bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic review: the effects of proton pump inhibitors on the microbiome of the digestive tract—evidence from next‐generation sequencing studies
Authors: Macke Lukas , Schulz Christian , Koletzko Leandra , Malfertheiner Peter
Published: January 2020

Background

Proton pump inhibitors (PPI) are widely used to treat acid‐related disorders of the upper gastrointestinal tract. However, large observational studies have raised concerns about PPI‐associated adverse events. In recent years, data from next‐generation sequencing studies suggested that PPIs affect the composition of the intestinal microbiota, while a balanced gut microbiome is essential for maintaining health.

Aim

To review the available evidence from next‐generation sequencing studies on the effect of PPIs on the intestinal microbiome and to discuss possible implications of PPI‐induced dysbiosis in health and disease.

Methods

A systematic review was conducted following the recommendations of the Preferred Reporting Items for Systematic reviews and Meta‐Analyses statement. A PubMed query yielded 197 results. 19 publications met the prespecified eligibility criteria.

Results

Twelve observational study cohorts with 708 PPI users and 11 interventional cohorts with 180 PPI users were included in the review. In most studies, PPI treatment did not affect microbiological richness and diversity, but was associated with distinct taxonomic alterations: In the upper gastrointestinal tract, PPI users showed overgrowth of orally derived bacteria, mostly Streptococcaceae (findings based on six independent cohorts with 126 PPI users). In faecal samples, PPIs increased multiple taxa from the orders Bacillales (eg, Staphylococcaceae), Lactobacillales (eg, Enterococcaceae, Lactobacillaceae, Streptococcaceae) and Actinomycetales (eg, Actinomycetaceae, Micrococcaceae), the families Pasteurellaceae and Enterobacteriaceae and the genus Veillonella. Taxa decreased by PPIs include Bifidobacteriaceae, Ruminococcaceae, Lachnospiraceae and Mollicutes (findings in faecal samples based on 19 independent cohorts with 790 PPI users).

Conclusion

PPI use is associated with moderate alterations to upper and distal gut microbiota. The available data suggest that PPI‐induced hypochlorhydria facilitates colonization of more distal parts of the digestive tract by upper gastrointestinal microbiota.
Systematic review: hepatosplenic T‐cell lymphoma on biologic therapy for inflammatory bowel disease, including data from the Food and Drug Administration Adverse Event Reporting System
Authors: Shah Eric D. , Coburn Elliot S. , Nayyar Anil , Lee Kerry Jo , Koliani‐Pace Jenna L. , Siegel Corey A.
Published: January 2020

Background

Hepatosplenic T‐cell lymphoma (HSTCL) is a rare, poorly treatable malignancy associated with therapy for IBD. Current knowledge of HSTCL risk in IBD comes from an era of step‐up therapy, before earlier use of biologics or combination therapy was advocated to achieve deep mucosal healing. HSTCL risk among newer biologic classes has also not been evaluated.

Aims

To systematically characterise the association of HSTCL with biologic therapy for IBD.

Methods

We conducted a literature search and query of the Food and Drug Administration Adverse Event Reporting System to summarise HSTCL cases among IBD patients with prior biologic exposure. Demographics and immunosuppression exposure were extracted. Patients were stratified by current regimen (combination therapy, biologic monotherapy or no biologic), and biologic class (anti‐TNF, anti‐integrin, anti‐interleukin 12/23).

Results

Sixty‐two cases of HSTCL were identified from 2486 abstracts and 181 FDA Adverse Events Reporting System reports. The median age of affected patients was 28 years (range 12‐81), and 83.6% were male, 84.7% had Crohn's disease. Five of 62 patients had no reported azathioprine/mercaptopurine exposure. Three patients within the cohort developed HSTCL after exposure to natalizumab, vedolizumab or ustekinumab; all three also had anti‐TNF and azathioprine/mercaptopurine exposure. Forty‐three of 49 (87.8%) patients with known outcomes died with a median survival of 5 months.

Conclusions

Consistent with existing data, almost all identified HSTCL cases among IBD patients on biologic therapy had azathioprine/mercaptopurine exposure, and all cases on patients exposed to biologics had anti‐TNF exposure. These data suggest initiating a patient‐centred discussion before starting anti‐TNF therapy or other biologics.
Knowledge and power in the politics of property development
Authors: Colenutt Robert
Published: January 2020

There is a new politics of knowledge and skills, which is being used effectively by campaigning groups over planning, housing, and land, challenging the very basis of conventional property development. The new politics, articulated by Hilary Wainwright in a recent book, is grass roots local action which challenges top–down conventional knowledge and expertise. Using examples from campaigns for social and affordable housing in London, in which the author has been involved, this practitioner paper highlights how grass roots knowledge and organisation can challenge conventional power in land and property markets, and the language and expertise on which they rest. In these campaigns, the knowledge of local residents about their communities is combined with the skills of committed professionals in planning and land economics. Conventional property market expertise is extraordinarily powerful in UK social, economic, and environmental policy, yet it can and must be challenged at a fundamental level if alternative community‐led models of urban development are to be taken seriously. Examples of “People's Plans” and successful community challenges to the abuse of financial viability analysis by developers demonstrate that new knowledge and skills combined with grass roots organisation can create a new politics of opposition to conventional urban development.
The Future of the San Francisco System: Pressures and Prospects
Authors: Teo Sarah , Emmers Ralf
Published: January 2020

