bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of dietary protein on gut development, microbial compositions and mucin expressions in mice
Authors: Li Zuohua , Tang Wenjie , Gong Saiming , Li Yunxia , Xia Siting , Zhang Bin , Ma Jie
Published: August 2021

Aims

Dietary protein, as an important macronutrient, widely participates in host growth and metabolism. In this study, effects of different protein levels (14, 20 and 26%) on the gut development, microbial compositions and mucin expressions were studied in C57BL/6 mice.

Methods and Results

The results showed that body weight and the relative weight of stomach and gut were decreased in low-protein diet-fed mice, whereas high-protein diet significantly reduced the villus length and area of jejunum. Goblet cells number in the jejunum was reduced in the low-protein group, which was reversed by dietary a high-protein diet. In addition, high-protein diet notably reduced microbial diversity and changed the microbial compositions at the phylum level, such as Bacteroides, Proteobacteria, Actinomycetes and Deferribacteres. Furthermore, high-protein diet significantly increased mucin2, mucin3 and mucin4 expressions in the jejunum, but downregulated mucin1, mucin2, mucin4 and TFF3 in the ileum, indicating a tissue-dependent manner.

Conclusions

Together, high-protein diet may impair gut development, microbial balance and mucin system, and a low-protein diet is suggested to promote a healthy lifestyle.

Significance and Impact of Study

Mucin influenced gut development (villus index and goblet cell number) through remodelling gut microbes, as low and high protein levels resulted in contrary expression levels of mucin in jejunum and ileum.
“They don't think I can cope, because I have got a learning disability…”: Experiences of stigma in the lives of parents with learning disabilities
Authors: Franklin Laura , Theodore Kate , Foulds Daniel , Cooper Mary , Mallaghan Lisa , Wilshaw Paul , Colborne Alison , Flower Emilie , Dickinson Deborah , Lee Joyce Nga Yu
Published: August 2021

Background

Parents with learning disabilities report facing a widely held ‘presumption of incompetence’, placing them under pressure to prove their parenting competence. In collaboration with a learning disability theatre company, an inclusive research methodology explored experiences of parenting with learning disabilities, with a specific focus on the operation of stigma in parents' lives.

Method

Interviews with 17 mothers and 5 fathers who self‐identified as having learning disabilities were co‐facilitated by learning‐disabled co‐researchers, and analysed using thematic analysis, with input from people with learning disabilities.

Results

Thematic analysis generated four key themes; (1) positions of powerlessness, (2) assumptions of incompetence, (3) challenging assumptions and proving competence and (4) claiming power.

Conclusion

Parents reported experiencing stigma and disempowerment within their networks, yet continued to embrace their valued parental identity and drew strength from involvement with self‐advocacy organisations. The research informed arts‐based performance pieces and resources aimed at training professionals and raising public awareness.
CircTLK1 modulates sepsis‐induced cardiomyocyte apoptosis via enhancing PARP1/HMGB1 axis–mediated mitochondrial DNA damage by sponging miR‐17‐5p
Authors: Qiu Yu , Yu Ying , Qin Xiao‐Mei , Jiang Tao , Tan Yan‐Fang , Ouyang Wen‐Xian , Xiao Zheng‐Hui , Li Shuang‐Jie
Published: August 2021

Introduction

Septic cardiomyopathy is a common complication of sepsis with high morbidity and mortality, but lacks specific therapy. This study aimed to reveal the role of circTLK1 and its potential mechanisms in septic cardiomyopathy.

Materials and Methods

The in vitro and in vivo models of septic cardiomyopathy were established. Cell viability and apoptosis were detected by CCK8, TUNEL and flow cytometry, respectively. LDH, CK, SOD, MDA, ATP, 8‐OHdG, NAD+/NADH ratio, ROS level, mitochondrial membrane potential and cytochrome C distribution were evaluated using commercial kits. qRT‐PCR and western blotting were performed to detect RNA and protein levels. Mitochondrial DNA (mtDNA) copy number and transcription were assessed by quantitative PCR. Dual‐luciferase assay, RNA immunoprecipitation and co‐immunoprecipitation were performed to verify the interaction between circTLK1/PARP1 and miR‐17‐5p.

Results

CircTLK1, PARP1 and HMGB1 were up‐regulated in the in vitro and in vivo models of septic cardiomyopathy. CircTLK1 inhibition restrained LPS‐induced up‐regulation of PARP1 and HMGB1. Moreover, circTLK1 knockdown repressed sepsis‐induced mtDNA oxidative damage, mitochondrial dysfunction and consequent cardiomyocyte apoptosis by inhibiting PARP1/HMGB1 axis in vitro and in vivo. In addition, circTLK1 enhanced PARP1 expression via sponging miR‐17‐5p. Inhibition of miR‐17‐5p abolished the protective effects of circTLK1 silencing on oxidative mtDNA damage and cardiomyocyte apoptosis.

Conclusion

CircTLK1 sponged miR‐17‐5p to aggravate mtDNA oxidative damage, mitochondrial dysfunction and cardiomyocyte apoptosis via activating PARP1/HMGB1 axis during sepsis, indicating that circTLK1 may be a putative therapeutic target for septic cardiomyopathy.
The association between halitosis and oral‐health‐related quality of life: A systematic review and meta‐analysis
Authors: Schertel Cassiano Luisa , Abdullahi Farhiya , Leite Fábio R. M. , López Rodrigo , Peres Marco A. , Nascimento Gustavo G.
Published: August 2021

Aim

To investigate whether halitosis is associated with impaired oral‐health‐related quality of life (OHRQoL).

