bluuebunny/crossref_metadata_2025 huggingface dataset:
The patent buyout price for human papilloma virus (HPV) vaccine and the ratio of R&D costs to the patent value
Authors: Songane Mario , Grossmann Volker
Published: January 2021

Human papillomavirus (HPV) is responsible for almost all of the 570,000 new cases of cervical cancer and approximately 311,000 deaths per year. HPV vaccination is an integral component of the World Health Organization’s (WHO) global strategy to fight the disease. However, high vaccine prices enforced through patent protection are limiting vaccine expansion, particularly in low- and middle-income countries. By limiting market power, patent buyouts could reduce vaccine prices and raise HPV vaccination rates while keeping innovation incentives. We estimate the global patent buyout price as the present discounted value (PDV) of the future profit stream over the remaining patent length for Merck’s HPV vaccines (Gardasil-4 and 9), which hold 87% of the global HPV vaccine market, in the range of US$ 15.6–27.7 billion (in 2018 US$). The estimated PDV of the profit stream since market introduction amounts to US$ 17.8–42.8 billion and the estimated R&D cost to US$ 1.05–1.21 billion. Thus, we arrive at a ratio of R&D costs to the patent value of the order of 2.5–6.8%. We relate this figure to typical estimates of the probability of success (POS) for clinical trials of vaccines to discuss if patent protection provides Merck with extraordinarily strong price setting power.
The impact of community based continuous training project on improving couples’ knowledge on birth preparedness and complication readiness in rural setting Tanzania; A controlled quasi-experimental study
Authors: Moshi Fabiola V. , Kibusi Stephen M. , Fabian Flora Masumbuo
Published: January 2021

Background

It is widely accepted that community-based interventions are vital strategies towards reduction of maternal and neonatal mortalities in developing counties. This study aimed at finding the impact a Community Based Continuous Training (CBCT) project in improving couples’ knowledge on birth preparedness and complication readiness in rural Tanzania.

Method

The quasi-experimental study design with control was adopted to determine the impact of CBCT in improving knowledge on birth preparedness and complication readiness. The study was conducted from June 2017 until March 2018. A multi-stage sampling technique was employed to obtain 561couples. Pre-test and post-training intervention information were collected using semi-structured questionnaires. The impact of CBCT was determined using both independent t-test and paired t-test. Linear regression analysis was used to establish the association between the project and the change in knowledge mean scores. The effect size was calculated using Cohen’s d.

Results

At post-test assessment, knowledge mean scores were significantly higher in the intervention group among both pregnant women (m = 14.47±5.49) and their male partners (m = 14.1±5.76) as compared to control group among both pregnant women (m = 9.09±6.44) and their male partners (m = 9.98±6.65) with large effect size of 0.9 among pregnant women and medium effect size of 0.66 among male respondents. When the mean scores were compared within groups among both pregnant women and male partners in the intervention group, there were a significant increase in knowledge mean scores at post-test assessment as compared to pre-test assessment with large effect size of Cohen’s d = 1.4 among pregnant women and 1.5 among male partners. After adjusting for the confounders, the predictors of change in knowledge among pregnant women were the CBCT project (β = 0.346, p<0.000) and ethnic group [Mambwe (β = -0.524, p = 0.001)] and the predictors of change in knowledge among male partners were the CBCT project (β = 1.058, p<0.001) and walking distance [more than five kilometers (β = -0.55, p< 0.05)].

Conclusion

This interventional study which focused on knowledge empowerment and behavior change among expecting couples was both feasible and effective on improving knowledge about birth preparedness and complication readiness in rural settings of Tanzania.
Effects of conditioning, source, and rest on indicators of stress in beef cattle transported by road
Authors: Meléndez Daniela M. , Marti Sonia , Haley Derek B. , Schwinghamer Timothy D. , Schwartzkopf-Genswein Karen S.
Published: January 2021

Consumers are increasingly concerned about the welfare of farm animals, especially during transportation. The Canadian transport regulations state that weaned cattle require an 8 h rest after 36 h of transport. There are, however, only a few studies that assess the effect of rest on the welfare of beef cattle. The aim of this study was to assess the effect of conditioning, source and rest on indicators of welfare in 7-8-month-old beef calves during long-distance transport. Treatments consisted of a 2 × 2 × 2 factorial design where the main factors were conditioning: conditioned (C;n= 160) or non-conditioned (N;n= 160); source: auction market (A;n= 160) or ranch direct (R;n= 160); and rest: 0 h (0 h;n= 160) or 8 h (8 h;n= 160). Means of non-esterified fatty acids (NEFA), serum amyloid-A, haptoglobin, creatine kinase (CK), and percentage of time standing from N calves were greater than C calves (allp≤ 0.05). Means of percentage of time standing and CK of R calves were greater than A calves (bothp≤ 0.05). The mean of NEFA of 0 h calves was greater than the 8 h calves (p< 0.01), while the percentage of time standing of 0 h calves was less than 8 h calves (p< 0.01). Statistically significant differences between means of NEFA and standing percentage, were observed between 0 h and 8h calves. Few and inconsistent indicators of reduced welfare were observed between auction market and ranch direct calves, while non-conditioning was associated with greater physiological and behavioural indicators of reduced welfare. Based on these results, conditioning should be implemented as a management practice to improve the welfare of transported calves.
Coral growth, survivorship and return-on-effort within nurseries at high-value sites on the Great Barrier Reef
Authors: Howlett Lorna , Camp Emma F. , Edmondson John , Henderson Nicola , Suggett David J.
Published: January 2021

