bluuebunny/crossref_metadata_2025 huggingface dataset:
Acral peeling in Nagashima type palmo‐plantar keratosis patients reveals the role of serine protease inhibitor B 7 in keratinocyte adhesion
Authors: Cohen‐Barak Eran , Azzam Wassim , Koetsier Jennifer L. , Danial‐Farran Nada , Barcan Moran , Hriesh Maysa , Khayat Morad , Edison Natalia , Krausz Judith , Gafni‐Amsalem Chen , Kubo Akiharu , Godsel Lisa M. , Ziv Michael , Allon‐Shalev Stavit
Published: August 2021

Acral peeling skin syndrome (APSS) is a heterogenous group of genodermatoses, manifested by peeling of palmo‐plantar skin and occasionally associated with erythema and epidermal thickening. A subset of APSS is caused by mutations in protease inhibitor encoding genes, resulting in unopposed protease activity and desmosomal degradation and/or mis‐localization, leading to enhanced epidermal desquamation. We investigated two Arab‐Muslim siblings with mild keratoderma and prominent APSS since infancy. Genetic analysis disclosed a homozygous mutation in SERPINB7, c.796C > T, which is the founder mutation in Nagashima type palmo‐plantar keratosis (NPPK). Although not previously formally reported, APSS was found in other patients with NPPK. We hypothesized that loss of SERPINB7 function might contribute to the peeling phenotype through impairment of keratinocyte adhesion, similar to other protease inhibitor mutations that cause APSS. Mis‐localization of desmosomal components was observed in a patient plantar biopsy compared with a biopsy from an age‐ and gender‐matched healthy control. Silencing of SERPINB7 in normal human epidermal keratinocytes led to increased cell sheet fragmentation upon mechanical stress. Immunostaining showed reduced expression of desmoglein 1 and desmocollin 1. This study shows that in addition to stratum corneum perturbation, loss of SERPINB7 disrupts desmosomal components, which could lead to desquamation, manifested by skin peeling.
Flight scheduling incorporating bad weather conditions through big data analytics: A comparison of metaheuristics
Authors: Erdem Ebru , Aydın Tolga , Erkayman Burak
Published: August 2021

The most important mode of long‐distance transportation for people to use time efficiently is air transportation. One of the most significant factors determining air traffic performance is the scheduling created by companies. When creating schedules, various parameters are used, mainly the demand for the determined route, and the availability of airplanes and flight crews. Known climatic conditions on the route are generally neglected. Within the scope of this study, the creation of flight schedules, which are normally the preparation of flight schedules by considering the monthly, daily, and hourly constraints that could cause flight delays, were determined by also considering weather conditions. In this determination process, 32‐year flight data between 1987 and 2018 were used as a basis. Apache Spark, one of the big data technologies, was used to determine these constraints. The scheduling was optimized by using the constraints used to prevent flight delays. It was observed in the results obtained that simulated annealing (SA) achieved the most optimal results compared to the genetic algorithm (GA) and the artificial bee colony (ABC) algorithm. As the dimensions of the searched space increased, solving the problem with metaheuristic approaches was more advantageous in terms of time compared to the classical method.
MANAGING INEQUALITY OVER BUSINESS CYCLES: OPTIMAL POLICIES WITH HETEROGENEOUS AGENTS AND AGGREGATE SHOCKS
Authors: Le Grand François , Ragot Xavier
Published: August 2021

We present a truncation theory of idiosyncratic histories for heterogeneous‐agent models. This method allows us to solve for optimal Ramsey policies in such models with aggregate shocks. The method can be applied to a large variety of settings, with occasionally binding credit constraints. We use this theory to characterize the optimal level of unemployment insurance over the business cycle in a production economy. We find that the optimal policy is countercyclical.
Histological and radiological evaluation of thermal denaturation depth using soft coagulation during partial nephrectomy in living pigs
Authors: Fujisaki Akira , Takayama Tatsuya , Teratani Takumi , Kubo Taro , Kamei Jun , Sugihara Toru , Ando Satoshi , Morita Tatsuo , Fujimura Tetsuya
Published: August 2021

Objectives

To evaluate thermal denaturation depth using soft coagulation in kidneys in vivo.

Methods

In experiment 1, nine kidneys from five pigs were cauterized using five soft‐coagulation settings at 80 W with effect 7 by VIO300D and one monopolar‐coagulation setting. The surface of the kidney was cauterized over a period of 2, 5 and 10 s. The temperature change was measured at depths of 5 and 10 mm. In experiment 2, three kidneys from two pigs were excised in a semicircular shape with a diameter of 5, 10 and 20 mm without clamping the renal artery. Cauterization was carried out until hemostasis was confirmed by soft coagulation at 80 W with effect 7. After completion of the experiments, pathology examinations of the kidneys were carried out.

Results

Experiment 1 showed that with proper saline dripping, denaturation spread with increased cauterization time, reaching a depth of 4 mm at 10 s with or without clamps. The depth remained at 2–3 mm at 10 s in the absence or excess of saline. The temperature increased by 15.6°C at a depth of 5 mm and 8.8°C at 10 mm. In experiment 2, the depth was 4.6 mm from the incision surface regardless of the cauterization time or excision size.

