subsets of the individuals into new lineages. Through simulations, we assess the magnitude of phenotypic jumps at cladogenesis under different modes of trait inheritance at speciation. We show that even small jumps can strongly alter both the results of model selection and parameter estimations, potentially affecting the biological interpretation of the estimated mode of evolution of a trait. Our results call for caution when interpreting analyses of trait evolution, while highlighting the importance of testing a wide range of alternative models. In the light of our findings, we propose that future methodological advances in comparative methods should more explicitly model the intraspecific variability around species mean phenotypes and how it is inherited at speciation.
Disease-Induced Microbial Shifts in Citrus Indicate Microbiome-Derived Responses to Huanglongbing Across the Disease Severity Spectrum
Authors: Ginnan Nichole A. , Dang Tyler , Bodaghi Sohrab , Ruegger Paul M. , McCollum Greg , England Gary , Vidalakis Georgios , Borneman James , Rolshausen Philippe E. , Roper M. Caroline
Published: July 2020

Plant microbiomes are critical components to plant health and can influence disease outcomes. We provide empirical data describing disease-induced shifts within the citrus microbiome at different levels of huanglongbing (HLB) disease severity. HLB is associated with an invasive phloem-limited bacterium, ‘Candidatus Liberibacter asiaticus’, that is introduced into the aerial portions of the tree by an insect vector. Disease manifests as aboveground foliar and fruit symptoms and significant root decline belowground. During the early phase of disease, there were depletions of putative keystone taxa in leaves and roots, followed by enrichments of putative beneficial taxa, suggesting a microbially derived immune response involved in plant protection that is ancillary to immune components encoded in the plant’s genome. In the late phase of disease, we observed enrichments of parasitic and saprophytic microorganisms, particularly in the roots. The community shifts within the root compartment are emblematic of a disease-induced dysbiosis where pathogens other than ‘Ca. L. asiaticus’ begin to dominate the community. Furthermore, we define key taxa enriched in trees with a slower rate of disease development, referred to as survivor trees, that are hallmarks of those found in trees in the early phase of disease that may be drivers of the survivor tree phenotype. We propose a disease ecology model that illustrates the relationship between the pathogen, the microbiome, and the host plant that highlights microorganisms that may serve as disease facilitators or antagonists.
Parastagonospora nodorum and Related Species in Western Canada: Genetic Variability and Effector Genes
Authors: Hafez Mohamed , Gourlie Ryan , Despins Therese , Turkington Thomas K. , Friesen Timothy L. , Aboukhaddour Reem
Published: July 2020

Parastagonospora nodorum is an important fungal pathogen that causes Septoria nodorum blotch (SNB) in wheat. This pathogen produces several necrotrophic effectors that act as virulence factors; three have been cloned, SnToxA, SnTox1, and SnTox3. In this study, P. nodorum and its sister species P. avenaria f. tritici (Pat1) were isolated from wheat node and grain samples collected from distanced sites in western Canada during 2018. The presence of effector genes and associated haplotypes were determined by PCR and sequence analysis. An internal transcribed spacer-restriction fragment length polymorphism test was developed to distinguish between leaf spotting pathogens (P. nodorum, Pat1, Pyrenophora tritici-repentis, and Bipolaris sorokiniana). P. nodorum was mainly recovered from wheat nodes and to a lesser extent from the grains, while Pat1 was exclusively isolated from grain samples. The effector genes were present in almost all P. nodorum isolates, with the ToxA haplotype 5 (H5) being most prevalent, while a novel ToxA haplotype (denoted here H21) is reported for the first time. In Pat1, only combinations of SnTox1 and SnTox3 genes were present. A ToxA haplotype network was also constructed to assess the evolutionary relationship among globally found haplotypes to date. Finally, cultivars representing wheat development in Canada for the last century were tested for sensitivity to Sn-effectors and to the presence of Tsn1, the ToxA sensitivity gene. Of tested cultivars, 32.9 and 56.9% were sensitive to SnTox1 and SnTox3, respectively, and Tsn1 was present in 59% of the cultivars. In conclusion, P. nodorum and Pat1 were prevalent wheat pathogens in Canada with a potential tissue-specific colonization capacity, while producing necrotrophic effectors to which wheat is sensitive.
Adult attention deficit/hyperactivity disorder in the ambulatory care setting
Authors: Hackett Adanna , Joseph Rose , Robinson Kevlin , Welsh Jeremy , Nicholas Joyce , Schmidt Eric
Published: July 2020

