bluuebunny/crossref_metadata_2025 huggingface dataset:
The social foundation of executive function
Authors: Marciszko Carin , Forssman Linda , Kenward Ben , Lindskog Marcus , Fransson Mari , Gredebäck Gustaf
Published: November 2019

In this study, we propose that infant social cognition may ‘bootstrap' the successive development of domain‐general cognition in line with the cultural intelligence hypothesis. Using a longitudinal design, 6‐month‐old infants (N = 118) were assessed on two basic social cognitive tasks targeting the abilities to share attention with others and understanding other peoples' actions. At 10 months, we measured the quality of the child's social learning environment, indexed by parent's abilities to provide scaffolding behaviors during a problem‐solving task. Eight months later, the children were followed up with a cognitive test‐battery, including tasks of inhibitory control and working memory. Our results showed that better infant social action understanding interacted with better parental scaffolding skills in predicting simple inhibitory control in toddlerhood. This suggests that infants' who are better at understanding other's actions are also better equipped to make the most of existing social learning opportunities, which in turn may benefit future non‐social cognitive outcomes.
How do you build back better so no one is left behind? Lessons from Sint Maarten, Dutch Caribbean, following Hurricane Irma
Authors: Collodi Jason , Pelling Mark , Fraser Arabella , Borie Maud , Di Vicenz Simone
Published: November 2019

The Sendai Framework for Disaster Risk Reduction 2015–2030 and the United Nations’ Sustainable Development Goals call for action to build back better in ways that leave no one behind. At the same time, ensuring a local voice is increasingly central to humanitarian engagement. These aims contrast with limited analysis of how local actors might be supported in these respects during response and recovery, and how far recommendations are specific or generalisable across richer and poorer national contexts. The paper begins by comparing lessons learnt by survivors and community organisations in Sint Maarten, Dutch Caribbean, following a high‐income state‐led response to Hurricane Irma in 2017 with the priorities of lower income, humanitarian‐led endeavours. The differences reveal the importance of economic resources as the basis for individual self‐reliance and a fragmented civil society with limited leadership ambitions in Sint Maarten. Strong cross‐cultural alignment nevertheless allows for a globally‐relevant and yet contextually‐sensitive framework for survivor‐led action and reconstruction.
Can agricultural subsidies reduce gendered productivity gaps? Panel data evidence from Zambia
Authors: Ngoma Hambulo , Machina Henry , Kuteya Auckland N.
Published: November 2019

Motivation

Farmer input support programmes (FISPs) have been implemented in sub‐Saharan Africa (SSA) since the 1970s in order to improve agricultural productivity and production. Whether FISPs are effective is much debated in the region. This article assesses whether FISPs can reduce gendered productivity gaps in agriculture, which in theory they should, by improving access to productive inputs for all farmers.

Purpose

Because FISPs improve access to productive inputs for women as well as men, this article asks whether subsidy programmes can reduce the gendered productivity gaps in agriculture. We assess the direct impacts of accessing FISP on maize productivity and whether these impacts are heterogeneous between women‐ and men‐managed plots.

Approach and methods

We combine the control function and the correlated random approaches to control for the endogeneity of access to FISPs and unobserved heterogeneity, and use the two‐wave panel of the Rural Agricultural Livelihoods Survey data collected in 2012 and 2015 in Zambia. The analysis is done at the level of farm plots.

Findings

Access to FISPs does not disproportionately raise maize productivity for women‐managed plots. This implies that a FISP alone is insufficient to address the gendered productivity gaps in agriculture. On average, FISPs were associated with average yield gains between 35 and 105 kg/ha in our sample, with larger gains for men‐managed subsamples. However, the use of fertilizers at these low rates of return is unlikely to be profitable for smallholder farmers.

Policy implications

Given that FISPs are likely to remain an important part of agricultural development policies in the region, there are reasons to believe they may have a role to play in reducing gendered gaps. However, reducing gendered productivity gaps in agriculture requires other non‐input factors that constrain women’s access to productive resources such as insecure land tenure and factors that limit the responsiveness of soils to fertilizer use among smallholder farmers to be addressed concomitantly.
Outcome and characteristics of non‐measurable myeloma: A cohort study with population‐based data from the Swedish Myeloma Registry
Authors: Wålinder Göran , Samuelsson Jan , Näsman Per , Hansson Markus , Juliusson Gunnar , Forsberg Karin , Svensson Ronald , Linder Olle , Carlson Kristina , Kristinsson Sigurdur Y. , Mellqvist Ulf Henrik , Hveding Blimark Cecilie , Turesson Ingemar , Nahi Hareth
Published: November 2019

Objective

We describe survival in patients with oligo‐ and non‐secretory multiple myeloma (MM). We refer to the whole group as non‐measurable MM and compare it with secretory MM.

Methods

Oligo‐secretory MM was defined as M protein in serum <10 g/L and M protein in urine <200 measured as mg/day, mg/liter or mg/mmol creatinine. If patients had no M protein, they were defined as non‐secretory. The groups were also subdivided by Free Light Chains (SFLC) level and ratio.

Results

Out of 4325 patients with symptomatic MM in the Swedish Myeloma Registry during 2008‐2016 eligible for the study, 389 patients (9%) had non‐measurable MM. Out of these, 253 patients (6%) had oligo‐secretory and 136 (3%) had non‐secretory MM. Median survival for secretory MM was 42.7 months, non‐measurable MM 40.2 months, oligo‐secretory MM 38.6 months, and non‐secretory MM 44.6 months. Difference in overall observed survival was non‐significant for all groups when compared with secretory MM. Within non‐secretory MM, stem cell transplantation (SCT), 95% being auto‐SCT, was significant for superior survival in multivariate analysis (HR 0.048. P = .0015).

