bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term outcomes after ascending aortic replacement and aortic root replacement for type A aortic dissection
Authors: Jormalainen Mikko , Kesävuori Risto , Raivio Peter , Vento Antti , Mustonen Caius , Honkanen Hannu-Pekka , Rosato Stefano , Simpanen Jarmo , Teittinen Kari , Biancari Fausto , Juvonen Tatu
Published: November 2021

OBJECTIVES

We investigated whether the selective use of supracoronary ascending aorta replacement achieves late outcomes comparable to those of aortic root replacement for acute Stanford type A aortic dissection (TAAD).

METHODS

Patients who underwent surgery for acute type A aortic dissection from 2005 to 2018 at the Helsinki University Hospital, Finland, were included in this analysis. Late mortality was evaluated with the Kaplan–Meier method and proximal aortic reoperation, i.e. operation on the aortic root or aortic valve, with the competing risk method.

RESULTS

Out of 309 patients, 216 underwent supracoronary ascending aortic replacement and 93 had aortic root replacement. At 10 years, mortality was 33.8% after aortic root replacement and 35.2% after ascending aortic replacement (P = 0.806, adjusted hazard ratio 1.25, 95% confidence interval, 0.77–2.02), and the cumulative incidence of proximal aortic reoperation was 6.0% in the aortic root replacement group and 6.2% in the ascending aortic replacement group (P = 0.65; adjusted subdistributional hazard ratio 0.53, 95% confidence interval 0.15–1.89). Among 71 propensity score matched pairs, 10-year survival was 34.4% after aortic root replacement and 36.2% after ascending aortic replacement surgery (P = 0.70). Cumulative incidence of proximal aortic reoperation was 7.0% after aortic root replacement and 13.0% after ascending aortic replacement surgery (P = 0.22). Among 102 patients with complete imaging data [mean follow-up, 4.7 (3.2) years], the estimated growth rate of the aortic root diameter was 0.22 mm/year, that of its area 7.19 mm2/year and that of its perimeter 0.43 mm/year.

CONCLUSIONS

When stringent selection criteria were used to determine the extent of proximal aortic reconstruction, aortic root replacement and ascending aortic replacement for type A aortic dissection achieved comparable clinical outcomes.
Integron detection for prediction of trimethoprim/sulfamethoxazole susceptibility in children with Enterobacterales urinary tract infections
Authors: Elias Peter , Barraud Olivier , El Hamel Chahrazed , Chainier Delphine , Dallochio Aymeric , Grélaud Carole , Ploy Marie-Cécile , Guigonis Vincent , Garnier Fabien
Published: November 2021

Objectives

In some countries, third-generation cephalosporins (3GCs) serve as first-line therapy in children with urinary tract infections (UTIs). However, their use may contribute to the emergence of antibiotic resistance, notably among Gram-negative bacteria (GNB). Integrons are bacterial genetic elements involved in antibiotic resistance in GNB. Their absence is associated with >97% susceptibility to trimethoprim/sulfamethoxazole in adults infected with GNB. The objective of this study was to examine the value of integron detection directly from urine samples as a predictive marker of resistance to trimethoprim/sulfamethoxazole in children with GNB-related UTIs.

Methods

Children admitted to the Limoges University Hospital’s paediatric emergency department between February 2018 and March 2019 with a suspicion of UTI were eligible for the study. Only confirmed cases presenting a positive urine culture with unique GNB were retained for further study analyses. Integrons were detected directly from urines using real-time PCR.

Results

The data of 72 patients were analysed and integrons were detected in 15 urine samples. The negative predictive value of integron detection for resistance to trimethoprim/sulfamethoxazole was 100% as all of the GNB (all were Enterobacterales) isolated from patients with no integrons detected in their urine samples were susceptible to trimethoprim/sulfamethoxazole.

Conclusions

The detection of integrons in cases of paediatric patients with suspected UTI could help limit 3GC empirical use and empower an empirical first-line strategy better tailored to the needs of each patient.
C-reactive protein-guided use of procalcitonin in COVID-19
Authors: Houghton Rebecca , Moore Nathan , Williams Rebecca , El-Bakri Fatima , Peters Jonathan , Mori Matilde , Vernet Gabrielle , Lynch Jessica , Lewis Henry , Tavener Maryanna , Durham Tom , Bowyer Jack , Saeed Kordo , Pollara Gabriele
Published: November 2021

Background

A low procalcitonin (PCT) concentration facilitates exclusion of bacterial co-infections in COVID-19, but high costs associated with PCT measurements preclude universal adoption. Changes in inflammatory markers, including C-reactive protein (CRP), can be concordant, and predicting low PCT concentrations may avoid costs of redundant tests and support more cost-effective deployment of this diagnostic biomarker.

Objectives

To explore whether, in COVID-19, low PCT values could be predicted by the presence of low CRP concentrations.

Methods

Unselected cohort of 224 COVID-19 patients admitted to hospital that underwent daily PCT and CRP measurements as standard care. Both 0.25 ng/mL and 0.5 ng/mL were used as cut-offs for positive PCT test results. Geometric mean was used to define high and low CRP values at each timepoint assessed.

