bluuebunny/crossref_metadata_2025 huggingface dataset:
Acinar cell NLRP3 inflammasome and gasdermin D (GSDMD) activation mediates pyroptosis and systemic inflammation in acute pancreatitis
Authors: Gao Lin , Dong Xiaowu , Gong Weijuan , Huang Wei , Xue Jing , Zhu Qingtian , Ma Nan , Chen Weiwei , Fu Xianghui , Gao Xiang , Lin Zhaoyu , Ding Yanbing , Shi Juanjuan , Tong Zhihui , Liu Tingting , Mukherjee Rajarshi , Sutton Robert , Lu Guotao , Li Weiqin
Published: April 2021

Background and Purpose

Pyroptosis is a lytic form of pro‐inflammatory cell death characterised as caspase 1 dependent with canonical NLRP3 inflammasome‐induced gasdermin D (GSDMD) activation. We aimed to investigate the role of acinar pyroptotic cell death in pancreatic injury and systemic inflammation in AP.

Experimental Approach

Pancreatic acinar pyroptotic cell death pathway activation upon pancreatic toxin stimulation in vitro and in vivo was investigated. Effects of pharmacological (NLRP3 and caspase‐1 inhibitors), constitutive (Nlrp3−/−, Casp1−/− and Gsdmd−/−) and acinar cell conditional (Pdx1CreNlrp3Δ/Δ and Pdx1CreGsdmdΔ/Δ) genetic inhibition on pyroptotic acinar cell death, pancreatic necrosis and systemic inflammation were assessed using mouse AP models (caerulein, sodium taurocholate and l‐arginine). Effects of Pdx1CreGsdmdΔ/Δ versus myeloid conditional knockout (Lyz2CreGsdmdΔ/Δ) and Gsdmd−/− versus receptor‐interacting protein 3 (RIP3) inhibitor were compared in CER‐AP.

Key Results

There was consistent pyroptotic acinar cell death upon pancreatic toxin stimulation both in vitro and in vivo, which was significantly reduced by pharmacological or genetic pyroptosis inhibition. Pdx1CreGsdmdΔ/Δ but not Lyz2CreGsdmdΔ/Δ mice showed significantly reduced pyroptotic acinar cell death, pancreatic necrosis and systemic inflammation in caerulein‐AP. Co‐application of RIP3 inhibitor on Gsdmd−/− mice further increased protection on caerulein‐AP.

Conclusion and Implications

This work demonstrates a critical role for NLRP3 inflammasome and GSDMD activation‐mediated pyroptosis in acinar cells, linking pancreatic necrosis and systemic inflammation in AP. Targeting pyroptosis signalling pathways holds promise for specific AP therapy.
Effects of basement structures and Carboniferous basin configuration on evaporite distribution and the development of salt structures in Nordkapp Basin, Barents Sea—Part I
Authors: Hassaan Muhammad , Inge Faleide Jan , Helge Gabrielsen Roy , Tsikalas Filippos
Published: April 2021

Potential field data, reprocessed regional 2D seismic reflection profiles and 3D seismic tied to wells were used to study the late Devonian‐Permian development of the Nordkapp Basin in Barents Sea. The composite basin can be subdivided into the northeastern, central and southwestern segments that developed above a basement that contains elements of the Timanian and Caledonian regimes. The transition between the Timanian and Caledonian structures is positioned below the central basin segment. The rheological properties, locations, orientations and interaction of inherited structures together with two subsequent extensional phases, defined the presalt rift architecture and gave rise to seven subbasins within Nordkapp Basin. During the late Devonian‐early Carboniferous NE‐SW oriented extension, the basin consisted of two regional half‐grabens (northern and southern) separated by an interbasin ridge. During the late Carboniferous, the shift of extension direction to NW‐SE orientation reshaped the two regional half‐grabens. In particular, an interbasin transfer zone divided the northern regional half‐graben by separating its hinged‐margin portion (incipient northeastern segment) from the deeper part (incipient central segment). At the same time, the elevated interbasin ridge separated the incipient central and southwestern segments. Internally within the seven subbasins, the evolving structural elements including cross‐cutting master faults and structural highs have influenced the deposition and character of the Pennsylvanian‐lower Permian layered evaporite sequence and the distribution of subsequent salt structures. We suggest that the synrift to early postrift processes, relative depth of each subbasin, arrangement of the structural highs and depositional palaeo‐environment all controlled the thickness and facies of the layered evaporite sequence. The latter in combination with the presalt architecture comprised a laterally varying in thickness and character substratum that during the earliest Triassic influenced the sediment routings and deposition of the progradational system arriving in Nordkapp Basin. The study outcomes are pertinent and applicable to other salt‐influenced rift basins worldwide.
The genetic underpinnings of anthracycline‐induced cardiomyopathy predisposition
Authors: Berkman Amy M. , Hildebrandt Michelle A. T. , Landstrom Andrew P.
Published: April 2021