This article discusses the pressures on the San Francisco System, and argues that despite these challenges, the hub‐and‐spokes framework is likely to persist. While the impact of these pressures on individual alliances may vary, this system as a whole is expected to modify in three primary ways. Specifically, the San Francisco System is likely to become more diffused, selectively interconnected, as well as characterized by more insecurity toward the alliances on the part of both the United States and its allies. The worst‐case scenario for all U.S. regional allies would be being forced to choose between the United States and China. In this sense, the evolution of the U.S. hub‐and‐spokes system toward something that is more diffused and interconnected might, in the longer term, help allies to avoid such a situation amid increasing pressures.
Fair Value Exposure, Changes in Fair Value and Audit Fees: Evidence from the Australian Real Estate Industry
Authors: Sangchan Pinprapa , Habib Ahsan , Jiang Haiyan , Bhuiyan Md. Borhan Uddin
Published: January 2020

This paper investigates the relationship between audit fees and both fair value exposure and changes in fair value of investment properties. The study is motivated by the limited and inconclusive evidence on the effect on audit fees of full fair value reporting for illiquid assets. Using hand‐collected data from the Australian real estate industry, we find a negative (positive) association between audit fees and fair value exposure (changes in fair value of investment properties). Our findings also indicate that the use of unobservable inputs in fair value estimates for investment properties does not significantly increase audit risk and audit fees. Further, we find that audit fees are higher for firms with fair values of investment – properties estimated by external and mixed valuers – compared to firms with fair values estimated by directors alone. This study enriches the audit fee literature by documenting auditors’ pricing decisions in an area that involves significant estimation and valuation risks.
Incidence and outcomes of heparin‐induced thrombocytopenia in solid malignancy: an analysis of the National Inpatient Sample Database
Authors: Kumar Rohit , Bhandari Shruti , Singh Sunny R. K. , Malapati Sindhu , Cisak Kamila I.
Published: January 2020

Heparin‐induced thrombocytopenia (HIT) is an immune‐mediated adverse reaction to heparin products characterized by thrombocytopenia with or without thrombosis. This study aimed to determine the incidence, morbidity, mortality and economic burden of HIT in solid‐malignancy‐related hospitalizations. We analyzed the National Inpatient Sample Database (NIS), the largest public database of hospital admissions in the United States, from January 2012 to September 2015. The primary outcome of the study was the incidence of HIT. Secondary outcomes included incidence of venous thrombosis (acute deep venous thrombosis and pulmonary embolism), arterial thrombosis (thrombotic stroke, myocardial infarctions and other arterial thromboembolism), mortality associated with HIT, length of stay, total hospital charges and disposition. During the study period, 7 437 049 hospitalizations had an associated diagnosis of solid malignancy. Approximately 0·08% (n = 6225) hospitalizations had a secondary diagnosis of HIT in this population. The standardized incidence of total thrombotic events was higher in the solid malignancy with HIT compared to the solid malignancy without HIT group (24·7% vs. 6·8%, P < 0·001). The standardized mortality rate was 4·8% in solid malignancy with HIT compared to 3·4% in the without HIT group (OR, 1·53; 95% CI, 1·25–1·89; P < 0·001). HIT in solid malignancy is a rare condition but associated with increased morbidity and mortality.
TSPO2 translocates 5‐aminolevulinic acid into human erythroleukemia cells
Authors: Manceau Hana , Lefevre Sophie D , Mirmiran Arienne , Hattab Claude , Sugier Hugo R , Schmitt Caroline , Peoc'h Katell , Puy Hervé , Ostuni Mariano A , Gouya Laurent , Lacapere Jean‐Jacques
Published: January 2020

Background

5‐Aminolevulinic acid (ALA) is the first precursor of heme biosynthesis pathway. The exogenous addition of ALA to cells leads to protoporphyrin IX (PPIX) accumulation that has been exploited in photodynamic diagnostic and photodynamic therapy. Several types of ALA transporters have been described depending on the cell type, but there was no clear entry pathway for erythroid cells. The 18 kDa translocator protein (TSPO) has been proposed to be involved in the transport of porphyrins and heme analogs.

Results

ALA‐induced PPIX accumulation in erythroleukemia cells (UT‐7 and K562) was impaired by PK 11195, a competitive inhibitor of both transmembrane proteins TSPO (1 and 2). PK 11195 did not modify the activity of the enzymes of heme biosynthesis, suggesting that ALA entry at the plasma membrane was the limiting factor. In contrast, porphobilinogen (PBG)‐induced PPIX accumulation was not affected by PK 11195, suggesting that plasma membrane TSPO2 is a selective transporter of ALA. Overexpression of TSPO2 at the plasma membrane of erythroleukemia cells increased ALA‐induced PPIX accumulation, confirming the role of TSPO2 in the import of ALA into the cells.

Conclusions

ALA‐induced PPIX accumulation in erythroid cells involves TSPO2 as a selective translocator through the plasma membrane.