Results

Admission PCT was <0.25 ng/mL in 160/224 (71.4%), 0.25–0.5 ng/mL in 27 (12.0%) and >0.5 ng/mL in 37 (16.5%). Elevated PCT was associated with increased risk of death (P = 0.0004) and was more commonly associated with microbiological evidence of bacterial co-infection (P < 0.0001). For high CRP values, significant heterogeneity in PCT measurements was observed, with maximal positive predictive value of 50% even for a PCT cut-off of 0.25 ng/mL. In contrast, low CRP was strongly predictive of low PCT concentrations, particularly <0.5 ng/mL, with a negative predictive value of 97.6% at time of hospital admission and 100% 48 hours into hospital stay.

Conclusions

CRP-guided PCT testing algorithms can reduce unnecessary PCT measurement and costs, supporting antimicrobial stewardship strategies in COVID-19.
Live yeast and yeast extracts with and without pharmacological levels of zinc on nursery pig growth performance and antimicrobial susceptibilities of fecalEscherichia coli
Authors: Chance Jenna A , DeRouchey Joel M , Amachawadi Raghavendra G , Ishengoma Victor , Nagaraja Tiruvoor G , Goodband Robert D , Woodworth Jason C , Tokach Mike D , Calderón Hilda I , Kang Qing , Loughmiller Joseph A , Hotze Brian , Gebhardt Jordan T
Published: November 2021

A total of 360 weanling barrows (Line 200 ×400, DNA, Columbus NE; initially 5.6 ± 0.03 kg) were used in a 42-d study to evaluate yeast-based pre- and probiotics (Phileo by Lesaffre, Milwaukee, WI) in diets with or without pharmacological levels of Zn on growth performance and antimicrobial resistance (AMR) patterns of fecal Escherichia coli. Pens were assigned to one of four dietary treatments with five pigs per pen and 18 pens per treatment. Dietary treatments were arranged in a 2 × 2 factorial with main effects of yeast-based pre- and probiotics (none vs. 0.10% ActiSaf Sc 47 HR+, 0.05% SafMannan, and 0.05% NucleoSaf from days 0 to 7, then concentrations were lowered by 50% from days 7 to 21) and pharmacological levels of Zn (110 vs. 3,000 mg/kg from days 0 to 7, and 2,000 mg/kg from days 7 to 21 with added Zn provided by ZnO). All pigs were fed a common diet from days 21 to 42 post-weaning. There were no yeast ×Zn interactions or effects from yeast additives observed on any response criteria. From days 0 to 21 and 0 to 42, pigs fed pharmacological levels of Zn had increased (P < 0.001) ADG and ADFI. Fecal samples were collected on days 4, 21, and 42 from the same three pigs per pen for fecal dry matter (DM) and AMR patterns of E. coli. On day 4, pigs fed pharmacological levels of Zn had greater fecal DM (P = 0.043); however, no differences were observed on day 21 or 42. Escherichia coli was isolated from fecal samples and the microbroth dilution method was used to determine the minimal inhibitory concentrations (MIC) of E. coli isolates to 14 different antimicrobials. Isolates were categorized as either susceptible, intermediate, or resistant based on Clinical and Laboratory Standards Institute (CLSI) guidelines. The addition of pharmacological levels of Zn had a tendency (P = 0.051) to increase the MIC values of ciprofloxacin; however, these MIC values were still well under the CLSI classified resistant breakpoint for ciprofloxacin. There was no evidence for differences (P > 0.10) for yeast additives or Zn for AMR of fecal E. coli isolates to any of the remaining antibiotics. In conclusion, pharmacological levels of Zn improved ADG, ADFI, and all isolates were classified as susceptible to ciprofloxacin although the MIC of fecal E. coli tended to be increased. Thus, the short-term use of pharmacological levels of Zn did not increase antimicrobial resistance. There was no response observed from live yeast and yeast extracts for any of the growth, fecal DM, or AMR of fecal E. coli criteria.
The (In)visible Woman at the International Monetary Fund: Engendering National Economic Rule-making
Authors: Duran Camila Villard
Published: November 2021

For decades, the International Monetary Fund (IMF) was silent about gender inequality. In 2013, the IMF finally adopted a discourse linking macroeconomic stability and gender inequality. Engendering means the integration of gender equality into the IMF’s activities, thus, generating change. By deploying different institutional mechanisms (e.g. the Article IV reports and conditionality in exchange for financial support), the IMF is contributing to engendering economic rulemaking process at the national level. Discourses matter. Economic laws at national level are shaped by the IMF’s ideas: the meaning-making process of rules at the global level is an integral part of the economic rulemaking process at the national level. Particularly, legal ideas are key to explain the structure of the IMF’s discourse and its potential to promote gender equality. The IMF is an important case study to understand the mechanisms of engendering international organizations with important repercussions for other international institutions.
Caecal volvulus: high index of suspicion is the key to early diagnosis
Authors: Rout Alexandra , Pillai Sandhya
Published: November 2021

Caecal volvulus represents an uncommon acute surgical presentation of bowel obstruction. Familiarity with particular long-term symptoms and pre-disposing factors can help a clinician identify caecal volvulus as a possible diagnosis. There has been a changing vogue of radiological investigation and surgical interventions. We present a summary of these options.
Protecting the Identity of Participants in Qualitative Research
Authors: Pascale Joanne , Lineback Joanna Fane , Bates Nancy , Beatty Paul
Published: November 2021

