bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural Cumulative Survival Models for Estimation of Treatment Effects Accounting for Treatment Switching in Randomized Experiments
Authors: Ying Andrew , Tchetgen Tchetgen Eric J.
Published: June 2022

Treatment switching in a randomized controlled trial occurs when a patient in one treatment arm switches to another arm during follow-up. This can occur at the point of disease progression, whereby patients in the control arm may be offered the experimental treatment. It is widely known that failure to account for treatment switching can seriously bias the estimated treatment causal effect. In this paper, we aim to account for the potential impact of treatment switching in a reanalysis evaluating the treatment effect of nucleoside reverse transcriptase inhibitors (NRTIs) on a safety outcome (time to first severe or worse sign or symptom) in participants receiving a new antiretroviral regimen that either included or omitted NRTIs in the optimized treatment that includes or omits NRTIs trial. We propose an estimator of a treatment causal effect for a censored time to event outcome under a structural cumulative survival model that leverages randomization as an instrumental variable to account for selective treatment switching. We establish that the proposed estimator is uniformly consistent and asymptotically Gaussian, with a consistent variance estimator and confidence intervals given, whose finite-sample performance is evaluated via extensive simulations. An R package ‘ivsacim’ implementing all proposed methods is freely available on R CRAN. Results indicate that adding NRTIs versus omitting NRTIs to a new optimized treatment regime may increase the risk for a safety outcome.
COVID‐19 and views of imprisonment in a sample of prison tourists
Authors: Côté‐Lussier Carolyn , Walby Kevin , Piché Justin
Published: June 2022

The COVID‐19 pandemic has exposed large segments of the global population to the experience of restricted freedoms. In Canada, COVID‐19‐related measures led to a decrease of mobility within the country, prohibiting access to public and private spaces for prolonged periods of time. This study addresses the effects of the pandemic and related restrictions on views of imprisonment, drawing on a sample of individuals who took part in a tour of the HI Ottawa Jail Hostel (N = 102) in pre‐ and peri‐COVID‐19 contexts. The results provide some support for the hypothesis that the uncertainty and existential threat brought about by the pandemic may have contributed to more stringent support for imprisonment and increased punitiveness. However, the results are limited by the small sample size and sample composition. Future directions for research on the impact of the pandemic on public views of imprisonment are discussed.
Dietary advanced glycation end products and cancer risk in Japan: From the Takayama study
Authors: Wada Keiko , Nakashima Yuma , Yamakawa Michiyo , Hori Akihiro , Seishima Mitsuru , Tanabashi Shinobu , Matsushita Shogen , Tokimitsu Naoki , Nagata Chisato
Published: June 2022

Few large epidemiological studies have evaluated the association between dietary advanced glycation end products (AGEs) and cancer risk. We evaluated the relationship between dietary AGE intake and the incidence of total cancer and site‐specific cancers in a population‐based prospective study in Japan. Participants were 14,173 men and 16,549 women who were 35 years of age or older in 1992. Dietary intake was assessed via a validated food frequency questionnaire. Intake of the AGE Nε‐carboxymethyl‐lysine (CML) was estimated using databases of CML content in foods determined using ultraperformance liquid chromatography–tandem mass spectrometry. Cancer incidence was confirmed through regional population‐based cancer registries. During a mean follow‐up period of 13.3 years, 1954 men and 1477 women developed cancer. We did not observe a significant association between CML intake and the risk of total cancer in men or women. In men, compared with the lowest quartile of CML intake, the hazard ratios of liver cancer for the second, third, and highest quartiles were 1.69 (95% CI: 0.92–3.10), 1.48 (95% CI: 0.77–2.84), and 2.10 (95% CI: 1.10–3.98; trend p = 0.04). Conversely, a decreased relative risk of male stomach cancer was observed for the second and highest quartiles of CML intake versus the lowest quartile, with hazard ratios of 0.73 and 0.67, respectively (trend p = 0.08). Our finding on the potential harmfulness of consuming AGEs on liver cancer risk is intriguing and warrants further study.
Unpacking the discourses of stunting in Indonesian early childhood education and parenting
Authors: Adriany Vina , Tesar Marek
Published: June 2022

This paper interrogates the discourses of stunting in Indonesia and its links to early childhood education. Here, stunting is analysed via Foucault's work, with data stemming from a long‐term ethnography study and analysis of relevant policy documents in Indonesia. We argue the discourses of stunting have been regulating children, teachers and parents by acting as a form of biopower of governing rationalities. Focusing merely on the individual and nutrition aspects, the discourses overlook larger societal problems. In such a space, the children, teachers and parents become a site of the state's surveillance and are produced as docile bodies.
Which one is the superior target? A comparison and pooled analysis between posterior subthalamic area and ventral intermediate nucleus deep brain stimulation for essential tremor
Authors: Fan Houyou , Bai Yutong , Yin Zixiao , An Qi , Xu Yichen , Gao Yuan , Meng Fangang , Zhang Jianguo
Published: June 2022

Background/Aims

The efficacy and safety of posterior subthalamic area (PSA) and ventral intermediate nucleus (VIM) deep brain stimulation (DBS) in the treatment of essential tremor (ET) have not been compared in large‐scale studies. We conducted a secondary analysis to identify the superior target of ET‐DBS treatment.

