bluuebunny/crossref_metadata_2025 huggingface dataset:
Host biomarkers to predict the severity of acute febrile illness: A scoping review
Authors: Robinson Matthew L. , Workneh Meklit , Dittrich Sabine , Kurlekar Spruha , Yee Rebecca , Nirmalraj Maya C. , Robinson Karen A. , Manabe Yukari C.
Published: December 2019

Background

Acute febrile illness (AFI) ranges from mild to mortal, yet severity is difficult to assess. Host biomarkers may identify patients with AFI who require a higher level of care; choosing appropriate biomarkers for this role among an expanding pool of candidates is challenging. We performed a scoping review to evaluate the performance of novel host biomarkers to predict AFI severity.

Methods

PubMed was systematically searched for manuscripts published January 1, 2013 to February 10, 2018 for studies reporting the association of host biomarker levels and a measure of disease severity among patients with a suspected or diagnosed cause of AFI. Identified abstracts and full text manuscripts were reviewed for eligibility by 2 reviewers. Biomarker performance was evaluated primarily by the area under the curve (AUC) of the receiver operator characteristic to distinguish severe disease. We aggregated data describing biomarker performance by AUC using weighted mean, fixed effects meta-analyses, and random effects meta-analyses.

Results

Among 2,303 manuscripts identified, 281 manuscripts met criteria for analysis. Data was extracted for 278 biomarkers evaluated in 45,737 participants. Among 89 biomarkers evaluated by ≥2 studies, there were 6 biomarkers (proadrenomedullin, copeptin, pro-atrial natriuretic peptide, serum triggering receptor expressed on myeloid cells-1, chitinase-3-like protein-1, and the pediatric sepsis biomarker risk model), that showed a weighted mean AUC >0.75 (range 0.75-0.84) in >500 patients over >2 studies.

Conclusions

Although several biomarkers show promise in predicting AFI severity across multiple studies, their test characteristics do not suggest that they may be used alone to determine AFI prognosis.

A systematic review and limited metanalysis of 89 host biomarkers revealed that most individual biomarkers offer modest performance in predicting the severity of acute febrile illness; several however have performance characteristics which have shown promise in multiple studies.
Mouse Aging Cell Atlas Analysis Reveals Global and Cell Type Specific Aging Signatures Revision 1
Authors: Zhang Martin Jinye , Pisco Angela Oliveira , Darmanis Spyros , Zou James
Published: December 2019

Aging is associated with complex molecular and cellular processes that are poorly understood. Here we leveraged the Tabula Muris Senis single-cell RNA-seq dataset to systematically characterize gene expression changes during aging across diverse cell types in the mouse. We identified aging-dependent genes in 76 tissue-cell types from 23 tissues and characterized both shared and tissue-cell-specific aging behaviors. We found that the aging-related genes shared by multiple tissue-cell types also change their expression congruently in the same direction during aging in most tissue-cell types, suggesting a coordinated global aging behavior at the organismal level. Scoring cells based on these shared aging genes allowed us to contrast the aging status of different tissues and cell types from a transcriptomic perspective. In addition, we identified genes that exhibit age-related expression changes specific to each functional category of tissue-cell types. All together, our analyses provide one of the most comprehensive and systematic characterizations of the molecular signatures of aging across diverse tissue-cell types in a mammalian system.
Molecular characterization and differential expression reveal functional divergence of stress-responsive enzymes in C4panicoid models,Setaria italicaandSetaria viridis
Authors: Muthamilarasan Mehanathan , Singh Roshan Kumar , Suresh Bonthala Venkata , Dulani Priya , Singh Nagendra Kumar , Prasad Manoj
Published: December 2019

Stress-responsive genes regulate the morpho-physiological as well as molecular responses of plants to environmental cues. In addition to known genes, there are several unknown genes underlying stress-responsive machinery. One such machinery is the sophisticated biochemical carbon-concentrating mechanism of the C4photosynthetic pathway that enables the plants to survive in high temperatures, high light intensities and drought conditions. Despite the importance of C4photosynthesis, no comprehensive study has been performed to identify and characterize the key enzymes involved in this process among sequenced Poaceae genomes. In the present study, five major classes of enzymes that are reported to play roles in C4biochemical carbon-concentrating mechanism were identified in sequenced Poaceae genomes with emphasis on the model crops,Setaria italicaandS. viridis. Further analysis revealed that segmental and tandem duplications have contributed to the expansion of these gene families. Comparative genome mapping and molecular dating provided insights into their duplication and divergence in the course of evolution. Expression profiling of candidate genes in contrastingS. italicacultivars subjected to abiotic stresses and hormone treatments showed distinct stress-specific upregulation ofSiαCaH1,SiβCaH5, SiPEPC2,SiPPDK2,SiMDH8andSiNADP-ME5in the tolerant cultivar. Altogether, the study highlights key stress-responsive genes that could serve as potential candidates for elucidating their precise roles in stress tolerance.

