bluuebunny/crossref_metadata_2025 huggingface dataset:
Epilepsy in the mTORopathies: opportunities for precision medicine
Authors: Moloney Patrick B , Cavalleri Gianpiero L , Delanty Norman
Published: September 2021

The mechanistic target of rapamycin signalling pathway serves as a ubiquitous regulator of cell metabolism, growth, proliferation and survival. The main cellular activity of the mechanistic target of rapamycin cascade funnels through mechanistic target of rapamycin complex 1, which is inhibited by rapamycin, a macrolide compound produced by the bacterium Streptomyces hygroscopicus. Pathogenic variants in genes encoding upstream regulators of mechanistic target of rapamycin complex 1 cause epilepsies and neurodevelopmental disorders. Tuberous sclerosis complex is a multisystem disorder caused by mutations in mechanistic target of rapamycin regulators TSC1 or TSC2, with prominent neurological manifestations including epilepsy, focal cortical dysplasia and neuropsychiatric disorders. Focal cortical dysplasia type II results from somatic brain mutations in mechanistic target of rapamycin pathway activators MTOR, AKT3, PIK3CA and RHEB and is a major cause of drug-resistant epilepsy. DEPDC5, NPRL2 and NPRL3 code for subunits of the GTPase-activating protein (GAP) activity towards Rags 1 complex (GATOR1), the principal amino acid-sensing regulator of mechanistic target of rapamycin complex 1. Germline pathogenic variants in GATOR1 genes cause non-lesional focal epilepsies and epilepsies associated with malformations of cortical development. Collectively, the mTORopathies are characterized by excessive mechanistic target of rapamycin pathway activation and drug-resistant epilepsy. In the first large-scale precision medicine trial in a genetically mediated epilepsy, everolimus (a synthetic analogue of rapamycin) was effective at reducing seizure frequency in people with tuberous sclerosis complex. Rapamycin reduced seizures in rodent models of DEPDC5-related epilepsy and focal cortical dysplasia type II. This review outlines a personalized medicine approach to the management of epilepsies in the mTORopathies. We advocate for early diagnostic sequencing of mechanistic target of rapamycin pathway genes in drug-resistant epilepsy, as identification of a pathogenic variant may point to an occult dysplasia in apparently non-lesional epilepsy or may uncover important prognostic information including, an increased risk of sudden unexpected death in epilepsy in the GATORopathies or favourable epilepsy surgery outcomes in focal cortical dysplasia type II due to somatic brain mutations. Lastly, we discuss the potential therapeutic application of mechanistic target of rapamycin inhibitors for drug-resistant seizures in GATOR1-related epilepsies and focal cortical dysplasia type II.
Contributions of Animal Studies to the Understanding of Infectious Diseases
Authors: Musher Daniel M , Arasaratnam Reuben J
Published: September 2021

Experiments in animals have played an integral role in furthering basic understanding of the pathophysiology, host immune response, diagnosis, and treatment of infectious diseases. However, competing demands of modern-day clinical training and increasingly stringent requirements to perform animal research have reduced the exposure of infectious disease physicians to animal studies. For practitioners of infectious diseases and, especially, for contemporary trainees in infectious diseases, it is important to appreciate this historical body of work and its impact on current clinical practice. In this article, we provide an overview of some major contributions of animal studies to the field of infectious diseases. Areas covered include transmission of infection, elucidation of innate and adaptive host immune responses, testing of antimicrobials, pathogenesis and treatment of endocarditis, osteomyelitis, intra-abdominal and urinary tract infection, treatment of infection associated with a foreign body or in the presence of neutropenia, and toxin-mediated disease.
Squirrel Search Deer Hunting-Based Deep Recurrent Neural Network for Survival Prediction Using PAN-Cancer Gene Expression Data
Authors: Majji Ramachandro , Rajeswari R , Vidyadhari Ch , Cristin R
Published: September 2021

This paper devises a novel technique, namely Squirrel Search Deer Hunting-based deep recurrent neural network (SSDH-based DRNN) for cancer-survival rate prediction using gene expression (GE) data. Initially, the input GE data are transformed using the polynomial kernel data transformation. Then entropy-based Bayesian fuzzy clustering is employed for gene selection. Then, the selected features are strengthened through survival indicators based on time series data features, like simple moving average (SMA) and rate of change. Finally, the survival rate prediction is performed using a deep recurrent neural network (DRNN), in which the training is carried out with squirrel search deer hunting (SSDH). The proposed SSDH algorithm is devised by combining Squirrel Search Algorithm (SSA) and deer hunting optimization algorithm (DHOA). The performance of the proposed methodology is analyzed using Pan-Cancer (PANCAN) dataset with a prediction error of 4.05%, RMSE of 7.58, the accuracy of 90.98%, precision of 90.80%, recall of 92.03% and F1-score of 91.41%. The devised method with higher prediction accuracy and the lower prediction error is employed for the cancer survival prediction of the patients for the cancer prognosis. Besides, it will be helpful for the clinical management of cancer patients.
Pre-oviposition Period and Immature Development of Maconellicoccus hirsutus (Hemiptera: Pseudococcidae) on Cucurbita moschata ‘Black Futsu’ Squash
Authors: Ruais Danielle R , Ganjisaffar Fatemeh , Perring Thomas M
Published: September 2021

