bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutrient limitation, bioenergetics and stoichiometry: A new model to predict elemental fluxes mediated by fishes
Authors: Schiettekatte Nina M. D. , Barneche Diego R. , Villéger Sébastien , Allgeier Jacob E. , Burkepile Deron E. , Brandl Simon J. , Casey Jordan M. , Mercière Alexandre , Munsterman Katrina S. , Morat Fabien , Parravicini Valeriano
Published: June 2020

Energy flow and nutrient cycling dictate the functional role of organisms in ecosystems. Fishes are key vectors of carbon (C), nitrogen (N) and phosphorus (P) in aquatic systems, and the quantification of elemental fluxes is often achieved by coupling bioenergetics and stoichiometry. While nutrient limitation has been accounted for in several stoichiometric models, there is no current implementation that permits its incorporation into a bioenergetics approach to predict ingestion rates. This may lead to biased estimates of elemental fluxes.

Here, we introduce a theoretical framework that combines stoichiometry and bioenergetics with explicit consideration of elemental limitations. We examine varying elemental limitations across different trophic groups and life stages through a case study of three trophically distinct reef fishes. Further, we empirically validate our model using an independent database of measured excretion rates.

Our model adequately predicts elemental fluxes in the examined species and reveals species‐ and size‐specific limitations of C, N and P. In line with theoretical predictions, we demonstrate that the herbivore Zebrasoma scopas is limited by N and P, and all three fish species are limited by P in early life stages. Further, we show that failing to account for nutrient limitation can result in a greater than twofold underestimation of ingestion rates, which leads to severely biased excretion rates.

Our model improved predictions of ingestion, excretion and egestion rates across all life stages, especially for fishes with diets low in N and/or P. Due to its broad applicability, its reliance on many parameters that are well‐defined and widely accessible, and its straightforward implementation via the accompanying r‐package fishflux, our model provides a user‐friendly path towards a better understanding of ecosystem‐wide nutrient cycling in the aquatic biome.

A free Plain Language Summary can be found within the Supporting Information of this article.
Aridity exacerbates grazing‐induced rangeland degradation: A population approach for dominant grasses
Authors: Oñatibia Gastón R. , Amengual Gerónimo , Boyero Luciano , Aguiar Martín R.
Published: June 2020

The current human‐induced intensification of grazing pressure and the aridity increase as a result of climate change are unprecedented and have been identified as the main drivers that cause desertification in rangelands world‐wide. In these ecosystems, human well‐being mostly depends on plant species that provide forage for domestic herbivores. However, scarce evidence exists about the interaction between regional aridity level and human‐induced disturbances as determinants of forage plant populations' structure and dynamics.

We studied the effects of domestic grazing intensification on the population structure of dominant native grasses, in three rangeland sites located across a regional aridity gradient: a semi‐desert (high‐aridity site), a shrub–grass steppe (intermediate‐aridity site) and a grass steppe (low‐aridity site). We also studied the effect of 2‐year grazing exclusion on the growth of defoliated plants of a key native forage grass species common to the three sites.

Grazing decreased total grass density and increased the frequency of small plants in all sites, particularly for forage species. However, the size of the grazing intensification effect was the greatest in the high‐aridity site, where intensive grazing produced a ten‐fold reduction of grass density. Moreover, defoliated plants recovery (growth) was lower as aridity increased.

Synthesis and applications. Our study provides evidence of a negative synergistic effect of grazing pressure and aridity that may lead to the collapse of grass populations. Long‐term grazing intensification degrades the population structure of grasses, particularly in high‐aridity sites, where the forage provision is substantially reduced. These results refute the hypothesis that plant traits of dominant species adapted to high aridity allow them to resist herbivory. Besides, high aridity delays plant recovery after defoliation (low resilience). The management of both grazing pressure and the length of grazing rest according to ecological‐site aridity are key aspects for maintaining the forage provision of rangelands. Monitoring plant populations' structure through time and space strengthens inferences about responses of forage species to ongoing changes in disturbance and stress regimes. This knowledge is complementary to regional and world‐wide monitoring endeavours based on land cover, and it contributes to the robust design of sustainable management of global rangelands.
The importance of personal vote intentions for the responsiveness of legislators: A field experiment
Authors: BOL DAMIEN , GSCHWEND THOMAS , ZITTEL THOMAS , ZITTLAU STEFFEN
Published: June 2020

Individual legislators can be important agents of political representation. However, this is contingent upon their responsiveness to constituency requests. To study this topic, an increasing number of studies use field experiments in which the researcher sends a standardized email to legislators on behalf of a constituent. In this paper, we report the results of an original field experiment of this genre with the members of the German Bundestag. Supplementing previous research, we explore whether constituency requests in which voters mention a personal vote intention (rather than a partisan vote intention) increase legislators’ responsiveness, and how this treatment relates to electoral system's incentives. We find that legislators treated with a personal vote intention were more likely to respond (67 per cent) and respond faster than those treated with a partisan vote intention (59 per cent). However, we also show that the treatment effect is moderated by electoral system incentives: it is larger for nominally‐elected legislators than for those elected via a party list. Our results suggest that electoral system's incentives matter for legislators’ responsiveness only when constituents explicitly signals an intention to cast a personal vote.
Recent advances in processing food powders by using superfine grinding techniques: A review
Authors: Gao Wenjie , Chen Feng , Wang Xi , Meng Qingran
Published: June 2020