Conclusion

In this population‐based study, we found no difference in survival between oligo‐ or non‐secretory MM when compared with secretory MM. SCT appears to be important also for patients with non‐secretory disease.
Predicting evolutionary responses to interspecific interference in the wild
Authors: Grether Gregory F. , Drury Jonathan P. , Okamoto Kenichi W. , McEachin Shawn , Anderson Christopher N.
Published: November 2019

Many interspecifically territorial species interfere with each other reproductively, and in some cases, aggression towards heterospecifics may be an adaptive response to interspecific mate competition. This hypothesis was recently formalised in an agonistic character displacement (ACD) model which predicts that species should evolve to defend territories against heterospecific rivals above a threshold level of reproductive interference. To test this prediction, we parameterised the model with field estimates of reproductive interference for 32 sympatric damselfly populations and ran evolutionary simulations. Asymmetries in reproductive interference made the outcome inherently unpredictable in some cases, but 80% of the model’s stable outcomes matched levels of heterospecific aggression in the field, significantly exceeding chance expectations. In addition to bolstering the evidence for ACD, this paper introduces a new, predictive approach to testing character displacement theory that, if applied to other systems, could help in resolving long‐standing questions about the importance of character displacement processes in nature.
Schwann cells as underestimated, major players in human skin physiology and pathology
Authors: Bray Eric R. , Chéret Jérémy , Yosipovitch Gil , Paus Ralf
Published: November 2019

Schwann cells (SCs) have long been recognized for their ability to support repair and promote axon regeneration following injury to the peripheral nervous system. In response to nerve injury, they rapidly dedifferentiate into a precursor‐like state, secrete an array of inflammatory mediators and growth factors, proliferate, undergo epithelial‐to‐mesenchymal‐like transformation to facilitate migration, phagocytose cellular debris and remodel the extracellular environment to promote regeneration of axons through the site of injury. However, even though a cutaneous role for SCs is becoming increasingly recognized, we argue in this Viewpoint essay that the likely complex functions of SCs in skin physiology and pathology beyond skin sensation and nerve repair deserve more attention and systemic research than they have received so far. For example, SCs promote wound healing, disseminate infection in leprosy, support the growth of neurofibromas/schwannomas and facilitate/accelerate the growth and invasion of melanoma. Despite representing a major dermal cell population, comparatively little is still known about the role of SCs in other dermatoses. To quintessentially illustrate the opportunities that promise to arise from a new skin research focus on SCs, we focus on two dermatoses that are not traditionally associated with SCs, that is, psoriasis and atopic dermatitis (AD), since both show distinct SC changes along with continuous nerve fibre degeneration and regeneration, and an impact of denervation on skin lesions. Specifically, we critically discuss the hypothesis that repeated activation of the SC repair programme occurs in and contributes to psoriasis and AD and delineate experimental approaches how to probe this clinically relevant hypothesis.
Identifying pseudoenzymes using functional annotation: pitfalls of common practice
Authors: Ribeiro Antonio J. M. , Tyzack Jonathan D. , Borkakoti Neera , Thornton Janet M.
Published: November 2019

Pseudoenzymes are proteins that are evolutionary related to enzymes but lack relevant catalytic activity. They are usually evolved from enzymatic ancestors that have lost their catalytic activities. The loss of catalytic function is one extreme amongst the other evolutionary changes that can occur to enzymes, like the changing of substrate specificity or the reaction catalysed. However, the loss of catalytic function events remain poorly characterised, except for some notable examples, like the pseudokinases. In this review, we aim to analyse current knowledge related to pseudoenzymes across a large number of enzymes families. This aims to be a review of the data available in biological databases, rather than a more traditional literature review. In particular, we use UniProtKB as the source for functional annotation and M‐CSA (Mechanism and Catalytic Site Atlas) for information on the catalytic residues of enzymes. We show that explicit annotation of lack of activity is not exhaustive in UniProtKB and that a protocol using lack of catalytic annotation as an indication for lack of function can be an adequate alternative, after some corrections. After identifying pseudoenzymes related to enzymes in M‐CSA, we were able to comment on their prevalence across enzyme families, and on the correlation between lack of catalytic function and the mutation of catalytic residues. These analyses challenge two common ideas in the emerging literature: that pseudoenzymes are ubiquitous across enzyme families and that mutations in the catalytic residues of enzyme homologues are always a good indication of lack of activity.
Fatigue crack growth analysis of different adhesive systems: Effects of mode mixity and load level
Authors: Rocha Ana V.M. , Akhavan‐Safar Alireza , Carbas Ricardo , Marques Eduardo A.S. , Goyal Rakesh , El‐zein Mohamad , da Silva Lucas F.M.
Published: November 2019

