bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular targets and the use of biologics in the management of small bowel fibrosis in inflammatory bowel disease
Authors: Abdulla Muaad , Chew Thean Soon
Published: March 2021

Purpose of review

Small bowel fibrosis is a significant burden on Crohn's disease patients with limited effective medical treatments that then requires surgery. A better understanding of the molecular mechanisms causing fibrosis and the evidence of benefit of available biologics will potentially lighten this burden and avoid the need for surgery.

Recent findings

Transforming growth factor-beta and it's associated pathways remain the central cog in the wheel of fibrosis formation. Various new enzymes, cellular pathways, interleukins and molecules have been associated with beneficial modification of the fibrotic process. Licensed biologics such as antitumour necrosis factors continue to show evidence of efficacy in the treatment of fibrostenotic small bowel disease as well as the newer biologics ustekinumab and vedolizumab.

Fibrostenotic disease of the small bowel is a significant and common debilitating complication in Crohn's disease patients. Multiple new molecular targets have been identified that may prove to become effective therapies in future. Antitumour necrosis factors remain the treatment with the best available evidence to date in fibrostenotic Crohn's disease.
Characteristics of Injuries Sustained Under the Influence of Alcohol in a Group of Adolescents
Authors: Milczarek Olga , Kuzaj Julia , Stanuszek Agnieszka , Kwiatkowska Karolina , Brzewski Paweł , Kwiatkowski Stanisław
Published: March 2021

Objectives

Fractures of the limbs and craniocerebral trauma are the most common injuries in children and adolescents. Their frequency ranges widely from 32% to 85% and is the main reason for hospitalization in pediatric population. The number of injuries sustained under the influence of alcohol is increasing although the data concerning that subject is limited and usually includes both adult and teenage patients.

Methods

A group of 111 adolescents (age, 9–18 years), hospitalized after traumatic brain injury with and without alcohol intoxication, was included in the study. We performed the assessment of the severity of the course of the multiorgan and craniocerebral injuries. The study was accepted by the Ethics Committee of the Jagiellonian University Medical College (no: KBET/8/B/2010).

Results

The injuries of upper limbs and head and their serious consequences were observed more often in the examined group. The differences of the degree of head and neck injuries measured in the Injury Severity Score between the groups were statistically significant, although the injuries within the examined group were less often serious. There was a negative correlation between the patients' condition according to the Glasgow Coma Scale and the concentration of alcohol in their blood. No link between the patients' assessment in the Injury Severity Score and concentration of alcohol in the blood was noticed.

Conclusions

Traumatic brain injury under the influence of alcohol in adolescents differs from trauma in patients who had not drunk alcohol. Similar areas of injury result in a more severe course of illness in the examined group.
Factors Contributing to Nonvisualization of the Appendix on Ultrasound in Children With Suspected Appendicitis
Authors: Harel Svetlana , Mallon Mary , Langston Jessica , Blutstein Rebekah , Kassutto Zach , Gaughan John
Published: March 2021

Objective

This study aimed to identify the patient characteristics, history factors, physical examination findings, and sonographic findings, which contribute to a higher risk of the appendix not being visualized on ultrasound evaluation (ie, nondiagnostic or equivocal study) in patients being evaluated for appendicitis. Secondarily, this study assessed the utility of an equivocal ultrasound, specifically in the ability to predict the absence of appendicitis.

Methods

A retrospective case review was performed, of children (age, 0–18 years) presenting to a pediatric emergency department with clinical suspicion for appendicitis, who underwent sonographic studies during the 12-month study period.

Results

Five hundred forty-three cases were reviewed, of which 75 (14%) were diagnosed with appendicitis. The sensitivity of ultrasound diagnosis of appendicitis was 62.7% and specificity was 79.1%. The appendix was not visualized in 398 (73%) cases. Of the cases where the appendix was not visualized, 370 did not have appendicitis (negative predictive value, 93%). In cases where the appendix was not visualized and the white blood cell count was less than 10,000, the negative predictive value rose to 97%. The patient's age (odds ratio [OR], 1.049), weight (OR, 1.015), presence of appendicolith (OR, 0.426), presence of right lower quadrant fat stranding on sonography (OR, 0.081), and presence of hyperemia on sonography (OR, 0.094) were found to be significant in affecting the visualization of the appendix on ultrasound.

Conclusions

Increasing patient's age and weight leads to increased likelihood that the appendix will not be visualized on ultrasound, whereas the presence of an appendicolith, right lower quadrant fat stranding or hyperemia will increase the likelihood of visualization. The sensitivity and specificity of ultrasound for the diagnosis of appendicitis are moderate but the negative predictive value of an equivocal study is high. Clinicians can use supporting clinical examination and laboratory findings, in conjunction with a nondiagnostic ultrasound evaluation of the appendix to exclude the diagnosis of appendicitis, without the need for further imaging.
Assessing the Potential Impact of Disruptions Due to COVID-19 on HIV Among Key and Lower-Risk Populations in the Largest Cities of Cameroon and Benin
Authors: Silhol Romain , Geidelberg Lily , Mitchell Kate M. , Mishra Sharmistha , Dimitrov Dobromir , Bowring Anna , Béhanzin Luc , Guédou Fernand , Diabaté Souleymane , Schwartz Sheree , Billong Serge C. , Njindam Iliassou Mfochive , Levitt Daniel , Mukandavire Christinah , Maheu-Giroux Mathieu , Rönn Minttu M. , Dalal Shona , Vickerman Peter , Baral Stefan , Alary Michel , Boily Marie-Claude
Published: March 2021