Adult attention deficit/hyperactivity disorder (ADHD) is a significant and prevalent disorder. ADHD can impair adults' quality of life, so clinicians in multiple specialties should be able to recognize and treat the disorder. Much of the current literature has focused on childhood ADHD. However, adult ADHD is a common comorbidity in patients with mental illness, and it is essential that patients diagnosed with the disorder are treated appropriately, which can significantly improve outcomes. Adults with untreated ADHD are more likely to have substance dependence, job instability, and an overall poorer quality of life. This article reviews the screening and assessment for adult ADHD along with pharmacologic and nonpharmacologic recommendations for the management of the disorder.
Red flags of low back pain
Authors: DePalma Michael G.
Published: July 2020

Low back pain is a frequent complaint of patients seeking care at private offices, ambulatory clinics, and EDs. Key signs and symptoms can guide clinicians in differentiating acute and persistent mechanical low back pain from back pain resulting from a specific cause. Awareness of these findings can reduce the number of missed or incorrect diagnoses that lead to poor patient outcomes. The ability to recognize the red flag findings of serious causes of low back pain ensures prompt diagnosis and initiation of appropriate treatment. This article highlights the history and physical examination findings that will improve identification of red flags associated with emergency or serious causes.
Original Research: Understanding Nursing Home Staff Attitudes Toward Death and Dying: A Survey
Authors: Bui Nhat , Halifax Elizabeth , David Daniel , Hunt Lauren , Uy Edyssa , Ritchie Christine , Stephens Caroline
Published: July 2020

Background:

Nearly 70% of nursing home residents are eligible for palliative care, yet few receive formal palliative care outside of hospice. Little is known about nursing home staff attitudes, knowledge, skills, and behaviors related to palliative care.

Methods:

We administered a modified survey measuring attitudes toward death to 146 nursing home staff members, including both clinical and nonclinical staff, from 14 nursing homes.

Results:

Nursing home staff generally reported feeling comfortable caring for the dying, but half believed the end of life is a time of great suffering. Pain control (63%), loneliness (52%), and depression (48%) were the most important issues identified with regard to these patients, and there was ambivalence about the use of strong pain medications and the utility of feeding tubes at the end of life. Top priorities identified for improving palliative care included greater family involvement (43%), education and training in pain control (50%) and in management of other symptoms (37%), and use of a palliative care team (35%) at their facility.

Conclusions:

Findings show there is a need for more palliative care training and education, which should be built on current staff knowledge, skills, and attitudes toward palliative care.
Opportunities and challenges associated with the evaluation of chimeric antigen receptor T cells in real-life
Authors: McGrath Eoin , Chabannon Christian , Terwel Sofie , Bonini Chiara , Kuball Jurgen
Published: July 2020

Purpose of review

With the approval of the first chimeric antigen receptor (CAR)-T cell products on the market, the European Medicines Agency (EMA) required market authorization holders (MAHs) to monitor the long-term efficacy and safety of CAR-T cells for 15 years after administration. In 2019, the cellular therapy module of the European Society for Blood and Marrow Transplantation (EBMT) registry received a positive qualification opinion from the EMA indicating that the registry fulfills the essential needs to capture such data. We investigated its broader implication.

Recent findings

Since 2020, the cellular therapy module of the EBMT registry captures data to support postauthorization studies for MAHs and EMA. The process toward a positive qualification opinion has attracted interest from many other stakeholders, such as scientists and Health Technology Assessment bodies, and was the spin-off for a stimulating development which defined the need for a registry to comply with regulatory requirements, and also inspired ways to deal with CAR-T cell programs in terms of center qualifications and educational standards for professionals.