The developmental time of pink hibiscus mealybug, Maconellicoccus hirsutus (Green), immatures was investigated on the host plant Cucurbita moschata Duchesne ex Poiret variety ‘Black Futsu.’ Because host plant species influences developmental rates of M. hirsutus, understanding the life history of this specific host plant has implications for the mass rearing protocols of its natural enemy, Anagyrus callidus Triapitsyn, Andreason and Perring, currently being released in California, United States. Fruit from ‘Black Futsu’ squash were infested with first instar pink hibiscus mealybug and kept at 26.6 ± 2°C, 50 ± 10% RH, and 0:24 (L:D) h photoperiod for the duration of the experiment. Every 24 h the life stages of pink hibiscus mealybug individuals on the squash were recorded. After adult eclosion, observations of adult females continued until the first eggs hatched, which revealed an average pre-oviposition period of 7.2 ± 0.1 d and an average length of the egg stage of 7.0 ± 0.0 d. The average developmental times for both sexes were similar from the egg stage through the second instar. Third instar females took nearly twice as long (7.2 d) to develop into adults as did third instar males. However, females have just three immature instars while males have four. The males spent an average of 4.5 ± 0.3 d as third instars and 4.8 ± 0.4 d as fourth instars before developing into winged adults. On average, female immature developmental time was 27.8 ± 0.2 d from egg to adult and male developmental time was 29.4 ± 0.2 d from egg to adult. The implications of these results on rearing A. callidus are discussed.
Normal values and reference ranges for left atrial strain by speckle-tracking echocardiography: the Copenhagen City Heart Study
Authors: Nielsen Anne Bjerg , Skaarup Kristoffer Grundtvig , Hauser Raphael , Johansen Niklas Dyrby , Lassen Mats Christian Højbjerg , Jensen Gorm Boje , Schnohr Peter , Møgelvang Rasmus , Biering-Sørensen Tor
Published: September 2021

Aims 

Left atrial (LA) function assessed by two-dimensional speckle-tracking echocardiography has shown increasing clinical and prognostic significance. We sought to establish age- and sex-based normative values of LA strain in the general population and to assess the prognostic yield of lower limits of normality of LA strain in relation to future atrial fibrillation (AF).

Methods and results 

We determined normative values of peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS), and LA strain during the conduit phase (LACS) in 1641 healthy participants included in the fifth Copenhagen City Heart Study. In a secondary analysis, a validation cohort of 2016 participants, regardless of health status, were included to assess the prognostic value of the established reference values. In the healthy cohort, median age was 46 years (interquartile range 32–57), 62% were female. Median PALS, PACS, and LACS and corresponding limits of normality in the healthy participants were 39.4% (23.0–67.6%), 15.5% (6.4–28.0%), and 23.7% (8.8–44.8%), respectively. There was a tendency of lower values of PALS and LACS in males and older participants, while PACS tended to increase with advancing age. The established lower limits of normality showed high specificity (range 93–94%) regarding future AF, implying a low risk of developing AF in participants with LA strain above the lower limits of normality in their respective sex and age group.

Conclusion 

We report normal values for LA strain stratified by sex and age. The lower limits of normality showed high specificity regarding future AF.
Left atrial strain predicts incident atrial fibrillation in the general population: the Copenhagen City Heart Study
Authors: Hauser Raphael , Nielsen Anne Bjerg , Skaarup Kristoffer Grundtvig , Lassen Mats Christian Højbjerg , Duus Lisa Steen , Johansen Niklas Dyrby , Sengeløv Morten , Marott Jacob Louis , Jensen Gorm , Schnohr Peter , Søgaard Peter , Møgelvang Rasmus , Biering-Sørensen Tor
Published: September 2021

Background

Left atrial (LA) strain parameters have been demonstrated to be valuable predictors of atrial fibrillation (AF) in several patient cohorts. The purpose of this study was to investigate whether LA strain, assessed by two-dimensional speckle-tracking echocardiography, can be used to predict the development of AF in the general population.

Methods and results

This prospective longitudinal study included 4466 participants from the fifth Copenhagen City Heart Study. All participants underwent a health examination, including echocardiographic measurements of LA strain. Participants with prevalent AF at baseline were excluded. The primary endpoint was incident AF. During a median follow-up period of 5.3 years, 154 (4.3%) participants developed AF. In univariable analysis, peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS), and LA strain during the conduit phase were significantly associated with the development of AF. PALS [hazard ratio (HR) 1.05, 95% confidence interval (CI) (1.03–1.07), P < 0.001, per 1% decrease] and PACS (HR 1.08, 95% CI (1.05–1.12), P < 0.001, per 1% decrease] remained independent predictors of AF in multivariable analysis. In addition, PALS and PACS remained significantly associated with AF development even in participants with normal-sized atria and normal left ventricular (LV) systolic function.