Food powders are ubiquitous in people's daily life and food industry production with numerous advantages. With the increasing use of food powder in the world, it is increasingly important to understand the processing methods of food powder and the changes in physicochemical properties after processing in order to control the processing conditions and the quality of final products. Among the many processing methods for food powders, superfine grinding technique is an emerging and useful tool for superfine powder manufacturing with some unique and promising properties, which has made the technique successfully applied in food processing over the recent decades. This review highlights the information of the main superfine grinding methods in the field of food processing and the changes in performance after superfine grinding treatment. Also, potential challenges, promising opportunities, and perspectives of this technology are covered in the review. This review will provide theoretical foundation and guideline for superfine food powder processing, which can provide new approaches and ideas for the high‐value utilization of food raw materials as well as the food design.
Who holds the key? Negotiating gatekeepers, community politics, and the “right” to research in Indigenous spaces
Authors: Sullivan Corrinne Tayce
Published: June 2020

This article considers key methodological and ethical issues for qualitative research with Aboriginal sex workers based on the author's experiences conducting research with this diverse group of people. Issues gaining access to this group through Indigenous community organisations and sex worker community organisations are considered. The aim is to share critical reflections about some of the assumptions underpinning the research process, ethical engagement with Indigenous communities, and research participants and to outline researcher responsibilities. In navigating these factors, it was found that working with and for community‐based organisations requires considerable attention to power and the dynamics of representation.
Comparing steady‐state to unsteady‐state respiration rate measurement methods for design of modified atmosphere packaging of grape tomatoes and blueberries with microperforations
Authors: Boz Ziynet , Welt Bruce A. , Canter James , Brecht Jeffrey K. , Pelletier William
Published: June 2020

Designing modified atmosphere packages (MAPs) for fresh produce requires respiration rate (RR) data. A steady‐state (SS) approach is widely used but is expensive, tedious, and time‐consuming. Unsteady‐state (USS) methods mitigate shortcomings of the SS approach, but comparisons between the two approaches have not been done to verify the design outcomes of MAPs, especially those with microperforations. RR measurement methods for grape tomatoes and blueberries were compared. Data were then used to design microperforated MAP packages to compare predicted design specifications created from RR data with observed shelf life. Results show that the USS method provides similar magnitudes of RR and predicts similar numbers of perforations as the SS method. Observations of packages produced using 100 µm perforations, using measured respiration data, suggest that both methods underestimated what might have been deemed correct by about one microperforation.

Practical Application

Designing packaging for fresh produce requires the knowledge of produce respiration. Steady‐state methods are conceptually simple, but time‐consuming. Unsteady‐state methods are rapid. This work compares methods on design of packages.
A novel eicosapentaenoic acid‐derived anti‐inflammatory lipid mediator 5,6‐DiHETE is abundant in blue back fish intestines
Authors: Kida Misato , Nakamura Tatsuro , Murata Takahisa
Published: June 2020

Because omega‐3 fatty acids, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and their metabolites are known to possess anti‐inflammatory and health‐promoting functions in human and experimental animals, their intake is assumed to be beneficial for maintaining our health. We previously identified a cytochrome P450‐metabolite of EPA, 5,6‐dihydroxy‐8Z,11Z,14Z,17Z‐eicosatetraenoic acid (5,6‐DiHETE), as a novel bioactive lipid, which inhibits vascular hyperpermeability in inflammation. Because blue back fishes including sardine, mackerel, and horse mackerel are reported to contain high concentrations of omega‐3 fatty acids, we investigated which tissue of blue back fish is suitable as a source of 5,6‐DiHETE. We measured the concentration of 5,6‐DiHETE as well as major fatty acids in muscle, bone, heart, liver, and intestine of blue back fishes. Arachidonic acid was detected richer in intestines than other tissues of blue back fishes. The concentrations were between 4.45 and 5.62 µg/g tissue weight. EPA and DHA are also detected richer in intestines of blue back fishes. The concentrations were between 75.95 and 358.04 µg/g, and 203.09 and 464.88 µg/g, respectively. Especially, mackerel intestine contained the highest levels of both EPA and DHA. 5,6‐DiHETE was present in greater amount in livers and intestines of blue back fishes. The livers contained 118.98 to 476.11 ng/g, whereas intestines contained 156.14 to 970.22 ng/g of 5,6‐DiHETE. Of interest, sardine intestine contained much higher level of 5,6‐DiHETE than the other fish tissues. These results suggest that visceral organs of blue back fishes, remarkably sardine intestine, can be a good source of 5,6‐DiHETE.