Methods

PubMed, Embase, Cochrane Library, and Google Scholar were searched for relevant studies before September 2021. The tremor‐suppression efficacy and rate of stimulation‐related complications (SRCR) after PSA‐DBS and VIM‐DBS treating ET were quantitatively compared. Secondary outcomes, including tremor subitem scores and quality of life results, were also analyzed. Subgroup analyses were further conducted to stratify by follow‐up (FU) periods and stimulation lateralities. This study was registered in Open Science Framework (DOI: 10.17605/OSF.IO/7VJQ8).

Results

A total of 23 studies including 122 PSA‐DBS patients and 326 VIM‐DBS patients were analyzed. The average follow‐up time was 12.81 and 14.66 months, respectively. For the percentage improvement of total tremor rating scale (TRS) scores, PSA‐DBS was significantly higher, when compared to VIM‐DBS in the sensitivity analysis (p = 0.030) and main analysis (p = 0.043). The SRCR after VIM‐DBS was higher than that of PSA‐DBS (p = 0.022), and bilateral PSA‐DBS was significantly superior to both bilateral and unilateral VIM‐DBS (p = 0.001).

Conclusions

This study provided level IIIa evidence that PSA‐DBS was more effective and safer for ET than VIM‐DBS in 12–24 months, although both PSA‐DBS and VIM‐DBS were effective in suppressing tremor in ET patients. Further prospective large‐scale randomized clinical trials are warranted in the future.
Pharmacogenetic variants and risk of remdesivir‐associated liver enzyme elevations in Million Veteran Program participants hospitalized with COVID‐19
Authors: Tuteja Sony , Yu Zhihong , Wilson Otis , Chen Hua‐Chang , Wendt Frank , Chung Cecilia P. , Shah Shailja C. , Hunt Christine M. , Suzuki Ayako , Chanfreau Catherine , Gorman Bryan R. , Joseph Jacob , Luoh Shiuh‐Wen , Napolioni Valerio , Robinson‐Cohen Cassianne , Tao Ran , Zhou Jin , Chang Kyong‐Mi , Hung Adriana M. ,   the VA Million Veteran Program COVID‐19 Science Initiative
Published: June 2022

Remdesivir is the first US Food and Drug Administration (FDA)‐approved drug for the treatment of coronavirus disease 2019 (COVID‐19). We conducted a retrospective pharmacogenetic study to examine remdesivir‐associated liver enzyme elevation among Million Veteran Program participants hospitalized with COVID‐19 between March 15, 2020, and June 30, 2021. Pharmacogene phenotypes were assigned using Stargazer. Linear regression was performed on peak log‐transformed enzyme values, stratified by population, adjusted for age, sex, baseline liver enzymes, comorbidities, and 10 population‐specific principal components. Patients on remdesivir had higher peak alanine aminotransferase (ALT) values following treatment initiation compared with patients not receiving remdesivir. Remdesivir administration was associated with a 33% and 24% higher peak ALT in non‐Hispanic White (NHW) and non‐Hispanic Black (NHB) participants (p < 0.001), respectively. In a multivariable model, NHW CYP2C19 intermediate/poor metabolizers had a 9% increased peak ALT compared with NHW normal/rapid/ultrarapid metabolizers (p = 0.015); this association was not observed in NHB participants. In summary, remdesivir‐associated ALT elevations appear to be multifactorial, and further studies are needed.
Inferring trends in pollinator distributions across the Neotropics from publicly available data remains challenging despite mobilization efforts
Authors: Boyd Robin J. , Aizen Marcelo A. , Barahona‐Segovia Rodrigo M. , Flores‐Prado Luis , Fontúrbel Francisco E. , Francoy Tiago M. , Lopez‐Aliste Manuel , Martinez Lican , Morales Carolina L. , Ollerton Jeff , Pescott Oliver L. , Powney Gary D. , Saraiva Antonio Mauro , Schmucki Reto , Zattara Eduardo E. , Carvell Claire
Published: June 2022

Aim

Aggregated species occurrence data are increasingly accessible through public databases for the analysis of temporal trends in the geographic distributions of species. However, biases in these data present challenges for statistical inference. We assessed potential biases in data available through GBIF on the occurrences of four flower‐visiting taxa: bees (Anthophila), hoverflies (Syrphidae), leaf‐nosed bats (Phyllostomidae) and hummingbirds (Trochilidae). We also assessed whether and to what extent data mobilization efforts improved our ability to estimate trends in species' distributions.

Location

The Neotropics.

Methods

We used five data‐driven heuristics to screen the data for potential geographic, temporal and taxonomic biases. We began with a continental‐scale assessment of the data for all four taxa. We then identified two recent data mobilization efforts (2021) that drastically increased the quantity of records of bees collected in Chile available through GBIF. We compared the dataset before and after the addition of these new records in terms of their biases and estimated trends in species' distributions.

Results

We found evidence of potential sampling biases for all taxa. The addition of newly‐mobilized records of bees in Chile decreased some biases but introduced others. Despite increasing the quantity of data for bees in Chile sixfold, estimates of trends in species' distributions derived using the postmobilization dataset were broadly similar to what would have been estimated before their introduction, albeit more precise.

