bluuebunny/crossref_metadata_2025 huggingface dataset:
Stereo-EEG reveals rich cortical dynamics in humans coping with difficult action discrimination
Authors: Platonov A. , Pelliccia V. , Sartori I. , LoRusso G. , Avanzini P. , Orban G.A.
Published: January 2020

Visual perception of others’ actions is important for social interactions, and the ability to do so, even when one gets only brief glimpses of others’ behavior, may be crucial for survival. At present it is unknown how the human brain solves this problem. Imaging studies have promoted the idea that the multiple demand (MD) system, a domain general system of the human brain, operates in difficult cognitive and perceptual tasks, but not in tasks in which sensory information is reduced. Functional imaging, based on slow hemodynamic responses, may miss or standardize neural events with very diverse time courses. Here we exploited the temporal resolution of stereo-EEG to study directly cortical activity when human subjects must judge the actions of others, but only get brief glimpses of others’ activity, because the videos were truncated. Multiple cortical regions increased their activity in the difficult action discrimination, relative to the easy task when the complete video was visible. The majority of these regions belonged to the MD system, being located in parietal or prefrontal cortex. The variety of time courses, lasting from a few 100ms to several seconds, allowed us to disentangle control from effector regions, the latter processing observed actions. This distinction was further supported by relationships with behavior. A key operation within the control clusters was the prediction of erroneous responses, which was initiated in the PPC soon after the end of the truncated video. The time courses further suggested that MD regions not only exert control, but also perform various evaluations of the effort, important for efficient and intelligent behavior. We observed also increases outside the MD system, in temporo-parietal cortex, which may provide contextual information about variables related to the observed action, such as the actor, the object or the scene. Furthermore, to cope with the brief sensory input, the MD system called upon warning regions reacting to the static picture of the actor presented just before the video. We conclude that discrimination of brief observed actions indeed involves the MD system, which is thus is more general than assumed so far. WE also show that the MD system is more complex than assumed, as it includes evaluation of control, and more flexible, as it interacts with other systems than simply the effector circuit of the task.
Hox-dependent coordination of cardiac progenitor cell patterning and differentiation
Authors: Stefanovic Sonia , Laforest Brigitte , Desvignes Jean-Pierre , Lescroart Fabienne , Argiro Laurent , Maurel-Zaffran Corinne , Salgado David , de Bono Christopher , Pazur Kristijan , Théveniau-Ruissy Magali , Béroud Christophe , Pucéat Michel , Gavalas Anthony , Kelly Robert G. , Zaffran Stéphane
Published: January 2020

Perturbation of addition of second heart field (SHF) cardiac progenitor cells to the poles of the heart tube results in congenital heart defects (CHD). The transcriptional programs and upstream regulatory events operating in different subpopulations of the SHF remain unclear. Here, we profile the transcriptome and chromatin accessibility of anterior and posterior SHF sub-populations at genome-wide levels and demonstrate that Hoxb1 negatively regulates differentiation in the posterior SHF. Spatial mis-expression ofHoxb1in the anterior SHF results in hypoplastic right ventricle. Activation ofHoxb1in embryonic stem cells arrests cardiac differentiation, whereasHoxb1-deficient embryos display premature cardiac differentiation. Moreover, ectopic differentiation in the posterior SHF of embryos lacking bothHoxb1and its paralogHoxa1results in atrioventricular septal defects. Our results show that Hoxb1 plays a key role in patterning cardiac progenitor cells that contribute to both cardiac poles and provide new insights into the pathogenesis of CHD.
A chemical tool for improved culture of human pluripotent stem cells
Authors: Silpa Laurence , Schuessler Maximilian , Liu Gu , Olivecrona Marcus , Groizard-Payeras Lucia , Couper Elizabeth , Bataille Carole J. R. , Stevenson Mark , Seymour Len W. , Davies Stephen G. , James William S. , Cowley Sally A. , Russell Angela J.
Published: January 2020

The large-scale and cost-effective production of quality-controlled human pluripotent stem cells (hPSC) for use in cell therapy and drug discovery requires chemically-defined xenobiotic-free culture systems that enable easy and homogeneous expansion of pluripotent cells. Through phenotypic screening, we have identified a small molecule, OXS8360 (an optimized derivative of (-)-Indolactam V ((-)-ILV)), that stably disrupts hPSC cell-cell contacts. Proliferation of hPSC in OXS8360 is normal, as are pluripotency signatures, directed differentiation to hallmark lineages and karyotype over extended passaging. In 3D culture, OXS8360-treated hPSC form smaller, more uniform aggregates, that are easier to dissociate, greatly facilitating expansion. The mode of action of OXS8360 involves disruption of the localisation of the cell-cell adhesion molecule E-cadherin, via activation of unconventional Protein Kinase C isoforms. OXS8360 media supplementation is therefore able to yield more uniform, disaggregated 2D and 3D hPSC cultures, providing the hPSC field with an affordable tool to improve hPSC quality and scalability.
The resolution revolution in cryoEM requires high-quality sample preparation: a rapid pipeline to a high-resolution map of yeast fatty acid synthase
Authors: Joppe Mirko , D'Imprima Edoardo , Salustros Nina , Paithankar Karthik S. , Vonck Janet , Grininger Martin , Kühlbrandt Werner
Published: January 2020

