Neural classification of Norwegian radiology reports: using NLP to detect findings in CT-scans of children.

Abstract:
BACKGROUND
With a motivation of quality assurance, machine learning techniques were trained to classify Norwegian radiology reports of paediatric CT examinations according to their description of abnormal findings.

METHODS
13.506 reports from CT-scans of children, 1000 reports from CT scan of adults and 1000 reports from X-ray examination of adults were classified as positive or negative by a radiologist, according to the presence of abnormal findings. Inter-rater reliability was evaluated by comparison with a clinician's classifications of 500 reports. Test-retest reliability of the radiologist was performed on the same 500 reports. A convolutional neural network model (CNN), a bidirectional recurrent neural network model (bi-LSTM) and a support vector machine model (SVM) were trained on a random selection of the children's data set. Models were evaluated on the remaining CT-children reports and the adult data sets.

RESULTS
Test-retest reliability: Cohen's Kappa = 0.86 and F1 = 0.919. Inter-rater reliability: Kappa = 0.80 and F1 = 0.885. Model performances on the Children-CT data were as follows. CNN: (AUC = 0.981, F1 = 0.930), bi-LSTM: (AUC = 0.978, F1 = 0.927), SVM: (AUC = 0.975, F1 = 0.912). On the adult data sets, the models had AUC around 0.95 and F1 around 0.91.

CONCLUSIONS
The models performed close to perfectly on its defined domain, and also performed convincingly on reports pertaining to a different patient group and a different modality. The models were deemed suitable for classifying radiology reports for future quality assurance purposes, where the fraction of the examinations with abnormal findings for different sub-groups of patients is a parameter of interest.

Dahl|Fredrik A|FA|0000-0002-6835-0985
Rama|Taraka|T|
Hurlen|Petter|P|
Brekke|Pål H|PH|
Husby|Haldor|H|
Gundersen|Tore|T|
Nytrø|Øystein|Ø|0000-0002-8163-2362
Øvrelid|Lilja|L|

Machine learning
Natural language processing
Reproducibility of results
Tomography
X-ray computed


Crystal structure of bis-[μ-bis-(di-phenyl-phosphanyl)methane-κ(2) P:P']digold(I) dichloride acetone monosolvate monohydrate.

Abstract: In the title complex salt, [Au2{(C6H5)2PCH2P(C6H5)2}]Cl2·(CH3)2C=O·H2O, the dication forms an eight-membered {-PCPAu}2 ring with a transannular aurophilic inter-action [Au⋯Au = 2.9743 (2) Å]. The ring approximates a flattened boat conformation, with the two methyl-ene C atoms lying ca 0.58-0.59 Å above the least-squares plane defined by the Au2P4 atoms (r.m.s. deviation = 0.0849 Å). One Cl(-) anion functions as a weak bridge between the Au(I) atoms [Au⋯Cl = 2.9492 (13) and 2.9776 (12) Å]. The second Cl(-) anion forms two (water)O-H⋯Cl hydrogen bonds about a centre of inversion, forming a centrosymmetric eight-membered {⋯HOH⋯Cl}2 supra-molecular square. Globally, the dications and loosely associated Cl(-) anions assemble into layers lying parallel to the ac plane, being connected by C-H⋯Cl,π(phen-yl) inter-actions. The supra-molecular squares and solvent acetone mol-ecules are sandwiched in the inter-layer region, being connected to the layers on either side by C-H⋯Cl,O(acetone) inter-actions.

Yeo|Chien Ing|CI|
Tan|Yee Seng|YS|
Tiekink|Edward R T|ER|

crystal structure
hydrogen bonding
aurophilic interaction
phosphanegold(I) salt
pseudopolymorph


Exploring the genetic pathogenicity of aortic dissection from 72 Han Chinese individuals using next-generation sequencing.

Abstract: Aortic dissection (AD) is a heterogeneous genetic disease with high morbidity and mortality. Although many genes predispose patients to AD, the pathogenic spectrum remains incomplete. This study aims to (a) investigate whether genotype differences exist between Stanford A and B AD individuals, and (b) broaden the pathogenic genetic spectrum of AD and reported novel variants of AD-associated genes. The DNA of 72 unrelated Han Chinese individuals with AD was tested by whole-exome sequencing. Of 142 AD-associated genes, 10 pathogenic variants, and 48 likely pathogenic variants in 36 genes were identified among 39 cases. The diagnostic yield was 54.2%. Of the 58 positive variants, 27 were novel. FBN1 was the most frequently positive gene in both Stanford A and Stanford B. Twenty-seven positive variants from 18 COL family genes were distributed in 36.8% of Stanford A and 6.7% of Stanford B cases. We emphasize that positive variants of COL family genes show distribution predominance and strong pathogenicity in Stanford A, while positive variants of smooth muscle cell pathway genes present distribution advantages mainly in Stanford B cases. Our findings provide a new perspective for both the pathogenic mechanism and the treatment of AD.

Pan|Meichen|M| Chen|Shu|S| Wang|Haihao|H| Wu|Shifan|S| Ding|Zijiao|Z| Wang|Yuning|Y| Li|Lianjie|L| Li|Zehao|Z| Liu|Qian|Q|0000-0001-8598-5256

D020022:Genetic Predisposition to Disease

aortic dissection
FBN1
COL family genes
distribution differences
genetic factors


Air quality in enclosed railway stations: Quantifying the impact of diesel trains through deployment of multi-site measurement and random forest modelling.

Abstract: Concentrations of the air pollutants (NO2 and particulate matter) were measured for several months and at multiple locations inside and outside two enclosed railway stations in the United Kingdom - Edinburgh Waverly (EDB) and London King's Cross (KGX) - which, respectively, had at the time 59% and 18% of their train services powered by diesel engines. Average concentrations of NO2 were above the 40 μg m-3 annual limit value outside the stations and were further elevated inside, especially at EDB. Concentrations of PM2.5 inside the stations were 30-40% higher at EDB than outside and up to 20% higher at KGX. Concentrations of both NO2 and PM2.5 were highest closer to the platforms, especially those with a higher frequency of diesel services. A random-forest regression model was used to quantify the impact of numbers of different types of diesel trains on measured concentrations allowing prediction of the impact of individual diesel-powered rolling stock.

Font|Anna|A|
Tremper|Anja H|AH|
Lin|Chun|C|
Priestman|Max|M|
Marsh|Daniel|D|
Woods|Michael|M|
Heal|Mathew R|MR|
Green|David C|DC|

D000393:Air Pollutants
D000397:Air Pollution
D004784:Environmental Monitoring
D008131:London
D052638:Particulate Matter
D006113:United Kingdom
D001335:Vehicle Emissions

Enclosed railway stations
Diesel trains
Random forest
Diesel exhaust


Near-full length sequencing of 16S rDNA and RFLP indicates that Rhizobium etli is the dominant species nodulating Egyptian winter Berseem clover (Trifolium alexandrinum L.).

Abstract: Egyptian winter Berseem clover (EWBC) is one of the main important forage legume crops in Egypt that is used for animal feeding in winter and it occupies about 2.5 million feddans (Feddan=4200m(2)) in winter agricultural rotation systems. Forty-eight rhizobial isolates that nodulated this legume host from different geographical regions within Egypt were isolated. RFLP analyses of 16S rDNA (1.5kb) and whole ribosomal DNA (5kb), the sequencing of 16S rDNA, and the sequencing of nodC, nifH and house keeping genes were used to identify these isolates. The RFLP analysis of 16S rDNA (1.5kb) among 15 representative strains with three enzymes generated two genotypes. The largest genotype was similar to Rhizobium etli CFN42T (93.33%) except for strain 902 that failed to re-nodulate EWBC. RFLP analysis of complete ribosomal DNA (5kb) produced five genotypes. The majority of tested strains shared the genotype with R. etli CFN42T (53.33%). Only one strain (1002) shared the genotype with Rhizobium leguminosarum sv. trifolii 3023. The other four strains were comprised of two unique genotypes. Phylogenetic analysis of 16S rDNA sequences revealed that seven representative strains could be divided into two genetic clusters sharing the ancestral clad with R. etli CFN42T. A phylogenetic tree based on nodC gene sequence confirmed that all the examined strains shared the genetic lineage with R. leguminosarum sv. trifolii WSM1325. The phylogenetic trees of house keeping genes are supported strongly the identification of majority of strains as a novel symbiovar of R. etli with new lineages.

Shamseldin|Abdelaal|A|
Moawad|Hassan|H|
Abd El-Rahim|Wafaa M|WM|
Sadowsky|Michael J|MJ|

D012150:Polymorphism, Restriction Fragment Length

16S rDNA and complete rDNA
Clover symbionts
Egyptian soils
Genetic diversity
Symbiotic genes


Erectile Dysfunction and Associated Anxiety and Depression in Male Hemodialysis Patients: A Cross-Sectional Study at Karachi Institute of Kidney Diseases.

Abstract: Objectives Chronic kidney disease (CKD) is one of the most prevailing diseases in the world and is associated with sequelae of depression, anxiety, and sexual dysfunction. The goal of our study is to measure the prevalence of erectile dysfunction, depression, and anxiety among patients suffering from CKD and to establish a correlation between them. Methodology The research was a single-centered, descriptive cross-sectional study. All male patients present at the time of the survey were interviewed, and then based on the inclusion and exclusion criteria, 84 were selected. The questionnaire comprised demographic variables, erectile function scoring using the International Index of Erectile Function (IIEF) scale, and Hospital Anxiety and Depression Scale (HADS) for depression and anxiety. All data were analyzed using SPSS Software 25.0 (IBM Corp., Armonk, USA). Results Out of 84 male patients, 47.6% had erectile dysfunction (ED). 10% of the affected individuals had depression and 3% reported having anxiety. No known external factors had any contribution to erectile malfunction, depression, and/or anxiety. Conclusion We found no correlation of depression and/or anxiety with ED in this population of male subjects undergoing hemodialysis.

Jarullah|Furqan Ahmad|FA|
Yaseen|Mahjabeen|M|
Abdullah|Hassan|H|
Yaqoob|Sadia|S|

erectile dysfunction
anxiety
depression
hemodialysis


On the Finiteness of the Weighted Likelihood Estimator of Ability.

Abstract: The purpose of this note is to focus on the finiteness of the weighted likelihood estimator (WLE) of ability in the context of dichotomous and polytomous item response theory (IRT) models. It is established that the WLE always returns finite ability estimates. This general result is valid for dichotomous (one-, two-, three- and four-parameter logistic) IRT models, the class of polytomous difference models and divide-by-total models, independently of the number of items, the item parameters and the response patterns. Further implications of this result are outlined.

finiteness
weighted likelihood estimation
item response theory
Bayesian estimation
dichotomous models
polytomous models


Acoustic shock waves to modify calcific plaques - Intravascular lithotripsy in the peripheral circulation.

Abstract: Intravascular lithotripsy (IVL) is a new technique for treatment of severely calcified lesions that uses acoustic shockwaves in a balloon-based system to induce fracture in calcific plaque, facilitating luminal gain and vessel expansion. In this review, we provide a concise summary of the available data and clinical experience of IVL in various peripheral vascular beds, including facilitating vascular access for large-bore devices. We discuss the physics and mode of action of IVL in modifying calcified plaques, include several illustrative examples of utility of IVL in peripheral interventions, and discuss the future directions for adoption of the technique in peripheral interventions.