Main conclusions

Our results highlight the challenges associated with drawing robust inferences about trends in species' distributions using publicly available data. Mobilizing historic records will not always enable trend estimation because more data do not necessarily equal less bias. Analysts should carefully assess their data before conducting analyses: this might enable the estimation of more robust trends and help to identify strategies for effective data mobilization. Our study also reinforces the need for targeted monitoring of pollinators worldwide.
Hiking trails shift plant species' realized climatic niches and locally increase species richness
Authors: Wedegärtner Ronja E. M. , Lembrechts Jonas J. , van der Wal René , Barros Agustina , Chauvin Aurélie , Janssens Ilias , Graae Bente Jessen
Published: June 2022

Aim

The presence and use of trails may change plant species' realized climatic niches via modified abiotic and biotic conditions including propagule transport, allowing competition‐pressed alpine species to expand their rear edges towards warmer locations and lowland species to extend their leading edges towards cooler locations. We investigated whether mountain trails indeed act as corridors for colonization and shift species' realized climatic niches, resulting in higher species richness in trailsides.

Location

Dovrefjell and Abisko area in the Scandes mountains of Norway and Sweden.

Methods

We surveyed plant community composition and disturbances along 16 hiking trails in summer 2018 (Dovrefjell) and 2019 (Abisko). We linked changes in species' realized climatic niches to their climatic optimum and variation in species richness to climate, trail effects and resident plant community characteristics.

Results

Plant species richness was on average 24% greater in trailside than in interior vegetation plots. Proximity to trails accounted for 9% and climatic harshness for 55% of variation in species richness explained in our model. Trailsides increased in richness, especially in relatively species‐poor sites and close to introduction points (each accounting for 24% of variation in our model of species gains). Shifts in rear edges and optima of realized climatic niches along trails related to species' undisturbed climatic optimum, with alpine species being more likely to move into warmer locations. While some disturbance‐associated species shifted their leading edges towards colder locations, contrary to expectations this was not the case for lowland species. Overall, shifts in climatic niches resulted in more species' niches overlapping in trailsides than in the interior vegetation.

Main conclusion

Trails can locally increase species richness by creating opportunities for colonizing species and weaker competitors. Because of prevailing disturbance, they may even provide opportunities for persistence and downward expansion of alpine species, aiding conservation efforts.
Temporal trends, clinical characteristics, and sociodemographic profile of post‐neonatally acquired cerebral palsy in Australia, 1973–2012: A population‐based observational study
Authors: Waight Emma , McIntyre Sarah , Woolfenden Susan , Watson Linda , Reid Susan , Scott Heather , Martin Tanya , Webb Annabel , Badawi Nadia , Smithers‐Sheedy Hayley ,   Australian Cerebral Palsy Register Group
Published: June 2022

Aim

To describe post‐neonatally acquired (PNN) cerebral palsy (CP) in terms of temporal trends in prevalence, clinical and sociodemographic profiles, known causes and associations between causes, and sociodemographic variables.

Method

Numerator data, a count of children with PNN‐CP confirmed at 5 years of age (n = 523), was drawn from two Australian state CP registers (birth years 1973–2012). Poisson regression was used to investigate temporal trends in the prevalence of PNN‐CP by 5‐year intervals, calculated per 10 000 live births. Using data from all state and territory Australian CP registers (n = 469), distributions of clinical characteristics, PNN‐CP causes, and sociodemographic factors were tabulated (birth years 1995–2012). χ2 and logistic regression analyses were used to assess associations between sociodemographic profile, Australian reference data, and known causes.

Results

A significant temporal decline in PNN‐CP in Victoria (p = 0.047) and Western Australia (p = 0.033) was observed. The most common proximal causes of PNN‐CP were cerebrovascular accidents (34%, n = 158), infection (25%, n = 117), and non‐accidental injuries (12%, n = 58). Children born to teenage mothers, Aboriginal and/or Torres Strait Islander mothers, or children born in remote areas were over‐represented in this cohort compared with reference data (all p ≤ 0.001). Infectious causes were strongly associated with teenage motherhood (odds ratio 3.0 [95% confidence interval 1.1–8.2], p = 0.028) and remote living (odds ratio 4.5 [95% confidence interval 2.0–10.2], p < 0.001).

Interpretation

Although prevalence of PNN‐CP has declined, the over‐representation of priority populations, and the relative severity of a condition that is largely preventable, suggest the need for more specific primary preventive measures and support.

What this paper adds

Prevalence of post‐neonatally acquired (PNN) cerebral palsy (CP) in Australia significantly declined between 1973 and 2012.

Cerebrovascular accidents are the most common proximal cause of PNN‐CP.

Children born in remote areas are at greater risk of PNN‐CP.
Dystonia in individuals with spastic cerebral palsy and isolated periventricular leukomalacia
Authors: Ueda Keisuke , Aravamuthan Bhooma R. , Pearson Toni S.
Published: June 2022

Aim

To determine the prevalence of dystonia in individuals with periventricular leukomalacia (PVL) and spastic cerebral palsy (CP), but without basal ganglia and thalamic injury (BGTI) on brain magnetic resonance imaging (MRI).

Method

This was a retrospective study of individuals with spastic CP and PVL on MRI evaluated between 2005 and 2018 in a CP center. Individuals with non‐PVL brain lesions on MRI, including BGTI, were excluded. Dystonia was assessed via blinded review of neurological exam videos by pediatric movement disorders specialists.