Coral reefs are deteriorating worldwide prompting reef managers and stakeholders to increasingly explore new management tools. Following back-to-back bleaching in 2016/2017, multi-taxa coral nurseries were established in 2018 for the first time on the Great Barrier Reef (GBR) to aid reef maintenance and restoration at a “high-value” location–Opal Reef–frequented by the tourism industry. Various coral species (n = 11) were propagated within shallow water (ca. 4-7m) platforms installed across two sites characterised by differing environmental exposure–one adjacent to a deep-water channel (Blue Lagoon) and one that was relatively sheltered (RayBan). Growth rates of coral fragments placed onto nurseries were highly variable across taxa but generally higher at Blue Lagoon (2.1–10.8 cm2 month-1 over 12 months) compared to RayBan (0.6–6.6 cm2 month-1 over 9 months). Growth at Blue Lagoon was largely independent of season, except for Acropora tenuis and Acropora hyacinthus, where growth rates were 15–20% higher for December 2018-July 2019 (“warm season”) compared to August-December 2018 (“cool season”). Survivorship across all 2,536 nursery fragments was ca. 80–100%, with some species exhibiting higher survivorship at Blue Lagoon (Acropora loripes, Porites cylindrica) and others at RayBan (A. hyacinthus, Montipora hispida). Parallel measurements of growth and survivorship were used to determine relative return-on-effort (RRE) scores as an integrated metric of “success” accounting for life history trade-offs, complementing the mutually exclusive assessment of growth or survivorship. RRE scores within sites (across species) were largely driven by growth, whereas RRE scores between sites were largely driven by survivorship. The initial nursery phase of coral propagation therefore appears useful to supplement coral material naturally available for stewardship of frequently visited Great Barrier Reef tourism (high-value) sites, but further assessment is needed to evaluate how well the growth rates and survival for nursery grown corals translate once material is outplanted.
Intravitreal bevacizumab versus intravitreal triamcinolone for diabetic macular edema–Systematic review, meta-analysis and meta-regression
Authors: Abdel-Maboud Mohamed , Menshawy Esraa , Bahbah Eshak I. , Outani Oumaima , Menshawy Amr
Published: January 2021

Background

The most frequent cause of vision loss from diabetic retinopathy is diabetic macular edema (DME). Earlier clinical trials tried to examine the role of intravitreal triamcinolone (IVT) and intravitreal bevacizumab (IVB) in DME; they either qualified IVT over IVB or IVB over IVT or did not exhibit a significant difference.

Objective

This paper aims to compare the efficacy and safety of IVB versus IVT alone or combined IVB+IVT in the treatment of DME.

Methods

We systematically searched PubMed, CENTRAL, Scopus, Embase, Science Direct, OVID, and Web of Science for randomized controlled trials of IVB versus IVT alone or combined IVB+IVT and IVT versus the combined IVB+IVT in DME patients.

Results

A total of 1243 eyes of 17 trials were included in our meta-analysis and regression. Repeated injections of IVB were superior at improving VA comparing with those of IVT at 12, 24, 48-weeks, and IVB+IVT at 12, 24, 48-weeks. Single injections were comparable across the three arms regarding BCVA improvement. CMT reductions were also comparable across the three arms. Meanwhile, the overall safety regarding intraocular pressure and intraocular hypertension significantly favored the IVB group. Improvement in VA was best modified with CMT reduction from 480 um to 320um. This association was significant at 12-weeks in the three arms and persisted till 24-weeks and 48-weeks exclusively in the IVB group.

Conclusions and relevance

Our analysis reveals that repeated successive injections associate with better BCVA compared to single injection. Current evidence affirms that IVB is superior to IVT and IVB+IVT at improving BCVA, comparable at reducing CMT, and presents a better safety profile in the treatment of DME.
A novel dietary multi-strain yeast fraction modulates intestinal toll-like-receptor signalling and mucosal responses of rainbow trout (Oncorhynchus mykiss)
Authors: Rawling Mark , Leclercq Eric , Foey Andrew , Castex Mathieu , Merrifield Daniel
Published: January 2021

This study was conducted to evaluate the mucosal immune responses of rainbow trout when supplementing an experimental formulated feed with multi-strain yeast fraction product (Saccharomyces cerevisiae and Cyberlindnera jardinii). In total, 360 fish (initial BW 23.1 ± 0.2 g) were randomly allotted into three dietary treatments in an 8-week feeding trial. The dietary treatments included basal diet (control) and control + 1.5 g/kg multi-strain yeast fraction product (MsYF) fed continuously and pulsed every two weeks between control and MsYF diet. No negative effects on growth performance of feeding the MsYF supplemented diet were observed. SGR and FCR averaged 2.30 ± 0.03%/day and 1.03 ± 0.03, respectively, across experimental groups. Muscularis thickness in the anterior intestine after 8 weeks of feeding was significantly elevated by 44.3% in fish fed the MsYF continuously, and by 14.4% in fish fed the MsYF pulsed (P < 0.02). Significant elevations in goblet cell density in the anterior and posterior (>50% increase) intestine were observed after 8 weeks of feeding the MsYF supplemented diet (P< 0.03). In contrast, lamina propria width was significantly lower in fish fed the experimental diets (>10% reduction). The gene expression analysis of the intestine revealed significant elevations in expression of tlr2, il1r1, irak4, and tollip2 after 4 weeks of feeding the MsYF. Significant elevations in effector cytokines tnfα, il10 and tgfβ were observed after 4 weeks of feeding the MsYF regime. After 8 weeks significant elevations in the gene expression levels of il1β, ifnγ, and il12 were observed in fish fed the MsYF. Likewise, the expression of the transcription factor gata3 was significantly elevated (P<0.01). Supplementation of the multi-strain yeast fraction product positively modulates the intestinal mucosal response of rainbow trout through interaction with toll-like receptor two signalling pathway and potential for increased capacity of delivery of antigens to the underlying mucosal associated lymphoid tissue.
Prevalence and correlates of metabolic syndrome and its components in adults with psychotic disorders in Eldoret, Kenya
Authors: Kwobah Edith , Koen Nastassja , Mwangi Ann , Atwoli Lukoye , Stein Dan J.
Published: January 2021