Anthracyclines, chemotherapeutic agents that have contributed to significant improvements in cancer survival, also carry risk of both acute and chronic cardiotoxicity. This has led to significantly elevated risks of cardiac morbidity and mortality among cancer survivors treated with these agents. Certain treatment related, demographic, and medical factors increase an individual's risk of anthracycline induced cardiotoxicity; however, significant variability among those affected suggests that there is an underlying genetic predisposition to anthracycline induced cardiotoxicity. The current narrative review seeks to summarize the literature to date that has identified genetic variants associated with anthracycline induced cardiotoxicity. These include variants found in genes that encode proteins associated with anthracycline transportation and metabolism, those that encode proteins associated with the generation of reactive oxygen species, and those known to be associated with cardiac disease. While there is strong evidence that susceptibility to anthracycline induced cardiotoxicity has genetic underpinnings, the majority of work to date has been candidate gene analyses. Future work should focus on genome‐wide analyses including genome‐wide association and sequencing‐based studies to confirm and expand these findings.
Autoantibodies to LG3 are associated with poor long‐term survival after liver retransplantation
Authors: Xu Qingyong , McAlister Vivian C. , House Andrew A. , Molinari Michele , Leckie Steve , Zeevi Adriana
Published: April 2021

Autoantibodies are detrimental to the survival of organ transplantation. We demonstrated that Angiotensin II Type I Receptor agonistic autoantibodies (AT1R‐AA) were associated with poor outcomes after liver retransplantation. To examine the effect of other autoantibodies, we studied a retrospective cohort of 93 patients who received a second liver transplant. Pre‐retransplant sera were tested with Luminex‐based solid‐phase assays. Among 33 tested autoantibodies, 15 were significantly higher in 48 patients who lost their regrafts than 45 patients whose regrafts were still functioning. Specifically, patients with autoantibodies to the C‐terminal laminin‐like globular domain of Perlecan (LG3) experienced significantly worse regraft survival (p = .002) than those with negative LG3 autoantibodies (LG3‐A). In multivariate analysis, LG3‐A (HR = 2.35 [1.11–4.98], p = .027) and AT1R‐AA (HR = 2.09 [1.07–4.10], p = .032) remained significant predictors of regraft loss after adjusting for recipient age and sex. There were synergistic deleterious effects on regraft survival in patients who were double‐positive for LG3‐A and donor‐specific antibody (DSA) (HR = 5.26 [2.15–12.88], p = .001), or LG3‐A and AT1R‐AA (HR = 3.23 [1.37–7.66], p = .008). All six double‐positive patients lost their liver regrafts. In conclusion, LG3‐A is associated with inferior long‐term outcomes of a second liver transplant. Screening anti‐HLA antibodies and autoantibodies such as LG3‐A/AT1R‐AA identifies patients with a higher risk for liver transplantation.
Topical oxygen therapy for diabetes‐related foot ulcers: A systematic review and meta‐analysis
Authors: Thanigaimani Shivshankar , Singh Tejas , Golledge Jonathan
Published: April 2021

Introduction

Topical oxygen therapy (TOT) has been suggested as a treatment for diabetes‐related foot ulcer (DFU) but no prior meta‐analyses of randomised clinical trials (RCT) have been reported. This systematic review and meta‐analysis examined the randomised evidence for the benefit of TOT in healing DFU.

Methods

Publicly available databases were searched for RCTs investigating the effect of TOT on wound healing in participants with a DFU. The primary outcome was ulcer healing defined as full epithelialisation. Meta‐analyses were performed using random effect models and reported as risk ratios (RR) and 95% confidence intervals (CI). Study quality and publication bias were assessed using a modified version of the Cochrane Collaboration's tool and funnel plots, respectively.

Results

Six RCTs involving 530 participants with a DFU testing TOT were included. Meta‐analysis suggested that TOT significantly increased the likelihood of ulcer healing compared to controls (Risk ratio [RR] 1.94; 95% CI 1.19, 3.17; I2 = 57%; NNT = 5.33) and findings were robust in sensitivity analyses. Risk of bias was high, moderate and low in two, one and three studies, respectively. Analysis of the three trials judged to be at low risk of bias suggested that TOT increased the likelihood of ulcer healing compared to controls (RR 2.37; 95% CI 1.52, 3.68; I2 = 0%). Funnel plots suggested the possibility of publication bias. Data on amputation were too limited for meta‐analysis.

Conclusion

This meta‐analysis suggests that TOT improves the likelihood of DFU healing; however, its effect on amputation and cost‐effectiveness are unclear.
Magnesium supplementation reduces inflammation in rats with induced chronic kidney disease
Authors: López‐Baltanás Rodrigo , Encarnación Rodríguez‐Ortiz Maria , Canalejo Antonio , Díaz‐Tocados Juan M. , Herencia Carmen , Leiva‐Cepas Fernando , Torres‐Peña José D. , Ortíz‐Morales Ana , Muñoz‐Castañeda Juan Rafael , Rodríguez Mariano , Almadén Yolanda
Published: April 2021

Background

Inflammation is a common feature in chronic kidney disease (CKD) that appears specifically associated with cardiovascular derangements in CKD patients. Observational studies have revealed a link between low Mg levels and inflammation. In this study, we hypothesize that Mg might have a modulatory effect on the inflammation induced under the uraemic milieu.

Methods

In vivo studies were performed in a 5/6 nephrectomized rat model of CKD. Furthermore, a possible direct effect of Mg was addressed through in vitro studies with vascular smooth muscle cells (VSMCs).