Results

Eighty‐five participants (45 males, 40 females; mean age at videotaping 12 years [standard deviation 5 years 6 months], range 4–26 years) met inclusion and exclusion criteria. Of these participants, 50 (59%) displayed dystonia in their exam videos. The most common locations of dystonia were the fingers and hip adductors. The prevalence of dystonia was unaffected by the gestational age or severity of PVL, and was affected by Gross Motor Function Classification System level.

Interpretation

Dystonia is common in individuals with spastic CP and PVL, even without BGTI on MRI. Our findings suggest vigilance for dystonia in individuals with spastic CP should remain high, even without MRI evidence of BGTI.

What this paper adds

Individuals with spastic cerebral palsy and isolated periventricular leukomalacia on magnetic resonance imaging commonly display dystonia.

Common sites of dystonia are in the fingers and hip adductors.
Can motor problems overlooked in infancy as ‘low‐normal’ affect function in later childhood?
Authors: Kerem Günel Mintaze
Published: June 2022

This commentary is on the original article by Danks et al. on pages 1517–1523 of
this issue.
Susceptibility of germinating seedlings of European and Eurasian populations of Pinus sylvestris to damping‐off caused by Fusarium circinatum
Authors: Woodward Steve , Flores‐Pacheco J. Asdrubel , Muñoz‐Adalia E. Jordán , Martínez‐Álvarez Pablo , Martín‐García Jorge , Diez Julio J.
Published: June 2022

The effect of inoculation with Fusarium circinatum on survival of seed and seedlings of 19 populations of Pinus sylvestris was examined under environmentally controlled conditions, with four treatments (0, 50, 103, 106 spores ml−1). A single seed source of P. radiata was included as a positive control. Germination (emergence of the plumule above the compost) and health of seedlings was assessed daily, for 85 days. Spore density had a significant effect on germination: at 50 spores ml−1, only germination of a Northeast Scotland population was reduced. Treatment with 1000 spores ml−1, however, reduced germination of six populations of P. sylvestris and of P. radiata.

Survival of emerged seedlings also varied with inoculum dose. Approximately 75% of seedlings survived 85 days after germination after inoculation with 50 spores ml−1. Seedlings of all populations were killed within 12–16 days of germination by the 103 and 106 spores ml−1 treatments.

Emerged seedlings of the Austrian populations showed the highest susceptibility to F. circinatum following treatment with 50 spores ml−1, although 15% of seedlings of one Austrian population (AU3) survived to the end of the experiment (85 days after germination). There was no clear pattern in survival rates of the P. sylvestris seedlings from other populations treated with 1000 or 1 million spores ml−1 due to death of all emerged seedlings within a short period.

Variations in susceptibility of different populations of P. sylvestris to F. circinatum may be used in future selection and breeding programmes to reduce the impact of the pathogen as it spreads over wider areas in Europe and Eurasia.
Valproate in status epilepticus: Correlation between loading dose, serum levels, and clinical response
Authors: Vijiala Sergiu , André Pascal , Buclin Thierry , Decosterd Laurent A. , Rossetti Andrea O. , Novy Jan
Published: June 2022

Background and purpose

Intravenous valproate (VPA) is an established treatment of status epilepticus (SE), but optimal loading dose was not fully assessed. We aimed at analyzing the correlation between VPA loading dose and subsequent plasma levels with clinical response in SE.

Methods

This was a retrospective study in one referral center of all consecutive VPA‐naïve SE episodes treated with VPA between January 2013 and June 2019, in which total VPA trough plasma levels after intravenous loading dose were available. Response to VPA, defined as last antiseizure medication introduced before SE resolution (without the need for additional treatment), was correlated with VPA loading dose and trough level. Correlations were adjusted for other SE characteristics.

Results

Among 128 SE episodes, 53 (41%) responded to VPA. Median VPA loading dose was 25.2 mg/kg (range, 7–58 mg/kg). Loading doses and total plasma levels were not associated with the probability of response or mortality. Correcting for other possible confounders (number of previously tried treatment, demographics, SE severity) did not alter these findings. Only 3.8% of SE episodes that responded to VPA received >30 mg/kg.

Conclusions

A high loading dose (>30 mg/kg) is not associated with a greater response rate in patients with SE. Therefore, it seems to bring little benefit. If confirmed in further studies, a dosage of 25–30 mg/kg appears adequate in SE.
Opposing global change drivers counterbalance trends in breeding North American monarch butterflies
Authors: Crossley Michael S. , Meehan Timothy D. , Moran Matthew D. , Glassberg Jeffrey , Snyder William E. , Davis Andrew K.
Published: June 2022