Karimi Galougahi|Keyvan|K|
Soukas|Peter A|PA|
Kolski|Brian|B|
Tayal|Rajiv|R|
Parikh|Sahil A|SA|
Armstrong|Ehrin J|EJ|
Petrossian|George|G|
Kaki|Amir|A|
Rosenfield|Kenneth|K|
Gray|William A|WA|
Ali|Ziad A|ZA|

Calcification
Intravascular lithotripsy
Endovascular therapy
Percutaneous transluminal angioplasty


Chapter 17 Sterile Plate-Based Vitrification of Adherent Human Pluripotent Stem Cells and Their Derivatives Using the TWIST Method.

Abstract: Due to their high biological complexity, e.g., their close cell-to-cell contacts, cryopreservation of human pluripotent stem cells with standard slow-rate protocols often is inefficient and can hardly be standardized. Vitrification that means ultrafast freezing already showed very good viability and recovery rates for this sensitive cell system, but is only applicable for low cell numbers, bears a high risk of contamination, and can hardly be implemented under GxP regulations. In this chapter, a sterile plate-based vitrification method for adherent pluripotent stem cells and their derivatives is presented based on a procedure and device for human embryonic stem cells developed by Beier et al. (Cryobiology 66:8-16, 2013). This protocol overcomes the limitations of conventional vitrification procedures resulting in the highly efficient preservation of ready-to-use adherent pluripotent stem cells with the possibility of vitrifying cells in multi-well formats for direct application in high-throughput screenings.

Neubauer|Julia C|JC|
Stracke|Frank|F|
Zimmermann|Heiko|H|

Sterile plate-based vitrification
Stem cells
Adherent cells
GMP compliant


Chyme Reinfusion Is Associated with Lower Rate of Postoperative Ileus in Crohn's Disease Patients After Stoma Closure.

Abstract:
BACKGROUND
The rate of postoperative ileus following stoma closure is high in patients with Crohn's disease and temporary enterostomy.

AIMS
To evaluate the effect of chyme reinfusion on postoperative outcomes including ileus in these patients.

METHODS
Patients were screened from January 2012 to December 2017 and divided into chyme reinfusion group (n = 33) and non-chyme reinfusion group (n = 84). The following 30-day postoperative outcomes were evaluated. Univariate and multivariate analyses and propensity score matching were performed to identify risk factors for these postoperative outcomes.

RESULTS
The incidence of postoperative ileus was significantly lower in the chyme reinfusion than in non-chyme reinfusion group, which had been confirmed by the results after matching (3/26 vs 11/26, p = 0.012). The rate of postoperative diarrhea was significantly lower in the chyme reinfusion group compared with non-chyme reinfusion group, whereas the difference was not significant after matching (2/26 vs 6/26, p = 0.191). Additionally, the postoperative length of stay was significantly shorter in the chyme reinfusion than in non-chyme reinfusion group before and after propensity score matching. In the multivariate analysis, chyme reinfusion was an independent protective factor for postoperative ileus (odds ratio 0.218; 95% confidence interval 0.05-0.95; p = 0.042) and for postoperative length of stay (coefficient - 0.191; 95% confidence interval - 0.350 to - 0.032, p = 0.019).

CONCLUSIONS
Chyme reinfusion was associated with lower rate of postoperative ileus and shorter length of stay following stoma closure in Crohn's patients with temporary ileostomy. Further randomized clinical trial between patients with or without chyme reinfusion was needed to confirm these conclusions.

Duan|Ming|M| Cao|Lei|L| Gao|Lei|L| Gong|Jianfeng|J| Li|Yi|Y| Zhu|Weiming|W|

Chyme reinfusion
Ileus
Enterostomy
Crohn’s disease


The Early Impact of the COVID-19 Lockdown on Stress and Addictive Behaviors in an Alcohol-Consuming Student Population in France.

Abstract: Background: This study evaluated factors linked with perceived stress related to the COVID-19 pandemic and lockdown and addictive behaviors prior to and during lockdown in a sample of students who indicated engaging in alcohol consumption behaviors before lockdown. Methods: Cross-sectional study. French students from four universities participated in this study, and 2,760 students reported alcohol use. During the first week of lockdown, students reported their perceived levels of stress regarding COVID-19. Substance use and addictive behaviors were reported before and during lockdown, and media exposure, demographical, living conditions, and environmental stressors were reported during lockdown. Results: Women reported greater levels of stress (95% CI: 1.18 to 1.93, p < 0.001). Highly-stressed students also report less social support (95% CI: -1.04 to -0.39, p < 0.001) and were more likely to worry about the lockdown (95% CI: 0.27 to -0.65, p < 0.001). Alcohol-related problemswere more prevalent among the most stressed students (95% CI: 0.02 to 0.09, p = 0.004) as well as eating problems (95% CI: 0.04 to 0.36, p = 0.016) and problematic internet use (95% CI, 0.06 to 0.14, p < 0.001). Students reporting the highest levels of stress also indicated more compulsive eating during the previous seven days (95% CI, 0.21 to 1.19, p = 0.005). Conclusions: The level of stress was strongly related to four categories of variables: (i) intrinsic characteristics, (ii) addictive behaviors before lockdown, (iii) lockdown-specific conditions, and (iv) addictive behaviors during the lockdown. Several variables linked to COVID-19 were not directly linked with perceived stress, while perceived stress was found to correlate with daily life organization-related uncertainty and anticipated consequences of lockdown. Importantly, social support seems to be a protective factor on high level of stress.

Flaudias|Valentin|V|
Zerhouni|Oulmann|O|
Pereira|Bruno|B|
Cherpitel|Cheryl J|CJ|
Boudesseul|Jordane|J|
de Chazeron|Ingrid|I|
Romo|Lucia|L|
Guillaume|Sébastien|S|
Samalin|Ludovic|L|
Cabe|Julien|J|
Bègue|Laurent|L|
Gerbaud|Laurent|L|
Rolland|Benjamin|B|
Llorca|Pierre-Michel|PM|
Naassila|Mickael|M|
Brousse|Georges|G|

COVID-19
LockDown
addiction
alcohol
stressors
Coronavirus
public health


Measuring Perceptions of the Therapeutic Alliance in Individual, Family, and Group Therapy from a Systemic Perspective: Structural Validity of the SOFTA-s.

Abstract: This study examined the multidimensional structure of the client and therapist versions of the self-report measure, System for Observing Family Therapy Alliances (SOFTA-s; Friedlander, Escudero, & Heatherington, Therapeutic alliances in couple and family therapy: An empirically informed guide to practice. Washington, DC: American Psychological Association, 2006) across three distinct therapeutic modalities (individual, family, group). Specifically, we investigated whether the originally theorized model of four first-order factors (Engagement in the Therapeutic Process, Emotional Connection with the Therapist, Safety within the Therapeutic System, and Shared Sense of Purpose within the Family) would be reflected in a second-order factor (Therapeutic Alliance). The sample included 105 therapists who worked with 858 clients (165 individuals, 233 families, and 43 groups) in several Spanish community agencies. To control for dependent data, we used multilevel modeling. Results of the multilevel confirmatory factor analyses showed adequate reliabilities, fit indices, and factor loadings across the three therapy contexts for both versions of the measure (client and therapist). Adequate measurement invariance was also found across respondents and therapy modalities. Taken together, these results support the structural validity of the SOFTA-s, a brief and flexible self-report alliance measure that can be used reliably in clinical practice as well as in studies of individual, family, and group therapy.

análisis factorial confirmatorio multinivel


Understanding Food Loss and Waste-Why Are We Losing and Wasting Food?

Abstract: The Food and Agricultural Organization (FAO) reported that approximately one-third of all produced foods (1.3 billion tons of edible food) for human consumption is lost and wasted every year across the entire supply chain. Significant impacts of food loss and waste (FLW) have increased interest in establishing prevention programs around the world. This paper aims to provide an overview of FLW occurrence and prevention. Economic, political, cultural, and socio-demographic drivers of FLW are described, highlighting the global variation. This approach might be particularly helpful for scientists, governors, and policy makers to identify the global variation and to focus on future implications. The main focus here was to identify the cause of the FLW occurrence throughout the food supply chain. We have created a framework for FLW occurrence at each stage of the food supply chain. Several feasible solutions are provided based on the framework.

Ishangulyyev|Rovshen|R|
Kim|Sanghyo|S|
Lee|Sang Hyeon|SH|0000-0003-1610-9994

food loss
food security
food waste
waste management
waste prevention


The Spread of Helicoverpa armigera (Lepidoptera: Noctuidae) and Coexistence with Helicoverpa zea in Southeastern Brazil.

Abstract: Helicoverpa armigera, one of the world's most destructive crop pests, was first documented in Brazil in 2013. Within a few months, this polyphagous insect had spread over the Northeast and Central-West of Brazil, causing great agricultural losses. With several reports of populations resistant to pesticides and Bt crops around the world, there is great concern about the spread of this pest in Brazil. There is confusion about the actual distribution of this species due to the high morphological similarity with the native corn earworm Helicoverpa zea, which may also coexist with H. armigera in the field. Our aims here were (i) to confirm its presence in the State of Minas Gerais, one of the most important agricultural regions in the country; and (ii) to assess the co-occurrence of this pest with the congeneric corn earworm H. zea. Using molecular screening, we confirmed the presence of H. armigera in Bt-crops of soybean and cotton, and non-Bt-crops of soybean, cotton and maize. Mixed infestations of H. armigera with H. zea were found in non-Bt maize (Viçosa, Southeastern Minas Gerais). These results highlight the need for adequate control strategies for H. armigera in Brazil, to deal with its polyphagous feeding habits, high dispersal capacity and possible risks of hybridization with congeneric species.

Pinto|Fábio A|FA|
Mattos|Marcos V V|MVV|
Silva|Farley W S|FWS|
Rocha|Silma L|SL|
Elliot|Simon L|SL|

Noctuidae pest DNA PCR-RFLP mitochondrial


Prospective survey-based study on the categorization quality of hospital pharmacists' interventions using DokuPIK.

Abstract: Background There is a growing need to categorize pharmacists' interventions (PIs) in Germany to document their impact on solving or avoiding drug-related problems. Objective To validate the categorization of drug-related problems-one aspect of the categorical internet database DokuPIK, designed for recording routinely PIs. To identify case-specific predictive values. Setting German hospitals. Methods Within a prospective, nationwide survey-based study, 37 of 498 registered database users volunteered to evaluate 24 standardized case reports independently. Case evaluation was restricted to classify problems, based on 26 given categories with no limit on the number of item choices. Ratings were conducted electronically and anonymously. A gold standard of one or more problems per case was developed by majority consensus of five senior clinical pharmacists. Agreement of raters' case classification with the gold standard was assessed by calculating sensitivity, specificity and positive and negative predictive value and was reported as median and range. Main outcome Level of agreement. Results Independent assessment yielded a median agreement of 90% [79-94%]. Sensitivity and specificity were 37% [21-57%] and 99% [97-100%], respectively. Median positive and negative predicted value were both 90% [60-100%] and 90% [78-95%]. Mean case-specific agreement was robust (≥ 79%) with respect to a majority and maximum consensus (three and five out of five raters). Conclusion DokuPIK seems to have a high level of agreement and a good specificity according to the majority of clinical pharmacists in a panel of assessors. Despite the allowance of multiple choices, predictive values were high and indicated a well-constructed classification by pharmacists.

D016208:Databases, Factual
D005858:Germany
D006801:Humans
D008508:Medication Errors
D010607:Pharmacy Service, Hospital
D011446:Prospective Studies
D012680:Sensitivity and Specificity
D011795:Surveys and Questionnaires

Germany
Drug-related problems
Classification system
Clinical pharmacy services
Medication safety
Pharmaceutical care
Pharmacist interventions


A Micronutrient Fortified Beverage Given at Different Dosing Frequencies Had Limited Impact on Anemia and Micronutrient Status in Filipino Schoolchildren.