Significance

This is the first characterisation of molecular mechanisms involving a new actor in ALA transport in ALA‐induced PPIX accumulation in erythroleukemia cells, which could be inhibited by specific drug ligands.
Discovery of inner centromere protein‐derived small peptides for cancer imaging and treatment targeting survivin
Authors: Fuchigami Takeshi , Ishikawa Natsumi , Nozaki Iori , Miyanari Yusuke , Yoshida Sakura , Yamauchi Motohiro , Soejima Ayumi , Haratake Mamoru , Nakayama Morio
Published: January 2020

Survivin belongs to the inhibitor of apoptosis protein family, which is consistently overexpressed in most cancer cells but rarely expressed in normal adult tissues. Therefore, the detection and inhibition of survivin are regarded as attractive strategies for cancer‐specific treatment. In this study, we designed and synthesized 7‐19 residues of inner centromere protein (INCENP)‐derived small peptides (INC peptides) as novel survivin‐targeting agents. The INC peptides showed binding affinity for the human survivin protein (Kd = 91.4‐255 nmol L−1); INC16‐22, which contains residues 16‐22 of INCENP, showed the highest affinity (91.4 nmol L−1). Confocal fluorescence imaging showed consistent colocalization of FITC‐INC16‐22 and survivin in cell lines. Nona‐arginine‐linked INC16‐22 (r9‐INC16‐22) rendered INC16‐22 cells penetrable and strongly inhibited cell growth of MIA PaCa‐2 cells (52% inhibition at 1.0 µmol L−1) and MDA‐MB‐231 cells (60% inhibition at 10 µmol L−1) as determined by MTT assays. The exposure of MIA PaCa‐2 cells to 40 µmol L−1 r9‐INC16‐22 apparently reduced the intracellular protein expression levels of survivin. However, cleaved caspase‐3 was significantly increased in cells treated with r9‐INC16‐22, even at 10 µmol L−1, compared to untreated cells. Flow cytometry revealed that r9‐INC16‐22 strongly induced apoptosis in MIA PaCa‐2 cells. These results indicate that the cytotoxic effects of r9‐INC16‐22 could be mediated mainly through the disruption of survivin‐dependent antiapoptotic functions and partly because of the direct degradation of the survivin protein. Our findings suggest that INC peptides can act as useful scaffolds for novel cancer imaging and anticancer agents.
The Effect of Birth weight on Child Development Prior to School Entry
Authors: Hines Caitlin T. , Padilla Christina M. , Ryan Rebecca M.
Published: January 2020

The present study examines variation in the effect of birth weight on children’s early cognitive and socioemotional outcomes by family socioeconomic status (SES). It is hypothesized that not only will lower birth weight children display worse cognitive and socioemotional outcomes prior to school entry, as prior research has found, but that effects will be stronger for lower‐SES children. Using data from the Early Childhood Longitudinal Study–Birth Cohort, the study compares the age 4 outcomes of twins discordant for birth weight (N ~ 1,400). Twin fixed‐effects models are run on the full twin sample and separately for low‐ and high‐SES children. Results support the study’s hypotheses, suggesting that socioeconomic risk accentuates the effects of birth weight on early development.
Comparison of elapegademase and pegademase in ADA-deficient patients and mice
Authors: Murguia-Favela L , Min W , Loves R , Leon-Ponte M , Grunebaum E
Published: January 2020

The absence of adenosine deaminase (ADA) causes severe combined immune deficiency (SCID), which has been treated with PEGylated bovine-extracted ADA (ADAGEN). ADAGEN was recently replaced by a PEGylated recombinant bovine ADA, expressed in Escherichia coli (elapegademase, ELA–ADA). Limited information on ELA–ADA is available.  ADA enzymatic activity of ELA–ADA and ADAGEN was assessed in vitro at diverse dilutions. ADA activity and immune reconstitution in an ADA–SCID patient treated with ELA–ADA were compared with age-matched patients previously treated with ADAGEN. ADA activity and thymus reconstitution were evaluated in ADA-deficient mice following ELA–ADA or ADAGEN administered from 7 days postpartum. In vitro, ADA activity of ELA–ADA and ADAGEN were similar at all dilutions. In an ADA–SCID patient, ELA–ADA treatment led to a marked increase in trough plasma ADA activity, which was 20% higher than in a patient previously treated with ADAGEN. A marked increase in T cell numbers and generation of naive T cells was evident following 3 months of ELA–ADA treatment, while T cell numbers increased following 4 months in 3 patients previously treated with ADAGEN. T cell proliferations stimulation normalized and thymus shadow became evident following ELA–ADA treatment. ADA activity was significantly increased in the blood of ADA-deficient mice following ELA–ADA compared to ADAGEN, while both treatments improved the mice weights, the weight, number of cells in their thymus and thymocyte subpopulations. ELA–ADA has similar in- vitro and possibly better in-vivo activity than ADAGEN. Future studies will determine whether ELA–ADA results in improved long-term immune reconstitution.
Mechanisms of checkpoint inhibition-induced adverse events
Authors: Urwyler P , Earnshaw I , Bermudez M , Perucha E , Wu W , Ryan S , Mcdonald L , Karagiannis S N , Taams L S , Powell N , Cope A , Papa S
Published: January 2020

