bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure‐Antioxidant Activity Relationships of Luteolin and Catechin
Authors: Ahmadi Seyed Mohammad , Farhoosh Reza , Sharif Ali , Rezaie Mitra
Published: January 2020

Antioxidant activity of the natural flavonoids luteolin and catechin, which shows inconsistent comparative results in literature, was extensively evaluated as affected by the 1,4‐pyrone moiety and 3–OH group. Catechin and luteolin were compared to the synthetic antioxidant‐butylated hydroxytoluene for their 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH●) scavenging activity in polar protic and aprotic solvents and ferric reducing‐antioxidant power (FRAP). Moreover, their effect on lipid oxidation kinetics of canola and olive oil triacylglycerols as well as their oil‐in‐water (O/W) emulsions, in addition to oil stability indices (OSIs), was evaluated. In the DPPH● assay, catechin's 3–OH group led to lower IC50 values than luteolin's 1,4‐pyrone moiety in acetone (3.4 µM compared with 9.4 µM), while there was no significant difference in methanol (IC50 = approximately 18.3 µM) or tetrahydrofuran (IC50 = approximately 27.2 µM). The FRAP test indicated a higher reducing power for catechin than for luteolin (689.4 µM compared with 573.1 µM). The antioxidants showed various performances in the oil triacylglycerols and their O/W emulsions due predominantly to the interfacial phenomena. A better OSI was found for catechin than for luteolin (20.0 to 52.7 hr compared with 3.5 to 4.2 hr) in Rancimat test.
Effects of germination conditions on enzyme activities and starch hydrolysis of long‐grain brown rice in relation to flour properties and bread qualities
Authors: Wunthunyarat Wipada , Seo Han‐Seok , Wang Ya‐Jane
Published: January 2020

Gluten‐free products from rice are gaining popularity because of its hypoallergenic characteristic. The absence of gluten results in inferior bread qualities such as hard texture, reduced volume, and shorter shelf‐life. Hydrolytic enzymes are activated during germination to stimulate plant growth, and germinated brown rice (GBR) has been shown to improve gluten‐free bread properties. However, the changes in hydrolytic enzyme activities under different germination conditions and their relationship with the properties of germinated rice flour and bread have not been reported. Therefore, the objectives of this work were to investigate the activities of amylases and protease in GBR under aerobic and anaerobic germination for 2 and 4 days and their impacts on starch hydrolysis, flour properties, and bread qualities. Greater enzyme activities were observed in GBR germinated under aerobic condition and a longer time, and correlated with increased sugar content and foaming capacity. Breads were prepared from GBR along with brown rice (control). GBR breads showed a greater specific volume (4% to 10%), a reduced hardness (34% to 90%), and a lower starch retrogradation (66% to 90%) compared with the control. Bread prepared from 4‐day aerobic GBR had the largest reduction in starch molecular size and displayed the lowest hardness and starch retrogradation. After stored for 5 days, GBR breads exhibited no change in specific volume and less hardness and retrogradation than the control bread. In conclusion, greater activities of protease and amylases in GBR significantly increased foaming capacity and reduced starch molecule size, respectively, which were responsible for the improved GBR bread qualities.

Practical Application

Rice flour is widely used as the main ingredient in gluten‐free breads, which however tend to have poor texture and reduced shelf‐life due to the absence of gluten. The qualities of gluten‐free breads are usually improved by the addition of many ingredients such as tapioca and potato starches. Germination process naturally produces bioactive compounds and activates enzymes. Germination conditions that produce greater activities of amylases and protease can be used to produce gluten‐free breads with better qualities and longer shelf‐life without the addition of starch.
R&D Investments and Tax Incentives: The Role of Intra‐Firm Cross‐Border Collaboration*
Authors: Huang Jing , Krull Linda , Ziedonis Rosemarie
Published: January 2020

U.S. multinational corporations increasingly use intra‐firm, cross‐border research collaboration to disperse R&D across different countries. This paper investigates the implications of such collaboration on the abilities of firms to garner benefits from R&D tax incentives. We find that the association between R&D intensity and tax incentives is three to five times larger when firms have extensive cross‐border collaboration connected to a country. We also find that the effect is stronger when local intellectual property protection is weaker and when local innovation resources are higher. Our results suggest that cross‐border collaboration helps firms achieve more tax‐efficient R&D investments both by reducing the nontax frictions posed by weak intellectual property protection and by increasing the nontax benefits of foreign R&D.
Concept Development of Identification of Discomfort for Nursing Home Patients With Advanced Dementia
Authors: Lee Su Jung , Park Min Sun , Choi Young‐Rim , Chang Sung Ok
Published: January 2020

PURPOSE

The aim of this study is to clarify the concept of discomfort identification by concept development in the nursing home.

METHODS

The Schwartz–Barcott and Kim's hybrid model was used.

FINDINGS

The identification of discomfort can be explained as an interactive and confirmative process of sympathetically responding to patients with dementia's problem behavior expressions that communicate unmet needs.

CONCLUSIONS

The identification of discomfort has the potential to improve the detection of multidimensional discomfort related to nursing diagnosis as a holistic and patient‐centered approach.

