bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of the 7- and 13-Valent Pneumococcal Conjugate Vaccines Against Vaccine-Serotype Otitis Media
Authors: Dagan Ron , Van Der Beek Bart Adriaan , Ben-Shimol Shalom , Pilishvili Tamara , Givon-Lavi Noga
Published: January 2021

Background

Despite the demonstrated impact of pneumococcal vaccine (PCV) implementation on otitis media (OM), demonstration of real-life serotype-specific effectiveness of the 7-valent and 13-valent PCVs (PCV7 and PCV13) is lacking owing to the paucity of culture-positive cases. Furthermore, prelicensure PCV13 efficacy against OM was not studied.

Methods

The study was conducted from October 2009 to July 2013. Case patients were children aged 5–35 months with OM (mostly complex OM [recurrent/nonresponsive, spontaneously draining, chronic with effusion]) from whom middle-ear fluid culture was obtained; controls were contemporary children with rotavirus-negative gastroenteritis in a prospective population-based rotavirus surveillance, from the same age group with similar ethnic distribution and geographic location. Vaccine effectiveness (VE) was estimated as 1 minus the odds ratio using unconditional logistic regression, adjusting for time since PCV implementation, age, and ethnicity.

Results

A total of 223 case patients and 1370 controls were studied. Serotypes 19F and 19A together caused 56.1% of all vaccine-type (VT) OM. VE of ≥2 PCV doses in children aged 5–35 months was demonstrated as follows: PCV7 against OM due to PCV7 serotypes, 57.2% (95% confidence interval, 6.0%–80.5%); PCV13 against OM due to PCV13 serotypes, 77.4% (53.3%–92.1%); PCV13 against OM due to the 6 additional non-PCV7 serotypes 67.4% (17.6%–87.1%); PCV13 against OM due to serotype 19F, 91.3% (1.4%–99.2%); and PCV13 against OM due to serotype 3, 89.0% (23.9%–98.4%). PCV7 and PCV13 VE against OM due to serotype 19A in children aged 12–35 months was 72.4% (95% confidence interval, 6.2%–91.9%) and 94.6% (33.9%–99.6%), respectively.

Conclusions

PCV7 and PCV13 were effective against complex OM caused by the targeted serotypes.
Transcontinental Dissemination of the L2b/D-Da Recombinant Chlamydia trachomatis Lymphogranuloma venereum (LGV) Strain: Need of Broad Multi-Country Molecular Surveillance
Authors: Borges Vítor , Isidro Joana , Correia Cristina , Cordeiro Dora , Vieira Luís , Lodhia Zohra , Fernandes Cândida , Rodrigues Ana Maria , Azevedo Jacinta , Alves João , Roxo João , Rocha Miguel , Côrte-Real Rita , Toscano Cristina , Pessanha Maria Ana , Nissan Israel , Pilo Shlomo , Rorman Efrat , Dveyrin Zeev , Paitan Yossi , Paran Haim , Wagner-Kolasko Gal , Beirnes Jennifer , Gibbons Suzanne , Severini Alberto , Borrego Maria José , Gomes João Paulo
Published: January 2021

Previously, we identified a Chlamydia trachomatis lymphogranuloma venereum (LGV) recombinant strain possessing a non-LGV ompA genotype. Here, culture-independent genome sequencing confirms its circulation in Europe, Middle East, and North America, and unveils emergence of antibiotic resistance. Broad surveillance is needed.
Adverse clinical outcomes associated with RAAS inhibitor discontinuation: analysis of over 400 000 patients from the UK Clinical Practice Research Datalink (CPRD)
Authors: Humphrey Toby J L , James Glen , Wittbrodt Eric T , Zarzuela Donna , Hiemstra Thomas F
Published: January 2021

Background

Users of guideline-recommended renin–angiotensin–aldosterone system (RAAS) inhibitors may experience disruptions to their treatment, e.g. due to hyperkalaemia, hypotension or acute kidney injury. The risks associated with treatment disruption have not been comprehensively assessed; therefore, we evaluated the risk of adverse clinical outcomes in RAAS inhibitor users experiencing treatment disruptions in a large population-wide database.

Methods

This exploratory, retrospective analysis utilized data from the UK’s Clinical Practice Research Datalink, linked to Hospital Episodes Statistics and the Office for National Statistics databases. Adults (≥18 years) with first RAAS inhibitor use (defined as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) between 1 January 2009 and 31 December 2014 were eligible for inclusion. Time to the first occurrence of adverse clinical outcomes [all-cause mortality, all-cause hospitalization, cardiac arrhythmia, heart failure hospitalization, cardiac arrest, advancement in chronic kidney disease (CKD) stage and acute kidney injury] was compared between RAAS inhibitor users with and without interruptions or cessations to treatment during follow-up. Associations between baseline characteristics and adverse clinical outcomes were also assessed.

Results

Among 434 027 RAAS inhibitor users, the risk of the first occurrence of all clinical outcomes, except advancement in CKD stage, was 8–75% lower in patients without interruptions or cessations versus patients with interruptions/cessations. Baseline characteristics independently associated with increased risk of clinical outcomes included increasing age, smoking, CKD, diabetes and heart failure.