Practical Application

A novel anti‐inflammatory lipid, 5,6‐DiHETE, was detected in each tissues of blue back fishes. Especially their intestines contain the highest concentration of this lipid.
Effect of the wheat starch/wheat protein ratio in a batter on fat absorption and quality attributes of fried battered and breaded fish nuggets
Authors: Chen Chaofan , Chen Jiwang , Yuan Zijun , Liao E , Xia Wenshui , Wang Haibin , Xiong Youling L.
Published: June 2020

Battered and breaded fish nuggets (BBFNs) were prepared by treating fish with a batter composed of wheat starch (WS) and wheat protein (WP) blends (at the ratios of 15:1, 13:1, 11:1, 9:1, and 7:1, w/w), frying at 170 °C (40 s) followed by 190 °C (30 s). Fried BBFNs were evaluated for moisture and fat contents, color, shrinkage, acrylamide content, and fat distribution. Results showed that moisture content and brightness (L* value from colorimetry) increased with a decrease of WS/WP ratio to 11:1 w/w, then decreased as WS/WP ratio further decreased, while fat content, fat distribution level, and shrinkage of fried BBFNs presented opposite results. However, there was a slight influence of WS/WP ratio on yellowness (b* value), redness (a* value), and acrylamide content of fried BBFNs. Among WS/WP ratios, fried BBFNs with 11:1 w/w have the highest moisture content (16.43%) and the lowest fat content (23.39%), fat distribution level, shrinkage (10.72%), and acrylamide content (57 mg/kg), while a crust with golden‐yellow color was observed. This study demonstrates that moisture evaporation and fat absorption were significantly influenced by WS/WP ratio in the batter (P < 0.05), with the most effective results in quality attributes improvement of fried BBFNs.

Practical Application

This study clearly showed that the fat content and quality attributes of fried BBFNs were significantly affected by WS/WP ratio in the batter (P < 0.05). The inhibition of fat absorption and improvement of shrinkage and color in fried BBFNs was the most effective for a 11:1 w/w WS/WP ratio.
CT imaging features of skeletal muscle metastasis: A rare tumour group with different patterns
Authors: Meyer Hans‐Jonas , Ullrich Sebastian , Surov Alexey
Published: June 2020

Introduction

Skeletal muscle metastasis (SMM) are rare and can have different patterns on computed tomography (CT). Our aim was to estimate the frequency of the different patterns, primary tumours and localizations of SMM in a large single‐centre sample.

Methods

A retrospective search in the database of our radiological institution was performed for patients with SMM. The primary tumour, affected muscles and CT patterns were estimated.

Results

Overall, 104 SMM were diagnosed in 82 patients. In 11 patients (13.4%), SMM were the isolated manifestation of metastatic disease in clinical work up. Regarding primary tumours, gastrointestinal tumours (24.4%), lung cancer (20.4%) and malignant melanoma (13.4%) were identified most frequently. Other malignancies were rare. Most commonly, the trunk musculature was affected (41.3% of the cases). SMM type 1 were identified in 37 cases (35.6%), type 2 in 64 cases (61.5%), type 3 in 2 cases (1.9%) and type 4 in one case (1%).

Conclusions

The present study shows typical imaging appearances of SMM based on a large patient sample in a single centre. SMM has a rare occurrence with several different patterns, which can impose diagnostic difficulties and varies possible differential diagnoses.
Age‐at‐onset‐dependent effects of sulfur amino acid restriction on markers of growth and stress in male F344 rats
Authors: Nichenametla Sailendra N. , Mattocks Dwight A. L. , Malloy Virginia L
Published: June 2020

Trade‐offs in life‐history traits are clinically and mechanistically important. Sulfur amino acid restriction (SAAR) extends lifespan. But whether this benefit comes at the cost of other traits including stress resistance and growth is unclear. We investigated the effects of SAAR on growth markers (body weight, IGF1, and IGFBP3) and physiological stresses. Male‐F344 rats were fed control (0.86% Met) and SAAR (0.17% Met) diets starting at 2, 10, and 20 months. Rats were injected with keyhole‐limpet‐hemocyanin (KLH) to measure immune responses (anti‐KLH‐IgM, anti‐KLH‐IgG, and delayed‐type‐hypersensitivity [DTH]). Markers of ER stress (FGF21 and adiponectin), detoxification capacity (glutathione [GSH] concentrations, GSH‐S‐transferase [GST], and cytochrome‐P450‐reductase [CPR] activities), and low‐grade inflammation (C‐reactive protein [CRP]) were also determined. SAAR decreased body weight, liver weight, food intake, plasma IGF1, and IGFBP3; the effect size diminished with increasing age‐at‐onset. SAAR increased FGF21 and adiponectin, but stress damage markers GRP78 and Xbp1s/us were unchanged, suggesting that ER stress is hormetic. SAAR increased hepatic GST activity despite lower GSH, but CPR activity was unchanged, indicative of enhanced detoxification capacity. Other stress markers were either uncompromised (CRP, anti‐KLH‐IgM, and DTH) or slightly lower (anti‐KLH‐IgG). Increases in stress markers were similar across all ages‐at‐onset, except for adiponectin, which peaked at 2 months. Overall, SAAR did not compromise stress responses and resulted in maximal benefits with young‐onset. In survival studies, median lifespan extension with initiation at 52 weeks was 7 weeks (p = .05); less than the 33.5‐week extension observed in our previous study with 7‐week initiation. Findings support SAAR translational studies and the need to optimize Met dose based on age‐at‐onset.
Microecological Relationships Between Area Income, Off‐Premise Alcohol Outlet Density, Drinking Patterns, and Alcohol Use Disorders: The East Bay Neighborhoods Study
Authors: Mair Christina , Sumetsky Natalie , Gruenewald Paul J. , Lee Juliet P.
Published: June 2020

Background

Distinguishing the impacts of neighborhood income and off‐premise alcohol outlet density on alcohol use has proven difficult, particularly given the conflation of these measures across neighborhood areas. We explicitly test for differential effects related to individual and area income and outlet densities on alcohol use and alcohol use disorders (AUDs) by implementing a stratified microecological sample.