Materials and Methods

This is a systematic review of the literature. Electronic searches were performed in PubMed via Medline, Web of Science, Scopus, and EMBASE up to and including June 2021. Observational studies that assessed halitosis in association with OHRQoL were included. The pooled standardized mean difference (SMD) was estimated by meta‐analysis.

Results

Thirteen studies were included in the review; however, the meta‐analysis included only 10 studies, all cross‐sectional, comprising 2692 individuals. The overall meta‐analysis showed an association between halitosis and impaired OHRQoL (SMD 0.51; 95% confidence interval 0.27–0.75). Subgroup analyses, however, indicated that this association remained only among adults. Neither the OHRQoL instrument nor the halitosis assessment method, or the cultural background, influenced the pooled estimates. Meta‐regression analyses revealed that the OHRQoL instrument, the halitosis assessment method, and the sample composition did not explain the between‐study heterogeneity. Methodological quality appeared to explain 20% of the overall heterogeneity, as studies with high risk of bias overestimated the magnitude of the association.

Conclusion

Our findings suggest that halitosis is associated with impaired OHRQoL.
Canine hepatobiliary anatomy, physiology and congenital disorders
Authors: Jaffey J. A.
Published: August 2021

The biliary system is an integral component of normal physiologic homeostasis and essential for survival. It acts as a conduit for the removal of detoxified and catabolised compounds as well as aids in fat digestion and absorption. Derangements in this system can have dangerous sequela that are associated with varying degrees of morbidity and mortality. Moreover, abnormalities in development of the biliary system can have varied and unpredictable changes on function and long‐term outcome. The aims of this article were to review canine hepatobiliary anatomy, physiology and cholestasis as well as summarise congenital biliary disorders including human corollaries.
Comparison of Prolift, Perigee‐Apogee, Prosima, and Elevate transvaginal mesh systems in pelvic organ prolapse surgery: Clinical outcomes of a long‐term observational study
Authors: Huang Kuan‐Hui , Chen Wen‐Hsin , Yang Tsai‐Hwa , Wu Ling‐Ying , Chang Yu‐Wei , Chuang Fei‐Chi
Published: August 2021

Objectives

To evaluate and compare the long‐term clinical outcomes of four different transvaginal mesh systems.

Methods

This retrospective study included 695 patients classified into four groups (Prolift, n = 132; Perigee‐Apogee, n = 186; Prosima, n = 60; Elevate; n = 317), with a median follow‐up time of 5.8 years (range 0.5‐12.2 years). The outcomes were objective anatomic success (Pelvic Organ Prolapse [POP] Quantification system stage ≤1), mesh exposure, and urologic functional assessments.

Results

For anatomic outcomes, we stepwise analyzed the short‐term (within 3 years) and long‐term (after 3 years) results. Prolift had the highest long‐term success rate (9 years: 82.1%, P = .007). Elevate had a comparable short‐term success rate (3 years: 87.5%), but its long‐term success rate significantly decreased over time (5 years: 78.6%, 9 years: 66.8%, P = .007). Prosima had the lowest short‐term success rate (P = .027). For the long‐term mesh exposure rate (9‐year cumulative), Elevate had the lowest with 11.1%; next were Perigee‐Apogee (18.8%) and Prolift (24.6%); and Prosima had the highest with 39.4%, with a significant difference. In terms of urinary functional results, we observed no significant differences in voiding dysfunction, de novo stress urinary incontinence, or de novo overactive bladder symptoms among the four mesh groups, whether combined with midurethral sling surgery or not.

Conclusion

Different vaginal mesh designs have various advantages and features. Prolift provided the best long‐term anatomic success but had a high mesh exposure rate. Elevate gave comparable short‐term success but had a decreased long‐term success rate. However, Elevate is superior with the lowest long‐term mesh exposure rate. Prosima had the worst anatomic correction and highest mesh exposure rates. This study provides a comprehensive long‐term comparative result for POP patients and surgeons.
Multi‐parental QTL mapping of resistance to white spot of maize (Zea mays) in southern Brazil and relationship to QTLs of other foliar diseases
Authors: Kistner María Belén , Galiano‐Carneiro Ana Luísa , Kessel Bettina , Presterl Thomas , Miedaner Thomas
Published: August 2021

Maize white spot (MWS) is one of the most important foliar diseases in Brazil causing significant yield losses. Breeding genotypes with MWS resistance is the most sustainable alternative for managing such losses; however, their genetic control is poorly understood. Our objectives were to identify genomic regions controlling MWS resistance and to explore the presence of common regions controlling resistance to MWS, grey leaf spot (GLS) and northern corn leaf blight (NCLB). We performed a multi‐parental QTL mapping for MWS and GLS resistance with a total of 474 testcrosses and phenotypic data collected in southern Brazil. Six QTLs for MWS resistance on bins 1.03, 1.04, 6.02, 8.05, 1.03, and 10.06 were detected. These findings were compared with previously reported QTLs for NCLB in the same populations, and a common QTL region (bin 8.05) controlling MWS and NCLB resistances was identified. Our findings contribute to a better understanding of MWS resistance by revealing three QTLs (bin 6.02, 1.03, and 10.06), to the best of our knowledge, not yet described in the literature, that are valuable for improving MWS resistance and one promising candidate region for multiple disease resistance.
Does phosphorus influence performance of a native hemiparasite and its impact on a native legume?
Authors: Cirocco Robert M. , Facelli Evelina , Delean Steven , Facelli José M.
Published: August 2021