Abstract: This study evaluated the effects of a multi-micronutrient fortified juice drink given in different frequencies of consumption on hemoglobin (Hb) concentration of schoolchildren. Hb was measured in 2423 schoolchildren aged 6- to 9-years-old at baseline. All anemic children (n = 246) were randomly allocated into groups: Daily dose (HD: high dose), 5X/week (MD: Moderate Dose), 3X/week (LD: Low Dose) and unfortified (Control). Pre- and post-study measurements of micronutrients were collected from 228 children. At the endpoint, significant Hb increases were observed in all groups, but there was no significant difference between groups. There was a significant reduction in anemia prevalence in all groups from 100% to 36% (Control), 30% (LD), 23% (MD) and 26% (HD). No dose-response effect was observed in Hb in this population. Most likely, this resulted from better than expected micronutrient status and lower than expected severity of anemia and micronutrient deficiencies in this cohort. It is unlikely that the addition of a fortified beverage to school feeding programs in this population would have a positive impact. Whether such an intervention would be cost-effective as a preventative approach needs to be assessed. This study demonstrates the importance of targeting such interventions to appropriate populations.

Angeles-Agdeppa|Imelda|I|
Magsadia|Clarita R|CR|
Aaron|Grant J|GJ|
Lloyd|Beate B|BB|
Hilmers|David C|DC|
Bhutta|Zulfiqar A|ZA|

dose response 2
hemoglobin 1
multi-nutrient fortified juice drink 3


Next Chapter in the Legend of Silphion: Preliminary Morphological, Chemical, Biological and Pharmacological Evaluations, Initial Conservation Studies, and Reassessment of the Regional Extinction Event.

Abstract: Silphion was an ancient medicinal gum-resin; most likely obtained from a Ferula species growing in the Cyrene region of Libya ca. 2500 years ago. Due to its therapeutic properties and culinary value, silphion became the main economic commodity of the Cyrene region. It is generally believed that the source of silphion became extinct in the first century AD. However, there are a few references in the literature about the cultivated silphion plant and its existence up to the fifth century. Recently, a rare and endemic Ferula species that produces a pleasant-smelling gum-resin was found in three locations near formerly Greek villages in Anatolia. Morphologic features of this species closely resemble silphion, as it appears in the numismatic figures of antique Cyrenaic coins, and conform to descriptions by ancient authors. Initial chemical and pharmacological investigations of this species have confirmed the medicinal and spice-like quality of its gum-resin supporting a connection with the long-lost silphion. A preliminary conservation study has been initiated at the growth site of this rare endemic Ferula species. The results of this study and their implications on the regional extinction event, and future development of this species will be discussed.

silphion
conservation
extinction
Ferula
F. drudeana
chemistry and pharmacology
medicinal oleo-gum-resin


Treatment of convulsive status epilepticus in childhood: recommendations of the Italian League Against Epilepsy.

Abstract: The Italian League Against Epilepsy Commission Guidelines Subcommittee on Status Epilepticus (SE) has published an article on the management of SE in adults, and now presents a report on the management of convulsive status epilepticus (CSE) in children, excluding the neonatal period. Children's greater susceptibility than adults to epileptic seizures results from many factors. Earlier maturation of excitatory than inhibitory synapses, increased susceptibility and concentration of receptors for excitatory neurotransmitters, peculiar composition of the receptor subunits resulting in slower and less effective inhibitory responses, all cause the high incidence of SE in the pediatric population. The related morbidity and mortality rates, although lower than in adults, require immediate diagnosis and therapy. The division into focal and generalized, nonconvulsive and convulsive SE is applied in children and adolescents, as is the distinction in the three different stages according to the time elapsed since the start of the event and the response to drugs (initial, defined, and refractory SE). In children and adolescents, an "operational definition" is also accepted to allow earlier treatment (starting at 5-10 min). Maintenance and stabilization of vital functions, cessation of convulsions, diagnosis, and initial treatment of potentially "life-threatening" causes are the objectives to be pursued in the management of children with CSE. The need for early pharmacologic intervention stresses the need for action in the prehospital setting, generally using rectal diazepam. In hospital, parenteral benzodiazepines are used (lorazepam, diazepam, or midazolam). When first-line drugs fail, sodium phenytoin and phenobarbital should be used. As alternatives to phenobarbital, the following can be considered for treatment of refractory CSE: valproate, levetiracetam, and lacosamide. In cases with refractory CSE, pharmacologic options can be thiopental, midazolam, or propofol in continuous intravenous infusions to suppress electroencephalographic bursts and convulsive activity. These drugs need to be administered in intensive care units to ensure the monitoring and support of vital signs and brain electrical activity.

Capovilla|Giuseppe|G| Beccaria|Francesca|F| Beghi|Ettore|E| Minicucci|Fabio|F| Sartori|Stefano|S| Vecchi|Marilena|M|


Altered SPECT (123)I-iomazenil Binding in the Cingulate Cortex of Children with Anorexia Nervosa.

Abstract: Several lines of evidence suggest that anxiety plays a key role in the development and maintenance of anorexia nervosa (AN) in children. The purpose of this study was to examine cortical GABA(A)-benzodiazepine receptor binding before and after treatment in children beginning intensive AN treatment. Brain single-photon emission computed tomography (SPECT) measurements using (123)I-iomazenil, which binds to GABA(A)-benzodiazepine receptors, was performed in 26 participants with AN who were enrolled in a multimodal treatment program. Sixteen of the 26 participants underwent a repeat SPECT scan immediately before discharge at conclusion of the intensive treatment program. Eating behavior and mood disturbances were assessed using Eating Attitudes Test with 26 items (EAT-26) and the short form of the Profile of Mood States (POMS). Clinical outcome scores were evaluated after a 1-year period. We examined association between relative iomazenil-binding activity in cortical regions of interest and psychometric profiles and determined which psychometric profiles show interaction effects with brain regions. Further, we determined if binding activity could predict clinical outcome and treatment changes. Higher EAT-26 scores were significantly associated with lower iomazenil-binding activity in the anterior and posterior cingulate cortex. Higher POMS subscale scores were significantly associated with lower iomazenil-binding activity in the left frontal, parietal cortex, and posterior cingulate cortex (PCC). "Depression-Dejection" and "Confusion" POMS subscale scores, and total POMS score showed interaction effects with brain regions in iomazenil-binding activity. Decreased binding in the anterior cingulate cortex and left parietal cortex was associated with poor clinical outcomes. Relative binding increases throughout the PCC and occipital gyrus were observed after weight gain in children with AN. These findings suggest that cortical GABAergic receptor binding is altered in children with AN. This may be a state-related change, which could be used to monitor and guide the treatment of eating disorders.

Nagamitsu|Shinichiro|S|
Sakurai|Rieko|R|
Matsuoka|Michiko|M|
Chiba|Hiromi|H|
Ozono|Shuichi|S|
Tanigawa|Hitoshi|H|
Yamashita|Yushiro|Y|
Kaida|Hayato|H|
Ishibashi|Masatoshi|M|
Kakuma|Tatsuki|T|
Croarkin|Paul E|PE|
Matsuishi|Toyojiro|T|

cingulate cortex
children
anorexia nervosa
GABA
iomazenil SPECT


Drugging cancer metabolism: Expectations vs. reality.

Abstract: As compared to their normal counterparts, neoplastic cells exhibit a variety of metabolic changes that reflect not only genetic and epigenetic defects underlying malignant transformation, but also the nutritional and immunobiological conditions of the tumor microenvironment. Such alterations, including the so-called Warburg effect (an increase in glucose uptake largely feeding anabolic and antioxidant metabolism), have attracted considerable attention as potential targets for the development of novel anticancer therapeutics. However, very few drugs specifically conceived to target bioenergetic cancer metabolism are currently approved by regulatory agencies for use in humans. This reflects the elevated degree of heterogeneity and redundancy in the metabolic circuitries exploited by neoplastic cells from different tumors (even of the same type), as well as the resemblance of such metabolic pathways to those employed by highly proliferating normal cells. Here, we summarize the major metabolic alterations that accompany oncogenesis, the potential of targeting bioenergetic metabolism for cancer therapy, and the obstacles that still prevent the clinical translation of such a promising therapeutic paradigm.

D000818:Animals
D000970:Antineoplastic Agents
D050260:Carbohydrate Metabolism
D063646:Carcinogenesis
D004035:Diet Therapy
D004734:Energy Metabolism
D006801:Humans
D050356:Lipid Metabolism
D053858:Metabolic Networks and Pathways
D058990:Molecular Targeted Therapy
D009369:Neoplasms
D059016:Tumor Microenvironment

Glutamine
Krebs cycle
Oxidative phosphorylation
Pentose phosphate pathway
Reductive carboxylation
Serine


A strategy to prevent a temperature-induced MRI artifact in warm liquid phantoms due to convection currents.

Abstract: MRI phantom studies often fail to mimic the temperature of the human body, which can negatively impact accuracy. An artifact induced by increasing temperature in liquid phantoms was observed, presenting a significant challenge to temperature-controlled experiments. In this study we characterize and provide a solution to eliminate this temperature-induced MRI artifact. Low concentration (0.5-2.5 mM) agar phantoms were prepared. Utilizing a temperature-controlled phantom holder, T1 - and T2 -weighted structural images were acquired at 7 T along with quantitative B0 , B1 , T1 , T2 and ADC maps at both 25 and 37°C. Additionally, computer simulations were conducted to demonstrate the fluid flow and thermal flux patterns in water to provide an insight into the origins of the artifact. Evidence from computer simulation and quantitative MRI strongly suggest the artifact was caused by heat transfer in the form of natural convection leading to structured patterns of signal loss in MR images. The artifact was present up to agar concentrations of 1.5 mM (T1 = 3068 ± 16 ms, T2 = 1052 ± 20 ms, ADC = 2.29 ± 0.36 × 10-3 mm2 /s at 25°C; T1 = 3928 ± 44 ms, T2 = 1122 ± 24 ms, ADC = 2.64 ± 0.49 × 10-3 mm2 /s at 37°C), above which point increased sample viscosity no longer allows for convection currents, thereby eliminating the artifact. The methodology described in this work simplifies quantitative MR acquisition of liquid phantoms at physiological temperature by suppressing convection currents with relatively small changes to intrinsic MR parameters (T1 increased by 1.4% and T2 decreased by 17% for 1.5 mM agar at 25°C).

convection current
temperature-controlled phantom holder
quantitative MRI
temperature-induced artifact


Controlling Tumor Progression with Cyclophosphamide, Vincristine, and Dacarbazine Treatment Improves Survival in Patients with Metastatic and Unresectable Malignant Pheochromocytomas/Paragangliomas.