IMPLICATION FOR NURSING PRACTICE

The findings could help nursing home nurses have a better understanding of identification of discomfort and can improve nurses and interdisciplinary caregivers' knowledge for developing appropriate comfort caring activities.
The Addictions Neuroclinical Assessment Negative Emotionality Domain Among Treatment‐Seekers with Alcohol Use Disorder: Construct Validity and Measurement Invariance
Authors: Votaw Victoria R. , Pearson Matthew R. , Stein Elena , Witkiewitz Katie
Published: January 2020

Background

The Addictions Neuroclinical Assessment (ANA), a framework for measuring heterogeneity in alcohol use disorder (AUD), focuses on 3 domains that reflect neurobiological dysfunction in addiction and correspond to the cycles of addiction: executive function, incentive salience, and negative emotionality. Kwako and colleagues (Am J Psychiatry 176:744, 2019) validated a 3‐factor model of the ANA with neuropsychological and self‐report indicators among treatment‐seekers and non–treatment‐seekers with and without AUD. The present analysis replicated and extended these findings in a treatment‐seeking sample, focusing on the negative emotionality domain.

Methods

Participants (n = 563; 58.8% male; mean age = 34.3) were part of a multisite prospective study of individuals entering AUD treatment. We examined the factor structure of the negative emotionality domain at the baseline, 6‐month follow‐up, and 12‐month follow‐up assessments. The Beck Depression Inventory, Beck Anxiety Inventory, State‐Trait Anger Expression Inventory‐Trait Anger Subscale, and 3 Drinker Inventory of Consequences items assessing negative affective consequences were indicators in the model.

Results

Results indicated that a 1‐factor model was an excellent fit at all assessments and that the negative emotionality domain was time and gender invariant. Furthermore, negative emotionality was associated with drinking patterns and reasons for alcohol use (i.e., drinking because of negative emotions and urges/withdrawal) at all assessments.

Conclusions

This analysis provides evidence for the construct validity and measurement invariance of the ANA negative emotionality domain among AUD treatment‐seekers. Future studies are needed to evaluate prospective associations between negative emotionality and specific treatment modalities, and whether individuals with greater negative emotionality are more likely to respond to treatment that targets drinking to relieve negative affective states.
Effect of exercise prehabilitation on functional status of patients undergoing bowel resection: a systematic review
Authors: Teo Joshua Y. K. , Turner Richard , Self Mary
Published: January 2020

Background

Bowel resections have high morbidity and mortality rates and are becoming increasingly common in Australia. To reduce the burden on patients and the health system, measures for improving patient outcomes after resection must be investigated. One possible method for improving patient outcomes is prehabilitation with exercise. The aim of this systematic review is to determine the effect that exercise prehabilitation has on the functional status of patients undergoing colorectal resection.

Method

Studies examining the effect of exercise prehabilitation on colorectal patients were gathered from online databases, including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and the Australia New Zealand clinical trial registry. The study design, population, intervention and outcomes were extracted from each study.

Results

This systematic review included six studies involving a total of 415 patients. Three studies were randomized control trials and three were prospective cohort studies. Those that tested participants post‐operatively found that the intervention group improved their 6‐min walking distance more than the control group. This result was statistically significant in three studies. Similarly, two studies found that self‐reported physical activity was significantly greater in the intervention group than in control groups. The rate of complications and length of hospital stay were not significantly different between intervention and control groups in any study.

Conclusion

Prehabilitation significantly improves functional capacity and self‐reported physical activity but its effect on complication rate was not significant in this review.
Intramuscular pathway and fascicular characteristics of the segmental intercostal innervation to rectus abdominis
Authors: Grinsell Damien , Azizeddin Arshia , Overland Joseph
Published: January 2020

Background

Rectus abdominis is a muscle that is commonly used clinically as a muscle flap, especially in reconstructive surgery. Its intramuscular innervation, however, has rarely been examined in detail or accurately mapped. The purpose of this study was to use biopsied, histological specimens complemented with a staining technique to investigate intramuscular nerve connections and distribution of the rectus abdominis.

Methods

Four fresh human cadavers were included in the study and rectus abdominis was dissected bilaterally. Nerve sections innervating the rectus abdominis were biopsied and histologically processed. Sections were viewed under the microscope, and axons within each fascicle were counted using imaging software. All specimens were stained with a modified Sihler's staining technique. Intramuscular innervation was observed and the number as well as distribution was recorded.

Results

Macroscopically stained specimens showed that the eighth, ninth, 10th and 12th intercostal nerves innervated the eight muscle bellies of rectus abdominis. The greatest number of minor nerve branching as well as intramuscular nerve communications originated from nerve roots T9 and T10. Minor nerve branches crossed tendinous intersections to communicate with adjacent nerves and innervate adjacent muscle bellies. Nerves originating from T9 had the greatest number of nerve fascicles and the highest axon count in each cadaver.

Conclusion

The rectus abdominis is divided into four compartments with each receiving its own independent nerve supply. Minor nerve branches crossed tendinous intersections to communicate with adjacent muscle bellies and nerves suggesting that rectus abdominis can be used as a whole in innervated free flap transfer procedures.
Do anti‐tumour necrosis factor‐α biologics affect subclinical measures of atherosclerosis and arteriosclerosis? A systematic review
Authors: Knowles Laurence , Nadeem Nida , Chowienczyk Philip J.
Published: January 2020

Aims: Inflammatory cytokines, particularly tumour necrosis factor‐α (TNFα), are thought to promote arterial disease through a variety of mechanisms leading to arteriosclerosis and atherosclerosis. We reviewed the existing evidence of the effect of anti‐TNFα treatment on arteriosclerosis and atherosclerosis in chronic inflammatory disease.