Results

Uraemic rats fed a normal (0.1%) Mg diet showed a systemic inflammatory response evidenced by the elevation in plasma of the pro‐inflammatory cytokines TNF‐α, IL‐1β and IL‐6, and GPx activity, a marker of oxidative stress. Importantly, an increased expression of these cytokines in the aortic tissue was also observed. In contrast, a dietary Mg supplementation (0.6%) greatly prevented the oxidative stress and the pro‐inflammatory response. In vitro, in VSMCs cultured in a pro‐inflammatory high phosphate medium, incubation with Mg 1.6 mM inhibited the increase in the production of ROS, the rise in the expression of TNF‐α, IL‐1β, IL‐6 and IL‐8 and the activation of NF‐κB signalling that was observed in cells incubated with a normal (0.8 mM) Mg.

Conclusion

Mg supplementation reduced inflammation associated with CKD, exerting a direct effect on vascular cells. These findings support a possible beneficial effect of Mg supplementation along the clinical management of CKD patients.
Transferring an Agrobacterium‐mediated transformation protocol across eight genera in the Ceratocystidaceae
Authors: Lane Frances A. , Du Plessis Deanné , Wingfield Brenda D. , Wilken P. Markus
Published: April 2021

Establishing a transformation system is an essential first step for functional studies. Numerous transformation systems have been developed and optimized for filamentous ascomycetes, including Agrobacterium‐mediated transformation. Recently, such a system was developed for the African tree pathogen Ceratocystis albifundus. This fungus is part of the family Ceratocystidaceae, which includes many tree and plant pathogens of economic importance. Despite the many advantages associated with Agrobacterium‐mediated transformation, establishing and optimizing this system within a species are extremely arduous due to the many species‐specific parameters that must be optimized. This study aimed to apply the existing C. albifundus Agrobacterium‐mediated transformation protocol to eight diverse Ceratocystidaceae species from eight different genera. Minor adjustments were made to the already established protocol to increase transformant yield before it was used to successfully produce transformants for six of the eight targeted species without the need for any further species‐specific optimizations. Although the number of transformants obtained was less than for C. albifundus, this study proves that protocols for Agrobacterium‐mediated transformation might be more transferable than previously thought. It also provides a useful benchmark for future transformation studies in the Ceratocystidaceae and will make species‐specific optimization easier.
How early maternal deprivation changes the brain and behavior?
Authors: Čater Maša , Majdič Gregor
Published: April 2021

Early life stress can adversely influence brain development and reprogram brain function and consequently behavior in adult life. Adequate maternal care in early childhood is therefore particularly important for the normal brain development, and adverse early life experiences can lead to altered emotional, behavioral, and neuroendocrine stress responses in the adulthood. As a form of neonatal stress, maternal deprivation/separation is often used in behavioral studies to examine the effects of early life stress and for modeling the development of certain psychiatric disorders and brain pathologies in animal models. The temporary loss of maternal care during the critical postpartum periods remodels the offspring's brain and provokes long‐term effects on learning and cognition, the development of mental disorders, aggression, and an increased tendency for the drug abuse. Early life stress through maternal deprivation affects neuroendocrine responses to stress in adolescence and adulthood by dysregulating the hypothalamic–pituitary–adrenal axis and permanently disrupts stress resilience. In this review, we focused on how improper maternal care during early postnatal life affects brain development resulting in modified behavior later in life.
A practitioner's guide to understanding infectious disease diagnostics in the United Kingdom. Part 2: Serological diagnostic testing methods and diagnostic test result interpretation
Authors: Whitlock F. M. , Newton J. R.
Published: April 2021

This article is the second in a review series about infectious disease diagnostics and summarises serological testing techniques, diagnostic test validation and result interpretation. It highlights the requirement for results to be interpreted with testing limitations in mind and in conjunction with the case's clinical presentation. With these foundations, the treating clinician should always be well placed to deal with equine infectious diseases.
The role of structural dynamics in GPCR‐mediated signaling
Authors: Hilger Daniel
Published: April 2021

G protein‐coupled receptors (GPCRs) play critical roles in the regulation of human physiology in response to a wide array of different extracellular stimuli and thus represent one of the largest groups of therapeutic drug targets. Recent advances in the structural characterization of GPCRs in different conformations and in complex with G proteins and arrestins have provided important insights into the mechanism and function of GPCRs. However, in order to truly understand the molecular basis of the functional versatility of GPCRs, the structural snapshots obtained by X‐ray crystallography or cryo‐EM need to be complimented with information about the conformational dynamics of receptors and their signaling complexes. In the last decade, a combination of biophysical approaches and computational studies has been utilized to examine the molecular motions of GPCRs and their transducer complexes and how they are regulated by ligands of different efficacy and bias. These studies revealed that GPCRs are highly dynamic allosteric proteins that can sample multiple conformational states. Ligands with distinct signaling profiles not only impact the conformational landscape of GPCRs but also of the receptor‐engaged G proteins and arrestins. The conformational dynamics of GPCRs and their signaling complexes and the ligand‐dependent bias sampling of distinct functional states are important underlying principles behind the complex signaling behavior of GPCRs.
Parental whole life cycle exposure modulates progeny responses to ocean acidification in slipper limpets
Authors: Maboloc Elizaldy A. , Chan Kit Yu Karen
Published: April 2021

