bluuebunny/crossref_metadata_2025 huggingface dataset:
FoxO3 deficiency in cortical astrocytes leads to impaired lipid metabolism and aggravated amyloid pathology
Authors: Du Shuqi , Jin Feng , Maneix Laure , Gedam Manasee , Xu Yin , Catic Andre , Wang Meng C. , Zheng Hui
Published: July 2021

The rise of life expectancy of the human population is accompanied by the drastic increases of age‐associated diseases, in particular Alzheimer's disease (AD), and underscores the need to understand how aging influences AD development. The Forkhead box O transcription factor 3 (FoxO3) is known to mediate aging and longevity downstream of insulin/insulin‐like growth factor signaling across species. However, its function in the adult brain under physiological and pathological conditions is less understood. Here, we report a region and cell‐type‐specific regulation of FoxO3 in the central nervous system (CNS). We found that FoxO3 protein levels were reduced in the cortex, but not hippocampus, of aged mice. FoxO3 was responsive to insulin/AKT signaling in astrocytes, but not neurons. Using CNS Foxo3‐deficient mice, we reveal that loss of FoxO3 led to cortical astrogliosis and altered lipid metabolism. This is associated with impaired metabolic homoeostasis and β‐amyloid (Aβ) uptake in primary astrocyte cultures. These phenotypes can be reversed by expressing a constitutively active FOXO3 but not a FOXO3 mutant lacking the transactivation domain. Loss of FoxO3 in 5xFAD mice led to exacerbated Aβ pathology and synapse loss and altered local response of astrocytes and microglia in the vicinity of Aβ plaques. Astrocyte‐specific overexpression of FOXO3 displayed opposite effects, suggesting that FoxO3 functions cell autonomously to mediate astrocyte activity and also interacts with microglia to address Aβ pathology. Our studies support a protective role of astroglial FoxO3 against brain aging and AD.
Neuronal α‐amylase is important for neuronal activity and glycogenolysis and reduces in presence of amyloid beta pathology
Authors: Byman Elin , Martinsson Isak , Haukedal Henriette ,   The Netherlands Brain Bank, Gouras Gunnar , Freude Kristine K. , Wennström Malin
Published: July 2021

Recent studies indicate a crucial role for neuronal glycogen storage and degradation in memory formation. We have previously identified alpha‐amylase (α‐amylase), a glycogen degradation enzyme, located within synaptic‐like structures in CA1 pyramidal neurons and shown that individuals with a high copy number variation of α‐amylase perform better on the episodic memory test. We reported that neuronal α‐amylase was absent in patients with Alzheimer's disease (AD) and that this loss corresponded to increased AD pathology. In the current study, we verified these findings in a larger patient cohort and determined a similar reduction in α‐amylase immunoreactivity in the molecular layer of hippocampus in AD patients. Next, we demonstrated reduced α‐amylase concentrations in oligomer amyloid beta 42 (Aβ42) stimulated SH‐SY5Y cells and neurons derived from human‐induced pluripotent stem cells (hiPSC) with PSEN1 mutation. Reduction of α‐amylase production and activity, induced by siRNA and α‐amylase inhibitor Tendamistat, respectively, was further shown to enhance glycogen load in SH‐SY5Y cells. Both oligomer Aβ42 stimulated SH‐SY5Y cells and hiPSC neurons with PSEN1 mutation showed, however, reduced load of glycogen. Finally, we demonstrate the presence of α‐amylase within synapses of isolated primary neurons and show that inhibition of α‐amylase activity with Tendamistat alters neuronal activity measured by calcium imaging. In view of these findings, we hypothesize that α‐amylase has a glycogen degrading function within synapses, potentially important in memory formation. Hence, a loss of α‐amylase, which can be induced by Aβ pathology, may in part underlie the disrupted memory formation seen in AD patients.
Validation of a multi‐species‐specific PCR panel to diagnose patients with suspected postoperative bacterial endophthalmitis
Authors: van Halsema Justin , Jansen Ruud , Heineken Adriaan , van Ossewaarde Tjaco M. , Meester‐Smoor Magda A. , van Meurs Jan C.
Published: July 2021

Introduction

Currently, patients suspected of endophthalmitis are referred to a tertiary centre for a vitreous biopsy and bacterial culture, thereby causing a treatment delay for the intravitreal antibiotics injection. We developed a new diagnostic tool, multi‐mono‐PCR (mm‐PCR), not requiring viable bacteria, allowing antibiotic injection without delay. Performance of mm‐PCR was tested on biopsies from patients with suspected postoperative endophthalmitis with known bacterial culture results.

Methods

Most frequently occurring pathogens in endophthalmitis were determined using published data and treatment logs of endophthalmitis patient of the Rotterdam Eye Hospital.

Vitreous biopsies from patients with suspected endophthalmitis were aliquoted in two parts. One part was sent out for bacterial culture and another was stored at −80°C for mm‐PCR analysis and, as a backup, also by panbacterial PCR. Twelve vitreous samples from patients not suspected of having endophthalmitis were added as control samples.

Results

Concordancy between bacterial culture and mm‐PCR was 89% (24 of 27). All twelve control samples were negative. In three nonconcordant samples, the PCR results were most likely the correct ones.