Background

A high prevalence of metabolic syndrome and its components in patients with psychotic disorders may increase the risk for cardiovascular diseases. Unfortunately, relatively little work in this field has emerged from low-resourced contexts. This study investigated the prevalence, correlates, and treatment patterns of metabolic disorders in patients with psychotic disorders in Western Kenya.

Methods

300 patients with psychosis and 300 controls were recruited at Moi Teaching and Referral Hospital in Eldoret, Kenya. Data on demographic characteristics, weight, height, abdominal circumference, blood pressure, blood glucose, lipid profile, and treatments were collected. Categorical and continuous data were compared between the patient and control groups using Pearson’s chi-squared tests and t-tests, respectively. Variables found to be significantly different between these groups were included in logistic regression models to determine potential predictors of metabolic syndrome.

Results

Compared to controls, patients with psychosis were found to have a higher mean random blood glucose [5.23 vs 4.79, p = 0.003], higher body mass index [5.23 vs 4.79, p = 0.001], higher triglycerides [1.98 vs 1.56, p<0.001], larger waist circumference [89.23 vs 86.39, p = 0.009] and lower high density lipoprotein [1.22 vs 1.32, p<0.001]. The odds of developing metabolic syndrome were increased with age [OR = 1.05, CI: 1.02–1.07] and presence of a psychotic disorder [OR = 2.09 [CI 1.23–3.55]; and were reduced with female gender [OR 0.41, CI 0.25–0.67], among those who were never married [OR 0.52, CI 0.28–0.94] and among the widowed/separated/ divorced marital status [OR 0.38, CI 0.17–0.81]. While the majority of patients received treatment with olanzapine, there was no association between olanzapine use and metabolic syndrome and its components. More than half of the patients in this study sample were not receiving treatment for the various components of metabolic syndrome.

Conclusion

In the study setting of Eldoret, metabolic syndrome and its components were more prevalent among patients with psychotic disorders than in controls; and a clear treatment gap for these disorders was evident. There is a need for efforts to ensure adequate screening and treatment for these physical disorders in resource-limited settings.
Implementing a high-efficiency similarity analysis approach for firmware code
Authors: Wang Yisen , Wang Ruimin , Jing Jing , Wang Huanwei
Published: January 2021

The rapid expansion of the open-source community has shortened the software development cycle, but the spread of vulnerabilities has been accelerated, especially in the field of the Internet of Things. In recent years, the frequency of attacks against connected devices is increasing exponentially; thus, the vulnerabilities are more serious in nature. The state-of-the-art firmware security inspection technologies, such as methods based on machine learning and graph theory, find similar applications depending on the known vulnerabilities but cannot do anything without detailed information about the vulnerabilities. Moreover, model training, which is necessary for the machine learning technologies, requires a significant amount of time and data, resulting in low efficiency and poor extensibility. Aiming at the above shortcomings, a high-efficiency similarity analysis approach for firmware code is proposed in this study. First, the function control flow features and data flow features are extracted from the functions of the firmware and of the vulnerabilities, and the features are used to calculate the SimHash of the functions. The mass storage and fast query capabilities of the SimHash are implemented by the pigeonhole principle. Second, the similarity function pairs are analyzed in detail within and among the basic blocks. Within the basic blocks, the symbolic execution is used to generate the basic block semantic information, and the constraint solver is used to determine the semantic equivalence. Among the basic blocks, the local control flow graphs are analyzed to obtain their similarity. Then, we implemented a prototype and present the evaluation. The evaluation results demonstrate that the proposed approach can implement large-scale firmware function similarity analysis. It can also get the location of the real-world firmware patch without vulnerability function information. Finally, we compare our method with existing methods. The comparison results demonstrate that our method is more efficient and accurate than the Gemini and StagedMethod. More than 90% of the firmware functions can be indexed within 0.1 s, while the search time of 100,000 firmware functions is less than 2 s.
Decreasing patient-reported burden of treatment: A systematic review of quantitative interventional studies
Authors: Lesage Aurore , Leclère Brice , Moret Leïla , Le Glatin Clément
Published: January 2021

Objectives

To describe and analyse studies aiming at quantitatively assessing the impact of interventions on patient-reported burden of treatment as an outcome (primary or secondary).