Immune checkpoint inhibition has revolutionized the treatment of several solid cancers, most notably melanoma and non-small-cell lung cancer (NSCLC). Drugs targeting cytotoxic T lymphocyte antigen (CTLA)-4 and programmed cell death 1 (PD-1) have made their way into routine clinical use; however, this has not been without difficulties. Stimulation of the immune system to target cancer has been found to result in a reduction of self-tolerance, leading to the development of adverse effects that resemble autoimmunity. These adverse effects are erratic in their onset and severity and can theoretically affect any organ type. Several mechanisms for immune-related toxicity have been investigated over recent years; however, no consensus on the cause or prediction of toxicity has been reached. This review seeks to examine reported evidence for possible mechanisms of toxicity, methods for prediction of those at risk and a discussion of future prospects within the field.
Charcot–Marie–Tooth disease and neuroinflammation
Authors: Kokubun Norito
Published: January 2020

Patients with the misdiagnosis or co‐occurrence of Charcot–Marie–Tooth disease (CMT) and inflammatory neuropathies have been reported previously. Both CMT and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have similar clinical features, including flaccid weakness in four limbs with areflexia, demyelinating neurophysiological features and pathological demyelination. However, the symptoms of CIDP progress for several weeks or months, and typical CIDP shows proximal and distal muscle weakness. In contrast, CMT progresses for several decades and presents distal‐dominant muscle weakness, which is called length‐dependent neuropathy. On neurophysiological evaluation, CMT had been considered to show “uniform conduction slowing.” However, a recent study showed that CMT could show non‐uniform conduction abnormalities, which resemble inflammatory neuropathies. Furthermore, the incidence of inflammatory neuropathy in CMT is estimated to be higher than that in the general population. CMT1A with CIDP was the most common, followed by CMTX1 with CIDP and CMT1A with Guillain–Barré syndrome. Some patients showed macrophage‐associated demyelination or mononuclear cell infiltrations in their nerves. Most patients responded to immune therapies at least partly. The pathophysiology in such patients has not yet been elucidated. However, the involvement of the immune system in the development of demyelination in CMT was established by experimental animal studies, and vulnerability to immune abnormalities is suggested in abnormal myelin.
Facial alveolar bone alterations and gray value changes based on cone beam computed tomography around maxillary anterior implants: A clinical retrospective study of 1–3 years
Authors: Zhou Yi , Gao Jiayu , Sheng Min , Qi Wenting , Jin Jiali , He Fuming
Published: January 2020

Objectives

The purpose of this cone beam computed tomography (CBCT) study was to describe facial alveolar bone alterations and gray value (GV) changes around implants in aesthetic anterior maxilla with simultaneous guided bone regeneration (GBR) and to investigate potential influence of factors related to vertical alveolar bone stability, such as particle sizes of the deproteinized bovine bone mineral (DBBM) used.

Materials and Methods

A retrospective study design was adopted. Four facio‐palatal cross‐sectional CBCT images of 166 implants from 124 patients who had maxillary anterior implants were obtained. Measurements of the vertical facial alveolar bone level (VFBL), horizontal facial alveolar bone thickness (HFBT), and GV were identified of 1–3 years. Then, correlation coefficients for those parameters were calculated. Finally, linear mixed models were established to investigate potential factors influencing vertical alveolar bone resorption.

Results

Facial alveolar bone underwent fast bone modeling and remodeling during the first 6 months, with decreases of 1.00 ± 1.19 and 0.74 ± 0.86 mm in VFBL and HFBT in implant shoulder, respectively, and there was positive and significant correlation between the alterations in VFBL and HFBT1 (rs = .516, p = .000). Linear mixed models identified particle size of DBBM as a critical factor associated with vertical bone resorption (p = .000). The GV gradually increased during the follow‐up period.

Conclusions

Rapid and unavoidable peri‐implant bone resorption usually happened during the first 6 months after implant placement. GBR is a predictable treatment for maxillary anterior implants, since GV has an increasing trend. Large bone particles of DBBM help maintain vertical alveolar bone stability.
Freshwater fish diversity hotspots for conservation priorities in the Amazon Basin
Authors: Jézéquel Céline , Tedesco Pablo A. , Darwall William , Dias Murilo S. , Frederico Renata G. , Hidalgo Max , Hugueny Bernard , Maldonado‐Ocampo Javier , Martens Koen , Ortega Hernan , Torrente‐Vilara Gislene , Zuanon Jansen , Oberdorff Thierry
Published: January 2020

Conserving freshwater habitats and their biodiversity in the Amazon Basin is a growing challenge in the face of rapid anthropogenic changes. We used the most comprehensive fish‐occurrence database available (2355 valid species; 21,248 sampling points) and 3 ecological criteria (irreplaceability, representativeness, and vulnerability) to identify biodiversity hotspots based on 6 conservation templates (3 proactive, 1 reactive, 1 representative, and 1 balanced) to provide a set of alternative planning solutions for freshwater fish protection in the Amazon Basin. We identified empirically for each template the 17% of sub‐basins that should be conserved and performed a prioritization analysis by identifying current and future (2050) threats (i.e., degree of deforestation and habitat fragmentation by dams). Two of our 3 proactive templates had around 65% of their surface covered by protected areas; high levels of irreplaceability (60% of endemics) and representativeness (71% of the Amazonian fish fauna); and low current and future vulnerability. These 2 templates, then, seemed more robust for conservation prioritization. The future of the selected sub‐basins in these 2 proactive templates is not immediately threatened by human activities, and these sub‐basins host the largest part of Amazonian biodiversity. They could easily be conserved if no additional threats occur between now and 2050.
Using preoperative three‐dimensional endoanal ultrasound to determine operative procedure in patients with perianal fistulas
Authors: Mantoo S. , Mandovra P. , Goh S.
Published: January 2020

Aim

Accurate preoperative identification of perianal fistula tracts and internal openings can facilitate the choice of surgical procedure and may lead to improved healing rates. Our aim was to explore the effectiveness of three‐dimensional endoanal ultrasound (3D‐EAUS) in determining the type of perianal fistula and planning operative management.