The aim of this paper is to investigate the fatigue fracture behavior of three different adhesive systems (epoxy‐based, acrylic, and a rubber‐like adhesive). To achieve this, double cantilever beam specimens were manufactured with different adhesives and tested under several mode mixities and different load levels. Fatigue crack growth rate was evaluated through a Paris law equation. For postprocessing, the compliance‐based beam method was used. Results showed that the variation of the threshold energy with load level is more pronounced for the epoxy‐based adhesive. The crack propagation life is higher for the acrylic adhesive. Although, for pure mode I conditions, the normalized threshold of the rubber‐like adhesive is lower, for pure mode II, it was higher than the epoxy‐based adhesive. Due to the normalization by the static fracture energy, the slope of the Paris law was approximately constant for all the adhesive systems.
Dynamic splitting tensile properties of concrete and cement mortar
Authors: Liu Pengfei , Zhou Xiaoping , Qian Qihu , Berto Filippo , Zhou Lunshi
Published: November 2019

To investigate the dynamic tensile behaviours of concrete and cement mortar, a 50‐mm split Hopkinson pressure bar was applied on Brazilian disc specimens for dynamic tensile experiments, in which strain rate varied from 10−5 to 20 s−1. The high‐speed camera testing technique was used to capture the dynamic fractured process of the specimens at relative high strain rate. The experimental results revealed that the dynamic tensile strength of concrete specimens has a stronger strain rate effect than that of cement mortar specimens. Then three typical failure patterns of the specimens were confirmed in dynamic experiments. In addition, one‐parameter semi‐empirical relation between dynamic tensile strength and strain rate was established. Finally, the limitation of dynamic splitting experiments on Brazilian disc specimens was discussed in detail at high strain rate, in which the crack initiates from the contact point between the incident bar and specimens rather than the centre of the specimens.
Megacity development and the demise of coastal coral communities: Evidence from coral skeleton δ15N records in the Pearl River estuary
Authors: Duprey Nicolas N. , Wang Tony X. , Kim Taihun , Cybulski Jonathan D. , Vonhof Hubert B. , Crutzen Paul J. , Haug Gerald H. , Sigman Daniel M. , Martínez‐García Alfredo , Baker David M.
Published: November 2019

Historical coral skeleton (CS) δ18O and δ15N records were produced from samples recovered from sedimentary deposits, held in natural history museum collections, and cored into modern coral heads. These records were used to assess the influence of global warming and regional eutrophication, respectively, on the decline of coastal coral communities following the development of the Pearl River Delta (PRD) megacity, China. We find that, until 2007, ocean warming was not a major threat to coral communities in the Pearl River estuary; instead, nitrogen (N) inputs dominated impacts. The high but stable CS‐δ15N values (9‰–12‰ vs. air) observed from the mid‐Holocene until 1980 indicate that soil and stream denitrification reduced and modulated the hydrologic inputs of N, blunting the rise in coastal N sources during the early phase of the Pearl River estuary urbanization. However, an unprecedented CS‐δ15N peak was observed from 1987 to 1993 (>13‰ vs. air), concomitant to an increase of NH4+ concentration, consistent with the rapid Pearl River estuary urbanization as the main cause for this eutrophication event. We suggest that widespread discharge of domestic sewage entered directly into the estuary, preventing removal by natural denitrification hotspots. We argue that this event caused the dramatic decline of the Pearl River estuary coral communities reported from 1980 to 2000. Subsequently, the coral record shows that the implementation of improved wastewater management policies succeeded in bringing down both CS‐δ15N and NH4+ concentrations in the early 2000s. This study points to the potential importance of eutrophication over ocean warming in coral decline along urbanized coastlines and in particular in the vicinity of megacities.
Thresholds of fire response to moisture and fuel load differ between tropical savannas and grasslands across continents
Authors: Alvarado Swanni T. , Andela Niels , Silva Thiago S. F. , Archibald Sally
Published: November 2019

Aim

An emerging framework for tropical ecosystems states that fire activity is either “fuel build‐up limited” or “fuel moisture limited”, that is, as you move up along rainfall gradients, the major control on fire occurrence switches from being the amount of fuel, to the moisture content of the fuel. Here we used remotely sensed datasets to assess whether interannual variability of burned area is better explained by annual rainfall totals driving fuel build‐up, or by dry season rainfall driving fuel moisture.

Location

Pantropical savannas and grasslands.

Time period

2002–2016.

Methods

We explored the response of annual burned area to interannual variability in rainfall. We compared several linear models to understand how fuel moisture and fuel build‐up effect (accumulated rainfall during 6 and 24 months prior to the end of the burning season, respectively) determine the interannual variability of burned area and explore if tree cover, dry season duration and human activity modified these relationships.

Results

Fuel and moisture controls on fire occurrence in tropical savannas varied across continents. Only 24% of South American savannas were fuel build‐up limited against 61% of Australian savannas and 47% of African savannas. On average, South America switched from fuel limited to moisture limited at 500 mm/year, Africa at 800 mm/year and Australia at 1,000 mm/year of mean annual rainfall.