Single-particle electron cryo-microscopy (cryoEM) has undergone a `resolution revolution' that makes it possible to characterize megadalton (MDa) complexes at atomic resolution without crystals. To fully exploit the new opportunities in molecular microscopy, new procedures for the cloning, expression and purification of macromolecular complexes need to be explored. Macromolecular assemblies are often unstable, and invasive construct design or inadequate purification conditions and sample-preparation methods can result in disassembly or denaturation. The structure of the 2.6 MDa yeast fatty acid synthase (FAS) has been studied by electron microscopy since the 1960s. Here, a new, streamlined protocol for the rapid production of purified yeast FAS for structure determination by high-resolution cryoEM is reported. Together with a companion protocol for preparing cryoEM specimens on a hydrophilized graphene layer, the new protocol yielded a 3.1 Å resolution map of yeast FAS from 15 000 automatically picked particles within a day. The high map quality enabled a complete atomic model of an intact fungal FAS to be built.
Probing the role of the conserved residue Glu166 in a class A β-lactamase using neutron and X-ray protein crystallography
Authors: Langan Patricia S. , Sullivan Brendan , Weiss Kevin L. , Coates Leighton
Published: January 2020

The amino-acid sequence of the Toho-1 β-lactamase contains several conserved residues in the active site, including Ser70, Lys73, Ser130 and Glu166, some of which coordinate a catalytic water molecule. This catalytic water molecule is essential in the acylation and deacylation parts of the reaction mechanism through which Toho-1 inactivates specific antibiotics and provides resistance to its expressing bacterial strains. To investigate the function of Glu166 in the acylation part of the catalytic mechanism, neutron and X-ray crystallographic studies were performed on a Glu166Gln mutant. The structure of this class A β-lactamase mutant provides several insights into its previously reported reduced drug-binding kinetic rates. A joint refinement of both X-ray and neutron diffraction data was used to study the effects of the Glu166Gln mutation on the active site of Toho-1. This structure reveals that while the Glu166Gln mutation has a somewhat limited impact on the positions of the conserved amino acids within the active site, it displaces the catalytic water molecule from the active site. These subtle changes offer a structural explanation for the previously observed decreases in the binding of non-β-lactam inhibitors such as the recently developed diazobicyclooctane inhibitor avibactam.
Value co-creation in firm sponsored online communities
Authors: Priharsari Diah , Abedin Babak , Mastio Emmanuel
Published: January 2020

Purpose

The purpose of this paper is to explore enablers and constraints in value co-creation in sponsored online communities, and to identify firm roles in shaping value co-creation. The structured analysis is translated into strategies for practitioners and for guiding future research.

Design/methodology/approach

The authors systematically review and synthesise the literature to develop a comprehensive model of value co-creation.

Findings

The literature review findings have led to the identification of four actors in sponsored online communities, revealed enablers and constraints for value co-creation in online communities, and provided insight into the simultaneous roles of sponsoring firm (co-creator and facilitator) and the interrelationship between them.

Research limitations/implications

Like other systematic literature review studies, the findings are limited by what was reported in the papers selected for the review. The authors contribute to service-dominant logic (SDL) by bridging the macro level to the empirical level, and add to our understanding of the sociomateriality theory by capturing constraints and enablers coming from various actors.

Practical implications

The extracted enablers and constraints guide decision makers to better design, asses, monitor and support sponsored online communities. The findings also inform how to orchestrate the two sponsoring firm roles so that the online community is still attractive for the members and creates value for the sponsoring firm.

Originality/value

Given the variety of disciplines dealing with value co-creation, and given the plenitude of definitions and related concepts, this study consolidates the existing knowledge and models how value is co-created in online communities.
Examining the influence of factors critical for the consumer to accept the offered Islamic home financing
Authors: Amin Hanudin
Published: January 2020

Purpose

This study aims to examine the impacts ofShariah-compliant products, value-added benefits, mortgage repayment policy and well-versed bankers on the consumer acceptance of Islamic home financing. These variables, thereafter, are called the “critical success factors” (the CSFs) for Islamic home financing.

Design/methodology/approach

Guided by the Islamic theory of consumer behaviour (ITCB), this study intends to propose the specific CSFs that ensure consumer acceptance of Islamic home financing a success. The term success refers to consumers’ willingness to take up the facility. A questionnaire survey was conducted to elicit responses pertinent to the level of agreement/disagreement of the CSFs. A total of 460 respondents usable responses were obtained and analysed accordingly.

Findings

The results obtained indicate thatShariah-compliant products, value-added benefits, mortgage repayment policy and well-versed bankers are instrumental to influence the consumer acceptance of Islamic home financing.

Research limitations/implications

Like other works, this study has confined its context to capture only a limited geographical area, and the study’s contributions are restrained to the variables analysed to a specific context of Islamic home financing in Malaysia.

Practical implications

The results obtained can become as a yardstick to measure the consumer acceptance of Islamic home financing.