Key message

Comprehensive analysis of stress-responsive gene families in C4model plants,Setaria italicaandS. viridisidentifiedSiαCaH1,SiPEPC2,SiPPDK2,SiMDH8andSiNADP-ME5as potential candidates for engineering abiotic stress tolerance.
Auxin transport network underlies xylem bridge formation between the hemi-parasitic plantPhtheirospermum japonicumand host Arabidopsis
Authors: Wakatake Takanori , Yoshida Satoko , Shirasu Ken
Published: December 2019

Parasitic plants form vascular connections to host plants for efficient material transport. The haustorium is the responsible organ for host invasion and subsequent vascular connection. After invasion of host tissues, vascular meristem-like cells emerge in the central region of the haustorium, differentiate into tracheary elements, and establish a connection, known as a xylem bridge, between parasite and host xylem systems. Despite the importance of this parasitic connection, the regulatory mechanisms of xylem bridge formation are unknown. Here we show the role of auxin and auxin transporters during the process of xylem bridge formation using an Orobanchaceae hemiparasitic plant,Phtheirospermum japonicum. The auxin response marker DR5 has a similar expression pattern to tracheary element differentiation genes in haustoria. Auxin transport inhibitors alter tracheary element differentiation in haustoria, but biosynthesis inhibitors do not, demonstrating the importance of auxin transport during xylem bridge formation. The expression patterns and subcellular localization of PIN family auxin efflux carriers and AUX/LAX influx carriers correlate with DR5 expression patterns. The cooperative action of auxin transporters is therefore responsible for controlling xylem vessel connections between parasite and host.
Irrational rationalities and governmentality‐effected neglect in immigration practice: Legal migrants’ entitlements to services and benefits in the United Kingdom
Authors: Oliver Caroline
Published: December 2019

Governments’ attempts to manage immigration increasingly restrict immigrants’ eligibility to healthcare, education, and welfare benefits. This article examines the operation of these restrictions in the United Kingdom. It draws on qualitative research with civil servants and NGO expert advisors, and applies sociological theories on bureaucracy as a lens to interpret these data. Conceptually, the paper employs a generative synthesis of Ritzer’s notion of “irrational rationality” and Foucault’s perspective on “governmentality” to explain observed outcomes. Findings show that public service workers struggle with complex and opaque regulations, which grant different entitlements to different categories of migrants. The confusion results in mistakes, arbitrary decisions, and hypercorrection, but also a system‐wide indifference to irrational outcomes, supported by human factors in contexts of austerity. I consider this a form of governmentality‐effected neglect, where power operates as much through inaction as well as through intention, but which results in exclusions of legal migrants that are harsher in practice than in law.
Cardiac tamponade in multiple myeloma – A pictorial case review of FDG PET/CT findings
Authors: Chen Tony , Taubman Kim , Xiao Hao , Yap Kelvin , Schlicht Stephen
Published: December 2019

Pericardial involvement of multiple myeloma is a rare and late‐stage complication, with only a few cases reported in the literature. PET/CT has demonstrated a growing role in the diagnosis and follow‐up of patients with multiple myeloma. We present a case of pericardial multiple myeloma in a patient with relapsed/refractory disease, showcasing previously unpublished FDG PET/CT findings.
Prognostic value of baseline 18F‐FDG PET/CT metabolic parameters in paediatric lymphoma
Authors: Zhou Yeye , Hong Zhihui , Zhou Min , Sang Shibiao , Zhang Bin , Li Jihui , Li Qingru , Wu Yiwei , Deng Shengming
Published: December 2019

Introduction

In the present study, we aimed to investigate the prognostic value of metabolic parameters, including maximum standardized uptake value (SUVmax), total metabolic tumour volume (tMTV) and total lesion glycolysis (TLG), measured at baseline 18F‐FDG PET/CT in paediatric lymphoma.

Methods

From March 2013 to April 2019, 47 patients with paediatric lymphoma, including 38 males and nine females with an average age of 14.87 years, who underwent 18F‐FDG PET/CT scan prior to treatment were retrospectively included in this study. SUVmax, MTV and TLG were recorded. Survival curves were established according to the Kaplan–Meier curves and log‐rank test. Mann–Whitney U‐test was used to assess differences in metabolic parameters between different clinical outcomes.

Results

The median follow‐up time was 36 months (range of 3–74 months). The 2‐year progression‐free survival (PFS) of the low TLG and high TLG groups was 95.24% (20/21) and 57.69% (15/26), respectively (P = 0.004). TLG and tMTV were significantly higher in progression‐free patients compared with the progression group. Univariate analysis showed that B symptoms (P = 0.014), effusion (P = 0.010), tMTV (P = 0.008) and TLG (P = 0.004) were the predictive factors for PFS. The tMTV (P = 0.005), TLG (P = 0.005) and effusion (P = 0.003) were associated with OS. Multivariate analysis revealed that TLG was the only independent prognostic factor for PFS (HR = 11.133, 95% CI = 1.435–86.405, P = 0.021).

Conclusions

Collectively, TLG of baseline 18F‐FDG PET/CT was an independent prognostic factor for PFS in patients with paediatric lymphoma.
Estimation of direct cost of managing rheumatoid arthritis treatment to Pakistani patients using real‐world follow‐up data
Authors: Naqvi Atta Abbas , Hassali Mohamed Azmi , Naqvi Syed Baqir Shyum , Kachela Bharti , Khan Irfanullah
Published: December 2019

Objective

This study aimed to estimate annual direct cost attributed to rheumatoid arthritis (RA) treatment from a patient's perspective using real‐world patient follow‐up data from hospitals’ electronic database.

Methods

A prospective 1‐year study was conducted in rheumatology clinics of tertiary care hospitals of Karachi, Pakistan. Cost‐of‐illness methodology was used and all patient data related to costs of rheumatologist visits, physical therapy sessions, medications, assistive devices and laboratory investigations were obtained directly in printed hardcopies from patient electronic databases using their medical record numbers. Transportation cost was calculated from patient‐reported log books. Data were analyzed through IBM SPSS version 23. Patients were asked to sign a written consent and the study was ethically approved.

Results

The mean age of patients (N = 358) was 48 years. Most patients (73.7%) were female, married (86%) and had basic education (71.8%). Average cost of rheumatologist visits was PKR 11 510.61 (USD: 72.05) while it was PKR 66 947.37 (USD: 419.07) for physical therapy sessions. On average, medicines and medical devices costs were estimated at PKR 10 104.23 (USD: 63.25) and PKR 7848.48 (USD: 49.13) respectively. Cost attributed to diagnostic and laboratory charges was PKR 1962.12 (USD: 12.28) and travel expense was PKR 6541 (USD: 40.95). The direct expenditure associated with managing RA was PKR 37 558 (USD: 235.1). All costs were reported per annum.