Conclusion

In the general population, PALS and PACS independently predict incident AF. These findings remained consistent even in participants with normal-sized LA and normal LV systolic function.
Cropping systems impact changes in soil fungal, but not prokaryote, alpha-diversity and community composition stability over a growing season in a long-term field trial
Authors: Finn Damien R , Lee Sungeun , Lanzén Anders , Bertrand Michel , Nicol Graeme W , Hazard Christina
Published: September 2021

Crop harvest followed by a fallow period can act as a disturbance on soil microbial communities. Cropping systems intended to improve alpha-diversity of communities may also confer increased compositional stability during succeeding growing seasons. Over a single growing season in a long-term (18 year) agricultural field experiment incorporating conventional (CON), conservation (CA), organic (ORG) and integrated (INT) cropping systems, temporal changes in prokaryote, fungal and arbuscular mycorrhizal fungi (AMF) communities were investigated overwinter, during crop growth and at harvest. While certain prokaryote phyla were influenced by cropping system (e.g. Acidobacteria), the community as a whole was primarily driven by temporal changes over the growing season as distinct overwinter and crop-associated communities, with the same trend observed regardless of cropping system. Species-rich prokaryote communities were most stable over the growing season. Cropping system exerted a greater effect on fungal communities, with alpha-diversity highest and temporal changes most stable under CA. CON was particularly detrimental for alpha-diversity in AMF communities, with AMF alpha-diversity and stability improved under all other cropping systems. Practices that promoted alpha-diversity tended to also increase the similarity and temporal stability of soil fungal (and AMF) communities during a growing season, while prokaryote communities were largely insensitive to management.
Examination of Gene Loss in the DNA Mismatch Repair Pathway and Its Mutational Consequences in a Fungal Phylum
Authors: Phillips Megan A , Steenwyk Jacob L , Shen Xing-Xing , Rokas Antonis
Published: September 2021

The DNA mismatch repair (MMR) pathway corrects mismatched bases produced during DNA replication and is highly conserved across the tree of life, reflecting its fundamental importance for genome integrity. Loss of function in one or a few MMR genes can lead to increased mutation rates and microsatellite instability, as seen in some human cancers. Although loss of MMR genes has been documented in the context of human disease and in hypermutant strains of pathogens, examples of entire species and species lineages that have experienced substantial MMR gene loss are lacking. We examined the genomes of 1,107 species in the fungal phylum Ascomycota for the presence of 52 genes known to be involved in the MMR pathway of fungi. We found that the median ascomycete genome contained 49/52 MMR genes. In contrast, four closely related species of obligate plant parasites from the powdery mildew genera Erysiphe and Blumeria, have lost between five and 21 MMR genes, including MLH3, EXO1, and DPB11. The lost genes span MMR functions, include genes that are conserved in all other ascomycetes, and loss of function of any of these genes alone has been previously linked to increased mutation rate. Consistent with the hypothesis that loss of these genes impairs MMR pathway function, we found that powdery mildew genomes with higher levels of MMR gene loss exhibit increased numbers of mononucleotide runs, longer microsatellites, accelerated sequence evolution, elevated mutational bias in the A|T direction, and decreased GC content. These results identify a striking example of macroevolutionary loss of multiple MMR pathway genes in a eukaryotic lineage, even though the mutational outcomes of these losses appear to resemble those associated with detrimental MMR dysfunction in other organisms.
A mixture theory analysis for reflection phenomenon of homogeneous plane-P1-wave at the boundary of unsaturated porothermoelastic media
Authors: Liu Hongbo , Dai Guoliang , Zhou Fengxi , Cao Xiaolin
Published: September 2021

A mixture theory is employed to analyse the reflection behaviour of a homogeneous plane-P1-wave at the boundary of an unsaturated porothermoelastic medium. A non-isothermal dynamic model is employed which takes into account the interaction between the pore fluids and the solid phase of the porous material. In such an unsaturated porothermoelastic cases, the theoretical expressions of the amplitude reflectivity and energy ratio for five kinds of reflected waves generated by the incidence of homogeneous plane-P1-wave, that is reflected P1, P2, P3, S and thermal waves, are derived by taking into consideration of the traction-free, water-permeable, air-permeable and adiabatic boundary conditions. The numerical results are obtained and utilized to discuss the relationship between the amplitude reflectivity and energy ratio of each reflected wave and the thermophysical parameters of the unsaturated porothermoelastic media. The results show that the amplitude and energy carried by the incident wave are mainly occupied by reflected P1 wave and reflected S wave. The amplitude reflectivity and energy ratio of each reflected wave is not just related to the incident angle but also affected by the saturation, thermal expansion coefficient and initial reference temperature. The phase lags of the heat flux and temperature gradient and the thermal conductivity only have a large effect on the amplitude reflectivity and energy ratio of reflected thermal wave.
A joint inversion-segmentation approach to assisted seismic interpretation
Authors: Ravasi Matteo , Birnie Claire
Published: September 2021

Structural seismic interpretation and quantitative characterization are historically intertwined processes. The latter provides estimates of the properties of the subsurface, which can be used to aid structural interpretation alongside the original seismic data and a number of other seismic attributes. In this work, we redefine this process as an inverse problem which tries to jointly estimate subsurface properties (i.e. acoustic impedance) and a piece-wise segmented representation of the subsurface based on user-defined macroclasses. By inverting for the quantities simultaneously, the inversion is primed with prior knowledge about the regions of interest, whilst at the same time it constrains this belief with the actual seismic measurements. As the proposed functional is separable in the two quantities, these are optimized in an alternating fashion, where each subproblem is solved using the Primal-Dual algorithm. Subsequently, the final segmented model is used as input to an ad hoc workflow that extracts the perimeter of the detected shapes and produces a structural framework (i.e. seismic horizons) consistent with the estimated subsurface properties. The effectiveness of the proposed method is illustrated through numerical examples on synthetic and field data sets.
Association between Charlson Comorbidity Index and polypharmacy: a retrospective database study from Jordan
Authors: Arabyat Rasha M , Alazzam Ola M , Al-Azzam Sayer I , Nusair Mohammad B
Published: September 2021