Originality/value

New proposed CSFs can help to address the new demand of Islamic home financing accordingly, where a new area of improvement is brought into play. This study also extends the applicability of the ITCB to include Islamic home financing products.
Understanding customer brand engagement in user-initiated online brand communities: antecedents and consequences
Authors: Matute Jorge , Palau-Saumell Ramon , Occhiocupo Nicoletta
Published: January 2020

Purpose

The purpose of this study is to provide a better understanding of customer brand engagement (CBE) by proposing and empirically testing a model of antecedents and consequences of CBE for user-initiated online brand communities (OBCs).

Design/methodology/approach

The model is tested using a sample of 584 participants in two relevant OBCs created and managed by brand fans. Specifically, data were collected from two communities in the photography products category: Nikonistas and Canonistas.

Findings

The results indicate that community and brand identification positively and significantly influence CBE. Furthermore, the supporting role of OBCs’ moderators facilitates CBE and moderates the influence of community identification on CBE. Regarding the outcomes of CBE, the results show that higher levels of engagement are positively, directly and significantly associated with favorable intentions towards the brand and the community. These effects are then mediated by brand affective commitment.

Research limitations/implications

The study has been conducted in two Spanish OBCs of two specific high-involvement products category: it is cross-sectional and focuses on a limited number of antecedents and consequences.

Practical implications

Evidence from this research supports and emphasizes the potential that these platforms have for brand management such that firms’ resources could be best allocated on those elements that lead to superior CBE.

Originality/value

The study endorses the role of CBE in fostering brand and community-related favorable outcomes in the context of user-initiated OBCs. It shed lights on the potential that these online platforms have for brands and on the role that brand management should play in digital contexts that are outside the direct control of the company.
Integration versus conflict between schools of dream theory and dreamwork: integrating the psychological core qualities of dreams with the contemporary knowledge of the dreaming brain
Authors: Vedfelt Ole
Published: January 2020

The various ways schools of psychotherapy relate to dreams have been marked by isolationism and mutual conflict rather than self‐examination and then integrating the discoveries and methods of other schools. Jung’s method was in opposition to Freud’s psychoanalysis. Existential psychology was dismissive of Freud’s and Jung’s discoveries, while cognitive dream interpretation and cognitive therapy sought other roads entirely. In addition, scientific and neuropsychological dream research has been only insignificantly tied to the psychotherapeutic dream theories. These conflicts and the lack of a comprehensive dream theory has made it convenient for the current rationalist collective consciousness and treatment systems to reject the often times challenging knowledge about ourselves that dreams can provide.

This paper describes how contemporary theories of complex cybernetic information networks can create an overriding, constructive framework for uncovering common traits within the above‐mentioned branches of dream research and dreamwork. Within this framework, tencore qualitiesare delineated, supported by both therapeutic knowledge as well as scientific research: 1) Dreams deal with matters important to us; 2) Dreams symbolize; 3) Dreams personify; 4) Dreams are trial runs in a safe place; 5) Dreams are online to unconscious intelligence; 6) Dreams are pattern recognition; 7) Dreams are high level communication; 8) Dreams are condensed information; 9) Dreams are experiences of wholeness; 10) Dreams are psychological energy landscapes.

For each core quality I describe short dreamwork sequences from my own practice and a schematic image of how I perceive the overriding interaction between systems in the dreaming brain. For each core quality recommendations for practical dreamwork are provided.

Finally, I draw attention to dreams as a huge psychological resource for humankind.
Parents’ experiences of care following the loss of a baby at the margins between miscarriage, stillbirth and neonatal death: a UK qualitative study
Authors: Smith LK , Dickens J , Bender Atik R , Bevan C , Fisher J , Hinton L
Published: January 2020

Objective

To explore the healthcare experiences of parents whose baby died either before, during or shortly after birth between 20+0 and 23+6 weeks of gestation in order to identify practical ways to improve healthcare provision.

Design

Qualitative interview study.

Setting

England through two parent support organisations and four NHS Trusts.

Sample

A purposive sample of parents.

Methods

Thematic analysis of semi‐structured in‐depth narrative interviews.

Main outcome measures

Parents’ healthcare experiences.

Results

The key overarching theme to emerge from interviews with 38 parents was the importance of the terminology used to refer to the death of their baby. Parents who were told they were ‘losing a baby’ rather than ‘having a miscarriage’ were more prepared for the realities of labour, the birth experience and for making decisions around seeing and holding their baby. Appropriate terminology validated their loss, and impacted on parents’ health and wellbeing immediately following bereavement and in the longer term.

Conclusion

For parents experiencing the death of their baby at the margins between miscarriage, stillbirth and neonatal death, ensuring the use of appropriate terminology that reflects parents’ preferences is vital. This helps to validate their loss and prepare them for the experiences of labour and birth. Reflecting parents’ language preferences combined with compassionate bereavement care is likely to have a positive impact on parents’ experiences and improve longer‐term outcomes.

