bluuebunny/crossref_metadata_2025 huggingface dataset:
TCRpair: prediction of functional pairing between HLA-A*02:01-restricted T-cell receptor α and β chains
Authors: Mösch Anja , Frishman Dmitrij
Published: September 2021

The ability of a T cell to recognize foreign peptides is defined by a single α and a single β hypervariable complementarity determining region (CDR3), which together form the T-cell receptor (TCR) heterodimer. In ∼30–35% of T cells, two α chains are expressed at the mRNA level but only one α chain is part of the functional TCR. This effect can also be observed for β chains, although it is less common. The identification of functional α/β chain pairs is instrumental in high-throughput characterization of therapeutic TCRs. TCRpair is the first method that predicts whether an α and β chain pair forms a functional, HLA-A*02:01 specific TCR without requiring the sequence of a recognized peptide. By taking additional amino acids flanking the CDR3 regions into account, TCRpair achieves an AUC of 0.71.

Availability and implementation

TCRpair is implemented in Python using TensorFlow 2.0 and is freely available at https://www.github.com/amoesch/TCRpair.

Supplementary information

Supplementary data are available at Bioinformatics online.
Prowler: a novel trimming algorithm for Oxford Nanopore sequence data
Authors: Lee Simon , Nguyen Loan T , Hayes Ben J , Ross Elizabeth M
Published: September 2021

Motivation

Trimming and filtering tools are useful in DNA sequencing analysis because they increase the accuracy of sequence alignments and thus the reliability of results. Oxford nanopore technologies (ONT) trimming and filtering tools are currently rudimentary, generally only filtering reads based on whole read average quality. This results in discarding reads that contain regions of high-quality sequence. Here, we propose Prowler, a trimmer that uses a window-based approach inspired by algorithms used to trim short read data. Importantly, we retain the phase and read length information by optionally replacing trimmed sections with Ns.

Results

Prowler was applied to mammalian and bacterial datasets, to assess its effect on alignment and assembly, respectively. Compared to data filtered with Nanofilt, alignments of data trimmed with Prowler had lower error rates and more mapped reads. Assemblies of Prowler trimmed data had a lower error rate than those filtered with Nanofilt; however, this came at some cost to assembly contiguity.

Availability and implementation

Prowler is implemented in Python and is available at https://github.com/ProwlerForNanopore/ProwlerTrimmer.

Supplementary information

Supplementary data are available at Bioinformatics online.
DisoLipPred: accurate prediction of disordered lipid-binding residues in protein sequences with deep recurrent networks and transfer learning
Authors: Katuwawala Akila , Zhao Bi , Kurgan Lukasz
Published: September 2021

Motivation

Intrinsically disordered protein regions interact with proteins, nucleic acids and lipids. Regions that bind lipids are implicated in a wide spectrum of cellular functions and several human diseases. Motivated by the growing amount of experimental data for these interactions and lack of tools that can predict them from the protein sequence, we develop DisoLipPred, the first predictor of the disordered lipid-binding residues (DLBRs).

Results

DisoLipPred relies on a deep bidirectional recurrent network that implements three innovative features: transfer learning, bypass module that sidesteps predictions for putative structured residues, and expanded inputs that cover physiochemical properties associated with the protein–lipid interactions. Ablation analysis shows that these features drive predictive quality of DisoLipPred. Tests on an independent test dataset and the yeast proteome reveal that DisoLipPred generates accurate results and that none of the related existing tools can be used to indirectly identify DLBR. We also show that DisoLipPred’s predictions complement the results generated by predictors of the transmembrane regions. Altogether, we conclude that DisoLipPred provides high-quality predictions of DLBRs that complement the currently available methods.

Availability and implementation

DisoLipPred’s webserver is available at http://biomine.cs.vcu.edu/servers/DisoLipPred/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Amyloid-driven disruption of default mode network connectivity in cognitively healthy individuals
Authors: Ingala Silvia , Tomassen Jori , Collij Lyduine E , Prent Naomi , van ‘t Ent Dennis , ten Kate Mara , Konijnenberg Elles , Yaqub Maqsood , Scheltens Philip , de Geus Eco J C , Teunissen Charlotte E , Tijms Betty , Wink Alle Meije , Barkhof Frederik , van Berckel Bart N M , Visser Pieter Jelle , den Braber Anouk
Published: September 2021