Conclusions

These findings suggest that soft coagulation can be useful for preserving renal function and reducing complications in partial nephrectomy.
Activated invariant natural killer T cells infiltrate aortic tissue as key participants in abdominal aortic aneurysm pathology
Authors: Miao Tianyu , Wang Tiehao , Feng Ting , Yuan Ding , Guo Qiang , Xiong Fei , Yang Yi , Liu Lihua , He Zhangyu , Huang Bin , Zhao Jichun
Published: August 2021

Adaptive immunity and innate immunity have been implicated in the pathogenesis of abdominal aortic aneurysm (AAA), and damage and remodelling in the tunica media are a focus of the aneurysm development. Thus, identification of key immune cells or molecules that might be targets for the treatment of AAA is critical. We characterized the innate immune cells in human AAA tissue specimens by flow cytometry and found that apart from other lymphocytes, many invariant natural killer T (iNKT) cells marked as CD3 and Va24Ja18 had invaded the aortic tissues and were numerous, especially in the tunica media. These infiltrating iNKT cells have a high expression of CD69, indicating a highly active function. We were interested in whether iNKT cells could be the drivers of media damage in AAA. To answer this question, we used an AAA mouse model induced by angiotensin II (Ang II) infusion, which can reproduce the inflammatory response of AAA in mouse, which was confirmed by RNAseq. The results showed that the incidence of AAA was significantly higher after administration of α‐galactosylceramide (α‐GalCer), a synthetic glycolipid that activates iNKT cells via CD1d, compared with the Ang II‐induced AAA alone (61·54% vs 31·82%) in mice. Histopathological and immunofluorescent staining results showed significantly more severe inflammatory infiltration and pathological lesions in the Ang II+α‐GalCer treatment group. These results are highly suggestive that activated iNKT cells greatly contribute to AAA development and that the control of the activation state in iNKT cells may represent an important therapeutic strategy for AAA.
Illness scripts in nursing: Directed content analysis
Authors: Vreugdenhil Jettie , Döpp Donna , Custers Eugène J. F. M. , Reinders Marcel E. , Dobber Jos , Kusukar Rashmi A.
Published: August 2021

Aims

To explore the possible extension of the illness script theory used in medicine to the nursing context.

Design

A qualitative interview study.

Methods

The study was conducted between September 2019 and March 2020. Expert nurses were asked to think aloud about 20 patient problems in nursing. A directed content analysis approach including quantitative data processing was used to analyse the transcribed data.

Results

Through the analysis of 3912 statements, scripts were identified and a nursing script model is proposed; the medical illness script, including enabling conditions, fault and consequences, is extended with management, boundary, impact, occurrence and explicative statements. Nurses often used explicative statements when pathophysiological causes are absent or unknown. To explore the applicability of Illness script theory we analysed scripts’ richness and maturity with descriptive statistics. Expert nurses, like medical experts, had rich knowledge of consequences, explicative statements and management of familiar patient problems.

Conclusion

The knowledge of expert nurses about patient problems can be described in scripts; the components of medical illness scripts are also relevant in nursing. We propose to extend the original illness script concept with management, explicative statements, boundary, impact and occurrence, to enlarge the applicability of illness scripts in the nursing domain.

Impact

Illness scripts guide clinical reasoning in patient care. Insights into illness scripts of nursing experts is a necessary first step to develop goals or guidelines for student nurses’ development of clinical reasoning. It might lay the groundwork for future educational strategies.
High‐risk features and predictors of unexplained syncope in the young SCD‐SOS cohort
Authors: Carrington Mafalda , Pais João , Brás Diogo , Creta Antonio , Teixeira Rogério , Gonçalves Lino , Providência Rui
Published: August 2021

Introduction

The Sudden Cardiac Death‐Screening of Risk FactOrS survey included a 12‐lead electrocardiogram (ECG) plus a digital‐based questionnaire and aimed to screen for warning signs of diseases that may course with sudden cardiac death in children and young adults. We aimed to estimate the prevalence of unexplained syncope (US) and characterize its high‐risk features and predictors in this cohort.

Methods and Results

We determined the most probable etiology of transient loss of consciousness (TLOC) episodes based on clinical criteria. US was an exclusion diagnosis and we analyzed its potential clinical and ECG predictors. Among 11 878 individuals, with a mean age of 21 ± 6 (range 6–40) years old, the cumulative incidence of TLOC was 26.5%, 76.2% corresponding to females. Reflex syncope was present in 66.4%, orthostatic hypotension in 8.2%, and 14.8% of the individuals had US. Unexplained syncope was independently associated with age < 18 years old (odds ratio [OR] 1.695; 95% confidence interval [CI] 1.26–2.29, p = .001), male gender (OR 1.642; 95% CI 1.22–2.22, p = .001), participation in competitive sports (OR 1.644; 95% CI 1.01–2.66, p = .043), syncope during exertion and/or palpitations preceding syncope (OR 2.556; 95% CI 1.92–3.40, p < .001), syncope after exertion (OR 2.662; 95% CI 1.73–4.10, p < .001), fever context (OR 9.606; 95% CI 4.13–22.34, p < .001), isolated previous syncopal episode (OR 2.780; 95% CI 0.2.06–3.75, p < .001), and history of palpitations requiring medical care (OR 1.945; 95% CI 1.14–3.31, p = .014). We found no ECG predictors of US in this population.