Phosphorus (P) is an essential plant nutrient and can become limiting in terrestrial ecosystems where parasitic plant:host associations occur. Yet little is known on how P availability influences parasite performance and its impact on hosts. We investigated the performance of the Australian native stem hemiparasite Cassytha pubescens and its impact on the native leguminous shrub Acacia paradoxa in high or low P conditions in a glasshouse experiment. Infected plants had significantly lower total, shoot, root and nodule biomass and shoot:root ratio than uninfected plants, regardless of P supply. The significant negative effect of infection on arbuscular mycorrhizal colonisation of host roots was more severe in the high P treatment. Infection significantly decreased predawn quantum yield of A. paradoxa in low P but not high P conditions. This finding may be due to the parasite‐induced significant enrichment of aluminium in host foliage in low P but not high P treatments. A. paradoxa had significantly lower foliar phosphorus concentration [P] and nitrogen concentration in low P than high P conditions. Parasite biomass and photosynthetic performance were unaffected by P, whereas C. pubescens had significantly lower stem [P] in the low P than high P treatment. Parasite carbon isotope composition was significantly higher than that of the host, especially in low P conditions. Our results show that: (a) native parasite growth and its negative impact on growth of this native shrub was unaffected by P supply and (b) soil P conditions may have no influence on stem hemiparasite:host associations in nature.
Same same but different? Comparing institutional performance in the long‐term care systems of Japan and South Korea
Authors: Kim Hongsoo , Jeon Boyoung , Frisina Doetter Lorraine , Tamiya Nanako , Hashimoto Hideki
Published: August 2021

Responding to a rapidly aging population, Japan and South Korea introduced social insurance‐based long‐term care systems (LTCSs) in 2000 and 2008, respectively. Korea studied and took up key features of Japan's system while evolving along its own trajectory in line with its healthcare system. The aim of the present study is to unpack the broad category of ‘social insurance’ to explore how distinct system inputs and designs in Korea and Japan related to outcomes in performance measured in terms of coverage, quality of care, and sustainability. In doing so, the study serves as an important starting point for advancing a new stream of social policy research on the comparative performance of LTCSs. Our findings demonstrate that despite adopting a common system type, differences in implementation of the social insurance model (particularly in terms of financing and governance) contributed to divergent performance, with Japan outperforming Korea on most indicators during the observed period. This bears contrary implications for policymaking in the two countries: Whereas Japanese policymakers are faced with the challenge of promoting quality while containing spending, in Korea greater investment is required to strengthen the workforce and build up community care.
Beveridge, Bevan and institutional change in the UK welfare state
Authors: Greener Ian , Powell Martin
Published: August 2021

This paper explores the changes to social security and health proposed in the Beveridge Report through the lens of the framework proposed by Mahoney and Thelen for exploring the relationship between political and institutional contexts, change‐agents and types of institutional change. We find that, in terms of social security, the Beveridge Report led to ‘layering’ in that it both built on an inherited legacy of institutions from the earlier Liberal Reforms. Although Beveridge assumed the existing of a national health service for his social security plans to work, he did not specify what form such a service could take. Bevan had the advantage of being a Minister of Health with a large government majority, but had to deal with both internal (in Cabinet) and external (primarily from the medical profession) attempts to veto his reforms. Bevan's changes to healthcare have to be seen in that context, as well as in relation to his own pragmatism, in converting the wartime Emergency Medical Service into the National Health Service. By utilising the full Mahoney and Thelen framework in two cases that were near contemporary with one another, but when contrasted with one another, we show the potential of the framework in cross‐case analysis in illuminating the relationship between political and institutional context, change‐agents, the type of change that results.
O Gabro coronítico de Amparo, RJ: petrografia, química mineral e geotermometria
Authors: Ludka Isabel Pereira , Wiedemann Cristina Maria
Published: August 2021

A gabbroic body of probable Brasiliano age, cropping out in a 4 km2 area around Amparo, in the state of Rio de Janeiro, was studied under the petrographic microscope and the electron microprobe. The dominant mineral assemblage consists of plagioclase (An 89
Aspectos gerais da situação de lavra para granitos ornamentais no município do Rio de Janeiro
Authors: Baptista Filho João , Silva Aline T.
Published: August 2021

Rio de Janeiro is one of the most important producers of ornamental granites in Brazil. Environmental laws and tributary taxes have been a major hazard to mining activities, in a profitable way, making the miner's production decrease considerably. It is now important a development of a new political attitude towards a better improvement of the exploration.
A cidade do Rio de Janeiro e as chuvas de março/93: (des) organização urbana e inundações
Authors: Cambra Marcus Felipe Emerick S , Coelho Netto Ana Luiza
Published: August 2021