Cortical accumulation of amyloid beta is one of the first events of Alzheimer’s disease pathophysiology, and has been suggested to follow a consistent spatiotemporal ordering, starting in the posterior cingulate cortex, precuneus and medio-orbitofrontal cortex. These regions overlap with those of the default mode network, a brain network also involved in memory functions. Aberrant default mode network functional connectivity and higher network sparsity have been reported in prodromal and clinical Alzheimer’s disease. We investigated the association between amyloid burden and default mode network connectivity in the preclinical stage of Alzheimer’s disease and its association with longitudinal memory decline. We included 173 participants, in which amyloid burden was assessed both in CSF by the amyloid beta 42/40 ratio, capturing the soluble part of amyloid pathology, and in dynamic PET scans calculating the non-displaceable binding potential in early-stage regions. The default mode network was identified with resting-state functional MRI. Then, we calculated functional connectivity in the default mode network, derived from independent component analysis, and eigenvector centrality, a graph measure recursively defining important nodes on the base of their connection with other important nodes. Memory was tested at baseline, 2- and 4-year follow-up. We demonstrated that higher amyloid burden as measured by both CSF amyloid beta 42/40 ratio and non-displaceable binding potential in the posterior cingulate cortex was associated with lower functional connectivity in the default mode network. The association between amyloid burden (CSF and non-displaceable binding potential in the posterior cingulate cortex) and aberrant default mode network connectivity was confirmed at the voxel level with both functional connectivity and eigenvector centrality measures, and it was driven by voxel clusters localized in the precuneus, cingulate, angular and left middle temporal gyri. Moreover, we demonstrated that functional connectivity in the default mode network predicts longitudinal memory decline synergistically with regional amyloid burden, as measured by non-displaceable binding potential in the posterior cingulate cortex. Taken together, these results suggest that early amyloid beta deposition is associated with aberrant default mode network connectivity in cognitively healthy individuals and that default mode network connectivity markers can be used to identify subjects at risk of memory decline.
An investigation into the anaerobic spoilage microbiota of beef carcass and rump steak cuts using high- throughput sequencing
Authors: Esteves Eden , Whyte Paul , Mills John , Brightwell Gale , Gupta Tanushree B , Bolton Declan
Published: September 2021

The presence of anaerobic microflora on fresh beef carcass and rump steaks, which may contribute to meat spoilage, was explored in this study. A total of 120 carcass and 120 rump steak swabs were collected immediately after slaughtering and boning, respectively from five meat plants, anaerobically incubated and enriched at 4°C for 3 weeks. This was followed by DNA extraction and 16S rRNA amplicon sequencing using the Illumina MiSeq, with subsequent bioinformatics analysis. The enriched microbiota of the samples was classified and grouped into 149 operational taxonomic units (OTUs). The microbiota recovered from both sample types consisted mainly of Carnobacterium, with an average relative abundance of 28.4% and 32.8% in beef carcasses and beef rump steaks, respectively. This was followed by Streptococcus, Serratia, Lactococcus, Enterococcus, Escherichia-Shigella, Raoultella and Aeromonas ranging from 1.5 to 20% and 0.1 to 29.8% in enriched carcasses and rump steak swabs, respectively. Trichococcus, Bacteroides, Dysgomonas, Providencia, Paraclostridium and Proteus were also present ranging from 0 to 0.8% on carcass and 0 to 1.8% on rump steak swabs, respectively. Alpha and beta diversity measurements showed limited diversity between the two sample types, but some differences between samples from the beef plants investigated were evident. This study highlights the presence of potential spoilage bacteria, mainly anaerobic genera on and between carcass and rump steaks, as an indication of contamination on and between these samples.
Genome-wide characterization of Mariner-like transposons and their derived MITEs in the Whitefly Bemisia tabaci (Hemiptera: Aleyrodidae)
Authors: Zidi Marwa , Denis Françoise , Klai Khouloud , Chénais Benoît , Caruso Aurore , Djebbi Salma , Mezghani Maha , Casse Nathalie
Published: September 2021

The whitefly, Bemisia tabaci is a hemipteran pest of vegetable crops vectoring a broad category of viruses. Currently, this insect pest showed a high adaptability and resistance to almost all the chemical compounds commonly used for its control. In many cases, transposable elements (TEs) contributed to the evolution of host genomic plasticity. This study focuses on the annotation of Mariner-like elements (MLEs) and their derived Miniature Inverted repeat Transposable Elements (MITEs) in the genome of B. tabaci. Two full-length MLEs belonging to mauritiana and irritans subfamilies were detected and named Btmar1.1 and Btmar2.1, respectively. Additionally, 548 defective MLE sequences clustering mainly into 19 different Mariner lineages of mauritiana and irritans subfamilies were identified. Each subfamily showed a significant variation in MLE copy number and size. Furthermore, 71 MITEs were identified as MLEs derivatives that could be mobilized via the potentially active transposases encoded by Btmar 1.1 and Btmar2.1. The vast majority of sequences detected in the whitefly genome present unusual terminal inverted repeats (TIRs) of up to 400 bp in length. However, some exceptions are sequences without TIRs. This feature of the MLEs and their derived MITEs in B. tabaci genome that distinguishes them from all the other MLEs so far described in insects, which have TIRs size ranging from 20 to 40 bp. Overall, our study provides an overview of MLEs, especially those with large TIRs, and their related MITEs, as well as diversity of their families, which will provide a better understanding of the evolution and adaptation of the whitefly genome.
Understanding population structure in an evolutionary context: population-specificFST and pairwiseFST
Authors: Kitada Shuichi , Nakamichi Reiichiro , Kishino Hirohisa
Published: September 2021

