bluuebunny/crossref_metadata_2025 huggingface dataset:
Cenobamate: A New Adjunctive Agent for Drug-Resistant Focal Onset Epilepsy
Authors: Buckley Christopher T. , Waters Olivia R. , DeMaagd George
Published: July 2020

Objective

To review the pharmacology, efficacy, and safety of oral cenobamate in the treatment of uncontrolled focal epilepsy.

Data Sources

The PubMed database and ClinicalTrials.gov were searched using the following terms: cenobamate, Xcopri, and YKP3089.

Study Selection and Data Extraction

Articles published in English between January 2000 and April 2020 related to pharmacology, safety, and clinical trials were assessed.

Data Synthesis

In a phase 2 trial, cenobamate reduced the median percentage change in seizure frequency from baseline by 56% compared with 22% for placebo ( P < 0.0001). In another phase 2 trial of multiple cenobamate doses, cenobamate reduced seizure frequency by 36% ( P = 0.0071) in the 100-mg group and 55% ( P < 0.0001) in both the 200- and 400-mg groups, compared to 24% with placebo. Adverse effects of cenobamate appear to be similar to those of other antiseizure medications and primarily affect the neurological system.

Relevance to Patient Care and Clinical Practice

In patients taking antiseizure medications who continue to have focal seizures, cenobamate has efficacy at multiple doses and is generally well tolerated. Cenobamate may be distinguished from other antiseizure medications by high rates of seizure freedom not seen in previous placebo-controlled trials, which has the potential to significantly improve quality of life. However, despite this efficacy, Drug Reaction with Eosinophilia and Systemic Symptoms may remain a significant concern with cenobamate.

Conclusion

As seen in clinical trials, cenobamate as an adjunctive, once-daily treatment represents an efficacious and generally well-tolerated therapy for patients with drug-resistant focal epilepsy.
Free transverse vibrational analysis of axially functionally graded tapered beams via the variational iteration approach
Authors: Chen Yanfei , Dong Shaohua , Zang Zhipeng , Gao Modi , Zhang Juan , Ao Chuan , Liu Hao , Zhang Qi
Published: July 2020

Tapered beams constitute functionally graded materials that are widely used in various engineering fields. The vibrational characteristics of tapered beams made of axially varying functionally graded materials are investigated via variational iteration method. Natural frequencies and corresponding mode shapes of axially functionally graded tapered beams are examined, and calculated frequencies are compared with results provided by previous researchers using other approximate methods. The efficiency and accuracy of this technique are demonstrated. The effect of nonhomogeneous material distribution, taper ratio as well as boundary conditions on the dynamical behavior of axially functionally graded tapered beams is thoroughly investigated as well.
“Mongering Is a Weird Life Sometimes”: Discourse Analysis of a Sex Buyer Online Community
Authors: Alves Catarina D. B. , Cavalhieri Klaus E.
Published: July 2020

The purpose of this study was to examine the narrative of sex buyers in an unmoderated online forum. Using a feminist critical discourse analysis (FCDA) and intersectionality approach, we investigated overt and subtle ways power inequalities were present in the discourse of men who bought sex in Chicago. Four main themes emerged: (a) toxic masculinity; (b) violence against women; (c) intersectionality of sexuality, race, and age; and (d) the need to maintain the community. Our findings imply that johns’ self-described monger identity is closely associated with maintaining, perpetrating, and minimizing violence against women.
A Qualitative Study of Women’s Lived Experiences of Conflict and Domestic Violence in Afghanistan
Authors: Mannell Jenevieve , Grewal Gulraj , Ahmad Lida , Ahmad Ayesha
Published: July 2020

This article empirically explores women’s lived experiences of domestic violence and conflict in Afghanistan. A thematic analysis of 20 semistructured interviews with women living in safe houses produced three main themes about the relationship between conflict and domestic violence: (a) violence from loss of patriarchal support, (b) violence from the drug trade as an economic driver, and (c) violence from conflict-related poverty. We discuss the bidirectional nature of this relationship: Not only does conflict contribute to domestic violence, but domestic violence contributes to conflict through justifying armed intervention, separating women from economic and public life, and perpetuating patriarchy.
Review of Public Financing for Water, Sanitation, and Hygiene Sectors in Vietnam
Authors: Mai Vu Quynh , Ngoc Anh Hoang Thi , Thao Anh Hoang , Van Minh Hoang
Published: July 2020

Background:

Vietnam declared its national roadmap towards Sustainable Development Goals number 6 by 2030. However, specific supporting programmes and financial means to proceed with the roadmap have not been passed on. Evidence on the financing for water, sanitation, and hygiene (WASH) being allocated or spent has not been well documented in Vietnam. This study aimed to obtain an overview and assessed the public funding across the WASH sector of Vietnam in 3 fiscal years 2016, 2017, and 2018.

Methods:

A cross-sectional study was conducted for information about the public financing for WASH at both national and sub-national levels. An activity-based costing approach was applied to determine WASH-related public expenditure. Fourteen focus group discussions with key stakeholders were used to identify the WASH activities and to access financial reports of these relevant institutions. TrackFin methodology was used to assemble the public financing for WASH in Vietnam.