Social science researchers rely on study participants to provide information about themselves, and pledging to protect their identities is generally standard practice. This is usually specified through professional associations or policies and laws governing research agencies and institutions. Conventional methods of protecting participants’ identities in quantitative research are undergoing a major overhaul in response to relatively new threats brought about by the sheer volume of large publicly available datasets along with powerful and affordable computing capabilities that enable data linkages and respondent re-identification. These developments have raised new questions about qualitative research products that previously may have been considered less vulnerable to re-identification. In this paper, we first summarize a range of conventional methods of protecting respondents’ identities used in both quantitative and qualitative research. We then discuss the relatively new threats to confidentiality brought about by the internet, computing, and social media age. Next, we bring the focus to qualitative research specifically and discuss the development of a novel approach to a systematic method of disclosure avoidance for at least a subset of qualitative research products: typical research aimed at pretesting and evaluation of survey questions, data collection instruments, and related materials used for household surveys in the federal statistical system. We frame the discussion in terms of risk and mitigation. That is, we aim to articulate the nature of qualitative methods and data, the risks posed by the dissemination of qualitative information products, and consider how these risks might reasonably be mitigated while maximizing utility. Finally, we pull back the lens and discuss how the method could be applied to research outside the context of the federal statistical system if certain criteria are met.
Detective Fictions: The ‘baby-farming detective’ in Britain, 1867–97
Authors: Hinks Jim
Published: November 2021

This article examines a series of investigations into the activities of women engaged in the provision of paid childcare and collectively labelled with the term ‘baby-farmer’. This paper looks at the practice of writers representing themselves as ‘baby-farming detectives’. Along with exploring the use of the detective investigation as a stylistic device, it will contend that the strictures it imposed informed the relationship these writers have with paid child-carers. The article also explores how the notion of ‘detectives’ and ‘suspects’ spoke of an assumed right to subject working-class women to inspection. It concludes that these detective fantasies were ultimately unsuccessful as they were unable to solve either the cases they encountered, or the symbolic problem of baby-farming, leaving these narratives curiously unresolved and their writers impotent. This article not only seeks to explain how and why the link between pecuniary childcare and infant murder was forged and maintained but asserts that this narrative technique has wider implications for scholars of nineteenth-century culture.
The impact of the Internet on migration aspirations and intentions
Authors: Grubanov-Boskovic Sara , Kalantaryan Sona , Migali Silvia , Scipioni Marco
Published: November 2021

This study investigates the relationship between Internet access and migration aspirations and intentions in Africa. While empirical evidence on the role of telecommunications in shaping migration flows is increasing, the relationship between aspirations (desire to migrate) and intentions (migration preparation) has been paid little attention. The analysis is based on the nationally representative 2014 and 2015 surveys of Gallup World Poll in 29 African countries. We modelled migration desire and migration preparation through Probit and Heckman Probit models. The results indicate that having Internet access is positively associated with the desire to move abroad and preparations to migrate once controlling for the socio-demographic characteristics of the respondents. The association is higher in the case of migration preparation than in the case of migration desire. Slightly diverse effects are documented in low- and lower-middle-income countries, where the effect of Internet access on migration desire is somewhat higher than in the sample as a whole.
Deuterated ammonia in Galactic massive star-forming regions
Authors: Li Yuqiang , Wang Junzhi , Li Juan , Liu Shu , Luo Qiuyi
Published: November 2021

We present sensitive observations of NH2D $1_{11}^\mathrm{ a}\!-\!1_{01}^\mathrm{ s}$ at 110.153 599 GHz toward 50 Galactic massive star-forming regions with the Institut de Radioastronomie Millimétrique (IRAM) 30-m telescope. The NH2D $1_{11}^\mathrm{ a}\!-\!1_{01}^\mathrm{ s}$ transition is detected toward 36 objects, yielding a detection rate of 72 per cent. Column densities of NH2D, HC3N, and C18O for each source are derived by assuming local thermal equilibrium conditions with a fixed excitation temperature. The deuterium ratio of NH3, defined as the abundance ratio of NH2D to NH3, for 19 sources is also obtained with the NH3 information from the literature. The range of deuterium fractionation bends to be large in the late-stage star-forming regions in this work, with the value from 0.043 to 0.0006. The highest deuterium ratio of NH3 is 0.043 in G081.75+00.78 (DR21). We also find that the deuterium ratio of NH3 increases with Galactocentric distance and decreases with line width.
Multiple components in the molecular outflow of the red supergiant NML Cyg
Authors: Andrews H , De Beck E , Hirvonen P
Published: November 2021

Despite their large impact on stellar and galactic evolution, the properties of outflows from red supergiants are not well characterized. We used the Onsala 20m telescope to perform a spectral survey at 3 and 4 mm (68–116  GHz) of the red supergiant NML Cyg, alongside the yellow hypergiant IRC + 10420. Our observations of NML Cyg were combined with complementary archival data to enable a search for signatures of morphological complexity in the circumstellar environment, using emission lines from 15 molecular species. The recovered parameters imply the presence of three distinct, coherent, and persistent components, comprised of blue-shifted and red-shifted components, in addition to an underlying outflow centred at the stellar systemic velocity. Furthermore, to reproduce 12CO emission with 3D radiative transfer models required a spherical outflow with three superposed conical outflows, one towards and one away from the observer, and one in the plane of the sky. These components are higher in density than the spherical outflow by up to an order of magnitude. We hence propose that NML Cyg’s circumstellar environment consists of a small number of high-density large-scale coherent outflows embedded in a spherical wind. This would make the mass-loss history similar to that of VY CMa, and distinct from μ Cep, where the outflow contains many randomly distributed smaller clumps. A possible correlation between stellar properties, outflow structures, and content is critical in understanding the evolution of massive stars and their environmental impact.
Evolutionary Processes in the Emergence and Recent Spread of the Syphilis Agent,Treponema pallidum
Authors: Pla-Díaz Marta , Sánchez-Busó Leonor , Giacani Lorenzo , Šmajs David , Bosshard Philipp P , Bagheri Homayoun C , Schuenemann Verena J , Nieselt Kay , Arora Natasha , González-Candelas Fernando
Published: November 2021