Methods: We performed a systematic review of studies examining effects of monoclonal antibodies against TNFα on subclinical measures of arteriosclerosis (arterial pulse wave velocity) and atherosclerosis (endothelial function measured by flow‐mediated dilation or forearm blood flow responses to endothelium‐dependent agonists, and common carotid intima‐media thickness).

Results: We identified 60 studies (of 854 potential studies identified using a systematic search) in which effects of anti‐TNFα biologics on these measures were assessed in patients receiving anti‐TNFα therapy for a clinical indication (usually an inflammatory disease such as an inflammatory arthritis, psoriasis or inflammatory bowel disease). Of these, only 6 were randomised clinical controlled trials. Whilst many observational studies and noncontrolled studies reported positive findings, positive finding were reported in only 1 of 6 randomised clinical controlled trials.

Conclusions: There is no strong evidence for an effect of anti‐TNFα biologics on the subclinical measures of arteriosclerosis or atherosclerosis examined in this review. This does not exclude a positive effect of TNFα biologics on clinical outcomes through alternate pathways including those induced by remission of the primary inflammatory disease.
Disentangling drivers of small mammal diversity in a highly fragmented forest system
Authors: de la Sancha Noe U. , Maestri Renan , Bovendorp Ricardo S. , Higgins Christopher L.
Published: January 2020

The Atlantic Forest is the second most diverse forest system in South America, and only a fraction of its original distribution remains. In this study, we aim to use robust datasets of small mammals along the entire forest system to disentangle the main drivers for diversity along this gradient. More specifically, we aim to disentangle whether deforestation (recent), biogeographical variables, including 19 bioclimatic variables (historic), or historical trapping bias best describe patterns of taxonomic, functional, and phylogenetic diversities using small mammal assembles, from northeastern Brazil to eastern Paraguay. For that, we applied regression tree analyses to determine what environmental variables best describe each of the dimensions of diversity. Additionally, we implemented polynomial regression to test nonlinear relationships between biodiversity metrics and patch size. We found that patterns of overall taxonomic, functional, and phylogenetic diversities; rodent taxonomic diversity; and marsupial functional diversity were better explained by temperature variables. Meanwhile, marsupial taxonomic and phylogenetic diversities, and rodent functional and phylogenetic diversities were best explained by precipitation variables. Furthermore, patch area, trapping, and latitude were never the best descriptors for any of the diversity dimensions. Although all dimensions of biodiversity are correlated, they have unique information and should be considered individually to better understand biodiversity and inform conservation strategies. We found that fragmentation is impactful at a local scale and becomes less important at a biogeographical scale. Therefore, climatic variables drove biogeographical faunal patterns for all clades, probably reflecting important historical assembly process at large spatial scales.
The circular construction of “risk” for children of oppressed groups: Israeli social workers' perspectives on children of Ethiopian origin
Authors: Engdau‐Vanda Shelly
Published: January 2020

This article presents the findings of a research project that explored the perceptions and constructions of Israeli social workers, serving families of Ethiopian origin in Israel, regarding “risk” vis‐à‐vis the children of this community. Thirty semistructured in‐depth interviews with social workers of Ethiopian and non‐Ethiopian origin were conducted and thematically analysed. The study findings indicate that the risk posed to children from the Ethiopian community, as conceived by the social workers charged with their treatment, tends to emerge in the interface between four main contexts: the societal, the neighbourhood, the education system, and the welfare system. Resembling the cycle of poverty, in which a cyclical set of forces trap people in perpetual poverty, children from minority groups are often caught in a cycle of risk. In each of these four contexts, a circular movement was observed in the construction of risk. Breaking the circularity of “risk” requires a context‐informed approach that adopts the perspectives of critical theories, which consider structural factors, power relations, and sociopolitical context when assessing “risk” for children in general, and for children of oppressed groups in particular.
Variants in NGLY1 lead to intellectual disability, myoclonus epilepsy, sensorimotor axonal polyneuropathy and mitochondrial dysfunction
Authors: Panneman Daan M. , Wortmann Saskia B. , Haaxma Charlotte A. , van Hasselt Peter M. , Wolf Nicole I. , Hendriks Yvonne , Küsters Benno , van Emst‐de Vries Sjenet , van de Westerlo Els , Koopman Werner J.H. , Wintjes Liesbeth , van den Brandt Frans , de Vries Maaike , Lefeber Dirk J. , Smeitink Jan A.M. , Rodenburg Richard J.
Published: January 2020

NGLY1 encodes the enzyme N‐glycanase that is involved in the degradation of glycoproteins as part of the endoplasmatic reticulum‐associated degradation pathway. Variants in this gene have been described to cause a multisystem disease characterized by neuromotor impairment, neuropathy, intellectual disability, and dysmorphic features. Here, we describe four patients with pathogenic variants in NGLY1. As the clinical features and laboratory results of the patients suggested a multisystem mitochondrial disease, a muscle biopsy had been performed. Biochemical analysis in muscle showed a strongly reduced ATP production rate in all patients, while individual OXPHOS enzyme activities varied from normal to reduced. No causative variants in any mitochondrial disease genes were found using mtDNA analysis and whole exome sequencing. In all four patients, variants in NGLY1 were identified, including two unreported variants (c.849T>G (p.(Cys283Trp)) and c.1067A>G (p.(Glu356Gly)). Western blot analysis of N‐glycanase in muscle and fibroblasts showed a complete absence of N‐glycanase. One patient showed a decreased basal and maximal oxygen consumption rates in fibroblasts. Mitochondrial morphofunction fibroblast analysis showed patient specific differences when compared to control cell lines. In conclusion, variants in NGLY1 affect mitochondrial energy metabolism which in turn might contribute to the clinical disease course.
SPAG5‐AS1 inhibited autophagy and aggravated apoptosis of podocytes via SPAG5/AKT/mTOR pathway
Authors: Xu Jun , Deng Yujie , Wang Yi , Sun Xiaofang , Chen Shuqin , Fu Guoxiang
Published: January 2020