Methods

The East Bay Neighborhoods Study included a survey of 984 residents of 72 microenvironments within a geographically contiguous 6‐city area in California and Systematic social observations of each site. The sites included 18 areas in each of 4 strata (high/low median household income and off‐premise outlet density). We assessed 4 outcomes: 28‐day drinking frequency, average quantity of alcohol consumed per drinking occasion, 28‐day drinking volume, and Alcohol Use Disorders Identification Test (AUDIT) score. We used zero‐inflated negative binomial regression with standard errors adjusted for site clusters to relate drinking measures to individual‐level age, race/ethnicity, gender, marital status, education, and income, and neighborhood indicators of site strata, physical disorder, and physical decay. An interaction term was tested representing site‐level by individual‐level income.

Results

Living in a high‐income site, regardless of off‐premise alcohol outlet density, was associated with more frequent drinking and higher alcohol dependence/problems. Both individual‐level income and site‐level income were related to greater frequencies of use, but lower income drinkers in high‐income areas drank more than comparable drinkers in low‐income areas. Study participants living in high‐density off‐premise alcohol outlet sites drank less frequently but did not differ in terms of either AUDIT scores or heavy drinking from participants living in low‐density sites.

Conclusions

Using a stratified microecological sampling design, we were able to directly assess statistical associations of off‐premise outlet density and neighborhood median household income with patterns of drinking and AUDs. Caution should be used interpreting prior study findings linking off‐premise outlet densities to drinking.
Molecular Correlates of Topiramate and GRIK1 rs2832407 Genotype in Pluripotent Stem Cell–Derived Neural Cultures
Authors: Lieberman Richard , Jensen Kevin P. , Clinton Kaitlin , Levine Eric S. , Kranzler Henry R. , Covault Jonathan
Published: June 2020

Background

There is growing evidence that the anticonvulsant topiramate is efficacious in reducing alcohol consumption. Further, an intronic single nucleotide polymorphism (rs2832407, C A) in the GRIK1 gene, which encodes the GluK1 subunit of the excitatory kainate receptor, predicted topiramate’s effectiveness in reducing heavy drinking in a clinical trial. The molecular correlates of GRIK1 genotype that may relate to topiramate’s ability to reduce drinking remain unknown.

Methods

We differentiated induced pluripotent stem cells (iPSCs) characterized by GRIK1 rs2832407 genotype from 8 A/A and 8 C/C donors into forebrain‐lineage neural cultures. Our differentiation protocol yielded mixed neural cultures enriched for glutamatergic neurons. Basal mRNA expression of the GRIK1 locus was examined via quantitative polymerase chain reaction (qPCR). The effects of acute topiramate exposure on excitatory spontaneous synaptic activity were examined via whole‐cell patch‐clamp electrophysiology. Results were compared and contrasted between iPSC donor genotypes.

Results

Although characterization of the GRIK1 locus revealed no effect of rs2832407 genotype on GRIK1 isoform mRNA expression, a significant difference was observed on GRIK1 antisense‐2 expression, which was greater in C/C neural cultures. Differential effects of acute exposure to 5 μM topiramate were observed on spontaneous synaptic activity in A/A versus C/C neurons, with a smaller reduction in excitatory event frequency observed in C/C donor neurons.

Conclusions

This work highlights the use of iPSC technologies to study pharmacogenetic treatment effects in psychiatric disorders and furthers our understanding of the molecular effects of topiramate exposure in human neural cells.
Age‐based efficacy and safety of nivolumab for recurrent or metastatic head and neck squamous cell carcinoma: A multicenter retrospective study
Authors: Kondo Takahito , Okamoto Isaku , Sato Hiroki , Koyama Nobuyuki , Fushimi Chihiro , Okada Takuro , Masubuchi Tatsuo , Miura Kouki , Matsuki Takashi , Yamashita Taku , Omura Go , Takahashi Hideaki , Tsukahara Kiyoaki
Published: June 2020

Aim

This study retrospectively investigated the efficacy and safety of nivolumab for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) classified using age <65 years as the cutoff.

Methods

Overall, 88 patients with R/M HNSCC treated with nivolumab were classified into the young group (<65 years; n = 39) and elderly group (≥65 years; n = 49). Efficacy was evaluated using overall survival (OS), progression‐free survival (PFS), overall response rate (ORR) and disease control rate (DCR). Safety was evaluated considering immune‐related adverse events (irAEs).

Results

The median OS was 9.7 and 8.6 months in the young and elderly groups, respectively. The 1‐year OS rate was 42.0% and 29.4% in the young and elderly groups, respectively. The median PFS was 3.0 and 4.2 months in the young and elderly groups, respectively. The 1‐year PFS rate was 30.0% and 27.9% in the young and elderly groups, respectively. In the young group, the ORR was 10.3% and DCR was 33.3%. In the elderly group, the ORR was 18.4% and DCR was 53.1%. There were no significant differences in OS, PFS, ORR, and DCR (P = 0.36, 0.53, 0.29 and 0.06, respectively). Interstitial lung disease (ILD) as an irAE occurred in the young group at a significantly higher rate (20.5% vs 4.1%; P = 0.02).

