bluuebunny/crossref_metadata_2025 huggingface dataset:
Extraction Method of Fetal Phonocardiogram Based on Lifting wavelet analysis
Authors: Huimin Wang , Xingyu Liang
Published: June 2020

Long-term monitoring of fetal health status is important for high-risk pregnancies. In order to extract the pure fetal phonocardiogram(fPCG) and increase the calculating accuracy of fetal heart rate (FHR), a combination of Empirical Mode Decomposition (EMD), Cepstrum, Lifting Wavelet (LWT) and Hilbert transform (HT) method was proposed. First, the heart sound signal was decomposed into finite intrinsic mode functions (IMF) by EMD, and then the signal de-noising was implemented by LWT. Second, the envelope of the signal was obtained by HHT. Finally, the fetal heart rate was obtained by cepstrum analysis. The simulation result shows that the fetal heart rate extracted by this integrated signal processing method is right, and it enhances the precision of fetal heart rate greatly. The wavelet de-noising technology can reduce the noise very well with small computation. It is concluded that this integrated signal method is capable of extracting feature from fPCG.
Research on Image Quality Evaluation Method of Depth Learning Model Based on Core Concept
Authors: Huang Wen , Wang Juan
Published: June 2020

In view of the fact that the existing image quality evaluation methods are generally artificial design features, it is difficult to automatically and effectively extract image features that conform to the human visual system. Inspired by human visual characteristics, a new full reference image quality evaluation method based on depth learning model based on core concepts is proposed. Firstly, depth learning algorithm is used to extract multi-layer features from reference images and distorted images respectively. Then, the local similarity of the feature map of the reference image and the distorted image in each layer is calculated as the local quality description of the corresponding depth. Finally, the local quality of all layers is synthesized to obtain the overall quality score of the image. On the basis of the pre-training model, the depth model network is fine-tuned by using the image visual evaluation data set to obtain a depth model for evaluation. The standard experiment shows that fine-tuning training of each pre-training model on the standard data set achieves good classification results. Experiments show that the designed depth learning model based on core concepts is superior to the existing full reference image quality evaluation methods, and its prediction results have good accuracy and consistency with subjective quality evaluation.
HBase Connection Dynamic Keeping Method Based on Reactor Pattern
Authors: Lai Xinming , Wang Haitao , Zhao Jing , Zhang Fan , Zhao Chao , Wu Gang
Published: June 2020

This paper proposes a HBase connection dynamic keeping method based on the Reactor mode. This method uses the Reactor mode to implement the client connection maintenance mechanism based on the NSQ message queue. By only creating the TCP control block of the client connection and buffering it to the NSQ queue, it improves the response of the user connection and the concurrent processing capacity. By monitoring the active state of the connected TCP block in the message queue, the real-time processing capability of the connection is guaranteed. The reuse of HBase connection objects is realized through the listen-back callback mechanism, and the CPU and memory resource utilization is improved by dynamically adjusting the size of the connection object pool.
Design and Verification of Fuzzy Neural Network Automatic Control Algorithm in Intelligent Agriculture
Authors: Yan Wen , Zou Chengjun , Li Min , Yu Ye
Published: June 2020

Through the analysis and in-depth study of the fuzzy control system model and neural network, the optimal control strategy is obtained by the organic combination of fuzzy reasoning and neural network analysis training, and the automatic control algorithm based on fuzzy neural network is designed. The modified algorithm is applied and verified in Modern Agriculture Demonstration Park of Chengdu Agricultural College. The results show that the designed algorithm can meet the demand of automatic control in the field of intelligent agricultural control, and the control system has good universality and scalability. The application of automatic control algorithm based on fuzzy neural network can accelerate the development of agricultural modernization in China, and lay a solid foundation for the further research on the application of automatic control in other fields.
Influential Nodes Analysis Method of Tactical Mobile Ad Hoc Networks Based on Impact Factors Evaluation*
Authors: Peng Qinpeng , Wang Ying , Zhang Pingan
Published: June 2020

How to identify and analyze influential nodes of Tactical Mobile Ad Hoc Networks is an urgent problem. Existing researches fail to make full use of features of Tactical Mobile Ad Hoc Networks. In this paper, we propose an influential nodes analysis method of Tactical Mobile Ad Hoc Networks based on impact factors evaluation (TINE). The method evaluates node importance through two mechanisms: connectivity analysis and node importance evaluation. In connectivity analysis, the current network topology is reconstructed by placing nodes to monitor network data packets and resolve protocol. In node importance evaluation, node importance degree is calculated by adjacency matrix. The experimental results show that TINE we proposed has advantages over the existing methods in Tactical Mobile Ad Hoc Networks.
Spousal Influence on Diabetes Self-care: Moderating Effects of Distress and Relationship Quality on Glycemic Control
Authors: Soriano Emily C , Lenhard James M , Gonzalez Jeffrey S , Tennen Howard , Chow Sy-Miin , Otto Amy K , Perndorfer Christine , Shen Biing-Jiun , Siegel Scott D , Laurenceau Jean-Philippe
Published: June 2020

Background

Spouses often attempt to influence patients' diabetes self-care. Spousal influence has been linked to beneficial health outcomes in some studies, but to negative outcomes in others.

Purpose

We aimed to clarify the conditions under which spousal influence impedes glycemic control in patients with type 2 diabetes. Spousal influence was hypothesized to associate with poorer glycemic control among patients with high diabetes distress and low relationship quality.