Objectives

Podocyte injury is a prediction marker of diabetic nephropathy (DN), and AKT/mTOR pathway–mediated inhibition of autophagy is widely reported to contribute to podocyte damage. Recent study stated that sperm‐associated antigen 5 (SPAG5) activated AKT/mTOR signalling in bladder urothelial carcinoma, indicating SPAG5 might regulate autophagy and play a role in podocyte damage.

Materials and methods

Apoptosis and autophagy of human podocytes (HPCs) were detected by flow cytometry and immunofluorescence (IF). Gene level was assessed by Western blot and RT‐qPCR. Molecular interactions were determined by pulldown, RNA immunoprecipitation (RIP), co‐immunoprecipitation (co‐IP), chromatin immunoprecipitation (ChIP) and luciferase reporter assays.

Results

SPAG5 mRNA and protein levels were upregulated under high glucose treatment in HPCs. Silencing SPAG5 reversed the increase of apoptosis and decrease of autophagy in high glucose–treated HPCs. Later, we found a long non‐coding RNA (lncRNA) SPAG5 antisense RNA1 (SPAG5‐AS1) as a neighbour gene to SPAG5. Mechanistically, YY1 transcriptionally upregulated SPAG5‐AS1 and SPAG5 in high glucose–treated podocytes. SPAG5‐AS1 acted as a competitive endogenous RNA (ceRNA) to regulate miR‐769‐5p/YY1 axis and induce SPAG5. SPAG5‐AS1 interacted with ubiquitin‐specific peptidase 14 (USP14) and leads to de‐ubiquitination and stabilization of SPAG5 protein.

Conclusions

This study revealed that SPAG5‐AS1 inhibited autophagy and aggravated apoptosis of podocytes via SPAG5/AKT/mTOR pathway, indicating SPAG5‐AS1/SPAG5 as a potential target for the alleviation of podocyte injury and offering new thoughts for the treatments of DN.
A stroke volume‐based fluid resuscitation protocol decreases vasopressor support and may increase organ yield in brain‐dead donors
Authors: Marklin Gary F. , Klinkenberg William Dean , Helmers Benjamin , Ahrens Thomas
Published: January 2020

Brain‐dead donors are frequently hypovolemic and hypotensive requiring vasopressor support. We studied a stroke volume‐based fluid resuscitation and vasopressor weaning protocol prospectively on 64 hypotensive donors, with a recent control cohort of 30 hypotensive donors treated without a protocol. Stroke volume was measured every 30 minutes for 4 hours by pulse contour analysis or esophageal Doppler. A 500 mL saline fluid bolus was infused over 30 minutes and repeated if the stroke volume increased by 10%. No fluid was infused if the stroke volume did not increase by 10%. Vasopressors were weaned every 10 minutes if the mean arterial pressure was greater than 65 mm Hg. The protocol group received 1937 ± 906 mL fluid compared to 1323 ± 919 mL in the control group (P = .003). Mean time on vasopressors was decreased from 957.6 ± 586.2 to 176.3 ± 82.2 minutes (P<.001). Donors in the protocol group were more likely to donate four or more organs than donors in the control group (OR = 4.114, 95% Confidence Interval (CI) = 1.003‐16.876). While more organs were transplanted per donor in the protocol group (3.39 ± 1.52) than in the control group (2.93 ± 1.44) (P = .268), the difference did not reach statistical significance. A goal‐directed fluid resuscitation protocol decreased organ ischemia and may increase organs transplanted.
The cytopathologist's role in developing and evaluating artificial intelligence in cytopathology practice
Authors: McAlpine Ewen D. , Michelow Pamela
Published: January 2020

Artificial intelligence (AI) technologies have the potential to transform cytopathology practice, and it is important for cytopathologists to embrace this and place themselves at the forefront of implementing these technologies in cytopathology. This review illustrates an archetypal AI workflow from project conception to implementation in a diagnostic setting and illustrates the cytopathologist's role and level of involvement at each stage of the process. Cytopathologists need to develop and maintain a basic understanding of AI, drive decisions regarding the development and implementation of AI in cytopathology, participate in the generation of datasets used to train and evaluate AI algorithms, understand how the performance of these algorithms is assessed, participate in the validation of these algorithms (either at a regulatory level or in the laboratory setting), and ensure continuous quality assurance of algorithms deployed in a diagnostic setting. In addition, cytopathologists should ensure that these algorithms are developed, trained, tested and deployed in an ethical manner. Cytopathologists need to become informed consumers of these AI algorithms by understanding their workings and limitations, how their performance is assessed and how to validate and verify their output in clinical practice.
Appropriate fabrication method for vacuum‐formed mouthguards using polyolefin sheets
Authors: Mizuhashi Fumi , Koide Kaoru
Published: January 2020

Background/Aims

The appropriate heating conditions for polyolefin sheets have not yet been determined and polyolefin sheets are usually formed in the same manner as ethylene vinyl acetate sheets. The aim of this study was to examine the appropriate heating conditions for polyolefin sheets when fabricating vacuum‐formed mouthguards.