Conclusion

Patient with RA in Pakistan pay a considerable amount of their income for managing their condition. Most patients have no provision for insurance which is a need considering the nature of the disease and associated productivity loss that would significantly lower income as the disease progresses.
Economic Reforms in the Aftermath of Regime Change in Malaysia
Authors: Lee Cassey
Published: December 2019

The 14th general election in May 2018 brought about an unexpected change in political rule in Malaysia for the first time since the country's independence in 1957. In its first year of rule, the new Pakatan Harapan‐led government implemented several populist economic policies that were drawn from its election manifesto. While these policies may have moderated populist politics to some extent, they have also weakened the government's fiscal capacity. Ethnic fragmentation and a strengthened opposition alliance have also made it difficult for the new government to implement its ambitious institutional reform agenda.
Recurrent lichenoid reaction to black tattoo ink: A case report and brief review of the literature
Authors: Brown Hilary , Hannaford Rodney
Published: December 2019

Cutaneous reactions to tattoos are increasing as the prevalence of tattoos increases. Lichenoid reactions often occur in red tattoos and are usually localised to the tattoo. We present a case of recurrent lichenoid reaction occurring in both the black tattooed and adjacent non‐tattooed skin.
Medication safety challenges in Aboriginal Health Care services
Authors: Khalil Hanan , Gruis Hilton
Published: December 2019

Objective

The aim of this study is to examine the challenges faced by the Aboriginal Health Practitioners in the community assisting their clients to manage medicines.

Design

Qualitative, in depth interviews with eight Aboriginal Health Practitioners employed at various Aboriginal Community Controlled Health services in Victoria were undertaken.

Setting

Rural Aboriginal Community Controlled Health Service.

Participants

Aboriginal Health Practitioners who are registered with the Aboriginal and Torres Strait Islander Health Practice Board of Australia as an Aboriginal Health Practitioner and who have experience in the planning, provision, management and evaluation of health services within their scope of practice.

Results

This study revealed multiples challenges faced by Aboriginal Health Practitioners assisting clients with medication management. These were mainly divided into the attitudes and the culture of the workplace and barriers with medications use faced by the clients. The following subthemes were identified within the attitudes and workplace culture theme. These were reporting of errors, pamphlets not culturally appropriate, lack of education of Aboriginal Health Practitioner role and doctors' understanding of Aboriginal culture. The subthemes identified by the Aboriginal Health Practitioners that were specific to the clients included language barriers, immediacy, sharing medications by family members, medications disposal, self‐diagnosis, traditional medicine, not feeling comfortable with doctors, literacy and alcohol use.

Conclusion

This study has identified many barriers to medication safety in the Aboriginal community, and strategies to improve some of the challenges identified.
Avβ3 single‐stranded DNA aptamer attenuates vascular restenosis via Ras‐PI3K/MAPK pathway in rats after percutaneous transluminal coronary angioplasty
Authors: Wu Hong‐bing , Wang Zhi‐wei , Shi Feng , Ren Zong‐li , Li Luo‐cheng , Hu Xiao‐ping , Hu Rui , Li Bo‐wen
Published: December 2019

Our aim was to investigate the effect of avβ3 single‐stranded DNA aptamer (avβ3 ssDNA) on vascular restenosis in rats after percutaneous transluminal coronary angioplasty (PTCA) via the Ras‐PI3K/MAPK pathway. Sixty Sprague‐Dawley rats were randomly divided into six groups: sham‐operated, PTCA, PTCA+cilengitide (18 mg/kg, n = 8), and avβ3 ssDNA treatment at 50, 100, and 200 μg/kg. Hematoxylin‐eosin staining was performed to evaluate the successful establishment of the PTCA model and to assess the degree of intimal hyperplasia. Immunofluorescence and in situ hybridization were carried out to observe the level of avβ3. Immunohistochemistry was used to detect the expression of E‐cadherin, N‐cadherin, α‐smooth muscle actin (α‐SMA), angiotensin 1 (ANG1), and ANG2. The expression of osteopontin (OPN), focal adhesion kinase (FAK), Ras, mitogen‐activated protein kinase (MAPK), phosphatidylinositol‐4,5‐bisphosphate 3‐kinase (PI3K), signal transducer and activator of transcription 1 (STAT1), and GTPase was observed by the western blot and quantitative reverse transcription polymerase chain reaction. Compared with rats subjected to PTCA only, those treated with avβ3 ssDNA showed significantly decreased vascular occlusion rate (P < .05). The protein expression of avβ3, OPN, p‐FAK, ANG2, and E‐cadherin was significantly increased by avβ3 ssDNA (P < .05), while the levels of ANG1, α‐SMA, N‐cadherin Ras, MAPK, PI3K, STAT1, and GTPase were significantly decreased (P < .05). Avβ3 ssDNA reduced the proliferation, migration, epithelial‐mesenchymal transition, and vascular remodeling of vascular smooth muscle cells, and the mechanism may be related to the Ras‐PI3K/MAPK pathway.
A single centre experience of treatment outcomes for Helicobacter pylori infection among inner‐city children and adolescents
Authors: Mathews Jubin , Malik Preeti , Rai Anjali , Lin Juan , Kim Ryung S. , Pan Debra H.
Published: December 2019

Aim

This study assessed treatment outcomes of Helicobacter pylori (H pylori) infection among inner‐city children.