Method

This was a cohort longitudinal study. Patients with perianal fistulas from January 2017 to January 2018 who underwent 3D‐EAUS and subsequent surgery were included. Intra‐operative findings were considered as standard for comparison with clinical examination and 3D‐EAUS findings. The primary outcome measure was to evaluate the concordance between 3D‐EAUS and intra‐operative findings and the secondary outcome measure was healing rates.

Results

Sixty‐eight patients with a mean age of 43.1 ± 14.1 years were included. Twenty‐eight patients had inter‐sphincteric (41.2%) and 40 (14 high and 26 low) trans‐sphincteric fistulas (58.8%). 3D‐EAUS, clinical examination and intra‐operative exploration could predict the location of internal openings in 62/68 (91.2%), 48/68 (70.5%) and 56/68 (82.4%) patients, respectively. Hydrogen peroxide (H₂O₂)‐enhanced 3D‐EAUS accurately predicted the location of internal openings when compared with 3D‐EAUS without H₂O₂ (concordance K = 0.963, P = 0.05). High concordance rates were seen between intra‐operative and 3D‐EAUS findings on the type of perianal fistula. No significant difference was seen between the suggested surgical treatment based on 3D‐EAUS and the eventual surgical treatment (P > 0.05). Study limitations were the small sample size and lack of randomization.

Conclusion

3D‐EAUS may be considered as a first‐line investigation for patients with perianal fistulas because of high concordance with intra‐operative assessment and facilitation of surgical planning.
Revealing migration and reproductive habitat of invasive fish under an active population suppression program
Authors: Gutowsky Lee F.G. , Romine Jason G. , Heredia Nicholas A. , Bigelow Patricia E. , Parsley Michael J. , Sandstrom Philip T. , Suski Cory D. , Danylchuk Andy J. , Cooke Steven J. , Gresswell Robert E.
Published: January 2020

Endemic species face a variety of threats including predation from non‐native invaders. In some cases, however, invasive species can be managed by directly suppressing populations, and tracking technologies that allow researchers to identify movement patterns and aggregations representative of the population can facilitate suppression activities. In Yellowstone Lake (Yellowstone National Park, Wyoming), invasive lake trout (Salvelinus namaycush) have been the target of a population suppression program for over two decades. For this form of management, the reproductive period is particularly important because fish migrate to and from spawning grounds. From 2011 to 2014, adult lake trout (n = 317) in Yellowstone Lake were tracked using acoustic biotelemetry. After controlling for spatial and temporal dependency in the data, total abundance of unique individuals was estimated where migratory trajectories occurred at confirmed spawning sites. Aggregations and migratory trajectories were further estimated at locations where spawning had not previously been observed. Across years, the greatest number of individuals was observed along a migration corridor in the southwestern area of the lake. Novel strategies for analyzing acoustic telemetry data provided insights into the behavior of an invasive fish species. By betraying the positions of conspecifics, tagged fish revealed potentially important reproductive habitats and migration corridors that warranted further investigation as possible sites for population suppression.
Regional‐scale patterns of deep seafloor biodiversity for conservation assessment
Authors: O'Hara Timothy D. , Williams Alan , Althaus Franziska , Ross Andrew S. , Bax Nicholas J.
Published: January 2020

Aim

Mining and petroleum industries are exploring for resources in deep seafloor environments. Lease areas are often spatially aggregated and continuous over hundreds to thousands of kilometres. Sustainable development of these resources requires an understanding of the patterns of biodiversity at similar scales, yet these data are rarely available for the deep sea. Here, we compare biodiversity metrics and assemblage composition of epibenthic megafaunal samples from deep‐sea benthic habitats from the Great Australian Bight (GAB), a petroleum exploration zone off southern Australia, to similar environments off eastern Australia.

Location

The Great Australian Bight (34–36°S, 129–134°E) and south‐eastern (SE) and north‐eastern (NE) Australian continental margins (23–42°S, 149–155°E) in depths of 1,900–5,000 m.

Methods

A species–sample matrix was constructed from invertebrate and fish megafauna collected from beam trawl samples across regions at lower bathyal (1,900–3,200 m) and abyssal (>3,200 m) depths, and analysed using multivariate, rarefaction and model‐based statistics. We modelled rank abundance distributions (RAD) against environmental factors to identify drivers of abundance, richness and evenness.

Results

Multivariate analyses showed regional and bathymetric assemblage structure across the region. There was an almost complete turnover of sponge fauna between the GAB and SE. SE samples had the highest total faunal abundance and species richness. RAD models linked total abundance and species richness to levels of carbon flux. Evenness was associated with seasonality of net primary production.