The positive qualified opinion of the EBMT registry by EMA to monitor long-term efficacy and safety of commercial CAR-T cells created opportunities and challenges and was serving as linking-pin to launch a novel CAR-T cell community.
Most Orthopaedic Studies Using the National Inpatient Sample Fail to Adhere to Recommended Research Practices: A Systematic Review
Authors: Teng Teng L. , Menendez Mariano E. , Okike Kanu , Cassidy Charles , Salzler Matthew
Published: July 2020

Background

The National Inpatient Sample (NIS) database is accessible, inexpensive, and increasingly used in orthopaedic research, but it has complex design features that require nuanced methodological considerations for appropriate use and interpretation. A recent study showed poor adherence to recommended research practices for the NIS across a broad spectrum of medical and surgical fields, but the degree and patterns of nonadherence among orthopaedic publications remain unclear.

Questions/purposes

In this study, we sought: (1) to quantify nonadherence to recommended research practices provided by the Agency for Healthcare Research and Quality (AHRQ) for using the NIS data in orthopaedic studies from 2016-2017; and, (2) to identify the most common nonadherence practices.

Methods

We evaluated all 136 manuscripts published across the 74 orthopaedic journals listed on Scimago Journal & Country Rank that used the NIS from January 2016 through December 2017. Of those studies, 2% (3 of 136) were excluded because NIS was not used for analysis. The studies were evaluated for adherence to seven recommended research practices by the AHRQ: (1) identifying observations as hospitalization events rather than unique patients; (2) not performing state-level analyses; (3) limiting hospital-level analyses to data from year 1988-2011; (4) not performing physician-level analyses; (5) avoiding the use of nonspecific secondary diagnosis codes to infer in-hospital events; (6) using survey-specific analysis methods that account for clustering, stratification, and weighting; and (7) accounting for data changes in trend analyses spanning major transition periods in the data set (1997-1998 and 2011-2012).

Results

Overall, 93% (124 of 133) of the studies did not adhere to one or more practices. For each of the research practices assessed, 80% (106 of 133) of the studies did not account for the clustering and stratification in survey design; 56% (75 of 133) implied records were unique patients rather than hospitalization events; 41% (54 of 133) inappropriately used secondary diagnosis codes to infer in-hospital events.

Conclusions

Nearly all manuscripts published in orthopaedic journals using the NIS database in 2016 and 2017 failed to adhere to recommended research practices. Future research quantifying variations in study results on the basis of adherence to recommended research practices would be of value.

Clinical Relevance

With the ubiquitous presence of large-database studies in orthopaedic journals, our work points to the importance of rigorous methodological appraisal when evaluating results, and encourages journals to require the use of the methodology checklists upon submission of such studies. More research is needed to determine whether deviations from recommended research practices actually lead to biased conclusions that affect patient care and policy-related decisions.
Abaloparatide followed by alendronate in women ≥80 years with osteoporosis: post hoc analysis of ACTIVExtend
Authors: Greenspan Susan L. , Fitzpatrick Lorraine A. , Mitlak Bruce , Wang Yamei , Harvey Nicholas C. , Deal Chad , Cosman Felicia , McClung Michael
Published: July 2020

Objective:

Fracture risk increases with age, but few studies focus on persons ≥80 years. In the ACTIVE trial, treatment with abaloparatide for 18 months reduced osteoporotic fracture risk and increased bone mineral density. These effects were maintained with 24 months alendronate treatment in ACTIVExtend. We postulated that similar improvements in bone mineral density and safety would be demonstrated in women ≥80 years.

Methods:

Post hoc analyses of bone mineral density and fracture incidence in women with osteoporosis at high risk of fracture ≥80 years from ACTIVExtend.

Results:

In total, 56 women aged ≥80 years at ACTIVE baseline entered the ACTIVExtend study; 46 of these completed the study. Mean age was 83.3 years; other baseline characteristics were similar. At the end of ACTIVE, bone mineral density increased at all sites for abaloparatide versus placebo. Bone mineral density increased in parallel in both groups during alendronate therapy (19 to 43 months) in ACTIVExtend. At month 43, mean percent change in bone mineral density from baseline was 17.2% abaloparatide/alendronate versus 8.6% placebo/alendronate (P < 0.0001) at the lumbar spine, 5.3% abaloparatide/alendronate versus 3.0% placebo/alendronate (P = 0.024) at the total hip, and 4.6% abaloparatide/alendronate versus 3.1% placebo/alendronate (P = 0.044) at the femoral neck. Fracture incidence was low and did not differ significantly between groups. Sequential treatment with abaloparatide followed by alendronate was well tolerated; the proportion of participants reporting adverse events was similar between groups.