Methods

This was a retrospective study of patients aged 1‐21 years who underwent initial treatment for H pylori infection from 2011 to 2015. We included patients who completed 2 weeks of treatment with documented adequate compliance after H pylori infection was diagnosed. Treatment outcomes were measured based on stool H pylori antigen and/or histology.

Results

Of the total 261 patients diagnosed with H pylori, 239 completed the first‐line treatment. The regimens used included amoxicillin/clarithromycin/proton pump inhibitor (PPI) in 207/239 patients (86.6%), amoxicillin/metronidazole/PPI in 14/239 patients (5.8%) and other regimens in 18/239 patients (7.5%). H pylori eradication status was tested in 111/207 (53.6%) patients treated with amoxicillin/clarithromycin/PPI, and the eradication was achieved in 84/111(75.7%) patients. The treatment success rates for amoxicillin/metronidazole/PPI and other regimens were 71.4% (5/7) and 63.6% (7/11), respectively. There was no statistical significance of post‐treatment stool H pylori antigen results between PPI (n = 31) and no PPI (n = 43) users.

Conclusion

The study showed an eradication rate of 75.7% with the regimen amoxicillin/clarithromycin/PPI suggesting significant antibiotic resistance in our population. The use of PPI did not influence post‐treatment stool H pylori antigen results.
Editorial: establishing a joint approach to a common problem for gastroenterologists
Authors: Luber Raphael P. , Irving Peter M.
Published: December 2019

LINKED CONTENT

This article is linked to Varkas paper. To view this article, visit https://doi.org/10.1111/apt.15519.
Letter: hepatitis B virus infection and risk of multiple myeloma—a meta‐analysis of cohort studies. Authors' reply
Authors: Su Tung‐Hung , Chen Chi‐Ling , Kao Jia‐Horng
Published: December 2019

LINKED CONTENT

This article is linked to Su et al and An papers. To view these articles, visit https://doi.org/10.1111/apt.15132 and https://doi.org/10.1111/apt.15590.
ROC‐guided survival trees and ensembles
Authors: Sun Yifei , Chiou Sy Han , Wang Mei‐Cheng
Published: December 2019

Tree‐based methods are popular nonparametric tools in studying time‐to‐event outcomes. In this article, we introduce a novel framework for survival trees and ensembles, where the trees partition the dynamic survivor population and can handle time‐dependent covariates. Using the idea of randomized tests, we develop generalized time‐dependent receiver operating characteristic (ROC) curves for evaluating the performance of survival trees. The tree‐building algorithm is guided by decision‐theoretic criteria based on ROC, targeting specifically for prediction accuracy. To address the instability issue of a single tree, we propose a novel ensemble procedure based on averaging martingale estimating equations, which is different from existing methods that average the predicted survival or cumulative hazard functions from individual trees. Extensive simulation studies are conducted to examine the performance of the proposed methods. We apply the methods to a study on AIDS for illustration.
Pixantrone plus rituximab versus gemcitabine plus rituximab in patients with relapsed aggressive B‐cell non‐Hodgkin lymphoma not eligible for stem cell transplantation: a phase 3, randomized, multicentre trial (PIX306)
Authors: Pettengell Ruth , Długosz‐Danecka Monika , Andorsky David , Belada David , Georgiev Pencho , Quick Donald , Singer Jack W. , Singh Simran B. , Pallis Athanasios , Egorov Anton , Salles Gilles
Published: December 2019

PIX306 was a phase 3, randomised, single‐blind, multicentre trial conducted in adult patients with diffuse large B‐cell lymphoma (DLBCL) or follicular lymphoma (FL) grade 3 who relapsed after ≥1 rituximab‐containing regimen and were not eligible for a stem cell transplant. Patients were randomised 1:1 to pixantrone 50 mg/m2 or gemcitabine 1000 mg/m2 on days 1, 8 and 15 of a 28‐day cycle, combined with rituximab 375 mg/m2 on day 1, for up to six cycles. Patients were followed for up to 96 weeks. The primary endpoint was progression‐free survival (PFS). Secondary endpoints included overall survival (OS), complete response (CR) rate, overall response rate (ORR) and safety. Overall, 312 patients were randomised (median age 73·0 years). The study did not meet its primary endpoint. Median PFS [95% confidence interval (CI)] was 7·3 months (5·2–8·4) with pixantrone + rituximab (PIX + R) and 6·3 months (4·4–8·1) with gemcitabine + rituximab [GEM + R; hazard ratio (HR): 0·85; 95% CI 0·64–1·14; P = 0·28]. Median OS was 13·3 (10·1–19·8) months with PIX + R and 19·6 (12·4–31·9) months with GEM + R (HR: 1·13; 95% CI 0·83–1·53). ORR was 61·9% and 43·9% respectively and CR rate 35·5% and 21·7%. The incidence of adverse events, including cardiac events, was not statistically significant different between PIX + R and GEM + R.
Metabolic syndrome, neurohumoral modulation, and pulmonary arterial hypertension
Authors: Maron Bradley A. , Leopold Jane A. , Hemnes Anna R.
Published: December 2019

Pulmonary vascular disease, including pulmonary arterial hypertension (PAH), is increasingly recognized to be affected by systemic alterations including up‐regulation of the renin‐angiotensin‐aldosterone system and perturbations to metabolic pathways, particularly glucose and fat metabolism. There is increasing preclinical and clinical data that each of these pathways can promote pulmonary vascular disease and right heart failure and are not simply disease markers. More recently, trials of therapeutics aimed at neurohormonal activation or metabolic dysfunction are beginning to shed light on how interventions in these pathways may affect patients with PAH. This review will focus on underlying mechanistic data that supports neurohormonal activation and metabolic dysfunction in the pathogenesis of PAH and right heart failure as well as discussing early translational data in patients with PAH.
Prediction of Metabolite‐to‐Parent Drug Exposure: Derivation and Application of a Mechanistic Static Model
Authors: Callegari Ernesto , Varma Manthena V.S. , Obach R. Scott
Published: December 2019