Results:

The public expenditure of WASH declined by about 30.7% over the 3 fiscal years, from US $2016 million in 2016 to US $1397 million in 2018. Meanwhile, this expenditure allocated to the poor or mountainous areas increased by 3 folds. The highest proportion of WASH public funding was invested in sanitation through large network systems (59.07% of the total public expenditure), whereas the lowest was in hygiene promotion and handwashing facilities. The domestic budget was still the main source of public financing for WASH services, with 2 largest shares coming from government revenues (47.24%) and repayable loans (20.49%).

Conclusion:

The main source of financing for WASH was from the government, yet its public expenditure has been decreased. A refined roadmap with specific steps for a sustainable WASH financing system in Vietnam, particularly to leverage government and private sector resources, is required to ensure no one is left behind.
Bringing Morgenthau’s ethics in: pluralism, incommensurability and the turn from fragmentation to dialogue in IR
Authors: Karkour Haro L , Giese Dominik
Published: July 2020

Why did IR pluralism end with so many incommensurable camps? (How) can IR be demarcated as a discipline where these camps can find common ground for dialogue without glossing over theoretical pluralism? To answer the first question, the paper argues that Morgenthau’s critique of IR as social science can explain the proliferation of camps in IR pluralism that are incommensurable and cannot engage in dialogue. By transcending the dilemma of politics as highlighted in Morgenthau’s critique of social science, theories today are ideological camps that bestow on morality an ideological function that justifies their powers-that-be that serve particular means/ends hierarchies. This leads to the proliferation of empirical causal analyses that cannot be debated, since they rely on political interests that theory ideologically justifies and offers internal validation. To avoid this problem, the paper answers the second question by proposing to demarcate the discipline through Morgenthau’s concept of ‘interest defined as power’. It argues that demarcating the discipline on the basis of this concept opens room for engaging in dialogue in IR through leaving open the normative debate of means and ends, and thus acts as a bulwark against the proliferation of ideological camps, while promoting theoretical pluralism.
Heritage language learners’ written texts across pair types and interaction mode
Authors: Torres Julio
Published: July 2020

Task-based research has investigated the learning opportunities (e.g. language related episodes) that emerge during heritage and second language learner interactions during writing tasks. However, to date, it is unknown how these peer interactions involving heritage language learners contribute to written texts. Further, given the rise of social technologies in educational settings, a need exists to examine how interactions in digital platforms affect the production of written texts. To address these issues, 13 heritage-second language learner and 16 heritage–heritage learner pairs enrolled in advanced Spanish content courses completed two distinct versions of writing tasks. Participants were instructed that they were hired as business consultants for clothing and cellphone companies in Spain. While each participant wrote her or his own version, the pairs had to interact to compose formal business letters in Spanish to the CEO of each company justifying the hiring (Task A) or laying off (Task B) of employees. The main results first revealed that heritage–heritage pairs produced more syntactically complex business letters, as evidenced by a greater ratio of syntactic subordination along with a minor trend of greater morphosyntactic accuracy. Second, synchronous computer-mediated communication interactions led to a higher production of syntactic coordination, especially for the heritage-second language pairs. Findings are discussed in light of the interplay between learner factors and task environment.
Multi-component communication intervention for children with autism: A randomized controlled trial
Authors: Hampton Lauren H , Kaiser Ann P , Fuller Elizabeth A
Published: July 2020

The objective of this study is to evaluate the effectiveness of a multi-component communication intervention on social communication for young children with autism. As many as half of children with autism are not yet talking by age 3, and up to a third of children with autism will remain minimally verbal past age 5. Spoken language outcomes are greatest when parents and clinicians are delivering language interventions to children with autism as compared to parents or clinicians alone. This study incorporates caregiver training, Discrete Trial Teaching, and JASP + EMT + SGD. A total of 68 children between ages 3 and 5 with autism, and their caregivers, participated in this study. Children were randomly assigned to the treatment or control group. Children in the treatment group received 36 sessions of the multi-component intervention in the clinic and at home. Children in both groups received a speech-generating device and the caregivers received an individualized training on how to program the speech-generating device. All participants were evaluated prior to intervention, immediately following intervention, and 4 months following intervention. Children in the intervention group demonstrated significantly greater joint attention than those in the control group immediately following intervention. Children in the intervention group, additionally, demonstrated greater social communication with their caregivers 4 months following intervention. This brief, multi-component intervention may be effective for improving social communication in young children with autism who are at risk for remaining minimally verbal. Future research is needed to understand for whom and under what conditions this intervention is most effective.