Populations are shaped by their history. It is crucial to interpret population structure in an evolutionary context. Pairwise FST measures population structure, whereas population-specific FST measures deviation from the ancestral population. To understand the current population structure and a population’s history of range expansion, we propose a representation method that overlays population-specific FST estimates on a sampling location map, and on an unrooted neighbor-joining tree and a multi-dimensional scaling plot inferred from a pairwise FST distance matrix. We examined the usefulness of our procedure using simulations that mimicked population colonization from an ancestral population and by analyzing published human, Atlantic cod, and wild poplar data. Our results demonstrated that population-specific FST values identify the source population and trace the evolutionary history of its derived populations. Conversely, pairwise FST values represent the current population structure. By integrating the results of both estimators, we obtained a new picture of the population structure that incorporates evolutionary history. The generalized least squares estimate of genome-wide population-specific FST indicated that the wild poplar population expanded its distribution to the north, where daylight hours are long in summer, to coastal areas with abundant rainfall, and to the south where summers are dry. Genomic data highlight the power of the bias-corrected moment estimators of FST, whether global, pairwise, or population-specific, that provide unbiased estimates of FST. All FST moment estimators described in this paper have reasonable processing times and are useful in population genomics studies.
Age-Related Increase in Lactate Dehydrogenase Activity in Skeletal Muscle Reduces Life Span inDrosophila
Authors: Hunt Liam C , Demontis Fabio
Published: September 2021

Metabolic adaptations occur with aging but the significance and causal roles of such changes are only partially known. In Drosophila, we find that skeletal muscle aging is paradoxically characterized by increased readouts of glycolysis (lactate, NADH/NAD+) but reduced expression of most glycolytic enzymes. This conundrum is explained by lactate dehydrogenase (LDH), an enzyme necessary for anaerobic glycolysis and whose expression increases with aging. Experimental Ldh overexpression in skeletal muscle of young flies increases glycolysis and shortens life span, suggesting that age-related increases in muscle LDH contribute to mortality. Similar results are also found with overexpression of other glycolytic enzymes (Pfrx/PFKFB, Pgi/GPI). Conversely, hypomorphic mutations in Ldh extend life span, whereas reduction in PFK, Pglym78/PGAM, Pgi/GPI, and Ald/ALDO levels shorten life span to various degrees, indicating that glycolysis needs to be tightly controlled for optimal aging. Altogether, these findings indicate a role for muscle LDH and glycolysis in aging.
Regional seismic velocity changes following the 2019 Mw 7.1 Ridgecrest, California earthquake from autocorrelations and P/S converted waves
Authors: Lu Y , Ben-Zion Y
Published: September 2021

We examine regional transient changes of seismic velocities generated by the 2019 Mw 7.1 Ridgecrest earthquake in California, using autocorrelations of moving time windows in continuous waveforms recorded at regional stations. We focus on traveltime differences in a prominent phase generated by an interface around 2 km depth, associated with transmitted Pp waves and converted Ps waves from the ongoing microseismicity. Synthetic tests demonstrate the feasibility of the method for monitoring seismic velocity changes. Taking advantage of the numerous aftershocks in the early period following the main shock, we obtain a temporal resolution of velocity changes up to 20 min in the early post-main-shock period. The results reveal regional coseismic velocity drops in the top 1–3 km with an average value of ∼2 per cent over distances up to 100 km from the Ridgecrest event. These average velocity drops are likely dominated by larger changes in the shallow materials and are followed by rapid recoveries on timescales of days. Around the north end of the Ridgecrest rupture and the nearby Coso geothermal region, the observed coseismic velocity drops are up to ∼8 per cent. The method allows monitoring temporal changes of seismic velocities with high temporal resolution, fast computation and precise spatial mapping of changes. The results suggest that significant temporal changes of seismic velocities of shallow materials are commonly generated on a regional scale by large events.
2. The framework of company law
Authors: Hannigan Brenda
Published: September 2021

This chapter outlines the statutory framework of company law and the reforms put forward by the Company Law Review which were implemented by the Companies Act 2006 (CA 2006). Registered companies in the UK are governed by the CA 2006 and its predecessors. The remainder of the chapter covers the European framework of company law considering the harmonisation programme, simplification measures, and the modernisation Directives. The chapter outlines the impact of EU initiatives in areas such as corporate reporting, corporate governance, restructuring, and mobility. Freedom of establishment for companies is discussed with the relevant ECJ case law. A brief discussion of the European Company is included.
8. A statutory statement of directors’ duties
Authors: Hannigan Brenda
Published: September 2021

The Companies Act 2006 (CA 2006) includes for the first time a statutory statement of directors’ general duties in Pt 10, Ch 2. This chapter explains the background to the introduction of this statutory statement and discusses the duties which have been set out. The duties remain based on and will be interpreted in accordance with the pre-existing common law while evolving in the normal manner through judicial decisions. The chapter notes that the duties are cumulative and non-exhaustive and are not owed to the shareholders individually but to the company, though in very exceptional circumstances, the courts may find a duty owed to shareholders.
11. Duty of care, skill, and independent judgment
Authors: Hannigan Brenda
Published: September 2021

In addition to their fiduciary obligations, directors are subject to duties of care and skill. This chapter discusses the statutory standard of care, skill, and diligence; the content of the duty; and the duty to exercise independent judgement. In looking at care and skill, key issues are the extent to which delegation is possible and the degree to which the delegating director must maintain a residual duty of supervision. The chapter considers the law’s expectations of executive and non-executive directors, including the level of knowledge that they must bring to bear and examines how the standard required reflects their differing roles in the management of the business.
14. Directors’ liabilities for breach of duty
Authors: Hannigan Brenda
Published: September 2021