Multigenerational exposure is needed to assess the evolutionary potential of organisms in the rapidly changing seascape. Here, we investigate if there is a transgenerational effect of ocean acidification exposure on a calyptraeid gastropod such that long‐term exposure elevates offspring resilience. Larvae from wild type Crepidula onyx adults were reared from hatching until sexual maturity for over 36 months under three pH conditions (pH 7.3, 7.7, and 8.0). While the survivorship, growth, and respiration rate of F1 larvae were unaffected by acute ocean acidification (OA), long‐term and whole life cycle exposure significantly compromised adult survivorship, growth, and reproductive output of the slipper limpets. When kept under low pH throughout their life cycle, only 6% of the F1 slipper limpets survived pH 7.3 conditions after ~2.5 years and the number of larvae they released was ~10% of those released by the control. However, the F2 progeny from adults kept under the long‐term low pH condition hatched at a comparable size to those in medium and control pH conditions. More importantly, these F2 progeny from low pH adults outperformed F2 slipper limpets from control conditions; they had higher larval survivorship and growth, and reduced respiration rate across pH conditions, even at the extreme low pH of 7.0. The intragenerational negative consequences of OA during long‐term acclimation highlights potential carryover effects and ontogenetic shifts in stress vulnerability, especially prior to and during reproduction. Yet, the presence of a transgenerational effect implies that this slipper limpet, which has been widely introduced along the West Pacific coasts, has the potential to adapt to rapid acidification.
Multi‐decade tree mortality in temperate old‐growth forests of Europe and North America: Non‐equilibrial dynamics and species‐individualistic response to disturbance
Authors: Woods Kerry D. , Nagel Thomas A. , Brzeziecki Bogdan , Cowell C. Mark , Firm Dejan , Jaloviar Peter , Kucbel Stanislav , Lin Yiching , Maciejewski Zbigniew , Szwagrzyk Jerzy , Vencurik Jaroslav
Published: April 2021

Aim

Old‐growth, mesic temperate forests are often assumed to be structured by gap‐phase processes, resulting in quasi‐equilibrial long‐term dynamics. This assumption influences management focused on simulation of natural disturbance dynamics and is embedded in most models of forest successional dynamics. We use multi‐decade monitoring of permanent plots in old‐growth forests to assess demographic assumptions directly with respect to tree mortality rates.

Location

Sixteen sites in mesic, temperate old‐growth forests in eastern North America and Europe with multi‐decade monitoring.

Time period

Variable across sites, spanning c. 20–78 years from 1936 to 2014.

Major taxa studied

Tree species of late‐successional, cool‐temperate forests of Europe and eastern North America.

Methods

We calculated and compared the annualized mortality rates (m), with confidence intervals, by species, size class and measurement interval, for tree species of sufficient abundance.

Results

Retrospective analysis shows dynamic and diverse demographic properties across populations and sites. Stand‐scale mortality rates of 0.7–2.5%/year average higher than previous estimates for old‐growth temperate forests. Variations among species, over time and among size classes, suggest that gap‐phase models are inadequate to explain stand dynamics, implying instead that rare disturbance events of moderate severity have long‐lasting effects in old‐growth forests and that indirect anthropogenic influences affect old‐growth, unlogged forests.

Main conclusions

Multi‐decade baseline data, essential for understanding community assembly and long‐term dynamics in these “slow systems,” are rare and poorly integrated. Our analysis demonstrates the value of the few long‐term, “legacy” data sets. Results suggest that differences in life history interact with complex disturbance histories, resulting in non‐equilibrial dynamics in old‐growth temperate tree communities, and that changes in disturbance patterns through anthropogenic climate change might, therefore, be an important driver of ecosystem change.
Using δ18O and δ2H to Detect Hydraulic Connection Between a Sinkhole Lake and a First‐Magnitude Spring
Authors: Ahmed Nur , Ye Ming , Wang Yang , Greenhalgh Tom , Fowler Karlee
Published: April 2021

Oxygen and hydrogen isotopes were used in this study to detect a hydraulic connection between a sinkhole lake and a karst spring. In karst areas, surface water that flows to a lake can drain through sinkholes in the lakebed to the underlying aquifer, and then flows in karst conduits and through aquifer matrix. At the study site located in northwest Florida, USA, Lake Miccosukee immediately drains into two sinkholes. Results from a dye tracing experiment indicate that lake water discharges at Natural Bridge Spring, a first‐magnitude spring 32 km downgradient from the lake. By collecting weekly water samples from the lake, the spring, and a groundwater well 10 m away from the lake during the dry period between October 2019 and January 2020, it was found that, when rainfall effects on isotopic signature in spring water are removed, increased isotope ratios of spring water can be explained by mixing of heavy‐isotope‐enriched lake water into groundwater, indicating hydraulic connection between the lake and the spring. Such a detection of hydraulic connection at the scale of tens of kilometers and for a first‐magnitude spring has not been previously reported in the literature. Based on the isotope ratio data, it was estimated that, during the study period, about 8.5% the spring discharge was the lake water that drained into the lake sinkholes.
A priori power considerations in Endodontic Research. Do we miss the timeline?
Authors: Tzanetakis G. N. , Koletsi D.
Published: April 2021

Aim

To record the prevalence of a priori power calculations in manuscripts published in three endodontic journals between 2018 and 2020 and detect further associations with a number of study characteristics including journal, publication year, study design, geographic region, number of centres and authors, whether the primary outcome pertained to a statistically significant effect and whether confidence intervals (CIs) were reported.