Conclusion

mm‐PCR results are highly concordant with bacterial culture. mm‐PCR with panbacterial PCR as backup could be considered a diagnostic tool in patients with endophthalmitis, which would allow us to reverse the order of diagnosis and treatment while maintaining diagnostic surveillance, thereby preventing treatment delay.
Alcohol‐associated liver disease in the United States is associated with severe forms of disease among young, females and Hispanics
Authors: Singal Ashwani K. , Arsalan Arshad , Dunn Winston , Arab Juan P. , Wong Robert J. , Kuo Yong‐Fang , Kamath Patrick S. , Shah Vijay H.
Published: July 2021

Background

Alcohol use and alcohol‐associated liver disease (ALD) burden are increasing in young individuals.

Aim

To assess host factors associated with this burden.

Methods

National Health and Nutrition Examination Survey (NHANES), National Inpatient Sample (NIS), and United Network for Organ Sharing (UNOS) databases (2006‐2016) were used to identify individuals with harmful alcohol use, ALD‐related admissions, and ALD‐related LT listings respectively.

Results

Of 15 981 subjects in NHANES database, weighted prevalence of harmful alcohol use was 17.7%, 29.3% in <35 years (G1) versus 16.9% in 35‐64 years (G2) versus 5.1% in ≥65 years (G3). Alcohol use was about 11 and 4.7 folds higher in G1 and G2 versus G3, respectively. Male gender and Hispanic race associated with harmful alcohol use. Of 593 600 ALD admissions (5%, 77%, and 18% in G1‐G3 respectively), acute on chronic liver failure (ACLF) occurred in 7.2%, (7.2 in G2 vs 6.7% in G1 and G3, P < 0.001). After controlling for other variables, ACLF development among ALD hospitalizations was higher by 14% and 10% in G1 and G2 versus G3, respectively. Female gender and Hispanic race were associated with increased ACLF risk by 8% and 17% respectively. Of 20,245 ALD LT listings (3.4%, 84.4%, and 12.2% in G1‐G3 respectively), ACLF occurred in 28% candidates. Risk of severe (grade 2 or 3) ACLF was higher by about 1.7 fold in G1, 1.5 fold in females and 20% in Hispanics.

Conclusion

Young age, female gender, and Hispanic race are independently associated with ALD‐related burden and ACLF in the United States. If these findings are validated in prospective studies, strategies will be needed to reduce alcohol use in high risk individuals to reduce burden from ALD.
Systematic review with meta‐analysis: The effects of non‐steroidal anti‐inflammatory drugs and anti‐platelet therapy on the incidence and recurrence of hepatocellular carcinoma
Authors: Tan Regina Zi Hwei , Lockart Ian , Abdel Shaheed Christina , Danta Mark
Published: July 2021

Background

Chemoprevention with NSAIDs, including aspirin, and anti‐platelet therapy (APT), has been suggested to reduce the incidence and recurrence of hepatocellular carcinoma (HCC).

Aim

To determine by meta‐analysis whether NSAIDs and APT use affected HCC incidence, HCC recurrence and liver‐related mortality in at‐risk populations with chronic liver disease.

Method

Electronic databases including Pubmed, Scopus, Medline, Embase and Cochrane Library were searched (from inception to 31 May 2021) for eligible studies evaluating the impacts of NSAID or APT use on HCC incidence, recurrence and mortality. Data on HCC incidence, recurrence, liver‐related mortality or bleeding complications had to be available. Studies were included if they evaluated adults with hepatitis B virus (HBV), hepatitis C virus (HCV), alcohol‐related liver disease (ALD) or nonalcoholic steatohepatitis that were administered at least one NSAID or APT for a defined period of time and were followed for at least 6 months. The primary outcome was HCC incidence. Secondary outcomes included: HCC recurrence, liver‐related mortality and bleeding complications. Data were pooled using a random effects model with hazard ratios (HRs) or odds ratio (OR), and 95% confidence intervals (CIs) presented.

Results

Of 3773 articles screened, 19 studies were included, with a total of 147 283 participants. Aspirin use reduced the risk of HCC incidence (HR: 0.51, 95% CI: 0.36‐0.72); and improved liver‐related mortality (OR: 0.32, 95% CI: 0.15‐0.70), with a small increased risk of gastrointestinal bleeding events (OR: 1.32, 95% CI: 1.08‐1.94). With respect to HCC recurrence following treatment, analysis of all aspirin and NSAID treatment (including; aspirin only; non‐aspirin NSAIDs only; and combination NSAIDs groups) was associated with a decreased risk of HCC recurrence (HR: 0.80, 95% CI: 0.75‐0.86). By stratified analysis, only the non‐aspirin NSAID group showed significant risk reduction (HR: 0.73, 95% CI: 0.63‐0.84).

Conclusion

The study supports the use of aspirin in at‐risk individuals to reduce the incidence of HCC and liver‐related mortality. HCC recurrence following treatment was lower with NSAID treatment.
Continued 5ASA use after initiation of anti‐TNF or immunomodulator confers no benefit in IBD: a population‐based study
Authors: Bernstein Charles N. , Tenakoon Aruni , Singh Harminder , Targownik Laura E.
Published: July 2021

Background

With the advent of biological therapy in IBD, it is uncertain to what extent 5aminosalicylates (5ASA) are used.

Aims

To explore whether or not 5ASA is continued once biological or immunomodulator therapy is initiated, and the outcomes in those who continued the 5ASAs.

Methods

We conducted a retrospective cohort study using the population‐based University of Manitoba IBD Epidemiologic Database which includes prescription drug dispensation from 1996 through 2018. We assessed outcomes among 5ASA users who continued versus discontinued 5ASA after initiation of anti‐TNF therapy or immunomodulators.