Conclusions

The cumulative incidence of TLOC in children and young adults is high and remains unexplained in an important proportion of individuals. We identified eight clinical characteristics that may be useful for the risk stratification of individuals evaluated in a nonacute setting.
Overexpression of lncRNA SLC26A4‐AS1 inhibits papillary thyroid carcinoma progression through recruiting ETS1 to promote ITPR1‐mediated autophagy
Authors: Peng Dong , Li Wenfa , Zhang Bojuan , Liu Xuefen
Published: August 2021

Papillary thyroid carcinoma (PTC), accounting for approximately 85% cases of thyroid cancer, is a common endocrine tumour with a relatively low mortality but an alarmingly high rate of recurrence or persistence. Long non‐coding RNAs (lncRNAs) is emerging as a critical player modulating diverse cellular mechanisms correlated with the progression of various cancers, including PTC. Herein, we aimed to investigate the role of lncRNA SLC26A4‐AS1 in regulating autophagy and tumour growth during PTC progression. Initially, ITPR1 was identified by bioinformatics analysis as a differentially expressed gene. Then, Western blot and RT‐qPCR were conducted to determine the expression of ITPR1 and SLC26A4‐AS1 in PTC tissues and cells, both of which were found to be poorly expressed in PTC tissues and cells. Then, we constructed ITPR1‐overexpressing cells and revealed that ITPR1 overexpression could trigger the autophagy of PTC cells. Further, we performed a series of gain‐ and loss‐of function experiments. The results suggested that silencing of SLC26A4‐AS1 led to declined ITPR1 level, up‐regulation of ETS1 promoted ITPR1 expression, and either ETS1 knockdown or autophagy inhibitor Bafilomycin A1 could mitigate the promoting effects of SLC26A4‐AS1 overexpression on PTC cell autophagy. In vivo experiments also revealed that SLC26A4‐AS1 overexpression suppressed PTC tumour growth. In conclusion, our study elucidated that SLC26A4‐AS1 overexpression promoted ITPR1 expression through recruiting ETS1 and thereby promotes autophagy, alleviating PTC progression. These finding provides insight into novel target therapy for the clinical treatment of PTC.
Activation of formyl peptide receptor 1 elicits therapeutic effects against collagen‐induced arthritis
Authors: Park Byunghyun , Lee Mingyu , Kim Sang Doo , Jeong Yu Sun , Kim Ji Cheol , Yang Siyoung , Kim Hye Young , Bae Yoe‐Sik
Published: August 2021

Rheumatoid arthritis (RA) is an autoimmune disorder which shows production of autoantibodies, inflammation, bone erosion, swelling and pain in joints. In this study, we examined the effects of an immune‐modulating peptide, WKYMVm, that is an agonist for formyl peptide receptors (FPRs). Administration of WKYMVm into collagen‐induced arthritis (CIA) mice, an animal model for RA, attenuated paw thickness, clinical scores, production of type II collagen‐specific antibodies and inflammatory cytokines. WKYMVm treatment also decreased the numbers of TH1 and TH17 cells in the spleens of CIA mice. WKYMVm attenuated TH1 and TH17 differentiation in a dendritic cell (DC)‐dependent manner. WKYMVm‐induced beneficial effects against CIA and WKYMVm‐attenuated TH1 and TH17 differentiation were reversed by cyclosporin H but not by WRW4, indicating a crucial role of FPR1. We also found that WKYMVm augmented IL‐10 production from lipopolysaccharide‐stimulated DCs and WKYMVm failed to suppress TH1 and TH17 differentiation in the presence of anti‐IL‐10 antibody. The therapeutic administration of WKYMVm also elicited beneficial outcome against CIA. Collectively, we demonstrate that WKYMVm stimulation of FPR1 in DCs suppresses the generation of TH1 and TH17 cells via IL‐10 production, providing novel insight into the function of FPR1 in regulating CIA pathogenesis.
Real‐world effectiveness of adalimumab in patients with moderate‐to‐severe hidradenitis suppurativa: the 1‐year SOLACE study
Authors: Gulliver W. , Alavi A. , Wiseman M.C. , Gooderham M.J. , Rao J. , Alam M.S. , Papp K.A. , Desjardins O. , Jean C.
Published: August 2021

Background

Long‐term, real‐word data are needed to help manage patients with hidradenitis suppurativa (HS) through this recurrent, painful and debilitating disease.

Objectives

To primarily measure real‐world effectiveness of adalimumab in HS and to secondarily observe clinical course of HS in the light of patients’ response.

Methods

In SOLACE, adults with moderate‐to‐severe HS in need for change in ongoing therapy were treated with adalimumab for up to 52 weeks as per physician’s medical practice. Treatment effectiveness was measured by Hidradenitis Suppurativa Clinical Response (HiSCR). Inflammatory nodules, abscesses and draining fistulas were counted, Hurley stage was assessed, and disease severity was rated using the International HS Severity Scoring System (IHS4). A post hoc analysis further explored the HiSCR response by abscess and inflammatory nodule (AN) count at baseline (low, medium and high) and gender. Spontaneously reported safety events were collected.

Results

From 23 Canadian centres, 69% of the 138 patients achieved HiSCR at week 24, which increased to 82% and 75% at week 52 in patients with medium and high AN counts, respectively. Gender (4 times the odds for female) and age at HS onset (5% decrease with each additional year) had an effect on achieving HiSCR. Treatment with adalimumab led to an important decrease in number of lesions in responders, with most gains observed in inflammatory nodules, more frequently in the lower body area of patients in the high AN count group. The IHS4 scores of responders were substantially lowered, with a larger decrease in patients of the high AN count group. No new safety signal was detected.