Abstract: Evidence has not been established to support that combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine (CVD) improves survival in patients with malignant pheochromocytoma and paraganglioma (M-PPGL). To investigate the efficacy of CVD for this disease, we retrospectively analyzed data of 23 patients with metastatic and unresectable M-PPGL (mean age, 41.7 ± 15.4 years) who received at least 2 cycles of this regimen. The follow-up period after initiation of CVD ranged from 0.3 to 13.7 years, with a median of 3.3 years. CVD therapy achieved a complete tumor response (CR) in 1 patient (4%), a partial response (PR) in 5 (22%), stable disease (SD) in 5 (22%), and progressive disease (PD) in 13 (52%), respectively. All of the responders (CR and PR) but 6% of the non-responders (SD and PD) showed substantial biochemical improvement. The progression-free survival period in the responders was significantly longer than in the non-responders (p < 0.01). Although the overall survival and survival after the diagnosis of M-PPGL were longer in the responders than the non-responders, the difference was not statistically significant (p = 0.08). The progression-free and overall survival period were significantly longer in the non-progression group (CR, PR, and SD) than in the progression group (PD) (1.7 ± 3.3 vs. 0.3 ± 0.3 years, p < 0.01, and 4.6 ± 3.6 vs. 2.0 ± 3.7 years, p = 0.01, respectively). It is therefore suggested that CVD chemotherapy could be useful in controlling tumor progression and improving survival in patients with metastatic and progressive M-PPGL.

Asai|Shiko|S| Katabami|Takuyuki|T| Tsuiki|Mika|M| Tanaka|Yasushi|Y| Naruse|Mitsuhide|M|

D000971:Antineoplastic Combined Chemotherapy Protocols

Malignant pheochromocytoma
Paraganglioma
CVD therapy
Antineoplastic combined chemotherapy
Myelodysplastic syndromes
Survival time


Chronic inflammatory lesions of the placenta.

Abstract: The chronic inflammatory lesions of the placenta often run in the shadows of the better-known acute inflammatory processes of the placenta, such as acute chorioamnionitis and acute funisitis. A heterogeneous population of T-cell lymphocytes, plasma cells, and macrophages is the primary player in chronic villitis, chronic chorioamnionitis, chronic deciduitis, and chronic intervillositis, and eosinophils are an added component of eosinophilic/T-cell chorionic vasculitis. The histologic appearance, sites of occurrence in the placenta, and pathogeneses of these entities are reviewed.

Alloimmunity
Infection
Inflammation
Placenta disorders


Effect of Metamorphed Keratolytic Agent on the Behavior of Imiquimod Loaded Hybrid Vesicles Containing Gel.

Abstract: The cost, side effects, and patient compliance-related issues of topically effective imiquimod have prevented its widespread acceptance. The present work intends to evaluate the feasibility of overcoming the shortcomings of poorly soluble and skin-penetrating immunomodulator by using biocompatible keratolytic agent with drug-loaded hybrid vesicles. Salicylic acid was complexed with phospholipid through simple mixing and incorporated into carbopol 940 gel containing drug-loaded vesicles, prepared by thin-film hydration method. The morphology, physicochemical properties, rheological behavior, release profile, and dermatokinetics of developed gel were compared with control gel (developed gel without keratolytic agent). In ex vivo drug release studies across the rat skin, there was significant increase in the steady-state permeation flux (Jss) and skin retention of drug from developed gel in comparison with control. There was favorable change in almost every evaluated dermatokinetic parameter. The innocuous nature of control gel had not changed on addition of skin structure-altering agent. The developed gel was found to be stable at room temperature and humidity for 1 year.

Sharma|Mandeep|M|
Sharma|Gajanand|G|
Raza|Kaisar|K|
Singh|Bhupinder|B|
Katare|Om Prakash|OP|

biocompatibility
complexation
phospholipid
skin
drug delivery system
hydrogel
immune response
liposomes
pharmacokinetics
toxicity


Non-invasive diagnosis of viability in seeds and lichens by infrared thermography under controlled environmental conditions.

Abstract:
Background
Non-invasive procedures for the diagnosis of viability of plant or fungal tissues would be valuable for scientific, industrial and biomonitoring purposes. Previous studies showed that infrared thermography (IRT) enables non-invasive assessment of the viability of individual "orthodox" (i.e. desiccation tolerant) seeds upon water uptake. However, this method was not tested for rehydrating tissues of other desiccation tolerant life forms. Furthermore, evaporative cooling could obscure the effects of metabolic processes that contribute to heating and cooling, but its effects on the shape of the "thermal fingerprints" have not been explored. Here, we further adapted this method using a purpose-built chamber to control relative humidity (RH) and gaseous atmosphere. This enabled us to test (i) the influence of relative humidity on the thermal fingerprints during the imbibition of Pisum sativum (Garden pea) seeds, (ii) whether thermal fingerprints can be correlated with viability in lichens, and (iii) to assess the potential influence of aerobic metabolism on thermal fingerprints by controlling the oxygen concentration in the gaseous atmosphere around the samples. Finally, we developed a method to artificially "age" lichens and validated the IRT-based method to assess lichen viability in three lichen species.

Results
Using either 30% or 100% RH during imbibition of pea seeds, we showed that "live" and "dead" seeds produced clearly discernible "thermal fingerprints", which significantly differed by > |0.15| °C in defined time windows, and that RH affected the shape of these thermal fingerprints. We demonstrated that IRT can also be used to assess the viability of the lichens Lobaria pulmonaria, Pseudevernia furfuracea and Peltigera leucophlebia. No clear relationship between aerobic metabolism and the shape of thermal fingerprints was found.

Conclusions
Infrared thermography appears to be a promising method for the diagnosis of viability of desiccation-tolerant tissues at early stages of water uptake. For seeds, it is possible to diagnose viability within the first hours of rehydration, after which time they can still be re-dried and stored until further use. We envisage our work as a baseline study for the use of IR imaging techniques to investigate physiological heterogeneity of desiccation tolerant life forms such as lichens, which can be used for biomonitoring, and for sorting live and dead seeds, which is potentially useful for the seed trade.

Viability
Seeds
Lichen
Desiccation tolerance
Stress
Thermal imaging


Cancer death rates in US congressional districts.

Abstract: Knowledge of the cancer burden is important for informing and advocating cancer prevention and control. Mortality data are readily available for states and counties, but not for congressional districts, from which representatives are elected and which may be more influential in compelling legislation and policy. The authors calculated average annual cancer death rates during 2002 to 2011 for each of the 435 congressional districts using mortality data from the National Center for Health Statistics and population estimates from the US Census Bureau. Age-standardized death rates were mapped for all sites combined and separately for cancers of the lung and bronchus, colorectum, breast, and prostate by race/ethnicity and sex. Overall cancer death rates vary by almost 2-fold and are generally lowest in Mountain states and highest in Appalachia and areas of the South. The distribution is similar for lung and colorectal cancers, with the lowest rates consistently noted in districts in Utah. However, for breast and prostate cancers, while the highest rates are again scattered throughout the South, the geographic pattern is less clear and the lowest rates are in Hawaii and southern Texas and Florida. Within-state heterogeneity is limited, particularly for men, with the exceptions of Texas, Georgia, and Florida. Patterns also vary by race/ethnicity. For example, the highest prostate cancer death rates are in the West and north central United States among non-Hispanic whites, but in the deep South among African Americans. Hispanics have the lowest rates except for colorectal cancer in Wyoming, eastern Colorado, and northern New Mexico. These data can facilitate cancer control and stimulate conversation about the relationship between cancer and policies that influence access to health care and the prevalence of behavioral and environmental risk factors.

Siegel|Rebecca L|RL|
Sahar|Liora|L|
Portier|Kenneth M|KM|
Ward|Elizabeth M|EM|
Jemal|Ahmedin|A|

legislation
Congress
cancer mortality
geography


Intellectual functioning in clinically confirmed fetal valproate syndrome.

Abstract:
BACKGROUND
An increased risk of impaired intelligence (IQ) has been documented in valproate-exposed children, but investigations have not previously focused on those with a clinical diagnosis of Fetal Valproate Syndrome (FVS).

METHODS
This cross sectional observational study recruited individuals with a diagnosis of FVS and completed standardized assessments of intellectual abilities making comparisons to a normative comparison group. Both mean difference (MD) and prevalence of scores below the lower average range were analyzed.

RESULTS
The mean full-scale IQ in 31 individuals with FVS (mean age 14.97; range 6-27 years) was 19 points lower (19.55, 95% CI -24.94 to 14.15), and IQ scores <70 were present in 26%. The mean differences for verbal comprehension (21.07, 95% CI -25.84 to -16.29), working memory (19.77, 95% CI -25.00 to -14.55) and processing speed (16.87, 95% CI -22.24 to -11.50) performances were poorer than expected with the mean differences over one standard deviation from the comparison group. Sixty one percent of cases demonstrated disproportionately lower verbal comprehension ability. There were no significant group differences for IQ in high vs. moderate dose valproate or mono vs. polytherapy. There were no differences in IQ between those with and those without a major congenital malformation. The requirement for educational intervention was high at 74%.

CONCLUSION
Intellectual difficulties are a central feature of FVS and are more severe in their presentation in individuals with a diagnosis of valproate embryopathy. Individuals with FVS who present with the characteristic facial presentation should be considered at high risk of cognitive difficulties regardless of the dose of valproate exposure or the presence of a major congenital malformation.

Bromley|Rebecca L|RL|
Baker|Gus A|GA|
Clayton-Smith|Jill|J|
Wood|Amanda G|AG|

Fetal valproate syndrome
Intelligence
Epilepsy
Fetal anticonvulsant syndrome
Pregnancy
Sodium valproate
Teratology


Facile preparation of the N-acetyl-glucosaminylated asparagine derivative with TFA-sensitive protecting groups useful for solid-phase glycopeptide synthesis.

Abstract: In this study, a novel N-acetyl-glucosaminylated asparagine derivative was developed. This derivative carried TFA-sensitive protecting groups and was derived from commercially available compounds only in three steps. It was applicable to the ordinary 9-fluorenylmethoxycarbonyl (Fmoc)-based solid-phase peptide synthesis (SPPS) method, and the protecting groups on the carbohydrate moiety could be removed by a single step of TFA cocktail treatment generally used for the final deprotection step in Fmoc-SPPS.

glycopeptide
solid-phase peptide synthesis
N-acetylglucosamine
insulin-like androgenic gland factor


Effect of ultrasound on the isoflavonoid production in Genista tinctoria L. suspension cultures.

Abstract:
BACKGROUND
Application of ultrasound (US) to biotechnology is relatively new but several processes that take place in the presence of cells or enzymes are activated by ultrasonic waves. Genista tinctoria L. (Fabaceae) is rich on various kind of flavonoids, including isoflavones with valuable estrogenic activity.

OBJECTIVE
This study verified use of low-energy US elicitor to enhance secondary metabolite production in plant cell cultures.

MATERIALS AND METHODS
Suspension cultures of G. tinctoria cells was exposed to low-power US (with fixed frequency 35 kHz and power level 0.1 mW/cm(3)) for period 1-5 min.

RESULTS
The US exposure significantly stimulated genistin content (0.8 mg/g DW) after 3 min of US treatment (sampled after 72 h). The highest daidzein level (1.4 mg/g DW) was reached after US irradiation for 5 min and 168 h sampling.

CONCLUSION
The achieved results suggest that US can act as a potent abiotic elicitor to induce the defense responses of plant cells and to stimulate secondary metabolite production in plant cell cultures.

ultrasound
Genista tinctoria
suspension
genistin
Daidzein


Optimizing Preparative Regimen for Umbilical Cord Blood Transplantation in Adult Acute Leukemia Patients: Acute Lymphoblastic Leukemia Requires Myeloablative Conditioning but Not Acute Myeloid Leukemia.