Results

In all, 8379 (77%) of persons with IBD received at least one 5ASA dispensation (85% of ulcerative colitis, UC and 68% of Crohn’s disease, CD). There was a reduction in later years, particularly for CD. The most common pattern of 5ASA use was intermittent at 65.1% (stopping and restarting use) versus one‐time (4.1%), previous continuous (13.8%) and persistent (17%). Among the total IBD population use was 59% oral, 3% rectal and 14% combination. Of all 5ASA starts, only 25% were continued longer than 20 months. After immunomodulator or anti‐TNF initiation, there was no difference in either UC or CD for negative outcomes (hospitalisation, surgery, corticosteroid starts, colorectal cancers or drug‐related adverse events) between those who continued 5ASA versus those who discontinued.

Conclusions

5ASA remains commonly prescribed in UC and CD. Rates of persistent use in UC are low. Once an anti‐TNF or immunomodulator is initiated, continuation of 5ASA seems to add no benefit.
The osteohistological variability in the evolution of basal avialans
Authors: Monfroy Quentin T. , Kundrát Martin
Published: July 2021

Basal avialans have been the focus of numerous histological studies in the past decade, from which different osteohistological patterns have been described. In this review, we look at the osteohistology in selected specimens from the four major avian groups: the long‐tailed Avialae (Archaeopteryxand Jeholornithiformes), basal Pygostylia, Enantiornithes and Euornithes. Developmental and evolutionary changes in the three major bone layers are observed throughout the bone cortex of the limbs, may it be interspecific or intraspecific. Most noteworthy is the adaptive change from the overall lamellar/parallel‐fibered bone tissue to a fibrolamellar complex in the mid‐cortex as of the basal Pygostylia, potentially even as of the Jeholornithiformes. This change is generally associated with an increase in the density and complexity of the neurovascular network. Another evolutionary‐developmental feature is the progressive loss of post‐natal growth marks as of the non‐ornithurine Euornithes, indicative of uninterrupted bone growth as observed in extant Neornithes. Our comparisons of the osteohistological patterns allow us to better determine how and when specific features typical observed in the avian crown group developed, associated with external and internal factors, and how they lead to what is commonly observed in extant Neornithes.
Mutualistic relationships in marine angiosperms: Enhanced germination of seeds by mega‐herbivores
Authors: Tol Samantha J. , Jarvis Jessie C. , York Paul H. , Congdon Bradley C. , Coles Robert G.
Published: July 2021

Angiosperms have co‐evolved with animals over thousands of years leading to an array of mutualistic relationships. Passage of plant seeds through animal intestines leads to an important mutualism providing the animal with food and the plant with seed dispersal and enhanced germination. This phenomenon is well studied in terrestrial angiosperms, but there is less research in aquatic environments. We studied the effect of gut passage in marine mega‐herbivores (green sea turtles and dugongs) on seed germination for a common Australian seagrass, Zostera muelleri.

We collected fecal samples likely to contain seeds, as well as seagrass seeds from plants at two coastal seagrass meadows in the central Great Barrier Reef World Heritage Area, Australia. Seeds collected from feces and plants were subjected to germination trials across different temperature treatments: low (19°C), medium (26°C), and high (32°C). We found excreted seeds had a significantly greater germination probability (two to four times greater) and germinated significantly faster (18–61% faster) than seeds from the plant. Excreted seeds which had not germinated at the end of the experiment were significantly less likely to be viable compared with seeds taken from the plant. Seeds released from the plant have a slow germination and low germination probability compared with excreted seeds, but retain a high percentage of seed viability. Our study is the first record of marine mega‐herbivores enhancing germination of Z. muelleri seeds. By transporting seeds to new locations and enhancing germination, these animals are important in seagrass resilience and connectivity among metapopulations.
The Relation Between Cognitive Abilities and the Distribution of Semantic Features Across Speech and Gesture in 4‐year‐olds
Authors: Abramov Olga , Kern Friederike , Koutalidis Sofia , Mertens Ulrich , Rohlfing Katharina , Kopp Stefan
Published: July 2021

When young children learn to use language, they start to use their hands in co‐verbal gesturing. There are, however, considerable differences between children, and it is not completely understood what these individual differences are due to. We studied how children at 4 years of age employ speech and iconic gestures to convey meaning in different kinds of spatial event descriptions, and how this relates to their cognitive abilities. Focusing on spontaneous illustrations of actions, we applied a semantic feature (SF) analysis to characterize combinations of speech and gesture meaning and related them to the child's visual‐spatial abilities or abstract/concrete reasoning abilities (measured using the standardized SON‐R test). Results show that children with higher cognitive abilities convey significantly more meaning via gesture and less solely via speech. These findings suggest that young children's use of cospeech representational gesturing is positively related to their mental representation and reasoning abilities.
Climate risk and corporate tax avoidance: International evidence
Authors: Ni Yingzhao , Chen Zhian , Li Donghui , Yang Shijie
Published: July 2021

Research Question/Issue

This study investigates the relationship between climate risk and corporate tax avoidance. Previous studies on this relationship generate mixed results, theoretically and empirically. Our study addresses this empirical question by providing new evidence using a large international sample and a novel proxy for climate risk.

Research Findings/Insights

The empirical results show that higher climate risk is associated with higher tax avoidance. Mechanism analyses show that this positive association is due to the incentive to reserve cash in response to tightened financial constraints, rather than tax deductions granted by governments. This result is more pronounced in countries or regions that have poorer corporate governance and information environments, lower economic development, and a more uncertain policy environment.