Methods

The aim of the search strategy was to identify all publications describing a medical intervention intended to reduce patient-reported burden of treatment in adult patients with long-term conditions, from January 1, 2008 to July 15, 2019. Four databases (Medline, PsycINFO, the “Trials” section of the Cochrane-Library, and OpenGrey) were searched in English, French, Spanish, Italian and Portuguese. Each identified article was reviewed and the risk of bias was assessed using a tool adapted from the Cochrane Collaboration recommendations.

Results

Of 641 articles retrieved, 11 were included in this review. There were nine randomized controlled trials, one non-randomized controlled trial, and one before-and-after study. The sample sizes ranged from 55 to 1,546 patients. Eight out of the eleven studies reported significant positive outcomes of the studied interventions. Reducing dosing frequency, improving background therapy, offering home care or providing easier-to-use medical devices were associated with positive outcomes.

Conclusions

Only a few studies have specifically focused on decreasing the subjective burden of treatment. Small trials conducted in patients with a single specific disorder have reported positive outcomes. However, a large, high-quality study assessing the impact of a change in care process in patients with multiple morbidities did not show such results. Further studies are needed to implement this aspect of patient-centred care.
A three-dimensional habitat for C. elegans environmental enrichment
Authors: Guisnet Aurélie , Maitra Malosree , Pradhan Sreeparna , Hendricks Michael
Published: January 2021

As we learn more about the importance of gene-environment interactions and the effects of environmental enrichment, it becomes evident that minimalistic laboratory conditions can affect gene expression patterns and behaviors of model organisms. In the laboratory, Caenorhabditis elegans is generally cultured on two-dimensional, homogeneous agar plates abundantly covered with axenic bacteria culture as a food source. However, in the wild, this nematode thrives in rotting fruits and plant stems feeding on bacteria and small eukaryotes. This contrast in habitat complexity suggests that studying C. elegans in enriched laboratory conditions can deepen our understanding of its fundamental traits and behaviors. Here, we developed a protocol to create three-dimensional habitable scaffolds for trans-generational culture of C. elegans in the laboratory. Using decellularization and sterilization of fruit tissue, we created an axenic environment that can be navigated throughout and where the microbial environment can be strictly controlled. C. elegans were maintained over generations on this habitat, and showed a clear behavioral bias for the enriched environment. As an initial assessment of behavioral variations, we found that dauer populations in scaffolds exhibit high-frequency, complex nictation behavior including group towering and jumping behavior.
Hypoxia-induced mitochondrial abnormalities in cells of the placenta
Authors: Vangrieken Philippe , Al-Nasiry Salwan , Bast Aalt , Leermakers Pieter A. , Tulen Christy B. M. , Janssen Ger. M. J. , Kaminski Iris , Geomini Iris , Lemmens Titus , Schiffers Paul M. H. , van Schooten Frederik J. , Remels Alex H. V.
Published: January 2021

Introduction

Impaired utero-placental perfusion is a well-known feature of early preeclampsia and is associated with placental hypoxia and oxidative stress. Although aberrations at the level of the mitochondrion have been implicated in PE pathophysiology, whether or not hypoxia-induced mitochondrial abnormalities contribute to placental oxidative stress is unknown.

Methods

We explored whether abnormalities in mitochondrial metabolism contribute to hypoxia-induced placental oxidative stress by using both healthy term placentae as well as a trophoblast cell line (BeWo cells) exposed to hypoxia. Furthermore, we explored the therapeutic potential of the antioxidants MitoQ and quercetin in preventing hypoxia-induced placental oxidative stress.

Results

Both in placental explants as well as BeWo cells, hypoxia resulted in reductions in mitochondrial content, decreased abundance of key molecules involved in the electron transport chain and increased expression and activity of glycolytic enzymes. Furthermore, expression levels of key regulators of mitochondrial biogenesis were decreased while the abundance of constituents of the mitophagy, autophagy and mitochondrial fission machinery was increased in response to hypoxia. In addition, placental hypoxia was associated with increased oxidative stress, inflammation, and apoptosis. Moreover, experiments with MitoQ revealed that hypoxia-induced reactive oxygen species originated from the mitochondria in the trophoblasts.

Discussion

This study is the first to demonstrate that placental hypoxia is associated with mitochondrial-generated reactive oxygen species and significant alterations in the molecular pathways controlling mitochondrial content and function. Furthermore, our data indicate that targeting mitochondrial oxidative stress may have therapeutic benefit in the management of pathologies related to placental hypoxia.
HIV false positive screening serology due to sample contamination reduced by a dedicated sample and platform in a high prevalence environment
Authors: Linström Michael A. , Preiser Wolfgang , Nkosi Nokwazi N. , Vreede Helena W. , Korsman Stephen N. J. , Zemlin Annalise E. , van Zyl Gert U.
Published: January 2021