Methodology

The contents of the three leading endodontic journals with the highest impact factor (International Endodontic Journal, IEJ; Journal of Endodontics, JOE; and Australian Endodontic Journal, AEJ) were assessed from January 2018 to December 2020. The proportion of articles reporting a priori power calculations were recorded, and relevant associations as described above were assessed. Univariable and multivariable logistic regression were used to identify significant predictors, whilst interaction and linear trend effects were also considered.

Results

A total of 716 original research articles were included. The vast majority were published in the JOE (417/716; 58.2%), followed by the IEJ (225/716; 31.4%) and the AEJ (74/716; 10.4%). Overall, a priori power considerations were reported in 243 out of 716 articles (33.9%). The IEJ presented 1.61 times higher odds for including a priori power considerations compared to JOE (adjusted odds ratio, OR = 1.61; 95%CI: 1.11, 2.34), whilst for the AEJ, the corresponding odds were 41% lower in comparison to JOE (adjusted OR = 0.59; 95%CI: 0.31, 1.14). For each additional year indicating more recent publication, the odds for adopting appropriate reporting practices for power considerations were increased by 64% (adjusted OR = 1.64; 95%CIs: 1.32, 2.04). There was strong evidence that interventional research was associated with 10.54 times higher odds for a priori considerations compared to observational study design (adjusted OR = 10.54; 95%CIs: 5.50, 20.19).

Conclusions

The high prevalence of failure to include a priori power considerations was indicative of suboptimal reporting in endodontic research, in the three endodontic journals analysed. Although the condition improved over time, efforts to incorporate a correct determination of the required sample size at the design stage for any future study should be endorsed by journal editors, authors and the scientific community.
Three labour governance mechanisms for addressing decent work deficits in global value chains
Authors: ANNER Mark
Published: April 2021

The literature on global value chains (GVCs) has identified six governance mechanisms for addressing decent work deficits (Gereffi and Lee 2016). Drawing on research in Bangladesh, Honduras and Viet Nam, this article argues that the most effective governance mechanisms are those that mitigate GVC power asymmetries. Three such mechanisms are: (1) public governance, because it harnesses the power of the State; (2) encompassing collective bargaining agreements; and (3) multi‐actor global binding agreements. Variations in governance gaps in national labour relations regimes, and patterns and strategies of worker resistance will shape which mechanism most effectively addresses decent work deficits.
Reproduction, recruitment, and growth of the Arctic deep‐sea hydroid Bouillonia cornucopia
Authors: Meyer‐Kaiser Kirstin S. , Plowman Caitlin Q. , Soltwedel Thomas
Published: April 2021

Invertebrates in polar and deep‐sea environments that have complex life histories are exposed to unique environmental conditions that may favor non‐pelagic development and K‐strategist reproduction. Although many polar species follow this strategy, the numerically most abundant species tend to have more r‐strategist life‐history characteristics. We deployed artificial substrata over 3 years in the Arctic deep sea and collected hundreds of specimens of the athecate hydroid Bouillonia cornucopia. While this species has previously been described as rare, we report dense, patchy recruitment on artificial substrata, suggesting that B. cornucopia is highly opportunistic. This species has rapid growth compared to other sessile invertebrates in the study area, high fecundity, and continuous reproduction—all characteristics of an r‐selected life history. The species’ gonophores are simple, lacking an obvious spadix or radial canals. We observed nurse cells in histological sections of female gonophores, but no male gonophores were observed. Gonophores break away from the blastostyles in mature specimens and appear to have fertilization envelopes, suggesting that each gonophore is composed of a single oocyte and that embryological development occurs in the water column. Hydroids are typically the first invertebrates to recruit to substrata in the Arctic but are easily overgrown. The opportunistic life histories of B. cornucopia and other hydroids may be adaptive for maintaining populations in the face of high mortality. Our study demonstrates the utility of artificial substrata for collections of otherwise rare opportunistic species.
Letters from the pandemic: Nursing student narratives of change, challenges and thriving at the outset of COVID‐19
Authors: Heilferty Catherine McGeehin , Phillips Lorraine J. , Mathios Rebecca
Published: April 2021

Aim

The aim of this study is to explore the experience of third year baccalaureate nursing students during the outbreak of the COVID‐19 pandemic.

Design

Research design is a narrative analysis of archived letters written by nursing students in Spring 2020.

Methods

Letters and other media were written between 1 April and 20 May 2020. Fifty‐six letters, some with accompanying audio or visual media, were submitted in late May 2020. Approval from the University Institutional Review Board was obtained to explore the letters through narrative analysis (Riessman, 2008). As the letters were considered archival, consent from the students for the analysis was not indicated. Once thematic categories were identified independently, the authors discussed the findings until a list of narrative categories and narrative exemplars were agreed on.

Results

Three main thematic categories were found: stories of change, challenges and thriving.

Conclusion

Findings were consistent with prior research and reveal new opportunities for understanding the perspectives and needs of undergraduate nursing students during times of crisis. Action by administrators and faculty are recommended.
Promoting resilience for children of parents with opioid use disorder: A pilot study of a directed intervention
Authors: Mechling Brandy M. , Ahern Nancy R. , Palumbo Ruthanne
Published: April 2021

Problem

Having a parent with Opioid Use Disorder (OUD) is a childhood adverse experience (ACE), magnified by other accompanying ACEs. Outcomes for these children tend to include developing mental illness and/or Substance Use Disorders themselves. Few studies address these children's experiences and needs. Without child‐focused interventions to foster their resilience, generational ramifications of the OUD crisis will persist.