Conclusions

The effectiveness of adalimumab was maintained during this 1‐year period, and an optimal gain was documented for patients with medium and high AN counts. These real‐world data support a prompt treatment of HS patients and the use of IHS4 to monitor treatment.
The effectiveness of educational programmes in promoting sun protection among children under the age of 18: a systematic review and meta‐analysis
Authors: Sim W.M.B. , Zeng M.X. , Rojas‐Garcia A.
Published: August 2021

Childhood ultraviolet radiation exposure has a strong connection to the development of skin cancer in later life. Therefore, there have been numerous sun protection educational programmes targeted to this age group. However, the association between these have not been well established. This systematic review aims to summarize the evidence on, and assess, the effectiveness of educational programmes in improving sun protection among children under age‐18. The protocol was prospectively registered in the PROSPERO database (CRD42020178264). Per PRISMA guidelines, bibliographic databases CENTRAL, OVID (EMBASE, MEDLINE, PsycINFO), LILACS, trial registries, grey literature and other sources were systematically searched for randomized controlled and clinical controlled trials published between database inception to 9 June 2020. Dual independent review of abstracts and full texts was performed. Eligible studies were assessed for methodological quality using the Cochrane risk‐of‐bias tool. The primary outcome was postintervention scores [standardized mean difference (SMD)] for sun protection (i) knowledge (ii) attitudes and beliefs (iii) behavioural intentions and behaviours. Sidik‐Jonkman random effects meta‐analysis, sensitivity and subgroup analyses were performed for specific outcomes (sunscreen and sun‐safe hat use) which were sufficiently reported. 1350 publications were identified and 24 eligible trials, conducted across 8 different countries, with sufficient aggregate data were included. Small‐to‐moderate effects of educational programmes were observed across all sun protection outcomes of interest, but negligible effect sizes were demonstrated when specific outcomes were meta‐analysed – sunscreen use, SMD 0.18 (95% CI 0.07–0.29; n = 8) and sun‐safe hat use, SMD 0.08 (95% CI, 0.00–0.16; n = 6). A promising approach in the future may be to consider targeting children in secondary education with a digitally delivered interactive intervention. Current evidence, however, is insufficient to assess the effects of potential moderators and change in sun protection outcomes is likely not one‐size‐fits‐all. Further research is warranted to direct intervention design and public policy.
Dispersal reduces interspecific competitiveness by spreading locally harmful traits
Authors: Freedberg Steven , Urban Caroline , Cunniff Brianna M.
Published: August 2021

Just as intraorganismal selection can produce “selfish” elements that lower individual fitness, selection at the organismal level can favour traits that reduce the fitness of conspecifics and potentially impact population survival. Because dispersal can affect how these traits are distributed within species, it may determine whether their negative consequences are restricted locally or spread throughout the species' range. We present an individual‐based simulation model that explores the interaction between dispersal rate and traits that increase individual fecundity at the expense of conspecific fitness. We first modelled dispersal as a trait that varied within species and then fixed the within‐species dispersal rates and modelled competition between species that differed only in dispersal rate. Reproductive isolation allowed species differences in dispersal rates to become associated with traits moulded by intraspecific competition, but this association did not occur when dispersal variation was distributed within species due to recombination between the dispersal and competition loci. Alleles that reduced the fitness of conspecifics were maintained at lower frequencies in low‐dispersal species, resulting in a competitive advantage over high‐dispersing species. Although high‐dispersal species initially outcompeted low‐dispersal species owing to enhanced colonization opportunities, low‐dispersal species ultimately showed greater representation across a range of ecological and genetic scenarios. This process may shift the makeup of communities over time towards a greater representation of low‐dispersal species.
Evaluation of the virulence of entomopathogenic nematodes as a biological control agents against Gryllotalpa gryllotalpa (Gryllotalpidae)
Authors: Nouh Gehan M. , Adly Dalia
Published: August 2021

The European mole cricket Gryllotalpa gryllotalpa Linnaeus (Orthoptera: Gryllotalpidae) is a key pest of several crops in different regions of the world. The mole crickets usually damage seedlings, feeding aboveground on foliage or stem tissue and belowground on roots and tubers. In biological control, entomopathogenic nematodes (EPNs) are used against many insect pests inhabiting the soil as safe alternatives to chemical pesticides. The present study aimed to evaluate the virulence of the EPNs Heterorhabditis bacteriophora strain (HP88) and Steinernema carpocapsae strain (All) against the adults of European mole cricket G. gryllotalpa under laboratory and field conditions. Three concentrations of each of the EPNs H. bacteriophora and S. carpocapsae were tested against G. gryllotalpa. Infected adults of the pest with nematodes, at the concentration of 2000/cup, attained a mortality rate of (96%), when treated with S. carpocapsae and (72%) when treated with H. bacteriophora 8 days post‐treatments. Mortality percentage of G. gryllotalpa adults increased as the concentration of the nematodes increased. Adults' mortality of G. gryllotalpa reached 100% when treated with the combination of the 2 nematode's strains at all concentrations 4 days post‐treatments. At the 3 tested concentrations, 500, 1,000 and 2,000 IJs/adults, H. bacteriophora showed a higher reproductive rate in vivo than S. carpocapsae. A single adult of G. gryllotalpa treated with H. bacteriophora produced the average of 29,972, 74,768 and 140,474 IJs/adult, at the 3 concentrations, respectively. Under field application, a combination of EPNs successfully reduced the loss of the cabbage seedlings and the population's number of the mole crickets after 3 applications in the 2 seasons of (2019 and 2020). Therefore, EPNs as biological control agents can be recommended against the mole cricket G. gryllotalpa in vegetable crops as s pest management practice in an integrated pest management programme.
Neurocognitive functioning of children with mild to borderline intellectual disabilities and psychiatric disorders: profile characteristics and predictors of behavioural problems
Authors: Santegoeds E. , van der Schoot E. , Roording‐Ragetlie S. , Klip H. , Rommelse N.
Published: August 2021

Background

The aim of the current study was twofold: first, to uncover a neurocognitive profile of normative and relative strengths and weaknesses that characterises an extremely vulnerable group of children with mild to borderline intellectual disabilities (MBID) and co‐morbid psychiatric disorders, and second, to investigate the relevance of these neurocognitive functions explaining internalising and externalising symptoms.