Theoretical/Academic Implications

Our evidence highlights the importance of considering the role of climate risk in corporate tax policies and of comparing the link between climate risk and tax avoidance across countries.

Practitioner/Policy Implications

Echoing environmental non‐governmental organizations' (NGOs) recent call on governments to strengthen tax administration, our study has policy implications that emphasize the necessity for policymakers to consider the link between climate risk and tax avoidance.
The effect of adverse childhood experiences on individuals with neurodisabilities
Authors: Msall Michael E
Published: July 2021

This commentary is on the invited review by Morgart et al. on pages 1149–1154 of this issue.
Sit‐to‐stand training for self‐care and mobility in children with cerebral palsy: a randomized controlled trial
Authors: Chaovalit Sirawee , Dodd Karen J , Taylor Nicholas F
Published: July 2021

Aim

To investigate if a sit‐to‐stand exercise programme for children with cerebral palsy (CP) would improve self‐care and mobility.

Method

Thirty‐eight children with CP (19 males, 19 females; mean age 8y 0mo, SD 2y 4mo, age range 4y 0mo–12y 4mo) classified in Gross Motor Function Classification System (GMFCS) levels III and IV and their caregivers were randomly allocated to sit‐to‐stand training plus routine physiotherapy (balance and gait training) or routine physiotherapy only (controls). Task‐specific sit‐to‐stand training was completed five times a week for 6 weeks under physiotherapist (twice weekly) and caregiver (three times weekly) supervision. Blinded outcome assessments at week 7 were the self‐care and mobility domains of the Functional Independence Measure for Children, Five Times Sit‐to‐Stand Test (FTSST), and Modified Caregiver Strain Index (MCSI).

Results

The sit‐to‐stand group self‐care increased by 2.2 units (95% confidence interval [CI] 1.3–3.1) and mobility increased by 2.2 units (95% CI 1.4–3.0) compared to the control group. In the sit‐to‐stand group, the FTSST was reduced by 4.0 seconds (95% CI −4.7 to −3.2) and the MCSI was reduced by 0.8 units (95% CI −1.2 to −0.4) compared to the control group.

Interpretation

A sit‐to‐stand exercise programme for children with CP classified in GMFCS levels III and IV improved sit‐to‐stand performance and resulted in small improvements in self‐care and mobility, while reducing caregiver strain.

What this paper adds

Sit‐to‐stand training improved independence in self‐care and mobility for children with cerebral palsy (CP).

Home‐based sit‐to‐stand training programmes for children with CP can reduce the burden on supervising caregivers.
Nutritional screening of children and adolescents with cerebral palsy: a scoping review
Authors: Sørensen Sarah J , Brekke Ghita , Kok Karin , Sørensen Jette L , Born Alfred P , Mølgaard Christian , Høi‐Hansen Christina E
Published: July 2021

Aim

To examine nutritional screening methods for children and adolescents with cerebral palsy.

Method

A scoping review was performed using established methodologies. In June 2020 we searched PubMed, Embase, CINAHL Complete, and the Cochrane Central Register of Controlled Trials to identify articles on tools/methods for nutritional screening of our target groups.

Results

Thirty studies were included, containing various tools/methods used to identify under‐ and/or overnutrition by weight/height, circumferences, skinfolds, questionnaires, and/or technically advanced or invasive methods. Questionnaires, weight/height, circumferences, and skinfolds were considered feasible based on clinical utility, whereas bioelectrical impedance analysis and blood samples were not.

Interpretation

We identified two screening tools for undernutrition that include no physical measurements, but did not find any screening tools for overweight and obesity. Most of the studies recommended one or more methods, indicating that determining nutritional status most likely includes a combination of methods, not all of which may be feasible in clinical practice.

What this paper adds

No nutritional screening tool using anthropometry or body composition was discovered.

Heterogenous methods to identify under‐ and/or overnutrition are recommended.

Preferable methods for nutritional screening include assessment of body composition.

A validated nutritional screening tool for identification of overweight is warranted.
Methodological quality of systematic reviews on interventions for children with cerebral palsy: the evidence pyramid paradox
Authors: Negrini Stefano , Côté Pierre , Kiekens Carlotte
Published: July 2021

This commentary is on the original article by Kolaski et al. on pages 1316–1326 of this issue.
Genetic convergence of developmental and epileptic encephalopathies and intellectual disability
Authors: Carvill Gemma L , Jansen Sandra , Lacroix Amy , Zemel Matthew , Mehaffey Michele , De Vries Petra , Brunner Han G , Scheffer Ingrid E , De Vries Bert B A , Vissers Lisenka E L M , Mefford Heather C
Published: July 2021

Aim

To determine whether genes that cause developmental and epileptic encephalopathies (DEEs) are more commonly implicated in intellectual disability with epilepsy as a comorbid feature than in intellectual disability only.

Method

We performed targeted resequencing of 18 genes commonly implicated in DEEs in a cohort of 830 patients with intellectual disability (59% male) and 393 patients with DEEs (52% male).

Results

We observed a significant enrichment of pathogenic/likely pathogenic variants in patients with epilepsy and intellectual disability (16 out of 159 in seven genes) compared with intellectual disability only (2 out of 671) (p<1.86×10−10, odds ratio 37.22, 95% confidence interval 8.60–337.0).