Abstract: Cord blood transplantation (CBT) is a valuable alternative to bone marrow transplantation in adults without readily available donors. We conducted this study to investigate the feasibility of CBT for adult patients with acute leukemia with regards to impact of different conditioning and graft-versus-host disease (GVHD) prophylaxis regimens on clinical outcomes. From 16 centers in Korea, 41 acute myeloid leukemia (AML) and 29 ALL (acute lymphoblastic leukemia) patients undergoing CBT were enrolled. For AML patients, the neutrophil engraftment was observed in 87.5% of reduced intensity conditioning (RIC) and 72.0% of myeloablative conditioning (MAC) (p = 0.242). The median RFS was 5 months and OS 7 months. Conditioning regimen did not affect relapse free survival (RFS) or overall survival (OS). GVHD prophylaxis using calcineurin inhibitors (CNI) plus methotrexate was associated with better RFS compared to CNI plus ATG (p = 0.032). For ALL patients, neutrophil engraftment was observed in 55.6% of RIC and 90.0% of MAC (p = 0.034). The median RFS was 5 months and OS 19 months. MAC regimens, especially total body irradiation (TBI)-based regimen, were associated with both longer RFS and OS compared to other conditioning regimens. In conclusion, individualized conditioning regimens will add value in terms of enhancing safety and efficacy of CBT.

Byun|Ja Min|JM|0000-0003-1780-5553
Hong|Junshik|J|
Oh|Doyeun|D|0000-0002-6981-3144
Yhim|Ho-Young|HY|
Do|Young Rok|YR|
Park|Joon Seong|JS|
Jung|Chul Won|CW|
Yang|Deok-Hwan|DH|
Won|Jong-Ho|JH|
Lee|Hong Ghi|HG|
Moon|Joon Ho|JH|
Mun|Yeung-Chul|YC|
Jo|Deog-Yeon|DY|
Han|Jae Joon|JJ|
Lee|Je-Hwan|JH|
Lee|Jae Hoon|JH|
Lee|Junglim|J|
Yoon|Sung-Soo|SS|0000-0003-2591-7459

cord blood transplantation
acute lymphoblastic leukemia
conditioning
acute myeloid leukemia


Water-Based Synthesis of Palladium Trigonal Bipyramidal/Tetrahedral Nanocrystals with Enhanced Electrocatalytic Oxidation Activity.

Abstract: Well-defined palladium trigonal bipyramidal/tetrahedral nanocrystals were synthesized by an aqueous-phase hydrothermal method. The final products were a mixture of trigonal bipyramidal and tetrahedral nanocrystals. Statistics indicated that there were more trigonal bipyramids than tetrahedra in the products. Ethylenediamine tetraacetic acid disodium salt (EDTA-2Na) was proven to be essential in controlling the final shapes of palladium nanocrystals. Some control experiments were also conducted to investigate the shape evolution and formation mechanisms. The synthesized palladium nanocrystals showed enhanced catalytic properties for ethanol and glycerol electrooxidation in alkaline medium. This work provides a new method in preparing Pd nanomaterials with well-defined shapes.

Shang|Changshuai|C| Hong|Wei|W| Guo|Yaxiao|Y| Wang|Jin|J| Wang|Erkang|E|

palladium
trigonal bipyramidal
tetrahedral
glycerol electrooxidation
ethanol electrooxidation
nanoparticles


The effect of constant-intensity endurance training and high-intensity interval training on aerobic and anaerobic parameters in youth.

Abstract:
INTRODUCTION
High-Intensity Interval Training (HIIT) and Constant-Intensity Endurance Training (CIET) improves peak oxygen uptake (V̇O2) similarly in adults; but in children this remains unclear, as does the influence of maturity.

METHODS
Thirty-seven boys formed three groups: HIIT (football; n = 14; 14.3 ± 3.1 years), CIET (distance runners; n = 12; 13.1 ± 2.5 years) and a control (CON) group (n = 11; 13.7 ± 3.2 years). Peak V̇O2 and gas exchange threshold (GET) were determined from a ramp test and anaerobic performance using a 30 m sprint pre-and-post a three-month training cycle.

RESULTS
The HIIT groups peak V̇O2 was significantly higher than the CON group pre (peak V̇O2: 2.54 ± 0.63 l·min-1 vs 2.03 ± 0.53 l·min-1, d = 0.88; GET: 1.41 ± 0.26 l·min-1 vs 1.13 ± 0.29 l·min-1, d = 1.02) and post-training (peak V̇O2: 2.63 ± 0.73 l·min-1 vs 2.08 ± 0.64 l·min-1, d = 0.80; GET: 1.32 ± 0.33 l·min-1 vs 1.15 ± 0.38 l·min-1, d = 0.48). All groups showed a similar magnitude of change during the training (p > 0.05).

CONCLUSION
HIIT was not superior to CIET for improving aerobic or anaerobic parameters in adolescents. Secondly, pre- and post-pubertal participants demonstrated similar trainability.

maturity
adolescence
Peak V̇O
peak power
pre-pubertal
pubertal


Utilization of Patient-Generated Data Collected Through Mobile Devices: Insights From a Survey on Attitudes Toward Mobile Self-Monitoring and Self-Management Apps for Depression.

Abstract:
BACKGROUND
Depression is a severe psychiatric disease with high prevalence and an elevated risk for recurrence and chronicity. A substantial proportion of individuals with a diagnosis of unipolar depressive disorder do not receive treatment as advised by national guidelines. Consequently, self-monitoring and self-management become increasingly important. New mobile technologies create unique opportunities to obtain and utilize patient-generated data. As common adherence rates to mobile technologies are scarce, a profound knowledge of user behavior and attitudes and preferences is important throughout any developmental process of mobile technologies and apps.

OBJECTIVE
The aim of this survey was to provide descriptive data upon usage and anticipated usage of self-monitoring and self-management of depression and preferences of potential users in terms of documented parameters and data-sharing options.

METHODS
A Web-based survey comprising 55 questions was conducted to obtain data on the usage of mobile devices, app usage, and participant's attitudes and preferences toward mobile health apps for the self-monitoring and self-management of depression.

RESULTS
A total of 825 participants provided information. Moreover, two-thirds of the sample self-reported to be affected by depressive symptoms, but only 12.1% (81/668) of those affected by depression have ever used any mobile self-monitoring or self-management app. Analysis showed that people want personally relevant information and feedback but also focus on handling sensitive data.

CONCLUSIONS
New mobile technologies and smartphone apps, especially in combination with mobile sensor systems, offer unique opportunities to overcome challenges in the treatment of depression by utilizing the potential of patient-generated data. Focus on patient-relevant information, security and safe handling of sensitive personal data, as well as options to share data with self-selected third parties should be considered mandatory throughout any development process.

depression
adherence
mHealth
mobile applications, self-management


Effects of dietary-induced alterations in rat brain docosahexaenoic acid accrual on phospholipid metabolism and mitochondrial bioenergetics: An in vivo31P MRS study.

Abstract: Evidence from 31P magnetic resonance spectroscopy (31P MRS) studies suggest that different psychiatric disorders, which typically emerge during adolescence and young adulthood, are associated with abnormalities in mitochondrial bioenergetics and membrane phospholipid metabolism. These disorders are also associated with deficits in omega-3 polyunsaturated fatty acids (n-3 PUFA), including docosahexaenoic acid (DHA) which accumulates in mitochondrial and synaptic membranes. The present study investigated the effects of dietary-induced alterations in brain DHA accrual during adolescence on phospholipid metabolism and bioenergetics in the adult rat brain using 31P MRS. During the peri-adolescent period (P21-P90), male rats were fed a diet with no n-3 fatty acids (Deficient, DEF, n = 20), a diet fortified with preformed DHA (fish oil, FO, n = 20), or a control diet fortified with alpha-linolenic acid (18:3n-3, n = 20). On P90, 31P MRS was performed under isoflurane anesthetic using a 7 T Bruker Biospec system. Compared with controls, brain DHA levels were significantly lower in adult rats fed the DEF diet (-17%, p ≤ 0.0001) and significantly higher in rats fed the FO diet (+14%, p ≤ 0.0001). There were no significant group differences for indices of bioenergetics, including adenosine triphosphate and phosphocreatine levels, or indices of membrane phospholipid metabolism including phosphomonoesters and phosphodiesters. Therefore, the present 31P MRS data suggest that rat brain DHA levels are not a significant predictor of mitochondrial bioenergetics or membrane phospholipid metabolism.

Lindquist|Diana M|DM|
Asch|Ruth H|RH|
Schurdak|Jennifer D|JD|
McNamara|Robert K|RK|

Rat
Brain
Docosahexaenoic acid (DHA)
Phosphocreatine
Phosphomonoester
ATP
Omega-3 fatty acids


Enhanced surface plasmon microscopy based on multi-channel spatial light switching for label-free neuronal imaging.

Abstract: In this paper, we have investigated multi-channel switching of light incidence in multiple directions to improve image clarity in surface plasmon microscopy (SPM) for robust and consistent imaging performance regardless of the pattern geometry and shape. Multi-channel light switching in SPM allows significant reduction of adverse scattering effects by surface plasmon (SP). For proof of concept, an eight-channel spatially switched SPM (ssSPM) system has been set up. The results with reference objects including square arrays and Siemens stars experimentally confirm much improved images with ssSPM by reducing the artifacts of SP scattering significantly. On a quantitative basis, contrast analysis preformed with square arrays shows image contrast enhanced by more than three times over conventional SPM. Three image reconstruction algorithms were evaluated for optimal image acquisition. It is suggested that averaging combined with minimum-filtering produces the highest resolution. ssSPM was applied to label-free imaging of primary neuron cultures and shown to present enhanced images with clarity far better than conventional SPM.

Son|Taehwang|T| Lee|Changhun|C| Moon|Gwiyeong|G| Lee|Dongsu|D| Cheong|Eunji|E| Kim|Donghyun|D|

Surface plasmon
Surface plasmon microscopy
Neuron
Label-free imaging
Light-switching


Testing equality of means in partially paired data with incompleteness in single response.

Abstract: In testing differentially expressed genes between tumor and healthy tissues, data are usually collected in paired form. However, incomplete paired data often occur. While extensive statistical researches exist for paired data with incompleteness in both arms, hardly any recent work can be found on paired data with incompleteness in single arm. This paper aims to fill this gap by proposing some new methods, namely, P-value pooling methods and a nonparametric combination test. Simulation studies are conducted to investigate the performance of the proposed methods in terms of type I error and power at small to moderate sample sizes. A real data set from The Cancer Genome Atlas (TCGA) breast cancer study is analyzed using the proposed methods.

Differentially expressed genes
-value pooling
RNA sequencing
meta-analysis
nonparametric test


The Effects of Trypsin Inhibitor on Insulin Secretion Using Rat Pancreas in an Organ Bath.

Abstract:
BACKGROUND/AIM
We developed an experimental method to reproduce insulin secretion from isolated rat pancreas preparations using an organ bath system. However, secretion of trypsin, another pancreatic enzyme, interferes with insulin production in such systems. We aimed to ascertain the minimum trypsin inhibitor (TI), dose for obtaining a sustained, stable rate of insulin secretion.

MATERIALS AND METHODS
The action of TI (1-10 μg/ml) on pancreatic preparations of male Wistar-Imamichi rats in organ bath experiments was assessed by measuring insulin, amylase, and trypsin activity.

RESULTS
The level of insulin outflow remained steady in the TI-treated samples, in contrast to that in the untreated control, where insulin secretion decreased over time. The level of amylase outflow did not change significantly. Trypsin activity was significantly lower in the TI-treated samples than in the control.

CONCLUSION
Even low concentrations of TI can maintain insulin secretion by inhibiting trypsin activity in organ bath experiments.