Conclusions

These findings highlight the need for effective management of factors associated with RAAS inhibitor interruptions or cessations in patients for whom guideline-recommended RAAS inhibitor treatment is indicated.
Clonotypic Features of Rearranged Immunoglobulin Genes Yield Personalized Biomarkers for Minimal Residual Disease Monitoring in Multiple Myeloma
Authors: Langerhorst Pieter , Brinkman Arie B , VanDuijn Martijn M , Wessels Hans J C T , Groenen Patricia J T A , Joosten Irma , van Gool Alain J , Gloerich Jolein , Scheijen Blanca , Jacobs Joannes F M
Published: January 2021

Background

Due to improved treatment, more patients with multiple myeloma (MM) reach a state of minimal residual disease (MRD). Different strategies for MM MRD monitoring include flow cytometry, allele-specific oligonucleotide–quantitative PCR, next-generation sequencing, and mass spectrometry (MS). The last 3 methods rely on the presence and the stability of a unique immunoglobulin fingerprint derived from the clonal plasma cell population. For MS-MRD monitoring it is imperative that MS-compatible clonotypic M-protein peptides are identified. To support implementation of molecular MRD techniques, we studied the presence and stability of these clonotypic features in the CoMMpass database.

Methods

An analysis pipeline based on MiXCR and HIGH-VQUEST was constructed to identify clonal molecular fingerprints and their clonotypic peptides based on transcriptomic datasets. To determine the stability of the clonal fingerprints, we compared the clonal fingerprints during disease progression for each patient.

Results

The analysis pipeline to establish the clonal fingerprint and MS-suitable clonotypic peptides was successfully validated in MM cell lines. In a cohort of 609 patients with MM, we demonstrated that the most abundant clone harbored a unique clonal molecular fingerprint and that multiple unique clonotypic peptides compatible with MS measurements could be identified for all patients. Furthermore, the clonal immunoglobulin gene fingerprints of both the light and heavy chain remained stable during MM disease progression.

Conclusions

Our data support the use of the clonal immunoglobulin gene fingerprints in patients with MM as a suitable MRD target for MS-MRD analyses.
The complex network of mTOR signalling in the heart
Authors: Sciarretta Sebastiano , Forte Maurizio , Frati Giacomo , Sadoshima Junichi
Published: January 2021

The mechanistic target of rapamycin (mTOR) integrates several intracellular and extracellular signals involved in the regulation of anabolic and catabolic processes. mTOR assembles into two macromolecular complexes, named mTORC1 and mTORC2, which have different regulators, substrates and functions. Studies of gain- and loss-of-function animal models of mTOR signalling revealed that mTORC1/2 elicits both adaptive and maladaptive functions in the cardiovascular system. Both mTORC1 and mTORC2 are indispensable for driving cardiac development and cardiac adaption to stress, such as pressure overload. However, persistent and deregulated mTORC1 activation in the heart is detrimental during stress and contributes to the development and progression of cardiac remodelling and genetic and metabolic cardiomyopathies. In this review, we discuss the latest findings regarding the role of mTOR in the cardiovascular system, both under basal conditions and during stress, such as pressure overload, ischemia, and metabolic stress. Current data suggest that mTOR modulation may represent a potential therapeutic strategy for the treatment of cardiac diseases.
Extraction of causal relations based on SBEL and BERT model
Authors: Shao Yifan , Li Haoru , Gu Jinghang , Qian Longhua , Zhou Guodong
Published: January 2021

Extraction of causal relations between biomedical entities in the form of Biological Expression Language (BEL) poses a new challenge to the community of biomedical text mining due to the complexity of BEL statements. We propose a simplified form of BEL statements [Simplified Biological Expression Language (SBEL)] to facilitate BEL extraction and employ BERT (Bidirectional Encoder Representation from Transformers) to improve the performance of causal relation extraction (RE). On the one hand, BEL statement extraction is transformed into the extraction of an intermediate form—SBEL statement, which is then further decomposed into two subtasks: entity RE and entity function detection. On the other hand, we use a powerful pretrained BERT model to both extract entity relations and detect entity functions, aiming to improve the performance of two subtasks. Entity relations and functions are then combined into SBEL statements and finally merged into BEL statements. Experimental results on the BioCreative-V Track 4 corpus demonstrate that our method achieves the state-of-the-art performance in BEL statement extraction with F1 scores of 54.8% in Stage 2 evaluation and of 30.1% in Stage 1 evaluation, respectively.

Database URL: https://github.com/grapeff/SBEL_datasets
Rheumatoid arthritis mimicking infective endocarditis with severe aortic regurgitation and aortic root abscess: a case report
Authors: Kyhl Frederik , Rasmussen Rasmus Vedby , Lindhardsen Jesper , Smerup Morten , Fosbøl Emil L
Published: January 2021

Background

Rheumatoid arthritis (RA) may involve the cardiovascular system and can cause significant structural cardiac disease. RA mimicking infective endocarditis (IE) is rarely reported.

Case summary

A 46-year-old man with a medical history of seropositive RA attended a planned outpatient visit for infliximab treatment. The pre-infusion examination revealed a pulse of 41 b.p.m. and the following electrocardiogram showed 3rd degree atrioventricular block. A temporary pacemaker was inserted, and subsequent transthoracic and transoesophageal echocardiograms showed severe aortic valve regurgitation with thickened cusps and thus raised suspicion of infective aortic endocarditis with root abscess. The patient underwent surgery with valve and root replacement the next day. What was thought to be IE, proved to be suppurative and granulomatous inflammation with sporadic necrosis and hyaline fibrosis, compatible with a rheumatoid nodule linked to the patient’s RA diagnosis.