Methods

Nine children (ages 12–17), in Department of Social Services' custody, participated in this pilot study. The intervention delivered was Substance Abuse and Mental Health Administration's Children's Program Kit (CPK): Supportive Education for Children of Addicted Parents. Measures included OUD knowledge pre/posttests and the Behavioral and Emotional Rating Scale (BERS‐2).

Findings

Findings from paired‐samples t tests showed a significant increase in youth OUD knowledge from pre to posttest. Affective strength on the parent version (foster parent or social worker's perception of participant) and overall strength index on the youth's version BERS‐2 increased significantly from pre to posttest. Career strength, a separate strength index, showed significant increased scores on both youth and parent BERS‐2 versions pre to posttest.

Conclusions

Results support Psychiatric Mental Health nurses to lead development and implementation of interventions, such as the CPK, with a strength‐based approach to promote the knowledge and resilience of these children.
The International Spillovers of the 2010 U.S. Flash Crash
Authors: JANSEN DAVID‐JAN
Published: April 2021

This paper studies the intraday spillovers of the 2010 U.S. Flash Crash to international equity markets. We document a substantial and almost immediate echo of the crash in Latin America. Using data for 148 firms trading in Argentina, Brazil, Chile, or Mexico, we estimate price declines of up to 10% within minutes after the U.S. crash. Estimates for two different factor models indicate that this echo followed from normal interdependence rather than financial contagion.
Toll‐like receptor 2 activation and up‐regulation by high mobility group box‐1 contribute to post‐operative neuroinflammation and cognitive dysfunction in mice
Authors: Lin Fei , Shan Weiran , Zheng Yuxin , Pan Linghui , Zuo Zhiyi
Published: April 2021

Post‐operative cognitive dysfunction (POCD) is common and is associated with poor clinical outcome. Toll‐like receptor (TLR) 3 and 4 have been implied in the development of POCD. The role of TLR2, a major brain TLR, in POCD is not clear. High mobility group box‐1 (HMGB1) is a delayed inflammatory mediator and may play a role in POCD. The interaction between HMGB1 and TLRs in the perioperative period is not known. We hypothesize that TLR2 contributes to the development of POCD and that HMGB1 regulates TLR2 for this effect. To test these hypotheses, 6‐ to 8‐week old male mice were subjected to right carotid artery exposure under isoflurane anesthesia. CU‐CPT22, a TLR1/TLR2 inhibitor, at 3 mg/kg was injected intraperitoneally 30 min before surgery and 1 day after surgery. Glycyrrhizin, a HMGB1 antagonist, at 200 mg/kg was injected intraperitoneally 30 min before surgery. Mice were subjected to Barnes maze and fear conditioning tests from 1 week after surgery. Hippocampus and cerebral cortex were harvested 6 hr or 12 hr after the surgery for Western blotting, ELISA, immunofluorescent staining, and chromatin immunoprecipitation. There were neuroinflammation and impairment of learning and memory in mice with surgery. Surgery increased the expression of TLR2 and TLR4 but not TLR9 in the brain of CD‐1 male mice. CU‐CPT22 attenuated surgery‐induced neuroinflammation and cognitive impairment. Similarly, surgery induced neuroinflammation and cognitive dysfunction in C57BL/6J mice but not in TLR2−/− mice. TLR2 staining appeared in neurons and microglia. Surgery increased HMGB1 in the cell nuclei of the cerebral cortex and hippocampus. Glycyrrhizin ameliorated this increase and the increase of TLR2 in the hippocampus after surgery. Surgery also increased the amount of tlr2 DNA precipitated by an anti‐HMGB1 antibody in the hippocampus. Our results suggest that TLR2 contributes to surgery‐induced neuroinflammation and cognitive impairment. HMGB1 up‐regulates TLR2 expression in the hippocampus after surgery to facilitate this contribution. Thus, TLR2 and HMGB1 are potential targets for reducing POCD.

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Multilingualism and climate justice: The role of linguistic diversity in environmental conservation
Authors: Edmonds Rosalie
Published: April 2021

This commentary examines environmental conservation work as a site of climate (in)justice, drawing from fieldwork at a highly multilingual Cameroonian wildlife sanctuary, as well as prior work on linguistic diversity, language ideologies, and intercultural communication. Across the world, climate justice work is occurring in landscapes that are often linguistically diverse. Alongside indigenous languages, globallingua francas(predominantly (ex)‐colonial languages) play a central role in facilitating communication between government officials, foreign NGO workers and volunteers, and people living in areas undergoing conservation. In these contexts, beliefs about language and communication – as well as unequal access or fluency in particular languages — can serve to magnify racialized and (neo)colonial hierarchies. While work in environmental anthropology has taken an ethnographic approach to understanding conflicts and miscommunication between the different actors involved in environmental conservation, this commentary argues that the methodologies of sociolinguistics and related fields are uniquely situated to examine in detail the interactions, language choices, and ideologies involved in designing and implementing climate justice work, and the impact these have on how this work is carried out.
Environmental variables and dispersal barriers explain broad‐scale variation in tree species composition across Neotropical non‐flooded evergreen forests
Authors: Cupertino‐Eisenlohr Mônica A. , Eisenlohr Pedro V. , Barros‐Rosa Lucas , Oliveira‐Filho Ary Teixeira de , Simon Marcelo F.
Published: April 2021

Questions

We examined the drivers of tree species variation across Neotropical non‐flooded evergreen forests (NNFEFs) to answer the following questions: can floristic groups be differentiated based on environmental predictors? How do bioclimatic, topographic, edaphic predictors and dispersal barriers contribute to explain the floristic variation throughout NNFEFs?