Methods

Patients with type 2 diabetes and their spouses (N = 63 couples) completed self-report measures before patients initiated a 7-day period of continuous glucose monitoring. Mean glucose level and coefficient of variation (CV) were regressed on spousal influence, diabetes distress, relationship quality, and their two- and three-way interactions.

Results

The three-way interaction significantly predicted glucose variability, but not mean level. Results revealed a cross-over interaction between spousal influence and diabetes distress at high (but not low) levels of relationship quality, such that spousal influence was associated with less variability among patients with low distress, but more among those with high distress. Among patients with high distress and low relationship quality, a 1 SD increase in spousal influence predicted a difference roughly equivalent to the difference between the sample mean CV and a CV in the unstable glycemia range.

Conclusions

This was the first study to examine moderators of the link between spousal influence and glycemic control in diabetes. A large effect was found for glucose variability, but not mean levels. These novel results highlight the importance of intimate relationships in diabetes management.
What Makes a Kind an Art-kind?
Authors: Xhignesse Michel-Antoine
Published: June 2020

The premise that every work belongs to an art-kind has recently inspired a kind-centred approach to theories of art. Kind-centred analyses posit that we should abandon the project of giving a general theory of art and focus instead on giving theories of the arts. The main difficulty, however, is to explain what makes a given kind an art-kind in the first place. Kind-centred theorists have passed this buck on to appreciative practices, but this move proves unsatisfactory. I argue that the root of this dissatisfaction stems not from the act of kicking the can down the road, but from not kicking it far enough. The missing ingredient, I argue, is a notion of convention which does the work of marking the difference between art and non-art for a given physical medium.
Pyrexia of unknown origin associated with a non-infected vaginal shelf pessary
Authors: Gilbert Mathew , Laurenson Myra , Casson James , Alsawaf Ali
Published: June 2020

An 82-year-old female was admitted with pyrexia and rigors. Bloods showed a raised C-reactive protein and she was commenced on empirical intravenous antibiotics. Chest X-ray, urine microscopy and computed tomography scan of the patient’s abdomen and pelvis did not demonstrate a source of infection, and blood cultures did not grow a microorganism.

A collateral history was taken from the patient’s husband who raised concerns regarding her vaginal shelf pessary and it was therefore removed. Subsequently the patient’s fever subsided, her inflammatory markers improved and she was discharged 2 days later.

We believe this is the first reported case of pyrexia secondary to a non-infected vaginal pessary, and may provide clinicians with an additional line of enquiry when presented with patients with pyrexia of unknown origin.
Cost-effectiveness of a preventive self-care health management program for community-dwelling older adults: a randomised controlled trial
Authors: Wong Arkers Kwan Ching , Wong Frances Kam Yuet , So Ching
Published: June 2020

Objective

To examine the cost-effectiveness of a preventive self-care health management program for community-dwelling older adults as compared to usual care.

Design/Intervention

A cost-effectiveness analysis was executed alongside a randomised controlled trial. Nurse case managers provided interventions, including holistic assessment, empowerment of self-care, preventive health behaviours and self-efficacy with co-produced care planning, supported by nursing students. The control group received social control calls.

Participants/Setting

Community-dwelling older adults were randomly assigned to the intervention (n = 271) or control (n = 269) group. The intervention was conducted in collaboration with 11 community centres under four non-government organisations in various districts of Hong Kong.

Measurements

Cost and quality-adjusted life years (QALYs) were collected pre (baseline, 0 months) and post intervention (3 months) and 3 months after completion of the program (6 months). Incremental cost-effectiveness ratios between the groups were calculated, dividing the difference in cost by the difference in QALYs.

Results

Analysis showed that the net incremental QALY gain was 0.0014 (3 months) and 0.0033 (6 months) when the intervention group was compared to the control group. The probability of being cost-effective at 6 months was 53.2% and 53.4%, based on the cost-effectiveness thresholds recommended by both the National Institute for Health and Clinical Excellence ($200,000/QALYs) and the World Health Organization (Hong Kong gross domestic product/capita, HK$381,780).

Conclusions

The results provide some evidence to suggest that the addition of a home-based, preventive self-care health management program may have effects on cost outcomes for community-dwelling older adults in Hong Kong.
Strangled by Dr Strangelove? Anarchic hand following a posterior cerebral artery territory ischemic stroke
Authors: Murdoch Mhairi , Hill Jenny , Barber Mark
Published: June 2020

Anarchic hand is a rare condition where the complex movements of one hand appear to be goal directed and smoothly executed and yet are unintended and unwanted. Unlike alien hand syndrome, the patients recognise that the affected hand is part of their own body. They know the hand is theirs, but they deny having control over its actions. The syndrome has been reported after surgery on the corpus callosum and with brain tumours, aneurysms, degenerative diseases of the brain and uncommonly with stroke. We present a case of a 74-year-old man who developed an anarchic right hand following thrombolysis for a posterior cerebral artery territory ischemic stroke.
Histology of Liver of the Deceased Due to Harmful Use of Alcohol
Authors: Rorat Marta , Hałoń Agnieszka , Jurek Tomasz
Published: June 2020

Aim

To study types and incidence of histological changes in liver of people deceased due to harmful use of alcohol.