Conclusions

There were no significant differences in OS, PFS, ORR, and DCR between the young and elderly groups. DCR tended to be better in the elderly group (P = 0.06). ILD occurred at a significantly higher rate in the young group.
Advances in immune neoadjuvant/adjuvant therapy‐related adverse events of non‐small cell lung cancer
Authors: Zhao Qingchun , Liu Chao , Liu Hongyu , Chen Jun
Published: June 2020

Lung cancer has been the leading cause of cancer‐related death for decades and years. For the patients with early stage non‐small cell lung cancer, surgical resection is the mainstay of therapy. Treatment before and after surgery, such as chemotherapy, can bring benefit to these patients, improving the 5 years survival rate by 5% approximately. Recently, the advent of immunotherapy significantly improved prognosis for the patient with lung cancer. Programmed death 1 and its ligand have become a powerful treatment option for lung cancer. In this review, we will discuss the role immunotherapy played in preoperative neoadjuvant and postoperative adjuvant treatment in lung cancer.
Placental location and risk of retained placenta in women with a previous cesarean section: A population‐based cohort study
Authors: Granfors Michaela , Sandström Anna , Stephansson Olof , Belachew Johanna , Axelsson Ove , Wikström Anna‐Karin
Published: June 2020

Introduction

Some studies have shown that women with a previous cesarean section, compared with women with a previous vaginal delivery, have an increased risk of retained placenta during a subsequent vaginal delivery. It is unknown whether this is mediated by anterior placental location, when the placenta might cover the uterine scar. The aim of this study was to evaluate whether the increased risk of retained placenta in women with a previous cesarean section is mediated by anterior placental location.

Material and methods

This is a population‐based cohort study, with data from the regional population‐based Stockholm‐Gotland Obstetric Cohort, Sweden, from 2008 to 2014. The overall study population included 49 598 women with a vaginal second delivery, where adequate information about placental location from the second‐trimester ultrasound scan was available. For the main analysis, including the 3921 women with a previous cesarean section, we calculated the relative risk of retained placenta in women with an anterior placental location, using women with non‐anterior placental locations as reference. Relative risks were calculated as odds ratios (OR) with 95% CI. In a second model, adjustments were made for maternal age, height, country of birth, smoking in early pregnancy, infant sex, and in vitro fertilization.

Results

In the overall study population, the rate of retained placenta at the second delivery was 2.0%. The proportion of women with a retained placenta was higher among women with a previous cesarean compared with those with a previous vaginal delivery (3.4% vs 1.9%; P < .0001). In the main analysis, including women with a previous cesarean section, the risk for retained placenta was not increased with anterior compared with non‐anterior placental location (OR 0.84, 95% CI 0.60‐1.20). Adjustments did not affect the estimates in a significant way.

Conclusions

The increased risk of retained placenta in women with a previous cesarean section is not mediated by anterior placental location.
The mean age of menarche among Chinese schoolgirls declined by 6 months from 2005 to 2014
Authors: Lei Yuanting , Luo Dongmei , Yan Xiaojin , Zhang Jingshu , Hu Peijin , Ma Jun , Song Yi , Lau Patrick W. C.
Published: June 2020

Aim

This study assessed the trends in the age at menarche in Chinese schoolgirls from the majority Han group and 21 ethnic minorities from 2005 to 2014. We also compared the group differences during the study period.

Methods

A total of 344 230 girls aged 9‐18 years were extracted from the 2005, 2010 and 2014 Chinese National Survey on Students' Constitution and Health. The age at menarche for each subgroup was estimated by probit analysis. The chi‐square test and Z‐test were used to compare the differences between the groups.

Results

The overall average age at menarche in Chinese schoolgirls decreased from 12.8 years in 2005 to 12.3 years in 2014. The Han girls and girls from 17 ethnic minorities showed decreasing trends in the age at menarche, while four ethnic minorities demonstrated fluctuating increasing trends over time. The gaps in age at menarche between the Han group and 14 of the ethnic minorities became smaller over the study period and were similar by 2014.

Conclusion

The overall findings were a decrease in the age at menarche in China and smaller gaps between the majority Han group and ethnic minority groups. Ethnic‐specific public health policies are urgently needed on issues such as contraception.
No benefit of continuing vs stopping 5‐aminosalicylates in patients with ulcerative colitis escalated to anti‐metabolite therapy
Authors: Singh Siddharth , Kim Jihoon , Zhu Wenhong , Dulai Parambir S. , Sandborn William J. , Jairath Vipul
Published: June 2020

Background

Whilst continuation of 5‐aminosalicylates (5‐ASA) after escalation to biologic therapy is considered ineffective in patients with ulcerative colitis (UC), their role in patients escalated to anti‐metabolites is unclear.

Aim

To compared patterns and outcomes of continuing vs stopping 5‐ASA in patients with UC who escalated to anti‐metabolite monotherapy, using a de‐identified administrative claims database.

Methods

We identified patients with UC who were new users of anti‐metabolite monotherapy who were receiving 5‐ASA, and were followed for at least 12 months after starting anti‐metabolite therapy. We evaluated patterns of 5‐ASA use (stopped 5‐ASA, short‐term 5‐ASA use for <6 months after starting anti‐metabolites, persistent 5‐ASA use for >6 months after starting anti‐metabolites). We compared outcomes (risk of UC‐related hospitalisation and/or surgery, need for corticosteroids, treatment escalation to biologic therapy) by pattern of 5‐ASA use, using Cox proportional hazard analysis adjusting for age, sex, race, comorbidity burden, and hospitalisation or emergency department visit, abdominal surgery and corticosteroid use in the previous 12 months (as measures of disease severity), with a 12‐month immortal time period.