Location

Neotropical region.

Methods

Based on 1,843 sites (circular areas with a diameter of 10 km), 15,072 species and 509,793 occurrence records of trees, as well as on environmental variables (42 bioclimatic, 13 edaphic and four topographic variables) and dispersal barriers (based on ecological and geographical dispersal suitability), we tested whether environmental predictive variables can discriminate NNFEF floristic groups, and built canonical models and variation partitioning to assess which variables contributed most to the floristic variation.

Results

Despite extensive overlap in predictive variables, Amazon and Atlantic Forest were the most differentiated among the nine NNFEF groups. Floristic variation along NNFEFs was mainly determined by environmental factors (54.1%), with topographic and edaphic variables, mainly topographic wetness index and pH respectively, representing the most important predictors followed by a combination of environmental factors and dispersal barriers (22.7%). The fraction of pure dispersal barriers also contributed significantly to our model (3.7%), especially considering the second canonical axis.

Conclusions

The high importance of soil and topographic variables indicates that the species have a relatively narrow niche driven by such factors, suggesting that conservation strategies should not be generalized for NNFEFs. In addition, dispersal barriers do not seem to have prevented floristic exchanges between most NNFEF groups, except in the Atlantic Forest.
SNHG1/miR‐186/FUT8 regulates cell migration and invasion in oral squamous cell carcinoma
Authors: Zhao Yanxia , Shi Jun , Zhao Yankun , Lu Zhifang
Published: April 2021

Recently, lncRNAs are associated with the progression and development of various cancers. We aimed to explore the effects of lncRNA SNHG1 on the proliferation, apoptosis, migration, and invasion of oral squamous cell carcinoma (OSCC) cells. Quantitative real‐time PCR (RT‐qPCR) was used for measurement of SNHG1 in OSCC cells. Cell proliferation, apoptosis, migration, and invasion were detected by CCK‐8 assay, flow cytometry, Cell Death Detection ELISA PLUS kit, and transwell assays. Dual‐luciferase reporter assay and RNA‐binding protein immunoprecipitation (RIP) assay were used to clarify the relationship between SNHG1 and miR‐186. SNHG1 was overexpressed in OSCC cells. SNHG1 silencing prevented cell proliferation and increased the incidence of apoptosis, DNA fragments, cleaved‐caspase 3, and Bax protein levels. Cell migration and invasion were reduced after SNHG1 deletion, and MMP2 and MMP9 protein levels were decreased. SNHG1 overexpression promoted cell survival, migration, and invasion, reduced DNA fragments formation. Mechanistically, we demonstrated that SNHG1 could directly bind to miR‐186 and positively regulated α1, 6‐fucosyltransferase (FUT8) level. Functional investigation showed that miR‐186 depletion reversed the roles of SNHG1 silencing in cell proliferation, apoptosis, and migration. Taken together, our findings illuminated that SNHG1 regulated cell proliferation, migration, and invasion by sponging miR‐186 to depress FUT8 expression.
THE EARLIEST BOAT DEPICTION IN NORTHERN EUROPE: NEWLY DISCOVERED EARLY MESOLITHIC ROCK ART AT VALLE, NORTHERN NORWAY
Authors: Gjerde Jan Magne
Published: April 2021

The oldest boat depictions in rock art from northern Europe have previously been dated to about 5500–5000 BC. A recent discovery of rock art boat depictions at Valle in Nordland County, northern Norway, made in the ground technique, pre‐dates the earlier known boat depictions by more than 3000 years. The rock art at Valle is dated by shoreline dating to be between 10,000 and 11,000 years old. The find has implications for the rock art material record, is likely to alter current views and have an impact on the research history of rock art in northern Norway. The boat is depicted in outline, life size, measuring more than 4 m in length. The closest parallels are the Arctic skin boats found in the ethnographic record. The settlement record from northernmost Europe during the Early Mesolithic supports a maritime and highly mobile strategy that would require boats and an advanced maritime technology. It would not be possible to settle the numerous islands along the coast without seaworthy boats. The boat find has implications for the appreciation of the maritime colonization of seascapes in northern Norway during the Early Mesolithic, being part of the pioneer settling of northernmost Europe after the Ice Age.
BY INVITATION ONLY. ACCESSIBILITY OF VILLA BATHS IN THE ROMAN NORTH‐WEST
Authors: Maréchal Sadi
Published: April 2021

This paper examines how bathhouses of Roman villas in the north‐western part of the Empire can further our understanding of the amount of penetration the Roman cultural sphere had in less urbanised regions. The articulation of these baths to the villa, whether integrated, attached to it or completely freestanding, indicates degrees of accessibility beyond the inhabitants of the house. Rather than being merely private bathrooms for an elite that wished to enjoy the commodities of the city in the countryside, villa baths were social hubs for intra‐elite networking and possibly enabled a form of euergetism towards small rural communities in a landscape otherwise devoid of cities and small civic centres.
Resting electrocardiographic differences in ventricular repolarization between children and young adults with congenital heart disease and those with a structurally normal heart are diminished by exercise
Authors: Kohli Utkarsh , Nayak Hemal M. , Romme Angela G. , Nguyen Hoang H.
Published: April 2021

Objective

Exercise‐induced repolarization changes have not been systematically evaluated in children and young adults with congenital heart disease (CHD). We carried out this study to assess the QTc responses during exercise in children and young adults (≤ 21 years) with CHD with comparison to those with structurally normal hearts.