Objectives

Polypharmacy is usually associated with duplication of therapy, unnecessary medications and adverse drug reactions. Therefore, it is crucial to study the factors that increase the risk of polypharmacy. The objective of this study was to assess the risk factors for polypharmacy (i.e. the concomitant use of at least five medications) with a special focus on comorbidity in Jordan.

Methods

Using a retrospective cross-sectional study design, medical records of patients (age ≥55 years), which covered slightly over one-fourth of the population, found in a national electronic healthcare database from 2018 to 2019 were retrieved. Polypharmacy, the main outcome, was defined as the current use of at least five medications (the patient should have at least one chronic condition, one medication refill and continuous use of the medication for at least 30 days). Comorbidity, the main exposure, was summarized using the Charlson Comorbidity Index (CCI). Potential predictors of polypharmacy were examined using a multivariable logistic regression analysis.

Key findings

An eligible sample of 113 834 individuals (mean age 68 years, 51.5% female) were included in the analysis, of whom 38% met the polypharmacy definition (28% were categorized as having major [5–9 medications] and 10.2% exhibited excessive polypharmacy [≥10 medications]). Approximately, 20% of the patients had a CCI of ≥1. The most significant predictors of polypharmacy were a CCI score between 3 and 4 (adjusted odds ratio [AOR] = 5.89; 95% CI, 5.10 to 6.80; P < 0.001), gender (AOR = 0.86; 95% CI, 0.82 to 0.86; P < 0.001), and age ≥75 years (AOR = 1.62; 95% CI, 1.57 to 1.67; P < 0.001).

Conclusions

Polypharmacy is common among patients in Jordan. Comorbidity is positively, independently and strongly related to polypharmacy. Identifying groups who are at the greatest risk for polypharmacy can help optimize patients’ treatment, which can lead to better outcomes and improved quality of life.
A Comparative Study on the Biological Characteristics of Parthenogenetic and Bisexual Restored Trichogramma pretiosum Lines
Authors: Xiao Zhuangting , Tao Xiaobing , Xu Xin , Zhu Congying , Nian Xiaoge , Han Dongliang , Wang Desen , He Yurong
Published: September 2021

In order to investigate the effect of Wolbachia on fitness of their hosts, the biological characteristics of a primarily parthenogenetic line and a bisexual restored line (obtained by antibiotic treatment) of Trichogramma pretiosum were compared in the laboratory. Results indicated that both the mean longevity and fecundity of parthenogenetic line (14.2 d and 165 eggs/female) were significantly higher than those in bisexual restored line (8.4 d and 124.2 eggs/female). Both lines of T. pretiosum had the highest daily fecundity (23.3 eggs/female for parthenogenetic line and 19.8 eggs/female for bisexual restored line) on the first day during their reproduction period, and their survival rate and daily fecundity decreased gradually with age; however, the survival rate and daily fecundity of the parthenogenetic line were always higher than those of bisexual restored line, during the entire experimental period. There was no significant difference in emergence rate and deformity rate between the two T. pretiosum lines. The life-table parameter results indicated that net reproduction rate (R0) and mean generation time (T) in parthenogenetic line (133 and 16.8) were significantly higher than those in bisexual restored line (61.7 and 15.5); intrinsic rate of natural increase (rm) and finite rate of increase (λ) in parthenogenetic line (0.29 and 1.34) were higher than those in bisexual restored line (0.26 and 1.3). Based on these results, it can be confirmed that the removal of Wolbachia in the parthenogenetic line had an adverse effect on fitness of T. pretiosum.
Dry and Rainy Seasons Significantly Alter the Gut Microbiome Composition and Reveal a KeyEnterococcussp. (Lactobacillales: Enterococcaceae) Core Component inSpodoptera frugiperda(Lepidoptera: Noctuidae) Corn Strain From Northwestern Colombia
Authors: Higuita Palacio Marlon Felipe , Montoya Olga I , Saldamando Clara I , García-Bonilla Erika , Junca Howard , Cadavid-Restrepo Gloria E , Moreno-Herrera Claudia Ximena
Published: September 2021