Results

Of 4068 patients with UC who were new‐users of anti‐metabolite monotherapy, 578 (14.2%), 782 (19.2%) and 2708 (66.6%) stopped 5‐ASA, used 5‐ASA transiently or persistently, respectively. Compared to patients who stopped 5‐ASA after starting anti‐metabolites, persistent 5‐ASA use was associated with a higher risk of UC‐related hospitalisation (HR, 1.40 [1.07‐1.83]) and corticosteroid use (HR, 1.48 [1.28‐1.70]), without an increase in risk of UC‐related surgery (HR, 1.32 [0.86‐2.00]) or treatment escalation (HR, 0.80 [0.53‐1.20]). Sensitivity analyses using a 3 months window after initiation of anti‐metabolites to classify patients as continuing vs stopping 5‐ASA showed similar results. Residual confounding by disease severity could not be excluded.

Conclusion

5‐ASA are usually continued long‐term even after escalating to anti‐metabolite therapy in patients with UC without clinical benefit.
Quality improvement project identifies factors associated with delay in IBD diagnosis
Authors: Walker Gareth J. , Lin Simeng , Chanchlani Neil , Thomas Amanda , Hendy Peter , Heerasing Neel , Moore Lucy , Green Harry D. , Chee Desmond , Bewshea Claire , Mays Joseph , Kennedy Nicholas A. , Ahmad Tariq , Goodhand James R.
Published: June 2020

Background

Delay in the diagnosis of inflammatory bowel disease (IBD) is common and contemporary UK studies are lacking.

Aim

To determine factors associated with, and the consequences of, a prolonged time to diagnosis in IBD.

Methods

This quality improvement study included 304 adults with a new IBD diagnosis made between January 2014 and December 2017 across 49 general practices (GP) and gastroenterology secondary care services. Outcome measures were demographic, clinical and laboratory factors associated with a delayed time, defined as greater than upper quartile, to: (a) patient presentation (b) GP referral (c) secondary care diagnosis, and factors associated with a complicated disease course (hospitalisation and/or surgery and/or biologic treatment) in the year after diagnosis.

Results

The median [IQR] diagnosis sub‐intervals were: (a) patient = 2.1 months [0.9‐5.1]; (b) GP = 0.3 months [0.0‐0.9]; (c) secondary care = 1.1 months [0.5‐2.1]. 50% of patients were diagnosed within 4 months and 92% were diagnosed within 2 years of symptom onset. Diagnostic delay was more common in Crohn's disease (7.6 months [3.1‐15.0]) than ulcerative colitis (3.3 months [1.9‐7.3]) (P < 0.001). Patients who presented as an emergency (P < 0.001) but not those with a delayed overall time to diagnosis (P = 0.35) were more likely to have a complicated disease course.

Conclusion

Time to patient presentation is the largest component of time to IBD diagnosis. Emergency presentation is common and, unlike a delayed time to diagnosis, is associated with a complicated disease course.
Pyrrolidin‐2‐one linked benzofused heterocycles as novel small molecule monoacylglycerol lipase inhibitors and antinociceptive agents
Authors: Altamimi Abdulmalik Saleh Alfawaz , Bawa Sandhya , Athar Fareeda , Hassan Md Quamrul , Riadi Yassine , Afzal Obaid
Published: June 2020

Eighteen pyrrolidin‐2‐one linked benzothiazole, and benzimidazole derivatives (10–27) were designed and synthesized. The structure of the compounds was confirmed by elemental and spectral (IR, 1H‐NMR and MS) data analysis. All the compounds were screened by human monoacylglycerol lipase (hMAGL) inhibition assay. Three benzimidazole compounds, 22 (4‐Cl phenyl), 23 (3‐Cl,4‐F phenyl) and 25 (4‐methoxy phenyl) were found to be the most potent, having an IC50 value of 8.6, 8.0 and 9.4 nm, respectively. Among them, the halogen‐substituted phenyl derivatives, compound 22 (4‐Cl phenyl) and compound 23 (3‐Cl,4‐F phenyl), showed micromolar potency against fatty acid amide hydrolase (FAAH), having an IC50 value of 35 and 24 µm, respectively. Benzimidazole derivative having 4‐methoxyphenyl substitution (compound 25) was found to be a selective MAGL inhibitor (IC50 = 9.4 nm), with an IC50 value above 50 µm against FAAH. In the formalin‐induced nociception test, compound 25 showed a dose‐dependent reduction of pain response in both acute and late phases. At 30 mg/kg dose, it significantly reduced the pain response and showed greater potency than the reference drug gabapentin (GBP).
Enhanced Verbal Statistical Learning in Glossolalia
Authors: Kéri Szabolcs , Kállai Imre , Csigó Katalin
Published: June 2020