Conclusions:

Sequential treatment with abaloparatide followed by alendronate (43 months follow-up) in this small subgroup of ACTIVExtend participants suggests abaloparatide is well tolerated and effective in women aged ≥80 years.

Video Summary:
http://links.lww.com/MENO/A618.
The Role of Psychology in the Care of Children With Pancreatitis
Authors: Rich Kristin Loiselle , Abu-El-Haija Maisam , Nathan Jaimie D. , Lynch-Jordan Anne
Published: July 2020

Children with acute recurrent and chronic pancreatitis experience severe abdominal pain that may be intermittent or chronic. Pain is often debilitating, causing interference with academic, social, family, and extracurricular activities that are important to youth. Disruption of these routines and the unpredictability of pain flares place children with pancreatitis at increased risk for development of anxious or depressive symptoms. Pediatric psychologists trained in cognitive-behavioral treatment are well suited to intervene on functional disability and mood disturbance, as well as teach coping skills. In an era where there is movement away from opioids, nonpharmacological strategies have an important place for pain management. In fact, positive outcomes following for children with other recurrent abdominal pain syndromes have been reported for this evidence-based intervention. In addition to pain management, pediatric psychologists can address other co-occurring behavioral and emotional problems in children with pancreatitis, such as needle phobia and poor adherence to the prescribed medical regimen.
End-of-Life Care Among Patients With Bipolar Disorder and Cancer: A Nationwide Cohort Study
Authors: Fond Guillaume , Baumstarck Karine , Auquier Pascal , Pauly Vanessa , Bernard Cecile , Orleans Veronica , Llorca Pierre-Michel , Lancon Christophe , Salas Sebastien , Boyer Laurent
Published: July 2020

Objective

This study aimed to describe end-of-life (EOL) care in individuals with bipolar disorder (BD) who died of cancer compared with mentally healthy individuals.

Methods

This was a nationwide cohort study of all adult individuals who died of cancer in hospitals in France between 2013 and 2016. Outcomes were compared between individuals with BD and mentally healthy individuals in the last month of life including palliative care and high-intensity EOL care (chemotherapy, artificial nutrition, and other interventions). A subanalysis explored differences between patients with BD and patients with schizophrenia.

Results

The study included 2015 individuals with BD and 222,477 mentally healthy controls. Compared with the controls, individuals with BD died 5 years earlier, more often had comorbidities and thoracic cancer, and had fewer metastases, but did not have shorter delays from cancer diagnosis to death. After matching and adjustment for covariates, individuals with BD more often received palliative care in the last 3 days of life (25% versus 13%, p < .001) and less high-intensity care (e.g., chemotherapy 12% versus 15%, p = .004), but more artificial nutrition (6% versus 4.6%, p = .003). Compared with the schizophrenia comparison group, chemotherapy was received more by individuals with BD in the last 14 days of life (12.5% for BD versus 9.4%, p < .001).

Conclusions

Individuals with BD were more likely to receive palliative care and less likely to receive high-intensity EOL care, except for artificial nutrition. These results may not be specific to BD, as no difference was found between patients with BD and schizophrenia except for chemotherapy.
Hepatitis C virus modulates IgG glycosylation in HIV co-infected antiretroviral therapy suppressed individuals
Authors: Giron Leila B. , Azzoni Livio , Yin Xiangfan , Lynn Kenneth M. , Ross Brian N. , Fair Matthew , Damra Mohammad , Sciorillo Amanda C. , Liu Qin , Jacobson Jeffrey M. , Mounzer Karam , Kostman Jay R. , Abdel-Mohsen Mohamed , Montaner Luis J. , Papasavvas Emmanouil
Published: July 2020

Objective:

Glycosylation plays a critical role in mediating several antibody (mainly immunoglobulin G; IgG) immunological functions, including antibody-dependent cell-mediated cytotoxicity (ADCC), and anti-inflammatory activities. We investigated whether IgG glycosylation and immune profile patterns are differentially modulated in mono and dual infection using samples from untreated hepatitis C virus (HCV)-infected individuals with and without co-infection with antiretroviral therapy (ART)-suppressed HIV.