Method

We recruited 45 children (Mage = 9.5, SDage = 1.7; range 6–13 years) with MBID (Full‐Scale IQ 50–85) and at least one psychiatric disorder. Neurocognitive functioning was examined utilising the Wechsler Intelligence Scale for Children – Fifth Edition (WISC‐V) indices and the Cognitive Task Application (COTAPP), a comprehensive computerised self‐paced task designed in such a manner that ‘g’ (an overall tendency of children with MBID to execute tasks with a slower reaction time and a higher error rate) has been corrected for in the administration of the task (i.e. completely self‐paced) and in the operationalisation of outcome measures. Behavioural problems were measured using the CBCL and TRF. One‐sample t‐tests and binomial tests were carried out to compare performance with normative data. Regression analyses were used to examine the relationship between neurocognitive parameters and mental health.

Results

Compared with normative data, very small to very large effect sizes were found, indicating clear heterogeneity amongst neurocognitive domains relevant for children with MBID. Two prominent neurocognitive weaknesses emerged: processing speed – characterised by slowness and unstableness combined with a high drift rate and delayed processing of the previous trial, particularly under higher cognitive demands – and working memory – in terms of a weaker central executive and ‘slave’ systems to temporarily store information. Both domains were not clearly predictive of internalising or externalising problems.

Conclusion

Children with MBID and psychiatric disorders are hampered by a strongly diminished processing speed and working memory capacity, together resulting in an overall limited processing capacity that may underlie the general developmental delays on domains that depend on fast and parallel processing of information (i.e. language, reading, mathematics and more complex forms of social cognition). Neurocognitive vulnerabilities are neither necessary nor sufficient to explain internalising and externalising problems; rather, a mismatch between the support needs and adaptations these children need, arising from their diminished processing capacity, and the inadequacy of the environment to compensate for this vulnerability may be of relevance.
Suppression of amyloid‐β secretion from neurons by cis‐9, trans‐11‐octadecadienoic acid, an isomer of conjugated linoleic acid
Authors: Hata Saori , Kano Kuniyuki , Kikuchi Kazunori , Kinoshita Shoichi , Sobu Yuriko , Saito Haruka , Saito Takashi , Saido Takaomi C. , Sano Yoshitake , Taru Hidenori , Aoki Junken , Komano Hiroto , Tomita Taisuke , Natori Shunji , Suzuki Toshiharu
Published: August 2021

Two common conjugated linoleic acids (LAs), cis‐9, trans‐11 CLA (c9,t11 CLA) and trans‐10, cis‐12 CLA (t10,c12 CLA), exert various biological activities. However, the effect of CLA on the generation of neurotoxic amyloid‐β (Aβ) protein remains unclear. We found that c9,t11 CLA significantly suppressed the generation of Aβ in mouse neurons. CLA treatment did not affect the level of β‐site APP‐cleaving enzyme 1 (BACE1), a component of active γ‐secretase complex presenilin 1 amino‐terminal fragment, or Aβ protein precursor (APP) in cultured neurons. BACE1 and γ‐secretase activities were not directly affected by c9,t11 CLA. Localization of BACE1 and APP in early endosomes increased in neurons treated with c9,t11 CLA; concomitantly, the localization of both proteins was reduced in late endosomes, the predominant site of APP cleavage by BACE1. The level of CLA‐containing phosphatidylcholine (CLA‐PC) increased dramatically in neurons incubated with CLA. Incorporation of phospholipids containing c9,t11 CLA, but not t10,c12 CLA, into the membrane may affect the localization of some membrane‐associated proteins in intracellular membrane compartments. Thus, in neurons treated with c9,t11 CLA, reduced colocalization of APP with BACE1 in late endosomes may decrease APP cleavage by BACE1 and subsequent Aβ generation. Our findings suggest that the accumulation of c9,t11 CLA‐PC/LPC in neuronal membranes suppresses the production of neurotoxic Aβ in neurons.

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Systemic inflammation induced the delayed reduction of excitatory synapses in the CA3 during ageing
Authors: Manabe Tatsuya , Rácz Ildikó , Schwartz Stephanie , Oberle Linda , Santarelli Francesco , Emmrich Julius V. , Neher Jonas J. , Heneka Michael T.
Published: August 2021

Sepsis‐associated encephalopathy (SAE) represents diverse cerebral dysfunctions in response to pathogen‐induced systemic inflammation. Peripheral exposure to lipopolysaccharide (LPS), a component of the gram‐negative bacterial cell wall, has been extensively used to model systemic inflammation. Our previous studies suggested that LPS led to hippocampal neuron death and synaptic destruction in vivo. However, the underlying roles of activated microglia in these neuronal changes remained unclear. Here, LPS from two different bacterial strains (Salmonella enterica or E. coli) were compared and injected in 14‐ to 16‐month‐old mice and evaluated for neuroinflammation and neuronal integrity in the hippocampus at 7 or 63 days post‐injection (dpi). LPS injection resulted in persistent neuroinflammation lasting for seven days and a subsequent normalisation by 63 dpi. Of note, increases in proinflammatory cytokines, microglial morphology and microglial mean lysosome volume were more pronounced after E. coli LPS injection than Salmonella LPS at 7 dpi. While inhibitory synaptic puncta density remained normal, excitatory synaptic puncta were locally reduced in the CA3 region of the hippocampus at 63 dpi. Finally, we provide evidence that excitatory synapses coated with complement factor 3 (C3) decreased between 7 dpi and 63 dpi. Although we did not find an increase of synaptic pruning by microglia, it is plausible that microglia recognised and eliminated these C3‐tagged synapses between the two time points of investigation. Since a region‐specific decline of CA3 synapses has previously been reported during normal ageing, we postulate that systemic inflammation may have accelerated or worsened the CA3 synaptic changes in the ageing brain.