Many insects are in clear decline, with monarch butterflies (Danaus plexippus) drawing particular attention as a flagship species. It is well documented that, among migratory populations, numbers of overwintering monarchs have been falling across several decades, but trends among breeding monarchs are less clear. Here, we compile >135,000 monarch observations between 1993 and 2018 from the North American Butterfly Association's annual butterfly count to examine spatiotemporal patterns and potential drivers of adult monarch relative abundance trends across the entire breeding range in eastern and western North America. While the data revealed declines at some sites, particularly the US Northeast and parts of the Midwest, numbers in other areas, notably the US Southeast and Northwest, were unchanged or increasing, yielding a slightly positive overall trend across the species range. Negative impacts of agricultural glyphosate use appeared to be counterbalanced by positive effects of annual temperature, particularly in the US Midwest. Overall, our results suggest that population growth in summer is compensating for losses during the winter and that changing environmental variables have offsetting effects on mortality and/or reproduction. We suggest that density‐dependent reproductive compensation when lower numbers arrive each spring is currently able to maintain relatively stable breeding monarch numbers. However, we caution against complacency since accelerating climate change may bring growing threats. In addition, increases of summer monarchs in some regions, especially in California and in the south, may reflect replacement of migratory with resident populations. Nonetheless, it is perhaps reassuring that ubiquitous downward trends in summer monarch abundance are not evident.
ADVERSE SELECTION, LEARNING, AND COMPETITIVE SEARCH
Authors: Mayr‐Dorn Karin
Published: June 2022

I develop a model that allows for an analysis of the effects of time on adverse selection in the presence of search frictions. I find that, as a firm takes longer to adjust a worker's contract in response to learning about his type, inefficient overwork during the time before wage adjustment (probation) decreases. This provides a rationale for an optimal (minimum) probation period of about one month in the baseline scenario. Optimal probation duration varies with the degree of search frictions, the cost of effort, the relative productivity of different types of workers, and minimum wage regulations.
Consumer intentions to use collaborative economy platforms: A meta‐analysis
Authors: Ertz Myriam , Sarigöllü Emine
Published: June 2022

Collaborative economy platforms (CEP) have been investigated from various disciplines, theoretical frameworks and methodological approaches. Subsequently, numerous models emerged to explain the cognitive process underlying intentions to use CEP. Yet, their findings are fragmented and diverse, impeding thereby theory development and management practice. This article addresses this deficiency by a meta‐analysis of psychosocial determinants of collaborative economy platforms (CEP) use intentions. Based on information from a total of 27 independent samples, we find support for the relation between psychosocial determinants and CEP use intentions, as well as willingness to pay a premium price for CEP. The findings show that (1) emotional and flexibility utility exert the strongest influence on use intentions; (2) functional and social utility exert more influence on willingness to pay a premium price; (3) CEP are primarily used for enjoyment and practical purposes; and (4) hedonism does not strongly lead to an increased willingness to pay.
Preinoculation with Endophytic fungus Phomopsis liquidambaris reduced rice bakanae disease caused by Fusarium proliferatum via enhanced plant resistance
Authors: Zhu Qiang , Wu Yi-Bo , Chen Man , Lu Fan , Sun Kai , Tang Meng-Jun , Zhang Wei , Bu Yuan-Qing , Dai Chuan-Chao
Published: June 2022

Aims

This study evaluated the control effect of the endophytic fungus Phomopsis liquidambaris B3 against rice bakanae disease (RBD) caused by Fusarium proliferatum and the disease control result of different inoculation times of beneficial micro-organisms.

Methods and Results

Rice seedlings preinoculated, coinoculated and noninoculated with B3 were exposed to F. proliferatum stress and grown under controlled conditions. Greenhouse experimental results showed that rice preinoculation with B3 significantly reduced rice bakanae disease by 21.45%, inhibited the colonization of F. proliferatum, increased defence-related enzyme activities, upregulated the expression of defence genes and promoted plant photosynthesis. However, bakanae disease in rice coinoculation with B3 increased by 11.45%, resulted in excessive reactive oxygen species (ROS) bursts and plant cell death.

Conclusions

Preinoculation with the endophytic fungus P. liquidambaris B3 significantly reduced rice bakanae disease by triggering the SA-dependent defence pathways of plants, and promoted plant growth. However, coinoculatiton with P. liquidambaris B3 activated excessive defence responses, resulting in plants cell death and aggravation of bakanae disease.

Significance and Impact of the Study

This study indicated that P. liquidambaris B3 was an effective method for agricultural control against rice bakanae disease caused by F. proliferatum, and provides an experimental basis for the development of sustainable endophytic fungal resources to effectively control plant diseases caused by pathogenic fungi, and suggests that precise application of beneficial micro-organisms may be become a key factor in farmland crop disease management.
Reconstruction of Acinetobacter johnsonii ICE_NC genome using hybrid de novo genome assemblies and identification of the 12α-hydroxysteroid dehydrogenase gene
Authors: Favale Nicoletta , Costa Stefania , Scapoli Chiara , Carrieri Alberto , Sabbioni Silvia , Tamburini Elena , Benazzo Andrea , Bernacchia Giovanni
Published: June 2022

Aims

The role of a Acinetobacter johnsonii strain, isolated from a soil sample, in the biotransformation of bile acids (BAs) was already described but the enzymes responsible for these transformations were only partially purified and molecularly characterized.

Methods and Results

This study describes the use of hybrid de novo assemblies, that combine long-read Oxford Nanopore and short-read Illumina sequencing strategies, to reconstruct the entire genome of A. johnsonii ICE_NC strain and to identify the coding region for a 12α-hydroxysteroid dehydrogenase (12α-HSDH), involved in BAs metabolism. The de novo assembly of the A. johnsonii ICE_NC genome was generated using Canu and Unicycler, both strategies yielded a circular chromosome of about 3.6 Mb and one 117 kb long plasmid. Gene annotation was performed on the final assemblies and the gene for 12α-HSDH was detected on the plasmid.