Interpretation

We identified seven genes that are more likely to cause epilepsy and intellectual disability than intellectual disability only. Conversely, two genes, GRIN2B and SCN2A, can be implicated in intellectual disability without epilepsy; in these instances intellectual disability is not a secondary consequence of ongoing seizures but rather a primary cause.

What this paper adds

A subset of genes are more commonly implicated in epilepsy than other neurodevelopmental disorders.

GRIN2B and SCN2A are implicated in intellectual disability and epilepsy independently.
Dysautonomia and functional impairment in rare developmental and epileptic encephalopathies: the other nervous system
Authors: Berg Anne T , Coffman Keith , Gaebler‐Spira Deborah
Published: July 2021

Aim

To determine whether functional impairments and autonomic symptoms are correlated in young people with developmental and epileptic encephalopathies (DEEs).

Method

Cross‐sectional, online surveys (2018–2020) of parents recruited from family groups obtained information on several aspects of children’s conditions including functional abilities (mobility, hand use, eating, and communication), 18 autonomic symptoms in six groups (cardiac, respiratory, sweating, temperature, gastrointestinal, and other), and parental stress. Bivariate and multivariable logistic regression analyses examined associations of dysautonomias with functional impairment, adjusted for type of DEE and age.

Results

Of 313 participants with full information on function and dysautonomias, 156 (50%) were females. The median age was 8 years (interquartile range 4–12y); 255 (81%) participants had symptoms in at least one autonomic symptom group; 283 (90%) had impairment in at least one functional domain. The number of functional impairment domains and of autonomic symptom groups varied significantly across DEE groups (both p<0.001). The number of functional impairment domains and of autonomic symptom groups were correlated (Spearman’s r=0.35, p<0.001) on bivariate and multivariable analysis adjusted for DEE group and age. Parental stress was also independently correlated with dysautonomias (p<0.001).

Interpretation

Parent‐reported dysautonomias are common in children with DEEs. They correlate with extent of functional impairment and may contribute to caregiver stress.

What this paper adds

Dysautonomic symptoms are common in young people with developmental and epileptic encephalopathies (DEEs).

Burden of dysautonomias is strongly correlated with burden of functional impairments.

Aspects of dysautonomic function may provide biomarkers of DEE disease severity.
Levetiracetam dosing in patients receiving continuous renal replacement therapy
Authors: Chaijamorn Weerachai , Charoensareerat Taniya , Rungkitwattanakul Dhakrit , Phunpon Sathian , Sathienluckana Thanompong , Srisawat Nattachai , Pattharachayakul Sutthiporn
Published: July 2021

Objective

The study was aimed to define appropriate levetiracetam dosing regimens from available published pharmacokinetics (PK) studies in critically ill patients with and without cirrhosis receiving continuous renal replacement therapy (CRRT) via Monte Carlo simulation (MCS).

Methods

Mathematical pharmacokinetic models were developed using published demographic and PK data in adult critically ill patients with known variability and correlations between PK parameters. CRRT modalities (continuous venovenous hemofiltration and continuous venovenous hemodialysis) with different effluent rates were modeled. Levetiracetam regimens from available clinical resources were evaluated on the probability of target attainment (PTA) using pharmacodynamics (PD) target of the trough concentrations and area under the time‐concentration curve within a range of 6–20 mg/L and 222–666 mg × hour/L for the initial 72 hours of therapy, respectively. Optimal regimens were defined from regimens that yielded the highest PTA. Each regimen was tested in a group of different 10,000 virtual patients.

Results

Our results showed the optimal levetiracetam dosing regimen of 750–1000 mg every 12 hours is recommended for adult patients receiving both CRRT modalities with two different effluent rates of 25 and 35 mL/kg/h. Child‐Pugh class C cirrhotic patients undergoing CRRT required lower dosing regimens of 500–750 mg every 12 ours due to smaller non‐renal clearance. Of interest, some of literature‐based dosing regimens were not able to attain the PK and PD targets.

Significance

Volume of distribution, non‐renal clearance, CRRT clearance, and body weight were significantly correlated with the PTA targets. Dosing adaptation in this vulnerable population should be concerned. Clinical validation of our finding is absolutely needed.
On seizure semiology
Authors: McGonigal Aileen , Bartolomei Fabrice , Chauvel Patrick
Published: July 2021

The clinical expression of seizures represents the main symptomatic burden of epilepsy. Neural mechanisms of semiologic production in epilepsy, especially for complex behaviors, remain poorly known. In a framework of epilepsy as a network rather than as a focal disorder, we can think of semiology as being dynamically produced by a set of interconnected structures, in which specific rhythmic interactions, and not just anatomical localization, are likely to play an important part in clinical expression. This requires a paradigm shift in how we think about seizure organization, including from a presurgical evaluation perspective. Semiology is a key data source, albeit with significant methodological challenges for its use in research, including observer bias and choice of semiologic categories. Better understanding of semiologic categorization and pathophysiological correlates is relevant to seizure classification systems. Advances in knowledge of neural mechanisms as well as anatomic correlates of different semiologic patterns could help improve knowledge of epilepsy networks and potentially contribute to therapeutic innovations.
Optimal deep learning based fusion model for biomedical image classification
Authors: Mansour Romany F. , Alfar Nada M. , Abdel‐Khalek Sayed , Abdelhaq Maha , Saeed Rashid A. , Alsaqour Raed
Published: July 2021