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Tumor diameter as a predictor of lymph node involvement in endometrioid type endometrial adenocarcinomas
Authors: Akış Serkan , Kabaca Canan , Keleş Esra , Öztürk Uğur Kemal , Özyürek Eser , Api Murat , Çetiner Handan , Bostancı Evrim
Published: August 2021

Aim

To analyze the risk factors of lymph node involvement in pure endometrioid type endometrial cancer and assess factors that necessitate lymphadenectomy.

Methods

Patients who had been operated on due to endometrial cancer and whose final pathology was reported as pure endometrioid carcinoma between January 2014 and January 2020 were assessed. Hysterectomy, bilateral salpingo‐oophorectomy, and systematic lymphadenectomy were performed in all patients. All specimens were reported by expert gynecopathologists.

Results

The lymph node positivity rate was 14.4%. When the study population was classified according to the Mayo risk criteria; lymph node involvement in the low‐risk and high‐risk groups was 9.1% and 14.8%, respectively and there was no statistically difference (p > 0.05). The median of tumor size and the rate of deep myometrial invasion, lymphovascular space invasion, adnexal involvement, FIGO grade 3 tumor were found significantly higher in the positive lymph node group in univariate analysis. In the receiver operating characteristic curve analysis, the cut‐off value of the tumor diameter was determined as 47.5 mm (sensitivity 85%, specificity 62%). Every 10 mm increase in tumor diameter increased the risk of lymph node involvement 10 times.

Conclusion

This study defined that the tumor diameter is an independent predictor for lymphatic dissemination. In the future, it could be shown that even with new modeling based on tumor diameter, lymphadenectomy or adjuvant radiotherapy requirements would be reevaluated.
Fatherhood and wage inequality in Britain, Finland, and Germany
Authors: Icardi Rossella , Hägglund Anna Erika , Fernández‐Salgado Mariña
Published: August 2021

Objective

This study investigates whether and how fatherhood shapes the wage distribution in Britain, Finland, and Germany.

Background

Existing research debates whether fatherhood is associated with greater wages. However, it remains unclear whether the association between fatherhood and wages varies along the wage distribution as well as institutional contexts. To explore this, we compare three countries that differ in their wage bargaining institutions and family policies.

Method

We use unconditional quantile regression on longitudinal data from the 1995 to 2016 waves of the Finnish Linked Employer Employee data, German Socio‐Economic Panel, and UK Longitudinal Household Study. To control for selection into fatherhood, we combine quantile regressions with fixed effects techniques.

Results

Results show little evidence of substantial fatherhood wage effects along men's wage distribution. In all countries, fathers' higher wages at the median and top of the wage distribution are mostly accounted for by selection, but fatherhood shifts the bottom part of the distribution to the left particularly in the UK.

Conclusions

The extent to which having a child affects men's wages across the wage distribution is similar across three diverse policy contexts. Yet, differences across the wage distribution are larger in the UK. We argue this may be linked to its higher level of inequality typical of liberal labour markets.
Effects of Pathogen‐Avoidance Tendency on Infection‐Prevention Behaviors and Exclusionary Attitudes toward Foreigners: A Longitudinal Study of the COVID‐19 Outbreak in Japan1
Authors: Yamagata Mei , Teraguchi Tsukasa , Miura Asako
Published: August 2021

This study investigated the changes in public behaviors and attitudes following the spread of COVID‐19 in Japan. Using a longitudinal approach that analyzes the movement of an unpredictable and real infection threat to explain and predict human behavior during the pandemic—a novel approach in behavioral immune system research—a panel survey was conducted on Japanese citizens. The results of the survey, conducted in late January, mid‐February, and early March 2020, indicated that the influence of the interaction between the changes in situational infection threat and individual differences in pathogen‐avoidance tendency on infection‐prevention behaviors and exclusionary attitudes toward foreigners was not significant. Moreover, frequent contact with foreigners had a mitigating effect on exclusionary attitudes. The study thus provided a valuable contribution to the application of behavioral immune‐system responses to problems associated with infection threats. Moreover, consideration of the aspects of adaptive reaction and social learning allowed us to observe the process of adaptive strategies in novel environments under conditions of high ecological validity and to accurately understand the psychological response to infectious disease outbreaks.
Hepatitis C virus treatment with direct‐acting antivirals induces rapid changes in the hepatic proteome
Authors: Ball Lauren E. , Agana Bernice , Comte‐Walters Susana , Rockey Don C. , Masur Henry , Kottilil Shyam , Meissner Eric G.
Published: August 2021