Conclusions

Significant assemblage structure at regional scales is reported for the first time at lower bathyal and abyssal depths in the southern Indo‐Pacific region along latitudinal and longitudinal gradients. The GAB fauna was distinct from other studied areas. Relatively high species richness, previously reported from the GAB continental shelf, did not occur at lower bathyal or abyssal depths. Instead, the abundance, richness and evenness of the benthic fauna are linked to surface primary production, which is elevated off SE Australia.
Do you understand what I want to tell you? Early sensitivity in bilinguals' iconic gesture perception and production
Authors: Wermelinger Stephanie , Gampe Anja , Helbling Natascha , Daum Moritz M.
Published: January 2020

Previous research has shown differences in monolingual and bilingual communication. We explored whether monolingual and bilingual pre‐schoolers (N = 80) differ in their ability to understand others' iconic gestures (gesture perception) and produce intelligible iconic gestures themselves (gesture production) and how these two abilities are related to differences in parental iconic gesture frequency. In a gesture perception task, the experimenter replaced the last word of every sentence with an iconic gesture. The child was then asked to choose one of four pictures that matched the gesture as well as the sentence. In a gesture production task, children were asked to indicate ‘with their hands’ to a deaf puppet which objects to select. Finally, parental gesture frequency was measured while parents answered three different questions. In the iconic gesture perception task, monolingual and bilingual children did not differ. In contrast, bilinguals produced more intelligible gestures than their monolingual peers. Finally, bilingual children's parents gestured more while they spoke than monolingual children's parents. We suggest that bilinguals' heightened sensitivity to their interaction partner supports their ability to produce intelligible gestures and results in a bilingual advantage in iconic gesture production.
Health professionals' views about who would benefit from using a closed‐loop system: a qualitative study
Authors: Lawton J. , Kimbell B. , Rankin D. , Ashcroft N. L. , Varghese L. , Allen J. M. , Boughton C. K. , Campbell F. , Randell T. , Besser R. E. J. , Trevelyan N. , Hovorka R. ,   the CLOuD Consortium
Published: January 2020

Aim

To explore health professionals' views about who would benefit from using a closed‐loop system and who should be prioritized for access to the technology in routine clinical care.

Methods

Health professionals (n = 22) delivering the Closed Loop from Onset in type 1 Diabetes (CLOuD) trial were interviewed after they had ≥ 6 months' experience supporting participants using a closed‐loop system. Data were analysed thematically.

Results

Interviewees described holding strong assumptions about the types of people who would use the technology effectively prior to the trial. Interviewees described changing their views as a result of observing individuals engaging with the closed‐loop system in ways they had not anticipated. This included educated, technologically competent individuals who over‐interacted with the system in ways which could compromise glycaemic control. Other individuals, who health professionals assumed would struggle to understand and use the technology, were reported to have benefitted from it because they stood back and allowed the system to operate without interference. Interviewees concluded that individual, family and psychological attributes cannot be used as pre‐selection criteria and, ideally, all individuals should be given the chance to try the technology. However, it was recognized that clinical guidelines will be needed to inform difficult decisions about treatment allocation (and withdrawal), with young children and infants being considered priority groups.

Conclusions

To ensure fair and equitable access to closed‐loop systems, prejudicial assumptions held by health professionals may need to be addressed. To support their decision‐making, clinical guidelines need to be made available in a timely manner.
The impact of DRP1 on myocardial fibrosis in the obese minipig
Authors: Chen Ching‐Yi , Li Sin‐Jin , Wang Chia‐Yu , Mersmann Harry J. , Ding Shih‐Torng
Published: January 2020

Background

The heart is a highly oxidative tissue, thus mitochondria play a major role in maintaining optimal cardiac function. Our previous study established a dietary‐induced obese minipig with cardiac fibrosis. The aim of this study was to elucidate the role of mitochondrial dynamics in cardiac fibrosis of obese minipigs.

Design

Four‐month‐old Lee‐Sung minipigs were randomly divided into two groups: a control group (C) and an obese group (O) by feeding a control diet or a high‐fat diet (HFD) for 6 months. Exposure of H9c2 cardiomyoblasts to palmitate was used to explore the effects of high‐fat on induction of myocardial injury in vitro.

Results

The O pigs displayed greater heart weight and cardiac collagen accumulation. Obese pigs exhibited a lower antioxidant capacity, ATP concentration, and higher oxidative stress in the left ventricle (LV). The HFD caused downregulation in protein expression of PGC‐1α and OPA1, and upregulation of DRP1, FIS1, and PINK1 in the LV of O compared to C pigs. Furthermore, palmitate induced apoptosis and decreased ATP content in H9c2 cells. Palmitate elevated the protein expression of DRP1 and PINK1 in these cells. Inhibition of DRP1 protein expression by siDRP1 in H9c2 cells resulted in enhanced ATP and decreased palmitate‐induced apoptosis.

Conclusions

These results suggest that mitochondrial dynamics were linked to the progression of obesity‐related cardiac injury. Inhibition of DRP1 after palmitate exposure in H9c2 cells resulted in improved ATP level and decreased apoptosis in vitro suggesting that mitochondrial fission serves a key role in progression of obesity‐induced cardiac fibrosis.
Clonal selection in therapy‐related myelodysplastic syndromes and acute myeloid leukemia under azacitidine treatment
Authors: Calleja Anne , Yun Seongseok , Moreilhon Chimène , Karsenti Jean Michel , Gastaud Lauris , Mannone Lionel , Komrokji Rami , al Ali Najla , Dadone‐montaudie Bérangère , Robert Guillaume , Auberger Patrick , Raynaud Sophie , Sallman David A. , Cluzeau Thomas
Published: January 2020

Introduction

Therapy‐related myelodysplastic syndrome and acute myeloid leukemia (t‐MDS/AML) are defined as complications of previous cytotoxic therapy. Azacitidine (AZA), a hypomethylating agent, has showed activity in t‐MDS/AML.