Methods

A retrospective review of medico-legal autopsy of 236 adults who died in the years 2015–2016 due to harmful use of alcohol was done. Histopathological liver samples taken during autopsies were evaluated. Blood alcohol content was analyzed. Serological tests for hepatitis B surface antigen and anti-hepatitis C virus (HCV) were performed.

Results

The most common liver pathology (83.1%) was steatosis, mainly mixed type (50%); 66.9% had high-grade steatosis. Liver fibrosis was detected in 39.4% of cases, with fibrosis of higher than or equal to third grade in 14%, hepatitis in 44.5% and steatohepatitis in 19.1%. Toxic hepatocyte injury features (ballooning degeneration, Mallory–Denk bodies) were found in 20.8% cases and degenerative-damage changes in 41.1%. The correlation between the grade of steatosis and fibrosis (P = 0.0005), toxic injury (0.00000101) and degenerative–traumatic changes (P = 0.00000741) was found. The correlation was found between hepatitis and higher than or equal to third grade steatosis (P = 0.037), cholestasis (P = 0.0139), toxic injury features (P = 2.58 × 10−13), degenerative–damage changes (P = 7.9 × 10−12) and presence of anti-HCV (P = 0.00723) and between progression of fibrosis and presence of toxic injury features (2.28 × 10−19), degenerative–damage changes (P = 4.25 × 10−11) and anti-HCV (P = 0.0263).

Conclusions

Spectrum of histopathological liver changes is broad regardless of sex, and various traits are present in various patterns. Comorbidities have strong influence on the picture of changes in the liver. Exact evaluation how often and what histopathological changes will develop in alcohol liver disease is not possible by reason of variability of external factors.
Epilepsy-causing STX1B mutations translate altered protein functions into distinct phenotypes in mouse neurons
Authors: Vardar Gülçin , Gerth Fabian , Schmitt Xiao Jakob , Rautenstrauch Pia , Trimbuch Thorsten , Schubert Julian , Lerche Holger , Rosenmund Christian , Freund Christian
Published: June 2020

Syntaxin 1B (STX1B) is a core component of the N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex that is critical for the exocytosis of synaptic vesicles in the presynapse. SNARE-mediated vesicle fusion is assisted by Munc18-1, which recruits STX1B in the auto-inhibited conformation, while Munc13 catalyses the fast and efficient pairing of helices during SNARE complex formation. Mutations within the STX1B gene are associated with epilepsy. Here we analysed three STX1B mutations by biochemical and electrophysiological means. These three paradigmatic mutations cause epilepsy syndromes of different severity, from benign fever-associated seizures in childhood to severe epileptic encephalopathies. An insertion/deletion (K45/RMCIE, L46M) mutation (STX1BInDel), causing mild epilepsy and located in the early helical Habc domain, leads to an unfolded protein unable to sustain neurotransmission. STX1BG226R, causing epileptic encephalopathies, strongly compromises the interaction with Munc18-1 and reduces expression of both proteins, the size of the readily releasable pool of vesicles, and Ca2+-triggered neurotransmitter release when expressed in STX1-null neurons. The mutation STX1BV216E, also causing epileptic encephalopathies, only slightly diminishes Munc18-1 and Munc13 interactions, but leads to enhanced fusogenicity and increased vesicular release probability, also in STX1-null neurons. Even though the synaptic output remained unchanged in excitatory hippocampal STX1B+/− neurons exogenously expressing STX1B mutants, the manifestation of clear and distinct molecular disease mechanisms by these mutants suggest that certain forms of epilepsies can be conceptualized by assigning mutations to structurally sensitive regions of the STX1B−Munc18-1 interface, translating into distinct neurophysiological phenotypes.
Brain Networks Processing Temporal Information in Dynamic Facial Expressions
Authors: Skiba Rafal M , Vuilleumier Patrik
Published: June 2020

This fMRI study examines the role of local and global motion information in facial movements during exposure to novel dynamic face stimuli. We found that synchronous expressions distinctively engaged medial prefrontal areas in the rostral and caudal sectors of anterior cingulate cortex (r/cACC) extending to inferior supplementary motor areas, as well as motor cortex and bilateral superior frontal gyrus (global temporal-spatial processing). Asynchronous expressions in which one part of the face unfolded before the other activated more the right superior temporal sulcus (STS) and inferior frontal gyrus (local temporal-spatial processing). These differences in temporal dynamics had no effect on visual face-responsive areas. Dynamic causal modeling analysis further showed that processing of asynchronous expression features was associated with a differential information flow, centered on STS, which received direct input from occipital cortex and projected to the amygdala. Moreover, STS and amygdala displayed selective interactions with cACC where the integration of both local and global motion cues could take place. These results provide new evidence for a role of local and global temporal dynamics in emotional expressions, extracted in partly separate brain pathways. Importantly, we show that dynamic expressions with synchronous movement cues may distinctively engage brain areas responsible for motor execution of expressions.
Should Contact Bans Have Been Lifted More in Germany?
Authors: Donsimoni Jean Roch , Glawion René , Plachter Bodo , Wälde Klaus , Weiser Constantin
Published: June 2020