Morita|Asuka|A| Ouchi|Motoshi|M| Satoh|Keitaro|K| Kobayashi|Shunsuke|S| Terada|Misao|M| Wakashin|Hidefumi|H| Kon|Hiroe|H| Hayashi|Keitaro|K| Anzai|Naohiko|N| Shimizu|Akira|A| Sugihara|Hitoshi|H| Oba|Kenzo|K| Fujita|Tomoe|T|

trypsin inhibitor
Insulin
pancreas
organ bath
amylase


Are Ephemeroptera, Plecoptera and Trichoptera traits reliable indicators of semi-urban pollution in the Tsitsa River, Eastern Cape Province of South Africa?

Abstract: The taxonomy-based response pattern of macroinvertebrates to pollution gradient is well established, with tolerant taxa increasing in impacted conditions, while sensitive taxa increase with decreasing deterioration, typical of rural pollution. This study identified rural indicator and sensitive traits of Ephemeroptera, Plecoptera and Trichoptera (EPT) taxa by examining their trait distribution pattern in relation to rural pollution. Physicochemical parameters and EPT were sampled seasonally from August 2016 to April 2017. Eight sites were selected and categorised into three site groups. Site group 1 served as the least impacted site group and Site group 2 as the moderately influenced, whereas Site group 3 was the most impacted. Seven traits were selected and categorised into 27 trait modalities. The response of EPT traits to physicochemical parameters was analysed using the simultaneous analysis of the information contained in three tables: R (environmental characteristics of samples), L (taxa distribution across samples) and Q (species traits) (RLQ) and confirmed with fourth-corner analysis. Three trait attributes, large (10-20 mm), swimming, shredding, streamlined body shape and large body size (≥ 10-20), were considered tolerant signature traits of semi-urban pollution. These trait attributes were associated with the influenced Site group 3 and indicated a significant positive affinity with at least one physicochemical indicator of increasing semi-urban pollution (NH4-N, NO3-N, NO2-N, PO4-P, EC, turbidity, temperature and pH). Conversely, small body size (< 10 mm), operculate gills, spherical body shape and a preference for sediments were correlated with the least influenced Site group 1 and were considered sensitive traits of semi-urban disturbance. Overall, this study provided critical insights into EPT responses to disturbance, revealing that semi-urban activities influenced EPT traits differently in the Tsitsa River.

South Africa
Biomonitoring
Functional ecology
Macroinvertebrate traits
Water quality


Increased Resistance to Intradermal Francisella tularensis LVS Infection by Inactivation of the Sts Phosphatases.

Abstract: The Suppressor of TCR signaling proteins (Sts-1 and Sts-2) are two homologous phosphatases that negatively regulate signaling pathways in a number of hematopoietic lineages, including T lymphocytes. Mice lacking Sts expression are characterized by enhanced T cell responses. Additionally, a recent study demonstrated that Sts-/- mice are profoundly resistant to systemic infection by Candida albicans, with resistance characterized by enhanced survival, more rapid fungal clearance in key peripheral organs, and an altered inflammatory response. To investigate the role of Sts in the primary host response to infection by a bacterial pathogen, we evaluated the response of Sts-/- mice to infection by a Gram-negative bacterial pathogen. Francisella tularensis is a facultative bacterial pathogen that replicates intracellularly within a variety of cell types and is the causative agent of tularemia. Francisella infections are characterized by a delayed immune response, followed by an intense inflammatory reaction that causes widespread tissue damage and septic shock. Herein, we demonstrate that mice lacking Sts expression are significantly resistant to infection by the live vaccine strain (LVS) of F. tularensis Resistance is characterized by reduced lethality following high-dose intradermal infection, an altered cytokine response in the spleen, and enhanced bacterial clearance in multiple peripheral organs. Sts-/- bone marrow-derived monocytes and neutrophils, infected with F. tularensis LVS ex vivo, display enhanced restriction of intracellular bacteria. These observations suggest the Sts proteins play an important regulatory role in the host response to bacterial infection, and they underscore a role for Sts in regulating functionally relevant immune response pathways.

Parashar|Kaustubh|K|
Kopping|Erik|E|
Frank|David|D|
Sampath|Vinaya|V|
Thanassi|David G|DG|
Carpino|Nick|N|

D000825:Animal Structures
D000818:Animals
D058491:Bacterial Load
D016207:Cytokines
D004195:Disease Models, Animal
D004198:Disease Susceptibility
D005604:Francisella tularensis
D008297:Male
D051379:Mice
D018345:Mice, Knockout
D010744:Phosphoric Monoester Hydrolases
D017027:Protein Tyrosine Phosphatases
D011948:Receptors, Antigen, T-Cell
D016019:Survival Analysis
D014406:Tularemia

Francisella
host resistance
host-pathogen interactions


Typography-Like 3D-Printed Templates for the Lithography-Free Fabrication of Microfluidic Chips.

Abstract: Typography-like templates for polydimethylsiloxane (PDMS) microfluidic chips using a fused deposition modeling (FDM) three-dimensional (3D) printer are presented. This rapid and fast proposed scheme did not require complicated photolithographic fabrication facilities and could deliver resolutions of ~100 μm. Polylactic acid (PLA) was adopted as the material to generate the 3D-printed units, which were then carefully assembled on a glass substrate using a heat-melt-curd strategy. This craft of bonding offers a cost-effective way to design and modify the templates of microfluidic channels, thus reducing the processing time of microfluidic chips. Finally, a flexible microfluidic chip to be employed for cell-based drug screening was developed based on the modularized 3D-printed templates. The lithography-free, typography-like, 3D-printed templates create a modularized fabrication process and promote the prevalence of integrated microfluidic systems with minimal requirements and improved efficiency.

Su|Wenqiong|W|0000-0003-4914-346X Li|Yulong|Y| Zhang|Lulu|L| Sun|Jiahui|J| Liu|Shuopeng|S| Ding|Xianting|X|

D004354:Drug Screening Assays, Antitumor

typography-like
lithography-free
microfluidic chip
drug screening
3D printing


Determination of the Optimal Location for Bone Graft Harvest in the Distal Radius.

Abstract: Background: The distal radius is commonly used as a bone graft donor site for surgery in the hand and wrist. The aim of this study was to evaluate the volume and relative density of cancellous bone in the distal radius. Methods: Thirty-four consecutive computed tomographic scans of the wrist in 33 patients without distal radius pathology were included. For each subject, 6 spherical regions of interest (ROIs) were identified within the distal radius. In each ROI, volumetric measurements and mean Hounsfield unit (HFU) values were recorded by 2 observers using a 3-dimensional imaging reconstruction software. Results: Compared with proximal bone, distal bone had larger volume (0.82 vs 0.27 cm3) and greater relative density (178 vs 152 HFU) on average. Among the 6 ROIs, the distal-central region had the largest average volume (1.20 cm3) and the distal-ulnar ROI had the greatest average relative density (193 HFU). Conclusion: Based on these results, we recommend performing cancellous autograft harvest relatively distal and ulnar within the distal radius.

Matson|Andrew P|AP|
Federer|Andrew E|AE|
Meisel|Erin M|EM|
Barchick|Stephen R|SR|
Ruch|David S|DS|
Richard|Marc J|MJ|

bone graft harvest
bone density
computed tomography
distal radius bone graft
scaphoid nonunion


Allocation of intensive care resources during an infectious disease outbreak: a rapid review to inform practice.

Abstract:
BACKGROUND
The COVID-19 pandemic has placed sustained demand on health systems globally, and the capacity to provide critical care has been overwhelmed in some jurisdictions. It is unknown which triage criteria for allocation of resources perform best to inform health system decision-making. We sought to summarize and describe existing triage tools and ethical frameworks to aid healthcare decision-making during infectious disease outbreaks.

METHODS
We conducted a rapid review of triage criteria and ethical frameworks for the allocation of critical care resources during epidemics and pandemics. We searched Medline, EMBASE, and SCOPUS from inception to November 3, 2020. Full-text screening and data abstraction were conducted independently and in duplicate by three reviewers. Articles were included if they were primary research, an adult critical care setting, and the framework described was related to an infectious disease outbreak. We summarized each triage tool and ethical guidelines or framework including their elements and operating characteristics using descriptive statistics. We assessed the quality of each article with applicable checklists tailored to each study design.

RESULTS
From 11,539 unique citations, 697 full-text articles were reviewed and 83 articles were included. Fifty-nine described critical care triage protocols and 25 described ethical frameworks. Of these, four articles described both a protocol and ethical framework. Sixty articles described 52 unique triage criteria (29 algorithm-based, 23 point-based). Few algorithmic- or point-based triage protocols were good predictors of mortality with AUCs ranging from 0.51 (PMEWS) to 0.85 (admitting SOFA > 11). Most published triage protocols included the substantive values of duty to provide care, equity, stewardship and trust, and the procedural value of reason.

CONCLUSIONS
This review summarizes available triage protocols and ethical guidelines to provide decision-makers with data to help select and tailor triage tools. Given the uncertainty about how the COVID-19 pandemic will progress and any future pandemics, jurisdictions should prepare by selecting and adapting a triage tool that works best for their circumstances.

Fiest|Kirsten M|KM|
Krewulak|Karla D|KD|
Plotnikoff|Kara M|KM|
Kemp|Laryssa G|LG|
Parhar|Ken Kuljit S|KKS|
Niven|Daniel J|DJ|
Kortbeek|John B|JB|
Stelfox|Henry T|HT|
Parsons Leigh|Jeanna|J|

Intensive care
COVID-19
Critical care
Triage
Medical ethics
Practice guideline
Resource allocation


Sex Differences in Oral Health and the Consumption of Sugary Diets in a Saudi Arabian Population.

Abstract:
Background and Purpose
Adolescence is a crucial period for developing healthy lifestyle and dietary habits. The growing consumption of high-sugar foods and beverages constitutes a serious public health concern. The aim of this study was to evaluate sex differences in the consumption of a sugary diet and oral health among Saudi adolescents.

Subjects and Methods
This cross-sectional study was conducted in the Eastern Province of the Kingdom of Saudi Arabia between January and February 2019. A multistage sampling technique was used to recruit 2265 middle-school children aged 12-16 years. Data were collected via the Food Frequency Questionnaire and via an oral health examination, using the WHO criteria. The chi-squared test, Student's t-test, and Mann-Whitney U-test were used to investigate the associations between the study variables.

Results
The most consumed foods and beverages reported were water, juices, and biscuits (90%), while the least consumed were energy drinks and jams. A significant difference was found between males and females in the frequency of consumed sugary foods (P=0.01) and the quantity of consumed sugary beverages (P=0.000); males over all consumption were greater than their counterpart. However, no differences were found between sexes in the frequency of sugary drink consumption (P=0.2). The decayed-missing-filled index score was significantly higher in females (4.29 ± 3.44) than in males (3.61 ± 3.14; P=0.001). The mean plaque index among males and females was 1.72 (±0.79) and 1.20 (±0.78), respectively, while the mean gingival index was 1.31 (±0.77) in males and 0.69 (±0.73) in females-a statistically significant difference (P=0.001).

Conclusion
Sex differences were found in sugary diet consumption and oral health status. Thus, policy makers are encouraged to consider sex-based differences when planning preventative programs and initiatives. Nevertheless, further research is needed on the dietary intake patterns of young adults.

sex
adolescents
caries
oral hygiene
sugar intake


A retrospective clinical analysis of 5 cases of vaginal melanoma.