Materials and methods

Mouthguard sheets of 3.0 mm polyolefin were vacuum formed on working models at three heating temperatures: 90°C, 105°C, and 120°C. The thickness of the mouthguard was measured at the labial surface of the central incisor, and the buccal and occlusal surfaces of the first molar. The fit of the mouthguard was examined at the central incisor and the first molar by measuring the distance between the mouthguard and the cervical margin of the working model. Differences in the thickness and fit of the mouthguards according to the heating conditions and the measured regions were analyzed by two‐way analysis of variance.

Results

Mouthguard thickness varied among the measured regions of the central incisors and first molars (P < .01). The smallest thickness was found at the labial surface of the central incisor in mouthguards fabricated at 90°C (P < .01). The smallest thickness was found at the buccal and occlusal surface of the first molar in mouthguards fabricated at 120°C (P < .01). The worst fit was obtained with the heating temperature of 90°C (P < .01).

Conclusions

The appropriate heating temperature for polyolefin sheets was 105°C to maintain mouthguard thickness and to obtain proper fit.
“I'm tired of being pulled from pillar to post”: A qualitative analysis of barriers to mental health care for trauma‐exposed young people
Authors: Ellinghaus Carli , Truss Katie , Liao Siling Jocelyn , Phillips Lisa , Eastwood Oliver , Medrano Carmen , Bendall Sarah
Published: January 2020

Aim

Traumatic experiences in childhood are pervasive and associated with a range of deleterious mental health outcomes. Despite this, trauma‐exposed young people often do not seek help from mental health services. While barriers to care for general mental health concerns are well established, less is known about those specifically facing young people who have experienced trauma. The present paper sought to examine the barriers in seeking mental health care faced by trauma‐exposed young people through a qualitative analysis of online forums where individuals discuss and seek informal support for trauma.

Methods

This study used a qualitative, netnographic design, following the six‐step LiLEDDa framework, developed for the analysis of online forums. Posts about trauma written in 2016 from five Internet forums targeting young people were included and analysed via thematic analysis.

Results

Barriers to mental health care for trauma‐exposed young people were categorized into two interrelated themes: (a) structural and (b) relational barriers. Structural barriers related to practical challenges faced when accessing and engaging with mental health services. Relational barriers focused on interpersonal relationships with mental health service providers and how these influenced experiences of, and consequent engagement with, services.

Conclusions

Trauma‐exposed young people appear to experience multiple barriers to mental health care, whereby interactions between structural and relational barriers determine ongoing engagement. Service‐wide reform including trauma‐informed mental health training for practitioners is urgently needed to improve access to care and engagement for this vulnerable group.
Genetic diagnoses in epilepsy: The impact of dynamic exome analysis in a pediatric cohort
Authors: Rochtus Anne , Olson Heather E. , Smith Lacey , Keith Louisa G. , El Achkar Christelle , Taylor Alan , Mahida Sonal , Park Meredith , Kelly McKenna , Shain Catherine , Rockowitz Shira , Rosen Sheidley Beth , Poduri Annapurna
Published: January 2020

Objective

We evaluated the yield of systematic analysis and/or reanalysis of whole exome sequencing (WES) data from a cohort of well‐phenotyped pediatric patients with epilepsy and suspected but previously undetermined genetic etiology.

Methods

We identified and phenotyped 125 participants with pediatric epilepsy. Etiology was unexplained at the time of enrollment despite clinical testing, which included chromosomal microarray (57 patients), epilepsy gene panel (n = 48), both (n = 28), or WES (n = 8). Clinical epilepsy diagnoses included developmental and epileptic encephalopathy (DEE), febrile infection‐related epilepsy syndrome, Rasmussen encephalitis, and other focal and generalized epilepsies. We analyzed WES data and compared the yield in participants with and without prior clinical genetic testing.

Results

Overall, we identified pathogenic or likely pathogenic variants in 40% (50/125) of our study participants. Nine patients with DEE had genetic variants in recently published genes that had not been recognized as epilepsy‐related at the time of clinical testing (FGF12, GABBR1, GABBR2, ITPA, KAT6A, PTPN23, RHOBTB2, SATB2), and eight patients had genetic variants in candidate epilepsy genes (CAMTA1, FAT3, GABRA6, HUWE1, PTCHD1). Ninety participants had concomitant or subsequent clinical genetic testing, which was ultimately explanatory for 26% (23/90). Of the 67 participants whose molecular diagnoses were "unsolved" through clinical genetic testing, we identified pathogenic or likely pathogenic variants in 17 (25%).