Discussion

IE is a disease with high mortality and morbidity. In some cases of IE perivalvular cavities develop, most commonly abscesses and/or pseudoaneurysms, which necessitates surgery. Several conditions may mimic IE: for example, malignant and benign tumours, rheumatic diseases, and common age-related valve calcification. In patients with valvular vegetations that are ‘culture-negative’, alternative pathologies should be considered.
Fewer guns, less crime: evidence from Brazil
Authors: Schneider Rodrigo
Published: January 2021

This paper studies the effects of legislation in Brazil that banned the right to carry guns and provided for a voter referendum regarding whether to ban the sale of all firearms. Using a regression discontinuity design, I find that gun-related homicides decreased by 12.2% and gunshot wounds that were ‘intended to kill’ by 16.3%, with the reduction of the former being especially pronounced in high-crime areas and among black males. There is no evidence of substitution effect as non-gun-related homicides were not affected. Two pieces of evidence suggest that the mechanism explaining this result is a decrease in the number of people carrying guns in response to the legislation: first, the number of cases of illegal gun carrying decreased and second, only gun-related homicides taking place outside the residence were reduced. Analysis of the subsequent voter referendum, which was defeated by a wide margin, shows stronger support for the complete firearms ban in the areas more affected by gun violence.
Liquidity, hedging and the survival of North German dairy farms
Authors: Hoehl Stephan , Hess Sebastian
Published: January 2021

Increasingly, European dairy farmers have to manage the raw milk price risk. Price hedging for raw milk and an increasing number of individual fixed-price contracts with processors are now available. However, the choice of hedging a certain share of milk output still leaves individual farmers facing a complex decision. The cash flow model in this study explains the probability of a typical northern European dairy farm surviving illiquidity over an 18-month period under common milk price volatility. The probability of farm survival was modelled in relation to available liquidity buffers and different levels of farm-specific production costs. The model allowed minimum shares of milk output to be determined, for which a fixed price should be hedged if the objective is farm survival at a given probability. Using these modelling results, practitioners are able to determine this share graphically.
Diagnostic yield and financial implications of a nationwide electrocardiographic screening programme to detect cardiac disease in the young
Authors: Dhutia Harshil , Malhotra Aneil , Finocchiaro Gherardo , Parpia Sameer , Bhatia Raghav , D’Silva Andrew , Gati Sabiha , Mellor Greg , Narain Rajay , Chandra Navin , Behr Elijah , Tome Maite , Papadakis Michael , Sharma Sanjay
Published: January 2021

Aims

There is limited information on the role of screening with electrocardiography (ECG) for identifying cardiovascular diseases associated with sudden cardiac death (SCD) in a non-select group of adolescents and young adults in the general population.

Methods and results

Between 2012 and 2014, 26 900 young individuals (aged 14–35 years) were prospectively evaluated with a health questionnaire and ECG. Individuals with abnormal results underwent secondary investigations, the costs of which were being based on the UK National Health Service tariffs. Six hundred and seventy-five (2.5%) individuals required further investigation for an abnormal health questionnaire, 2175 (8.1%) for an abnormal ECG, and 114 (0.5%) for both. Diseases associated with young SCD were identified in 88 (0.3%) individuals of which 15 (17%) were detected with the health questionnaire, 72 (81%) with ECG and 2 (2%) with both. Forty-nine (56%) of these individuals received medical intervention beyond lifestyle modification advice in the follow-up period of 24 months. The overall cost of the evaluation process was €97 per person screened, €17 834 per cardiovascular disease detected, and €29 588 per cardiovascular disease associated with SCD detected. Inclusion of ECG was associated with a 36% cost reduction per diagnosis of diseases associated with SCD compared with the health questionnaire alone.

Conclusion

The inclusion of an ECG to a health questionnaire is associated with a five-fold increase in the ability to detect disease associated with SCD in young individuals and is more cost effective for detecting serious disease compared with screening with a health questionnaire alone.
Genetic mapping and transcriptomic characterization of a new fuzzless-tufted cottonseed mutant
Authors: Zhu Qian-Hao , Stiller Warwick , Moncuquet Philippe , Gordon Stuart , Yuan Yuman , Barnes Scott , Wilson Iain
Published: January 2021

Fiber mutants are unique and valuable resources for understanding the genetic and molecular mechanisms controlling initiation and development of cotton fibers that are extremely elongated single epidermal cells protruding from the seed coat of cottonseeds. In this study, we reported a new fuzzless-tufted cotton mutant (Gossypium hirsutum) and showed that fuzzless-tufted near-isogenic lines (NILs) had similar agronomic traits and a higher ginning efficiency compared to their recurrent parents with normal fuzzy seeds. Genetic analysis revealed that the mutant phenotype is determined by a single incomplete dominant locus, designated N5. The mutation was fine mapped to an approximately 250-kb interval containing 33 annotated genes using a combination of bulked segregant sequencing, SNP chip genotyping, and fine mapping. Comparative transcriptomic analysis using 0–6 days post-anthesis (dpa) ovules from NILs segregating for the phenotypes of fuzzless-tufted (mutant) and normal fuzzy cottonseeds (wild-type) uncovered candidate genes responsible for the mutant phenotype. It also revealed that the flanking region of the N5 locus is enriched with differentially expressed genes (DEGs) between the mutant and wild-type. Several of those DEGs are members of the gene families with demonstrated roles in cell initiation and elongation, such as calcium-dependent protein kinase and expansin. The transcriptome landscape of the mutant was significantly reprogrammed in the 6 dpa ovules and, to a less extent, in the 0 dpa ovules, but not in the 2 and 4 dpa ovules. At both 0 and 6 dpa, the reprogrammed mutant transcriptome was mainly associated with cell wall modifications and transmembrane transportation, while transcription factor activity was significantly altered in the 6 dpa mutant ovules. These results imply a similar molecular basis for initiation of lint and fuzz fibers despite certain differences.
ASNS disruption shortens CTPS cytoophidia in Saccharomyces cerevisiae
Authors: Zhang Shanshan , Feng Han-Chao , Liu Ji-Long
Published: January 2021