This chapter focuses on the extent of a director’s civil liability for breach of fiduciary duty and the liability of third parties involved in some way in that breach of duty. One of the most important issues is the extent of a director’s liability to account. Liability can range from accounting for secret profits to claims for equitable compensation and from personal to proprietary claims. Often, a claim will be affected by limitation issues. It may be complicated by the involvement of third party accessories. Mitigation through reliance on indemnity provisions, insurance and by applying to the court for relief is also considered. The discussion covers: breach of fiduciary duty, liability of third parties, claims for negligence, and managing potential liabilities.
20. The derivative claim and the rule in Foss v Harbottle
Authors: Hannigan Brenda
Published: September 2021

This chapter discusses further aspects of shareholder remedies, namely the common law multiple derivative claim; derivative claims under Companies Act 2006 (CA 2006), Part 11; the reflective loss principle; personal actions at common law; and specific statutory rights under the CA 2006. At common law, a shareholder aggrieved by a breach of duty by a director could bring a derivative claim on behalf of the company, as an exception to the rule in Foss v Harbottle. That common law claim now remains as a common law multiple derivative claim whereas the ‘ordinary’ derivative claim now is a statutory claim under CA 2006, Part 11. This chapter explores both types of derivative claim and assesses their value to shareholders. An important constraint on shareholder recovery is the principle governing reflective loss which has recently been restated by the Supreme Court. This chapter considers the current position in the light of that development.
Globalization, deglobalization and Great Power politics
Authors: Ripsman Norrin M
Published: September 2021

Commercial liberalism would suggest that whereas globalization was conducive to great power cooperation—or at least moderated competition—deglobalization is likely to ignite greater competition amongst the Great Powers. In reality, however, the picture is much more complex. To begin with, the intense globalization of the 1990s and 2000s is not responsible for moderating Great Power tensions; instead, it is itself a product of the security situation resulting from the end of the Cold War. Furthermore, while globalization did serve to reinforce cooperation between the United States and rising challengers, such as China, which sought to harness the economic gains of globalization to accelerate their rise, it also created or intensified fault-lines that have led to heightening tensions between the Great Powers. Finally, while we are currently witnessing increasing tensions between the US and both China and Russia, deglobalization does not appear to be the primary cause. Thus, geoeconomic conditions do not drive security relations; instead, the geoeconomic environment, which is itself influenced by Great Power politics, is better understood as a medium of Great Power competition, which may affect the character of Great Power competition and its intensity, but does not determine it.
Globalization, deglobalization and knowledge production
Authors: Behera Navnita Chadha
Published: September 2021

Although globalization processes have brought the world closer through the exchange of knowledge, ideas and practices, advances in knowledge dissemination have not been mirrored by expansion in sites and modes of knowledge production. This article probes this disjuncture and asks how deglobalization might chart different pathways by delving into the intellectual history of the making of International Relations (IR). Focusing its gaze on the structuring principles of knowledge creation and modes of knowing rather than specific issues and problematiques of IR, it analyses the historical impact of western Enlightenment thinking through centuries-long imperialism, which continues to limit the agency of many states in the re-making of their life-worlds. The article describes deglobalization as a longue durée historical response that offers different possibilities for countering or challenging the discursive hegemony of the ‘West’. It discusses a ‘nationalist’ response by China—a rising power and a more dispersed, global academic endeavour seeking to decolonize IR's modes of knowledge production to better account for the diverse ground realities of its many worlds.
Predictors: How to Approach the Individualization of Treatment
Authors: Ceballos Daniel
Published: September 2021

The “big data” in inflammatory bowel disease opens a route of detection of predictors that can determine the prognosis of each patient and allow the individualized selection of more efficient and safe therapeutic strategies. Immune biomarkers are a promising field to explore thoroughly.
Racial and Ethnic Distribution of Inflammatory Bowel Disease in the United States
Authors: Barnes Edward L , Nowell William B , Venkatachalam Shilpa , Dobes Angela , Kappelman Michael D
Published: September 2021

Background

The current burden of Crohn’s disease (CD) and ulcerative colitis (UC) in minority populations is largely unknown. We sought to evaluate the relative prevalence of CD and UC across racial and ethnic groups within the National Patient-Centered Clinical Research Network (PCORnet).

Methods

We queried electronic health records from 337 centers from January 2013 to December 2018. We compared the relative prevalence of CD and UC across racial/ethnic groups to the general PCORnet populations using χ 2 and univariable logistic regression.

Results

Among 39,864,077 patients, 114,168 had CD, and 98,225 had UC. Relative to the overall PCORnet population, Black adult patients were significantly less likely than White patients to have a diagnosis of CD (odds ratio [OR], 0.53; 95% CI, 0.52–0.54) or UC (OR, 0.41; 95% CI, 0.40–0.43). Pediatric Black patients were also less likely to have a diagnosis of CD (OR, 0.41; 95% CI, 0.39–0.43) or UC (OR, 0.38; 95% CI, 0.35–0.41). Adult Hispanic patients were less likely to have a diagnosis of CD (OR, 0.33; 95% CI, 0.32–0.34) or UC (OR, 0.45; 95% CI, 0.44–0.46) compared with non-Hispanic patients. Similarly, pediatric Hispanic patients were less likely to have a diagnosis of CD (OR, 0.34; 95% CI, 0.32–0.36) or UC (OR, 0.50; 95% CI, 0.47–0.53).