Objectives

We evaluated the clonal dynamics of AZA‐treated t‐MDS/AML.

Methods

We collected bone marrow samples, at diagnosis and during treatment, from AZA‐treated t‐MDS/AML patients. NGS on 19 myeloid genes was performed, and candidate mutations with a variant allele frequency >5% were selected.

Results

Seven t‐AML and 12 t‐MDS were included with median age of 71 (56‐82) years old, median number of AZA cycles of 6 (1‐15), and median overall survival (OS) of 14 (3‐29) months. We observed correlation between AZA response and clonal selection. Decrease of TP53‐mutated clone was correlated with response to AZA, confirming AZA efficacy in this subgroup. In some patients, emergence of mutations was correlated with progression or relapse without impact on OS. Clones with mutations in genes for DNA methylation regulation frequently occurred with other mutations and remained stable during AZA treatment, independent of AZA response.

Conclusion

We confirmed that the molecular complexity of t‐MNs and that the follow‐up of clonal selection during AZA treatment could be useful to define treatment combination.
On the design of hybrid bio‐inspired meta‐heuristics for complex multiattribute vehicle routing problems
Authors: Nogareda Ana‐Maria , Del Ser Javier , Osaba Eneko , Camacho David
Published: January 2020

This paper addresses a multiattribute vehicle routing problem, the rich vehicle routing problem, with time constraints, heterogeneous fleet, multiple depots, multiple routes, and incompatibilities of goods. Four different approaches are presented and applied to 15 real datasets. They are based on two meta‐heuristics, ant colony optimization (ACO) and genetic algorithm (GA), that are applied in their standard formulation and combined as hybrid meta‐heuristics to solve the problem. As such ACO‐GA is a hybrid meta‐heuristic using ACO as main approach and GA as local search. GA‐ACO is a memetic algorithm using GA as main approach and ACO as local search. The results regarding quality and computation time are compared with two commercial tools currently used to solve the problem. Considering the number of customers served, one of the tools and the ACO‐GA approach outperforms the others. Considering the cost, ACO, GA, and GA‐ACO provide better results. Regarding computation time, GA and GA‐ACO have been found the most competitive among the benchmark.
Nationwide survey of continence status among older adult residents living in long‐term care facilities in Japan: The prevalence and associated risk factors of incontinence and effect of comprehensive care on continence status
Authors: Suzuki Motofumi , Okochi Jiro , Iijima Katsuya , Murata Taro , Kume Haruki
Published: January 2020

Aim

This study aimed to identify the prevalence of urinary, fecal and double incontinence among Japanese residents aged ≥65 years living in long‐term care facilities. Furthermore, the association between baseline characteristics and changes in toileting activity after a 3‐month comprehensive care among older individuals was investigated.

Methods

We examined the prevalence of incontinence and its significant predictors. The association between the Functional Independence Measure score at baseline and each type of incontinence (urinary, fecal or double incontinence) was examined using a logistic regression model. Similarly, the association between the Functional Independence Measure score at baseline and improvement in toileting activity after a 3‐month comprehensive care was examined.

Results

In total, 2517 residents (670 men and 1847 women) were recruited. The prevalence rates of urinary, fecal and double incontinence were 66.9%, 42.8% and 41.1%, respectively. In multivariate analysis, the sum of the motor subscales after removing four continence items and the sum of the cognitive subscales of the Functional Independence Measure score at baseline were significantly associated with all types of incontinence. The sum of the motor subscales after removing four continence items of the Functional Independence Measure score was associated with improved toileting activity.

Conclusions

This study presented the prevalence of urinary, fecal and double incontinence among residents living in long‐term care facilities in Japan. The Functional Independence Measure items at baseline were associated with not only continence status, but also improved toileting activity after 3‐month comprehensive care. Geriatr Gerontol Int 2020; 20: 285–290.
Trade credit insurance in a capital‐constrained supply chain
Authors: Li Hongping , Bi Gongbing , Yuan Xiaoyong , Wang Dong
Published: January 2020

We examine the role of trade credit insurance in a capital‐constrained supply chain with one (or two) loss‐neutral retailer(s) and one loss‐averse manufacturer. We model the interplay between these supply chain participants as a Stackelberg game and analyze their operating and financing decisions. In one capital‐constrained retailer case, we find that either the manufacturer's high loss aversion level or the retailer's low initial capital motivates the manufacturer to adopt insurance. Insurance drives more credit financing with more attractive financing terms (a lower wholesale price), which promotes the manufacturer to collect better product sales and performance. Although the retailer enjoys improved profit from insurance, its default risk increases. In contrast, in one capital‐constrained retailer and one well‐funded retailer scenario, numerically, when the manufacturer's loss aversion level is high or the weak retailer's initial capital is low, insurance is also adopted but is not always preferred by the capital‐constrained retailer due to competition. In addition, as the demand substitution rate increases, the manufacturer is more likely to prefer insurance due to better performance.
Exploring Longitudinal Industry‐Level Large Truckload Driver Turnover
Authors: Miller Jason W. , Bolumole Yemisi , Muir William A.
Published: January 2020