Treatment of chronic hepatitis C virus with direct‐acting antivirals usually eradicates infection, but liver fibrosis does not resolve concurrently. In patients who develop cirrhosis prior to hepatitis C virus treatment, hepatic decompensation and hepatocellular carcinoma can still occur after viral elimination due to residual fibrosis. We hypothesized the liver proteome would exhibit meaningful changes in inflammatory and fibrinogenic pathways change upon hepatitis C virus eradication, which could impact subsequent fibrosis regression. We analysed the liver proteome and phosphoproteome of paired liver biopsies obtained from 8 hepatitis C virus‐infected patients before or immediately after treatment with direct‐acting antivirals. Proteins in interferon signalling and antiviral pathways decreased concurrent with hepatitis C virus treatment, consistent with prior transcriptomic analyses. Expression of extracellular matrix proteins associated with liver fibrosis did not change with treatment, but the phosphorylation pattern of proteins present within signalling pathways implicated in hepatic fibrinogenesis, including the ERK1/2 pathway, was altered concurrent with hepatitis C virus treatment. Hepatitis C virus treatment leads to reduced expression of hepatic proteins involved in interferon and antiviral signalling. Additionally, changes in fibrosis signalling pathways are detectable before alteration in extracellular matrix proteins, identifying a putative chronology for the dynamic processes involved in fibrosis reversal.
Genomic time‐series data show that gene flow maintains high genetic diversity despite substantial genetic drift in a butterfly species
Authors: Gompert Zachariah , Springer Amy , Brady Megan , Chaturvedi Samridhi , Lucas Lauren K.
Published: August 2021

Effective population size affects the efficacy of selection, rate of evolution by drift and neutral diversity levels. When species are subdivided into multiple populations connected by gene flow, evolutionary processes can depend on global or local effective population sizes. Theory predicts that high levels of diversity might be maintained by gene flow, even very low levels of gene flow, consistent with species long‐term effective population size, but tests of this idea are mostly lacking. Here, we show thatLycaeidesbutterfly populations maintain low contemporary (variance) effective population sizes (e.g. ~200 individuals) and thus evolve rapidly by genetic drift. However, populations harboured high levels of genetic diversity consistent with an effective population size several orders of magnitude larger. We hypothesized that the differences in the magnitude and variability of contemporary versus long‐term effective population sizes were caused by gene flow of sufficient magnitude to maintain diversity but only subtly affect evolution on generational timescales. Consistent with this hypothesis, we detected low but nontrivial gene flow among populations. Furthermore, using short‐term population‐genomic time‐series data, we documented patterns consistent with predictions from this hypothesis, including a weak but detectable excess of evolutionary change in the direction of the mean (migrant gene pool) allele frequencies across populations and consistency in the direction of allele frequency change over time. The documented decoupling of diversity levels and short‐term change by drift inLycaeideshas implications for our understanding of contemporary evolution and the maintenance of genetic variation in the wild.
Comparative genomics provides structural and functional insights into Bacteroides RNA biology
Authors: Prezza Gianluca , Ryan Daniel , Mädler Gohar , Reichardt Sarah , Barquist Lars , Westermann Alexander J.
Published: August 2021

Bacteria employ noncoding RNA molecules for a wide range of biological processes, including scaffolding large molecular complexes, catalyzing chemical reactions, defending against phages, and controlling gene expression. Secondary structures, binding partners, and molecular mechanisms have been determined for numerous small noncoding RNAs (sRNAs) in model aerobic bacteria. However, technical hurdles have largely prevented analogous analyses in the anaerobic gut microbiota. While experimental techniques are being developed to investigate the sRNAs of gut commensals, computational tools and comparative genomics can provide immediate functional insight. Here, using Bacteroides thetaiotaomicron as a representative microbiota member, we illustrate how comparative genomics improves our understanding of RNA biology in an understudied gut bacterium. We investigate putative RNA‐binding proteins and predict a Bacteroides cold‐shock protein homolog to have an RNA‐related function. We apply an in silico protocol incorporating both sequence and structural analysis to determine the consensus structures and conservation of nine Bacteroides noncoding RNA families. Using structure probing, we validate and refine these predictions and deposit them in the Rfam database. Through synteny analyses, we illustrate how genomic coconservation can serve as a predictor of sRNA function. Altogether, this work showcases the power of RNA informatics for investigating the RNA biology of anaerobic microbiota members.
Consequences of the first and secondCOVID‐19 wave on kidney transplant recipients at a large Indian transplant centre
Authors: Kute Vivek B. , Meshram Hari Shankar , Navadiya Vijay V. , Chauhan Sanshriti , Patel Dev D. , Desai Sudeep N. , Shah Nauka , Dave Ruchir B. , Banerjee Subho , Engineer Divyesh P. , Patel Himanshu V. , Rizvi Syed Jamal , Mishra Vineet V.
Published: August 2021

Background

There is a scarcity of data comparing the consequences of first and second COVID‐19 waves on kidney transplant recipients (KTRs) in India.

Methods

We conducted a single‐centre retrospective study of 259 KTRs with COVID‐19 to compare first wave (March 15–December 31 2020, n = 157) and second wave (April 1–May 31 2021, n = 102).

Results

KTRs during second wave were younger (43 vs. 40 years;p‐value .04) and also included paediatric patients (0 vs. 5.9%;p‐value .003). Symptoms were milder during the second wave (45 vs. 62.7%;p‐value .007); COVID‐19 positive patients had less frequent cough (32 vs. 13.8%;p‐value .001), fever was less frequent (58 vs. 37%;p‐value .001), and we observed fewer co‐morbidities (11 vs. 20.6%;p‐value .04). The percentages of neutrophils (77 vs. 83%;p‐value .001) and serum ferritin (439 vs. 688;p‐value .0006) were higher during second wave, while lymphocyte counts were reduced (20 vs. 14%;p‐value .0001). Hydroxychloroquine (11 vs. 0%;p‐value .0001) and tocilizumab (7 vs. 0%;p‐value .004) were more frequently prescribed during first wave, while utilization of dexamethasone (6 vs. 27%;p‐value .0001) and remdesivir (47 vs. 65%;p‐value .03) increased during the second wave. Mucormycosis (1.3 vs. 10%;p‐value .01) and ICU admissions (20 vs. 37.2%;p‐value .002) were more frequent during second wave. The 28‐day mortality rate (9.6 vs. 10%;p‐value 1) was not different.