Main conclusions

In 42% of tropical savannas (accounting for 41% of current area burned) increased drought and higher temperatures will not increase fire, but there are savannas, particularly in South America, that are likely to become more flammable with increasing temperatures. These findings highlight that we cannot transfer knowledge of fire responses to global change across ecosystems/regions—local solutions to local fire management issues are required, and different tropical savanna regions may show contrasting responses to the same drivers of global change.
Development of INSOL‐tag for proteome‐wide protein handling and its application in protein array analysis
Authors: Fukuda Eriko , Mori Masatoshi , Shiku Hiroshi , Miyahara Yoshihiro , Kawamura Yoshifumi , Ogawa Koji , Ogura Toshihiko , Goshima Naoki
Published: November 2019

Proteomic analysis requires protein tags that enable high‐throughput handling; however, versatile tags that can be used in in vitro expression systems are currently lacking. In this study, we developed an insoluble protein tag, INSOL‐tag, derived from human transcription factor MafG. The INSOL‐tagged target protein is expressed in a eukaryotic in vitro expression system and recovered as a pellet following centrifugation at 19,000 × g for 20 min. Comparisons of the target protein recovery rates of GST‐tag and INSOL‐tag using 111 cytoplasmic proteins revealed a fourfold increase in the yield of INSOL‐tagged proteins. Using 267 cancer antigens purified with INSOL‐tag, we subsequently developed an INSOL‐CTA array method, for profiling autoantibodies in sera of cancer patients. The detection limit of the array was approximately 11.1 pg IgG, and the correlation with ELISA was high (R2 = .993, .955). Moreover, when autoantibody profiling of digestive cancer patient sera was performed, antigen spreading was observed. These data suggest that INSOL‐tag is a versatile tag that can insolubilize a wide range of target proteins. It is therefore expected to become a powerful tool in comprehensive protein preparation for protein arrays, antibody production, and mass spectrometry.
Characterization of genetic‐origin‐dependent monoallelic expression in mouse embryonic stem cells
Authors: Ohishi Hiroaki , Au Yeung Wan Kin , Unoki Motoko , Ichiyanagi Kenji , Fukuda Kei , Maenohara Shoji , Shirane Kenjiro , Chiba Hatsune , Sado Takashi , Sasaki Hiroyuki
Published: November 2019

Monoallelic gene expression occurs in various mammalian cells and can be regulated genetically, epigenetically and/or stochastically. We identified 145 monoallelically expressed genes (MoEGs), including seven known imprinted genes, in mouse embryonic stem cells (ESCs) derived from reciprocal F1 hybrid blastocysts and cultured in 2i/LIF. As all MoEGs except for the imprinted genes were expressed in a genetic‐origin‐dependent manner, we focused on this class of MoEGs for mechanistic studies. We showed that a majority of the genetic‐origin‐dependent MoEGs identified in 2i/LIF ESCs remain monoallelically expressed in serum/LIF ESCs, but become more relaxed or even biallelically expressed upon differentiation. These MoEGs and their regulatory regions were highly enriched for single nucleotide polymorphisms. In addition, some MoEGs were associated with retrotransposon insertions/deletions, consistent with the fact that certain retrotransposons act as regulatory elements in pluripotent stem cells. Interestingly, most MoEGs showed allelic differences in enrichment of histone H3K27me and H3K4me marks, linking allelic epigenetic differences and monoallelic expression. In contrast, there was little or no allelic difference in CpG methylation or H3K9me. Taken together, our study highlights the impact of genetic variation including single nucleotide polymorphisms and retrotransposon insertions/deletions on monoallelic epigenetic marks and expression in ESCs.
Distinctive clinicopathological features and KRAS and IDH1/2 mutation status of cholangiolocellular carcinoma
Authors: Kusano Hironori , Naito Yoshiki , Mihara Yutaro , Kondo Reiichiro , Ogasawara Sachiko , Akiba Jun , Nakashima Osamu , Yano Hirohisa
Published: November 2019

Aim

Cholangiolocellular carcinoma (CLC) is classified as a subtype of combined hepatocellular cholangiocarcinoma with stem‐cell features (CHC‐SC) in the latest World Health Organization classification. This subclassification of CHC‐SCs is controversial and the relevance of such classification is unclear.

Methods

We analyzed a series of CHC‐SCs and intrahepatic cholangiocarcinoma (iCCA) to clarify the clinicopathological features and mutational status of each tumor.

Results

Background liver disease, fibrosis stage, microvascular invasion, nodal metastasis, and IDH1/2 mutation status were associated with their histology. Compared with the intermediate cell subtype of CHC‐SC (CHCs‐SC‐int), CLCs were less frequently associated with chronic viral hepatitis, and showed lower levels of serum alpha‐fetoprotein. Compared with iCCAs, CLCs showed lower levels of serum carbohydrate antigen 19‐9 (CA19‐9) and a lower frequency of expression of S100P. Patients with iCCA showed worse overall survival than those with CLC or CHC‐SC‐int. In patients with iCCA, CLC, or CHC‐SC‐int, a histology of iCCA, microvascular invasion, and serum CA19‐9 value of >100 U/mL were significant poor prognostic factors for overall survival in univariate analysis. Multivariate analysis showed that a high serum CA19‐9 value was an independent poor prognostic factor for overall survival.

Conclusions

Patients with CLC are likely to have a different etiology and mutational background from those with CHC‐SC‐int. Their clinicopathological manifestations are also different from those with classic iCCA. Our results suggest that CLC might be a distinct entity among primary liver carcinomas.
Patients’ and providers’ perspectives on medication relatedness and potential preventability of hospital readmissions within 30 days of discharge
Authors: Uitvlugt Elien B. , Janssen Marjo J. A. , Siegert Carl E. H. , Leenders Anna J. A. , van den Bemt Bart J. F. , van den Bemt Patricia M. L. A. , Karapinar‐Çarkit Fatma
Published: November 2019

Background

Hospital readmissions are increasingly used as an indicator of quality in health care. One potential risk factor of readmissions is polypharmacy. No studies have explored the patients’ perspectives on the medication relatedness and potential preventability of their readmissions.