Lay abstract

This study reports the results of a randomized trial for preverbal preschoolers with autism that demonstrates the effects of multiple intervention strategies including caregiver training. About 50% of children with autism are not talking by age 3 and up to 30% of children with autism will remain minimally verbal past age 5. Interventions delivered by clinicians and caregivers have the greatest effects on spoken language and may reduce the rate of those who remain minimally verbal. Sixty-eight children ages 3–5 with autism and their caregivers participated in this randomized trial comparing the communication intervention to a comparison group. A brief, multi-component, communication intervention (including a speech-generating device) for children with autism that addresses core deficits may be effective in improving joint attention skills immediately following intervention and social communication skills 4 months following intervention. Future research is needed to understand for whom and under what conditions this intervention is most effective.
Promoting CRISPRa for Targeted Treatment of Epilepsy
Authors: Wagnon Jacy L.
Published: July 2020

[Box: see text]
Susceptibility Assessment of Multidrug Resistant Bacteria to Natural Products
Authors: Mohamed Essam Hassan , Alghamdi Youssef Saeed , Mostafa Abdel-Hafez Salama , Soliman Mohamed Mohamed , Alotaibi Saad H. , Hassan Magdy Yassin , Hany Nasr Al-Deen , Amer Hamada H.
Published: July 2020

Objective:

The aim of this study was to examine the effect of some natural compounds against multidrug-resistant bacteria.

Methods:

Forty-three bacterial strains were collected. Disc diffusion and minimum inhibitory concentration (MIC) tests were carried out for natural compounds including quercetin, Acacia nilotica, Syzygium aromaticum, and Holothuria atra. Scanning electron microscope analysis and bacterial DNA apoptosis assays were performed.

Results:

Staphylococcus aureus strains were resistant to imipenim, ampicillin, and penicillin. Most Escherichia coli strains were resistant to amoxicillin, clavulanat, and ampicillin. Finally, tigecycline was effective with Klebsiella pneumoniae and was resistant to all antibiotics. Only S aromaticum had an antibacterial effect on K pneumoniae. Most S aureus strains were sensitive to S aromaticum, A nilotica, and quercetin. All examined natural extracts had no effect on E coli. Holothuria atra had no effect on any of the strains tested. Minimum inhibitory concentration and minimum bactericidal concentration values for examined plants against S aureus were 6.25 to 12, 1.6 to 3.2, and 9.12 to 18.24 mg/mL, respectively. Syzygium aromaticum was active against K pneumoniae with an MIC of 12.5 mg/mL. Scanning electron microscope analysis performed after 24 and 48 hours of incubation showed bacterial strains with distorted shapes and severe cell wall damage. Syzygium aromaticum, quercetin, and A nilotica showed clear fragmentations of S aureus DNA.

Conclusions:

Current findings confirmed the beneficial effect of using natural products such as clove (S aromaticum), quercetin, and A nilotica as a promising therapy to overcome multidrug resistant bacteria.
Effectiveness of social media (Facebook), targeted mailing, and in-person solicitation for the recruitment of young adult in a diabetes self-management clinical trial
Authors: Salvy Sarah-Jeanne , Carandang Kristine , Vigen Cheryl LP , Concha-Chavez Alyssa , Sequeira Paola A , Blanchard Jeanine , Diaz Jesus , Raymond Jennifer , Pyatak Elizabeth A
Published: July 2020

Background/Aims

Research is needed to identify promising recruitment strategies to reach and engage diverse young adults in diabetes clinical research. The aim of this study was to examine the relative strengths and weaknesses of three recruitment strategies used in a diabetes self-management clinical trial: social media advertising (Facebook), targeted mailing, and in-person solicitation of clinic patients.

Methods

Strategies were compared in terms of (1) cost-effectiveness (i.e. cost of recruitment/number of enrolled participants), (2) ability to yield participants who would not otherwise be reached by alternative strategies, and (3) likelihood of participants recruited through each strategy to adhere to study procedures. We further explored the appeal (overall and among age and gender subgroups) of social media advertisement features.

Results

In-person recruitment of clinic patients was overall the most cost-effective strategy. However, differences in demographic, clinical, and psychosocial characteristics of participants recruited via different strategies suggest that the combination of these approaches yielded a more diverse sample than would any one strategy alone. Once successfully enrolled, there was no difference in study completion and intervention adherence between individuals recruited by the three recruitment strategies.

Conclusions

Ultimately, the utility of a recruitment strategy is defined by its ability to effectively attract people representative of the target population who are willing to enroll in and complete the study. Leveraging a variety of recruitment strategies appears to produce a more representative sample of young adults, including those who are less engaged in diabetes care.
The 6 to 8-week check
Authors: Jones Bethan L
Published: July 2020

The ‘6-week check’ is a head-to-toe assessment that forms part of the newborn and infant physical examination (NIPE). This NHS screening programme comprises two stages: the neonatal component takes place within 72 hours of birth, usually before discharge home, and the infant examination is performed between 6 and 8 weeks of age, typically in the community by the GP. The NIPE aims to detect abnormalities of the eyes, heart, hips and testes, and to ensure appropriate follow up of positive findings. It also presents an opportunity for care providers to monitor a child’s general health and development, and to provide information, health promotion, and support to parents and carers. This article seeks to describe in more detail the background and purpose of the infant check, to provide a systematic approach for performing the examination with a focus on four key conditions and to recommend referral pathways for positive findings.
Welfare Stereotypes and Conditional Cash Transfer Programmes: Evidence from Brazil’s Bolsa Família
Authors: Layton Matthew L.
Published: July 2020