Tweetable abstract

Describing baby loss shortly before 24 weeks of gestation as a ‘miscarriage’ does not prepare parents for labour and birth, seeing their baby and making memories.
Optimal conditions for the encapsulation of Weissella cibaria JW15 using alginate and chicory root and evaluation of capsule stability in a simulated gastrointestinal system
Authors: Kim Mina , Nam Dong‐Geon , Im Pureum , Choe Jeong‐Sook , Choi Ae‐Jin
Published: January 2020

The delivery of active probiotic cells in capsules can reduce probiotic cell loss induced by detrimental external factors during digestion. In this study, we determined the optimal conditions for the encapsulation of Weissella cibaria JW15 (JW15) within calcium and polyethylene glycol (PEG)‐alginate with chicory root extract powder (CREP). JW15 was encapsulated as the core material (109 cells/mL, 2 mL/min), and a solution containing a mixture of 1.5% sodium alginate and 1% CREP was extruded into a receiving bath with 0.1 M calcium chloride (CaCl2) and 0.05% PEG. Capsule morphology and size were measured using optical microscopy. The optimal air pressure and frequency vibration for capsules containing alginate only (Al) were 200 mbar and 200 Hz, respectively and 100 mbar and 350 Hz for capsules containing alginate with CREP (Ch), respectively. The voltage for both capsules types was fixed at 1.35 kV. Then, the capsules were incubated in a simulated gastrointestinal (GI) system for 6 hr at 37 °C. The addition of PEG in a CaCl2 hardening solution led to degradation of the Ch capsule (Ch–PEG) and the release of cells into the small intestine vessel in the simulated GI system. By contrast, the cells were trapped within the Al capsules. Based on these data, effective encapsulation using alginate with CREP and PEG can enable JW15 to be released at a targeted anatomical site of activity within the GI system, thereby, enhancing the efficacy of probiotic cells. These protective effects can be leveraged during the development of probiotic products.

Practical Application

Weissella cibaria JW15 (109 cells/mL) was encapsulated in biodegradable and biocompatible capsules, prepared by mixing 1.5% alginate with 1% chicory root extract powder (CREP) in 0.1 M CaCl2 and 0.05% PEG using an encapsulator. The optimal processing parameters were as follows: pressure, 100 mbar; vibration frequency, 350 Hz; voltage, 1.35 kV; and core flow rate, 2 mL/min. When the resulting capsules were subjected to a simulated gastrointestinal system for 6 hr, the cells were released into the small intestine, and up to 95% cell viability was preserved. These results suggest that capsules made from alginate with CREP and formulated using calcium and PEG are a promising delivery system for probiotic cells.
Nutritional and safety evaluation of locust (Caelifera) powder as a novel food material
Authors: Ochiai Masaru , Inada Mako , Horiguchi Seiya
Published: January 2020

Insects are considered edible food resources with sufficient nutrients, but their nutrient composition and safety evaluation have not been fully investigated yet. In this study, we investigated the nutrient composition and the acute and sub‐chronic toxicity of locust powder in male rats. In the acute oral toxicological experiment, rats were administered locust powder at a dose of 10 or 20 g/kg/dose, followed by monitoring general signs of toxicity for 14 days. In the sub‐chronic toxicological experiments, rats were fed with a diet containing 1% and 3% locust powder for 28 and 90 days. General signs of toxicity, body weight, plasma and blood components, weight and fat accumulation in tissues, and fecal fat excretion were investigated. The locust powder was rich in proteins, essential amino acids, minerals, and polyunsaturated fatty acids. In the acute toxicological experiment, no general signs of acute toxicity were observed at a dose of 20 g/kg. In the sub‐chronic toxicological experiments, parameters related to red blood cell were lowered by the 3% locust powder for 28 days, but not for 90 days. Liver lipid accumulation and fecal fat excretion were increased by the 3% locust powder for 90 days, but the liver lipids contents were considered to be within a nontoxic level. Cecum contents and cecum short‐chain fatty acids were lowered by the locust powder, which can be caused by its fiber and fiber‐like components. In conclusion, acute and sub‐chronic intake of locust powder had little effect on general, biochemical, and hematological signs of toxicity in rats.

Practical Application

Edible insects are increasingly viewed as new sustainable protein sources for human foods and livestock feeds worldwide because of their high nutritional balance, high food conversion rate, and environmental merits. Here, we have clarified that a locust powder contains high levels of protein, polyunsaturated functional fatty acids, and minerals (iron, zinc, and magnesium), and intake of locust powder (3% in diet) had little effects on general, biochemical, and hematological signs of toxicity in male rats. Locust as an edible insect, in powder form, can contribute to human dietary needs.
Factors associated with accessing aged care services in Australia after approval for services: Findings from the historical cohort of the Registry of Senior Australians
Authors: Inacio Maria C. , Amare Azmeraw T. , Whitehead Craig , Bray Sarah C. E. , Corlis Megan , Visvanathan Renuka , Wesselingh Steve
Published: January 2020

Objective

To evaluate the access of approved aged care services and factors associated with accessing these services.

Methods

A retrospective cohort study was conducted (1/7/2003‐30/6/2013). The incidence of accessing permanent residential, home and respite care services within one year or transition care within 28 days of approval was evaluated. The association of participants’ socio‐demographic characteristics, limitations, health conditions and assessment characteristics with service use was evaluated.

Results

In 799 750 older Australians, the incidence of accessing approved permanent residential care within one year was 70.9% (95% confidence interval [CI] 70.8%‐71.0%), home care 49.5% (95% CI 49.3%‐49.7%) and respite 41.8% (95% CI 41.7%‐41.9%). The incidence of accessing transition care at 28 days was 78.5% (95% CI 78.2%‐78.7%). Aged care seekers’, assessments’ and assessors’ characteristics are associated with service access.