Many countries consider the lifting of restrictions of social contacts (RSC). We quantify the effects of RSC for Germany. We initially employ a purely statistical approach to predicting prevalence of Covid-19 if RSC had been upheld after 20 April. We employ these findings and feed them into our theoretical model. We find that the peak of the number of sick individuals would have been reached already end of April. The number of sick individuals would have fallen below 1000 at the beginning of July. If restrictions had been lifted completely on April 20, the number of sick should have risen quickly again from around 27 April. A balance between economic and individual costs of RSC and public health objectives consists in lifting RSC for activities that have high economic benefits but low health costs. In the absence of large-scale representative testing of CoV-2 infections, these activities can most easily be identified if federal states of Germany adopted exit strategies that differ across states.
Vacuum-formed retainers and bonded retainers for dental stabilization—a randomized controlled trial. Part II: patients’ perceptions 6 and 18 months after orthodontic treatment
Authors: Krämer Anke , Sjöström Mats , Hallman Mats , Feldmann Ingalill
Published: June 2020

Objective

To compare removable vacuum-formed Essix C retainers with bonded cuspid-to-cuspid retainers (CTCs) regarding patients’ perceptions after debonding and 6 and 18 months of retention.

Trial design

A single-centre two-arm parallel-group randomized controlled trial.

Methods

This trial included 104 adolescent patients, computer-generated randomized, with sequentially numbered, opaque and sealed envelopes, into two groups and stratified by gender. They were treated with fixed appliances with and without tooth extractions in both jaws and were ready for debond. Patients in the intervention arm received a vacuum-formed retainer (VFR) in the mandible (n = 52), and patients in the active comparator arm received a CTC (n = 52). Both groups had a VFR in the maxilla. Treatment outcome satisfaction, quality of care and attention, side-effects during the retention phase, and retainer acceptance and compliance were assessed with questionnaires at baseline (T1, 2 weeks after debond) and after 6 (T2) and 18 months (T3) of retention. Operator was blinded to group assignment during measurements.

Results

Ninety-five patients completed the questionnaires at all three time points. Patients were overall satisfied with treatment outcome, quality of care and attention, and how their retainers worked at all three time points, with no differences between groups. At T1 and T3, the VFR group reported significantly more pain and discomfort (T1: P = 0.005, T3: P < 0.0001) and soreness (T1: P = 0.001, T3: P = 0.011) in the mandible compared to the CTC group. The CTC group found it easier to get used to their retainers. After 18 months, 70.5 per cent in the VFR group and 73.9 per cent in the CTC group reported the recommended wear-time of the VFRs. Decreased wear-time was correlated to perceived pain and discomfort (rs = −0.421, P < 0.0001).

Limitations

The results were limited by our retainer design and recommended wear regimen.

Conclusions

Both groups reported high treatment outcome satisfaction and low levels of side-effects during the retention phase. Nevertheless, the VFR group reported more pain and discomfort at T1 and at T3. Self-reported compliance was the same in both groups. The VFR group was more concerned about relapse.

Trial registration

NCT03070444 (https://clinicaltrials.gov).
Designing ELF-aware lessons in high-stakes exam contexts
Authors: Sifakis Nicos C , Tsantila Natasha , Masina Aristea , Vourdanou Katerina
Published: June 2020

In ELT contexts, the concept of ELF awareness has been proposed as a means of developing the skills, strategies, and overall outlook that learners require to competently participate in ELF interactions. Depending on the teaching context, this can be a demanding process. We discuss the ELF-aware instructional interventions carried out by two practitioners working in high-stakes exam preparation contexts in Greece. These contexts are predominantly Standard English oriented. The interventions described an attempt to put into practice the principles of ELF-aware pedagogy, namely awareness of language and language use, awareness of instructional practice, and awareness of learning. The innovative aspect of these interventions is that they do not run contrary to the curriculum of these high-stakes exam preparation classes. On the contrary, they complement the courseware used in these contexts with authentic audiovisual materials and original metalinguistic activities that boost learners’ self-confidence as ELF speakers and as candidates of these exams.
Bacteriophage-mediated manipulation of the gut microbiome – promises and presents limitations
Authors: Rasmussen Torben Sølbeck , Koefoed Anna Kirstine , Jakobsen Rasmus Riemer , Deng Ling , Castro-Mejía Josué L , Brunse Anders , Neve Horst , Vogensen Finn Kvist , Nielsen Dennis Sandris
Published: June 2020

Gut microbiome (GM) composition and function are linked to human health and disease, and routes for manipulating the GM have become an area of intense research. Due to its high treatment efficacy, the use of fecal microbiota transplantation (FMT) is generally accepted as a promising experimental treatment for patients suffering from GM imbalances (dysbiosis), e.g. caused by recurrent Clostridioides difficile infections (rCDI). Mounting evidence suggests that bacteriophages (phages) play a key role in successful FMT treatment by restoring the dysbiotic bacterial GM. As a refinement to FMT, removing the bacterial component of donor feces by sterile filtration, also referred to as fecal virome transplantation (FVT), decreases the risk of invasive infections caused by bacteria. However, eukaryotic viruses and prophage-encoded virulence factors remain a safety issue. Recent in vivo studies show how cascading effects are initiated when phage communities are transferred to the gut by e.g. FVT, which leads to changes in the GM composition, host metabolome, and improve host health such as alleviating symptoms of obesity and type-2-diabetes (T2D). In this review, we discuss the promises and limitations of FVT along with the perspectives of using FVT to treat various diseases associated with GM dysbiosis.
Functional Studies with Primary Cells Provide a System for Genome-to-Phenome Investigations in Marine Mammals
Authors: Lam Emily K , Allen Kaitlin N , Torres-Velarde Julia María , Vázquez-Medina José Pablo
Published: June 2020