Some observers claim that conditional cash transfer programmes limit the stigma of taking welfare and thereby promote social inclusion for beneficiaries. This article uses data from the 2014 AmericasBarometer to test these claims in relation to Brazil’s Bolsa Família programme (BFP). The results show that, despite the programme’s innovative design, beneficiaries encounter the stigmatisation and negative self-stereotypes that characterise more traditional anti-poverty programmes. Many Brazilians, recipient and non-recipient alike, endorse explicitly negative stereotypes of Bolsa Família assistance recipients. Moreover, the level to which respondents endorse these stereotypes strongly predicts their level of support for the BFP. These results highlight the pervasive nature of negative stereotypes towards the poor, even in the context of the developing world, and are consistent with the predictions of social psychological theories of system justification.
The Impact of Law Enforcement Centralisation and Professionalisation on Public Opinion of the Mexican Police
Authors: Esparza Diego , Ugues Antonio
Published: July 2020

Pandemic violence and criminality are anathema to a democratic society. And yet, in Latin America, both operate side by side. Illicit activity has propagated precisely because the democratic states of the region have been ineffective at establishing and maintaining the rule of law via public security mechanisms like the police. This ineffectiveness has significant consequences for public support of police forces. Hence, an important question for students of state-building and democratisation is: What factors explain public perceptions of the police? We argue that police forces that are local and unprofessional will be less trusted and viewed as less effective than their more centralised and professional counterparts of state and federal police. In short, we find that centralisation and professionalisation mitigate the impact of crime victimisation and police corruption on the public opinion of the police in Mexico. These findings are drawn from an analysis of the National Survey of Victimisation and Perceptions of Public Security (ENVIPE) in Mexico for 2012 and 2018.
Ugliness Judgments Alert us to Cues of Pathogen Presence
Authors: Klebl Christoph , Greenaway Katharine H. , Rhee Joshua Ju-suk , Bastian Brock
Published: July 2020

Little is known about the psychology of ugliness. We propose that ugliness judgments are linked to the behavioral immune system, alerting us to objects that may contain potentially harmful diseases. Exploring this possibility, in five studies ( N = 1,552), we found that ugly human faces (Studies 1a and 1b), ugly animals (Study 2), and—to a lesser degree—ugly buildings (Study 2) elicit disgust controlling for other avoidance-motivated emotional responses. Furthermore, the presence (vs. absence) of disease cues were found to elicit ugliness judgments (Studies 3 and 4) suggesting that ugliness judgments respond to cues of pathogen presence. As such, ugliness may activate the behavioral immune system, alerting us to stimuli that pose pathogen risk.
Covid-19 and labour law in Italy
Authors: Biasi* Marco
Published: July 2020

This article provides an account of the Italian response to the Covid-19 pandemic in the labour law field. The author focuses on the policy measures in the matters of income support, parental leave, rest and holiday leave, agile working (i.e. teleworking), dismissal, as well as on the special provisions arranged by the social partners and later adopted by the legislator to preserve the health and safety of the employees and also to prevent the spread of coronavirus in the workplace. Ultimately, the author hints at the potential development of employee participation in Italy in the wake of the upsurge of social dialogue during the coronavirus emergency.
Covid-19 and labour law in the Netherlands
Authors: Bennaars Hanneke
Published: July 2020

Against the backdrop of an ‘intelligent lockdown’ the Dutch government has launched a threefold emergency package to support businesses and safeguard employment as much as possible. This ‘Emergency Jobs and Economy Package’ contains, amongst others, measures that aim to ensure the safeguarding of income and salaries for employees as well as self-employed workers. It concerns mainly subsidy law and the extension of social security legislation, not employment law. However, the safeguarding of income for employees (NOW) entails a fine on redundancies during the period of support. Not only employees, but also self-employed workers can apply for income support. From a health and safety perspective (during lockdown as well as going forward to relaxation), no specific national measures have been taken. The general rules on social distancing and hygiene have to be implemented as part of the general obligation to provide a safe working place. No specific care arrangements for working parents that have to work from home have been put in place.
Do neuroendocrine carcinomas and mixed neuroendocrine–non-neuroendocrine neoplasm of the gastrointestinal tract have the same prognosis? A SEER database analysis of 12,878 cases
Authors: Shi Huiying , Qi Cuihua , Meng Lingjun , Yao Hailing , Jiang Chen , Fan Mengke , Pang Suya , Zhang Qin , Lin Rong
Published: July 2020

Background:

Neuroendocrine carcinomas (NECs) and mixed neuroendocrine–non-neuroendocrine neoplasm (MiNEN) in the gastrointestinal (GI) tract are both rare and malignant; however, it is unclear whether their prognosis is the same.

Methods:

In this cross-sectional study, a total of 12,878 patients with NEC or MiNEN in the GI tract were reviewed retrospectively by searching the Surveillance, Epidemiology, and End Results ( SEER) program database. Next, we compared the characteristics and survival between patients with NEC or MiNEN and further analyzed the prognostic factors for the patients.