Conclusion

Monitoring the use of aged care service approvals is necessary for the identification of service access barriers to support evidence‐based policy changes.
Hierarchical clustering of PI3K and MAPK pathway proteins in breast cancer intrinsic subtypes
Authors: Kruger Dinja T. , Opdam Mark , Sanders Joyce , van der Noort Vincent , Boven Epie , Linn Sabine C.
Published: January 2020

The phosphatidylinositol‐3‐kinase (PI3K) and mitogen‐activated protein kinase (MAPK) pathways are frequently activated in breast cancer. We recently demonstrated the importance of analyzing multiple proteins as read‐out for pathway activation in ER+/HER2− breast cancer, since single proteins are known to provide insufficient information. Here, we determined pathway activation in other primary breast cancer intrinsic subtypes derived from postmenopausal patients. Tumor blocks were recollected, and immunohistochemistry was performed using antibodies against PTEN, p‐AKT(Thr308), p‐AKT(Ser473), p‐p70S6K, p‐4EBP1, p‐S6RP(Ser235/236) and p‐ERK1/2, followed by unsupervised hierarchical clustering. In 32 ER+/HER2+, 37 ER−/HER2+ and 74 triple‐negative breast cancer patients, subgroups were identified with preferentially activated (A) and preferentially not activated (N) proteins. These subgroups likely reflect tumors with differences in biological behavior as well as treatment outcome.
Strategies to persist in the community: Soil seed bank and above‐ground vegetation in Patagonian pine plantations
Authors: Rago María Melisa , Urretavizcaya María Florencia , Orellana Ivonne Alejandra , Defossé Guillermo Emilio
Published: January 2020

Questions

In terms of biodiversity conservation, forest plantations are often considered problematic because they usually have negative effects on natural ecosystems. Soil seed banks could play an important role in restoring vegetation that was originally present, by recruiting species that have disappeared above‐ground. We addressed this topic in plantations located in the Patagonian steppe by asking the following questions: Are richness, abundance and composition of steppe above‐ground vegetation and soil seed bank affected by plantations? Is species composition of the above‐ground vegetation and soil seed bank similar in plantations and in the steppe?

Location

NW of Chubut Province, Patagonia, Argentina.

Methods

We selected three plantations located in the steppe, and delimited three sectors: steppe, plantation edge and plantation interior. We compared richness and abundance by species origin and growth form among sectors for the above‐ground vegetation and soil seed bank compartments, using generalized linear mixed models. We compared species composition for each compartment and between them using permutational multivariate analysis of variance and non‐metric multidimensional scaling.

Results

In above‐ground vegetation, we found a decrease in richness and abundance, and changes in composition from the steppe to the plantation interior. Richness and abundance of the soil seed bank did not show differences among steppe and the plantation sectors, although composition was different among them. Above‐ground vegetation and soil seed bank species composition were always different; native perennial herbs and shrubs were predominant in the above‐ground vegetation while exotic annual herbs dominated the soil seed bank.

Conclusions

Our findings suggest that plant recruitment from the soil seed bank would not be sufficient for restoring depleted species pools in the above‐ground vegetation of plantations. Therefore, actions promoting native species reestablishment and control of exotics should be considered to reach the aim of restoring biodiversity in former plantations.
Mortality associated with Fournier’s gangrene remains unchanged over 25 years
Authors: Radcliffe Robert S. , Khan Masood A.
Published: January 2020

Objectives

To report a case series of Fournier’s gangrene (FG) from our institution, and to investigate its mortality over the past 25 years.

Patients and Methods

Case notes of men presenting to our institution from 2013 to 2016 with FG were reviewed. As well as age, diabetic history, length of stay, length of stay in critical care, and mortality; we calculated (where possible) the Uludag Fournier’s Gangrene Severity Index (UFGSI).

Published studies and cases series reporting the mortality rates for FG were reviewed from 1993 to 2018. The size of the study, country of origin, average age and gender ratio were collected, alongside mortality.

Results

Two of the 11 patients treated for FG at out institution died within 90 days of admission, a mortality rate of 18%. Predicted mortality was significantly higher.

A total of 173 publications were identified from the Medical Literature Analysis and Retrieval System Online (MEDLINE) database published between 1993 and 2018, reporting data from 1975 to 2018. Analysis of heterogeneity, by both time and precision, supported exclusion of four retrospective coded database‐driven studies from the analysis.

From the remaining studies, mortality ranged from 0% to 42%. Of the 6152 reported cases, there were 1220 deaths, giving an overall mortality rate of 19.8%. There was no evidence of a significant change in the mortality rate for FG over time (P = 0.996).

Conclusions

In our case series, the mortality rate for FG was 18%, despite a higher predicated mortality (based on UFGSI scores). The treatment of FG remains appropriate resuscitation, aggressive surgical debridement, and critical care management. Perceived high risk of mortality should not deter aggressive management.