The incidence of syphilis has risen worldwide in the last decade in spite of being an easily treated infection. The causative agent of this sexually transmitted disease is the bacterium Treponema pallidum subspecies pallidum (TPA), very closely related to subsp. pertenue (TPE) and endemicum (TEN), responsible for the human treponematoses yaws and bejel, respectively. Although much focus has been placed on the question of the spatial and temporary origins of TPA, the processes driving the evolution and epidemiological spread of TPA since its divergence from TPE and TEN are not well understood. Here, we investigate the effects of recombination and selection as forces of genetic diversity and differentiation acting during the evolution of T. pallidum subspecies. Using a custom-tailored procedure, named phylogenetic incongruence method, with 75 complete genome sequences, we found strong evidence for recombination among the T. pallidum subspecies, involving 12 genes and 21 events. In most cases, only one recombination event per gene was detected and all but one event corresponded to intersubspecies transfers, from TPE/TEN to TPA. We found a clear signal of natural selection acting on the recombinant genes, which is more intense in their recombinant regions. The phylogenetic location of the recombination events detected and the functional role of the genes with signals of positive selection suggest that these evolutionary processes had a key role in the evolution and recent expansion of the syphilis bacteria and significant implications for the selection of vaccine candidates and the design of a broadly protective syphilis vaccine.
Beneficial effects of apremilast on genital ulcers, skin lesions, and arthritis in patients with Behçet’s disease: A systematic review and meta-analysis
Authors: Iizuka Yuki , Takase-Minegishi Kaoru , Hirahara Lisa , Kirino Yohei , Soejima Yutaro , Namkoong H o , Horita Nobuyuki , Yoshimi Ryusuke , Takeuchi Masaki , Takeno Mitsuhiro , Mizuki Nobuhisa , Nakajima Hideaki
Published: November 2021

Objectives

This study aimed to determine the clinical efficacy of apremilast for oral ulcers (OUs), extra-oral manifestations, and overall disease activity in patients with Behçet’s disease (BD).

Methods

A systematic literature search was performed in PubMed, Embase, Cochrane Library, and Web of Science Core Collection. Studies assessing the treatment effects of apremilast in BD were included. The odds ratios (ORs) of being symptom-free for individual manifestations and mean difference (MD) of Behçet’s Disease Current Activity Form (BDCAF) scores were calculated with 95% confidence intervals (CIs) at 12 and 24 weeks using a random-model meta-analysis.

Results

Of 259 screened articles, eight were included. After 12 weeks of apremilast treatment the OR of symptom-free was as followings: OUs, 45.76 (95% CI, 13.23–158.31); genital ulcers, 4.56 (95% CI, 2.47–8.44); erythema nodosum, 3.59 (95% CI, 1.11–11.61); pseudofolliculitis, 2.81 (95% CI, 1.29–6.15); and arthritis, 3.55 (95% CI, 1.71–7.40). Furthermore, BDCAF scores at 12 weeks were significantly reduced (MD=−1.38; −1.78 to −0.99). However, the proportion of oral-ulcer-free patients increased at 24 weeks (OR = 14.88; 4.81 to 46.07).

Conclusions

The currently accumulated data indicate an improvement in mucocutaneous and articular symptoms by short-term apremilast treatment in patients with BD.
Rhea, the reaction knowledgebase in 2022
Authors: Bansal Parit , Morgat Anne , Axelsen Kristian B , Muthukrishnan Venkatesh , Coudert Elisabeth , Aimo Lucila , Hyka-Nouspikel Nevila , Gasteiger Elisabeth , Kerhornou Arnaud , Neto Teresa Batista , Pozzato Monica , Blatter Marie-Claude , Ignatchenko Alex , Redaschi Nicole , Bridge Alan
Published: November 2021

Rhea (https://www.rhea-db.org) is an expert-curated knowledgebase of biochemical reactions based on the chemical ontology ChEBI (Chemical Entities of Biological Interest) (https://www.ebi.ac.uk/chebi). In this paper, we describe a number of key developments in Rhea since our last report in the database issue of Nucleic Acids Research in 2019. These include improved reaction coverage in Rhea, the adoption of Rhea as the reference vocabulary for enzyme annotation in the UniProt knowledgebase UniProtKB (https://www.uniprot.org), the development of a new Rhea website, and the designation of Rhea as an ELIXIR Core Data Resource. We hope that these and other developments will enhance the utility of Rhea as a reference resource to study and engineer enzymes and the metabolic systems in which they function.
Regulation of PDGFR-β gene expression by targeting the G-vacancy bearing G-quadruplex in promoter
Authors: Chen Juan-nan , He Yi-de , Liang Hui-ting , Cai Ting-ting , Chen Qi , Zheng Ke-wei
Published: November 2021