Conclusions

Despite the increasing racial and ethnic diversity in the United States, these data suggest that CD and UC are modestly less prevalent among patients of non-White races and Hispanic ethnicity.
699Are we treating our older generations appropriately?
Authors: Abbas Shazia Shehzad , Majeed Tazeen , Nair Balakrishnan R , Forder Peta M. , Weaver Natasha , Byles Julie
Published: September 2021

Background

This study aims to understand the disease burden of Atrial Fibrillation (AF) and how it is treated among older Australian women.

Methods

Data from the oldest cohort (born 1921-26) of the Australian Longitudinal Study of Women’s Health were linked to state based hospital data to identify AF and to Pharmaceutical Benefit Scheme data for medication details. Yearly prevalence and incidence of AF was calculated, followed by calculation of proportions for different medications received.

Results

A total of 6671 women were eligible for the analysis. About 1827 women from were identified as having AF between 2000-2015. Despite steady incidence, prevalence of AF increased from 2.7% (95%CI=1.6%-3.8%) when women were aged 74-79 years to 24.8% (95%CI=23.2%-26.4%) in 2015 when women were 89-94 years. About 10% of women with AF did not receive any treatment for AF and another 60% did not receive any prophylaxis for thromboembolism within 3 years of AF onset. More than three quarters of women with AF received a combination of medications. Rate control with Vitamin K Inhibitors and Rate control with Platelet Aggregation Inhibitors were the most common combinations.

Conclusions

Older women have high prevalence of AF. These women are undertreated for the prevention of the most common and disabling complication of AF, stroke.

Key messages

Prevalence of AF is increasing and women receive inadequate treatment rendering them at risk of serious complications like stroke. This results in reduced quality of life for patients as well as burdens the health care system.
107Antecedent cardiovascular disease, medication use, and risk of developing ALS: a population-based nested case-control study
Authors: Magid Hoda Abdel , Topal Barbara , McGuire Valerie , Hinman Jessica , Karasakis Edward , Nelson Lorene
Published: September 2021

Background

We investigated the association between hypertension, ischemic heart disease, heart failure, acute myocardial infarction, and atrial fibrillation with the risk of amyotrophic lateral sclerosis (ALS). This study also examined associations with use of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptors blockers (ARBs), calcium channel blockers, beta blockers, and antiarrhythmics

Methods

We conducted a population-based nested case-control study in the Medicare fee for service population, including 3,714 enrollees ages 65 and above with newly diagnosed ALS between 2006-2014. Cases were compared with 18,750 sex-, age, county, and enrollment-matched controls. Odds ratios (OR) and 95% Confidence Intervals (CIs) were estimated using conditional logistic regression models adjusting for diabetes, obesity, tobacco use, socioeconomic status, and controlling for confounding by indication. Medication use was identified through claims pharmacy data and similarly analyzed using a dose response approach.

Results

The fully adjusted OR for any CVD diagnosis was 0.93 (95% CI 0.86–1.02). Our results varied across cause-specific CVD diagnoses. We observed inverse associations for heart failure (OR 0.79; 95% CI 0.70–0.89) and atrial fibrillation (OR 0.81; 95% CI 0.76–0.92). ALS risk was reduced with use of ACEIs (OR 0.84; 95% CI 0.77–0.91), calcium channel blockers (OR 0.64; 95% CI 0.59–0.70), and beta blockers (OR 0.76; 95% CI 0.71–0.83).

Conclusions

In this large population-based Medicare study, the risk of ALS was 7% lower among individuals with any CVD diagnosis.

Key messages

Our findings suggest having a cardiovascular condition or use of a CVD medication may be protective for ALS.
1261Epidemiology of Kawasaki disease in Japan, 2017–2018: results from the nationwide survey
Authors: Ae Ryusuke , Makino Nobuko , Kosami Koki , Matsubara Yuri , Nakamura Yosikazu
Published: September 2021

Background

Kawasaki disease (KD) is the most common cause of acquired pediatric heart disease in developed countries. The study aimed to summarize the epidemiologic characteristics, treatments, and cardiac complications of KD, using data from the nationwide survey in Japan.

Methods

The nationwide survey in Japan has been conducted biennially since 1970. The survey respondents were hospitals specializing in pediatrics and those with ≥100 beds and a pediatric department throughout Japan, where KD patients were eventually hospitalized. The most recent survey was completed in 2019, obtaining information for patients who developed KD during 2017–2018.

Results

The survey identified 32528 KD patients, which comprised 15164 (47%) in 2017 and 17364 (53%) in 2018. The highest annual incidence rate was recorded in 2018 (359 per 100,000 children aged 0–4 years). After 1982, patients with ≤4 principal KD signs increased, resulting in 6847 (21%) patients diagnosed during 2017–2018. Among 30784 patients who received initial intravenous immunoglobulin administration, 6061 (20%) did not respond. Within 30 days of KD onset, 9.0% of patients were diagnosed with cardiac complications, and consequently, 2.6% of patients developed cardiac sequelae after the acute illness.

Conclusions

The annual number of patients developing KD in Japan increased from 1970 through 2018, while the proportion of KD patients with cardiac complications decreased. Recent advances in KD treatments might have contributed to preventing the development of cardiac complications.