Automated testing of HIV serology on clinical chemistry analysers has become common. High sample throughput, high HIV prevalence and instrument design could all contribute to sample cross-contamination by microscopic droplet carry-over from seropositive samples to seronegative samples resulting in false positive low-reactive results. Following installation of an automated shared platform at our public health laboratory, we noted an increase in low reactive and false positive results. Subsequently, we investigated HIV serology screening test results for a period of 21 months. Of 485 initially low positive or equivocal samples 411 (85%) tested negative when retested using an independently collected sample. As creatinine is commonly requested with HIV screening, we used it as a proxy for concomitant clinical chemistry testing, indicating that a sample had likely been tested on a shared high-throughput instrument. The contamination risk was stratified between samples passing the clinical chemistry module first versus samples bypassing it. The odds ratio for a false positive HIV serology result was 4.1 (95% CI: 1.69–9.97) when creatinine level was determined first, versus not, on the same sample, suggesting contamination on the chemistry analyser. We subsequently issued a notice to obtain dedicated samples for HIV serology and added a suffix to the specimen identifier which restricted testing to a dedicated instrument. Low positive and false positive rates were determined before and after these interventions. Based on measured rates in low positive samples we estimate that before the intervention, of 44 117 HIV screening serology samples, 753 (1.71%) were false positive, declining to 48 of 7 072 samples (0.68%) post-intervention (p<0.01). Our findings showed that automated high throughput shared diagnostic platforms are at risk of generating false-positive HIV test results, due to sample contamination and that measures are required to address this. Restricting HIV serology samples to a dedicated platform resolved this problem.
Efficient gene expression signature for a breast cancer immuno-subtype
Authors: Galili Ben , Tekpli Xavier , Kristensen Vessela N. , Yakhini Zohar
Published: January 2021

Motivation and background

The patient’s immune system plays an important role in cancer pathogenesis, prognosis and susceptibility to treatment. Recent work introduced an immune related breast cancer. This subtyping is based on the expression profiles of the tumor samples. Specifically, one study showed that analyzing 658 genes can lead to a signature for subtyping tumors. Furthermore, this classification is independent of other known molecular and clinical breast cancer subtyping. Finally, that study shows that the suggested subtyping has significant prognostic implications.

Results

In this work we develop an efficient signature associated with survival in breast cancer. We begin by developing a more efficient signature for the above-mentioned breast cancer immune-based subtyping. This signature represents better performance with a set of 579 genes that obtains an improved Area Under Curve (AUC). We then determine a set of 193 genes and an associated classification rule that yield subtypes with a much stronger statistically significant (log rank p-value < 2 × 10−4in a test cohort) difference in survival. To obtain these improved results we develop a feature selection process that matches the high-dimensionality character of the data and the dual performance objectives, driven by survival and anchored by the literature subtyping.
Digestive tract morphology and enzyme activities of juvenile diploid and triploid Atlantic salmon (Salmo salar) fed fishmeal-based diets with or without fish protein hydrolysates
Authors: Martínez-Llorens Silvia , Peruzzi Stefano , Falk-Petersen Inger-Britt , Godoy-Olmos Sergio , Ulleberg Lars Olav , Tomás-Vidal Ana , Puvanendran Velmurugu , Odei Derrick Kwame , Hagen Ørjan , Fernandes Jorge M. O. , Jobling Malcolm
Published: January 2021

Triploid, sterile Atlantic salmon (Salmo salar) could make a contribution to the development of the farming industry, but uncertainties about the performance and welfare of triploids have limited their adoption by farmers. In this study, we compared the ontogeny of digestive tract morphology and enzyme activities (pepsin, trypsin, chymotrypsin, alkaline phosphatase and aminopeptidase) of diploid and triploid Atlantic salmon. Fish were fed diets based on fishmeal (STD) or a mix of fishmeal and hydrolysed fish proteins (HFM) whilst being reared at low temperature from start-feeding to completion of the parr-smolt transformation. Fish weights for each ploidy and feed combination were used to calculate thermal growth coefficients (TGCs) that spanned this developmental period, and the data were used to examine possible relationships between enzyme activities and growth. At the end of the experiment, faeces were collected and analyzed to determine the apparent digestibility coefficients (ADCs) of the dietary amino acids (AAs). Digestive tract histo-morphology did not differ substantially between ploidies and generally reflected organ maturation and functionality. There were no consistent differences in proteolytic enzyme activities resulting from the inclusion of HFM in the diet, nor was there improved digestibility and AA bioavailability of the HFM feed in either diploid or triploid fish. The triploid salmon had lower ADCs than diploids for most essential and non-essential AAs in both diets (STD and HFM), but without there being any indication of lower intestinal protease activity in triploid fish. When trypsin-to-chymotrypsin activity and trypsin and alkaline phosphatase (ALP) ratios (T:C and T:ALP, respectively) were considered in combination with growth data (TGC) low T:C and T:ALP values coincided with times of reduced fish growth, and vice versa, suggesting that T:C and T:ALP may be used to predict recent growth history and possible growth potential.
Multi-view classification with convolutional neural networks
Authors: Seeland Marco , Mäder Patrick
Published: January 2021

Humans’ decision making process often relies on utilizing visual information from different views or perspectives. However, in machine-learning-based image classification we typically infer an object’s class from just a single image showing an object. Especially for challenging classification problems, the visual information conveyed by a single image may be insufficient for an accurate decision. We propose a classification scheme that relies on fusing visual information captured through images depicting the same object from multiple perspectives. Convolutional neural networks are used to extract and encode visual features from the multiple views and we propose strategies for fusing these information. More specifically, we investigate the following three strategies: (1) fusing convolutional feature maps at differing network depths; (2) fusion of bottleneck latent representations prior to classification; and (3) score fusion. We systematically evaluate these strategies on three datasets from different domains. Our findings emphasize the benefit of integrating information fusion into the network rather than performing it by post-processing of classification scores. Furthermore, we demonstrate through a case study that already trained networks can be easily extended by the best fusion strategy, outperforming other approaches by large margin.
Adaptation and validation of the Physical Activity Questionnaire for Older Children (PAQ-C) among Czech children
Authors: Cuberek Roman , Janíková Marcela , Dygrýn Jan
Published: January 2021