The mountainous arcas of Rio de Janeiro act as water divergent areas, converging to the valley-flats. In the last decades, urban expansion has advanced fastly to still forested upward lands, mainly on the north slope of the Tijuca Massif, where numerous "favelas" are located. Changes in the slopes and valley-flats hydrologic behaviour generate major runoff budgets. So major flows-sediment's and flows-garbage's concentrations into the drained valley-axis, naturally or artificially (channels and pluvial tubulations), spreading inundations on the respectives street of the districts's major density population . The Joana, Maracanã and Comprido basins studied in detail show that the mud-flows and garbage-flows concentrate on the knick slopes and the floods on the valley-axis. These events are aggravated by the cumulated rainstorms due to the inadequacy of the urban pluvial drainage system.
Atomic layer etching of Si3N4 with high selectivity to SiO2 and poly-Si
Authors: Miyoshi Nobuya , Shinoda Kazunori , Kobayashi Hiroyuki , Kurihara Masaru , Kouzuma Yutaka , Izawa Masaru
Published: August 2021

Atomic layer etching (ALE) is usually classified into ion-driven anisotropic etching or thermally driven isotropic etching. In this work, we present a thermal ALE process for Si3N4 with high selectivity to SiO2 and poly-Si. This ALE process consists of exposure to a CH2F2/O2/Ar downstream plasma to form an (NH4)2SiF6-based surface-modified layer, followed by infrared (IR) annealing to remove the modified layer. CH2F2-based chemistry was adopted to achieve high selectivity to SiO2 and poly-Si. This chemistry was expected to reduce the number density of F atoms (radicals), which contributes to decreasing the etching rate of SiO2 and poly-Si films. X-ray photoelectron spectroscopy analysis confirmed the formation of an (NH4)2SiF6-based modified layer on the surface of the Si3N4 after exposure to the plasma and subsequent removal of the modified layer using IR annealing. An in situ ellipsometry measurement revealed that the etch per cycle of the ALE process saturated with respect to the radical exposure time at 0.9 nm/cycle, demonstrating the self-limiting nature of this etching process. In addition, no etching was observed on SiO2 and poly-Si films, successfully demonstrating the high selectivity of this ALE process. This high selectivity to SiO2 and poly-Si is attributed to the fact that the spontaneous etching rates of these films are negligibly small and that there is no surface reaction to etch these films during the IR annealing step.
Perceptual equivalence of the Liljencrants–Fant and linear-filter glottal flow models
Authors: Perrotin Olivier , Feugère Lionel , d'Alessandro Christophe
Published: August 2021

Speech glottal flow has been predominantly described in the time-domain in past decades, the Liljencrants–Fant (LF) model being the most widely used in speech analysis and synthesis, despite its computational complexity. The causal/anti-causal linear model (LFCALM) was later introduced as a digital filter implementation of LF, a mixed-phase spectral model including both anti-causal and causal filters to model the vocal-fold open and closed phases, respectively. To further simplify computation, a causal linear model (LFLM) describes the glottal flow with a fully causal set of filters. After expressing these three models under a single analytic formulation, we assessed here their perceptual consistency, when driven by a single parameter Rd related to voice quality. All possible paired combinations of signals generated using six Rd levels for each model were presented to subjects who were asked whether the two signals in each pair differed. Model pairs LFLM–LFCALM were judged similar when sharing the same Rd value, and LF was considered the same as LFLM and LFCALM given a consistent shift in Rd. Overall, the similarity between these models encourages the use of the simpler and more computationally efficient models LFCALM and LFLM in speech synthesis applications.
Babbling in a vocal learning bat resembles human infant babbling
Authors: Fernandez Ahana A. , Burchardt Lara S. , Nagy Martina , Knörnschild Mirjam
Published: August 2021

Babbling bats

A notable aspect of language development in humans is the babbling stage. During this time, toddlers make a range of specific sounds as they practice and imitate adult speech. Humans are not the only vocal learners, however, so might we expect such babbling among others? Fernandezet al. recorded the vocalizations of sac-winged bat pups in the wild and found clear evidence of babbling that was consistent with that seen in humans. The shared babbling components suggest that vocal learning may have similar specific mechanisms across a wide array of mammalian species. —SNV
Mechanisms that ensure speed and fidelity in eukaryotic translation termination
Authors: Lawson Michael R. , Lessen Laura N. , Wang Jinfan , Prabhakar Arjun , Corsepius Nicholas C. , Green Rachel , Puglisi Joseph D.
Published: August 2021

How translation stops

Protein synthesis concludes when a ribosome encounters a stop codon in a transcript, which triggers the recruitment of highly conserved release factors to liberate the protein product. Lawson
et al
. used traditional biochemical methods and single-molecule fluorescence assays to track the interplay of release factors with ribosomes and reveal the molecular choreography of termination. They identified two distinct classes of effectors, small molecules and mRNA sequences, that directly inhibited the release factors and promoted stop codon readthrough. These findings may buttress ongoing efforts to treat diseases caused by premature stop codons, which cause 11% of all heritable human diseases. —DJ
Malaria infection and severe disease risks in Africa
Authors: Paton Robert S. , Kamau Alice , Akech Samuel , Agweyu Ambrose , Ogero Morris , Mwandawiro Charles , Mturi Neema , Mohammed Shebe , Mpimbaza Arthur , Kariuki Simon , Otieno Nancy A. , Nyawanda Bryan O. , Mohamed Amina F. , Mtove George , Reyburn Hugh , Gupta Sunetra , Bejon Philip , Lourenço José , Snow Robert W.
Published: August 2021