In the development of new drugs, the prediction of metabolite‐to‐parent plasma exposure ratio in humans prior to administration in a clinical study has emerged as an important need. In this work, we derived a mechanistic static model based on first principles to estimate metabolite‐to‐parent plasma exposure ratio, considering the contribution of liver and gut metabolism and drug transport. Knowledge (or assumptions) of mechanisms of clearance and organs involved is required. Input parameters needed included intrinsic clearance, fraction of clearance to the metabolite of interest, various binding values, and, in some cases, active transport clearance. The principles are illustrated with four drugs that yield six metabolites, with one in which clearance is dependent on a pathway subject to genetic polymorphism. Overall, the approach yielded metabolite‐to‐parent ratios within about twofold of the actual values and, thus, can be valuable in decision making in the drug development process.
Maximum impact heights of currently used mouthguards in field hockey
Authors: van Vliet Kirsten E. , Kleverlaan Cees J. , Lobbezoo Frank , de Lange Jan , van Wijk Arjen J.
Published: December 2019

Background/Aim

The effectiveness of mouthguards used in field hockey is unknown. The aim of this study was to compare the maximum impact heights between currently used mouthguards in field hockey to prevent dental injury.

Methods

Four boil‐and‐bite mouthguards (Dita, Shock Doctor, SISU, and Stag) and one custom‐made mouthguard (Elysee) were tested for maximum impact height. A hockey ball was released in a tube from increasing heights onto plaster and polymethylmethacrylate (PMMA) dental models. Models were tested without mouthguard as a control. The experiment was repeated 10 times per mouthguard and for the control on each dental model. The maximum impact height for when the dental model broke was used to calculate the speed. The mouthguards and controls were compared.

Results

The maximum impact heights (median [25%‐75%] in meters) onto plaster dental models were as follows: control 0.23 (0.15‐0.25), Dita 0.35 (0.30‐0.35), Elysee 0.45 (0.34‐0.50), Shock Doctor 0.68 (0.60‐0.74), SISU 0.23 (0.20‐0.26), and Stag 0.35 (0.35‐0.46). The maximum impact height for Shock Doctor was significantly higher than all other mouthguards and the control (all P < .05). The maximum impact heights onto PMMA dental models were as follows: control 2.00 (1.30‐2.50), Dita 3.80 (2.65‐6.95), Elysee 3.30 (2.30‐4.20), Shock Doctor 6.20 (2.80‐8.10), SISU 2.60 (1.90‐3.15), and Stag 3.90 (1.25‐5.15). The maximum impact height for Shock Doctor was significantly higher than for SISU, Stag, and the control (all P < .05), but did not differ significantly from Dita (P = .43) and Elysee (P = .12).

Conclusion

Shock Doctor had the highest maximum impact height compared to the other mouthguards and appears to be the most effective mouthguard tested in this study.
Quality of life is maintained with ixazomib maintenance in post‐transplant newly diagnosed multiple myeloma: The TOURMALINE‐MM3 trial
Authors: Schjesvold Fredrik , Goldschmidt Hartmut , Maisnar Vladimir , Spicka Ivan , Abildgaard Neils , Rowlings Philip , Cain Lauren , Romanus Dorothy , Suryanarayan Kaveri , Rajkumar Vincent , Odom Dawn , Gnanasakthy Ari , Dimopoulos Meletios
Published: December 2019

Objectives

Health‐related quality of life (HRQoL) is particularly important during maintenance therapy (MT) in newly diagnosed multiple myeloma post‐transplant, when disease symptoms are limited.

Methods

We assessed HRQoL in patients randomised to 26 cycles of MT (ixazomib vs placebo) in TOURMALINE‐MM3 (NCT02181413).

Results

The characteristics at study entry were well‐balanced between ixazomib (n = 386) and placebo (n = 251) arms. At study entry, EORTC QLQ‐C30 and MY20 scores were high for functional scales and low for symptom scales and were comparable with those of the general population. Changes in subscale scores across intervals, analysed over 30 four‐week intervals using a linear mixed‐effects model, were generally small and similar between arms for the EORTC QLQ‐C30 Global Health Status/QoL, Physical Functioning, and Pain subscales and EORTC QLQ‐MY20 Disease Symptoms subscale and Peripheral Neuropathy item. EORTC QLQ‐C30 Nausea/Vomiting and Diarrhoea subscales were consistently worse for ixazomib than for placebo, in line with the ixazomib toxicity profile. Even when least‐squares mean differences between arms were statistically significant, none reached the established minimal important clinical difference of 10 in multiple myeloma.

Conclusions

In addition to improvement in progression‐free survival with ixazomib, HRQoL was maintained in both arms. Active treatment with ixazomib did not have an adverse impact on HRQoL.
Bacterial microbiota composition of a common ectoparasite of cavity‐breeding birds, the Hen Flea Ceratophyllus gallinae
Authors: Aivelo Tuomas , Tschirren Barbara
Published: December 2019