Synopsis

Marine mammals exhibit some of the most dramatic physiological adaptations in their clade and offer unparalleled insights into the mechanisms driving convergent evolution on relatively short time scales. Some of these adaptations, such as extreme tolerance to hypoxia and prolonged food deprivation, are uncommon among most terrestrial mammals and challenge established metabolic principles of supply and demand balance. Non-targeted omics studies are starting to uncover the genetic foundations of such adaptations, but tools for testing functional significance in these animals are currently lacking. Cellular modeling with primary cells represents a powerful approach for elucidating the molecular etiology of physiological adaptation, a critical step in accelerating genome-to-phenome studies in organisms in which transgenesis is impossible (e.g., large-bodied, long-lived, fully aquatic, federally protected species). Gene perturbation studies in primary cells can directly evaluate whether specific mutations, gene loss, or duplication confer functional advantages such as hypoxia or stress tolerance in marine mammals. Here, we summarize how genetic and pharmacological manipulation approaches in primary cells have advanced mechanistic investigations in other non-traditional mammalian species, and highlight the need for such investigations in marine mammals. We also provide key considerations for isolating, culturing, and conducting experiments with marine mammal cells under conditions that mimic in vivo states. We propose that primary cell culture is a critical tool for conducting functional mechanistic studies (e.g., gene knockdown, over-expression, or editing) that can provide the missing link between genome- and organismal-level understanding of physiological adaptations in marine mammals.
Respiratory Syncytial Virus Consortium in Europe (RESCEU) Birth Cohort Study: Defining the Burden of Infant Respiratory Syncytial Virus Disease in Europe
Authors: Wildenbeest Joanne G , Zuurbier Roy P , Korsten Koos , van Houten Marlies A , Billard Marie N , Derksen-Lazet Nicole , Snape Matthew D , Drysdale Simon B , Robinson Hannah , Pollard Andrew J , Heikkinen Terho , Cunningham Steve , Leach Amanda , Martinón-Torres Federico , Rodríguez-Tenreiro Sánchez Carmen , Gómez-Carballa Alberto , Bont Louis J ,   RESCEU Investigators, Wildenbeest Joanne , Zuurbier Roy , Korsten Koos , van Houten Marlies , Billard Marie , Derksen-Lazet Nicole , Bont Louis , Drysdale Simon , Snape Matthew , Robinson Hannah , Pollard Andrew , Martinón-Torres Federico , Sánchez Carmen Rodríguez-Tenreiro , Gómez-Carballa Alberto , Heikkinen Terho , Cunningham Steve , Nair Harish , Campbell Harry , Leach Amanda , Openshaw Peter , Beutels Philippe , Molero Eva , Meijer Adam , Sanders Elisabeth , Fischer Thea Kølsen , van den Berge Maarten , Giaquinto Carlo , Esser Mark , Knirsch Charles , Gallichan Scott , Aerssens Jeroen , Rosen Brian , Wildenbeest Joanne , Zuurbier Roy , Korsten Koos , van Houten Marlies , Billard Marie , Derksen-Lazet Nicole , Bont Louis , Drysdale Simon , Snape Matthew , Robinson Hannah , Pollard Andrew , Martinón-Torres Federico , Sánchez Carmen Rodríguez-Tenreiro , Gómez-Carballa Alberto , Heikkinen Terho , Cunningham Steve , Nair Harish , Campbell Harry , Leach Amanda , Openshaw Peter , Beutels Philippe , Molero Eva , Meijer Adam , Sanders Elisabeth , Fischer Thea Kølsen , van den Berge Maarten , Giaquinto Carlo , Esser Mark , Knirsch Charles , Gallichan Scott , Aerssens Jeroen , Rosen Brian
Published: June 2020

Background

Respiratory syncytial virus (RSV) causes significant morbidity and mortality in infants worldwide. Although prematurity and cardiopulmonary disease are risk factors for severe disease, the majority of infants hospitalized with RSV are previously healthy. Various vaccines and therapeutics are under development and expected to be available in the near future. To inform the use of these new vaccines and therapeutics, it is necessary to determine the burden of RSV disease in Europe. We will prospectively follow-up a birth cohort to obtain incidence data on RSV acute respiratory tract infection (ARTI).

Methods

Multicenter prospective study of a birth cohort consisting of 10 000 healthy infants, recruited during 3 consecutive years. RSV associated hospitalization in the first year of life will be determined by questionnaires and hospital chart reviews. A nested cohort of 1000 infants will be actively followed. In case of ARTI, a respiratory sample will be collected for RSV molecular diagnosis.

Results

The primary outcome is the incidence rate of RSV-associated hospitalization in the first year of life. In the active cohort the primary outcome is RSV associated ARTI and MA-ARTI.

Conclusions

We will provide key information to fill the gaps in knowledge about the burden of RSV disease in healthy infants.