Childhood malaria

Understanding how changes in community parasite prevalence alter the rate and age distribution of severe malaria is essential for optimizing control efforts. Paton
et al
. assessed the incidence of pediatric severe malaria admissions from 13 hospitals in East Africa from 2006 to 2020 (see the Perspective by Taylor and Slutsker). Each 25% increase in community parasite prevalence shifted hospital admissions toward younger children. Low rates of lifetime infections appeared to confer some immunity to severe malaria in very young children. Children under the age of 5 years thus need to remain a focus of disease prevention for malaria control. —CA
Structural hierarchy defeats alloy cracking
Authors: An Xianghai
Published: August 2021

Internal herringbone structures in a ductile multicomponent alloy enable crack tolerance
Tracking severe malaria disease
Authors: Taylor Terrie , Slutsker Laurence
Published: August 2021

Malaria infection prevalence predicts malaria mortality—at least for now
Banking on protein structural data
Authors: Berg Jeremy
Published: August 2021

In 1953, the proposed structure of DNA magnificently linked biological function and structure. By contrast, 4 years later, the first elucidation of the structure of a protein—myoglobin, by Kendrew and colleagues—revealed an inelegant shape, described disdainfully as a “visceral knot.” Additional complexity, as well as some general principles, was revealed as more protein structures were solved over the next decade. In 1971, scientists at Brookhaven National Laboratory launched the Protein Data Bank (PDB) as a repository to collect and make available the atomic coordinates of structures (seven at the time) to interested parties. The PDB now includes more than 180,000 structures, and this resource has fueled an incalculable number of advances, including the recent development of powerful structure prediction tools.
X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19
Authors: Asano Takaki , Boisson Bertrand , Onodi Fanny , Matuozzo Daniela , Moncada-Velez Marcela , Maglorius Renkilaraj Majistor Raj Luxman , Zhang Peng , Meertens Laurent , Bolze Alexandre , Materna Marie , Korniotis Sarantis , Gervais Adrian , Talouarn Estelle , Bigio Benedetta , Seeleuthner Yoann , Bilguvar Kaya , Zhang Yu , Neehus Anna-Lena , Ogishi Masato , Pelham Simon J. , Le Voyer Tom , Rosain Jérémie , Philippot Quentin , Soler-Palacín Pere , Colobran Roger , Martin-Nalda Andrea , Rivière Jacques G. , Tandjaoui-Lambiotte Yacine , Chaïbi Khalil , Shahrooei Mohammad , Darazam Ilad Alavi , Olyaei Nasrin Alipour , Mansouri Davood , Hatipoğlu Nevin , Palabiyik Figen , Ozcelik Tayfun , Novelli Giuseppe , Novelli Antonio , Casari Giorgio , Aiuti Alessandro , Carrera Paola , Bondesan Simone , Barzaghi Federica , Rovere-Querini Patrizia , Tresoldi Cristina , Franco Jose Luis , Rojas Julian , Reyes Luis Felipe , Bustos Ingrid G. , Arias Andres Augusto , Morelle Guillaume , Kyheng Christèle , Troya Jesús , Planas-Serra Laura , Schlüter Agatha , Gut Marta , Pujol Aurora , Allende Luis M. , Rodriguez-Gallego Carlos , Flores Carlos , Cabrera-Marante Oscar , Pleguezuelo Daniel E. , Pérez de Diego Rebeca , Keles Sevgi , Aytekin Gokhan , Metin Akcan Ozge , Bryceson Yenan T. , Bergman Peter , Brodin Petter , Smole Daniel , Smith C. I. Edvard , Norlin Anna-Carin , Campbell Tessa M. , Covill Laura E. , Hammarström Lennart , Pan-Hammarström Qiang , Abolhassani Hassan , Mane Shrikant , Marr Nico , Ata Manar , Al Ali Fatima , Khan Taushif , Spaan András N. , Dalgard Clifton L. , Bonfanti Paolo , Biondi Andrea , Tubiana Sarah , Burdet Charles , Nussbaum Robert , Kahn-Kirby Amanda , Snow Andrew L. ,   COVID Human Genetic Effort,   COVID-STORM Clinicians,   COVID Clinicians,   Imagine COVID Group,   French COVID Cohort Study Group,   CoV-Contact Cohort,   Amsterdam UMC Covid-19 Biobank,   NIAID-USUHS COVID Study Group, Bustamante Jacinta , Puel Anne , Boisson-Dupuis Stéphanie , Zhang Shen-Ying , Béziat Vivien , Lifton Richard P. , Bastard Paul , Notarangelo Luigi D. , Abel Laurent , Su Helen C. , Jouanguy Emmanuelle , Amara Ali , Soumelis Vassili , Cobat Aurélie , Zhang Qian , Casanova Jean-Laurent
Published: August 2021

TLR7 and plasmacytoid dendritic cells are essential for type I IFN–dependent immunity to SARS-CoV-2 in the lungs.
Complete Genome Sequence of
Gelria
sp. Strain Kuro-4, a Thermophilic Anaerobe Isolated from a Thermophilic Anaerobic Digestion Reactor Treating Poly(
L
-Lactic Acid)
Authors: Yamada Takeshi , Hamada Masako , Kurobe Misaki , Narihiro Takashi , Tsuji Hideto , Daimon Hiroyuki
Published: August 2021