The study aimed to adapt the standardized Physical Activity Questionnaire for Older Children (PAQ-C) into the Czech language and assess its psychometric properties. A forwards-and-backwards translation method was carried out to prepare the Czech PAQ-C version (PAQ-C/CZ), followed by adjustments based on socio-cultural aspects. In the next phase, participants (n = 169) wore accelerometers for seven days. On the 8th day, participants completed the PAQ-C/CZ in school so that it was possible to determine the concurrent validity (correlation between the accelerometer and PAQ-C/CZ data, Spearman’s r), internal consistency (Cronbach’s alpha), item/scale properties (corrected item-total correlations, CITCs), and factor structure (exploratory factor analysis, EFA) for PAQ-C/CZ. In the last phase, participants (n = 63) completed the PAQ-C/CZ twice on two consecutive school days in the morning to determine the test-retest reliability (intraclass correlation coefficient, ICC; independent sample T-test). The PAQ-C/CZ indicated moderate internal consistency (alpha = 0.77), acceptable item/scale properties (CITCs = 0.29–0.61), and good test-retest reliability (ICC = 0.73–0.94). The EFA findings suggested a single factor model (factor load = 0.32–0.73) for PAQ-C/CZ, with items 2, 3, and 4 contributing low to the total score. Results on concurrent validity showed low but significant association (r = 0.28, p < 0.05) between accelerometer and PAQ-C/CZ data. Considering the study results, the PAQ-C/CZ can be recommended as a tool for moderate-to-vigorous physical activity assessment in large-sample research studies only, but with an emphasis on the interpretation of the correct results.
A tale of five stories: Defence spending and economic growth in NATO´s countries
Authors: Gómez-Trueba Santamaría Paula , Arahuetes García Alfredo , Curto González Tomás
Published: January 2021

This article examines the relationship between defence expenditure and its impact on the growth of NATO’s countries between 2005 and 2018. The aim is to determine if this relation exists and to test if it is possible to discover different models across the countries. The results obtained using the Arellano–Bond estimator, suggest that there is more than one model, and confirm, through the poolability test, the existence of five different groups of countries within the Alliance, with different impacts of the defence expenditure on their gross domestic product. These findings are in line with the review of existing literature that reveals heterogeneity in the results due to different parameters used.
Effect of ethanol in carbon monoxide poisoning and delayed neurologic sequelae: A prospective observational study
Authors: Choi Sungwoo , Han Sangsoo , Nah Sangun , Lee Young Hwan , Cho Young Soon , Lim Hoon , Kim Myeong Sik , Kim Gi Woon
Published: January 2021

Objectives

Carbon monoxide (CO) is one of the most common poisoning substances, which causes mortality and morbidity worldwide. Delayed neurologic sequelae (DNS) have been reported to occur from several days to months after exposure to CO. Thus, there is a need for prevention, recognition, and treatment of DNS. Patients with CO poisoning as a component of intentional suicide often also consume ethanol, but there is debate regarding its role in DNS. We explored whether ethanol has a neuroprotective effect in CO poisoning.

Methods

This prospective observational study included patients who visited the emergency department from August 2016 to August 2019 due to CO poisoning. After treatment of acute CO poisoning, patients were interviewed by telephone to ascertain whether DNS had occurred within 2 weeks, 1 month, and 3 months from the time of CO exposure.

Results

During the study period, 171 patients were enrolled. 28 patients (16.37%) developed DNS. The initial Glasgow Coma Scale (GCS) scores were 15 (10.5–15) for the non-DNS group and 10 (7–15) for the DNS group (p = 0.002). The ethanol levels were 11.01 ± 17.58 mg/dL and 1.49 ± 2.63 mg/dL for each group (p < 0.001). In multivariate logistic regression analysis, the GCS score had an odds ratio of 0.770 (p < 0.001) and the ethanol level had 0.882 (p < 0.030) for onset of DNS.

Conclusions

Higher ethanol level and higher initial GCS score were associated with lower incidence of DNS. Ethanol could have a neuroprotective effect on the occurrence of DNS in CO poisoning patients.
Exploring barriers to the adoption and utilization of improved latrine facilities in rural Ethiopia: An Integrated Behavioral Model for Water, Sanitation and Hygiene (IBM-WASH) approach
Authors: Tamene Aiggan , Afework Abel
Published: January 2021

Background

Even though evidence shows that access to and use of improved latrines is related to healthful families and the public, obstacles to the adoption and use of improved latrine facilities remain. Globally, not many inquiries appear to have been carried out to satisfactorily inform us regarding the multi-level barriers influencing the adoption and utilization of improved latrines facilities. Related studies in Ethiopia are even fewer.

Methods

Two qualitative data gathering methods, viz., key informant interviews and focus group discussions, were employed to collect data for this study. A total of fifteen focus group discussions were conducted with members of the community in the rural Wonago district of Ethiopia. Similarly, ten key informant interviews were conducted with water, sanitation, and hygiene officers, and health extension workers responsible for coordinating sanitation and hygiene activities. Open code software 4.03 was used for thematic analysis.

Result

Barriers to adoption and use of improved latrine facilities were categorized into Contextual factors (e.g. Gender, educational status, personal preference for using the field, limited space, population density, the status of land ownership), Psychosocial factors (Culture, beliefs, attitudes, and perceptions of minimal health threat from children's feces), and Technological factors (inconveniences in acquiring materials and cost of constructing a latrine).