Clinical Trials Registration

NCT03627572.
Synthetic minority oversampling of vital statistics data with generative adversarial networks
Authors: Koivu Aki , Sairanen Mikko , Airola Antti , Pahikkala Tapio
Published: June 2020

Objective

Minority oversampling is a standard approach used for adjusting the ratio between the classes on imbalanced data. However, established methods often provide modest improvements in classification performance when applied to data with extremely imbalanced class distribution and to mixed-type data. This is usual for vital statistics data, in which the outcome incidence dictates the amount of positive observations. In this article, we developed a novel neural network-based oversampling method called actGAN (activation-specific generative adversarial network) that can derive useful synthetic observations in terms of increasing prediction performance in this context.

Materials and Methods

From vital statistics data, the outcome of early stillbirth was chosen to be predicted based on demographics, pregnancy history, and infections. The data contained 363 560 live births and 139 early stillbirths, resulting in class imbalance of 99.96% and 0.04%. The hyperparameters of actGAN and a baseline method SMOTE-NC (Synthetic Minority Over-sampling Technique-Nominal Continuous) were tuned with Bayesian optimization, and both were compared against a cost-sensitive learning-only approach.

Results

While SMOTE-NC provided mixed results, actGAN was able to improve true positive rate at a clinically significant false positive rate and area under the curve from the receiver-operating characteristic curve consistently.

Discussion

Including an activation-specific output layer to a generator network of actGAN enables the addition of information about the underlying data structure, which overperforms the nominal mechanism of SMOTE-NC.

Conclusions

actGAN provides an improvement to the prediction performance for our learning task. Our developed method could be applied to other mixed-type data prediction tasks that are known to be afflicted by class imbalance and limited data availability.
Evaluation of the Solus One Salmonella Assay in Select Foods: Collaborative Study: First Action 2020.03
Authors: Bastin Benjamin , Benzinger M Joseph , Crowley Erin S , Agin James , Wakefield Raymond
Published: June 2020

Background

The Solus One Salmonella immunoassay utilizes Salmonella specific selective media and automated liquid handling, for the rapid and specific detection of Salmonella species in select food types.

Objective

The candidate method was evaluated using 375 g test portions in an unpaired study design for a single matrix, instant non-fat dry milk (NFDM) powder.

Method

The matrix was compared to the United States Food and Drug Administration/Bacteriological Analytical Manual (FDA/BAM) Chapter 5 Salmonella reference method. Eleven participants from 10 laboratories within academia and industry, located within the United States, Mexico, South Africa, Germany, and the United Kingdom, contributed data for the collaborative study. Three levels of contamination were evaluated for each matrix: an uninoculated control level [0 colony forming units (CFU)/test portion], a low inoculum level (0.2–2 CFU/test portion) and a high inoculum level (2–5 CFU/test portion). Statistical analysis was conducted according to the Probability of Detection (POD) statistical model.

Results

Results obtained for the low inoculum level test portions produced a dLPOD value with a 95% confidence interval between the candidate method confirmed (both alternative and conventional confirmation procedures) and the reference method of 0.07 (−0.02, 0.15).

Conclusions

The dLPOD results indicate equivalence between the candidate method and the reference method for the matrix evaluated and the method demonstrated acceptable inter-laboratory reproducibility as determined in the collaborative evaluation. False positive and false negative rates were determined for the matrix and produce values of <2%.

Highlights

Based on the data generated, the method demonstrated acceptable inter-laboratory reproducibility data and statistical analysis.
Drought-mediated changes in black-tailed prairie dog colonies in the Northern Great Plains
Authors: Bruggeman Jason E , Licht Daniel S
Published: June 2020

Populations of many mammal species living in grassland ecosystems across North America have been reduced greatly over the past 200 years due to conversion of native prairie to human-related uses. Foremost among these species is the black-tailed prairie dog (Cynomys ludovicianus), populations of which have declined an estimated 98% during that time. In addition to anthropogenic factors including plague, black-tailed prairie dog populations can vary in size in response to grazing by native ungulates, fire, and precipitation. Colonies in the Northern Great Plains have expanded and contracted during dry and wet periods, respectively. Drought reduces vegetation height; tall vegetation is known to limit colony expansion, possibly due to increased predation risk. We used mixed-effects models to analyze data sets of colony areas of black-tailed prairie dogs spanning 16–22 years and 983 total colony counts, from 142 unique colonies at Badlands National Park and Wind Cave National Park, South Dakota, United States, and Scotts Bluff National Monument, Nebraska, United States, to relate areal dynamics of colonies over time to total annual precipitation, drought stress, and plague. We also analyzed the relationship between active-burrow densities and precipitation and drought stress using 7 years of data from 271 colony counts at Badlands National Park. Black-tailed prairie dog colonies expanded in response to drought conditions in all three national parks, with colonies in Wind Cave National Park exhibiting a time-delayed response. In addition, colony area was negatively related to total accumulated precipitation for the preceding 12 months for Scotts Bluff National Monument. Active-burrow density at Badlands National Park decreased in response to drought stress with a time lag of 24–36 months. Plague first was reported at Badlands National Park in 2008 and colony areas decreased dramatically and rapidly during plague epizootic events. Our results support observations that black-tailed prairie dog colonies in the Northern Great Plains expand and contract in response to drought stress and wet weather. Furthermore, our findings provide new insights into the role of climate on a keystone species of conservation importance and demonstrate the value of collecting long-term ecological data.
Long-term Persistence of Oral HPV Over 7 Years of Follow-up
Authors: D’Souza Gypsyamber , Clemens Gwendolyn , Strickler Howard D , Wiley Dorothy J , Troy Tanya , Struijk Linda , Gillison Maura , Fakhry Carole
Published: June 2020

Background

Human papillomavirus–related oropharyngeal cancer (HPV-OPC) incidence is increasing, but the natural history of the precursor—oral HPV—has not been well described.