Mortality due to FG does not appear to have changed over the past 25 years, and is estimated at 19.8%. In studies identifying cases of FG, careful attention should be paid to case definition, particularly when cases are being abstracted retrospectively from large coded databases.
Acid‐sensing ion channel 3 blockade inhibits durovascular and nitric oxide‐mediated trigeminal pain
Authors: Holton Christopher M. , Strother Lauren C. , Dripps Isaac , Pradhan Amynah A. , Goadsby Peter J. , Holland Philip R.
Published: January 2020

Background and Purpose

There is a major unmet need to develop new therapies for migraine. We have previously demonstrated the therapeutic potential of the acid‐sensing ion channel (ASIC) blockade in migraine, via an ASIC1 mechanism. ASIC3 is expressed in the trigeminal ganglion and its response is potentiated by NO that can trigger migraine attacks in patients. Thus we sought to explore the potential therapeutic effect of ASIC3 blockade in migraine.

Experimental Approach

To investigate this, we utilised validated electrophysiological and behavioural rodent preclinical models. In rats, ASIC3 blockade using APETx2 (50 or 100 μg·kg−1, i.v.) was measured by using durovascular and NO‐evoked trigeminal nociceptive responses along with cortical spreading depression models. In mice, we sought to determine if periorbital mechanical sensitivity, induced by acute nitroglycerin (10 mg·kg−1, i.p.), was attenuated by APETx2 (230 μg·kg−1, i.p.), as well as latent sensitisation induced by bright light stress in a chronic nitroglycerin model.

Key Results

Here, we show that the ASIC3 blocker APETx2 inhibits durovascular‐evoked and NO‐induced sensitisation of trigeminal nociceptive responses in rats. In agreement, acute and chronic periorbital mechanosensitivity induced in mice by nitroglycerin and subsequent bright light stress‐evoked latent sensitivity as a model of chronic migraine are all reversed by APETx2.

Conclusion and Implications

These results support the development of specific ASIC3 or combined ASIC1/3 blockers for migraine‐related pain and point to a potential role for ASIC‐dependent NO‐mediated attack triggering. This has key implications for migraine, given the major unmet need for novel therapeutic targets.
A neglected population in the study of children with HIV infection and stroke
Authors: Benjamin Laura A
Published: January 2020

This commentary is on the original article by Dlamini et al. on pages 735–741 of this issue.
Factors associated with initiation of community‐based therapy for emerging adults with mood and anxiety disorders
Authors: Saunders Hailey , Osuch Elizabeth , Anderson Kelly , Martin Janet , Kunnilathu Abraham , John‐Baptiste Ava
Published: January 2020

Aim

The First Episode Mood and Anxiety Program (FEMAP) is a community‐based early intervention program that has been shown to improve health outcomes for emerging adults (EAs) with mood and anxiety disorders. However, not all EAs who are admitted to the program initiate treatment. Our aim was to identify factors that distinguish those who initiated treatment from those who did not.

Methods

FEMAP administered questionnaires to EAs upon first contact with the program, collecting information on a range of socioeconomic, patient and condition‐related factors. We compared EAs who initiated treatment in the program (n = 318, 87.4%) to those who did not (n = 46, 12.6%). To examine factors associated with treatment initiation, we specified a parsimonious logistic regression model, using the method of purposeful selection to choose from a range of candidate variables.

Results

Anxiety Sensitivity Index ‐ Revised (ASI‐R), binge drinking and cannabis use were included in the final logistic regression model. Each one‐point increment in the ASI‐R score was associated with a 1% increase in the odds of treatment initiation (OR = 1.014; 95% CI [1.003, 1.026]). No other variable was significantly associated with treatment initiation.

Conclusions

Our study provides insight on the differences between EAs with mood and anxiety disorders who initiated targeted treatment services and those who did not. Anxiety sensitivity was significantly associated with treatment initiation at FEMAP. Our findings suggest that it may be anxiety sensitivity, rather than depression or functional impairment per se that drive treatment initiation among EAs.
From silos to solutions: How one district is building a culture of collaboration and learning between school principals and central office leaders
Authors: King Smith Angela , Watkins Karen E. , Han Seung‐Hyun
Published: January 2020

Large urban school districts often struggle with hierarchy, fragmented processes and cultures whereby organisational silos between school and central office staff serve as a major barrier for reaching the desired strategic goals of improving student achievement. In addition, school district staff are undergoing change requiring leaders and staff in these organisations to adapt and build their capacity to support changing demands. However, little attention is paid to how to build the necessary systems and learning environments to support capacity building and leader development. This article reports on an action research study using mixed methods that reveal how central office leaders and school principals break down organisational silos to build a culture of learning using learning organisation principles. Using the Dimensions of the Learning Organization Questionnaire (DLOQ) short form, participants completed questions related to the school district's capacity for learning. Data from the survey and interviews outline key findings that illustrate how the learning organisation framework served as a model to create the organisational conditions and culture to enable support and cooperation for learning, capacity, change and improvement to occur. This action research case study is a look at one organisation's approach to addressing a gap in learning organisation research in the area of learning organisation interventions. In addition, it extends current research on schools as learning organisations with an example of data‐informed change in one large school district in the southern United States.
Multiple decades of stocking has resulted in limited hatchery introgression in wild brook trout (Salvelinus fontinalis) populations of Nova Scotia
Authors: Lehnert Sarah J. , Baillie Shauna M. , MacMillan John , Paterson Ian G. , Buhariwalla Colin F. , Bradbury Ian R. , Bentzen Paul
Published: January 2020