Conclusion

There are a series of multi-leveled barriers to the sustained adoption and use of latrines. Providing funding opportunities for the underprivileged and offering training on the engineering skills of latrine construction at the community level based on the contextual soil circumstances could expand the latrine coverage and use. Similarly, taking into account the variability in motivations for adopting and using latrines among our study in Ethiopia and other studies, we implore public health experts to recognize behaviors and norms in their target communities in advance of implementing sanitation interventions.
The psychological effects of COVID-19 on hospital workers at the beginning of the outbreak with a large disease cluster on the Diamond Princess cruise ship
Authors: Ide Keiko , Asami Takeshi , Suda Akira , Yoshimi Asuka , Fujita Junichi , Nomoto Munetaka , Roppongi Tomohide , Hino Kousuke , Takahashi Yuichi , Watanabe Kaori , Shimada Tomoko , Hamasaki Toyoko , Endo Emi , Kaneko Tomoko , Suzuki Michiko , Kubota Kazumi , Saigusa Yusuke , Kato Hideaki , Odawara Toshinari , Nakajima Hideaki , Takeuchi Ichiro , Goto Takahisa , Aihara Michiko , Hishimoto Akitoyo
Published: January 2021

The aim of the present study was to investigate the psychological effects of the COVID-19 outbreak and associated factors on hospital workers at the beginning of the outbreak with a large disease cluster on the Diamond Princess cruise ship. This cross-sectional, survey-based study collected demographic data, mental health measurements, and stress-related questionnaires from workers in 2 hospitals in Yokohama, Japan, from March 23, 2020, to April 6, 2020. The prevalence rates of general psychological distress and event-related distress were assessed using the 12-item General Health Questionnaire (GHQ-12) and the 22-item Impact of Event Scale-Revised (IES-R), respectively. Exploratory factor analysis was conducted on the 26-item stress-related questionnaires. Multivariable logistic regression analysis was performed to identify factors associated with mental health outcomes for workers both at high- and low-risk for infection of COVID-19. A questionnaire was distributed to 4133 hospital workers, and 2697 (65.3%) valid questionnaires were used for analyses. Overall, 536 (20.0%) were high-risk workers, 944 (35.0%) of all hospital workers showed general distress, and 189 (7.0%) demonstrated event-related distress. Multivariable logistic regression analyses revealed that ‘Feeling of being isolated and discriminated’ was associated with both the general and event-related distress for both the high- and low-risk workers. In this survey, not only high-risk workers but also low-risk workers in the hospitals admitting COVID-19 patients reported experiencing psychological distress at the beginning of the outbreak.
Observational cohort study of IP-10’s potential as a biomarker to aid in inflammation regulation within a clinical decision support protocol for patients with severe COVID-19
Authors: Lev Shaul , Gottesman Tamar , Sahaf Levin Gal , Lederfein Doron , Berkov Evgeny , Diker Dror , Zaidman Aliza , Nutman Amir , Ilan Ber Tahel , Angel Alon , Kellerman Lior , Barash Eran , Navon Roy , Boico Olga , Israeli Yael , Rosenberg Michal , Gelman Amir , Kalfon Roy , Simon Einav , Avni Noa , Hainrichson Mary , Zarchin Oren , Gottlieb Tanya M. , Oved Kfir , Eden Eran , Tadmor Boaz
Published: January 2021

Background

Treatment of severely ill COVID-19 patients requires simultaneous management of oxygenation and inflammation without compromising viral clearance. While multiple tools are available to aid oxygenation, data supporting immune biomarkers for monitoring the host-pathogen interaction across disease stages and for titrating immunomodulatory therapy is lacking.

Methods

In this single-center cohort study, we used an immunoassay platform that enables rapid and quantitative measurement of interferon γ-induced protein 10 (IP-10), a host protein involved in lung injury from virus-induced hyperinflammation. A dynamic clinical decision support protocol was followed to manage patients infected with severe acute respiratory syndrome coronavirus 2 and examine the potential utility of timely and serial measurements of IP-10 as tool in regulating inflammation.

Results

Overall, 502 IP-10 measurements were performed on 52 patients between 7 April and 10 May 2020, with 12 patients admitted to the intensive care unit. IP-10 levels correlated with COVID-19 severity scores and admission to the intensive care unit. Among patients in the intensive care unit, the number of days with IP-10 levels exceeding 1,000 pg/mL was associated with mortality. Administration of corticosteroid immunomodulatory therapy decreased IP-10 levels significantly. Only two patients presented with subsequent IP-10 flare-ups exceeding 1,000 pg/mL and died of COVID-19-related complications.

Conclusions

Serial and readily available IP-10 measurements potentially represent an actionable aid in managing inflammation in COVID-19 patients and therapeutic decision-making.