Asparagine synthetase (ASNS) and CTP synthase (CTPS) are two metabolic enzymes that catalyze the biosynthesis of asparagine and CTP, respectively. Both CTPS and ASNS have been identified to form cytoophidia in Saccharomyces cerevisiae. Glutamine is a common substrate for both these enzymes, and they play an important role in glutamine homeostasis. Here, we find that the ASNS cytoophidia are shorter than the CTPS cytoophidia, and that disruption of ASNS shortens the length of CTPS cytoophidia. However, the deletion of CTPS has no effect on the formation and length of ASNS cytoophidia, or on the ASNS protein level. We also find that Asn1 overexpression induces the formation of a multi-dot structure in diauxic phase which suggests that the increased protein level may trigger cytoophidia formation. Collectively, our results reveal a connection between ASNS cytoophidia and CTPS cytoophidia.
Seismic images of the Northern Chilean subduction zone at 19°40′S, prior to the 2014 Iquique earthquake
Authors: Storch Ina , Buske Stefan , Victor Pia , Oncken Onno
Published: January 2021

The Northern Chilean subduction zone is characterized by long-term subduction erosion with very little sediment input at the trench and the lack of an accretionary prism. Here, multichannel seismic reflection (MCS) data were acquired as part of the CINCA (Crustal Investigations off- and onshore Nazca Plate/Central Andes) project in 1995. These lines cover among others the central part of the MW 8.1 Iquique earthquake rupture zone before the earthquake occurred on 1 April 2014. We have re-processed one of the lines crossing the updip parts of this earthquake at 19°40′S, close to its hypocentre. After careful data processing and data enhancement, we applied a coherency-based pre-stack depth migration algorithm, yielding a detailed depth image. The resulting depth image shows the subduction interface prior to the Iquique megathrust earthquake down to a depth of approximately 16 km and gives detailed insight into the characteristics of the seismogenic coupling zone. We found significantly varying interplate reflectivity along the plate interface which we interpret to be caused by the comparably strong reflectivity of subducted fluid-rich sediments within the grabens and half-grabens that are predominant in this area due to the subduction-related bending of the oceanic plate. No evidence was found for a subducted seamount associated to the Iquique Ridge along the slab interface at this latitude as interpreted earlier from the same data set. By comparing relocated fore- and aftershock seismicity of the Iquique earthquake with the resulting depth image, we can divide the continental wedge into two domains. First, a frontal unit beneath the lower slope with several eastward dipping back-rotated splay faults but no seismicity in the upper plate as well as along the plate interface. Secondly, a landward unit beneath the middle slope with differing reflectivity that shows significant seismicity in the upper plate as well as along the plate interface. Both units are separated by a large eastward dipping mega splay fault, the root zone of which shows diffuse seismicity, both in the upper plate and at the interface. The identification of a well-defined nearly aseismic frontal unit sheds new light on the interplate locking beneath the lower continental slope and its controls.
What Is the Significance of a FRAND License Declaration for Standard Essential Patents with Regard to their Transferability? – News from Germany
Authors: Czychowski Christian
Published: January 2021

There has been considerable movement in German licensing law for some years now. Based on the fate of the license in the case of the granting of sub-licenses and in the case of insolvency of one of the contracting parties involved, a number of court decisions have been handed down which mainly deal with the legal nature of licenses and their mode of operation.

Moreover, there is now an internationally significant development in licensing law, namely the increasing independence of patents used in standards, which have increasingly become the subject of economic considerations – and not only of the companies or inventors filing them.1 These so-called standard essential patents (SEPs) are the subject of numerous legal disputes and legislative activities and constitute a scientific discourse around the globe.

In 2015, the European Court of Justice (ECJ) created the first leading case for the EU with regard to SEPs in its highly regarded Huawei/ZTE ruling.2 Although an abundance of decisions of the courts of first instances are now available, many questions still remain unanswered since the fundamental decision of the ECJ. There is controversy both over the dogmatic classification of the FRAND declaration and the legal consequences of the declaration’s binding effect. It is particularly unclear what happens to the FRAND declaration when the SEP is transferred to a third party and whether, how and to what extent the acquirer is bound by this declaration of the transferor. In a decision that can certainly be described as bold, a Higher Regional Court has now ruled on some of these issues for the first time, thus providing further food for discussion.3
A systematic review and meta-analysis of the effectiveness of maternity waiting homes in low- and middle-income countries
Authors: McRae Daphne N , Bergen Nicole , Portela Anayda G , Muhajarine Nazeem
Published: January 2021