Objective

To compare the patients’ perspectives on the medication relatedness and potential preventability of their readmissions with the providers’ perspectives.

Methods

Patients unplanned readmitted within 30 days after discharge at one of the participating departments of OLVG Hospital in Amsterdam were interviewed during their readmission. Patients’ perspectives regarding medication relatedness of their readmissions, the potential preventability, possible preventable interventions, and satisfaction with medication information were examined. Health‐care providers also reviewed files of these readmitted patients. Primary outcome was the percentage of medication‐related and potentially preventable readmissions according to the patient vs the provider. Descriptive data analysis was used.

Results

According to patients, 36 of 172 (21%) readmissions were medication‐related, and of these, 21 (58%) were potentially preventable. According to providers, 26 (15%) readmissions were medication‐related and 6 (23%) of these were potentially preventable. Patients and providers agreed on the medication relatedness in 11 of the 172 readmissions, and in two of these, agreement on the potential preventability existed. According to patients, preventive interventions belonged mostly to the hospital level, followed by the primary care level and patient level.

Conclusion

Patients and providers differ substantially on their perspectives regarding the medication relatedness and preventability of readmissions. Patients were more likely to view medication‐related readmissions as preventable.
Comparison of Lupinus angustifolius protein digestibility in dependence on protein, amino acids, trypsin inhibitors and polyphenolic compounds content
Authors: Zielińska‐Dawidziak Magdalena , Tomczak Aneta , Burzyńska Marta , Rokosik Ewa , Dwiecki Krzysztof , Piasecka‐Kwiatkowska Dorota
Published: November 2019

Lupine seeds are proposed as a source of valuable protein in human and animal nutrition. However, not only protein content but its bioavailability is important. Thus, the protein digestibility of twenty Lupinus angustifolius varieties seeds and the impact of some factors (protein and polyphenols content, trypsin inhibition and amino acids composition) on the protein digestion were discussed. Composition as well as the digestibility of these seeds was influenced by variety, weather conditions (precipitations) and place of cultivation (soil quality). The average digestibility of the seeds was 46%. The positive impact on the digestibility had the extractivity of the protein. Higher than it was expected activity of trypsin inhibitors (even up to ~32%) in some varieties influenced the protein availability, while the lysine and phenolic compounds content did not affect digestibility. The content of compounds influencing protein digestibility depends both on variety as well as on agronomical conditions.
Nondestructive determination of salmon fillet freshness during storage at different temperatures by electronic nose system combined with radial basis function neural networks
Authors: Jia Zhixin , Shi Ce , Wang Yanbo , Yang Xinting , Zhang Jiaran , Ji Zengtao
Published: November 2019

This study develops a predictive model for determining freshness of salmon fillets during cold storage at different temperatures using electronic nose combined with principal component analysis (PCA) and radial basis function neural networks (RBFNNs). The electronic nose sensed ammonia/amines, hydrocarbons, solvents and aromatics that increased during storage. The concentrations of the volatiles were compared with the increased thiobarbituric acid (TBA), total volatile basic nitrogen (TVB‐N), total aerobic bacteria count (TAC) and decreased of sensory assessments (SA). Gas chromatograph–ion mobility spectrometry analysis confirmed the changes in gas species. RBFNNs and PCA were used to establish predictive models and the relative errors of TBA, TVB‐N and TAC by the PCA‐RBFNNs model were all within ±10% and SA was within ±15%. These results suggest that the PCA‐RBFNNs model can be used to predict changes in the freshness of salmon fillets stored at −2 to 10 °C.
B‐cell memory in malaria: Myths and realities
Authors: Pérez‐Mazliah Damián , Ndungu Francis M. , Aye Racheal , Langhorne Jean
Published: November 2019

B‐cell and antibody responses to Plasmodium spp., the parasite that causes malaria, are critical for control of parasitemia and associated immunopathology. Antibodies also provide protection to reinfection. Long‐lasting B‐cell memory has been shown to occur in response to Plasmodium spp. in experimental model infections, and in human malaria. However, there are reports that antibody responses to several malaria antigens in young children living with malaria are not similarly long‐lived, suggesting a dysfunction in the maintenance of circulating antibodies. Some studies attribute this to the expansion of atypical memory B cells (AMB), which express multiple inhibitory receptors and activation markers, and are hyporesponsive to B‐cell receptor (BCR) restimulation in vitro. AMB are also expanded in other chronic infections such as tuberculosis, hepatitis B and C, and HIV, as well as in autoimmunity and old age, highlighting the importance of understanding their role in immunity. Whether AMB are dysfunctional remains controversial, as there are also studies in other infections showing that AMB can produce isotype‐switched antibodies and in mouse can contribute to protection against infection. In light of these controversies, we review the most recent literature on either side of the debate and challenge some of the currently held views regarding B‐cell responses to Plasmodium infections.
Passive immune therapy and other immunomodulatory agents for the treatment of severe influenza: Systematic review and meta‐analysis
Authors: Lim Vanessa W. , Tudor Car Lorainne , Leo Yee‐Sin , Chen Mark I‐Cheng , Young Barnaby
Published: November 2019

Background

A range of immunomodulatory therapies have been proposed as adjuncts to conventional antivirals to suppress harmful inflammation during severe influenza infection. We conducted a systematic review to assess available data of the effect of adjunctive non‐corticosteroid immunomodulatory therapy and potential adverse effects.