Methods

Baseline QRS duration, calculated baseline QTc, QTc at 4 min of recovery and delta QTc was measured in 360 exercise stress tests which were performed in 360 subjects (137 stress tests in patients with CHD [CHD group] and 223 stress tests in patients with structurally normal hearts). The effects of presence of CHD and potential confounders on primary outcome measure, change in QTc (delta QTc), and secondary outcome measures (QTc at baseline and QTc at 4 min of recovery) were determined using multiple linear regression analyses.

Results

The baseline QTc and the QTc at 4 min of recovery in the CHD group was longer than patients with structurally normal hearts (respective p values = .00 and .001). No significant difference was noted in delta QTc between the CHD and structurally normal heart groups.

Conclusions

While patients with CHD had a longer QRS duration and QTc interval at baseline than those with structurally normal hearts, these differences did not persist or augment with exercise.
Delayed diagnosis of holocarboxylase synthetase deficiency in three patients with prominent skin findings
Authors: Cadieux‐Dion Maxime , Gannon Jennifer , Newell Brandon , Nopper Amy Jo , Jenkins Janda , Heese Bryce , Saunders Carol
Published: April 2021

Holocarboxylase deficiency (HLCSD) is caused by biallelic pathogenic variants in HLCS and is associated with poor feeding, emesis, lethargy, seizures, life‐threatening metabolic acidosis, and hyperammonemia. Skin involvement in HLCSD is typically described as scaly, erythrodermic, seborrhea‐like, or ichthyosiform, but there is a paucity of reports. We report three patients, including two siblings, with HLCSD and significant cutaneous manifestations including ichthyosiform dermatitis and a presentation with features of annular pustular psoriasis. In this report, we show that persistent, unexplained rash, even in the absence of other clinical findings, should warrant consideration and potential workup for HLCSD.
Progression from youth to professional soccer: A longitudinal study of successful and unsuccessful academy graduates
Authors: Dugdale James H. , Sanders Dajo , Myers Tony , Williams A. Mark , Hunter Angus M.
Published: April 2021

To optimize use of available resources, professional academies develop strategies to assess, monitor, and evaluate players as they progress through adolescence toward adulthood. However, few published reports exist using longitudinal study designs to examine performance throughout adolescence and the transition from youth to professional soccer. We examined differences in the age of player recruitment alongside longitudinal performance differences on field‐based fitness tests of successful vs. unsuccessful graduates across the entire age spectrum recruited by a professional soccer academy. Altogether, 537 youth soccer players volunteered to participate. We recorded the age of recruitment, biannual fitness test performance, and subsequent success in attaining a senior professional contract at the club across a period of 12 years. Only 53 (10%) of players were successful in obtaining a professional contract, with 68% of players who became professional being recruited at 12 years of age or older. Individuals recruited at an earlier age did not display a higher probability of success in attaining a professional contract. Bayesian regression models reported a consistent interaction between age and group for data on all performance measures. Moreover, “successful” academy graduates only physically outperformed their “unsuccessful” counterparts from age ~13‐14 years onward, with either no differences in performance, or performance on physical fitness tests favoring “unsuccessful” players prior to this age. Findings suggest that high achievers during childhood and early adolescence may not develop into successful senior professionals, raising concerns about the predictive utility of talent identification models.
Longitudinal changes in maximal oxygen uptake in adolescent girls and boys with different training backgrounds
Authors: Landgraff Hege Wilson , Riiser Amund , Lihagen Maren , Skei Marius , Leirstein Svein , Hallén Jostein
Published: April 2021

The purpose of this study was to investigate the effects of high‐volume endurance training on the development of maximal oxygen uptake (VO2max) in physically active boys and girls between the ages of 12 and 15 years, using a longitudinal design. The children participated in organized training in sports clubs for an average of 7‐10 hours per week, with one group undertaking a high volume of endurance training (~7 hours per week; End boys, n = 23 and End girls, n = 17) and the other group having a primary focus on technical and tactical skill development, undertaking low volumes of endurance training (~1.6 hours per week; non‐End boys, n = 29 and non‐End girls, n = 9). VO2max and anthropometrics were assessed at age 12, 13, and 15. At age 12, VO2max was 58.9 (5.6), 65.5 (7.2), 56.5 (6.5), and 58.8 (7.9) mL·kg−1·min−1 in End girls, End boys, non‐End girls, and non‐End boys, respectively. Over the three years, there was no difference between the training groups in the development of VO2max independent of scaling. In boys, VO2max relative to body mass (BM) did not change from age 12 to 15, while VO2max tended to decrease relative to fat‐free mass (FFM). In girls, VO2max relative to BM decreased slightly from age 12 to 15, with no changes over the years relative to FFM. The present longitudinal study suggests that in growing active children during puberty, high volumes of systematic endurance training do not have an additional effect on VO2max compared with similar volume of training mainly aiming at developing motor skills.