Strain Kuro-4 was isolated as a novel member of the genus
Gelria
from a thermophilic anaerobic digestion reactor treating poly(
l
-lactic acid). Here, we report a 2,880,462-bp complete circular genome sequence of Kuro-4, with a G+C content of 61.9%. The chromosome harbors 2,831 protein-coding genes and 62 RNA-coding genes.
Timing of neonatal stoma closure: a survey of health professional perspectives and current practice
Authors: Ducey Jonathan , Kennedy Ann M , Linsell Louise , Woolfall Kerry , Hall Nigel J , Gale Chris , Battersby Cheryl , Penman Gareth , Knight Marian , Lansdale Nick
Published: August 2021

Optimal timing for neonatal stoma closure remains unclear. In this study, we aimed to establish current practice and illustrate multidisciplinary perspectives on timing of stoma closure using an online survey sent to all 27 UK neonatal surgical units, as part of a research programme to determine the feasibility of a clinical trial comparing ‘early’ and ‘late’ stoma closure. 166 responses from all 27 units demonstrated concordance of opinion in target time for closure (6 weeks most commonly stated across scenarios), although there was a high variability in practice. A sizeable proportion (41%) of respondents use weight, rather than time, to determine when to close a neonatal stoma. Thematic analysis of free text responses identified nine key themes influencing decision-making; most related to nutrition, growth and stoma complications. These data provide an overview of current practice that is critical to informing an acceptable trial design.
Sudden cardiac death in a young boy with multisystemic inflammatory syndrome in children (MISC)
Authors: Venkatesha Gurudutta Avathi , Srinivas Nidhi , Mohamedali Saril , Chandrasekar Supraja
Published: August 2021

A previously healthy 12-year-old boy presented to the emergency department on the seventh day of illness with classical symptoms of postinflammatory multisystemic syndrome in children temporally associated with SARS-CoV-2 (fever, vomiting, loose stools and rashes all over the body) with COVID-19 seropositivity, high inflammatory markers and elevated cardiac enzymes with cardiogenic shock with multiple organ dysfunction syndrome. After having improved over the first 48 hours following intravenous immunoglobulin and pulsed steroids, this young boy developed sudden cardiac arrest and died. No reversible cause could be identified at the time of resuscitation. Despite an apparent clinical recovery in the myocardial function, it is likely that the myocardium remains arrhythmogenic due to cytokine-induced myocardial inflammation. There are several reports in the literature of fatality in multisystemic inflammatory syndrome in children (MISC) due to cardiovascular complication during the acute phase of the illness. To the best of our knowledge, this is the first report of sudden cardiac death in a child with MISC days after recovery from critical illness, suggesting that fatal outcome remains a potential risk during follow-up, even when there is no evidence of coronary aneurysm. Further studies are needed to identify clinical characteristics of such high-risk children presenting with MISC. We will need to follow these children closely to understand what implications they may have in the long term, and this helps in raising awareness among families of such children.
Adult-onset recurrent Kawasaki disease: an unusual cause of fever of unknown origin
Authors: Jones Timothy Peter Wynne , Petrie Colin , Sykes Catriona
Published: August 2021

We present the case of a 20-year-old man with a background of transposition of the great arteries presenting with fever of unknown origin, who developed a shock like syndrome with respiratory failure necessitating intubation. After extensive investigation, a diagnosis of adult-onset Kawasaki disease was made, and he was successfully treated with IVIg and corticosteroids. We present the clinical findings clinicians should be aware of, and review the literature on managing this rare presentation in adult, highlighting the importance of early diagnosis in improving outcomes. Both children and adults with Kawasaki disease require long-term follow-up, as they remain at increased risk of both coronary artery aneurysms and early acute coronary syndrome.
Atypical presentation of rapid-onset dystonia–parkinsonism in a toddler with a novel mutation in the ATP1A3 gene
Authors: Ganesh Aishwarya , Sivakumar Samyuktha , Manokaran RanjithKumar , Narasimhan Udayakumar
Published: August 2021

ATP1A3 gene mutations can result in a spectrum of diseases with diverse neurological manifestations. One such disorder linked to this mutation is rapid-onset dystonia–parkinsonism (RDP), which manifests as dystonia with features of parkinsonism, such as tremors, rigidity, muscle spasms, and bulbar symptoms. Affected patients are typically adolescents or young adults, with symptoms occurring in a rostrocaudal pattern. We report a unique case of a 2-year-old child with an early onset, atypical presentation of RDP. In addition to motor developmental delay, he presented with muscle rigidity and mild asymmetric dystonia of the limbs, with the lower limbs being more affected than the upper limbs. Genetic sequencing of the child revealed a novel heterozygous autosomal dominant mutation of ATP1A3 gene c.173A>G (p. Tyr58Cys). This report highlights that RDP can present with atypical presentations in the paediatric population and adds to existing medical literature on the clinical spectrum of ATP1A3 genetic channelopathy.
Successful endoscopic resection of an unusually enlarged and pedunculated type I gastric carcinoid tumour
Authors: Odisho Tanya , Shi Dongping , Aburashed Ahmad
Published: August 2021