Key messages

We analyzed large-scale data and summarized the epidemiologic characteristics, treatments, and cardiac complications of KD in Japan.
1072Mental health difficulties among adolescents in Ghana, coping mechanisms and the support systems: a mixed-methods study
Authors: Agbozo Faith , Amobaa Noella Dufie , Runge-Ranzinger Silvia , Grys Pauline
Published: September 2021

Background

Despite their vulnerability, mental health of adolescents has received little attention in developing countries. We investigated the mental health difficulties faced by adolescents, their coping strategies and school-based support systems.

Methods

Design was a convergent mixed-methods study. Quantitative data was collected

using the validated strengths and difficulties questionnaire to assess the mental health of 405 adolescents in four senior high schools (SHS) in the Techiman Municipality, Ghana. Qualitative data was collected through in-depth interview with 18 teachers and seven focused group discussions among 35 students. Adjusted odds ratio (OR) for mental health difficulties were estimated through ordinal logistic regression in Stata 14.2. Qualitative data were analysed by thematic content analysis using ATLAS.ti 7.1.

Results

Over half (58.5%) experienced abnormalities related to peer (20.5%), emotional (16.3%), conduct (13.3%) and hyperactivity (3.0%) problems and prosocial behaviours (5.4%). Significant determinants were being female (OR = 2.27, 95% confidence interval [CI]:1.47-3.50), bullied (OR = 1.72, CI:1.07-2.75), domestic violence (OR = 1.87, CI:1.10-3.17), substance abuse (OR = 8.14, CI: 1.41-46.8), academic pressure (OR = 2.40, CI:1.30-4.42), and perceived poor performance (OR = 7.36 CI:2.83-19.16). Mental health difficulties were attributed to financial challenges, spiritual influences, intimate relationships, bullying, and domestic violence. Coping strategies included isolation, substance abuse and spiritual help. Guidance and counselling unit, the main support system, was ineffective due to issues with trust, confidentially, and qualified counsellors.

Conclusions

As mental health difficulties were prevalent, school-based support systems, particularly guidance and counselling needs strengthening, including being manded by trained personnel. It is time to incorporate mental health education into school curricula.

Key messages

Mental disorders among adolescents are common. While guardians and religious bodies are critical, many of the triggers occur in school necessitating mental health-friendly school environments.
1287Grief and mourning and its relation with anxiety and depressive symptoms during COVID-19 pandemic
Authors: Aguiar Ana , Pinto Marta , Duarte Raquel
Published: September 2021

Background

During these unprecedented times, individuals who experience the sudden death of a family member or friend, already miss the anticipatory grief and are now also prevented from a proper farewell. This study aimed to address prolonged grief disorder since the beginning of the COVID-19 pandemic

Methods

A virtual snowball sampling survey was disseminated through social networking channels. The study enrolled participants from general resident population in Portugal with ≥18 years. Characteristics of the sample were summarized using descriptive statistics. Anxiety and depression symptoms are described by absolute and relative frequencies and compared through the Chi-square test.

Results

A total of 929 participants completed the survey; 17.9% (n = 166) have lost someone since the beginning of the pandemic, making our final sample. Most were female (66.9%); median age of 35 years and 70.5% had a high education degree. Participants who had lost a grandparent consisted of 28.3% of the sample, father and/or mother 9.0%, and a friend 22.3%. We found a prevalence of 30.7% of anxiety symptoms and 10.2% of depression symptoms (p = 0.030). Also, 16.8% have had a high score on the PG13, which show that these people can mourned for longer periods.

Conclusions

Paying the last tribute to a loved one is a mental health gesture that allows individuals to make amends and reconcile with life.

Key messages

The need arises to give timely attention to the psychological consequences due to the COVID-19 pandemic concerning grief
1491Impact of COVID19 on years of life lost with and without disability across 18 European-countries
Authors: Ahmadi-Abhari Sara , Bandosz Piotr , Kivimaki Mika , Middleton Lefkos
Published: September 2021

Background

To accurately assess the impact of COVID19 on life-expectancy, years of life lost, and prevalence of dementia and disability, a model integrating calendar-trends in cardiovascular-disease, dementia, disability and mortality is required. We estimated these impacts in Austria, Belgium, Czech-Republic, Denmark, Estonia, France, Germany, Greece, Hungary, Italy, The Netherlands, Poland, Portugal, Slovenia, Spain, Sweden, Switzerland, and the UK.

Methods

Data to inform the ten-state Monte-Carlo Markov-model for the 18 European countries were derived from official-statistics for population-numbers and mortality-rates (age&sex-specific) and from Survey for Health, Ageing and Retirement in Europe for prevalence-estimates and transition-probabilities. Impact of COVID19 was measured comparing the estimates derived from incorporating expected mortality rates assuming calendar-trends in mortality and incidence of dementia, disability, and cardiovascular-disease continue those of the past two-decades, and those incorporating excess COVID19 mortality.

Results

Assuming COVID-19 vaccination and termination of the pandemic will be accomplished by the end of 2021, the pandemic will have resulted in a loss of 9.3M (95% Uncertainty-Interval 1.3M-29.8M) person-years of life, including 7.1M person-years of dementia-free life and 5.2M person-years of disability-free life among the 289M population (as of 2019) above age-35. The effects on prevalence of dementia, disability and life-expectancy will be presented.