Glossolalia (“speaking in tongues”) is a rhythmic utterance of word‐like strings of sounds, regularly occurring in religious mass gatherings or various forms of private religious practices (e.g., prayer and meditation). Although specific verbal learning capacities may characterize glossolalists, empirical evidence is lacking. We administered three statistical learning tasks (artificial grammar, phoneme sequence, and visual‐response sequence) to 30 glossolalists and 30 matched control volunteers. In artificial grammar, participants decide whether pseudowords and sentences follow previously acquired implicit rules or not. In sequence learning, they gradually draw out rules from repeating regularities in sequences of speech sounds or motor responses. Results revealed enhanced artificial grammar and phoneme sequence learning performances in glossolalists compared to control volunteers. There were significant positive correlations between daily glossolalia activity and artificial grammar learning. These results indicate that glossolalists exhibit enhanced abilities to extract the statistical regularities of verbal information, which may be related to their unusual language abilities.
Strict selection criteria in uncontrolled donation after circulatory death provide excellent long‐term kidney graft survival
Authors: Miñambres Eduardo , Rodrigo Emilio , Suberviola Borja , Valero Rosalía , Quintana Alfredo , Campos Félix , Ruiz‐San Millán Juan Carlos , Ballesteros María Á.
Published: June 2020

Background

We aimed to report our experience in uncontrolled donation after circulatory death (uDCD) kidney transplantation applying a strict donor selection and preservation criteria.

Methods

All kidney recipients received a graft from a local uDCD. As controls, we included all renal transplants from local standard criteria donation after brain death (SDBD) donors. Normothermic regional perfusion was the preservation method in all cases.

Results

A total of 19 kidneys from uDCD donors were included and 67 controls. Delayed graft function (DGF) was higher in the uDCD group (42.1% vs 17.9%; P = .033), whereas no differences were observed in primary nonfunction (0% cases vs 3% controls; P = .605). The estimated glomerular filtration rate was identical in both groups. No differences were observed in graft survival censored for death between the uDCD and the SDBD groups at 1‐year (100% vs 95%) or 5‐year follow‐up (92% vs 91%). uDCD kidney recipients did not have higher risk of graft loss in the multivariate analysis adjusted by recipient age, cold ischemic time, presence of DGF, and second kidney transplant (HR: 0.4; 95% CI 0.02‐6; P = .509).

Conclusions

Obtaining renal grafts from uDCD is feasible in a small city and provides similar outcomes compared to standard DBD donors.
Survival and renal function after liver transplantation alone in patients meeting the new United Network for Organ Sharing simultaneous liver‐kidney criteria
Authors: Jiang Da David , Roayaie Kayvan , Woodland David , Orloff Susan , Scott David
Published: June 2020

In 2017, United Network for Organ Sharing (UNOS) implemented a simultaneous liver‐kidney transplant (SLK) allocation policy. Our institution uses a more restrictive criteria for SLK; thus, we have a group of patients that would have qualified for SLK under the new allocation policy but received liver transplantation alone (LTA). We compared survival and post‐operative renal function in patients that received LTA stratified by whether they met the new UNOS SLK criteria. There was no difference in graft and patient survival. The majority (95%) of LTA patients meeting the UNOS SLK criteria did not need dialysis at 1 year, with a mean eGFR increase from 23 mL/min preoperatively to 48 mL/min at 1 year. Of those with eGFR ≤ 20 mL/min at 1 month after surgery, the majority did regain adequate renal function. The implementation of the UNOS SLK allocation policy was appropriate in the previously unregulated area. This policy provides an excellent framework for those that may benefit from SLK. Our data suggest that a more restrictive policy may be possible in order to promote the best use of donated organs. The current safety net is appropriately positioned to capture patients in need of subsequent kidney transplant.
Quality Reference in Consumer Product Recalls
Authors: Dong Yan , Xu Kefeng , Song Sining , Zhou Chen
Published: June 2020

Product recalls are often associated with quality failures and may negatively affect customer satisfaction and firm performance. Motivated by counterintuitive anecdotal evidence on the positive relationship between recalls and sales, we develop an endogenous consumer reference model with stochastic quality levels and consumer valuation of gain‐loss utility to examine the consumer's willingness to buy in the event of a recall. A consumer makes purchasing decisions by evaluating gain‐loss values against a quality reference point. The theory of endogenous reference points incorporates the consumer's expectations of buying into forming a reference point based on the consumer's beliefs about quality outcomes (Kőszegi & Rabin, 2006, 2007). The uncertainty of the consumer's quality expectations combined with the consumer's personal equilibrium makes the reference point endogenous, generating predictions different from those under conventional exogenous reference point and in the case of deterministic quality expectations. We find that a product recall may revise the consumer's belief toward a more negative quality outcome, and therefore, a lower reference point, when quality expectations are uncertain and the consumer's reference point is endogenous. The consumer expects a greater gain from buying the product against the lower reference point, leading to a higher willingness to buy. In addition, we find that supply chain offshoring, which may be associated with consumer evaluation of gain‐loss utility or consumer loss aversion, may complicate the effect of recalls on a consumer's willingness to buy. These results suggest that firms should consider consumer preferences under uncertainty when designing and developing their global supply chain strategies in quality management.
Together we lived, and alone you died: Loneliness and solidarity in Gaza
Authors: Lederman Zohar
Published: June 2020