Many populations of freshwater fishes are threatened with losses, and increasingly, the release of hatchery individuals is one strategy being implemented to support wild populations. However, stocking of hatchery individuals may pose long‐term threats to wild populations, particularly if genetic interactions occur between wild and hatchery individuals. One highly prized sport fish that has been heavily stocked throughout its range is the brook trout (Salvelinus fontinalis). In Nova Scotia, Canada, hatchery brook trout have been stocked since the early 1900s, and despite continued stocking efforts, populations have suffered declines in recent decades. Before this study, the genetic structure of brook trout populations in the province was unknown; however, given the potential negative consequences associated with hatchery stocking, it is possible that hatchery programs have adversely affected the genetic integrity of wild populations. To assess the influence of hatchery supplementation on wild populations, we genotyped wild brook trout from 12 river systems and hatchery brook trout from two major hatcheries using 100 microsatellite loci. Genetic analyses of wild trout revealed extensive population genetic structure among and within river systems and significant isolation‐by‐distance. Hatchery stocks were genetically distinct from wild populations, and most populations showed limited to no evidence of hatchery introgression (<5% hatchery ancestry). Only a single location had a substantial number of hatchery‐derived trout and was located in the only river where a local strain is used for supplementation. The amount of hatchery stocking within a watershed did not influence the level of hatchery introgression. Neutral genetic structure of wild populations was influenced by geography with some influence of climate and stocking indices. Overall, our study suggests that long‐term stocking has not significantly affected the genetic integrity of wild trout populations, highlighting the variable outcomes of stocking and the need to evaluate the consequences on a case‐by‐case basis.
The effects of mesoscale oceanographic structures and ambient conditions on the catch of albacore tuna in the South Pacific longline fishery
Authors: Zhou Cheng , He Pingguo , Xu Liuxiong , Bach Pascal , Wang Xuefang , Wan Rong , Tang Hao , Zhang Yu
Published: January 2020

Albacore tuna (Thunnus alalunga) exhibit patchy concentrations associated with biological process at a wide range of spatial scales, resulting in variations in their catchability by fishing gears. Here, we investigated the association of catch variation for pelagic longlines in the South Pacific Ocean with oceanographic mesoscale structures (in horizontal dimension) and ambient conditions (in vertical dimension). The distribution of albacore tuna as indicated by catch per unit effort (CPUE) of longlines was significantly related to the presence of mesoscale structures, with higher CPUE found at locations closer to thermal fronts and with greater gradient magnitudes, as well as areas marked by peripheral contour line of the anticyclone indicated by Sea Surface Height Anomalies ~0.05 m. Surface mesoscale current velocity had the negative effect on the catch, probably as a result of decreased catchability by shoaling the hook depth. Vertical distribution of albacore in the survey region of South Pacific Ocean was hardly restricted by ambient temperature and oxygen concentration, though effect of ambient temperature was relevant and showed a negatively linear correlation with CPUE at the range of 20–24°C. On the contrary, albacore distribution was evidently dominated by the water depth and showed strong preference on water depth of 200 m, which was likely a representative feeding layer. The presence of prey resources and their accessibility by albacore revealed by mesoscale structures in the biological and physical processes, and catchability determined by the location of the baited hooks comprehensively contribute to the variability of catch.
Renal dysplasia masquerading as a renal mass in a child on hemodialysis
Authors: Acharya Ratna , Bowser Meghan , Choudhari Pooja , Upadhyay Kiran K.
Published: January 2020

Pathological renal mass is uncommon in children. It is important to differentiate this from a benign mass or mass‐like lesion (pseudomass) for proper management. Renal dysplasia is a common finding in patients with end stage renal disease and can mimic a renal mass. Here, we report a 16‐year‐old girl on hemodialysis who was found to have a nodular right renal mass in the sonogram. Magnetic resonance imaging confirmed the nodular mass. She underwent right nephrectomy and the histopathology revealed features of renal dysplasia and end stage kidney disease without any evidence of malignancy. No further treatments were necessary. This case demonstrates that a nodular renal mass in dialysis patients does not always mean malignancy and could be a pseudomass from severe renal dysplasia. Since a sonogram may not be able to clearly define the etiology of solid mass in these patients, further evaluations including a renal histology and/or other imaging modalities are often necessary.
Electrogram‐only guided approach to His bundle pacing with minimal fluoroscopy: A single‐center experience
Authors: Zanon Francesco , Marcantoni Lina , Zuin Marco , Pastore Gianni , Baracca Enrico , Tiribello Antonella , Raffagnato Paola , Boaretto Graziano , Roncon Loris , Vijayaraman Pugazhendhi
Published: January 2020

Introduction

His bundle pacing (HBP) is the most physiological pacing. The standard technique based on fluoroscopic approach might be challenging and fluoro consuming. Targeting the His guided exclusively by the electrical signals could enable a precise lead implant, thus reducing fluoroscopy time (FT) and X‐ray dose, desirable both for patients and operators. The aim of the study is to evaluate the feasibility, efficacy, and safety both acutely and at 30 days of the electrogram (EGM)‐guided HBP with minimal or no fluoroscopy.