Maternity waiting homes (MWHs) in low- and middle-income countries (LMICs) provide women with accommodation close to a health facility to enable timely access to skilled care at birth. We examined whether MWH use and availability compared with non-use/unavailability were associated with facility birth, birth with a skilled health professional, attendance at postnatal visit(s) and/or improved maternal and newborn health, in LMICs. We included (non-)randomized controlled, interrupted time series, controlled before–after, cohort and case–control studies published since 1990. Thirteen databases were searched with no language restrictions. Included studies (1991–2020) were assessed as either moderate (n = 9) or weak (n = 10) on individual quality using the Effective Public Health Practice Project tool. Quality was most frequently compromised by selection bias, confounding and blinding. Only moderate quality studies were analyzed; no studies examining maternal morbidity/mortality met this criterion. MWH users had less relative risk (RR) of perinatal mortality [RR 0.65, 95% confidence intervals (CIs): 0.48, 0.87] (3 studies) and low birthweight (RR 0.34, 95% CI: 0.20, 0.59) (2 studies) compared with non-users. There were no significant differences between MWH use and non-use for stillbirth (RR 0.75, 95% CI: 0.47, 1.18) (3 studies) or neonatal mortality (RR 0.51, 95% CI: 0.25, 1.02) (2 studies). Single study results demonstrated higher adjusted odds ratios (aOR) for facility birth (aOR 5.8, 95% CI: 2.6, 13.0) and attendance at all recommended postnatal visits within 6 weeks of birth (aOR 1.99, 95% CI: 1.30, 3.07) for MWH users vs. non-users. The presence vs. absence of an MWH was associated with a 19% increase in facility birth (aOR 1.19, 95% CI: 1.10, 1.29). The presence vs. absence of a hospital-affiliated MWH predicted a 47% lower perinatal mortality rate (P  <  0.01), but at a healthcare centre-level a 13 higher perinatal mortality rate (P  <  0.01). Currently, there remains a lack of robust evidence supporting MWH effectiveness. We outline a six-point strategy for strengthening the evidence base.
Maternal and perinatal death surveillance and response in low- and middle-income countries: a scoping review of implementation factors
Authors: Kinney Mary V , Walugembe David Roger , Wanduru Phillip , Waiswa Peter , George Asha
Published: January 2021

Maternal and perinatal death surveillance and response (MPDSR), or any form of maternal and/or perinatal death review or audit, aims to improve health services and pre-empt future maternal and perinatal deaths. With expansion of MPDSR across low- and middle-income countries (LMIC), we conducted a scoping review to identify and describe implementation factors and their interactions. The review adapted an implementation framework with four domains (intervention, individual, inner and outer settings) and three cross-cutting health systems lenses (service delivery, societal and systems). Literature was sourced from six electronic databases, online searches and key experts. Selection criteria included studies from LMIC published in English from 2004 to July 2018 detailing factors influencing implementation of MPDSR, or any related form of MPDSR. After a systematic screening process, data for identified records were extracted and analysed through content and thematic analysis. Of 1027 studies screened, the review focuses on 58 studies from 24 countries, primarily in Africa, that are mainly qualitative or mixed methods. The literature mostly examines implementation factors related to MPDSR as an intervention, and to its inner and outer setting, with less attention to the individuals involved. From a health systems perspective, almost half the literature focuses on the tangible inputs addressed by the service delivery lens, though these are often measured inadequately or through incomparable ways. Though less studied, the societal and health system factors show that people and their relationships, motivations, implementation climate and ability to communicate influence implementation processes; yet their subjective experiences and relationships are inadequately explored. MPDSR implementation contributes to accountability and benefits from a culture of learning, continuous improvement and accountability, but few have studied the complex interplay and change dynamics involved. Better understanding MPDSR will require more research using health policy and systems approaches, including the use of implementation frameworks.
Mosaic IL6ST variant inducing constitutive GP130 cytokine receptor signaling as a cause of neonatal onset immunodeficiency with autoinflammation and dysmorphy
Authors: Materna-Kiryluk Anna , Pollak Agnieszka , Gawalski Karol , Szczawinska-Poplonyk Aleksandra , Rydzynska Zuzanna , Sosnowska Anna , Cukrowska Bożena , Gasperowicz Piotr , Konopka Ewa , Pietrucha Barbara , Grzywa Tomasz M , Banaszak-Ziemska Magdalena , Niedziela Marek , Skalska-Sadowska Jolanta , Stawiński Piotr , Śladowski Dariusz , Nowis Dominika , Ploski Rafal
Published: January 2021

Interleukin-6 signal transducer (IL6ST) encodes the GP130 protein which transduces the proinflammatory signaling of the IL6 cytokine family through Janus kinase signal transducers and activators of transcription pathway (JAK/STAT) activation. Biallelic loss-of-function IL6ST variants cause autosomal recessive hyper-IgE syndrome or a variant of the Stuve–Wiedemann syndrome. Somatic gain-of-function IL6ST mutations, in particular, small monoallelic in-frame deletions of which the most prevalent is the IL6ST Ser187_Tyr190del, are an established cause of inflammatory hepatocellular tumors, but so far, no disease caused by such mutations present constitutively has been described. Herein, we report a pediatric proband with a novel syndrome of neonatal onset immunodeficiency with autoinflammation and dysmorphy associated with the IL6ST Tyr186_Tyr190del variant present constitutively. Tyr186_Tyr190del was found by exome sequencing and was shown to be de novo (absent in proband’s parents and siblings) and mosaic (present in approximately 15–40% of cells depending on the tissue studied—blood, urine sediment, hair bulbs and buccal swab). Functional studies were performed in the Epstein–Barr virus-immortalized patient’s B cell lymphoblastoid cell line, which carried the variant in approximately 95% of the cells. Western blot showed that the patient’s cells exhibited constitutive hyperphosphorylation of Tyr705 in STAT3, which is indicative of IL6-independent activation of GP130. Interestingly, the STAT3 phosphorylation could be inhibited with ruxolitinib as well as tofacitinib, which are clinically approved JAK1 and JAK3 (to lesser extent JAK2 and JAK1) inhibitors, respectively. Given our results and the recent reports of ruxolitinib and tofacitinib use for the treatment of diseases caused by direct activation of STAT3 or STAT1, we speculate that these drugs may be effective in the treatment of our patient’s condition.
Scenario analysis can guide aquaculture planning to meet sustainable future production goals
Authors: Couture Jessica L , Froehlich Halley E , Buck Bela H , Jeffery Keith R , Krause Gesche , Morris Jr James A , Pérez Montse , Stentiford Grant D , Vehviläinen Harri , Halpern Benjamin S
Published: January 2021