Driver turnover remains a pervasive challenge for truckload (TL) motor carriers. For more than two decades, carriers in this segment have faced the deleterious effects brought on by a persistently high driver turnover rate, including increased costs, decreased productivity, and the erosion of safety performance. In light of these issues, logistics scholars have conducted numerous driver‐level and carrier‐level investigations to better understand the antecedents of TL driver turnover. Yet, since driver turnover is an industry‐wide issue, critical industry‐level questions remain unanswered. This paper seeks to complement prior work by adopting labor economic theory and methods to investigate how the industry‐level driver turnover rate evolves over time. In particular, we focus on how changing industry employment and wages impact the TL driver turnover rate across large carriers. We test our theory of industry‐level turnover using the American Trucking Association's proprietary turnover data for large TL carriers as well as governmental archives on industry and economic conditions obtained from the U.S. Bureau of Labor Statistics and the U.S. Federal Reserve. Estimation results from time‐series regression modeling corroborate our theoretical arguments and hold important implications for TL motor carriers, shippers, and other industry stakeholders.
Chicoric acid ameliorate inflammation and oxidative stress in Lipopolysaccharide and d‐galactosamine induced acute liver injury
Authors: Li Zheng , Feng Haihua , Han Lu , Ding Lu , Shen Bingyu , Tian Ye , Zhao Lilei , Jin Meiyu , Wang Qi , Qin Haiyan , Cheng Jiaqi , Liu Guowen
Published: January 2020

Chicoric acid is polyphenol of natural plant and has a variety of bioactivity. Caused by various kinds of stimulating factors, acute liver injury has high fatality rate. The effect of chicoric acid in acute liver injury induced by Lipopolysaccharide (LPS) and d‐galactosamine (d‐GalN) was investigated in this study. The results showed that CA decreased the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum and reduced the mortality induced by LPS/d‐GalN. CA can restrain mitogen‐activated protein kinases (MAPKs) and nuclear factor‐kappa B (NF‐κB) to alleviate inflammation. Meanwhile, the results indicated CA can active nuclear factor‐erythroid 2‐related factor 2 (Nrf2) pathway with increasing the level of AMP‐activated protein kinase (AMPK). And with the treatment of CA, protein levels of autophagy genes were obvious improved. The results of experiments indicate that CA has protective effect in liver injury, and the activation of AMPK and autophagy may make sense.
A stroma‐related lncRNA panel for predicting recurrence and adjuvant chemotherapy benefit in patients with early‐stage colon cancer
Authors: Zhou Rui , Sun Huiying , Zheng Siting , Zhang Jingwen , Zeng Dongqiang , Wu Jianhua , Huang Zhenhua , Rong Xiaoxiang , Bin Jianping , Liao Yulin , Shi Min , Liao Wangjun
Published: January 2020

The heterogeneity in prognoses and chemotherapeutic responses of colon cancer patients with similar clinical features emphasized the necessity for new biomarkers that help to improve the survival prediction and tailor therapies more rationally and precisely. In the present study, we established a stroma‐related lncRNA signature (SLS) based on 52 lncRNAs to comprehensively predict clinical outcome. The SLS model could not only distinguish patients with different recurrence and mortality risks through univariate analysis, but also served as an independent factor for relapse‐free and overall survival. Compared with the conventionally used TNM stage system, the SLS model clearly possessed higher predictive accuracy. Moreover, the SLS model also effectively screened chemotherapy‐responsive patients, as only patients in the low‐SLS group could benefit from adjuvant chemotherapy. The following cell infiltration and competing endogenous RNA (ceRNA) network functional analyses further confirmed the association between the SLS model and stromal activation‐related biological processes. Additionally, this study also identified three phenotypically distinct colon cancer subtypes that varied in clinical outcome and chemotherapy benefits. In conclusion, our SLS model may be a significant determinant of survival and chemotherapeutic decision‐making in colon cancer and may have a strong clinical transformation value.
Optimization design of cane sugar evaporative crystallizer based on orthogonal test and computational fluid dynamics
Authors: Zhang Jinlai , Meng Yanmei , Wang Hui , Yao Tao , Yu Shuangshuang , Chen Ji
Published: January 2020

This article describes an optimization design of a sugar evaporative crystallizer using numerical simulation experiments. Computational fluid dynamics (CFD) is used to simulate the circulation flow of sugar juice in the crystallizer, and the numerical experiments are designed according to orthogonal experiment matrix. First, based on the specific working characteristics of sugar evaporative crystallizer, major factors influencing the cane sugar evaporative crystallization process were identified. Then CFD software was utilized to establish various three‐dimensional CFD models of the sugar evaporative crystallization with different factors and levels. Statistics software (IBM SPSS) is used to analyze the CFD simulation results. In order to measure circulation velocity under different conditions, physical experiments were conducted in the experiment platform in our laboratory. The circulation velocity measured under the optimal condition was increased by 128%, and the crystallization efficiency could be guaranteed.

Practical Applications

Computation fluid dynamics (CFD) enables studying the details within the crystallizer, making the invisible become visible. The orthogonal test replaces all tests with partial tests. The orthogonal test coupled CFD technique can hugely decrease the cost of optimization design. The application of this method will benefit the optimization design of food engineering.