Experimental field studies have demonstrated negative fitness consequences of Hen Flea Ceratophyllus gallinae infestations for bird hosts, yet it is currently unclear whether these negative effects are a direct consequence of flea‐induced blood loss or a result of flea‐borne pathogen transmission. Here we used a 16S rRNA gene sequencing approach to characterize the bacterial microbiota community of Hen Fleas collected from Great Tit Parus major nests and found that Brevibacterium (Actinobacteria), Staphylococcus (Firmicutes), Stenotrophomonas (Proteobacteria), Massilia (Proteobacteria), as well as the arthropod endosymbionts ‘Candidatus Lariskella’ and ‘Candidatus Midichloria’ were most abundant. We found evidence for the occurrence of Staphylococcus spp. in Hen Fleas, which may cause opportunistic infections in bird hosts, but not of other known pathogens commonly transmitted by other flea species, such as Bartonella spp. or Rickettsia spp. However, Hen Fleas might transmit other pathogens (e.g. viruses or bacteria that are not currently recognized as bird pathogens), which may contribute to the negative fitness consequences of Hen Flea infestations in addition to direct blood loss or secondary infections of wounds caused by biting fleas.
Efficacy of reciprocating and ultrasonic activation of 6% sodium hypochlorite in the reduction of microbial content and virulence factors in teeth with primary endodontic infection
Authors: Aveiro E. , Chiarelli‐Neto V. M. , de‐Jesus‐Soares A. , Zaia A. A. , Ferraz C. C. R. , Almeida J. F. A. , Marciano M. A. , Feres M. , Gomes B. P. F. A.
Published: December 2019

Aim

To evaluate in a clinical trial the efficacy of reciprocating and ultrasonic activation of 6% sodium hypochlorite (NaOCl) in the microbial composition and reduction in microbial load as well as in levels of lipopolysaccharide (LPS) and lipoteichoic acid (LTA) in teeth with primary endodontic infections.

Methodology

Samples were collected from 24 root canals with pulp necrosis and periapical lesions, before and after chemo‐mechanical canal preparation. The teeth were randomly divided according to the activation protocol as follows: control group without activation (WA, n = 8), reciprocating activation group using Easy Clean tip (EC, n = 8) and ultrasonic activation group using Irrisonic insert (US, n = 8). Microbiological specimens were processed using a culture technique and microbiota composition was analysed using the checkerboard technique. The levels of LPS and LTA were quantified using limulus amebocyte lysate (LAL) and enzyme‐linked immunosorbent assay (ELISA), respectively. The Fisher's exact test, Kruskal–Wallis, Dunn’s and Wilcoxon’s test with a significance level of P < 0.05 were used for statistical analysis.

Results

All initial specimens had growth of viable bacteria in fastidious anaerobe agar (FAA), with an average of 105 CFU mL−1, whereas only one case had such growth after chemo‐mechanical canal preparation. LPS and LTA were recovered in 100% of the cases. Chemo‐mechanical canal preparation significantly decreased the levels of LPS and LTA (P < 0.05), but no significant differences were found between the groups (P > 0.05). Through the checkerboard technique, bacteria were found in 100% of the initial specimens with concentrations between <105 and 106. The most frequently identified microorganisms were Prevotella nigrescens and Enterococcus hirae. After chemo‐mechanical canal preparation, many species were not detected in any of the three groups tested. A significant reduction occurred in Group US, followed by Groups EC and WA.

Conclusions

Activation of 6% NaOCl reduced the levels of LPS and LTA with no differences between the groups. However, ultrasonic activation was associated with a greater reduction in microbial load within root canals.
Angiotensin‐I‐converting enzyme (ACE)‐inhibitory peptides from Thai jasmine rice bran protein hydrolysates
Authors: Suwannapan Orapa , Wachirattanapongmetee Kwanruedee , Thawornchinsombut Supawan , Katekaew Somporn
Published: December 2019

Rice bran protein hydrolysate (<50 kDa RBPH) from Thai jasmine variety demonstrating a high Angiotensin I converting enzyme (ACE) inhibitory activity was purified and characterised. ACE inhibitory peptides were obtained from a two‐step purification process: gel filtration and preparative reverse‐phase high‐performance chromatography (RP‐HPLC) and then identified by mass spectrometer hybrid quadrupole‐time‐of‐flight. A novel peptide GSGYF in the RBPH was firstly identified and found to have a partial sequence homology of Oryza sativa Japonica Group. This sequence was further synthesised to exhibit as good an inhibition potency with IC50 value of 2.11 µg mL−1 as Captopril (1.15 µg mL−1). The cytotoxicity test revealed that this RBPH is non‐toxic against Vero cells. In addition, the <50 kDa RBPH was resistant to in vitro digestion by pepsin and trypsin. These findings suggest that the RBPH containing ACE inhibitory peptides is likely to be safer and healthier than synthetic drugs and can be an effective food supplement for lowering blood pressure.
Introduction: What does the future promise for work, employment and society?
Authors: RANI Uma , GRIMSHAW Damian
Published: December 2019

In introducing this double Special Issue, the authors draw on the articles contained therein to highlight the main areas for consideration in research on the future of work. They present the fast‐paced changes affecting the world of work as offering an opportunity to move towards equality‐inducing growth, while warning of the dangers posed by mismanaged technological change, inequalities (highlighting the persistent and intersectional nature of gender inequality), global supply chains and opportunities for social dialogue. In this light, they also propose policy recommendations focusing on strengthening worker protection and representative institutions, rethinking regulatory frameworks and taxation systems, and ensuring just transitions.
¿Hacia dónde evoluciona el tejido social contemporáneo? Nuevas tecnologías y viejas tendencias socioeconómicas
Authors: DOSI Giovanni , VIRGILLITO Maria Enrica
Published: December 2019

En este artículo se investiga si las sociedades asisten a una nueva revolución industrial, y cuál es la repercusión del cambio tecnológico en el tejido socioeconómico, principalmente con respecto al empleo, la distribución de la renta, las condiciones de trabajo y las relaciones laborales. Los autores sostienen que los procesos de innovación y la expansión de lo que denominan «automatización inteligente» tienden a exacerbar los actuales patrones de desigualdad de poder y de renta, que ya estaban presentes mucho antes la aparición de las tecnologías en cuestión. A tenor de esos procesos, proponen algunas recomendaciones para la formulación de políticas.
Tres escenarios para el futuro del trabajo
Authors: MÉDA Dominique
Published: December 2019