Method

We searched MEDLINE, Embase, Web of Science and clinical trial databases for published and unpublished studies, and screened the references of included articles. We included RCTs, quasi‐RCTs and observational studies of virologically confirmed influenza infections in hospitalised patients. We did not restrict studies by language of publication, influenza type/subtype or age of participants. Where possible, we pooled estimates of effect using random‐effects meta‐analysis models.

Results

We identified 11 eligible studies for inclusion: five studies (4 RCTs and 1 observational; 693 individuals) of passive immune therapy; four studies (3 RCTs and 1 observational; 1120 individuals) of macrolides and/or non‐steroidal anti‐inflammatory drugs (NSAIDs), one RCT of mTOR inhibitors (38 individuals), and one RCT of statin therapy (116 individuals). Meta‐analysis of RCTs of passive immune therapy indicated no significant reduction in mortality (OR 0.84, 0.37‐1.90), but better clinical outcomes at Day 7 (OR 1.42, 1.05‐1.92). There was a significant reduction in mortality associated with macrolides and/or NSAIDs (OR 0.28; 0.10‐0.77).

Conclusions

Passive immune therapy is unlikely to offer substantial mortality benefit in treatment of severe seasonal influenza, but may improve clinical outcomes. The effect of other immunomodulatory agents is uncertain, but promising. There is a need for high‐quality RCTs with sufficient statistical power to address this evidence gap.
Role of situational context in use continuance after critical exergaming incidents
Authors: Kari Tuomas , Salo Markus , Frank Lauri
Published: November 2019

Use continuance is crucial in terms of information systems (IS) success. Previous research has shown that situational context can be central for IS use continuance but has paid limited attention to its specific characteristics. Furthermore, the link between situational context and use continuance has remained unexplored in the novel area of “exergames,” which are defined as digital games requiring physical effort from the player that determines the outcome of the game. Studying exergames is deemed important due to their potential in providing health benefits for users, revenues for providers, and well‐being for societies. However, their potential remains unreached because users tend to discontinue usage after their initial experiences. To address these gaps, we investigate the relationships between specific situational characteristics and use continuance after critical exergaming incidents, in which the user has an exceptionally positive or negative experience. To do this, we quantitatively and qualitatively examined 461 actual critical exergaming incidents. Our findings provide a greater understanding of IS use continuance by revealing new knowledge about the relationships between specific situational characteristics (ie, purpose of use, type of gaming platform, social setting, place, and exertion level) and use continuance. We also offer explanations for these relationships, thus providing a first understanding of the previously unmapped area of how users behave situation‐dependently after critical exergaming incidents. Thus, we contribute both to the general IS continuance literature as well as to the specific area of exergaming. The context specificity of our study matches the calls for heavily contextualised IS research.
Playful learning with sound‐augmented toys: comparing children with and without visual impairment
Authors: Verver Suzanne H. , Vervloed Mathijs P.J. , Yuill Nicola , Steenbergen Bert
Published: November 2019

Sound‐augmented toys producing factual knowledge were thought to encourage incidental, playful learning in children with visual impairments (VIs). A group of 15 children with VIs and 22 sighted controls played with a sound‐augmented savannah landscape and listened to an informative story in a counterbalanced order. Children's knowledge about savannah animals was assessed at baseline and after each condition in order to quantitatively compare knowledge gains between conditions. Results indicated that children with VIs gained more knowledge than sighted controls from playing with the sound‐augmented toy. Furthermore, offering both the augmented toy and the informative story led to higher knowledge gains than a single medium, especially in children with VIs. Sound‐augmented toys could therefore be a useful addition to the current curriculum in special education for children with VIs.
Down‐regulated lncRNA HOTAIR alleviates polycystic ovaries syndrome in rats by reducing expression of insulin‐like growth factor 1 via microRNA‐130a
Authors: Jiang Bin , Xue Min , Xu Dabao , Song Jiayu , Zhu Shujuan
Published: November 2019

It has been found that long noncoding RNA HOTAIR, microRNA‐130a (miR‐130a) and insulin‐like growth factor 1 (IGF1) expression are associated with ovarian cancer, thus, we hypothesised that the HOTAIR/miR‐130a/IGF1 axis might associate with endocrine disorders and biological behaviours of ovarian granulosa cells in rat models of polycystic ovary syndrome (PCOS). PCOS rat models were established by injection of dehydro‐isoandrosterone, followed by treatment of si‐HOTAIR, oe‐HOTAIR, miR‐130a mimics or miR‐130a inhibitors. Serum hormonal levels were determined to evaluate endocrine conditions. The effect of HOTAIR and miR‐130a on activities of isolated ovarian granulosa cells was assessed, as well as the involvement of IGF1.In the ovarian tissues and granulosa cells of PCOS rat models, highly expressed HOTAIR and IGF1 and poorly expressed miR‐130a were identified. In response to oe‐HOTAIR, serum levels of E2, T and LH were increased and serum levels of FSH were reduced; the proliferation of granulosa cells was reduced and apoptosis was promoted; notably, expression of miR‐130a was reduced while expression of IGF1 was increased. The treatment of si‐HOTAIR reversed the situation. Furthermore, the binding of HOTAIR to miR‐130a and targeting relationship of miR‐130a and IGF1 were confirmed. LncRNA HOTAIR up‐regulates the expression of IGF1 and aggravates the endocrine disorders and granulosa cell apoptosis through competitive binding to miR‐130a in rat models of PCOS. Based on our finding, we predict that competitive binding of HOTAIR to miR‐130a may act as a novel target for the molecular treatment of PCOS.
MicroRNA‐1275 induces radiosensitization in oesophageal cancer by regulating epithelial‐to‐mesenchymal transition via Wnt/β‐catenin pathway
Authors: Xie Congying , Wu Youyi , Fei Zhenghua , Fang Ya , Xiao Shenlan , Su Huafang
Published: November 2019