Spodoptera frugiperda is a polyphagous pest of several crops of economic importance. Nowadays, the insect is broadly distributed in America and, recently, in Africa, Asia, and Australia. The species has diverged into corn and rice strains. The role of the gut microbiota in insect physiology is relevant due to its participation in crucial functions. However, knowledge of seasonal variations that alter the gut microbiome in pests is limited. Gut microbiome composition between the dry and rainy seasons was analyzed with cultured and uncultured approaches in S. frugiperda corn strain larvae collected at Northwest Colombia, as seasonal microbiome changes might fluctuate due to environmental changes. On the basis of culture-dependent methods, results show well-defined microbiota with bacterial isolates belonging to Enterococcus, Klebsiella (Enterobacteriales: Enterobacteriaceae), Enterobacter (Enterobacterales: Enterobacteriaceae), and Bacillus (Bacillales: Bacillaceae) genera. The community composition displayed a low bacterial diversity across all samples. The core community detected with uncultured methods was composed of Enterococcus, Erysipelatoclostridium (Erysipelotrichales: Erysipelotrichaceae), Rasltonia (Burkholderiales: Burkholderiaceae), and Rhizobium (Hyphomicrobiales: Rhizobiaceae) genera, and Enterobacteriaceae family members. Significant differences in microbiome diversity were observed between the two seasons. The relative abundance of Erysipelatoclostridium was high in the dry season, while in the phylotype ZOR0006 (Erysipelotrichales: Erysipelotrichaceae) and Tyzzerella (Lachnospirales: Lachnospiraceae) genus, the relative abundance was high in the rainy season. The overall low gut bacterial diversity observed in the S. frugiperda corn strain suggests a strong presence of antagonist activity as a selection factor possibly arising from the host, the dominant bacterial types, or the material ingested. Targeting the stability and predominance of this core microbiome could be an additional alternative to pest control strategies, particularly in this moth.
Application of Deep Learning to Community-Science-Based Mosquito Monitoring and Detection of Novel Species
Authors: Khalighifar Ali , Jiménez-García Daniel , Campbell Lindsay P , Ahadji-Dabla Koffi Mensah , Aboagye-Antwi Fred , Ibarra-Juárez Luis Arturo , Peterson A Townsend
Published: September 2021

Mosquito-borne diseases account for human morbidity and mortality worldwide, caused by the parasites (e.g., malaria) or viruses (e.g., dengue, Zika) transmitted through bites of infected female mosquitoes. Globally, billions of people are at risk of infection, imposing significant economic and public health burdens. As such, efficient methods to monitor mosquito populations and prevent the spread of these diseases are at a premium. One proposed technique is to apply acoustic monitoring to the challenge of identifying wingbeats of individual mosquitoes. Although researchers have successfully used wingbeats to survey mosquito populations, implementation of these techniques in areas most affected by mosquito-borne diseases remains challenging. Here, methods utilizing easily accessible equipment and encouraging community-scientist participation are more likely to provide sufficient monitoring. We present a practical, community-science-based method of monitoring mosquito populations using smartphones. We applied deep-learning algorithms (TensorFlow Inception v3) to spectrogram images generated from smartphone recordings associated with six mosquito species to develop a multiclass mosquito identification system, and flag potential invasive vectors not present in our sound reference library. Though TensorFlow did not flag potential invasive species with high accuracy, it was able to identify species present in the reference library at an 85% correct identification rate, an identification rate markedly higher than similar studies employing expensive recording devices. Given that we used smartphone recordings with limited sample sizes, these results are promising. With further optimization, we propose this novel technique as a way to accurately and efficiently monitor mosquito populations in areas where doing so is most critical.
Food Allergy-Related Bullying Among Children and Adolescents
Authors: Cooke Frances , Ramos Ashley , Herbert Linda
Published: September 2021

Objective

Food allergy (FA) management requires youth to avoid allergens and carry emergency medication which can impact participation in social activities. Previous research indicates that some youth experience FA-related bullying, but many studies are limited by single-item assessment methods and a narrow definition of bullying. This study describes FA-related bullying among a diverse cohort of youth with FA and evaluates parent–child disagreement and bullying assessment methods.

Methods

Youth ages 9–15 years (n = 121) diagnosed with an IgE-mediated FA and their primary caregivers were recruited from pediatric FA clinics to complete surveys about their FA-related bullying experiences. Descriptive statistics were conducted to assess overall FA-related bullying and McNemar tests were utilized to assess disagreement among parent–child report and between multi-item and single-item assessment methods.

Results

Seventeen percent and 31% of youth reported FA-related bullying on single-item and multi-item assessments, respectively. Twelve percent of parents reported their child had experienced FA-related bullying. Youth reported overt physical (51%), overt non-physical (66%), and relational FA-related bullying (20%). FA-related bullying was most common among classmates. Assessment method significantly affected the rates of FA-related bullying reported by youth, and parents and youth only agreed on FA-bullying experiences when assessed via the single-item measure.

Conclusions

A subset of a diverse sample of youth with FA reported FA-related bullying. Clinicians should use multi-item assessment methods and ask both parents and children about their experiences to fully capture the experiences of families managing FA. School policies that facilitate FA safety and social inclusion should be promoted.