Methods and Results

Between October and December 2018, 41 consecutive patients underwent EGM‐guided HBP. Successful HBP was obtained in 39 (95%) patients, (30 males, 78 ± 10 years). Selective HBP (S‐HBP) was achieved in 23 (59%), nonselective HBP (NS‐HBP) in 16 (41%) patients. The final HBP lead position was reached in 31 (79.4%) patients without fluoroscopy, only guided by electrical signals. In eight patients a minimal fluoroscopy (mean, 8 seconds) has been required. The sheath's cutting and the slack of the lead were routinely performed under fluoroscopy. No difference was observed in FT for HBP lead placement in S‐HBP and NS‐HBP (mean, 8.1 ± 25 vs 7.5 ± 20 seconds, P = .8; median value 0 vs 0 seconds). No differences were observed in FT for the entire procedure, total dose area product and total procedural time in S‐HBP and NS‐HBP. Lead dislodgement occurred in one (2.6%) patient 1 day after the procedure.

Conclusions

HBP could be performed safely and efficiently using the EGMs, with minimal or no fluoroscopy. Fluoroscopy was required during sheath removal and atrial lead placement.
Metformin upregulates mitophagy in patients with T2DM: A randomized placebo‐controlled study
Authors: Bhansali Shipra , Bhansali Anil , Dutta Pinaki , Walia Rama , Dhawan Veena
Published: January 2020

Impaired mitochondrial autophagy (mitophagy) and NLRP3 inflammasome activation have been incriminated in the pathogenesis of T2DM. Metformin besides being an insulin sensitizer also induces autophagy; however, its effect on mitophagy and NLRP3 activation in patients with T2DM still remains elusive. Forty‐five drug‐naïve T2DM patients with HbA1C 7%‐9% (53‐75 mmol/mol) were randomly assigned to receive either metformin, voglibose, or placebo for 3 months, and were also recommended for lifestyle intervention programme (n = 15 each). Mitochondrial oxidative stress (MOS) parameters, qPCR and immunoblotting of mitophagy‐related markers (PINK1, PARKIN, MFN2, NIX, LC3‐II, LAMP2), p‐AMPKα (T172), and NLRP3 proteins, as well as transmission electron microscopy (TEM) for assessing mitochondrial morphology were performed in the mononuclear cells of study patients. Both metformin and voglibose showed a similar efficacy towards the reduction in HbA1c and MOS indices. However, multivariate ANCOVA divulged that mRNA and protein expression of mitophagy markers, NLRP3 and p‐AMPKα (T172), were significantly increased only with metformin therapy. Moreover, PINK1 expression displayed a significant positive association with HOMA‐β indices, and TEM studies further confirmed reduced distortions in mitochondrial morphology in the metformin group only. Our observations underscore that metformin upregulates mitophagy and subsequently ameliorates the altered mitochondrial morphology and function, independent of its glucose‐lowering effect. Further, restoration of normal mitochondrial phenotype may improve cellular function, including β‐cells, which may prevent further worsening of hyperglycaemia in patients with T2DM.
A novel inhibitory role of microRNA‐224 in particulate matter 2.5‐induced asthmatic mice by inhibiting TLR2
Authors: Li Ping , Wang Jinpeng , Guo Fengjun , Zheng Baihong , Zhang Xuelei
Published: January 2020

Epidemiological studies have shown that elevated concentrations of particulate matter 2.5 (PM2.5) correlate with increased incidence of asthma. Studies have highlighted the implication of microRNAs (miRNAs) in asthmatic response. Here, the objective of this study is to explore the effect of miR‐224 on PM2.5‐induced asthmatic mice. Ovalbumin (OVA) was utilized to establish asthmatic mouse models, which were then exposed to PM2.5, followed by miR‐224 expression detection. Next, lesions and collagen deposition area in lung tissue, ratio Treg/Th17, the expression of TLR4 and MYD88, inflammation, eosinophils (EOS) and airway remodelling were evaluated in OVA mice after injection with miR‐224 agomir. Following isolation of mouse primary bronchial epithelial cells, miR‐224 mimic and TLR2/TLR4 inhibitor were introduced to assess inflammation and the expression of TGF‐β, MMP9, TIMP‐1, Foxp3, RORγt, TLR2, TLR4 and MYD88. After exposure to PM2.5, lesions and collagen deposition were promoted in lung tissues, inflammation and EOS were increased in bronchoalveolar lavage fluid (BALF), and airway remodelling was enhanced in OVA mice. miR‐224 was down‐regulated, whereas TLR2/TLR4/MYD88 was up‐regulated in OVA mice after treatment with PM2.5, accompanied by Treg/Th17 immune imbalance. Of note, bioinformatic prediction and dual luciferase reporter gene assay confirmed that TLR2 was a target gene of miR‐224. Overexpressed miR‐224 reduced expression of TGF‐β, MMP9, TIMP‐1 and RORγt and inflammation but increased Foxp3 expression in bronchial epithelial cells through down‐regulating TLR2. In summary, overexpressed miR‐224 suppressed airway epithelial cell inflammation and airway remodelling in PM2.5‐induced asthmatic mice through decreasing TLR2 expression.