Tras pasar revista a la evolución del concepto de trabajo a lo largo de la historia y a las diferentes acepciones que se han dado al término en el curso de los siglos, la autora analiza la relación que mantienen los europeos con ese valor, así como el impacto en el trabajo y el empleo del actual discurso en boga sobre la revolución tecnológica y sus consecuencias «ineluctables». A continuación, considera el futuro del trabajo a la luz de tres escenarios, a saber, el «desmantelamiento del derecho del trabajo», la «revolución tecnológica» (que postula el fin del empleo debido a la automatización) y la «reconversión ecológica», último modelo compatible no solo con el imperativo medioambiental, sino también con las expectativas asociadas al trabajo y el empleo.
Los nietos de Keynes y los trabajadores de Marx en las plataformas digitales. Por qué el trabajo humano todavía es importante
Authors: EKBIA Hamid R. , NARDI Bonnie A.
Published: December 2019

El miedo a la automatización y al «futuro del trabajo», a la superfluidad de los trabajadores y del ser humano en general, se basa en ideas recurrentes sobre la tecnología, el trabajo y el valor económico. El debate se remonta a destacados pensadores como Karl Marx y John Maynard Keynes. Para entender el momento actual, los autores revisan este debate en relación con la historia del capitalismo. Desde una perspectiva centrada en el trabajo y la tecnología, examinan las formas ocultas de creación de valor en la economía actual y las lagunas del debate histórico, y esbozan varias situaciones hipotéticas de cara al futuro.
Mejoras económicas y sociales en las cadenas mundiales de suministro. Las experiencias del Cono Sur
Authors: REINECKE Gerhard , POSTHUMA Anne
Published: December 2019

El objeto del presente artículo es investigar hasta qué punto las mejoras económicas y sociales están concatenadas y se extienden de las empresas líderes a los proveedores en nueve estudios de casos de cadenas mundiales de suministro en el Cono Sur. Los resultados son heterogéneos, pero cabe distinguir tres patrones de evolución económica y social entre los segmentos de la cadena, a saber: desarrollo antagónico, desarrollo truncado y mejora integrada. A partir de esa tipología, se examina de qué manera las políticas públicas, las empresas y los interlocutores sociales pueden ayudar a corregir los desequilibrios, y se formulan recomendaciones al respecto.
La igualdad de género y la gobernanza de las cadenas de valor mundiales. Promoción de los derechos de las trabajadoras
Authors: BARRIENTOS Stephanie , BIANCHI Lara , BERMAN Cindy
Published: December 2019

La gobernanza privada, canalizada por conducto de programas de cumplimiento social e iniciativas de las empresas multinacionales en favor de la igualdad de género, no basta por sí sola para poner coto a la discriminación por razón de género en las cadenas de valor mundiales (CVM). Los Principios Rectores de las Naciones Unidas sobre las empresas y los derechos humanos (en adelante, Principios Rectores) proporcionan un marco que conjuga la gobernanza pública y la gobernanza privada a fin de abordar los derechos humanos en su globalidad, con inclusión de la igualdad de género. En el presente artículo se analiza si tales principios pueden ofrecer un marco de gobernanza más eficaz para atender los derechos de las trabajadoras en las CVM. Se sostiene que para poner fin a la discriminación por razón de género en las CVM y promover el ejercicio de la debida diligencia en materia de derechos humanos con una perspectiva de género es indispensable recurrir a una gobernanza en la que se articulen, en colaboración sinérgica, las entidades públicas, privadas y sociales.
Evaluation of polymorphisms in microRNA‐binding sites and pancreatic cancer risk in Chinese population
Authors: Ke Juntao , Peng Xiating , Mei Shufang , Tian Jianbo , Ying Pingting , Yang Nan , Wang Xiaoyang , Zou Danyi , Yang Yang , Zhu Ying , Gong Yajie , Gong Jing , Zhong Rong , Chang Jiang , Fang Zemin , Miao Xiaoping
Published: December 2019

As promising biomarkers and therapy targets, microRNAs (miRNAs) are involved in various physiological and tumorigenic processes. Genetic variants in miRNA‐binding sites can lead to dysfunction of miRNAs and contribute to disease. However, systematic investigation of the miRNA‐related single nucleotide polymorphisms (SNPs) for pancreatic cancer (PC) risk remains elusive. We performed integrative bioinformatics analyses to select 31 SNPs located in miRNA‐target binding sites using the miRNASNP v2.0, a solid database providing miRNA‐related SNPs for genetic research, and investigated their associations with risk of PC in two large case‐control studies totally including 1847 cases and 5713 controls. We observed that the SNP rs3802266 is significantly associated with increased risk of PC (odds ratio (OR) = 1.21, 95% confidence intervals (CI) = 1.11‐1.31, P = 1.29E‐05). Following luciferase reporter gene assays show that rs3802266‐G creates a stronger binding site for miR‐181a‐2‐3p in 3′ untranslated region (3′UTR) of the gene ZHX2. Expression quantitative trait loci (eQTL) analysis suggests that ZHX2 expression is lower in individuals carrying rs3802266‐G with increased PC risk. In conclusion, our findings highlight the involvement of miRNA‐binding SNPs in PC susceptibility and provide new clues for PC carcinogenesis.
Girls' brain structural connectivity in late adolescence relates to history of depression symptoms
Authors: Chahal Rajpreet , Weissman David G. , Marek Scott , Rhoads Shawn A. , Hipwell Alison E. , Forbes Erika E. , Keenan Kate , Guyer Amanda E.
Published: December 2019

Background

Girls’ depressive symptoms typically increase in adolescence, with individual differences in course and severity being key risk factors for impaired emotional functioning in young adulthood. Given the continued brain white matter (WM) maturation that occurs in adolescence, the present study tested whether structural connectivity patterns in late adolescence are associated with variation in the course of depression symptom severity throughout adolescence.