Abstract: Vaginal melanoma is a rare tumor, accounting for <1% of all melanomas and ~1-5% of all vaginal malignant tumors. The prognosis of vaginal melanoma is extremely poor, as it is often resistant to chemotherapy and radiotherapy, and metastases may develop in the early stages of the disease. The present study investigated 5 patients with vaginal melanoma treated at the Department of Gynecology of Osaka City University Hospital (Osaka, Japan) between October, 2000 and April, 2014. All the cases presented with abnormal genital bleeding as the main complaint. Notably, in 3 of the 5 cases the tumors appeared as non-pigmented polyps. Local resection was performed as the primary treatment in all 5 cases. After surgery, dermal injection of interferon β (feron maintenance therapy) was performed in 3 cases, and dacarbazine, nimustine, vincristine and interferon β (DAVFeron therapy) was administered in 1 case as adjuvant therapy. All 5 cases recurred within 1 year. The site of recurrence varied, and included the vaginal wall, liver, brain and lung. The median overall survival was 419 days and the median progression-free survival 177 days. In this cohort, all the cases presented with abnormal genital bleeding as the main complaint. Therefore, malignant melanoma of the vagina must be considered along with other gynecological malignancies in patients with abnormal genital bleeding. In this study, over half of the cases had a non-pigmented polypoid lesion of the vagina. Therefore, malignant melanoma of the vagina must be considered when a polypoid lesion is identified on the vaginal wall.

Tasaka|Reiko|R| Fukuda|Takeshi|T| Wada|Takuma|T| Kawanishi|Masaru|M| Imai|Kenji|K| Kasai|Mari|M| Hashiguchi|Yasunori|Y| Ichimura|Tomoyuki|T| Yasui|Tomoyo|T| Sumi|Toshiyuki|T|

vaginal melanoma
vaginal malignant tumor
abnormal genital bleeding
malignant melanoma
vaginal polyp


Cross-Sectional and Longitudinal Associations Between Athlete Burnout, Insomnia, and Polysomnographic Indices in Young Elite Athletes.

Abstract: Few studies have examined the association between sleep and burnout symptoms in elite athletes. We recruited 257 young elite athletes (Mage = 16.8 years) from Swiss Olympic partner schools. Of these, 197 were reassessed 6 months later. Based on the first assessment, 24 participants with clinically relevant burnout symptoms volunteered to participate in a polysomnographic examination and were compared with 26 (matched) healthy controls. Between 12% and 14% of young elite athletes reported burnout symptoms of potential clinical relevance, whereas 4-11% reported clinically relevant insomnia symptoms. Athletes with clinically relevant burnout symptoms reported significantly more insomnia symptoms, more dysfunctional sleep-related cognitions, and spent less time in bed during weeknights (p < .05). However, no significant differences were found for objective sleep parameters. A cross-lagged panel analysis showed that burnout positively predicted self-reported insomnia symptoms. Cognitive-behavioral interventions to treat dysfunctional sleep-related cognitions might be a promising measure to reduce subjective sleep complaints among young elite athletes.

Gerber|Markus|M|
Best|Simon|S|
Meerstetter|Fabienne|F|
Isoard-Gautheur|Sandrine|S|
Gustafsson|Henrik|H|
Bianchi|Renzo|R|
Madigan|Daniel J|DJ|
Colledge|Flora|F|
Ludyga|Sebastian|S|
Holsboer-Trachsler|Edith|E|
Brand|Serge|S|

D007319:Sleep Initiation and Maintenance Disorders

sleep complaints
EEG
polysomnography
rumination


G2-quadruplex in the 3'UTR of IE180 regulates Pseudorabies virus replication by enhancing gene expression.

Abstract: RNA secondary structure elements in the mRNA 3'-untranslated regions (3'UTR) play important roles in post-transcriptional regulation. RNA structure elements in the viral RNA provide valuable model for studying diverse regulation mechanisms. Herpesvirus genomes are double-stranded DNA with GC-rich sequences, which can be transcribed into abundant GC-rich RNAs. It is valuable to explore the structures and function of those GC-rich RNAs. We identified a G2-quadruplex-forming sequence named PQS18-1 in the 3'UTR of the unique immediate early gene of Pseudorabies virus (PRV), an important member of Alphaherpesvirinae subfamily. The RNA PQS18-1 was folded into parallel G-quadruplex structure, enhancing gene expression. Both non-G-quadruplex mutant and G3-quadruplex mutant in the 3'UTR showed lower gene expression level than the wildtype G2-quadruplex. TMPyP4 destroyed PQS18-1 G2-quadruplex and suppressed gene expression, accordingly reducing PRV replication by one titre in the PK15 cells at 24 h post infection. Our findings indicated that the RNA G2-quadruplex in 3'UTR was essential for high expression of IE180 gene, and it could be a specific post-transcription regulation element in response to small molecules or other macromolecules. This study discovers a novel RNA G2-quadruplex in the 3'UTR of an immediate early gene of alphaherpesvirus and provides a new nucleic acid target for anti-virus drug design.

Zhang|Yashu|Y| Liu|Sisi|S|0000-0002-6814-134X Jiang|Hui|H| Deng|Hui|H| Dong|Chen|C| Shen|Wei|W| Chen|Haifeng|H| Gao|Chao|C| Xiao|Shaobo|S| Liu|Zheng-Fei|ZF| Wei|Dengguo|D|0000-0001-9923-789X

D015967:Gene Expression Regulation, Viral

post-transcription regulation
immediate early gene
Alphaherpesvirinae
G-quadruplex
3ʹ-untranslated region


Late toxicities burden in patients with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib.

Abstract:
PURPOSE
Radioactive-iodine (RAI)-resistant differentiated thyroid cancer (DTC) patients benefit from multi-kinase inhibitors (MKIs), such as lenvatinib. Incidence of treatment-related (TR) late toxicities has been not yet described.

METHODS
From January 2015 to June 2019 we retrospectively reviewed clinical records of patients with RAI-resistant DTC treated with lenvatinib at Istituto Nazionale dei Tumori (Milan, Italy). New side effect of any grade, appeared after 12 months of lenvatinib, was defined as late adverse event (AE). Descriptive analyses were performed. Survival curves were estimated with Kaplan-Meier method and compared with log-rank test.

RESULTS
Thirty-seven patients were included, 65% had ≥65 years and 68% were female. Thirty patients received lenvatinib for >12 months. Lenvatinib was started at ≤20 mg/daily in 59% of patients, 64% were ≥65 years. The frequency of late AEs was 80% and cardiovascular toxicity was the most common (57%). There was no difference in the incidence of late AEs between younger/older population (77% and 82%, respectively). Median lenvatinib treatment duration (TD) was 39.96 months (95% CI 21.64-NR): 39.96 months for patients <65 years (95% CI: 13.25-NR) and 37.53 months for those ≥65 years, respectively (95% CI: 15.85-NR). Median overall survival (OS) was 39.96 months (95% CI: 21.84-NR), no statistically differences in OS was observed between younger (<65 years) and older patients (≥65 years) (HR 1.013; 95% CI 0.963-1.065; p = 0.62).

CONCLUSION
Late toxicity burden of lenvatinib is not negligible. Cardiovascular toxicity remains the principal side effect even after a prolonged lenvatinib exposition.

Platini|F|F|
Cavalieri|S|S|
Alfieri|S|S|
Bergamini|C|C|
Resteghini|C|C|
Bottiglieri|A|A|
Colombo|E|E|
Mazzeo|L|L|
Licitra|L|L|
Paolini|B|B|
Seregni|E|E|
Locati|L D|LD|

D000970:Antineoplastic Agents
D005260:Female
D006801:Humans
D007457:Iodine Radioisotopes
D010671:Phenylurea Compounds
D047428:Protein Kinase Inhibitors
D011804:Quinolines
D012189:Retrospective Studies
D013964:Thyroid Neoplasms

Late toxicities
Thyroid cancer
Lenvatinib
RAI-resistant


Bioaccumulation and tissue distribution of antibiotics in wild marine fish from Laizhou Bay, North China.

Abstract: Information about bioaccumulation and tissue distribution of antibiotics in wild marine fish is still limited. In the present study, tissue levels, bioaccumulation and distribution patterns of 9 sulfonamide (SA), trimethoprim (TMP), 5 fluoroquinolone (FQ), and 4 macrolide (ML) antibiotics were investigated in gill, muscle, kidney, and liver tissues of seven wild fish species collected from Laizhou Bay, North China in 2016. All the 19 antibiotics were detected in these fish tissues with the total concentrations ranging from 22ng/g dry weight (dw) to 500ng/g dw. The mean values of logarithm bioaccumulation factors (BAFs) in the gills, muscles, kidneys, and livers ranged from 2.2 to 4.8, 1.9 to 4.0, 2.5 to 4.9, and 2.5 to 5.4, respectively. Log BAFs of antibiotics in these tissues significantly increased (r=0.61-0.77, p<0.001) with their logarithm values of liposome-water distribution coefficient (Dlipw) except in the muscles, suggesting that Dlipw can well assess the bioaccumulation potentials of antibiotics in phospholipid-rich tissues. In general, the SAs, TMP, and FQs were primarily accumulated in the muscles and the MLs were primarily in the livers, which may be related to their toxicokinetic processes of these marine fish. The present study for the first time reported the tissue distribution patterns of antibiotics in wild marine fish.

Liu|Sisi|S| Bekele|Tadiyose-Girma|TG| Zhao|Hongxia|H| Cai|Xiyun|X| Chen|Jingwen|J|

Bioaccumulation
Tissue distribution
Antibiotics
Marine fish
Laizhou Bay


Surgical skin adhesive bond is safe and feasible wound closure method to reduce surgical site infection following minimally invasive colorectal cancer surgery.

Abstract:
Purpose
Minimally invasive colorectal surgery had reduced the rate of surgical site infection. The use of surgical skin adhesive bond (2-octyl cyanoacrylate) for wound closure reduces postoperative pain and provides better cosmetic effect compared to conventional sutures or staples. But role of surgical skin adhesive bond for reducing surgical site infection is unclear. Our objective in this study was to evaluate the role of surgical skin adhesive bond in reducing surgical site infection following minimally invasive colorectal surgery.

Methods
We performed a retrospective analysis of 492 patients treated using minimally invasive surgery for colorectal cancer at Seoul St. Mary's Hospital, the Catholic University of Korea. Of these, surgical skin adhesive bond was used for wound closure in 284 cases and skin stapling in 208. The rate of surgical site infection including deep or organ/space level infections was compared between the 2 groups.

Results
The rate of superficial surgical site infection was significantly lower in the group using skin adhesive (P = 0.024), and total costs for wound care were significantly lower in the skin adhesive group (P < 0.001).

Conclusion
This study showed that surgical skin adhesive bond reduced surgical site infection and total cost for wound care following minimally invasive colorectal cancer surgery compared to conventional skin stapler technique. Surgical skin adhesive bond is a safe and feasible alternative surgical wound closure technique following minimally invasive colorectal cancer surgery.

Cyanoacrylates
Octyl 2-cyanoacrylate
Surgical stapling
Surgical wound infection
Tissue adhesives


Study of rapid reorganization of visual neurofunctions with the resting-state functional MRI in pituitary adenoma patients with vision improvement after transsphenoidal surgery.

Abstract:
INTRODUCTION
To investigate changes of vision-related resting-state activity in pituitary adenoma (PA) patients with visual improvement after transsphenoidal surgery.

METHODS
14 PA patients with visual improvement after surgery were enrolled. The resting-state functional MRI and neuro-ophthalmologic evaluation were performed before and after the operation. The functional connectivity (FC) of 8 seeds (the primary visual cortex (V1), the secondary visual cortex (V2), the middle temporal visual cortex (MT+), and fusiform gyrus(FG)) was evaluated. A paired t test was conducted to identify the differences between the two groups.