Significance

Our data argue for early consideration of WES with iterative reanalysis for patients with epilepsy, particularly those with DEE or epilepsy with intellectual disability. Rigorous analysis of WES data of well‐phenotyped patients with epilepsy leads to a broader understanding of gene‐specific phenotypic spectra as well as candidate disease gene identification. We illustrate the dynamic nature of genetic diagnosis over time, with analysis and in some cases reanalysis of exome data leading to the identification of disease‐associated variants among participants with previously nondiagnostic results from a variety of clinical testing strategies.
Blinking behavior in great‐tailed grackles (Quiscalus mexicanus) increases during simulated rainfall
Authors: Yorzinski Jessica L.
Published: January 2020

Animals often adjust their behavior in response to changes in environmental conditions, and these behavioral adjustments may result from sensory constraints. In particular, rainfall influences behavior but our understanding of its effects on visual abilities is limited. This study, therefore, tested the hypothesis that rainfall influences blinking behavior, a major component of visual processing, in captive great‐tailed grackles (Quiscalus mexicanus). The blinking behavior of the grackles was recorded when they were exposed to simulated rain that was direct (water falling directly atop them) or indirect (water falling at a distance from them). The grackles exhibited increased blinking behavior when they were exposed to the direct rain but not the indirect rain. These results suggest that rainfall may impact visual processing in birds through sensory impairments.
Origin of volatile organic compound emissions from subarctic tundra under global warming
Authors: Ghirardo Andrea , Lindstein Frida , Koch Kerstin , Buegger Franz , Schloter Michael , Albert Andreas , Michelsen Anders , Winkler J. Barbro , Schnitzler Jörg‐Peter , Rinnan Riikka
Published: January 2020

Warming occurs in the Arctic twice as fast as the global average, which in turn leads to a large enhancement in terpenoid emissions from vegetation. Volatile terpenoids are the main class of biogenic volatile organic compounds (VOCs) that play crucial roles in atmospheric chemistry and climate. However, the biochemical mechanisms behind the temperature‐dependent increase in VOC emissions from subarctic ecosystems are largely unexplored. Using 13CO2‐labeling, we studied the origin of VOCs and the carbon (C) allocation under global warming in the soil–plant–atmosphere system of contrasting subarctic heath tundra vegetation communities characterized by dwarf shrubs of the genera Salix or Betula. The projected temperature rise of the subarctic summer by 5°C was realistically simulated in sophisticated climate chambers. VOC emissions strongly depended on the plant species composition of the heath tundra. Warming caused increased VOC emissions and significant changes in the pattern of volatiles toward more reactive hydrocarbons. The 13C was incorporated to varying degrees in different monoterpene and sesquiterpene isomers. We found that de novo monoterpene biosynthesis contributed to 40%–44% (Salix) and 60%–68% (Betula) of total monoterpene emissions under the current climate, and that warming increased the contribution to 50%–58% (Salix) and 87%–95% (Betula). Analyses of above‐ and belowground 12/13C showed shifts of C allocation in the plant–soil systems and negative effects of warming on C sequestration by lowering net ecosystem exchange of CO2 and increasing C loss as VOCs. This comprehensive analysis provides the scientific basis for mechanistically understanding the processes controlling terpenoid emissions, required for modeling VOC emissions from terrestrial ecosystems and predicting the future chemistry of the arctic atmosphere. By changing the chemical composition and loads of VOCs into the atmosphere, the current data indicate that global warming in the Arctic may have implications for regional and global climate and for the delicate tundra ecosystems.
Partial river flow recovery with forest age is rare in the decades following establishment
Authors: Bentley Laura , Coomes David A.
Published: January 2020

Forest regeneration and expansion are occurring in many countries, with 80 million ha established from 2000 to 2012 under the Bonn accord and 17.5 million ha established from 1990 to 2005 according to the Food and Agriculture Organisation. Multiple reviews have linked increasing forest cover with reduced river flow and potentially detrimental effects downstream. Previous reviews have investigated trends in river flow response over time, but the influence of forest age remains uncertain. Partial river flow recovery (towards non‐forested conditions) has been reported in decades following forest establishment, but the role of climate in driving these trends has not been explored. Here, we evaluate river flow trends in 43 studies following forest establishment, which provide sufficient information to distinguish the effects of ageing forests from variable climate. Our meta‐analysis supports previous findings showing that forestation reduces annual river flow (by 23% after 5 years and 38% after 25 years) with greater reductions in catchments with higher mean annual precipitation, larger increases in forest cover, and which were idle, rather than agricultural land, prior to forestation. The impact of forests on river flow is sensitive to annual precipitation and potential evapotranspiration, but responses are highly variable. Forests affect river flow less when annual precipitation is low, and sensitivity to precipitation decreases as catchment aridity increases. The majority of catchments demonstrated persistent river flow declines after forest establishment. However, nine catchments showed partial flow recovery after an initial decrease, with peak flow reductions at an average age of 15 and across a range of tree species. The mean rate of recovery was 34 mm/year over 5 years. Partial flow recovery with forest age cannot be commonly expected, however, and forestation programmes should take into account that changes to annual river flow are likely to persist for up to five decades.
Remote sensing of forest gas exchange: Considerations derived from a tomographic perspective
Authors: Damm Alexander , Paul‐Limoges Eugenie , Kükenbrink Daniel , Bachofen Christoph , Morsdorf Felix
Published: January 2020