G-quadruplex is an essential element in gene transcription that serves as a promising drug target. Guanine-vacancy-bearing G-quadruplex (GVBQ) is a newly identified G-quadruplex that has distinct structural features from the canonical G-quadruplex. Potential GVBQ-forming motifs are widely distributed in gene promoter regions. However, whether GVBQ can form in genomic DNA and be an effective target for manipulating gene expression is unknown. Using photo-crosslinking, dimethyl sulfate footprinting, exonuclease digestion and in vitro transcription, we demonstrated the formation of a GVBQ in the G-rich nuclease hypersensitivity element within the human PDGFR-β gene promoter region in both single-stranded and double-stranded DNA. The formation of GVBQ in dsDNA could be induced by negative supercoiling created by downstream transcription. We also found that the PDGFR-β GVBQ was specifically recognized and stabilized by a new synthetic porphyrin guanine conjugate (mPG). Targeting the PDGFR-β GVBQ in human cancer cells using the mPG could specifically alter PDGFR-β gene expression. Our work illustrates that targeting GVBQ with mPG in human cells can regulate the expression level of a specific gene, thus indicating a novel strategy for drug development.
Chromosome segregation in Archaea: SegA– and SegB–DNA complex structures provide insights into segrosome assembly
Authors: Yen Cheng-Yi , Lin Min-Guan , Chen Bo-Wei , Ng Irene W , Read Nicholas , Kabli Azhar F , Wu Che-Ting , Shen Yo-You , Chen Chen-Hao , Barillà Daniela , Sun Yuh-Ju , Hsiao Chwan-Deng
Published: November 2021

Genome segregation is a vital process in all organisms. Chromosome partitioning remains obscure in Archaea, the third domain of life. Here, we investigated the SegAB system from Sulfolobus solfataricus. SegA is a ParA Walker-type ATPase and SegB is a site-specific DNA-binding protein. We determined the structures of both proteins and those of SegA–DNA and SegB–DNA complexes. The SegA structure revealed an atypical, novel non-sandwich dimer that binds DNA either in the presence or in the absence of ATP. The SegB structure disclosed a ribbon–helix–helix motif through which the protein binds DNA site specifically. The association of multiple interacting SegB dimers with the DNA results in a higher order chromatin-like structure. The unstructured SegB N-terminus plays an essential catalytic role in stimulating SegA ATPase activity and an architectural regulatory role in segrosome (SegA–SegB–DNA) formation. Electron microscopy results also provide a compact ring-like segrosome structure related to chromosome organization. These findings contribute a novel mechanistic perspective on archaeal chromosome segregation.
The hyperthermophilic archaeon Thermococcus kodakarensis is resistant to pervasive negative supercoiling activity of DNA gyrase
Authors: Villain Paul , da Cunha Violette , Villain Etienne , Forterre Patrick , Oberto Jacques , Catchpole Ryan , Basta Tamara
Published: November 2021

In all cells, DNA topoisomerases dynamically regulate DNA supercoiling allowing essential DNA processes such as transcription and replication to occur. How this complex system emerged in the course of evolution is poorly understood. Intriguingly, a single horizontal gene transfer event led to the successful establishment of bacterial gyrase in Archaea, but its emergent function remains a mystery. To better understand the challenges associated with the establishment of pervasive negative supercoiling activity, we expressed the gyrase of the bacterium Thermotoga maritima in a naïve archaeon Thermococcus kodakarensis which naturally has positively supercoiled DNA. We found that the gyrase was catalytically active in T. kodakarensis leading to strong negative supercoiling of plasmid DNA which was stably maintained over at least eighty generations. An increased sensitivity of gyrase-expressing T. kodakarensis to ciprofloxacin suggested that gyrase also modulated chromosomal topology. Accordingly, global transcriptome analyses revealed large scale gene expression deregulation and identified a subset of genes responding to the negative supercoiling activity of gyrase. Surprisingly, the artificially introduced dominant negative supercoiling activity did not have a measurable effect on T. kodakarensis growth rate. Our data suggest that gyrase can become established in Thermococcales archaea without critically interfering with DNA transaction processes.
Reevaluating surgery and re-irradiation for locally recurrent pediatric ependymoma—a multi-institutional study
Authors: Mak David Y , Laperriere Normand , Ramaswamy Vijay , Bouffet Eric , Murray Jeffrey C , McNall-Knapp Rene Y , Bielamowicz Kevin , Paulino Arnold C , Zaky Wafik , McGovern Susan L , Okcu M Fatih , Tabori Uri , Atwi Doaa , Dirks Peter B , Taylor Michael D , Tsang Derek S , Bavle Abhishek
Published: November 2021

Background

The goal of this study was to evaluate extent of surgical resection, and timing and volume of re-irradiation, on survival for children with locally recurrent ependymoma.

Methods

Children with locally recurrent ependymoma treated with a second course of fractionated radiotherapy (RT2) from 6 North American cancer centers were reviewed. The index time was from the start of RT2 unless otherwise stated.

Results

Thirty-five patients were included in the study. The median doses for first radiation (RT1) and RT2 were 55.8 and 54 Gy, respectively. Median follow-up time was 5.6 years. Median overall survival (OS) for all patients from RT2 was 65 months. Gross total resection (GTR) was performed in 46% and 66% of patients prior to RT1 and RT2, respectively. GTR prior to RT2 was independently associated with improved progression-free survival (PFS) for all patients (HR 0.41, P = 0.04), with an OS benefit (HR 0.26, P = 0.03) for infratentorial tumors. Median PFS was superior with craniospinal irradiation (CSI) RT2 (not reached) compared to focal RT2 (56.9 months; log-rank P = 0.03). All distant failures (except one) occurred after focal RT2. Local failures after focal RT2 were predominantly in patients with less than GTR pre-RT2.