Methods

This observational cohort study of people living with HIV and at-risk HIV uninfected people evaluated participants semiannually using 30-second oral rinse and gargle specimens over 7 years. Initially, 447 participants were followed for 4 years as part of the Persistent Oral Papillomavirus Study, and a subset of 128 who showed persistent infections at the last Persistent Oral Papillomavirus Study visit had an additional visit, as part of the Men and Women Understanding Throat HPV Study, on average 2.5 years later. Extracted DNA from oral rinse and gargle specimens was amplified using polymerase chain reaction and type specification of 13 oncogenic HPV types. Risk factors for oncogenic oral HPV clearance were evaluated using Cox models.

Results

The majority of oncogenic oral HPV infections cleared quickly, with a median time to clearance of 1.4 years (interquartile range = 0.5-3.9 years). After 7 years of follow-up, 97% of incident and 71% of prevalent infections had cleared. Lower HPV-16 viral load was statistically significantly associated with clearance (per 10-fold decrease in copy number: adjusted hazard ratio [aHR] = 2.51, 95% confidence interval [CI] = 1.20 to 5.26; P = .01). Adjusted analyses showed that oncogenic oral HPV clearance was lower among prevalent than incident-detected infections (aHR = 0.44, 95% CI = 0.35 to 0.55), among men than women (aHR = 0.74, 95% CI = 0.60 to 0.91), for older participants (aHR per 10 years increasing age = 0.81, 95% CI = 0.74 to 0.89), and among people living with HIV (aHR = 0.76, 95% CI = 0.60 to 0.95). One participant who had oral HPV-16 consistently detected at 10 study visits over 4.5 years was subsequently diagnosed with HPV-OPC.

Conclusions

This prospective study of oncogenic oral HPV infection is the longest and largest quantification of oral HPV-16 infections to date.
Impact of endoplasmic reticulum stress on oocyte aging mechanisms
Authors: Takehara Isao , Igarashi Hideki , Kawagoe Jun , Matsuo Koki , Takahashi Kyoko , Nishi Michi , Nagase Satoru
Published: June 2020

Endoplasmic reticulum (ER) stress is associated with several aging-related diseases; however, the mechanism underlying age-related deterioration of oocyte quality is unclear. Here, we used post-ovulatory, in vivo aged mouse oocytes as a model. Super-ovulated oocytes harvested from the oviduct at 14 h and 20 h post-hCG injection were designated as ‘fresh’ and ‘aged’, respectively. Embryo development following IVF was compared between fresh, aged and ER stress-induced oocytes. Expression of the ER stress marker GRP78 was examined at each stage. To evaluate the effect of salubrinal, an ER stress suppressor, on embryo development following IVF, expression levels of GRP78 and phospho-eukaryotic initiation factor 2 alpha were compared between aged and salubrinal-treated aged oocytes. Embryo transfer of salubrinal-treated aged oocytes was performed to examine the safety of salubrinal. Similar to aged oocytes, ER stress-induced oocytes showed lower fertilization rates and poor embryo development. Following IVF, expression of GRP78 decreased with embryo development. GRP78 expression was significantly higher in aged oocytes than in fresh oocytes. Salubrinal lowered GRP78 levels and improved embryo development. No adverse effect of salubrinal treatment was found on the birth weight of pups or on organogenesis in mice. The limitation of this study was that protein kinase-like ER kinase was the only ER stress pathway examined; the role of IRE1 and ATF6 pathways was not considered. Nevertheless, salubrinal can significantly improve embryo development in in vivo aged oocytes undergoing ER stress. Hence, regulation of ER stress might represent a promising therapeutic strategy to overcome poor oocyte quality.
qDRIP: a method to quantitatively assess RNA–DNA hybrid formation genome-wide
Authors: Crossley Magdalena P , Bocek Michael J , Hamperl Stephan , Swigut Tomek , Cimprich Karlene A
Published: June 2020

R-loops are dynamic, co-transcriptional nucleic acid structures that facilitate physiological processes but can also cause DNA damage in certain contexts. Perturbations of transcription or R-loop resolution are expected to change their genomic distribution. Next-generation sequencing approaches to map RNA–DNA hybrids, a component of R-loops, have so far not allowed quantitative comparisons between such conditions. Here, we describe quantitative differential DNA–RNA immunoprecipitation (qDRIP), a method combining synthetic RNA–DNA-hybrid internal standards with high-resolution, strand-specific sequencing. We show that qDRIP avoids biases inherent to read-count normalization by accurately profiling signal in regions unaffected by transcription inhibition in human cells, and by facilitating accurate differential peak calling between conditions. We also use these quantitative comparisons to make the first estimates of the absolute count of RNA–DNA hybrids per cell and their half-lives genome-wide. Finally, we identify a subset of RNA–DNA hybrids with high GC skew which are partially resistant to RNase H. Overall, qDRIP allows for accurate normalization in conditions where R-loops are perturbed and for quantitative measurements that provide previously unattainable biological insights.
Sodium zirconium cyclosilicate increases serum bicarbonate concentrations among patients with hyperkalaemia: exploratory analyses from three randomized, multi-dose, placebo-controlled trials
Authors: Roger Simon D , Spinowitz Bruce S , Lerma Edgar V , Fishbane Steven , Ash Stephen R , Martins Julian G , Quinn Carol Moreno , Packham David K
Published: June 2020