Marine aquaculture holds great promise for meeting increasing demand for healthy protein that is sustainably produced, but reaching necessary production levels will be challenging. The ecosystem approach to aquaculture is a framework for sustainable aquaculture development that prioritizes multiple-stakeholder participation and spatial planning. These types of approaches have been increasingly used to help guide sustainable, persistent, and equitable aquaculture planning, but most countries have difficulties in setting or meeting longer-term development goals. Scenario analysis (SA) for future planning uses similar approaches and can complement holistic methods, such as the ecosystem approach to aquaculture framework, by providing a temporal analogue to the spatially robust design. Here we define the SA approach to planning in aquaculture, outline how SA can benefit aquaculture planning, and review how this tool is already being used. We track the use of planning tools in the 20 International Council for the Exploration of the Sea member nations, with particular attention given to Norway’s development goals to 2050. We conclude that employing a combination of an ecosystem framework with scenario analyses may help identify the scale of development aquaculture goals over time, aid in evaluating the feasibility of the desired outcomes, and highlight potential social-ecological conflicts and trade-offs that may otherwise be overlooked.
Comparison of half-turned truncal switch and conventional operations
Authors: Hongu Hisayuki , Yamagishi Masaaki , Maeda Yoshinobu , Itatani Keiichi , Asada Satoshi , Fujita Shuhei , Nakatsuji Hiroki , Yaku Hitoshi
Published: January 2021

OBJECTIVES

To compare conventional procedures with the half-turned truncal switch operation (HTTSO) for the management of complete transposition of the great arteries with left ventricular outflow tract (LVOT) obstruction using time-resolved 3-dimensional magnetic resonance phase-contrast imaging.

METHODS

We identified 2 cases that underwent the Rastelli procedure and one case that underwent the Réparation a l'étage ventriculaire before 2002 [conventional procedures group (group C)], and 16 cases of HTTSO that were performed between 2002 and 2020 [HTTSO group (group H)]. Postoperative haemodynamics were assessed using time-resolved 3-dimensional magnetic resonance phase-contrast imaging in cases in both groups.

RESULTS

The median follow-up period was 20.4 years in group C, and 6.1 years in group H. In group C, all 3 patients underwent reoperation because of postoperative right ventricular outflow tract obstruction and/or insufficiency. In addition, permanent pacemaker implantation was needed in 1 patient because of complete atrioventricular block complicated by ventricular septal defect enlargement. In group H, reoperation for LVOT/right ventricular outflow tract obstruction was not needed. A time-resolved 3-dimensional magnetic resonance phase-contrast imaging examination revealed high energy loss and wall shear stress in the winding LVOT in the group C. In contrast, low energy loss and wall shear stress, with straight and smooth LVOT, were identified in group H.

CONCLUSIONS

HTTSO was shown to be superior to conventional procedures because a straight and wide LVOT could be obtained. Therefore, HTTSO should be the first choice for complete transposition of the great arteries with LVOT obstruction.
Role Theory, Foreign Policy, and the Social Construction of Sovereignty: Brexit Stage Right
Authors: Beasley Ryan K , Kaarbo Juliet , Oppermann Kai
Published: January 2021

The international roles states play in world politics are bound up with the ways in which sovereignty is constructed within the international system. While scholarship on sovereignty has recognized its social construction, and role research emphasizes social interactions as shaping roles and role behaviors, little work has explored the relationship between sovereignty and roles. Linking roles and sovereignty offers a distinct perspective on the social construction of sovereignty, providing a broad conception of socialization, emphasizing agency, and bridging domestic politics and international relations. We develop the concept of a “sovereignty–role nexus” through an examination of Brexit, revealing, through processes of role contestation and role socialization, multiple and competing constructions of the nature and value of sovereignty. While Brexit is unique, we suggest that these dynamics will affect other cases where states face role changes linked to sovereignty concerns.
Comparison of an oncology clinical decision-support system’s recommendations with actual treatment decisions
Authors: Suwanvecho Suthida , Suwanrusme Harit , Jirakulaporn Tanawat , Issarachai Surasit , Taechakraichana Nimit , Lungchukiet Palita , Decha Wimolrat , Boonpakdee Wisanu , Thanakarn Nittaya , Wongrattananon Pattanawadee , Preininger Anita M , Solomon Metasebya , Wang Suwei , Hekmat Rezzan , Dankwa-Mullan Irene , Shortliffe Edward , Patel Vimla L , Arriaga Yull , Jackson Gretchen Purcell , Kiatikajornthada Narongsak
Published: January 2021

Objective

IBM(R) Watson for Oncology (WfO) is a clinical decision-support system (CDSS) that provides evidence-informed therapeutic options to cancer-treating clinicians. A panel of experienced oncologists compared CDSS treatment options to treatment decisions made by clinicians to characterize the quality of CDSS therapeutic options and decisions made in practice.