Clinical Trial Registration

N/A.
Comparable neutralization of SARS-CoV-2 Delta AY.1 and Delta with individuals sera vaccinated with BBV152
Authors: Yadav Pragya D , Sahay Rima R , Sapkal Gajanan , Nyayanit Dimpal , Shete Anita M , Deshpande Gururaj , Patil Deepak Y , Gupta Nivedita , Kumar Sanjay , Abraham Priya , Panda Samiran , Bhargava Balram
Published: September 2021

Sera of COVID-19 naive vaccinees, COVID-19 recovered cases with vaccination and breakthrough cases demonstrated 1.3-, 2.5- and 1.9-fold reduction in neutralization titers against Delta and 1.5-, 3.5- and 2.8-fold against Delta AY.1 compared with B.1, respectively. However, high-neutralization titers would still effectively protect against Delta, Delta AY.1 and B.1.617.3 variants.
Strongyloidiasis in immunocompromised migrants to non-endemic countries in the era of COVID-19: what is the role for presumptive ivermectin?
Authors: Barkati Sapha , Greenaway Christina , Libman Michael D
Published: September 2021

The COVID-19 pandemic has led to widespread use of dexamethasone. Corticosteroid therapy is an important risk factor for Strongyloides hyperinfection. Challenges associated with the performance of Strongyloides tests, and the poor availability of high-quality and timely diagnostic testing, make the use of presumptive ivermectin reasonable in selected situations.
The Omid Litigation: Should Courts Hear Oral Evidence When Determining the Proportionality of Section 2(1) of the Suicide Act 1961?
Authors: Papadopoulou Nataly , Hobson Clark
Published: September 2021

This commentary reviews Mr Omid T’s legal challenge for a declaration of incompatibility under section 4 of the Human Rights Act 1998. Omid argued that section 2(1) of the Suicide Act 1961 is incompatible with his Articles 2 and 8 rights under the European Convention on Human Rights (ECHR). The Omid litigation considers whether it is appropriate and necessary that courts should hear primary oral evidence with cross-examination in determining the ethical, moral, and social policy issues that underlie the assessment of whether the Suicide Act is a disproportionate restriction on Omid’s rights. The question of what type of evidence would need to be available to courts to determine section 2(1)’s proportionality is an important question left unresolved by Nicklinson v Ministry of Justice. The Omid litigation concludes it is inappropriate and unnecessary that courts should hear oral evidence and permit cross-examination in determining section 2(1)’s proportionality. The commentary analyses the reasoning in the Omid litigation regarding why it is inappropriate to hear oral evidence with cross-examination in determining section 2(1)’s proportionality. The commentary then argues a persuasive case can be made for the appropriateness of oral evidence and cross-examination in assisted suicide proportionality cases.
Segregational Drift Constrains the Evolutionary Rate of Prokaryotic Plasmids
Authors: Garoña Ana , Hülter Nils F , Romero Picazo Devani , Dagan Tal
Published: September 2021

Plasmids are extrachromosomal genetic elements in prokaryotes that have been recognized as important drivers of microbial ecology and evolution. Plasmids are found in multiple copies inside their host cell where independent emergence of mutations may lead to intracellular genetic heterogeneity. The intracellular plasmid diversity is thus subject to changes upon cell division. However, the effect of plasmid segregation on plasmid evolution remains understudied. Here, we show that genetic drift during cell division—segregational drift—leads to the rapid extinction of novel plasmid alleles. We established a novel experimental approach to control plasmid allele frequency at the levels of a single cell and the whole population. Following the dynamics of plasmid alleles in an evolution experiment, we find that the mode of plasmid inheritance—random or clustered—is an important determinant of plasmid allele dynamics. Phylogenetic reconstruction of our model plasmid in clinical isolates furthermore reveals a slow evolutionary rate of plasmid-encoded genes in comparison to chromosomal genes. Our study provides empirical evidence that genetic drift in plasmid evolution occurs at multiple levels: the host cell and the population of hosts. Segregational drift has implications for the evolutionary rate heterogeneity of extrachromosomal genetic elements.
DDInter: an online drug–drug interaction database towards improving clinical decision-making and patient safety
Authors: Xiong Guoli , Yang Zhijiang , Yi Jiacai , Wang Ningning , Wang Lei , Zhu Huimin , Wu Chengkun , Lu Aiping , Chen Xiang , Liu Shao , Hou Tingjun , Cao Dongsheng
Published: September 2021

Drug-drug interaction (DDI) can trigger many adverse effects in patients and has emerged as a threat to medicine and public health. Despite the continuous information accumulation of clinically significant DDIs, there are few open-access knowledge systems dedicated to the curation of DDI associations. To facilitate the clinicians to screen for dangerous drug combinations and improve health systems, we present DDInter, a curated DDI database with comprehensive data, practical medication guidance, intuitive function interface, and powerful visualization to the scientific community. Currently, DDInter contains about 0.24M DDI associations connecting 1833 approved drugs (1972 entities). Each drug is annotated with basic chemical and pharmacological information and its interaction network. For DDI associations, abundant and professional annotations are provided, including severity, mechanism description, strategies for managing potential side effects, alternative medications, etc. The drug entities and interaction entities are efficiently cross-linked. In addition to basic query and browsing, the prescription checking function is developed to facilitate clinicians to decide whether drugs combinations can be used safely. It can also be used for informatics-based DDI investigation and evaluation of other prediction frameworks. We hope that DDInter will prove useful in improving clinical decision-making and patient safety. DDInter is freely available, without registration, at http://ddinter.scbdd.com/.
SYST-04. TRAM-01: A PHASE 2 STUDY OF TRAMETINIB FOR PATIENTS WITH PEDIATRIC GLIOMA WITH ACTIVATION OF THE MAPK/ERK PATHWAY
Authors: Perreault Sébastien , Larouche Valérie , Tabori Uri , Hawkins Cynthia , Lippé Sarah , Ellezam Benjamin , Decarie Jean-Claude , Ospina Luis H , Theoret Yves , Desjardins Leandra , Metras Marie-Élaine , Sultan Serge , Cantin Edith , Routhier Marie-Eve , Caru Maxime , Vairy Stephanie , Legault Genevieve , Bouffet Eric , Lafay-Cousin Lucie , Hukin Juliette , Erker Craig , Jabado Nada
Published: September 2021

BACKGROUND

Pediatric low-grade gliomas (PLGG) are the most frequent brain tumors in children. It is known that the majority of PLGG have activation of the MAPK/ERK pathway.