Results:

The data showed that patients with MiNEN had a worse prognosis as compared with patients with pure NEC in the small intestine (SI) and appendix, whereas there was no significant survival difference between NEC and MiNEN in the other parts of the GI system. On the whole, age ⩾55 years ( p < 0.0001), male ( p = 0.002), being diagnosed at TNM Stage II–IV ( p < 0.0001) or not receiving surgical treatment ( p < 0.0001) were the independent negative prognostic factors for NEC patients, whereas age ⩾55 years ( p = 0.003), being diagnosed at TNM Stage III–IV ( p < 0.001) or not receiving surgical treatment ( p < 0.001) were identified as the independent negative prognostic factors for the MiNEN patients. Furthermore, when NECs or MiNENs were classified based on the primary tumor site, the results showed that the prognostic factors for NEC and MiNEN varied between the tumor sites.

Conclusion:

The prognostic differences between NECs and MiNENs in the GI tract are heterogeneous and site-related. Patients with appendiceal or SI MiNEN have a poorer prognosis than patients with pure appendiceal or SI NEC. Therefore, we should pay more attention to patients with MiNEN in the SI and appendix and monitor them more closely.
Risk Factors for Severe Proximal Humerus Fracture and Correlation Between Deltoid Tuberosity Index and Bone Mineral Density
Authors: Kim Dong Min , Park Dongjun , Kim Hyojune , Lee Eui-Sup , Shin Myung Jin , Jeon In-Ho , Koh Kyoung Hwan
Published: July 2020

Introduction:

The aims of this study were to investigate (1) whether demographic factors would be risk factors for severe proximal humerus fracture (PHF), (2) relationship of radiological parameters with bone mineral density (BMD), deltoid tuberosity index (DTI), or severe PHF, and (3) correlation between DTI and BMD.

Methods:

We conducted a cross-sectional study based on radiographs and medical records taken during admission or the visit to the orthopedic clinic. We reviewed consecutive 100 adult patients who were diagnosed with PHF in our hospital from March 2014 to December 2016. Three- and 4-part fractures were regarded as severe PHFs. Univariable and multivariable logistic regression analyses were performed to evaluate risk factors for severe PHF. Also, we investigated the correlation between BMD and DTI using the additional BMD data of the patients who underwent shoulder surgeries.

Results:

This study included 62 nonsevere PHFs and 38 severe PHFs. There were 30 male and 70 female patients with a mean age of 66.4 ± 16.4 years. Mean T score of BMD was −2.5 ± 0.9 at the time of injury. Logistic regression analyses showed that age (odds ratio: 1.044, range: 1.011-1.079, P = .009) and sex (odds ratio of females: 3.763, range: 1.236-11.459, P = .020) were related to severe PHF. The group satisfying the radiological parameter criteria had significantly higher rates of severe PHF. The correlation coefficient (r) between DTI and T score was 0.555 ( P < .001).

Discussion and Conclusion:

Older age and female were the independent risk factors for severe PHF. Conversely, BMD and other medical comorbidities were not risk factors for severe PHF. Deltoid tuberosity index showed significantly high intraclass correlation coefficient and a strong correlation with the T score of BMD. Therefore, DTI may be useful for screening osteoporosis in PHF patients.

Level of Evidence:

Level IV, Cross-sectional study.
Indiscriminate friendliness in foster children: Associations with attachment security, foster parents’ sensitivity, and child inhibitory control
Authors: Schoemaker Nikita K. , Vermeer Harriet J. , Juffer Femmie , Spies Ruan , van Ee Elisa , Maras Athanasios , Alink Lenneke R. A.
Published: July 2020

Indiscriminate friendliness (IF) is atypical behavior often seen in postinstitutionalized and foster children. The current exploratory study examined the associations of children’s attachment security, parental sensitivity, and child inhibitory control with reported and observed IF in 60 family-reared, never-institutionalized foster children. IF was measured with a parent-report questionnaire (Indiscriminate Friendliness Questionnaire) and an observational measure (adapted version of the Stranger at the Door procedure; Bucharest Early Intervention Project). Attachment security and inhibitory control were related to reported IF (i.e., a secure attachment and poor inhibitory control were associated with higher levels of IF), but parental sensitivity was not. No associations were found between observed IF and attachment security, parental sensitivity, or inhibitory control. Thus, foster children with a secure attachment relationship may be more prone to socially interact with others including strangers, whereas better inhibitory control may serve as a buffer against IF but these results were found for reported IF only. More research is needed to gain more knowledge about different measures, other possible correlates, and underlying mechanisms of IF.
Administrative prevalence and incidence, characteristics and prescription patterns of patients with migraine in Germany: a retrospective claims data analysis
Authors: Roessler Tatjana , Zschocke Juergen , Roehrig Anne , Friedrichs Michael , Friedel Heiko , Katsarava Zaza
Published: July 2020

Background

Migraine is a frequent headache disorder with high disease burden. The aims of this study were to determine the administrative prevalence and incidence of migraine in Germany; and to elucidate disease characteristics, prescription patterns and the patient journey through the German healthcare system.