Conclusions

Our findings illustrate the added value of long read sequencing in addressing the challenges of whole genome characterization and plasmid reconstruction in bacteria. These approaches also allowed the identification of the A. johnsonii ICE_NC gene for the 12α-HSDH enzyme, whose activity was confirmed at the biochemical level.

Significance and impact or the study

At present, this is the first report on the characterization of a 12α-HSDH gene in an A. johnsonii strain able to biotransform cholic acid into ursodeoxycholic acid, a promising therapeutic agent for several diseases.
A mobile game‐based app to facilitate learners' motivation and achievement in learning Chinese reading activities: An individual differences perspective
Authors: Yang Jie Chi , Kuo Wen‐Chi
Published: June 2022

Background

Digital game‐based learning (DGBL) has been shown to be an effective strategy for promoting learning motivation. However, a lack of attention has been paid to investigating the effects of individual differences on elementary students' reading motivation and in‐gaming achievements in DGBL.

Objectives

This study developed an educational mobile game to facilitate learners' reading activities, and investigated how prior knowledge and gaming experience affected learners' reading motivation, gaming motivation, perceptions and in‐game achievements.

Methods

A total of 53 third to fifth grade elementary school students participated in this study, and were divided into the high prior knowledge (HPK)/low prior knowledge (LPK) and the high gaming experience (HGE)/low gaming experience (LGE) groups.

Results and Conclusions

The HPK learners had higher reading motivation, perceptions, gaming and social achievements than the LPK learners, whereas they had similar gaming motivation and reading achievements. In addition, the HGE learners had lower reading motivation, reading and gaming achievements than the LGE learners, whereas they had similar gaming motivation, perceptions and social achievements. Moreover, correlational results showed that similarities and differences were observed between the HPK/LPK and HGE/LGE learners.

Implications

The findings of this study suggest that learners' prior knowledge and gaming experience play influential roles in reading motivation, gaming motivation, perceptions and in‐game achievements. A framework is proposed for researchers or game designers to develop personalized DGBL systems to accommodate the HPK/LPK and HGE/LGE learners' individual needs or preferences in DGBL.
Identifying and treating resistant hypertension in PRECISION: A randomized long‐term clinical trial with aprocitentan
Authors: Danaietash Parisa , Verweij Pierre , Wang Ji‐Guang , Dresser George , Kantola Ilkka , Lawrence Mary Katherine , Narkiewicz Krzysztof , Schlaich Markus , Bellet Marc ,   the PRECISION investigators
Published: June 2022

The design and baseline data of the PRECISION study, which evaluates the effect of the dual endothelin receptor antagonist aprocitentan on blood pressure (BP) in patients with resistant hypertension (RHT) are presented. The study is a blinded, randomized, parallel‐group Phase 3 study and its three‐part design assesses the short‐term and sustained long‐term effects of aprocitentan on BP. Results are expected in 2022.

Patients with uncontrolled BP (measured as unattended automated office BP) despite the use of three or more antihypertensive medications for at least 1 year were screened. They were switched to a single‐tablet triple fixed combination antihypertensive therapy for at least 4 weeks before entering a single‐blind placebo run‐in period. The 4‐week placebo run‐in period further excluded placebo responders. The randomization period consisted of three sequential parts: (1) a 4‐week double‐blind part with aprocitentan 12.5 mg, 25 mg, or placebo (1:1:1 ratio); (2) a 32‐week single‐blind part with aprocitentan 25 mg; and (3) a 12‐week randomized withdrawal part with aprocitentan 25 mg or placebo (1:1 ratio). The purpose was to demonstrate the BP lowering effect of aprocitentan in RHT (Part 1) and the persistence of this effect (Parts 2 and 3).

Out of 1965 screened patients, 730 were randomized resulting in an overall inclusion failure rate of 62.8%. The most common reason for exclusion (44.4% of all screened patients) was failure to meet the BP inclusion criteria. These results underline the high proportion of pseudoresistant hypertension among patients referred for RHT.
Characterization of early phases of cardiomyopathy syndrome pathogenesis in Atlantic salmon (Salmo salar L.) through various diagnostic methods
Authors: Fritsvold Camilla , Mikalsen Aase B. , Haugland Øyvind , Tartor Haitham , Sindre Hilde
Published: June 2022