Acquired radioresistance is one of the main obstacles for the anti‐tumour efficacy of radiotherapy in oesophageal cancer (EC). Recent studies have proposed microRNAs (miRNAs) as important participators in the development of radioresistance in various cancers. Here, we investigated the role of miR‐1275 in acquired radioresistance and epithelial‐mesenchymal transition (EMT) in EC. Firstly, a radioresistant cell line KYSE‐150R was established, with an interesting discovery was observed that miR‐1275 was down‐regulated in KYSE‐150R cells compared to the parental cells. Functionally, miR‐1275 inhibition elevated radioresistance in KYSE‐150 cells via promoting EMT, whereas enforced expression of miR‐1275 increased radiosensitivity in KYSE‐150R cells by inhibiting EMT. Mechanically, we demonstrated that miR‐1275 directly targeted WNT1 and therefore inactivated Wnt/β‐catenin signalling pathway in EC cells. Furthermore, WNT1 depletion countervailed the promoting effect of miR‐1275 suppression on KYSE‐150 cell radioresistance through hampering EMT, whereas WNT1 overexpression rescued miR‐1275 up‐regulation‐impaired EMT to reduce the sensitivity of KYSE‐150R cells to radiation. Collectively, our findings suggested that miR‐1275 suppressed EMT to encourage radiosensitivity in EC cells via targeting WNT1‐activated Wnt/β‐catenin signalling, providing a new therapeutic outlet for overcoming radioresistance of patients with EC.
Comparison of dermoscopic features between congenital and acquired acral melanocytic nevi in Korean patients
Authors: Roh D. , Shin K. , Kim W.‐I. , Yang M.‐Y. , Lee W.‐K. , Kim H.‐S. , Ko H.‐C. , Kim B.‐S. , Kim M.‐B.
Published: November 2019

Background

The dermoscopic patterns of acral melanocytic nevi (AMNs) are crucial in differentiating them from acral melanoma. Several studies have reported the dermoscopic patterns of acquired acral melanocytic nevi (AAMNs). However, few have investigated the dermoscopic patterns of congenital acral melanocytic nevi (CAMNs).

Objective

To compare the clinical and dermoscopic features of CAMNs and AAMNs.

Methods

The present study included 43 patients with CAMNs and 40 with AAMNs. We reviewed their medical records as well as their clinical and dermoscopic findings.

Results

Congenital acral melanocytic nevis were more asymmetrical than AAMNs (P = 0.002) and presented more frequently as comma‐shaped (P = 0.005). Regarding dermoscopic findings, globular pattern (55.8%) was the most common feature of CAMNs, while parallel furrow pattern (37.5%) was the most common feature of AAMNs. The presence of fibrillar, globular, and parallel ridge patterns, and diffuse multi‐component pigmentation differed significantly between the groups (P < 0.05). Furthermore, CAMNs showed melanoma‐specific dermoscopic patterns, such as parallel ridge (18.6%) and diffuse multi‐component pigmentation (25.6%).

Conclusion

The dermoscopic patterns of CAMNs and AAMNs differed markedly. In terms of dermoscopic patterns, CAMNs resembled acral melanoma more often than AAMNs did.
Interactions between persons—Knowledge, decision making, and the co‐production of practice
Authors: Loughlin Michael , Buetow Stephen , Cournoyea Michael , Copeland Samantha Marie , Chin‐Yee Benjamin , Fulford K.W.M.
Published: November 2019

There is now broad agreement that ideas like person‐centred care, patient expertise and shared decision‐making are no longer peripheral to health discourse, fine ideals or merely desirable additions to sound, scientific clinical practice. Rather, their incorporation into our thinking and planning of health and social care is essential if we are to respond adequately to the problems that confront us: they need to be seen not as “ethical add‐ons” but core components of any genuinely integrated, realistic and conceptually sound account of healthcare practice.

This, the tenth philosophy thematic edition of the journal, presents papers conducting urgent research into the social context of scientific knowledge and the significance of viewing clinical knowledge not as something that “sits within the minds” of researchers and practitioners, but as a relational concept, the product of social interactions. It includes papers on the nature of reasoning and evidence, the on‐going problems of how to ‘integrate’ different forms of scientific knowledge with broader, humanistic understandings of reasoning and judgement, patient and community perspectives. Discussions of the epistemological contribution of patient perspectives to the nature of care, and the crucial and still under‐developed role of phenomenology in medical epistemology, are followed by a broad range of papers focussing on shared decision‐making, analysing its proper meaning, its role in policy, methods for realising it and its limitations in real‐world contexts.
Infection, antibiotic exposure, and risk of celiac disease: A systematic review and meta‐analysis
Authors: Jiang Hai‐yin , Zhang Xue , Zhou Yuan‐yue , Jiang Chun‐min , Shi Yu‐dan
Published: November 2019

Background and Aim

There is evidence of a relationship between infection (and the associated antibiotic exposure) and the risk of celiac disease (CD). This study performed a meta‐analysis to investigate this relationship.