Methods

In this retrospective, observational study, adult patients with migraine (International Classification of Diseases, 10th revision, German modification G43) were identified in the anonymised German Company Sickness Fund database (CSFD) from 2008 through 2016. The administrative prevalence and incidence of migraine were calculated for the total CSFD study population and extrapolated to the German Statutory Health Insurance (SHI) population. Migraine subtypes, concurrent diagnoses, prescription patterns and visited healthcare professional groups were analysed.

Results

A total of 243,471 patients with migraine were identified in the CSFD (2008–2016); 78.0% were female and 45.3% were aged 35–54 years. The administrative prevalence of migraine, extrapolated to the SHI population, ranged between 2.89% in 2008 and 3.98% in 2016; administrative incidence ranged from 0.587% in 2009 to 0.267% in 2016, and varied between 0.399% and 0.442% during 2011 to 2015. Overall, 29.1% of patients received at least one prescription for any preventive medication listed in the German guideline. Only 7.9% received the same preventive medication for more than 1 year, with 82.9% of these patients discontinuing the medication before study end. Regarding acute medications, 74.2% of prescriptions were for analgesics/non-steroidal anti-inflammatory drugs and 21.2% were for triptans. General practitioners most commonly diagnosed and treated migraine in the CSFD population. Patients with prescriptions for two or more different preventive therapy classes had higher use of acute and emergency medications, and visited healthcare professionals and hospitals more frequently than patients with no prescriptions or prescriptions for only one preventive therapy class.

Conclusions

The administrative prevalence of migraine in this claims database suggests many patients with migraine did not seek medical care. Of those who did, fewer than one-third received preventive medication, with most patients having been prescribed only one such medication and few having continued treatment beyond 1 year. These outcomes suggest there is scope for improvement in migraine management in Germany.
Optical map guided genome assembly
Authors: Leinonen Miika , Salmela Leena
Published: July 2020

Background

The long reads produced by third generation sequencing technologies have significantly boosted the results of genome assembly but still, genome-wide assemblies solely based on read data cannot be produced. Thus, for example, optical mapping data has been used to further improve genome assemblies but it has mostly been applied in a post-processing stage after contig assembly.

Results

We proposeOpticalKermitwhich directly integrates genome wide optical maps into contig assembly. We show how genome wide optical maps can be used to localize reads on the genome and then we adapt the Kermit method, which originally incorporated genetic linkage maps to the miniasm assembler, to use this information in contig assembly. Our experimental results show that incorporating genome wide optical maps to the contig assembly of miniasm increases NGA50 while the number of misassemblies decreases or stays the same. Furthermore, when compared to the Canu assembler,OpticalKermitproduces an assembly with almost three times higher NGA50 with a lower number of misassemblies on realA. thalianareads.

Conclusions

OpticalKermitsuccessfully incorporates optical mapping data directly to contig assembly of eukaryotic genomes. Our results show that this is a promising approach to improve the contiguity of genome assemblies.
Toward a more holistic method of genome assembly assessment
Authors: Thrash Adam , Hoffmann Federico , Perkins Andy
Published: July 2020

Background

A key use of high throughput sequencing technology is the sequencing and assembly of full genome sequences. These genome assemblies are commonly assessed using statistics relating to contiguity of the assembly. Measures of contiguity are not strongly correlated with information about the biological completion or correctness of the assembly, and a commonly reported metric, N50, can be misleading. Over the years, multiple research groups have rejected the overuse of N50 and sought to develop more informative metrics.

Results

This paper presents a review of problems that arise from relying solely on contiguity as a measure of genome assembly quality as well as current alternative methods. Alternative methods are compared on the basis of how informative they are about the biological quality of the assembly and how easy they are to use. A comprehensive method for using multiple metrics of measuring assembly quality is presented.

Conclusions

This study aims to report on the status of assembly assessment methods and compare them, as well as to offer a comprehensive method that incorporates multiple facets of quality assessment. Weaknesses and strengths of varying methods are presented and explained, with recommendations based on speed of analysis and user friendliness.
Drug-target interaction prediction using semi-bipartite graph model and deep learning
Authors: Eslami Manoochehri Hafez , Nourani Mehrdad
Published: July 2020

Background

Identifying drug-target interaction is a key element in drug discovery. In silico prediction of drug-target interaction can speed up the process of identifying unknown interactions between drugs and target proteins. In recent studies, handcrafted features, similarity metrics and machine learning methods have been proposed for predicting drug-target interactions. However, these methods cannot fully learn the underlying relations between drugs and targets. In this paper, we propose anew framework for drug-target interaction prediction that learns latent features from drug-target interaction network.

Results

We present a framework to utilize the network topology and identify interacting and non-interacting drug-target pairs. We model the problem as a semi-bipartite graph in which we are able to use drug-drug and protein-protein similarity in a drug-protein network. We have then used a graph labeling method for vertex ordering in our graph embedding process. Finally, we employed deep neural network to learn the complex pattern of interacting pairs from embedded graphs. We show our approach is able to learn sophisticated drug-target topological features and outperforms other state-of-the-art approaches.