Methods

This study included patients treated between 1/2017 and 7/2018 for breast, colon, lung, and rectal cancers at Bumrungrad International Hospital (BIH), Thailand. Treatments selected by clinicians were paired with therapeutic options presented by the CDSS and coded to mask the origin of options presented. The panel rated the acceptability of each treatment in the pair by consensus, with acceptability defined as compliant with BIH’s institutional practices. Descriptive statistics characterized the study population and treatment-decision evaluations by cancer type and stage.

Results

Nearly 60% (187) of 313 treatment pairs for breast, lung, colon, and rectal cancers were identical or equally acceptable, with 70% (219) of WfO therapeutic options identical to, or acceptable alternatives to, BIH therapy. In 30% of cases (94), 1 or both treatment options were rated as unacceptable. Of 32 cases where both WfO and BIH options were acceptable, WfO was preferred in 18 cases and BIH in 14 cases. Colorectal cancers exhibited the highest proportion of identical or equally acceptable treatments; stage IV cancers demonstrated the lowest.

Conclusion

This study demonstrates that a system designed in the US to support, rather than replace, cancer-treating clinicians provides therapeutic options which are generally consistent with recommendations from oncologists outside the US.
Exploring the relationship between electronic health records and provider burnout: A systematic review
Authors: Yan Qi , Jiang Zheng , Harbin Zachary , Tolbert Preston H , Davies Mark G
Published: January 2021

Objective

Stress and burnout due to electronic health record (EHR) technology has become a focus for burnout intervention. The aim of this study is to systematically review the relationship between EHR use and provider burnout.

Materials and Methods

A systematic literature search was performed on PubMed, EMBASE, PsychInfo, ACM Digital Library in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Inclusion criterion was original research investigating the association between EHR and provider burnout. Studies that did not measure the association objectively were excluded. Study quality was assessed using the Medical Education Research Study Quality Instrument. Qualitative synthesis was also performed.

Results

Twenty-six studies met inclusion criteria. The median sample size of providers was 810 (total 20 885; 44% male; mean age 53 [range, 34-56] years). Twenty-three (88%) studies were cross-sectional studies and 3 were single-arm cohort studies measuring pre- and postintervention burnout prevalence. Burnout was assessed objectively with various validated instruments. Insufficient time for documentation (odds ratio [OR], 1.40-5.83), high inbox or patient call message volumes (OR, 2.06-6.17), and negative perceptions of EHR by providers (OR, 2.17-2.44) were the 3 most cited EHR-related factors associated with higher rates of provider burnout that was assessed objectively.

Conclusions

The included studies were mostly observational studies; thus, we were not able to determine a causal relationship. Currently, there are few studies that objectively assessed the relationship between EHR use and provider burnout. The 3 most cited EHR factors associated with burnout were confirmed and should be the focus of efforts to improve EHR-related provider burnout.
The impact of electronic health record–integrated patient-generated health data on clinician burnout
Authors: Ye Jiancheng
Published: January 2021

Patient-generated health data (PGHD), such as patient-reported outcomes and mobile health data, have been increasingly used to improve health care delivery and outcomes. Integrating PGHD into electronic health records (EHRs) further expands the capacities to monitor patients’ health status without requiring office visits or hospitalizations. By reviewing and discussing PGHD with patients remotely, clinicians could address the clinical issues efficiently outside of clinical settings. However, EHR-integrated PGHD may create a burden for clinicians, leading to burnout. This study aims to investigate how interactions with EHR-integrated PGHD may result in clinician burnout. We identify the potential contributing factors to clinician burnout using a modified FITT (Fit between Individuals, Task and Technology) framework. We found that technostress, time pressure, and workflow-related issues need to be addressed to accelerate the integration of PGHD into clinical care. The roles of artificial intelligence, algorithm-based clinical decision support, visualization format, human-computer interaction mechanism, workflow optimization, and financial reimbursement in reducing burnout are highlighted.
The use of live yeast to increase intake and performance of cattle receiving low-quality tropical forages
Authors: Parra Mariano C , Costa Diogo F A , Palma Andre S V , Camargo Karine D V , Lima Lais O , Harper Karen J , Meale Sarah J , Silva Luis F P
Published: January 2021