RESULTS
Compared with the preoperation counterparts, the PA patients with improved vision exhibited decreased FC with the V1, V2, MT+, FG in the left paracentral lobule, bilateral lingual gyrus, precentral gyrus(BA 4), right superior temporal gyrus(BA 22), left fusiform gyrus, bilateral middle occipital gyrus (BA 19), left cuneus, right inferior occipital gyrus, left superior frontal gyrus, right cuneus, left superior parietal lobule(BA 7),the medulla, right postcentral gyrus, and increased FC in the right middle frontal gyrus, left inferior parietal lobule (BA 40), left declive, right lentiform nucleus, inferior frontal gyrus, right superior frontal gyrus(BA 11), cingulate gyrus(BA 32), right putamen, right thalamus, left medial frontal gyrus, left claustrum, left superior frontal Medial, right rectal gyrus(BA 25) and right parahippocampal gyrus.

CONCLUSIONS
The results show most subareas within the visual cortex exhibit decreased functional connectivity. The functional changes in subareas within default mode network (DMN), action observation network (AON) and the multisensory system in PAs propose that vision improvement may lead to function remodeling in higher-order cortex.

Wang|Fuyu|F|0000-0003-2232-5423 Wang|Peng|P| Liu|Yuyang|Y| Zhou|Tao|T| Meng|Xianghui|X| Jiang|Jinli|J|

D001921:Brain
D006801:Humans
D008279:Magnetic Resonance Imaging
D010296:Parietal Lobe
D010911:Pituitary Neoplasms
D014793:Visual Cortex

resting-state functional magnetic resonance imaging


Dissecting complex traits using the Drosophila Synthetic Population Resource.

Abstract: For most complex traits we have a poor understanding of the positions, phenotypic effects, and population frequencies of the underlying genetic variants contributing to their variation. Recently, several groups have developed multi-parent advanced intercross mapping panels in different model organisms in an attempt to improve our ability to characterize causative genetic variants. These panels are powerful and are particularly well suited to the dissection of phenotypic variation generated by rare alleles and loci segregating multiple functional alleles. We describe studies using one such panel, the Drosophila Synthetic Population Resource (DSPR), and the implications for our understanding of the genetic basis of complex traits. In particular, we note that many loci of large effect appear to be multiallelic. If multiallelism is a general rule, analytical approaches designed to identify multiallelic variants should be a priority for both genome-wide association studies (GWASs) and multi-parental panels.

Long|Anthony D|AD|
Macdonald|Stuart J|SJ|
King|Elizabeth G|EG|

complex traits
multiallelism
Drosophila melanogaster
missing heritability
multi-parental population


Low effect of young afforestations on bird communities inhabiting heterogeneous Mediterranean cropland.

Abstract: Afforestation programs such as the one promoted by the EU Common Agricultural Policy have spread tree plantations on former cropland. These afforestations attract generalist forest and ubiquitous species but may cause severe damage to open habitat species, especially birds of high conservation value. We investigated the effects of young (<20 yr) tree plantations dominated by pine P. halepensis on bird communities inhabiting the adjacent open farmland habitat in central Spain. We hypothesize that pine plantations located at shorter distances from open fields and with larger surface would affect species richness and conservation value of bird communities. Regression models controlling for the influence of land use types around plantations revealed positive effects of higher distance to pine plantation edge on community species richness in winter, and negative effects on an index of conservation concern (SPEC) during the breeding season. However, plantation area did not have any effect on species richness or community conservation value. Our results indicate that the effects of pine afforestation on bird communities inhabiting Mediterranean cropland are diluted by heterogeneous agricultural landscapes.

Sánchez-Oliver|Juan S|JS|
Rey Benayas|José M|JM|
Carrascal|Luis M|LM|

Pine plantations
Species richness
Land use types
CAP
Conservation status
Distance effects


Fluoropyrimidine-induced cardiac toxicity: challenging the current paradigm.

Abstract:
Background
Fluoropyrimidine chemotherapy [5-fluorouracil (5-FU) and capecitabine] are commonly used agents in the treatment of various solid malignancies. However, their use has been limited by cardiac toxicity, presenting as a wide spectrum of asymptomatic (e.g., EKG changes) and symptomatic (e.g., chest pain) manifestations related to coronary vasospasm leading to myocardial ischemia. Historically, patients with suspected coronary vasospasm have been treated with traditional acute ischemic workup and various combinations of anti-anginal therapies. In addition, most patients typically are not rechallenged with fluoropyrimidine after experiencing initial cardiovascular side-effects with resulting interruption of planned chemotherapy regimens.

Methods
We report a case series of 11 consecutive patients in a single-center with suspected fluoropyrimidine-induced coronary vasospasm who were successfully rechallenged with the culprit drug to allow for planned chemotherapy completion. Our protocol utilized rechallenge with bolus infusional regimen of intravenous fluoropyrimidine chemotherapy and oral capecitabine with cardioprotective pretreatment with two calcium blockers and long-acting oral nitrate therapy.

Results
We were successfully able to continue and complete the previously planned first-line chemotherapy regimen for all 11 patients with minimal therapeutic interruption. There have been no cardiac events or evidence of recurrent coronary spasm after completion of therapy with discontinuation of prophylactic medications upon therapy completion.

Conclusions
We report a single-institution experience of successful rechallenge with fluoropyrimidines with careful cardiac monitoring and the combined use of calcium channel blockers and long-acting nitrates. With further study, this algorithm can be used to safely continue fluoropyrimidines, a potentially curative regimen in the treatment of many solid tumors.

Clasen|Suparna C|SC|
Ky|Bonnie|B|
O'Quinn|Rupal|R|
Giantonio|Bruce|B|
Teitelbaum|Ursina|U|
Carver|Joseph R|JR|

5-fluorouracil (5-FU)
capecitabine
vasospasm
cardio-oncology
rechallenge chemotherapy


Gender by onset age interaction may characterize distinct phenotypic subgroups in bipolar patients.

Abstract:
OBJECTIVE
Although bipolar disorder (BD) is a common recurrent condition with highly heterogeneous illness course, data are limited regarding clinical implications of interactions between gender and onset age. We assessed relationships between onset age and demographic/illness characteristics among BD patients stratified by gender.

METHODS
Demographic and unfavorable illness characteristics, descriptive traits, and clinical correlates were compared in 502 patients from Stanford University BD Clinic patients enrolled in the Systematic Treatment Enhancement Program for BD between 2000 and 2011, stratified by gender, across pre-, peri-, and post-pubertal (<12, 13-16, and >17 years, respectively) onset-age subgroups.

RESULTS
Among 502 BD patients, 58.2% were female, of whom 21.9% had pre-pubertal, 30.7% peri-pubertal, and 47.4% post-pubertal onset. Between genders, although demographics, descriptive characteristics, and most clinical correlates were statistically similar, there were distinctive onset-age related patterns of unfavorable illness characteristics. Among females, rates of 6/8 primary unfavorable illness characteristics were significantly higher in pre-pubertal and peri-pubertal compared to post-pubertal onset patients. However, among males, rates of only 3/8 unfavorable illness characteristics were significantly higher in only pre-pubertal versus post-pubertal onset patients, and none between peri-pubertal versus post-pubertal onset patients.

LIMITATIONS
Caucasian, insured, suburban, American specialty clinic-referred sample limits generalizability, onset age based on retrospective recall.

DISCUSSION
We describe different phenotypic presentations across age at illness onset groups according to gender. Among females and males, peri-pubertal and post-pubertal onset age groups were more different and more similar, respectively. Further investigation is warranted to assess implications of gender-by-onset-age interactions to more accurately delineate distinctive BD phenotypes.

Holtzman|Jessica N|JN|
Miller|Shefali|S|
Hooshmand|Farnaz|F|
Wang|Po W|PW|
Chang|Kiki D|KD|
Goffin|Kathryn C|KC|
Hill|Shelley J|SJ|
Ketter|Terence A|TA|
Rasgon|Natalie L|NL|

D011569:Psychiatric Status Rating Scales

Gender
Onset age
Bipolar disorder
Illness course
Clinical comorbidity
Early onset


Rapid identification of drug-type strains in Cannabis sativa using loop-mediated isothermal amplification assay.

Abstract: In Cannabis sativa L., tetrahydrocannabinol (THC) is the primary psychoactive compound and exists as the carboxylated form, tetrahydrocannabinolic acid (THCA). C. sativa is divided into two strains based on THCA content-THCA-rich (drug-type) strains and THCA-poor (fiber-type) strains. Both strains are prohibited by law in many countries including Japan, whereas the drug-type strains are regulated in Canada and some European countries. As the two strains cannot be discriminated by morphological analysis, a simple method for identifying the drug-type strains is required for quality control in legal cultivation and forensic investigation. We have developed a novel loop-mediated isothermal amplification (LAMP) assay for identifying the drug-type strains of C. sativa. We designed two selective LAMP primer sets for on-site or laboratory use, which target the drug-type THCA synthase gene. The LAMP assay was accomplished within approximately 40 min. The assay showed high specificity for the drug-type strains and its sensitivity was the same as or higher than that of conventional polymerase chain reaction. We also showed the effectiveness of melting curve analysis that was conducted after the LAMP assay. The melting temperature values of the drug-type strains corresponded to those of the cloned drug-type THCA synthase gene, and were clearly different from those of the cloned fiber-type THCA synthase gene. Moreover, the LAMP assay with simple sample preparation could be accomplished within 1 h from sample treatment to identification without the need for special devices or techniques. Our rapid, sensitive, specific, and simple assay is expected to be applicable to laboratory and on-site detection.

Kitamura|Masashi|M| Aragane|Masako|M| Nakamura|Kou|K| Watanabe|Kazuhito|K| Sasaki|Yohei|Y|

D000595:Amino Acid Sequence
D015374:Biosensing Techniques
D002188:Cannabis

Tetrahydrocannabinolic acid synthase gene


Detailed analysis of the online near-infrared spectra of pharmaceutical blend in a rotary tablet press feed frame.

Abstract: The present study is an in-depth analysis of the online near-infrared (NIR) spectra acquired with a spectrometer mounted on the rotary tablet press feed frame. A 3.5% active pharmaceutical ingredient (API) formulation is analyzed. An attempt is made to determine the API univariately via the 2nd derivative spectra due to favorable appearance of the API and placebo bands in the formulation. However, the signal at the univariate API peak is ambiguous and principal component analysis is hence applied to understand better the structure of the data. To eliminate effect of the bias along the wavelength axis which is found to dominate the data, the analysis is restricted only to the spectral region that covers the API band of interest. This leads to significantly better results in terms of the univariate profile of the API now heavily overlapping with the first principal component and the elimination of the bias. Having thus proven that the univariate analysis is a viable option, an attempt is made to calibrate the API response by using some previous runs that involved alternation of the placebo and the formulation. This analysis produces mixed results due to baseline differences in the two sets of spectra. The final univariate profile of the API is therefore compared with the assay of the tablets and the two are found to agree very well. It is, therefore, concluded that the NIR probe in the feed frame can rapidly detect moderate changes in API concentration in the blend and be a good predictor of tablet potency at the same time point.

Šašić|Slobodan|S|
Blackwood|Daniel|D|
Liu|Angela|A|
Ward|Howard W|HW|
Clarke|Hugh|H|

Online near-infrared
Feed frame
API
Univariate analysis
Quantitative analysis