Method

Participants were girls (N = 115) enrolled in a multiyear prospective cohort study of risk for depression. Initial depression severity (intercept) at age 10 and change in severity (linear slope) across ages 10–19 were examined in relation to WM tractography collected at age 19. Network‐based statistic analyses were used to identify clusters showing variation in structural connectivity in association with depressive symptom intercept, slope, and their interaction.

Results

Higher initial depressive severity and steeper positive slope (separately) were associated with greater structural connectivity between temporal, subcortical socioaffective, and occipital regions. Intercept showed more connectivity associations than slope. The interaction effect indicated that higher initial symptom severity and a steeper negative slope (i.e., alleviating symptoms) were related to greater connectivity between cognitive control regions. Moderately severe symptoms that worsened over time were followed by greater connectivity between self‐referential and cognitive regions (e.g., posterior cingulate and frontal gyrus).

Conclusions

Higher depressive symptom severity in early adolescence and increasing symptom severity over time may forecast structural connectivity differences in late adolescence, particularly in pathways involving cognitive and emotion‐processing regions. Understanding how clinical course relates to neurobiological correlates may inform new treatment approaches to adolescent depression.
Failure to confirm a sodium–glucose cotransporter 2 inhibitor‐induced hematopoietic effect in non‐diabetic rats with renal anemia
Authors: Yamazaki Daisuke , Konishi Yoshio , Morikawa Takashi , Kobara Hideki , Masaki Tsutomu , Hitomi Hirofumhi , Osafune Kenji , Nakano Daisuke , Kittikulsuth Wararat , Nishiyama Akira
Published: December 2019

Aims/Introduction

Clinical studies have shown that treatment with inhibitors of sodium–glucose cotransporter 2 (SGLT2) significantly increases the hematocrit in patients with type 2 diabetes. To investigate whether SGLT2 inhibitors directly promote erythropoietin production independently on blood glucose reduction, the hematopoietic effect of the specific SGLT2 inhibitor, luseogliflozin, was examined in non‐diabetic rats with renal anemia.

Materials and Methods

Renal anemia was induced by treatment with adenine (200 or 600 mg/kg/day, orally for 10 days) in non‐diabetic Wistar–Kyoto or Wistar rats, respectively. Luseogliflozin (10 mg/kg bodyweight) or vehicle (0.5% carboxymethyl cellulose) was then administered for 6 weeks. The hematocrit and the hemoglobin (Hb), blood urea nitrogen, plasma creatinine, and plasma erythropoietin levels were monitored.

Results

Treatment with adenine decreased the hematocrit and the Hb level, which were associated with increases in the blood urea nitrogen and plasma creatinine levels. In Wistar–Kyoto rats treated with 200 mg/kg/day adenine, administration of luseogliflozin induced glycosuria, but did not change the blood urea nitrogen, plasma creatinine levels, hematocrit, Hb or plasma erythropoietin levels. Similarly, luseogliflozin treatment failed to change the hematocrit or the Hb levels in Wistar rats with renal anemia induced by 600 mg/kg/day of adenine. Plasma erythropoietin concentrations were also not different between luseogliflozin‐ and vehicle‐treated rats. Similarly, in human erythropoietin‐producing cells derived from pluripotent stem cells, luseogliflozin treatment did not change the erythropoietin level in the medium.

Conclusions

These data suggest that SGLT2 inhibitor fails to exert hematopoietic effects in non‐diabetic conditions.
Comparative efficacy of stents in endoscopic ultrasonography‐guided peripancreatic fluid collection drainage: A systematic review and network meta‐analysis
Authors: Park Chan Hyuk , Park Se Woo , Nam Eunwoo , Jung Jang Han , Jo Jung Hyun
Published: December 2019

Background

Although many studies have reported the efficacy of different stents for endoscopic ultrasonography (EUS)‐guided peripancreatic fluid collection (PFC) drainage, they have not completely determined which stent is superior. This network meta‐analysis comprehensively evaluated the comparative efficacy of stents used in EUS‐guided PFC.

Methods

We searched all relevant studies published up to February 2019 that examined the efficacy of double pigtail plastic stent (DPPS), fully covered self‐expanding metal stent (FCSEMS), and lumen‐apposing metal stent (LAMS) in EUS‐guided PFC drainage. We performed a Bayesian network meta‐analysis for clinical efficacy and adverse events.

Results

Fifteen studies comprising 1746 patients were included in the meta‐analysis. In terms of clinical success, no significant differences were noted in LAMS versus DPPS or LAMS versus FCSEMS (risk ratio [RR] 1.04 [95% credible interval (CrI) 0.99–1.11] and RR 0.96 [95% CrI 0.91–1.03]), respectively). FCSEMS was superior in terms of clinical success to DPPS (RR 1.09, 95% CrI 1.02–1.15). There was no significant difference in the recurrence of PFC among groups. Regarding adverse events, LAMS had a higher bleeding risk than FCSEMS (RR 6.70, 95% CrI 1.77–36.27) and tended to have a higher risk of bleeding than DPPS (RR 2.67, 95% CI 0.71–9.28). In terms of stent migration, there was no significant difference between any two groups compared.

Conclusions

FCSEMS had superior efficacy in terms of clinical success compared with DPPS stents. Significant superiority of LAMS to DPPS was not identified. Additionally, LAMS had the higher risk of bleeding than FCSEMS.