Trial registration

Clinicaltrials.gov, NCT04389645, retrospectively registered on May 15, 2020.
Melamine disrupts spatial reversal learning and learning strategy via inhibiting hippocampal BDNF-mediated neural activity
Authors: Sun Wei , Wu Yuanhua , Tang Dongxin , Li Xiaoliang , An Lei
Published: January 2021

Although several studies showed adverse neurotoxic effects of melamine on hippocampus (HPC)-dependent learning and reversal learning, the evidence for this mechanism is still unknown. We recently demonstrated that intra-hippocampal melamine injection affected the induction of long-term depression, which is associated with novelty acquisition and memory consolidation. Here, we infused melamine into the HPC of rats, and employed behavioral tests, immunoblotting, immunocytochemistry and electrophysiological methods to sought evidence for its effects on cognitive flexibility. Rats with intra-hippocampal infusion of melamine displayed dose-dependent increase in trials to the criterion in reversal learning, with no locomotion or motivation defect. Compared with controls, melamine-treated rats avoided HPC-dependent place strategy. Meanwhile, the learning-induced BDNF level in the HPC neurons was significantly reduced. Importantly, bilateral intra-hippocampal BDNF infusion could effectively mitigate the suppressive effects of melamine on neural correlate with reversal performance, and rescue the strategy bias and reversal learning deficits. Our findings provide first evidence for the effect of melamine on cognitive flexibility and suggest that the reversal learning deficit is due to the inability to use place strategy. Furthermore, the suppressive effects of melamine on BDNF-mediated neural activity could be the mechanism, thus advancing the understanding of compulsive behavior in melamine-induced and other neuropsychiatric disorders.
Reno-protective effect of IL-34 inhibition on cisplatin-induced nephrotoxicity in mice
Authors: Wada Yukihiro , Iyoda Masayuki , Matsumoto Kei , Suzuki Taihei , Tachibana Shohei , Kanazawa Nobuhiro , Honda Hirokazu
Published: January 2021

Introduction

Interleukin-34 (IL-34) shares a receptor (cFMS) with colony stimulating factor-1 (CSF-1), and these two ligands mediate macrophage proliferation. However, in contrast to CSF-1, the influence of IL-34 on tubular epithelial cells (TECs) injury remains unclear. We investigated the physiological effects of IL-34 on TEC damage caused by cisplatin nephrotoxicity (CP-N).

Methods

Mice were administered anti-mouse IL-34 antibody (anti-IL-34 Ab; 400 ng/kg) or vehicle from 1 day before and up to 2 days after CP-N induction. In vitro, mouse renal proximal TECs (MRPTEpiC) were cultured to analyze the inhibitory effects of IL-34 on CP-induced TEC apoptosis.

Results

Compared to vehicle treatment, anti-IL-34 Ab treatment significantly suppressed the intra-renal expression of IL-34 and its two receptors, cFMS and PTP-ζ, and significantly improved renal function, ameliorated tubulointerstitial injury, suppressed macrophage infiltration, and reduced apoptotic cell numbers in CP-N mice. It also significantly reduced the renal transcript levels of Kim-1, MIP-1/CCL3, TNF-α, and Bax in CP-N mice. Furthermore, anti-IL-34 Ab-treated CP-N mice showed less renal infiltration of F4/80+TNF-α+ cells. In vitro, stimulation with CP induced the expression of IL-34 and its two receptors in MRPTEpiC. Anti-IL-34 Ab treatment significantly suppressed CP-induced Bax expression with the degradation of ERK1/2 phosphorylation in damaged MRPTEpiC.

Conclusions

IL-34 secreted from damaged TECs appeared to be involved in the progression of CP-N. Inhibition of IL-34 with neutralizing antibody directly prevented CP-induced TEC apoptosis by inhibiting the phosphorylation of ERK 1/2. Blocking of IL-34 appears to suppress the proliferation of cytotoxic macrophages, which indirectly attenuates CP-N. Thus, IL-34 represents a potential therapeutic target for TEC injury, and the inhibition of IL-34 might have a reno-protective effect.
Whole genome sequencing of coagulase positive staphylococci from a dog-and-owner screening survey
Authors: Sahin-Tóth Judit , Kovács Eszter , Tóthpál Adrienn , Juhász János , Forró Barbara , Bányai Krisztián , Havril Kata , Horváth Andrea , Ghidán Ágoston , Dobay Orsolya
Published: January 2021

Background

Staphylococcus aureus and S. pseudintermedius are the two most common coagulase positive staphylococci (CPS). S. aureus is more prevalent among humans, whereas S. pseudintermedius is more commonly isolated from dogs, however, both can cause various community and hospital acquired diseases in humans.

Methods

In the current study we screened 102 dogs and 84 owners in Hungary. We tested the antibiotic susceptibility of the strains and in order to get a better picture of the clonal relationship of the strains, we used pulsed-field gel electrophoresis. In addition, three pairs of isolates with identical PFGE patterns were whole genome sequenced, MLST and spa types were established.

Results

Carriage rate of S. aureus was 23.8% in humans and 4.9% in dogs and two cases of co-carriage were found among dogs and owners. S. pseudintermedius carriage rate was 2.4% and 34.3%, respectively, with only one co-carriage. The isolates were generally rather susceptible to the tested antibiotics, but high tetracycline resistance of S. pseudintermedius strains was noted. The co-carried isolates shared almost the same resistance genes (including tet(K), bla(Z), norA, mepR, lmrS, fosB) and virulence gene pattern. Apart from the common staphylococcal enzymes and cytotoxins, we found enterotoxins and exfoliative toxins as well. The two S. aureus pairs belonged to ST45-t630, ST45-t671 and ST15-t084, ST15-t084, respectively. The co-carried S. pseudintermedius isolates shared the same housekeeping gene alleles determining a novel sequence type ST1685.

Conclusions

Based on the genomic data, dog-owner co-carried strains displayed only insignificant differences therefore provided evidence for potential human-to-dog and dog-to-human transmission.