The global exchange of gas (CO2, H2O) and energy (sensible and latent heat) between forest ecosystems and the atmosphere is often assessed using remote sensing (RS) products. Although these products are essential in quantifying the spatial variability of forest–atmosphere exchanges, large uncertainties remain from a measurement bias towards top of canopy fluxes since optical RS data are not sensitive for the vertically integrated forest canopy. We hypothesize that a tomographic perspective opens new pathways to advance upscaling gas exchange processes from leaf to forest stands and larger scales. We suggest a 3D modelling environment comprising principles of ecohydrology and radiative transfer modelling with measurements of micrometeorological variables, leaf optical properties and forest structure, and assess 3D fields of net CO2 assimilation (An) and transpiration (T) in a Swiss temperate forest canopy. 3D simulations were used to quantify uncertainties in gas exchange estimates inherent to RS approaches and model assumptions (i.e. a big‐leaf approximation in modelling approaches). Our results reveal substantial 3D heterogeneity of forest gas exchange with top of canopy An and T being reduced by up to 98% at the bottom of the canopy. We show that a simplified use of RS causes uncertainties in estimated vertical gas exchange of up to 300% and that the spatial variation of gas exchange in the footprint of flux towers can exceed diurnal dynamics. We also demonstrate that big‐leaf assumptions can cause uncertainties up to a factor of 10 for estimates of An and T. Concluding, we acknowledge the large potential of 3D assessments of gas exchange to unravelling the role of vertical variability and canopy structure in regulating forest–atmosphere gas and energy exchange. Such information allows to systematically link canopy with global scale controls on forest functioning and eventually enables advanced understanding of forest responses to environmental change.
Anthropogenic and lightning‐started fires are becoming larger and more frequent over a longer season length in the U.S.A.
Authors: Cattau Megan E. , Wessman Carol , Mahood Adam , Balch Jennifer K.
Published: January 2020

Aim

Over the past several decades, wildfires have become larger, more frequent, and/or more severe in many areas. Simultaneously, anthropogenic ignitions are steadily growing. We have little understanding of how increasing anthropogenic ignitions are changing modern fire regimes.

Location

Conterminous United States.

Time period

1984–2016.

Major taxa studied

Vegetation.

Methods

We aggregated fire radiative power (FRP)‐based fire intensity, event size, burned area, frequency, season length, and ignition type data from > 1.8 million government records and remote sensing data at a 50‐km resolution. We evaluated the relationship between fire physical characteristics and ignition type to determine if and how modern U.S.A. fire regimes are changing sensu stricto given increased anthropogenic ignitions, and how those patterns vary over space and time.

Results

At a national scale, wildfires occur over longer fire seasons (17% increase) and have become larger (78%) and more frequent (12%), but not necessarily more intense. Further, human ignitions have increased 9% proportionally. The proportion of human ignitions has a negative relationship with fire size and FRP and a positive relationship with fire frequency and season length. Areas dominated by lightning ignitions experience fires that are 2.4 times more intense and 9.2 times larger. Areas dominated by human ignitions experience fires that are twice as frequent and have a fire season that is 2.4 times longer. The effect of human ignitions on fire characteristics varies regionally. Ecoregions in the eastern U.S.A. and in some parts of the coastal western U.S.A. have no areas dominated by lightning ignitions. For the remaining ecoregions, more intense and larger fires are associated with lightning ignitions, and longer season lengths are associated with human ignitions.

Main conclusions

Increasing anthropogenic ignitions – in tandem with climate and land cover change – are contributing to a ‘new normal’ of fire activity across continental scales.
Comparison of four different regimens against Helicobacter pylori as a first‐line treatment: A prospective, cross‐sectional, comparative, open trial in Chinese children
Authors: Zhou Ying , Ye Ziqing , Wang Yuhuan , Zhang Ye , Tang Zifei , Yan Weili , Jiang Yuan , Huang Ying
Published: January 2020

Backgrounds

Due to the decreasing eradication rate of Helicobacter pylori, some novel alternatives have been developed, such as bismuth‐containing quadruple therapy and non‐bismuth‐containing quadruple therapy (sequential and concomitant treatment). Little is known about whether a success rate above 90% can be achieved with these regimens in Chinese children.

Methods

In this prospective, open, comparative cross‐sectional study, we recruited treatment‐naïve children (aged between 6 and 18 years) with H pylori infection. The patients were assigned either standard triple therapy, sequential therapy, bismuth‐based quadruple therapy, or concomitant therapy at the discretion of the prescribing physician. H pylori infection was evaluated at least 4 weeks after the completion of the treatment. A negative urea breath test (UBT) indicated successful eradication. The primary endpoint was the eradication frequency of H pylori in the full analysis set (FAS), which included all children who received at least one dose of the treatment and with available follow‐up data.

Results

Between September 2017 and December 2018, 228 patients were finally included in the FAS analyses. The eradication rates were 74.1% for standard triple therapy (43/58, [95% CI: 62.8%‐85.5%]), 69.5% for sequential therapy (41/59, [95% CI: 57.8%‐81.2%]), 89.8% for bismuth‐based quadruple therapy (53/59, [95% CI: 82.1%‐97.5%]), and 84.6% for concomitant therapy (44/52, [95% CI: 74.8%‐94.4%]). Bismuth‐based therapy was superior to triple therapy, while sequential therapy and concomitant therapy were not superior to triple therapy. The frequency of adverse events was 12.1% (7/58) in standard triple therapy, 6.8% (4/59) in sequential therapy, 15.3% (9/59) in bismuth‐based therapy, and 15.4% (8/52) in concomitant therapy. The rate of adverse events was similar among the four groups.