Conclusions

Patients with locally recurrent pediatric ependymoma should be considered for re-treatment with repeat maximal safe resection (ideally GTR) and CSI re-irradiation, with careful discussion of the potential side effects of these treatments.
What Helps and What Hinders the Creation of a Smoke-free Home: A Qualitative Study of Fathers in Scotland
Authors: O’Donnell Rachel , McCulloch Peter , Greaves Lorraine , Semple Sean , Amos Amanda
Published: November 2021

Introduction

Few studies have explored fathers’ views and experiences of creating a smoke-free home, with interventions largely targeting mothers. This study aimed to identify barriers and facilitators to fathers creating a smoke-free home, to inform future intervention development.

Methods

Eighteen fathers who were smokers and lived in Scotland were recruited from Dads’ community groups, Early Years Centres and through social media advertising. Semi-structured interviews explored their views and experiences of creating a smoke-free home. A theory-informed thematic analysis using the COM-B model highlighted ways in which capability, opportunity, and motivations shaped fathers’ home smoking behaviors.

Results

Several fathers understood the health risks of second-hand smoke exposure through public health messaging associated with recent smoke-free legislation prohibiting smoking in cars carrying children. Limited understanding of effective exposure reduction strategies and personal mental health challenges reduced some fathers’ ability to create a smoke-free home. Fathers were keen to maintain their smoke-free home rules, and their motivations for this largely centered on their perceived role as protector of their children, and their desire to be a good role model.

Conclusions

Fathers’ abilities to create a smoke-free home are shaped by a range of capabilities, opportunities, and motivations, some of which relate to their role as a father. Establishing a fuller understanding of the contextual and gender-specific factors that shape fathers’ views on smoking in the home will facilitate the development of interventions and initiatives that fathers can identify and engage with, for the broader benefit of families and to improve gender equity and health.

Implications

Our findings can inform future development of father-centered and household-level smoke-free home interventions. They identify fathers’ views and experiences and help reframe smoking in the home as a gendered family-wide issue, which is important in building consensus on how best to support parents to create a smoke-free home. Our findings highlight the need for additional research to develop understanding of the ways in which gender-related aspects of family structures, heterosexual relationships, and child living arrangements influence home smoking rules and how to tailor interventions accordingly.
Age-Related Interactions on Key Theoretical Determinants of Smoking Cessation: Findings from the ITC Four Country Smoking and Vaping Surveys (2016–2020)
Authors: Le Grande Michael , Borland Ron , Yong Hua-Hie , McNeill Ann , Fong Geoffrey , Cummings K Michael
Published: November 2021

Background

This paper explores whether plans to quit, wanting to quit, and quit efficacy add predictive value over measures of habit strength and dependence in making quit attempts and/or attaining smoking abstinence.

Aims and Methods

We used three waves of the International Tobacco Control (ITC) Four Country Smoking and Vaping Survey conducted in 2016, 2018, and 2020. Baseline daily smokers (N = 6710) who provided data for at least one wave-to-wave transition (W1 to W2, N = 3511 or W2 to W3, N = 3199) and provided outcome data at the next wave (follow-up) formed the analytic sample. Generalized estimating equations (GEE) logistic regression analyses examined predictors of quit attempts and abstinence at follow-up (1- and 6-month sustained abstinence).

Results

Wanting and planning to quit were significantly positively associated with making quit attempts, but negatively associated with smoking abstinence. A significant interaction between the Heaviness of Smoking Index and age warranted an age-stratified analysis for both abstinence outcomes. Lower HSI predicted abstinence in only the younger smokers Motivation and plans to quit were positively associated with abstinence in younger smokers, but surprisingly were negatively associated with abstinence in older smokers. Quit efficacy was associated with abstinence in the older, but not the younger smokers.

Conclusions

Models of smoking abstinence are significantly improved by including motivational predictors of smoking. Age was an important moderator of the association between abstinence for both dependence and motivational variables.

Implications

The findings from this large cohort study indicate there are age-related differences in predictors of smoking abstinence but not quit attempts. These associations may reflect differential experiences of older and younger cohorts of smokers, which may have implications for interventions to motivate and assist smokers in quitting.
A Measure of Illness Awareness in Individuals With Nicotine Dependence—Nicotine Use Awareness and Insight Scale
Authors: Kim Julia , Kambari Yasaman , Taggar Anmol , Quilty Lena C , Selby Peter , Caravaggio Fernando , Ueno Fumihiko , Song Jianmeng , Pollock Bruce G , Graff-Guerrero Ariel , Gerretsen Philip
Published: November 2021

Introduction

Impaired illness awareness or the inability to recognize that one has a dependence on nicotine may be a major barrier to seeking cessation treatment. To better understand the role of impaired illness awareness on treatment-seeking behavior and clinical outcomes, we developed and examined the psychometric properties of a novel scale measuring illness awareness in individuals with dependence on nicotine.

Aims and Methods

We developed the Nicotine Use Awareness and Insight Scale (NAS), a 7-item self-report measure to assess the theoretical construct of illness awareness in individuals with dependence on nicotine (www.illnessawarenessscales.com). Data from participants 18 years of age or older were collected via a web-based survey company, Dynata. Participants with moderate dependence on nicotine were included, defined by a score of four or more on the Fagerström Test for Cigarette Dependence (FTCD) or the FTCD adapted for electronic cigarettes (eFTCD).