Background:

The COVID-19 pandemic indirectly impacts HIV epidemiology in Central/West Africa. We estimated the potential impact of COVID–19-related disruptions to HIV prevention/treatment services and sexual partnerships on HIV incidence and HIV-related deaths among key populations including female sex workers (FSW), their clients, men who have sex with men, and overall.

Setting:

Yaoundé (Cameroon) and Cotonou (Benin).

Methods:

We used mathematical models of HIV calibrated to city population–specific and risk population–specific demographic/behavioral/epidemic data. We estimated the relative change in 1-year HIV incidence and HIV-related deaths for various disruption scenarios of HIV prevention/treatment services and decreased casual/commercial partnerships, compared with a scenario without COVID-19.

Results:

A 50% reduction in condom use in all partnerships over 6 months would increase 1-year HIV incidence by 39%, 42%, 31%, and 23% among men who have sex with men, FSW, clients, and overall in Yaoundé, respectively, and 69%, 49%, and 23% among FSW, clients, and overall, respectively, in Cotonou. Combining a 6-month interruption of ART initiation and 50% reduction in HIV prevention/treatment use would increase HIV incidence by 50% and HIV-related deaths by 20%. This increase in HIV infections would be halved by a simultaneous 50% reduction in casual and commercial partnerships.

Conclusions:

Reductions in condom use after COVID-19 would increase infections among key populations disproportionately, particularly FSW in Cotonou, who need uninterrupted condom provision. Disruptions in HIV prevention/treatment services have the biggest impacts on HIV infections and deaths overall, only partially mitigated by equal reductions in casual/commercial sexual partnerships. Maintaining ART provision must be prioritized to minimize short-term excess HIV-related deaths.
Anthropometrical Analysis of the Foramen Magnum in Ancient Children
Authors: Li Haijun , Chen Huimin , Duan Wanqi , Yang Shangbing , Xiao Xiaoyong , Wang Bo
Published: March 2021

Anthropometrical analysis of the foramen magnum (FM) was conducted on a sample of 32 children and 101 adults excavated from Zaghunluq cemetery dating between 2600 and 1900 cal. yr BP in Xinjiang, China. The FM features of children during age changes and growth spurt periods were explored by comparing the length of the FM, the width of the FM, and the values of the FM index among different age groups. The data presented in this study indicate that the size of the FM was smallest at 2 years old, and the FM size during 5 to 7 years of age was close to that of adults, supporting the view that the size of the 6-year-old skull is close to that of the adult and brain growth appears to terminate at 7 years. The FM likely experiences a growth spurt period during 2 to 5 years of age. Regression equations were established by regression analysis of the length and width of the FM. Study on the morphological variation of the FM provides further information about the growth of children.
Scalp Reconstruction in Delayed Diagnosed Dermal Leiomyosarcoma Mimicking Keloid Scar
Authors: Hwang Yong-Jae , Chung Jae-Ho , Yoon Eul-Sik
Published: March 2021

Leiomyosarcoma (LMS) of the skin is a rare smooth muscle neoplasm of all soft tissue sarcoma. Because of its prognostic importance, early diagnosis is critical for successful treatment. Since several features and clinical manifestations are similar to those of a keloid scar, the differential diagnosis between these two diseases is difficult, especially in the early stages of cancer that do not show any remarkable features in appearance, or when the patient has a history of previous wounds or surgery.

In our case report, a 71-year-old female patient who underwent a scalp reconstruction using an anterolateral thigh flap turned out to have, because of delayed diagnosis, a dermal LMS mimicking a keloid scar. The case emphasizes careful physical examination for early intervention, even if a lesion looks like a typical keloid scar. After resection, the appropriate reconstruction method can be selected based on the complexity of the defect site.
Long-term Efficacy and Safety of Everolimus Versus Mycophenolate in Kidney Transplant Recipients Receiving Tacrolimus
Authors: Nunes Ficher Klaus , Dreige Yasmin , Gessolo Lins Paulo Ricardo , Nicolau Ferreira Alexandra , Toniato de Rezende Freschi Juliana , Linhares Kamilla , Stopa Martins Suelen , Custodio Luciana , Cristelli Marina , Viana Laila , Wagner Santos Daniel , de Marco Renato , Gerbase-DeLima Maria , Proença Henrique , Aguiar Wilson , Nakamura Monica , Rosso Felipe Claudia , Medina Pestana Jose , Tedesco Silva Helio
Published: March 2021

Background.

The short-term efficacy and safety of everolimus in combination with tacrolimus have been described in several clinical trials. Yet, detailed long-term data comparing the use of everolimus or mycophenolate in kidney transplant recipients receiving tacrolimus are lacking.