Background

Sodium zirconium cyclosilicate (SZC) binds potassium and ammonium in the gastrointestinal tract. In addition to serum potassium reduction, Phase 2 trial data have shown increased serum bicarbonate with SZC, which may be clinically beneficial because maintaining serum bicarbonate ≥22 mmol/L preserves kidney function. This exploratory analysis examined serum bicarbonate and urea, and urine pH data from three SZC randomized, placebo-controlled Phase 3 studies among patients with hyperkalaemia [ZS-003 (n = 753), HARMONIZE (n = 258) and HARMONIZE-Global (n = 267)].

Methods

In all studies, patients received ≤10 g SZC 3 times daily (TID) for 48 h to correct hyperkalaemia, followed by randomization to maintenance therapy with SZC once daily (QD) versus placebo for ≤29 days among those achieving normokalaemia.

Results

Significant dose-dependent mean serum bicarbonate increases from baseline of 0.3 to 1.5 mmol/L occurred within 48 h of SZC TID in ZS-003 (all P < 0.05), which occurred regardless of chronic kidney disease (CKD) stage. Similar acute increases in HARMONIZE and HARMONIZE-Global were maintained over 29 days. With highest SZC maintenance doses, patient proportions with serum bicarbonate <22 mmol/L fell from 39.4% at baseline to 4.9% at 29 days (P = 0.005) in HARMONIZE and from 87.9% to 70.1%, (P = 0.006) in HARMONIZE-Global. Path analyses demonstrated that serum urea decreases (but not serum potassium or urine pH changes) were associated with SZC effects on serum bicarbonate.

Conclusions

SZC increased serum bicarbonate concentrations and reduced patient proportions with serum bicarbonate <22 mmol/L, likely due to SZC-binding of gastrointestinal ammonium. These SZC-induced serum bicarbonate increases occurred regardless of CKD stage and were sustained during ongoing maintenance therapy.
Geochemistry and Petrogenesis of Mafic and Ultramafic Inclusions in Sublayer and Offset Dikes, Sudbury Igneous Complex, Canada
Authors: Wang Yujian , Lesher C Michael , Lightfoot Peter C , Pattison Edward F , Golightly J Paul
Published: June 2020

The c. 1·85 Ga Sudbury Igneous Complex (SIC) is the igneous remnant of one of the oldest, largest and best-preserved impact structures on Earth and contains some of the world’s largest magmatic Ni–Cu–PGE sulfide deposits. Most of the mineralization occurs in Sublayer, Footwall Breccia and inclusion-bearing quartz diorite (IQD), all of which contain significant (Sublayer and IQD) to minor (Footwall Breccia) amounts of olivine-bearing mafic–ultramafic inclusions. These inclusions have only rare equivalents in the country rocks and are closely associated with the Ni–Cu–PGE sulfide mineralization. They can be divided into three groups on the basis of petrography and geochemical characteristics. Group I (n = 47) includes igneous-textured olivine melanorite and olivine melagabbronorite inclusions in the Whistle and Levack embayments on the North Range with Zr/Y, Zr/Nb, Nb/U and Zr/Hf similar to igneous-textured Sublayer matrix. Group I inclusions are interpreted to be anteliths that crystallized from a mixture of SIC impact melt and a more mafic melt, probably derived by melting of ultramafic footwall rocks. Group II includes Group IIA (n = 17) shock metamorphosed wehrlite and olivine clinopyroxenite inclusions in the Levack embayment and Group IIB (n = 2) shock metamorphosed olivine melanorite inclusions in the Foy Offset on the North Range. Group II inclusions have similar trace element patterns [e.g. negative Th–U, Nb–Ta–(Ti), Sr and Zr–Hf anomalies] and overlapping Nb/U to a layered mafic–ultramafic intrusion in the footwall of the Levack and Fraser deposits, which together with their limited distribution suggests that Group II inclusions are locally-derived xenoliths. Group III (n = 21) includes phlogopite lherzolite and feldspar lherzolite inclusions with igneous, recrystallized and shock-metamorphic textures in the Trill, Levack and Bowell embayments, and the Foy Offset dike on the North Range. They have no equivalents in the exposed country rocks. The calculated parental magma is similar to continental arc basalt formed by approximately 5% partial melting of garnet peridotite. Ol–Cpx–Pl thermobarometry of several Group III inclusions indicate equilibration at 900–1120 ºC and 210 ± 166 MPa to 300 ± 178 MPa, suggesting crystallization in the upper-middle crust (7·7 ± 6·6 to 10·9 ± 6·5 km), prior to being incorporated into the lower parts of the impact melt sheet during impact excavation. The exotic xenoliths provide information about the depth of impact and composition of upper-middle crust in the Sudbury region at 1850 Ma, the local xenoliths provide information about the thermomechanical erosion process that followed generation of the impact melt, the anteliths provide information about the early crystallization history of the SIC, and all of the inclusions provide constraints on the genesis of Sublayer, IQD, footwall breccia, and associated Ni–Cu–PGE mineralization.