Automated examination of biomedical signals plays a vital role to diagnose diseases and offers useful data to several applications in the areas of physiology, sports medicine, and human–computer interface. The latest advancements in Artificial Intelligence (AI) have the ability to manage and analyse enormous biomedical datasets resulting in clinical decision making and real time applications. At the same time, Colorectal cancer (CRC) is the third most deadly disease affecting people over the globe. The utilization of AI techniques for the earlier identification of CRC has gained significant interest among the research communities. Therefore, this paper presents a novel AI based fusion model for CRC disease diagnosis and classification, named AIFM‐CRC. The presented AIFM‐CRC model primarily undergoes Gaussian filtering based noise removal and contrast enhancement as a preprocessing stage. In addition, a fusion based feature extraction process takes place where the SIFT based handcrafted features and Inception v4 based deep features are fused together. Besides, whale optimization algorithm tuned deep support vector machine model is employed as a classification technique to determine the existence of CRC. In order to highlight the proficient results analysis of the AIFM‐CRC model, a comprehensive simulation analysis takes place. The resultant experimental values pointed out the betterment of the AIFM‐CRC model by accomplishing a maximum accuracy of 96.18%.
Reporting the whole story: Analysis of the ‘out‐of‐scope’ questions from the James Lind Alliance Teenage and Young Adult Cancer Priority Setting Partnership Survey
Authors: Gibson Faith , Fern Lorna A. , Phillips Bob , Gravestock Helen , Malik Sonia , Callaghan Amy , Dyker Karen , Groszmann Mike , Hamrang Leila , Hough Rachael , McGeachy Demi , Morgan Sue , Smith Sam , Upadhyaya Sheela , Veitch Helen , Williamson Max , Whelan Jeremy , Aldiss Susie
Published: July 2021

Objective

We conducted a UK‐wide survey to identify the top 10 research questions for young people's cancer. We conducted secondary analysis of questions submitted, which were ‘out‐of‐scope’ of the original survey aim. We sought to disseminate these questions, to inform practice, policy and the development of potential interventions to support young people with cancer.

Design

James Lind Alliance Priority Setting Partnership.

Participants

Young people aged 13‐24 with a current/previous cancer diagnosis, their families/friends/partners and professionals who work with this population.

Methods

Eight hundred and fifty‐five potential research questions were submitted, and 326 were classified as ‘out‐of‐scope’. These questions, along with 49 ‘free‐text’ comments, were analysed using thematic analysis.

Results

The 375 out‐of‐scope questions and comments were submitted by: 68 young people, 81 family members/partners/friends and 42 professionals. Ten overarching themes were identified: diagnostic experience; communication; coordination of care; information needs and lack of information; service provision; long‐term effects and aftercare support; family support; financial impact; end‐of life care; and research methods and current research.

Conclusions

The need to tailor services, information and communication is a striking thread evidenced across the ‘out‐of‐scope’ questions. Gaps in information highlight implications for practice in revisiting information needs throughout the cancer trajectory. We must advocate for specialist care for young people and promote the research priorities and these findings to funding bodies, charities, young people and health and social care policymakers, in order to generate an evidence base to inform effective interventions across the cancer trajectory and improve outcomes.

Patient/public contributions

Patients and carers were equal stakeholders throughout.
Nonuse of antimicrobial prophylaxis in clean surgeries for adrenal and renal tumors: Results of the risk‐based strategy in 1362 consecutive patients
Authors: Maruyama Riko , Fukushima Hiroshi , Fukuda Shohei , Yasuda Yosuke , Uehara Sho , Tanaka Hajime , Kijima Toshiki , Yoshida Soichiro , Yokoyama Minato , Matsuoka Yoh , Saito Kazutaka , Kihara Kazunori , Fujii Yasuhisa
Published: July 2021

Objectives

To evaluate the incidence of perioperative infections without antimicrobial prophylaxis in patients undergoing clean surgeries for adrenal and renal tumors.

Methods

We prospectively enrolled 1362 consecutive patients who underwent minimally invasive adrenalectomy (n = 303), radical nephrectomy (n = 499), and partial nephrectomy (n = 560) using the gasless laparoendoscopic single‐port surgery technique between 2005 and 2019. In 1059 patients, antimicrobial prophylaxis was not administered. The remaining 303 patients were considered at high risk for infection and received single‐dose antimicrobial prophylaxis. The endpoint was the incidence of perioperative infections within 1 month from the surgery date. Perioperative infections were classified into surgical site infections, urinary tract infections, and remote infections.

Results

Seventy‐four patients whose collecting systems were opened during partial nephrectomy were excluded, and the remaining 1013 patients with nonuse of antimicrobial prophylaxis and 275 patients with single‐dose antimicrobial prophylaxis were retrospectively analyzed. The incidence of superficial surgical site infections, deep/organ‐space surgical site infections, urinary tract infections, and remote infections was 1.6%, 0.7%, 2.8%, and 1.3%, respectively, in patients with nonuse of antimicrobial prophylaxis and 0.4%, 1.8%, 1.5%, and 1.5%, respectively, in patients with single‐dose antimicrobial prophylaxis. All patients who developed perioperative infections were successfully treated. No clinical or surgical variables were significantly associated with the incidence of surgical site infections. One limitation of the present study was its nonrandomized and noncontrolled design.