Three distinct gastric carcinoid (GC) tumour types have been described based on differing biological behaviour and prognoses. Type I GC tumours account for the vast majority (70%–80%), are associated with chronic atrophic gastritis and have a low metastatic potential. Type II carcinoid tumours are the least common (5%–10%), are related to Zollinger-Ellison syndrome and occur in relation to multiple neoplasia type I. Sporadic type III tumours (15%–25%) are the most aggressive type, are unrelated to gastrin over secretion and carry the worst prognosis. In this case report, we present a patient with longstanding gastroesophageal reflux disease (GERD) who presented with epigastric abdominal pain and tarry stools and was found to have a large gastric polyp on endoscopy. Despite current literature recommending surgical resection for larger GC tumours, endoscopic resection was successfully used to excise the tumour with pathology demonstrating complete resection with negative margins.
Molecular and pharmacological characterization of insulin icodec: a new basal insulin analog designed for once-weekly dosing
Authors: Nishimura Erica , Pridal Lone , Glendorf Tine , Hansen Bo Falk , Hubálek František , Kjeldsen Thomas , Kristensen Niels Rode , Lützen Anne , Lyby Karsten , Madsen Peter , Pedersen Thomas Åskov , Ribel-Madsen Rasmus , Stidsen Carsten Enggaard , Haahr Hanne
Published: August 2021

Introduction

Insulin icodec is a novel, long-acting insulin analog designed to cover basal insulin requirements with once-weekly subcutaneous administration. Here we describe the molecular engineering and the biological and pharmacological properties of insulin icodec.

Research design and methods

A number of in vitro assays measuring receptor binding, intracellular signaling as well as cellular metabolic and mitogenic responses were used to characterize the biological properties of insulin icodec. To evaluate the pharmacological properties of insulin icodec in individuals with type 2 diabetes, a randomized, double-blind, double-dummy, active-controlled, multiple-dose, dose escalation trial was conducted.

Results

The long half-life of insulin icodec was achieved by introducing modifications to the insulin molecule aiming to obtain a safe, albumin-bound circulating depot of insulin icodec, providing protracted insulin action and clearance. Addition of a C20 fatty diacid-containing side chain imparts strong, reversible albumin binding, while three amino acid substitutions (A14E, B16H and B25H) provide molecular stability and contribute to attenuating insulin receptor (IR) binding and clearance, further prolonging the half-life. In vitro cell-based studies showed that insulin icodec activates the same dose-dependent IR-mediated signaling and metabolic responses as native human insulin (HI). The affinity of insulin icodec for the insulin-like growth factor-1 receptor was proportionately lower than its binding to the IR, and the in vitro mitogenic effect of insulin icodec in various human cells was low relative to HI. The clinical pharmacology trial in people with type 2 diabetes showed that insulin icodec was well tolerated and has pharmacokinetic/pharmacodynamic properties that are suited for once-weekly dosing, with a mean half-life of 196 hours and close to even distribution of glucose-lowering effect over the entire dosing interval of 1 week.

Conclusions

The molecular modifications introduced into insulin icodec provide a novel basal insulin with biological and pharmacokinetic/pharmacodynamic properties suitable for once-weekly dosing.

Trial registration number

NCT02964104.
Governance factors that affect the implementation of health financing reforms in Tanzania: an exploratory study of stakeholders’ perspectives
Authors: Osei Afriyie Doris , Hooley Brady , Mhalu Grace , Tediosi Fabrizio , Mtenga Sally M
Published: August 2021

The development of effective and inclusive health financing reforms is crucial for the progressive realisation of universal health coverage in low-income and middle-income countries. Tanzania has been reforming health financing policies to expand health insurance coverage and achieve better access to quality healthcare for all. Recent reforms have included improved community health funds (iCHFs), and others are underway to implement a mandatory national health insurance scheme in order to expand access to services and improve financial risk protection. Governance is a crucial structural determinant for the successful implementation of health financing reforms, however there is little understanding of the governance elements that hinder the implementation of health financing reforms such as the iCHF in Tanzania. Therefore, this study used the perspectives of health sector stakeholders to explore governance factors that influence the implementation of health financing reforms in Tanzania. We interviewed 36 stakeholders including implementers of health financing reforms, policymakers and health insurance beneficiaries in the regions of Dodoma, Dar es Salaam and Kilimanjaro. Normalisation process theory and governance elements guided the structure of the in-depth interviews and analysis. Governance factors that emerged from participants as facilitators included a shared strategic vision for a single mandatory health insurance, community engagement and collaboration with diverse stakeholders in the implementation of health financing policies and enhanced monitoring of iCHF enrolment due to digitisation of registration process. Governance factors that emerged as barriers to the implementation were a lack of transparency, limited involvement of the private sector in service delivery, weak accountability for revenues generated from community level and limited resources due to iCHF design. If stakeholders do not address the governance factors that hinder the implementation of health financing reforms, then current efforts to expand health insurance coverage are unlikely to succeed on their own.
How to improve outbreak response: a case study of integrated outbreak analytics from Ebola in Eastern Democratic Republic of the Congo
Authors: Carter Simone E , Ahuka-Mundeke Steve , Pfaffmann Zambruni Jérôme , Navarro Colorado Carlos , van Kleef Esther , Lissouba Pascale , Meakin Sophie , le Polain de Waroux Olivier , Jombart Thibaut , Mossoko Mathias , Bulemfu Nkakirande Dorothée , Esmail Marjam , Earle-Richardson Giulia , Degail Marie-Amelie , Umutoni Chantal , Anoko Julienne Ngoundoung , Gobat Nina
Published: August 2021