Conclusions

There has been a different clinical spectrum of COVID‐19 amongst KTR with similar mortality between the two waves at a large Indian transplant centre.
Gastrointestinal symptoms and healthcare utilization have increased among patients with functional gastrointestinal and motility disorders during the COVID‐19 pandemic
Authors: Gubatan John , Zikos Thomas , Spear Bishop Estelle , Wu John , Gottfried Andrés , Becker Laren , Habtezion Aida , Neshatian Leila
Published: August 2021

Background

The coronavirus disease 2019 (COVID‐19) pandemic has led to unprecedented disruptions in healthcare. Functional gastrointestinal and motility disorders (FGIMD) are associated with significant healthcare utilization. The clinical implications of these healthcare disruptions due to the COVID‐19 pandemic on clinical outcomes in patients with FGIMD are unclear.

Methods

We performed a retrospective study of patients with three common FGIMD (irritable bowel syndrome [IBS], gastroparesis, functional dyspepsia [FD]) tested for SARS‐CoV‐2 to describe alterations in gastrointestinal symptoms, medication use, and healthcare utilization during and before the pandemic and factors associated with COVID‐19.

Key Results

The prevalence of COVID‐19 during the pandemic (03/2020–09/2020) was 3.20% (83/2592) among patients with FGIMD, 3.62% in IBS (57/1574), 3.07% in gastroparesis (23/749), and 2.44% in FD (29/1187) at our institution. Patients with FGIMD had increased abdominal pain, nausea/vomiting, diarrhea, constipation, and weight loss (p < 0.001) along with increased proton pump inhibitor, H2 blocker, and opioid use (p < 0.0001). Both inpatient hospitalizations and outpatient visits (p < 0.0001) and number of diagnostic tests including cross‐sectional imaging (p = 0.002), and upper and lower endoscopies (p < 0.0001) were significantly higher during the pandemic as compared to 6 months prior. Diarrhea‐predominant IBS was positively (OR 2.37, 95% CI 1.34–4.19, p = 0.003) associated with COVID‐19, whereas functional dyspepsia was negatively (OR 0.46, 95% CI 0.27–0.79, p = 0.004) associated.

Conclusions & Inferences

Patients with common functional gastrointestinal and motility disorders have reported more gastrointestinal symptoms during the COVID‐19 pandemic with concurrent increased medication use and healthcare utilization.
Early Cretaceous mealybug herbivory on a laurel highlights the deep‐time history of angiosperm–scale insect associations
Authors: Xiao Lifang , Labandeira Conrad C. , Ben‐Dov Yair , Maccracken S. Augusta , Shih Chungkun , Dilcher David L. , Ren Dong
Published: August 2021

Insect fluid‐feeding on fossil vascular plants is an inconspicuous and underappreciated mode of herbivory that can provide novel data on the evolution of deep‐time ecological associations and indicate the host‐plant preferences of ancient insect herbivores. Previous fossil studies have documented piercing‐and‐sucking herbivory but often are unable to identify culprit insect taxa.

One line of evidence are punctures and scale‐insect impression marks made by piercing‐and‐sucking insects that occasionally provide clues to the systematic identities and relationships of particular insect herbivores.

We report here the earliest occurrences of piercing and sucking on early angiosperms as evidenced by scale insect covers, impression marks, punctures and body fossils – notably a mealybug – from the Lower Cretaceous Rose Creek Flora of the Dakota Formation (c. 103 Ma), in southeastern Nebraska, USA. The mealybug, two other scale insect taxa, and several distinctive damage types on laurel leaves and seed‐plant stems at Rose Creek document a diverse guild of piercing‐and‐sucking insects on early angiosperms.

The discovery of an Early Cretaceous female mealybug indicates an early herbivorous association with a laurel host. These data provide direct evidence for co‐associations and possible coevolution of scale insects and their plant hosts during early angiosperm diversification.
Mobilizing governments and society to combat obesity: Reflections on how data from the WHO European Childhood Obesity Surveillance Initiative are helping to drive policy progress
Authors: Breda João , Farrugia Sant'Angelo Victoria , Duleva Vesselka , Galeone Daniela , Heinen Mirjam M. , Kelleher Cecily C. , Menzano Maria Teresa , Musić Milanović Sanja , Mitchell Lachlan , Pudule Iveta , Rito Ana Isabel , Shengelia Lela , Spinelli Angela , Spiroski Igor , Yardim Nazan , Buoncristiano Marta , Williams Julianne , Rakovac Ivo , McColl Karen
Published: August 2021

To meet the need for regular and reliable data on the prevalence of overweight and obesity among children in Europe, the World Health Organization (WHO) European Childhood Obesity Surveillance Initiative (COSI) was established in 2007. The resulting robust surveillance system has improved understanding of the public health challenge of childhood overweight and obesity in the WHO European Region. For the past decade, data from COSI have helped to inform and drive policy action on nutrition and physical activity in the region. This paper describes illustrative examples of how COSI data have fed into national and international policy, but the real scope of COSI's impact is likely to be much broader. In some countries, there are signs that policy responses to COSI data have helped halt the rise in childhood obesity. As the countries of the WHO European Region commit to pursuing United Action for Better Health in Europe in WHO's new European Programme of Work, COSI provides an excellent example of such united action in practice. Further collaborative action will be key to tackling this major public health challenge which affects children throughout the region.