This essay discusses and weaves together three interrelated topics: loneliness as a neglected bioethics problem, solidarity as one potential solution to loneliness, and the Israeli‐Palestinian Conflict as a neglected bioethics problem in which loneliness is stark. I first present and define various kinds of loneliness, focusing on ethical loneliness, defined as suffering injustice without a proper repair process. I next discuss current health conditions in Gaza, focusing on healthcare providers who, according to the UN, are being intentionally targeted by Israel. I explain how the various kinds of loneliness are reflected among people in Gaza. I lastly relate together the notions of solidarity, responsibility and personal autonomy, arguing that bioethicists and healthcare providers have a duty to support the people in Gaza, stemming from solidarity and an extended responsibility perspective.
Regulation of genes for ubiquitination and SUMO‐specific protease involved in larval development of the silkworm, Bombyx mori
Authors: Kitagawa Tsuyuki , Takiya Shigeharu
Published: June 2020

Protein modifications with highly conserved small proteins, such as ubiquitin (Ub) and small ubiquitin‐like modifier (SUMO), regulate various cellular processes; however, the contribution of these protein modifications to larval development in insects has not yet been elucidated. We investigated the regulation of genes for these protein modifications in the posterior silk gland (PSG) during larval development of the silkworm Bombyx mori. We found that several genes encoding enzymes (E1, E2, and E3) for ubiquitination and SUMO‐specific protease were upregulated by 20‐hydroxyecdysone (20E), and, consistently, increases in ubiquitinated proteins were observed during the fourth molting stage. An injection of 20E into larvae at the fourth feeding stage induced higher expression levels of these E1, E2, and E3 genes and ecdysis approximately one day earlier than in mock‐treated larvae. The expression of the fibroin heavy‐chain gene (fibH) was simultaneously suppressed approximately one day earlier in 20E‐injected larvae. The treatment of cultured PSG with 20E also induced these genes, which could be categorized into at least two types: those induced by a high dose of 20E, or by a pulse of 20E. In contrast to the 20E treatment, the administration of PR‐619, an inhibitor of Ub‐ and SUMO‐specific proteases in larvae, delayed ecdysis and prolonged the expression of fibH. These results suggest that the regulation of genes for ubiquitination and SUMO‐specific protease is involved in the larval development of B. mori.
Landscape scale variation in the hydrologic niche of California coast redwood
Authors: Francis Emily J. , Asner Gregory P. , Mach Katharine J. , Field Christopher B.
Published: June 2020

Topoclimatic diversity within forest landscapes can underlie variation in water availability, which may correspond to patterns in habitat suitability of tree species with differing hydrologic niches. However, the trade‐off between the collection of data at a fine grain size over large spatial extents has limited comprehensive analyses of landscape scale variation in habitat suitability. We present a fine scale analysis of the roles of topographic gradients in moisture availability, soil water storage and fog frequency in the spatial pattern of habitat suitability for coast redwood Sequoia sempervirens, at 10 m resolution across 34 800 ha and three landscapes spanning approximately one‐third of redwood's latitudinal range. A new 10 m resolution presence‐absence map derived from airborne imaging spectroscopy was used to characterize current redwood distributions in three landscapes. Access to belowground moisture was assessed through four measures calculated from a high‐resolution LiDAR digital elevation model, soil water storage was mapped from the USDA Soil Survey Geographic Database, and fog frequency was calculated from MODIS cloud cover data. Access to belowground moisture and fog predicted variation in suitability as redwood habitat from 22–75% and predicted redwood presence and absence at 10 m resolution with 63–74% accuracy. Across all three landscapes, redwood density consistently decreased with increasing interpolated height above a stream (IHAS), but the role of other predictors varied among the sites. Our results challenge previous assumptions that redwood habitat suitability within much coarser resolutions (800 m × 800 m) can be described by a single value. The elevated habitat suitability of sites close to streams suggests that these sites should be evaluated for their potential to become microrefugia within landscapes that may become climatically‐unsuitable for redwoods at a regional scale.
Agri‐environment conservation set‐asides have co‐benefits for connectivity
Authors: Threadgill Katie R. D. , McClean Colin J. , Hodgson Jenny A. , Jones Naomi , Hill Jane K.
Published: June 2020

Widespread declines in farmland biodiversity have led to state‐funded schemes which take land out of production to create (semi‐)natural habitats for biodiversity (e.g. EU agri‐environment schemes; US Conservation Reserve Program). Common features of such schemes are grassland strips at the edges of agricultural fields, and we examine potential co‐benefits of these biodiversity set‐asides for contributing to grassland connectivity. Although set‐aside strips had negligible impact on landscape‐scale species persistence (using metapopulation models parameterized for flying insects run on 267 landscapes of ~30 000 ha across England), they nonetheless improved connectivity in 74% (198/267) of landscapes (comparing landscapes with and without set‐asides), as shown by range expansion rates increasing by up to 100%. Benefits of set‐aside strips varied according to species type (high/low dispersal, high/low population density), but had little benefit for species with low dispersal and small population sizes, which generally failed to expand. High dispersal/high density species were already successful expanders regardless of set‐asides (> 75% of simulations were successful without set‐asides) although expansion rates were still improved when set‐asides were added. Whilst alternative strategies for placement of set‐aside strips (more/less aggregated), revealed no consensus ‘better’ strategy across species types, set‐aside benefits were generally greatest in landscapes with intermediate availability of semi‐natural grassland (0.5‐4% cover). We conclude that small‐scale set‐asides have the potential to improve connectivity, which we expect to help some species track climate change, and connect habitat patches within existing climate space for others. However, set‐asides are unlikely to benefit low dispersal species which are probably at greatest risk from agricultural intensification.