Methods

To identify relevant studies, we conducted systematic searches of the PubMed, Embase, and Cochrane databases for articles published up to April 2019. Random effects models were used to determine overall pooled estimates and 95% confidence intervals (CIs).

Results

The meta‐analysis included 19 observational studies (15 on infection and six on antibiotic exposure). Our results showed that any infection was associated with an increased risk of CD later in life (odds ratio, 1.37; 95% CI: 1.2–1.56; P < 0.001). The I2 was 94% (high heterogeneity among studies). Subgroup analyses suggested that the risk of CD is not affected by the type of infectious agent, timing of exposure, and site of infection. Exposure to antibiotics was also associated with new‐onset CD (odds ratio, 1.2; 95% CI: 1.04–1.39; P < 0.001).

Conclusion

Exposure to early infection or antibiotic appears to increase the odds of developing CD, suggesting that intestinal immune or microbiota dysbiosis may play a role in the pathogenesis of CD. These findings may influence clinical management and primary prevention of CD. However, noncausal explanations for these positive associations cannot be excluded.
Barriers to Prostate Cancer Screening by Men in Sub‐Saharan Africa: An Integrated Review
Authors: Baratedi William M. , Tshiamo Wananani B. , Mogobe Keitshokile D. , McFarland Ditsapelo M.
Published: November 2019

Purpose

The aim of this integrative review was to synthesize findings of the published studies on barriers to prostate cancer screening by men in sub‐Saharan Africa.

Design and Method

Five‐step Cooper integrative methodology guided this review. Electronic databases, including the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, EBSCOHOST, MEDLINE, ProQuest, and PsycINFO, were searched using specific search terms in combinations to identify relevant articles for the review. Through this process, 83 articles were retrieved and evaluated for duplications and relevance of titles, abstracts, and content. Seventeen articles met the inclusion criteria and were judged to be methodologically adequate. These articles were published between 2008 and 2018.

Findings

Studies that met the inclusion criteria were from seven sub‐Saharan countries, including Burkina Faso (n = 1), Ghana (n = 1), Kenya (n = 2), Namibia (n = 1), Nigeria (n = 8), South Africa (n = 3), and Uganda (n = 1). The most common barrier was lack of knowledge, followed by perceptions, attitudes, and beliefs that hindered screening and testing for prostate cancer.

Conclusions

The findings from the integrative review suggest that individuals with low levels of education tend to lack knowledge, cannot comprehend information, and are mistrustful about prostate cancer screening. Low socio‐economic status was also associated with poor prostate screening and testing uptake.

Clinical Relevance

Evidence from this review demonstrates that lack of knowledge is a major barrier for prostate screening among men in many parts of sub‐Saharan Africa.
Beyond Random Assignment: Credible Inference and Extrapolation in Dynamic Economies
Authors: HENNESSY CHRISTOPHER A. , STREBULAEV ILYA A.
Published: November 2019

We derive analytical relationships between shock responses and theory‐implied causal effects (comparative statics) in dynamic settings with linear profits and linear‐quadratic stock accumulation costs. For permanent profitability shocks, responses can have incorrect signs, undershoot, or overshoot depending on the size and sign of realized changes. For profitability shocks that are i.i.d., uniformly distributed, binary, or unanticipated and temporary, there is attenuation bias, which exceeds 50% under plausible parameterizations. We derive a novel sufficient condition for profitability shock responses to equal causal effects: martingale profitability. We establish a battery of sufficient conditions for correct sign estimation, including stochastic monotonicity. Simple extrapolation/error correction formulas are presented.
A global epidemic increase of an HPV‐induced tonsil and tongue base cancer – potential benefit from a pan‐gender use of HPV vaccine
Authors: Näsman A. , Du J. , Dalianis T.
Published: November 2019

In 2007, human papillomavirus (HPV) type 16 was finally recognized as a risk factor, besides smoking and alcohol, for oropharyngeal squamous cell carcinoma (OPSCC), including tonsillar squamous cell carcinoma (TSCC), by the International Agency for Research against Cancer. Just before, in 2006, the Food and Drug Administration had approved Gardasil, the first vaccine against HPV16, 18, 6 and 11, for preventive vaccination women against cervical cancer. Concurrently, some Western countries, where smoking was decreasing, disclosed an epidemic increase in the incidence of OPSCC, especially of TSCC and base of tongue cancer (BOTSCC), together accounting for 80–90% of all OPSCCs, and mainly affecting men. The epidemic was later revealed to be due to a rise in HPV‐positive cases, and scientists in the field suggested HPV vaccination also of boys. Globally, there are roughly 96 000 incident OPSCC cases/year of which 20–24% are caused by HPV, thereby accounting for around 22 000 OPSCC cases annually. Of these cases, 80–90% are due to HPV16 infection and would be prevented with the presently registered HPV vaccines. In Western countries, such as Sweden (with almost 400 TSCC and BOTSCC cases per year) and the United States, HPV prevalence in OPSCC is higher and around 70%. HPV vaccination of girls has been initiated in many countries, and the vaccines have been efficient and their side effects limited. HPV vaccination of boys has, however, been the exception, but should definitely not be delayed any further. It would benefit both girls and boys directly, and result in better and more robust herd immunity. Today, we have the possibility to eliminate several high‐risk HPV types in the younger generations and avoid more than 600 000 cancer cases annually worldwide, and this possibility should be embraced by offering global pan‐gender HPV vaccination.