Conclusions

In minimally invasive clean surgeries for adrenal and renal tumors, antimicrobial prophylaxis is not necessary when individual risk of infection is considered low.
Binding specificity of OBPs in the yellow peach moth Conogethes punctiferalis (Guenée)
Authors: Guo Honggang , Meng Li , Zhang Minzhao , Ren Zhengguang , Qin Xiaochun , Du Yanli
Published: July 2021

Odorant‐binding proteins (OBPs) are translators of the external chemical signals, which are critical for maintaining insect life. However, few OBPs were reported in the yellow peach moth (YPM), Conogethes punctiferalis (Guenée). In the current study, five OBPs (CpunOBP1, CpunOBP2, CpunOBP7, CpunPBP2 and CpunPBP4) were expressed and purified from the antennae of the YPM. The results showed that the proteins encoded by five CpunOBPs had six conserved cysteine residues, which were typical structural features of classic OBPs. Moreover, the fluorescence competitive binding assays indicated that the binding affinity of five CpunOBPs to the selected YPM female sex pheromones, host plant volatiles and Penicillium‐inoculated apple volatiles was obviously different. The binding affinities of CpunOBP1 and CpunOBP2 with β‐ionone were the strongest. CpunOBP7 could bind with 12 host plant volatiles but was unable to interact with any one of the three tested female sex pheromones. CpunPBP2 and CpunPBP4 exhibited the highest binding affinity to female sex pheromone trans‐10‐hexadecenal among 30 tested compounds. In conclusion, these results suggest the functional differentiation of the CpunOBPs in recognizing sex pheromones, host plant volatiles and fungus‐infected host plant volatiles, which will provide new insights into selecting target proteins for YPM biocontrol.
Running on empty? Freshwater feeding by spawning anadromous alewife Alosa pseudoharengus
Authors: Stewart Sarah I. D. , Spares Aaron D. , Varela José L. , McLellan Nic R. , Stokesbury Michael J. W.
Published: July 2021

Anadromous alewife Alosa pseudoharengus (n = 202; mean ± s.d. fork length = 231 ± 14 mm) were captured from 10 May to 27 June 2018 in an upper watershed lake on the Isthmus of Chignecto, Canada (45°57′N, 64°14′W). Thirty individuals (mean ± s.d. fork length = 250 ± 12 mm) were captured in an adjacent estuary downstream of a tide gate on 25 April 2018. Comparing estuarine to freshwater specimens, mean gonad mass and gonadosomatic indices in males and females decreased approximately 40% and 60%, and 31% and 50%, respectively. Individuals were characterized as pre‐spawners in the estuary and spawners in the lake. Males maintained similar body condition throughout the spawning run whereas female condition decreased 9.4% between the estuary and lake. Stomach fullness decreased comparing estuarine and freshwater specimens, yet 93% of stomachs examined from individuals captured in the lake contained prey. Most males fed throughout all spawning stages (3%–17% empty stomachs), while all females fed during pre‐ and post‐spawning stages and some fasted during spawning (11% empty stomachs). Cumulative prey curve never reached an asymptote, either weekly or for the entire sampling period, so freshwater diet may not have been completely described. Calanoid copepods (79.3%IA) were a diet staple, with the secondary prey of mayfly nymphs (O. Ephemeroptera) consumed more by females (13.6%IA) than males (6.2%IA). PERMANOVA and PERMDISP analyses revealed significant dietary differences in freshwater were weekly and not due to dispersion effects, thus most likely due to feeding on various development stages of insect species. Our results challenge the long‐held paradigm that anadromous A. pseudoharengus fast during the spawning migration.
Feeding habits and seasonal trophic guilds structuring fish community in the bay mouth region of a tropical estuarine habitat
Authors: Soe Kay Khine , Pradit Siriporn , Hajisamae Sukree
Published: July 2021

Understanding trophic relationships of fish in estuarine ecosystem is an important element for sustainable resource management. This study examined the feeding habits of 29 dominant fish species, characterized the trophic guilds, assessed the impact of season and clarified the role of diets in structuring the fish community in the mouth region of Pattani Bay, Thailand. Samples of 5792 fishes collected monthly by gillnets from March 2019 to February 2020 were used for stomach content analyses. It was found that the number of food types and fullness index differed between fish taxa (P < 0.001). Most fishes were specialist feeders feeding on specific food components and were categorized into five trophic guilds: piscivore, shrimp‐fish feeder, polychaete feeder, zooplanktivore and planktivore. Six species were piscivorous, considered as apex predators, that fed almost entirely on fishes. High diet overlaps among some species (>0.6) were recorded. Not much variation in seasonal guilds was observed: four guilds in the dry season, three in the moderate rainy season and four in the rainy season. Some species remained in the same guild the whole year round, but some fishes changed seasonally. Two fish communities from different regions of the bay were segregated based on feeding habits. The inner bay community comprised mainly copepod and plankton feeders, but there were more piscivores in the deeper bay mouth area. Results from this study help us to understand the feeding habits and trophic guilds of dominant fish species at the mouth of this tropical estuarine bay.
Supporting and Expanding Statewide CASA Programs
Authors: Brocious Heidi , Trawver Kathi R. , Griffin Rebecca
Published: July 2021

Court Appointed Special Advocate (CASA) programs around the U.S. are searching for ways to increase the number of volunteers they can recruit and retain so more youth in care can be served. Through focus groups and interviews, study authors collected and analyzed qualitative data on the essential tasks of CASA volunteers, while also soliciting ideas regarding program expansion. Four themes were identified: (1) CASA volunteers do what others on the case can’t always do; (2) CASA volunteers make an impact on case outcomes; (3) Statewide structures and resources are essential to the program’s success; and (4) Program innovations that will improve CASA practice.
The epidemiology of social isolation and loneliness among older adults during the last years of life
Authors: Kotwal Ashwin A. , Cenzer Irena S. , Waite Linda J. , Covinsky Kenneth E. , Perissinotto Carla M. , Boscardin W. John , Hawkley Louise C. , Dale William , Smith Alexander K.
Published: July 2021

Background

Social isolation and loneliness are critical to the health of older adults, but they have not been well‐described at the end of life.