Design:

IgG glycosylation, immune subsets, natural killer cell function, and liver enzymes were assessed in 14 HCV mono-infected and 27 ART-suppressed HIV/HCV co-infected participants naïve to HCV treatment. Historic IgG glycosylation data from 23 ART-suppressed chronically HIV-infected individuals were also used for comparisons.

Methods:

Plasma IgG glycosylation was assessed using capillary electrophoresis. Whole blood was used for immune subset characterization by flow cytometry. Peripheral blood mononuclear cells were used to measure constitutive and interferon-α-induced K562 target cell lysis. Statistical analysis was performed using R (3.5.0).

Results:

HIV/HCV had lower levels of pro-ADCC-associated nonfucosylated glycans when compared with HIV [e.g. di-sialylated A2 percentage (%): P = 0.04], and higher levels of T and myeloid cell activation/exhaustion when compared with HCV (e.g. CD3+CD8+CD38+ %: P < 0.001). Finally, in HCV high levels of the anti-inflammatory galactosylated and sialylated glycans were associated with low plasma levels of aspartate aminotransferase (AST), low CD8+ T-cell activation, and high CD8+ T-cell exhaustion.

Conclusion:

HCV modulates IgG glycosylation profile in HIV co-infected individuals on suppressive ART. These results could inform on the modulation of IgG glycans in other mono and dual infections.
Impact of HIV on the survival of hepatocellular carcinoma in hepatitis C virus-infected patients
Authors: Merchante Nicolás , Rodríguez-Fernández Miguel , Figueruela Blanca , Rodríguez-Arrondo Francisco , Revollo Boris , Ibarra Sofía , Téllez Francisco , Merino Esperanza , Montero-Alonso Marta , Galindo María J. , Rivero-Juárez Antonio , Santos Ignacio de Los , Delgado-Fernández Marcial , García-Deltoro Miguel , Vera-Méndez Francisco J. , García María A. , Aguirrebengoa Koldo , Portu Joseba , Ríos-Villegas María J. , Villalobos Marina , Alemán-Valls María R. , Mínguez Carlos , Galera Carlos , Macías Juan , Pineda Juan A.
Published: July 2020

Background:

Previous studies have suggested that hepatocellular carcinoma (HCC) has an aggressive presentation and a shorter survival in people with HIV (PWH). This could be due to later diagnosis or lower rates of HCC treatment, and not to HIV infection itself.

Aim: :

To assess the impact of HIV on HCC survival in hepatitis C virus (HCV)-infected patients.

Methods:

Multicenter cohort study (1999–2018) of 342 and 135 HCC cases diagnosed in HIV/HCV-infected and HCV-monoinfected patients. Survival after HCC diagnosis and its predictors were assessed.

Results:

HCC was at Barcelona-Clinic Liver-Cancer (BCLC) stage 0/A in 114 (33%) HIV/HCV-coinfected and in 76 (56%) HCV-monoinfected individuals (P < 0.001). Of them, 97 (85%) and 50 (68%) underwent curative therapies (P = 0.001). After a median (Q1–Q3) follow-up of 11 (3–31) months, 334 (70%) patients died. Overall 1 and 3-year survival was 50 and 31% in PWH and 69 and 34% in those without HIV (P = 0.16). Among those diagnosed at BCLC stage 0/A, 1 and 3-year survival was 94 and 66% in PWH whereas it was 90 and 54% in HIV-negative patients (P = 0.006). Independent predictors of mortality were age, BCLC stage and α-fetoprotein levels. HIV infection was not independently associated with mortality [adjusted hazard ratio (AHR) 1.57; 95% confidence interval: 0.88–2.78; P = 0.12].

Conclusion:

HIV coinfection has no impact on the survival after the diagnosis of HCC in HCV-infected patients. Although overall mortality is higher in HIV/HCV-coinfected patients, this seem to be related with lower rates of early diagnosis HCC in HIV-infected patients and not with HIV infection itself or a lower access to HCC therapy.