METHODS

This ongoing multicenter phase II trial includes three progressing/refractory PLGG groups: NF1 patients, KIAA1549-BRAF fusion patients and patients with other activation of the MAPK/ERK pathway (excluding V600E). The primary objective was to evaluate the overall response rate based on RANO criteria after daily oral trametinib administration for 18 cycles, lasting 28 days each. Secondary objectives include the assessment of progression-free survival, tolerability of trametinib, serum levels of trametinib and quality of life evaluation during treatment.

RESULTS

As of February 12 2021, 50 patients have been enrolled (NF1: n=10; KIAA1549-BRAF fusion: n=31; other: n=9 including 5 patients with FGFR1 alterations). Median age is 8.8 years (range 2.4-25.5). Median follow-up is 17.5 months (range 4.7-28.5). Forty-three patients are evaluable. The overall response includes: 4 partial response (PR) (9%), 18 minor response (MR) (42%), 17 stable disease (40%), 4 progressive disease (9%). Median time to response is 5.5 months (range 2.4-13.8). Median duration of response is 6.1 months (range 0.6-26.5). Progression free survival at 12 months is 79.9% (95% CI 68.5-93.6%) and median progression free survival has not yet been reached. Treatment was discontinued for 30 patients: 16 after completing 18 cycles as planned, 5 for progressive disease, 5 for adverse events, 4 for other reasons. A total of 8 patients progressed after discontinuation of treatment including 6 patients (37.5%) that completed 18 cycles. Five of these patients had achieved minor response prior to discontinuation.

CONCLUSION

Trametinib is a potentially effective targeted therapy for patients with recurrent/refractory PLGG. Treatment was overall well tolerated. This ongoing trial will continue to gather data on response rate, duration of response and safety of trametinib for PLGG.
On the Moral Impact Theory of Law
Authors: Monti Ezequiel H
Published: September 2021

Mark Greenberg argues that legal obligations are those moral obligations created by the actions of legal institutions in the legally proper way (Moral Impact Theory of Law, MITL). Here I defend three main claims. First, I argue that, although very often misunderstood, Joseph Raz is also a defender of MITL. Secondly, I argue that while both Greenberg and Raz are committed to MITL, they disagree about the conditions under which a moral obligation can be said to be created in the legally proper way. Finally, I argue that Raz’s variant of MITL is better than Greenberg’s. It rests on a more plausible account of authority and it avoids one of the crucial defects threatening Greenberg’s view, namely, its overinclusiveness.
Sexuality in Emerging Adulthood
Authors: Olmstead Spencer B. , Anders Kristin M.
Published: September 2021

Scientific theory is essential to research on sexuality and sexual experiences in emerging adulthood. Theory serves a number of important functions for research, including prediction and explanation. Research has often utilized theory to help enhance what is known about sexuality among those in the developmental period of emerging adulthood. This chapter offers a primer on theories that have been used regularly when studying sex and relationships using emerging adult samples, including life course development theory, symbolic interactionism, social exchange theory, and the theory of sexual possible selves. Following discussion of these theories and their role in guiding research and explaining findings on sex and sexuality, this chapter offers theoretical directions to enhance the rigor of the use of theory in future research on sexual experiences among emerging adults.
Emerging Adult Sexual Behavior
Authors: Vasilenko Sara A.
Published: September 2021

By emerging adulthood, the majority of individuals have engaged in some types of sexual behavior. However, during this period there is considerable variability and change in the prevalence of recent sexual behaviors and their relationship contexts. This chapter reviews the literature on the prevalence of multiple sexual behaviors, focusing on data from nationally representative studies where possible. Findings suggest that most emerging adults engage in behaviors such as kissing, oral sex, and vaginal intercourse during emerging adulthood, with peak prevalence of these behaviors in the late twenties or early thirties. Other behaviors, such as partnered masturbation, anal sex, and kink behaviors are also practiced by a sizeable minority of individuals. Although many individuals engage in casual sex during emerging adulthood, most instances of sexual behavior occur in relationships. Differences in sexual behavior across several subgroups are discussed, with a particular focus on gender and sexual orientation.
Brief Report
Authors: Palmer-Webb Carlie , Nelson Larry J , Millett Mallory A
Published: September 2021

Scholars have briefly examined the substantial impact of shyness on sexual attitudes and behaviors in emerging adulthood. However, shyness is only one form of social withdrawal that has been identified. Building on previous research, the purpose of this study was to examine the associations between three distinct forms of social withdrawal—shyness, avoidance, and unsociability—and the sexual attitudes and behaviors of emerging adults. Participants included 792 undergraduate and graduate students from throughout the United States gathered as a part of Project READY. Results revealed that each form of social withdrawal was uniquely associated with sexual attitudes and behaviors, with shyness leading the subtypes in its reach of influence across outcomes and gender.
Brief Report
Authors: Kaufman-Parks Angela M. , Longmore Monica A. , Manning Wendy D , Giordano Peggy C.
Published: September 2021