The objective was to evaluate the effects of a specific strain of live yeast (LY) on growth performance, fermentation parameters, feed efficiency, and bacterial communities in the rumen of growing cattle fed low-quality hay. In experiment (exp.) 1, 12 Droughtmaster bull calves (270 ± 7.6 kg initial body weight [BW]) were blocked by BW into two groups, allocated individually in pens, and fed ad libitum Rhodes grass hay (8.4% of crude protein [CP]) and 300 g/bull of supplement (52% CP) without (Control) or with LY (8 × 109 colony-forming unit [CFU]/d Saccharomyces cerevisiae CNCM I-1077; Lallemand Inc., Montreal, Canada) for 28 d, followed by 7 d in metabolism crates. Blood and rumen fluid were collected before feeding and 4 h after feeding. In exp. 2, for assessment of growth performance, 48 Charbray steers (329 ± 20.2 kg initial BW) were separated into two blocks by initial BW and randomly allocated into 12 pens. The steers were fed Rhodes grass hay (7.3% CP) and 220 g/steer of supplement (60% CP) without or with LY (8 × 109 CFU/d) for 42 d, after a 2-wk adaptation period. In exp. 1, fiber digestibility was calculated from total fecal collection, and, in exp 2, indigestible neutral detergent fiber (NDF) was used as a marker. Inclusion of LY increased (P = 0.03) NDF intake by 8.3% in exp. 1, without affecting total tract digestibility. No changes were observed in microbial yield or in the efficiency of microbial production. There was a Treatment × Time interaction (P < 0.01) for the molar proportion of short-chain fatty acids, with LY increasing propionate before feeding. Inclusion of LY decreased rumen ammonia 4 h after feeding (P = 0.03). The addition of LY reduced rumen bacterial diversity and the intraday variation in bacterial populations. Relative populations of Firmicutes and Verrucomicrobia varied over time (P < 0.05) only within the Control group. At the genus level, the relative abundance of an unclassified bacterial genus within the order Clostridiales, a group of cellulolytic bacteria, was reduced from 0 to 4 h after feeding in the Control group (P = 0.02) but not in the LY group (P = 1.00). During exp. 2, LY tended to increase average daily gain (ADG) (P = 0.08) and feed efficiency (P = 0.10), with no effect on NDF intake or digestibility. In conclusion, S. cerevisiae CNCM I-1077 reduced the intraday variation of rumen bacteria and increased the amount of NDF digested per day. These observations could be associated with the tendency of increased ADG and feed efficiency in growing cattle fed a low-quality forage.
Improvement, identification, and target prediction for miRNAs in the porcine genome by using massive, public high-throughput sequencing data
Authors: Fu Yuhua , Fan Pengyu , Wang Lu , Shu Ziqiang , Zhu Shilin , Feng Siyuan , Li Xinyun , Qiu Xiaotian , Zhao Shuhong , Liu Xiaolei
Published: January 2021

Despite the broad variety of available microRNA (miRNA) research tools and methods, their application to the identification, annotation, and target prediction of miRNAs in nonmodel organisms is still limited. In this study, we collected nearly all public sRNA-seq data to improve the annotation for known miRNAs and identify novel miRNAs that have not been annotated in pigs (Sus scrofa). We newly annotated 210 mature sequences in known miRNAs and found that 43 of the known miRNA precursors were problematic due to redundant/missing annotations or incorrect sequences. We also predicted 811 novel miRNAs with high confidence, which was twice the current number of known miRNAs for pigs in miRBase. In addition, we proposed a correlation-based strategy to predict target genes for miRNAs by using a large amount of sRNA-seq and RNA-seq data. We found that the correlation-based strategy provided additional evidence of expression compared with traditional target prediction methods. The correlation-based strategy also identified the regulatory pairs that were controlled by nonbinding sites with a particular pattern, which provided abundant complementarity for studying the mechanism of miRNAs that regulate gene expression. In summary, our study improved the annotation of known miRNAs, identified a large number of novel miRNAs, and predicted target genes for all pig miRNAs by using massive public data. This large data-based strategy is also applicable for other nonmodel organisms with incomplete annotation information.
Death by suicide, other externally caused injuries and cardiovascular diseases within 6 months of cancer diagnosis (J-SUPPORT 1902)
Authors: Harashima Saki , Fujimori Maiko , Akechi Tatsuo , Matsuda Tomohiro , Saika Kumiko , Hasegawa Takaaki , Inoue Keisuke , Yoshiuchi Kazuhiro , Miyashiro Isao , Uchitomi Yosuke , J Matsuoka Yutaka
Published: January 2021

Objective

To conduct the first national population-based study in Japan to characterize risks of death by suicide, other externally caused injuries and cardiovascular diseases within 6 months of cancer diagnosis.

Methods

Cancer patients diagnosed between 1 January and 30 June 2016 and registered in the National Cancer Registry in Japan were followed up until death or 6 months after diagnosis. We calculated standardized mortality ratios and excess absolute risks per 10 000 person-years for death by suicide, other externally caused injuries and cardiovascular diseases compared with the Japanese general population.

Results

Of 546 148 patients with cancer (249 116 person-years at risk), we observed 145 suicides, 298 deaths due to other externally caused injuries and 2366 cardiovascular deaths during the follow-up period. Standardized mortality ratios within 6 months were 2.68 for suicide (95% confidence interval, 2.26–3.16; excess absolute risk, 3.65), 1.49 for other externally caused injuries (95% confidence interval, 1.32–1.67; excess absolute risk, 3.92) and 1.38 for cardiovascular diseases (95% confidence interval, 1.33–1.44; excess absolute risk, 26.85). Risks were highest during the first month after cancer diagnosis (standardized mortality ratios: suicide, 4.06 [95% confidence interval, 2.90–5.53]; other externally caused injuries, 2.66 [95% confidence interval, 2.17–3.12] and cardiovascular diseases, 2.34 [95% confidence interval, 2.18–2.51]).

Conclusions

The first 6 months, and especially the first month, after cancer diagnosis were found to be a critical period for risks of death by suicide, other externally caused injuries and cardiovascular diseases. Our findings suggest that oncologists need to evaluate suicidal and cardiovascular risks of patients immediately after cancer diagnosis and provide preventive interventions.