Conclusions

The impact of the pandemic on disability-free person-years of life lost are devastating, marking a need for more rapid actions to halt the spread of epidemics.

Key messages

Accurate estimation of future prevalence of dementia and disability to quantify the impact of the pandemic on years of life lost needs to simultaneously account for the declining trends in incidence of dementia and the decline in cardiovascular disease incidence and mortality resulting in increased life-expectancy and a larger pool susceptible to dementia and disability.

The COVID19 pandemic is estimated to result in 9.3million person-years of life lost in 18 European countries including a loss of 7.1M person-years of dementia-free life and 5.2M person-years of disability-free life.
151Infant and young child feeding practices and ARI and diarrhoea in Ethiopia: A PSM approach
Authors: Ahmed Kedir Yimam
Published: September 2021

Background

Understanding the associations between infant and young child feeding (IYCF) and ARI and diarrhoea can inform IYCF policy interventions and advocacy in Ethiopia. This study aimed to investigate the relationship between IYCF practices and ARI and diarrhoea in Ethiopian children.

Methods

This study used the Ethiopia Demographic and Health Survey (EDHS) data for the years 2000 (n = 3680), 2005 (n = 3528), 2011 (n = 4037), and 2016 (n = 3861). The association between IYCF practices and (i) ARI and (ii) diarrhoea were investigated using propensity score matching and multivariable logistic regression models.

Results

Early initiation of breastfeeding (Odds ratio [OR]: 0.81; 95% confidence interval [CI]: 0.72, 0.92) and EBF (OR: 0.65; 95% CI: 0.51, 0.83) were associated with lower risk of ARI. Bottle-fed children had higher odds of ARI (OR: 1.36; 95% CI: 1.10, 1.68). Early initiation of breastfeeding and EBF were associated with a lower odds of diarrhoea (OR: 0.88; 95% CI: 0.79, 0.94 for Early initiation of breastfeeding and OR: 0.51; 95% CI: 0.39, 0.65 for EBF). Infants who were predominantly breastfed were less likely to experience diarrhoea (OR: 0.69; 95% CI: 0.53, 0.89).

Conclusions

Early initiation of breastfeeding and EBF were associated with a lower risk of ARI and diarrhoea. Bottle feeding was associated with a higher risk of ARI.

Key messages

Interventions targeting improved early initiation of breastfeeding, EBF, and avoidance of bottle feeding should be prioritised and scaled-up.
913Factors of premature atrial contractions among general Japanese men
Authors: Ahmed Sabrina , Miura Katsuyuki , Hisamatsu Takashi , Kadota Aya , Fujiyoshi Akira , Segawa Hiroyoshi , Torii Sayuki , Takashima Naoyuki , Kondo Keiko , Ueshima Hirotsugu
Published: September 2021

Background

Premature atrial contractions (PACs) are known predictor of atrial fibrillation; however very little has been revealed on its factors among Asian general population. We assessed the frequency of higher PAC counts and its association with relevant factors in general Japanese men.

Methods

We have conducted a population based cross sectional study among 517 healthy men from Kusatsu, Japan, aged between 40 and 79 years. 24 hours Holter electrocardiogram was performed to assess the PAC frequency. We divided participants into quartiles based on number of PACs/hour to compare the characteristics by using Cochran–Mantel–Hanzal test and ANOVA. We defined the highest quartile as event and multivariable logistic regression was performed to assess the significance with relevant factors.

Results

Median number of PACs was 2.84 PACs/hour. The highest quartile of PAC counts was >7.86PACs/hour. Age, triglycerides, blood pressure, ventricular contractions and heart rates were different among quartiles. In multivariable logistic regression analysis, higher age (OR, 95% CI: 1.35, 1.01-1.67), lower mean heart rates (OR, 95% CI: 0.97, 0.94-0.99), higher heart rate difference in a day (OR, 95% CI: 1.40, 1.12-1.75) and lower triglyceride (OR, 95% CI: 0.53, 0.33-0.82) were independently, significantly associated with highest quartile of PACs.

Conclusions

Higher PACs evaluated by Holter ECG was associated with higher age, lower heart rate, higher heart rate difference, and lower triglyceride in general Japanese men.

Key messages

The PAC frequency was high. Age, mean heart rates, difference between maximum and resting heart rates, triglycerides are possible risk factors for frequent PAC counts.
1348Childhood adversities and diurnal patterns of salivary cortisol in adulthood: two UK-based prospective cohort studies
Authors: Akasaki Mifuyu , Hardy Rebecca , Steptoe Andrew
Published: September 2021

Background

Dysregulation of diurnal cortisol patterns may mediate between chronic stress and health problems. Findings on the association of childhood adversities with adult cortisol, however, are equivocal, mainly due to low statistical power, sample selection, and unstandardised indices of cortisol.

Methods

Participants were from Whitehall II study (n = 3434), and National Child Development Study (NCDS) (n = 2072). In Whitehall II, multilevel models were used to examine associations of retrospectively measured childhood adversities with two indices of diurnal cortisol patterns (awakening response and diurnal slope) at a median age of 65. In NCDS, regression was used to investigate associations of prospectively measured adversities with two measures of morning cortisol at the age of 44/45. We then regressed predicted values of cortisol from these models against count of adversities to examine dose-response effects.