Since the first description of cardiomyopathy syndrome (CMS) in Atlantic salmon, in 1985, the disease caused by piscine myocarditisvirus (PMCV) has become a common problem in Atlantic salmon farming, not only in Norway, but also in other salmon farming countries like Scotland and Ireland. In the last years, CMS has been ranked as the most important salmon viral disease in Norway regarding both mortality and economic losses. Detailed knowledge of infection and pathogenesis is still lacking, a decade after the causal agent was first described, and there is a need for a wider range of methods/tools for diagnostic and research purposes. In this study, we compared the detection of PMCV‐ and CMS‐related tissue lesions using previously used and well‐known methods like histopathology and real‐time RT‐PCR to immunohistochemistry (IHC), a less used method, and a new method, RNAscope in situ hybridization. Tissue samples of three different cardiac compartments, mid‐kidney and skin/muscle tissue were compared with non‐lethal parallel samplings of blood and mucus. The development of pathological cardiac lesions observed in this experiment was in accordance with previous descriptions of CMS. Our results indicate a viremic phase 10‐ to 20‐day post‐challenge (dpc) preceding the cardiac lesions. In this early phase, virus could also be detected in relatively high amount in mid‐kidney by real‐time RT‐PCR. Plasma and/or mid‐kidney samples may, therefore, be candidates to screen for early‐phase PMCV infection. The RNAscope in situ hybridization method showed higher sensitivity and robustness compared with the immunohistochemistry and may be a valuable support to histopathology in CMS diagnostics, especially in cases of untypical lesions or mixed infections.
Translational control by ketamine and its implications for comorbid cognitive deficits in depressive disorders
Authors: Lewis Vern , Rodrigue Brandon , Arsenault Emily , Zhang Molly , Taghavi‐Abkuh Fatimeh‐Frouh , Silva Weverton Castro Coelho , Myers Mysa , Matta‐Camacho Edna , Aguilar‐Valles Argel
Published: June 2022

Ketamine has shown antidepressant effects in patients with major depressive disorder (MDD) resistant to first‐line treatments and approved for use in this patient population. Ketamine induces several forms of synaptic plasticity, which are proposed to underlie its antidepressant effects. However, the molecular mechanism of action directly responsible for ketamine's antidepressant effects remains under active investigation. It was recently demonstrated that the effectors of the mammalian target of rapamycin complex 1 (mTORC1) signalling pathway, namely, eukaryotic initiation factor 4E (eIF4E) binding proteins 1 and 2 (4E‐BP1 and 4E‐BP2), are central in mediating ketamine‐induced synaptic plasticity and behavioural antidepressant‐like effect. 4E‐BPs are a family of messenger ribonucleic acid (mRNA) translation repressors inactivated by mTORC1. We observed that their expression in inhibitory interneurons mediates ketamine's effects in the forced swim and novelty suppressed feeding tests and the long‐lasting inhibition of GABAergic neurotransmission in the hippocampus. In addition, another effector pathway that regulates translation elongation downstream of mTORC1, the eukaryotic elongation factor 2 kinase (eEF2K), has been implicated in ketamine's behavioural effects. We will discuss how ketamine's rapid antidepressant effect depends on the activation of neuronal mRNA translation through 4E‐BP1/2 and eEF2K. Furthermore, given that these pathways also regulate cognitive functions, we will discuss the evidence of ketamine's effect on cognitive function in MDD. Overall, the data accrued from pre‐clinical research have implicated the mRNA translation pathways in treating mood symptoms of MDD. However, it is yet unclear whether the pro‐cognitive potential of subanesthetic ketamine in rodents also engages these pathways and whether such an effect is consistently observed in the treatment‐resistant MDD population.

image
Ovary structure and symbiotic associates of a ground mealybug, Rhizoecus albidus (Hemiptera, Coccomorpha: Rhizoecidae) and their phylogenetic implications
Authors: Szklarzewicz Teresa , Kalandyk‐Kołodziejczyk Małgorzata , Michalik Anna
Published: June 2022

The ovary structure and the organization of its symbiotic system of the ground mealybug, Rhizoecus albidus (Rhizoecidae), were examined by means of microscopic and molecular methods. Each of the paired elongated ovaries of R. albidus is composed of circa one hundred short telotrophic‐meroistic ovarioles, which are radially arranged along the distal part of the lateral oviduct. Analysis of serial sections revealed that each ovariole contains four germ cells: three trophocytes (nurse cells) occupying the tropharium and a single oocyte in the vitellarium. The ovaries are accompanied by giant cells termed bacteriocytes which are tightly packed with large pleomorphic bacteria. Their identity as Brownia rhizoecola (Bacteroidetes) was confirmed by means of amplicon sequencing and fluorescence in situ hybridization techniques. Moreover, to our knowledge, this is the first report on the morphology and ultrastructure of the Brownia rhizoecola bacterium. In the bacteriocyte cytoplasm bacteria Brownia co‐reside with sporadic rod‐shaped smaller bacteria, namely Wolbachia (Proteobacteria: Alphaproteobacteria). Both symbionts are transmitted to the next generation vertically (maternally), that is, via female germline cells. We documented that, at the time when ovarioles contain oocytes at the vitellogenic stage, these symbionts leave the bacteriocytes and move toward the neck region of ovarioles (i.e. the region between tropharium and vitellarium). Next, the bacteria enter the cytoplasm of follicular cells surrounding the basal part of the tropharium, leave them and enter the space between the follicular epithelium and surface of the nutritive cord connecting the tropharium and vitellarium. Finally, they gather in the deep depression of the oolemma at the anterior pole of the oocyte in the form of a ‘symbiont ball’. Our results provide further arguments strongly supporting the validity of the recent changes in the classification of mealybugs, which involved excluding ground mealybugs from the Pseudococcidae family and raising them to the rank of their own family Rhizoecidae.
Analysis of vanishing endometrial cancer by pathological types
Authors: Görgülü Gökşen , Doğan Özdaş Emel , Özdaş Erol , Sayhan Sevil , Kuru Oğuzhan , Gökçü Mehmet , Sancı Muzaffer
Published: June 2022

Purpose

We asked why endometrial cancer sometimes vanishes.