The emerging field of outbreak analytics calls attention to the need for data from multiple sources to inform evidence-based decision making in managing infectious diseases outbreaks. To date, these approaches have not systematically integrated evidence from social and behavioural sciences. During the 2018–2020 Ebola outbreak in Eastern Democratic Republic of the Congo, an innovative solution to systematic and timely generation of integrated and actionable social science evidence emerged in the form of the Cellulle d’Analyse en Sciences Sociales (Social Sciences Analytics Cell) (CASS), a social science analytical cell. CASS worked closely with data scientists and epidemiologists operating under the Epidemiological Cell to produce integrated outbreak analytics (IOA), where quantitative epidemiological analyses were complemented by behavioural field studies and social science analyses to help better explain and understand drivers and barriers to outbreak dynamics. The primary activity of the CASS was to conduct operational social science analyses that were useful to decision makers. This included ensuring that research questions were relevant, driven by epidemiological data from the field, that research could be conducted rapidly (ie, often within days), that findings were regularly and systematically presented to partners and that recommendations were co-developed with response actors. The implementation of the recommendations based on CASS analytics was also monitored over time, to measure their impact on response operations. This practice paper presents the CASS logic model, developed through a field-based externally led consultation, and documents key factors contributing to the usefulness and adaption of CASS and IOA to guide replication for future outbreaks.
Cancer in Lahore, Pakistan, 2010–2019: an incidence study
Authors: Badar Farhana , Mahmood Shahid
Published: August 2021

Objectives

To study the cancer incidence rates over 10 years (2010–2019), in Lahore, Pakistan.

Design

An incidence study.

Setting

The population-based Punjab Cancer Registry was established in 2005 in Lahore, which is the provincial metropolis of the province of Punjab (five rivers), and is located in the northeast region of Pakistan. The coordinating office of the Registry is located within Shaukat Khanum Memorial Cancer Hospital and Research Center. Both the active and passive forms of data collection are used.

Participants

Residents of the district of Lahore diagnosed with cancer. The average annual population of Lahore was estimated at 11.1 million.

Outcome measures

Cancer counts and incidence rates per 100 000 population, by age-group, sex and cancer site/type, over 10 years.

Results

In Lahore, from 2010 to 2019, 58 394 incident cases were reported, with the majority seen in females (57.1%). Adults accounted for 92.2%, adolescents 2.2% and children 5.6% of the total cases. Per 100 000 population, the age-standardised incidence rate was 103.4 for females and 65.6 for males. Among females, the highest incidence rates were recorded for breast cancer (76.7) in adults, bone tumour (1.2) in adolescents and lymphoid leukaemia (1.6) in children, and among males, prostate cancer (10.7) in adults, bone tumour (2.2) in young adults and lymphoid leukaemia (2.4) in children. The age-specific incidence rates peaked in the 60–70 year group, reaching a high of 420 per 100 000 in women and 330 per 1 00 000 men.

Conclusions

In Lahore, the incidence rates for cancers of the breast, prostate, lymphoid leukaemia and bone were among the highest documented. More cases were recorded in females than in males. The results reported could be used as a reference point for assessing the effectiveness of future interventions.
Identification of factors associated with high-cost use of inpatient care in chronic kidney disease: a registry study
Authors: Sowa P. Marcin , Venuthurupalli Sree K. , Hoy Wendy E. , Zhang Jianzhen , Cameron Anne , Healy Helen G. , Connelly Luke B.
Published: August 2021

Objective

To explore factors behind inpatient admissions by high-cost users (HCUs) in pre-end-stage chronic kidney disease (CKD).

Design

Retrospective analysis of CKD.QLD Registry and hospital admissions of the Queensland Government Department of Health recorded between 1 July 2011 and 30 June 2016.

Setting

Queensland public and private hospitals.

Participants

5096 individuals with CKD who consented to the CKD.QLD Registry via 1 of 11 participating sites.

Main outcomes

Associations of HCU status with patient characteristics, pathways and diagnoses behind hospital admissions at 12 months.

Results

Age, advanced CKD, primary renal diagnosis, cardiovascular disease and hypertension were predictors of the high-cost outcome. HCUs were more likely than non-HCUs to be admitted by means of episode change (relative risk: 5.21; 95% CI 5.02 to 5.39), 30-day readmission (2.19; 2.13 to 2.25), scheduled readmission (1.29; 1.11 to 1.46) and emergency (1.07; 1.02 to 1.13), for diagnoses of the nervous (1.94; 1.74 to 2.15), circulatory (1.24; 1.14 to 1.34) and respiratory (1.2; 1.03 to 1.37) systems and other factors influencing health status (1.92; 1.74 to 2.09).

Conclusions

The high relevance of episode change and other factors influencing health status revealed that a substantial part of excess demand for inpatient care was associated with discordant conditions often linked to frailty, decline in psychological health and social vulnerability. This suggests that multidisciplinary models of care that aim to manage discordant comorbidities and address psychosocial determinants of health, such as renal supportive care, may play an important role in reducing inpatient admissions in this population.
Ocular surface angiography: from neovessels to neoplasia
Authors: Steger Bernhard
Published: August 2021

The ocular surface vascular system plays a key role in corneal and conjunctival inflammatory, infectious and neoplastic pathology. Angiographic vessel analysis using intravenous dyes and optical coherence tomography technology allow both the quantitative and functional assessment of conjunctival vasculature and corneal neovessels. Based on a thorough understanding of vascular alterations in ocular surface disease, angiographic assessment facilitates the clinical management of corneal neovascularisation, the grading of ocular surface inflammation and the identification of tumour angiogenesis in dysplastic or malignant lesions. This review summarises key aspects of the clinical application of corneal and conjunctival angiography as presented at the 2021 virtual Bowman Club meeting.