Conclusions

The proposed learning model on semi-bipartite graph model, can integrate drug-drug and protein-protein similarities which are semantically different than drug-protein information in a drug-target interaction network. We show our model can determine interaction likelihood for each drug-target pair and outperform other heuristics.
Enhanced tolerance to Phytophthora root and stem rot by over-expression of the plant antimicrobial peptide CaAMP1 gene in soybean
Authors: Niu Lu , Zhong Xiaofang , Zhang Yuanyu , Yang Jing , Xing Guojie , Li Haiyun , Liu Dongbo , Ma Rui , Dong Yingshan , Yang Xiangdong
Published: July 2020

Background

Antimicrobial peptides play important roles in both plant and animal defense systems. Moreover, over-expression of CaAMP1 (Capsicum annuum antimicrobial protein 1), an antimicrobial protein gene isolated from C. annuum leaves infected with Xanthomonas campestris pv. vesicatoria, confers broad-spectrum resistance to hemibiotrophic bacterial and necrotrophic fungal pathogens in Arabidopsis. Phytophthora root and stem rot (PRR), caused by the fungus Phytophthora sojae, is one of the most devastating diseases affecting soybean (Glycine max) production worldwide.

Results

In this study, CaAMP1 was transformed into soybean by Agrobacterium-mediated genetic transformation. Integration of the foreign gene in the genome of transgenic soybean plants and its expression at the translation level were verified by Southern and western blot analyses, respectively. CaAMP1 over-expression (CaAMP1-OX) lines inoculated with P. sojae race 1 exhibited enhanced and stable PRR tolerance through T2–T4 generations compared with the wild-type Williams 82 plants. Gene expression analyses in the transgenic plants revealed that the expression of salicylic acid-dependent, jasmonic acid-dependent, and plant disease resistance genes (R-genes) were significantly up-regulated after P. sojae inoculation.

Conclusions

These results indicate that CaAMP1 over-expression can significantly enhance PRR tolerance in soybean by eliciting resistance responses mediated by multiple defense signaling pathways. This provides an alternative approach for developing soybean varieties with improved tolerance against soil-borne pathogenic PRR.
RNA-Seq of three free-living flatworm species suggests rapid evolution of reproduction-related genes
Authors: Brand Jeremias N. , Wiberg R. Axel W. , Pjeta Robert , Bertemes Philip , Beisel Christian , Ladurner Peter , Schärer Lukas
Published: July 2020

Background

The genusMacrostomumconsists of small free-living flatworms and containsMacrostomum lignano, which has been used in investigations of ageing, stem cell biology, bioadhesion, karyology, and sexual selection in hermaphrodites. Two types of mating behaviour occur within this genus. Some species, includingM. lignano, mate via reciprocal copulation, where, in a single mating, both partners insert their male copulatory organ into the female storage organ and simultaneously donate and receive sperm. Other species mate via hypodermic insemination, where worms use a needle-like copulatory organ to inject sperm into the tissue of the partner. These contrasting mating behaviours are associated with striking differences in sperm and copulatory organ morphology. Here we expand the genomic resources within the genus to representatives of both behaviour types and investigate whether genes vary in their rate of evolution depending on their putative function.

Results

We present de novo assembled transcriptomes of threeMacrostomumspecies, namelyM. hystrix, a close relative ofM. lignanothat mates via hypodermic insemination,M. spirale, a more distantly related species that mates via reciprocal copulation, and finallyM. pusillum, which represents a clade that is only distantly related to the other three species and also mates via hypodermic insemination. We infer 23,764 sets of homologous genes and annotate them using experimental evidence fromM. lignano. Across the genus, we identify 521 gene families with conserved patterns of differential expression between juvenile vs. adult worms and 185 gene families with a putative expression in the testes that are restricted to the two reciprocally mating species. Further, we show that homologs of putative reproduction-related genes have a higher protein divergence across the four species than genes lacking such annotations and that they are more difficult to identify across the four species, indicating that these genes evolve more rapidly, while genes involved in neoblast function are more conserved.

Conclusions

This study improves the genusMacrostomumas a model system, by providing resources for the targeted investigation of gene function in a broad range of species. And we, for the first time, show that reproduction-related genes evolve at an accelerated rate in flatworms.
Genome-wide association analysis of canine T zone lymphoma identifies link to hypothyroidism and a shared association with mast-cell tumors
Authors: Labadie Julia D. , Elvers Ingegerd , Feigelson Heather Spencer , Magzamen Sheryl , Yoshimoto Janna , Dossey Jeremy , Burnett Robert , Avery Anne C.
Published: July 2020

Background

T zone lymphoma (TZL), a histologic variant of peripheral T cell lymphoma, represents about 12% of all canine lymphomas. Golden Retrievers appear predisposed, representing over 40% of TZL cases. Prior research found that asymptomatic aged Golden Retrievers frequently have populations of T zone-like cells (phenotypically identical to TZL) of undetermined significance (TZUS), potentially representing a pre-clinical state. These findings suggest a genetic risk factor for this disease and caused us to investigate potential genes of interest using a genome-wide association study of privately-owned U.S. Golden Retrievers.