Much prior research acknowledges that peers influence adolescents’ sexual behaviors. Yet few studies have explored whether and how peers influence sexual decision making among emerging adults, especially among those in committed intimate partnerships, while also accounting for dynamics specific to the intimate relationship and respondents’ sociodemographic characteristics. Drawing on longitudinal data from the Toledo Adolescent Relationships Study, this report examined multiple aspects of peer influence on three different sexual behaviors among emerging adults: sexual non-exclusivity, number of casual sex partners, and lifetime number of sex partners. It was found that having more sexually liberal peers and peers who engaged in criminal activity significantly influenced emerging adults’ self-reported numbers of casual and lifetime sex partners, as well as the frequency of engagement in sexually non-exclusive behaviors among those in committed dating, cohabiting, and marital partnerships. This report discusses potential theoretical mechanisms linking these relationships and provides suggestions for future research.
Sexual Health in Emerging Adulthood
Authors: Joppa Meredith , Cantor Nicole , Doremus Corey
Published: September 2021

Sexual health in emerging adulthood encompasses a wide spectrum of medical and mental health functioning and associated behaviors. This chapter addresses aspects of physical sexual health that are of concern to emerging adults, including prevalence rates, determinants, and consequences of sexually transmitted infections, including HIV, and unintended pregnancy among emerging adults. The chapter also discusses sexual dysfunction and its treatment. Whenever possible, the chapter highlights differences in prevalence, risk, and protective factors related to aspects of human diversity, guided by an intersectional approach based on the ADDRESSING framework. Both protective and risky sexual health behaviors and decision making about sexual behavior are discussed, with a focus on the role of substance use in sexual risk taking. The chapter concludes with implications for future research, particularly in the area of prevention.
Sexual Well-Being in Emerging Adulthood
Authors: Espinosa-Hernández Graciela , Vasilenko Sara A
Published: September 2021

This chapter reviews the literature on sexual well-being, defined as the positive cognitive and emotional evaluations of one’s sexuality. Components include sexual self-esteem, sexual self-efficacy, sexual self-reflection, sexual satisfaction and pleasure, and positive emotional response. Most researchers have examined condom use self-efficacy and sexual satisfaction. For some constructs, men, compared to women, report better sexual well-being (e.g., condom use self-efficacy and orgasm). Little is known about how sexual well-being changes in emerging adulthood, but it is known that constructs vary by sexual and romantic experience. Emerging adults who are more sexually experienced and engage in behaviors in the context of romantic relationships report better sexual well-being. Many sexual well-being constructs are also linked with less risky sexual behavior and better psychological adjustment (e.g., self-esteem and identity development). Future recommendations include measurement research to better understand overlapping constructs, examining diverse samples, and more longitudinal research.
New Perspectives on the Integration of Sexual Health Promotion and Sexual Violence Prevention During Emerging Adulthood
Authors: Maas Megan K. , Waterman Emily A.
Published: September 2021

Both sexual health promotion (i.e., prevention of adverse physical outcomes such as sexually transmitted infections and unwanted pregnancy and promotion of sexual experiences that are emotionally, mentally, relationally, and physically positive) and sexual violence prevention (i.e., prevent ion of sexual harassment consisting of unwanted sexual teasing, joking, or sexual requests and sexual assault that consists of any unwanted sexual contact) are important public health issues for emerging adults. This chapter discusses the opportunity for integrating sexual health promotion and sexual violence prevention for emerging adults. It discusses key topic areas for integration, including bystander intervention, sexual communication, consent education, gender transformative education, and media literacy. The chapter also discusses how preventionists can use existing infrastructure for sexual health promotion and sexual violence prevention to better integrate these initiatives. Integrating these efforts will help ensure that emerging adults think holistically about their sexual experiences as a fundamental part of their well-being throughout the life span.
Conceiving People
Authors: Groll Daniel
Published: September 2021

Each year, tens of thousands of children are conceived with donated sperm or eggs, aka donated gametes. By some estimates, there are over 1 million donor-conceived people in the United States and, of course, many more the world over. Some know they are donor-conceived. Some don’t. Some know the identity of their donors. Others never will. Conceiving People: Identity, Genetics and Gamete Donation argues that people who plan to create a child with donated gametes should choose a donor whose identity will be made available to the resulting child. This is not because having genetic knowledge is fundamentally important. Rather, it is because donor-conceived people are likely to develop a significant interest in having genetic knowledge and parents must help satisfy their children’s significant interests. In other words: because a donor-conceived person is likely to care about having genetic knowledge, their parents should care too. Questions about what the donor-conceived should know about their genetic progenitors are hugely significant for literally millions of people, including donor-conceived people, their parents, and donors. But the practice of gamete donation also provides a vivid occasion for thinking about questions that matter to everyone. What value, if any, is there in knowing who your genetic progenitors are? To what extent are our identities bound up with knowing where we come from? What obligations do parents have to their children? And what makes someone a parent—the person responsible for lovingly raising a child—in the first place?