Methods

A total of 454 patients diagnosed with endometrioid‐type endometrial cancer (EC) (via endometrial sampling) and treated in our clinic over the past 5 years were enrolled. The patients were divided into two groups: vanishing and residual, depending on whether a tumor was detected in the postoperative hysterectomy specimen. Patient age, numbers of pregnancies and deliveries, menopausal status, systemic disease status, hemogram parameters, International Federation of Gynecology and Obstetrics (FIGO) grade, and invasion status (evident on magnetic resonance imaging [MRI]) were compared between the groups.

Results

ECs vanished in 42 (9.25%) patients. The vanishing rates were 19.7% (37/187) in FIGO grade 1 patients, 2.1% (5/238) in grade 2 patients, and 0% (0/29) in grade 3 patients. The average age was lower in the vanishing than the residual group, but the premenopausal status and grade 1 tumor rates were higher (both p < 0.001). An absence of invasion (as revealed by MRI) was more common in the vanishing group (p < 0.001). No recurrence developed in the vanishing group, but recurrences were noted in 3.3% (14/412) of the residual group. There were no significant between‐group differences in any of the numbers of pregnancies or births, systemic disease status, or hemogram parameters (all p > 0.05).

Conclusion

Vanishing EC is more likely in premenopausal women with endometrioid grade 1 EC (as revealed by endometrial biopsy) who lack myometrial invasion on MRI.
Physical, Mechanical, and Anti‐Biofilm Formation Properties of CAD‐CAM Milled or 3D Printed Denture Base Resins: In Vitro Analysis
Authors: Freitas Rodrigo Falcão Carvalho Porto de , Duarte Simone , Feitosa Sabrina , Dutra Vinicius , Lin Wei‐Shao , Panariello Beatriz Helena Dias , Carreiro Adriana da Fonte Porto
Published: June 2022

Purpose

To investigate surface characteristics (roughness and contact angle), anti‐biofilm formation, and mechanical properties (mini‐flexural strength) of computer‐aided design and computer‐aided manufacturing (CAD‐CAM) polymethylmethacrylate (PMMA) polymer, and three‐dimensional (3D) printed resin for denture base fabrication compared with conventional heat polymerized denture base resins.

Materials and methods

A total of 60 discs and 40 rectangular specimens were fabricated from one CAD‐CAM (AvaDent), one 3D printed (Cosmos Denture), and two conventional heat polymerized (Lucitone 199 and VipiWave) materials for denture base fabrication. Roughness was determined by Ra value; the contact angle was measured by the sessile drop method. The biofilm formation inhibition behavior was analyzed through Candida albicans adhesion, while mini‐flexural strength test was done using a three‐point bending test. The data were analyzed using descriptive and analytical statistics (α = 0.05).

Results

The CAD‐CAM PMMA group showed the lowest C. albicans adhesion (log CFU/mL: 3.74 ± 0.57) and highest mini‐flexural strength mean (114.96 ± 16.23 MPa). 3D printed specimens presented the highest surface roughness (Ra: 0.317 ± 0.151 μm) and lowest mini‐flexural strength values (57.23 ± 9.07 MPa). However, there was no statistical difference between CAD‐CAM PMMA and conventional groups for roughness, contact angle, and mini‐flexural strength.

Conclusions

CAD‐CAM milled materials present surface and mechanical properties similar to conventional resins and show improved behavior in preventing C. albicans adhesion. Nevertheless, 3D printed resins present decreased mini‐flexural strength.
Testing Australian standard consumers' understanding of the language used to describe wine
Authors: Bianchi Ivana , Truong Hang , Russell Alex M. T. , Burro Roberto
Published: June 2022

With reference to 64 common descriptors of the sensory properties of wine (e.g., tannic, full‐bodied, etc.), we investigated the extent to which these terms are understood by Australian standard consumers in relation to an opposite property (i.e., as happens in the case of experts). The study also determined how consistently these dimensions were among the group of participants. The results confirmed that the sensorial dimensions relating to wine can be modeled in terms of opposites for standard wine consumers in more than 80% of cases. However, there was a great deal of variability between the properties in terms of the opposites which were elicited indicating that some terms are less open to ambiguity while others are associated with many different opposites. A comparison of the results with those from similar studies with Italian and Vietnamese participants is addressed in the final section.

Practical Applications

The aim of the study was to replicate previous research conducted with Italian participants, but in this case involving Australian participants, with a view to compare participants from a traditional wine‐producing country with those from a relatively newly established wine‐producing country. A similar study had already been carried out with Vietnamese participants, that is, with consumers from a country with less familiarity with grape wines. The importance of this study rests on the fact that English is one of the most commonly spoken languages in the world and, as such, the study represents a relevant evolution of the original research.

Opposites seem to be a useful point of reference for standard consumers in all of these countries in terms of their understanding of the terms used to describe wine. This and the fact that there seems to be a certain degree of uncertainty regarding people's understanding of many of these terms indicate that it may be necessary to reconceptualize the sensory dimensions relating to wine. From a practical point of view, this is certainly of interest to wine producers since it can help in the marketing of their products.