Results

Dogs were categorized as TZL (n = 95), TZUS (n = 142), or control (n = 101) using flow cytometry and genotyped using the Illumina CanineHD BeadChip. Using a mixed linear model adjusting for population stratification, we found association with genome-wide significance in regions on chromosomes 8 and 14. The chromosome 14 peak included four SNPs (Odds Ratio = 1.18–1.19, p = .3 × 10− 5–5.1 × 10− 5) near three hyaluronidase genes (SPAM1, HYAL4, and HYALP1). Targeted resequencing of this region using a custom sequence capture array identified missense mutations in all three genes; the variant in SPAM1 was predicted to be damaging. These mutations were also associated with risk for mast cell tumors among Golden Retrievers in an unrelated study. The chromosome 8 peak contained 7 SNPs (Odds Ratio = 1.24–1.42, p = 2.7 × 10− 7–7.5 × 10− 5) near genes involved in thyroid hormone regulation (DIO2 and TSHR). A prior study from our laboratory found hypothyroidism is inversely associated with TZL risk. No coding mutations were found with targeted resequencing but identified variants may play a regulatory role for all or some of the genes.

Conclusions

The pathogenesis of canine TZL may be related to hyaluronan breakdown and subsequent production of pro-inflammatory and pro-oncogenic byproducts. The association on chromosome 8 may indicate thyroid hormone is involved in TZL development, consistent with findings from a previous study evaluating epidemiologic risk factors for TZL. Future work is needed to elucidate these mechanisms.
Pervasive duplication, biased molecular evolution and comprehensive functional analysis of the PP2C family in Glycine max
Authors: Fan Kai , Chen Yunrui , Mao Zhijun , Fang Yao , Li Zhaowei , Lin Weiwei , Zhang Yongqiang , Liu Jianping , Huang Jinwen , Lin Wenxiong
Published: July 2020

Background

Soybean (Glycine max) is an important oil provider and ecosystem participant. The protein phosphatase 2C (PP2C) plays important roles in key biological processes. Molecular evolution and functional analysis of the PP2C family in soybean are yet to be reported.

Results

The present study identified 134 GmPP2Cs with 10 subfamilies in soybean. Duplication events were prominent in the GmPP2C family, and all duplicated gene pairs were involved in the segmental duplication events. The legume-common duplication event and soybean-specific tetraploid have primarily led to expanding GmPP2C members in soybean. Sub-functionalization was the main evolutionary fate of duplicated GmPP2C members. Meanwhile, massive genes were lost in the GmPP2C family, especially from the F subfamily. Compared with other genes, the evolutionary rates were slower in the GmPP2C family. The PP2C members from the H subfamily resembled their ancestral genes. In addition, some GmPP2Cs were identified as the putative key regulator that could control plant growth and development.

Conclusions

A total of 134 GmPP2Cs were identified in soybean, and their expansion, molecular evolution and putative functions were comprehensively analyzed. Our findings provided the detailed information on the evolutionary history of the GmPP2C family, and the candidate genes can be used in soybean breeding.
Prognostic role of red blood cell distribution width in patients with sepsis: a systematic review and meta-analysis
Authors: Zhang Lin , Yu Cui-hua , Guo Kuan-peng , Huang Cai-zhi , Mo Li-ya
Published: July 2020

Background

Outcome prediction for patients with sepsis may be conductive to early aggressive interventions. Numerous biomarkers and multiple scoring systems have been utilized in predicting outcomes, however, these tools were either expensive or inconvenient.

We performed a meta-analysis to evaluate the prognostic role of red blood cell distribution width (RDW) in patients with sepsis.

Methods

The online databases of Embase, Web of science, Pubmed, Corchrane library, Chinese Wanfang database, CNKI database were systematically searched from the inception dates to June, 24th, 2020, using the keywords red cell distribution width and sepsis. The odds ratio (OR) or Hazards ratio (HR) with corresponding 95% confidence intervals (95%CI) were pooled to evaluate the association between baseline RDW and sepsis. A random-effects model was used to pool the data, and statistical heterogeneity between studies was evaluated using the I2 statistic. Sensitivity and subgroup analyses were performed to detect the publication bias and origin of heterogeneity.

Results

Eleven studies with 17,961 patients with sepsis were included in the meta-analysis. The pooled analyses indicated that increased baseline RDW was associated with mortality (HR = 1.14, 95%CI 1.09–1.20, Z = 5.78, P < 0.001) with significant heterogeneity (I2 = 80%, Pheterogeneity < 0.001). Similar results were found in the subgroup analysis stratified by site of infection, comorbidity, Newcastle-Ottawa Scale (NOS) score, study design, patients’ country. The predefined subgroup analysis showed that NOS score may be the origin of heterogeneity.

Conclusions

For patients with sepsis, baseline RDW may be a useful predictor of mortality, patients with increased RDW are more likely to have higher mortality.