Conclusion

Bismuth quadruple therapy can achieve an eradication rate of 89.8% as first‐line treatment and is safe and well tolerated. Bismuth could be a promising alternative as a first‐line regimen in Chinese children.
Prospects of antibacterial bioactive glass nanofibers for wound healing: An in vitro study
Authors: Saha Suman , Bhattacharjee Arnab , Rahaman Sk. Hasanur , Ray Sayantan , Marei Mona K. , Jain Himanshu , Chakraborty Jui
Published: January 2020

The present communication reports the synthesis of silver‐containing bioactive glass by sol‐gel route, followed by fabrication of the antibacterial bioactive glass nanofibers (ABGnf, dia 200‐900 nm) using electrospinning technique. The ABGnf of composition 1‐2 mol% of B2O3, 68‐69 mol% of SiO2, ~1 × 10−3 mol% of Ag2O, and 29‐30 mol% of CaO was evaluated both for wound‐healing potential and for antibacterial efficacy. An in vitro cell proliferation/migration assay was performed using SV‐transformed GM00637 (skin fibroblast) cell line, wherein ABGnf exhibited significant cell proliferation (82%) compared to the control (47%) and ABGnf without boron (65%) in a period of 24 hours, thus establishing its wound‐healing potential. Further, the antibacterial activity was assessed in vitro using the bacterial strain of Staphylococcus aureus. The results showed the zone of inhibition to be almost two times the control group treated with a model aminoglycoside antibiotic, tobramycin. In addition to the above advantages, the in vitro cytotoxicity assay showed an excellent cellular response. All these results have established promising wound healing and antibacterial potential of ABGnf.
Heterozygous variant fibrinogen γA289V (Kanazawa III) was confirmed as hypodysfibrinogenemia by plasma and recombinant fibrinogens
Authors: Kaido Takahiro , Yoda Masahiro , Kamijo Tomu , Taira Chiaki , Higuchi Yumiko , Okumura Nobuo
Published: January 2020

Introduction

Congenital fibrinogen disorders are classified as afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia. However, difficulties are associated with discriminating between dysfibrinogenemia, hypofibrinogenemia, and hypodysfibrinogenemia using routine analyses. We previously reported a heterozygous variant fibrinogen (γA289V; Kanazawa III) as hypodysfibrinogenemia; however, the same variant had previously been described as hypofibrinogenemia. To clarify the production of γA289V fibrinogen, we expressed recombinant γA289V (r‐γA289V) fibrinogen and compared it with wild‐type (WT) and adjacent recombinant variant fibrinogens.

Methods

Target mutations were introduced into a fibrinogen γ‐chain expression vector by site‐directed mutagenesis, and the vector was then transfected into Chinese hamster ovary cells to produce recombinant fibrinogen. Fibrinogen was purified from the plasma of the proposita, and culture media and fibrinogen functions were analyzed using fibrin polymerization, plasmin protection, and FXIIIa‐catalyzed fibrinogen cross‐linking.

Results

The fibrinogen concentration ratio of the culture media to cell lysates was markedly lower for r‐γA289V fibrinogen than for WT. Because the secretion of recombinant γF290L (r‐γF290L) fibrinogen was similar to WT, we compared r‐γF290L fibrinogen functions with WT. The fibrin polymerization of Kanazawa III plasma (K‐III) fibrinogen was significantly weaker than normal plasma fibrinogen. Moreover, K‐III fibrinogen showed a markedly reduced “D:D” interaction. However, all functions of r‐γF290L fibrinogen were similar to WT. An in silico analysis confirmed the above results.

Conclusion

The present results demonstrated that γA289 is crucial for the γ‐module structure, and the γA289V substitution markedly reduced fibrinogen secretion. Moreover, K‐III fibrinogen showed markedly reduced fibrin polymerization and “D:D” interactions. γA289V fibrinogen was confirmed as hypodysfibrinogenemia.
OnabotulinumtoxinA (botulinum toxin type A) for the treatment of Japanese patients with overactive bladder and urinary incontinence: Results of single‐dose treatment from a phase III, randomized, double‐blind, placebo‐controlled trial (interim analysis)
Authors: Yokoyama Osamu , Honda Masashi , Yamanishi Tomonori , Sekiguchi Yuki , Fujii Kenji , Nakayama Takashi , Mogi Takao
Published: January 2020

Objective

To evaluate the efficacy and safety of onabotulinumtoxinA (botulinum toxin type A) 100 U in patients with overactive bladder and urinary incontinence.

Methods

This was a phase III, randomized, double‐blind, placebo‐controlled trial in Japanese patients who were inadequately managed with overactive bladder medications (anticholinergics and/or β3‐adrenergic receptor agonists). Eligible patients were randomized 1:1 to receive a single dose of either onabotulinumtoxinA or placebo into the detrusor muscle (n = 124 each). The primary end‐point was the change in the number of daily urinary incontinence episodes at week 12 from baseline. Secondary end‐points included volume voided per micturition, other symptomatic measures (urinary urgency incontinence, micturition, urgency and nocturia) and patient‐reported outcomes.

Results

In the onabotulinumtoxinA group, there was a significantly greater decrease from baseline in the mean number of daily urinary incontinence episodes compared with the placebo group (2.16; P < 0.001), and significantly greater improvement for all secondary end‐points (P < 0.05). Urinary tract infection, dysuria, urinary retention and post‐void residual urine volume increased represented adverse events occurring at a higher rate in the onabotulinumtoxinA group. The majority of these were mild or moderate in severity.

Conclusions

Statistically significant and clinically relevant improvements in symptoms and patient‐reported outcomes, and tolerability were seen in patients with overactive bladder and urinary incontinence who had been inadequately managed with overactive bladder medications after using onabotulinumtoxinA.