Results

The prevalence of reporting at least one adversity was 67.8% in Whitehall II, and 47.8% in NCDS. None of the individual adversities were associated with overall cortisol levels in either study. However, for each additional adversity, there was a 1% elevated awakening response (95%CI: 0.8% to 1.19%), and, among men only, a 1.2% lower cortisol level at awakening (-1.98 to -0.40) with flatter diurnal slope (0.1 to 0.1) in Whitehall II; and a 1.3% lower cortisol level (-1.78 to -0.70) at 3.75 hrs after awakening in NCDS.

Conclusions

Experience of multiple childhood adversities may be associated with dysregulated salivary cortisol patterns later in life.

Key messages

Accumulation of childhood adversities might be associated with dysregulated diurnal cortisol patterns in adulthood.
785Excess mortality in severe mental disorders: a systematic review and meta-regression
Authors: Ali Miss Suhailah , Charlson Fiona
Published: September 2021

Background

Decades worth of epidemiological studies, synthesised by systematic reviews and meta-analyses, have consistently shown that people with severe mental disorders (SMD) have a higher risk of mortality compared to the general population, which has not improved over time. One of the major limitations of previous reviews is the use of meta-analytic models to synthesise mortality estimates without taking into account potential sources of heterogeneity.

Methods

A systematic review of studies examining mortality in people with schizophrenia and bipolar disorder compared to the general population was conducted. Estimates of all-cause and cause-specific mortality were calculated using meta-regression models to quantify and adjust for the effects of covariates, including both study-level and population-level factors.

Results

A total of 76 studies were included in the analyses. The adjusted relative risk for all-cause mortality in schizophrenia was 2.80 (95% CI 2.30 to 3.41) and 2.33 (95%CI 2.01 to 2.71) for bipolar disorder. Mortality was elevated in each cause of death examined, across both unnatural and natural causes. Some heterogeneity was explained by age and sex.

Conclusions

The mortality gap for people with SMD compared to the general population remains unchanged. Most of the heterogeneity between studies could not be accounted for by the covariates included in our analyses.

Key messages

More work needs to be done towards understanding the causal factors underlying excess mortality in people with SMD in order to achieve more equitable health outcomes.
827Early life influences on timing of menarche in racial/ethnic minority and immigrant women
Authors: April-Sanders Ayana , Tehranifar Parisa , Argov Erica Lee , Suglia Shakira , McDonald Jasmine
Published: September 2021

Background

Early life adversity and infections may theoretically affect the timing and effort of reproductive development. We examined associations of childhood adversity and exposure to tonsillitis with age at menarche in women age 40-64 years.

Methods

A multi-ethnic cohort of 394 women reported on exposure to parental maltreatment and maladjustment during childhood (<18 years) and on any diagnosis of tonsillitis, an infection primarily acquired in early life and adolescence. We used linear and logistic regression models to examine the associations of cumulative/specific childhood adversity experience(s) and history of tonsillitis with average age at menarche and early onset of menarche (<12 years of age).

Results

The average age at menarche was 12.6 years, and was significantly lower for women who lived with a mentally ill caregiver (M = 12.4 (95% CI: 11.7-13.0)) and those with a history of tonsillitis (M = 12.6 (95% CI: 12.0-13.2)). In adjusted multivariable models, living with a mentally ill caretaker (RR = 1.5, 95% CI: 1.0-2.1) and a having a history of tonsillitis (RR = 1.7, 95% CI: 1.3-2.4) were associated with increased risk of early menarche compared with women without these exposures. Cumulative and other specific adversities were not statistically associated with early menarche.

Conclusions

These findings support growing evidence that early life experiences may influence reproductive development.

Key messages

Early life adversity related to living with mentally ill caretakers and a history of tonsillitis is associated with earlier menarche in racial/ethnic minority and immigrant women.
40An antenatal care indicator based on contact with services and content developed for 63 countries
Authors: Arroyave Luisa , Saad-Haddad Ghada , Victora Cesar G , Barros Aluisio
Published: September 2021

Background

Most antenatal care (ANC) indicators in use are criticized for considering only contact with services and not taking into account content of care. We aimed to create and validate a new indicator measured as a score, considering both contact and content, that can be used for monitoring.

Methods

We used data from national surveys conducted in low and middle-income countries (LMICs). Information on ANC was used to build an adequacy score (ANCq) that would be applicable to all women in need of ANC. We used a convergent validation approach, exploring the association of our proposed indicator with neonatal mortality.

Results

The ANCq score was derived from seven variables related to contact with services and content of care ranging from zero to ten. Surveys from 63 countries with all variables were used. The overall mean of ANCq was 6.7, ranging from 3.5 in Afghanistan to 9.3 in Cuba and the Dominican Republic. In most countries, the ANCq was inversely associated with neonatal mortality and the pooled for all surveys Odds Ratio was 0.90 (95% CI = 0.88-0.92).

Conclusions

The ANCq presented good validity properties, being a useful tool for assessing ANC coverage and adequacy of care in monitoring and accountability exercises.

Key messages

ANCq provides a standardized and comparable measure of ANC adequacy, allowing for comparisons between country population subgroups and between countries.