Results

A total of 100 participants (mean [SD] age = 49.1 [16.1] years, 52% women) that met the inclusion criteria for either FTCD (n = 50) or eFTCD (n = 50) were included. The NAS demonstrated good convergent (r = .74, p < .001) and discriminant validity (r = .03, p = .786). It also demonstrated good internal consistency (Cronbach’s alpha = 0.78) and one-month test-retest reliability (intra-class correlation = 0.86). An exploratory factor analysis yielded the retention of two components.

Conclusions

The NAS is a novel scale to asses illness awareness in individuals with dependence on nicotine. This study provides initial support for the psychometric validity and reliability of NAS.

Implications

The NAS may be used in research and clinical practice to evaluate the impact of impaired illness awareness on treatment-seeking behavior and clinical outcomes.
CFM6 is an Essential CRM Protein Required for the Splicing ofnad5Transcript in Arabidopsis Mitochondria
Authors: Lin Wei-Chih , Chen Ya-Huei , Gu Shin-Yuan , Shen Hwei-Ling , Huang Kai-Chau , Lin Wen-Dar , Chang Men-Chi , Chang Ing-Feng , Hong Chwan-Yang , Cheng Wan-Hsing
Published: November 2021

Plant chloroplast RNA splicing and ribosome maturation (CRM)-domain-containing proteins are capable of binding RNA to facilitate the splicing of group I or II introns in chloroplasts, but their functions in mitochondria are less clear. In the present study, Arabidopsis thaliana CFM6, a protein with a single CRM domain, was expressed in most plant tissues, particularly in flower tissues, and restricted to mitochondria. Mutation of CFM6 causes severe growth defects, including stunted growth, curled leaves, delayed embryogenesis and pollen development. CFM6 functions specifically in the splicing of group II intron 4 of nad5, which encodes a subunit of mitochondrial complex I, as evidenced by the loss of nad5 intron 4 splicing and high accumulation of its pretranscripts in cfm6 mutants. The phenotypic and splicing defects of cfm6 were rescued in transgenic plants overexpressing 35S::CFM6-YFP. Splicing failure in cfm6 also led to the loss of complex I activity and to its improper assembly. Moreover, dysfunction of complex I induced the expression of proteins or genes involved in alternative respiratory pathways in cfm6. Collectively, CFM6, a previously uncharacterized CRM domain-containing protein, is specifically involved in the cis-splicing of nad5 intron 4 and plays a pivotal role in mitochondrial complex I biogenesis and normal plant growth.
Early Paleogene Magmatism in the Pinaleño Mountains, Arizona: Evidence for Crustal Melting of Diverse Basement Assemblages during the Laramide Orogeny
Authors: Scoggin Shane H , Chapman James B , Shields Jessie E , Trzinski Adam E , Ducea Mihai N
Published: November 2021

Granitic rocks, interpreted to be related to crustal melting, were emplaced into regions of thickened crust in southern Arizona during the Laramide orogeny (80–40 Ma). Laramide-age anatectic rocks are exposed as plutons, sills, and dike networks that are commonly found in the exhumed footwalls of metamorphic core complexes. This study investigates newly discovered exposures of granodioritic–leucogranitic rocks from three intrusive phases in the footwall of the Pinaleño–Jackson Mountain metamorphic core complex of southeastern Arizona, called the Relleno suite. Zircon U–Pb geochronology indicates that the suite was emplaced from 58 to 52 Ma. Zircon Lu/Hf isotope geochemistry, whole-rock Sr and Nd isotope geochemistry, and mineral O isotope geochemistry were used to investigate the source of these rocks and evaluate whether they are related to crustal anatexis. Average zircon εHf(t) values of the suite range from −4.7 to −7.9, whole-rock εNd(i) and 87Sr/86Sr(i) values range from −9.4 to −11.8 and 0.7064 to 0.7094 respectively, and quartz δ18OVSMOW values range from 6.8 to 9.4 ‰. Isotopic and geochemical data of these rocks are consistent with derivation from and assimilation of intermediate–mafic (meta)igneous rocks, at deep crustal levels, and are supported by thermodynamic melt models of Proterozoic igneous rocks equivalent to those exposed in the Pinaleño Mountains. In comparison with other Laramide-age anatectic granites in SE Arizona, those exposed in the Pinaleño Mountains are temporally similar but present compositional and isotopic differences that reflect melting and assimilation of different lithologies, producing distinct mineralogical and isotopic characteristics. The results suggest that crustal melting during this interval was not limited to metasedimentary protoliths and may have affected large portions of the deep crust. The early Paleogene Relleno suite in the Pinaleño Mountains strengthens the relationship between crustal melting and regions of thickened crust associated with the Sevier and Laramide orogenies.
Use of Complementary and Integrative Health Therapies Before Intensive Functional Restoration in Active Duty Service Members with Chronic Pain
Authors: Flynn Diane M , McQuinn Honor , Burke Larisa , Steffen Alana , Fairchok Alexandra , Snow Tyler , Doorenbos Ardith Z
Published: November 2021

Objective

Psychosocial factors are known to predict chronic pain, and the use of complementary and integrative health (CIH) therapies to address pain is emerging among the military population. However, conflicting results on pain outcomes warrant additional research. This study aimed to 1) evaluate the benefit of adding a CIH pain management program to standard rehabilitative care (SRC), as compared with SRC alone, as a precursor to an intensive functional restoration (FR) program; 2) identify factors that predict improvement in pain outcomes after treatment; and 3) determine the proportion of participants who experience a clinically meaningful response.