Objectives

To determine the prevalence and correlates of social isolation and loneliness among older adults in the last years of life.

Design

Nationally representative, cross‐sectional survey.

Setting

Health and Retirement Study, 2006–2016 data.

Participants

Adults age > 50 interviewed once in the last 4 years of life (n = 3613).

Measurements

We defined social isolation using a 15‐item scale measuring household contacts, social network interaction, and community engagement, and frequent loneliness using the 3‐item UCLA Loneliness Scale. We used multivariable logistic regression to determine their adjusted prevalence by time prior‐to‐death and by subgroups of interest.

Results

Approximately 19% experienced social isolation, 18% loneliness, and 5% both in the last 4 years of life (correlation = 0.11). The adjusted prevalence of social isolation was higher for individuals nearer to death (4 years: 18% vs 0–3 months: 27%, p = 0.05) and there was no significant change in loneliness (4 years: 19% vs 0–3 months: 23%, p = 0.13). Risk factors for both isolation and loneliness included (p < 0.01): low net‐worth (Isolation: 34% vs 14%; Loneliness: 29% vs 13%), hearing impairment (Isolation: 26% vs 20%; Loneliness: 26% vs 17%), and difficulty preparing meals (Isolation: 27% vs 19%; Loneliness: 29% vs 15%). Factors associated with loneliness, but not social isolation, included being female, pain, incontinence, and cognitive impairment.

Conclusions

Social isolation and loneliness are common at the end of life, affecting 1 in 4 older adults, but few experience both. Rates were higher for older adults who were poor and experienced functional or sensory impairments. Results can inform clinical efforts to identify and address end‐of‐life psychosocial suffering and health policies which prioritize social needs at the end of life.
Tariff Pass‐Through and Welfare in the Tablet Computer Market*
Authors: Hiller R. Scott , Savage Scott J.
Published: July 2021

This paper estimates short‐run effects of tariffs on United States tablet prices and welfare. Market data are used to estimate a model of demand and supply and to simulate prices and sales in scenarios with tariffs. A 25 per cent tariff on firms assembling in China results in tariff elasticity of tablet prices for taxed firms of 1.108, a 29.6 per cent decline in profits, and a deadweight loss of 28.8 per cent. Firms assembling elsewhere benefit from the reduction in rivals’ competitiveness. Long‐run implications are that firms may decide to shift production from ‘uncompetitive’ facilities in China to countries that are politically favored.
New Product Introduction and Slotting Fees*
Authors: Chambolle Claire , Christin Clémence
Published: July 2021

The availability of a new product in a store creates an informative spillover that extends past the store itself through word‐of‐mouth advertising. Because of this spillover, each retailer is able to extract a slotting fee from the manufacturer at product introduction. Slotting fees may discourage innovation by the manufacturer and, in turn, reduce consumer surplus and social welfare. A manufacturer is more likely to pay lower slotting fees when it can advertise more heavily, or when it faces a larger buyer. These results are robust to variations in retail competition, firms’ discount factors, and the identity of the innovating firm.
Price Leadership and Uncertainty About Future Costs*
Authors: Lemus Jorge , Luco Fernando
Published: July 2021

Does uncertainty about future wholesale prices facilitate coordination among firms? To address this question, we exploit a policy intervention (Mepco) that limited the week‐to‐week variation in wholesale prices in the Chilean retail gasoline industry. We show that Mepco caused a decrease in retail gasoline margins in Chile. Further, using price leadership intensity as a proxy for the strength of market coordination, we show that margins decreased more in markets with higher leadership intensity. We rationalize these findings through a repeated‐game framework.
A War of Attrition with Experimenting Players*
Authors: Chen Chia‐Hui , Ishida Junichiro
Published: July 2021

A standard incomplete‐information war of attrition is extended to incorporate experimentation. We obtain a characterization of all equilibria in this extended setup and use this setup to illuminate a tradeoff between short‐run and long‐run gains of experimentation. The extension yields qualitative impacts on the strategic nature of the problem. The option value of experimentation serves as a credible commitment device to stay in the game, which is instrumental in inducing the other player to concede earlier. As a direct consequence, there may be an equilibrium in which the strictly less efficient player, but with a higher margin of experimentation, can get the better end of the deal. This result leads to an important empirical implication since the margin of experimentation is not directly observable, even ex post. Our analysis also gives insight into why an apparently inferior technology often survives in standards competitions and more broadly offers implications for technology adoption and industry dynamics.
Capping Bundle Discounts: Two Regulatory Rationales*
Authors: Byford Martin C. , King Stephen
Published: July 2021

Mixed‐bundling of groceries and gasoline is common, but it raises ‘predatory’ concerns. This paper extends the standard Hotelling approach to consider bundled discounts when two conglomerates and an independent gasoline retailer compete. We show that bundling may result in exit and analyze the effects of capping discounts—a regulatory solution adopted in Australia. The optimal cap depends on the regulator’s objective and the potential for exit. When unregulated discounting leads to exit, an intermediate cap maximises consumer surplus. A cap also ensures that no consumer is worse off with the discounts, an outcome that does not occur with unregulated discounts.