Design

Pragmatic randomized controlled clinical trial. Participants were randomized to a 3-week course of either SRC alone or SRC+CIH (stage 1), followed by a 3- to 6-week course of FR (stage 2).

Subjects

Active duty service members with chronic pain.

Methods

Participants completed either SRC alone or SRC+CIH (stage 1), followed by a course of FR (stage 2). Patient-reported and provider-determined outcomes were collected at baseline, after stage 1, and after stage 2. A covariance pattern model with an unstructured residual covariance matrix was used to compare treatment arms while accounting for dependency due to repeated measurements.

Results

A total of 210 service members participated. Most were in the Army (82%) and were male (84%). Participants randomized to the SRC+CIH intervention had greater improvement in the pain impact score than did those in the SRC-alone group. Predictors of outcomes were baseline impact score, anger, depression, and educational status.

Conclusions

This study found that military service members with the highest pain impact benefit the most from interdisciplinary pain care.
mTOR activation in CD8+ cells contributes to disease activity of rheumatoid arthritis and increases therapeutic response to TNF inhibitors
Authors: Zhang Mingzeng , Iwata Shigeru , Sonomoto Koshiro , Ueno Masanobu , Fujita Yuya , Anan Junpei , Miyazaki Yusuke , Ohkubo Naoaki , Sumikawa Maiko Hajime , Todoroki Yasuyuki , Miyata Hiroko , Nagayasu Atsushi , Kanda Ryuichiro , Hao He , Trimova Gulzhan , Lee Seunghyun , Nakayamada Shingo , Sakata Kei , Tanaka Yoshiya
Published: November 2021

Objective

This study aimed to understand the role of mammalian target of rapamycin (mTOR) in CD8+ cells in the pathogenicity of RA and the changes after treatment with biologic drugs.

Methods

Peripheral blood mononuclear cells (PBMCs) were isolated from 17 healthy controls and 86 patients with RA. Phosphorylation of mTOR (p-mTOR) and its clinical relevance were evaluated. The role of mTOR in CD8+ cells was also examined in vitro.

Results

Patients with RA who had a moderate or high disease activity, were biologic-naïve, and were refractory to MTX were enrolled in this study. The p-mTOR levels in CD8+ cells were higher in patients with RA than in healthy controls, and they positively correlated with the disease activity in such patients. However, after one year of treatment with TNF inhibitors, the p-mTOR levels in CD8+ cells were suppressed and showed a positive correlation with the treatment response, which was not observed in the abatacept-treatment group. In vitro stimulation of CD8+ cells with anti-CD3 and anti-CD28 antibodies induced mTOR phosphorylation and increased the production of granzyme B, granulysin, TNF-α and IFN-γ but decreased the production of granzyme K. However, on treatment with TNF inhibitors, p-mTOR levels in CD8+ cells and granzyme B production decreased, while granzyme K production increased. The production of granulysin and IFN-γ was not affected by the TNF inhibitors.

Conclusion

These results suggested that mTOR activation in CD8+ cells may be a novel evaluation marker for RA disease activity and a predictive marker of therapeutic response to TNF inhibitors.
Taking the pulse of science diplomacy and developing practices of valuation
Authors: Flink Tim
Published: November 2021

Science diplomacy has caught remarkable attention in public policy and academic research over the last fifteen years. However, the concept is plagued by a huge talk–action discrepancy: its public discourse has reached a problematic state of dazzling self-adulation, while it is unclear if and how the actual policies and associated organizations live up to these expectations. The article reconstructs three structural causes to explain the recent hype about science diplomacy. It further encourages actors to organize evaluations that ask whether and how actions of science diplomacy can be valuable. In this regard, a first set of fundamental principles is proposed for setting up an evaluative framework. In conclusion, the article advises science diplomacy actors from democratic states and institutions, from both academic research and public policy, to stop dreaming about soft power influence on authoritarian states and regimes but rather face new geopolitical realities.
GoldBricks: an improved cloning strategy that combines features of Golden Gate and BioBricks for better efficiency and usability
Authors: Chaudhari Vishalsingh R , Hanson Maureen R
Published: November 2021

With increasing complexity of expression studies and the repertoire of characterized sequences, combinatorial cloning has become a common necessity. Techniques like BioBricks and Golden Gate aim to standardize and speed up the process of cloning large constructs while enabling sharing of resources. The BioBricks format provides a simplified and flexible approach to endless assembly with a compact library and useful intermediates but is a slow process, joining only two parts in a cycle. Golden Gate improves upon the speed with use of Type IIS enzymes and joins several parts in a cycle but requires a larger library of parts and logistical inefficiencies scale up significantly in the multigene format. We present here a method that provides improvement over these techniques by combining their features. By using Type IIS enzymes in a format like BioBricks, we have enabled a faster and efficient assembly with reduced scarring, which performs at a similarly fast pace as Golden Gate, but significantly reduces library size and user input. Additionally, this method enables faster assembly of operon-style constructs, a feature requiring extensive workaround in Golden Gate. Our format allows such inclusions resulting in faster and more efficient assembly.