Methods.

This is a 5-y follow-up post hoc analysis of a prospective trial including 288 patients who were randomized to receive a single 3-mg/kg dose of rabbit antithymocyte globulin, tacrolimus, everolimus (EVR), and prednisone (rabbit antithymocyte globulin/EVR, n = 85); basiliximab, tacrolimus, everolimus, and prednisone (basiliximab/EVR, n = 102); or basiliximab, tacrolimus, mycophenolate, and prednisone (basiliximab/mycophenolate, n = 101).

Results.

There were no differences in the incidence of treatment failure (31.8% versus 40.2% versus 34.7%, P = 0.468), de novo donor-specific HLA antibodies (6.5% versus 11.7% versus 4.0%, P = 0.185), patient (92.9% versus 94.1% versus 92.1%, P = 0.854), and death-censored graft (87.1% versus 90.2% versus 85.1%, P = 0.498) survivals. Using a sensitive analysis, the trajectories of estimated glomerular filtration rate were comparable in the intention-to-treat (P = 0.145) and per protocol (P = 0.354) populations. There were no differences in study drug discontinuation rate (22.4% versus 30.4% versus 17.8%, P = 0.103).

Conclusions.

In summary, this analysis in a cohort of de novo low/moderate immunologic risk kidney transplant recipients suggests that the use of a single 3 mg/kg rabbit antithymocyte globulin dose followed by EVR combined with reduced tacrolimus concentrations was associated with similar efficacy and renal function compared with the standard of care immunosuppressive regimen.
Perceived gaze direction affects concreteness effects in words memory: an event-related potentials study
Authors: Zhao Chenyuan , Chen Yun , Jia Xi , Guo Chunyan , Liu Rong
Published: March 2021

Previous studies have revealed that word concreteness effects could be influenced by contextual cues such as emotional context. However, it is unclear whether concreteness effects might be influenced by social context such as perception of gaze direction, which plays an important role in social interaction. This study uses event-related potentials (ERPs) to investigate whether perceived gaze direction could affect concreteness effects in words memory. Concrete and abstract words were presented on direct- or averted-gaze faces, and participants were asked to memorize the words. Behavioral results verified the direct-gaze memory advantage, showing that memory performance was better for words presented with direct gaze than with averted gaze. ERP results showed that concrete words were associated with a larger N400 and a smaller late positive component (LPC) than abstract words. ERP results also revealed a significant interaction between gaze direction and word concreteness on the LPC component: specifically, the LPC concreteness effect occurred only in the direct-gaze condition. Our results suggested that the gaze direction could be interpreted as a complex social context that differs from pure emotional cues in its influence on mental imagery in concreteness effects. This study provides a new perspective for investigating word concreteness effects with contextual cues.
Palmitoylation of Hedgehog proteins by Hedgehog acyltransferase: roles in signalling and disease
Authors: Resh Marilyn D.
Published: March 2021

Hedgehog acyltransferase (Hhat), a member of the membrane-bound
O
-acyltransferase (MBOAT) family, catalyses the covalent attachment of palmitate to the N-terminus of Hedgehog proteins. Palmitoylation is a post-translational modification essential for Hedgehog signalling. This review explores the mechanisms involved in Hhat acyltransferase enzymatic activity, similarities and differences between Hhat and other MBOAT enzymes, and the role of palmitoylation in Hedgehog signalling.
In vitro
and cell-based assays for Hhat activity have been developed, and residues within Hhat and Hedgehog essential for palmitoylation have been identified. In cells, Hhat promotes the transfer of palmitoyl-CoA from the cytoplasmic to the luminal side of the endoplasmic reticulum membrane, where Shh palmitoylation occurs. Palmitoylation is required for efficient delivery of secreted Hedgehog to its receptor Patched1, as well as for the deactivation of Patched1, which initiates the downstream Hedgehog signalling pathway. While Hhat loss is lethal during embryogenesis, mutations in Hhat have been linked to disease states or abnormalities in mice and humans. In adults, aberrant re-expression of Hedgehog ligands promotes tumorigenesis in an Hhat-dependent manner in a variety of different cancers, including pancreatic, breast and lung. Targeting hedgehog palmitoylation by inhibition of Hhat is thus a promising, potential intervention in human disease.
Is there evidence for cross-domain congruency sequence effect? A replication of Kan
et al
. (2013)
Authors: Aczel Balazs , Kovacs Marton , Bognar Miklos , Palfi Bence , Hartanto Andree , Onie Sandersan , Tiong Lucas E. , Evans Thomas Rhys
Published: March 2021

Exploring the mechanisms of cognitive control is central to understanding how we control our behaviour. These mechanisms can be studied in conflict paradigms, which require the inhibition of irrelevant responses to perform the task. It has been suggested that in these tasks, the detection of conflict enhances cognitive control resulting in improved conflict resolution of subsequent trials. If this is the case, then this so-called congruency sequence effect can be expected to occur in cross-domain tasks. Previous research on the domain-generality of the effect presented inconsistent results. In this study, we provide a multi-site replication of three previous experiments of Kan
et al
. (Kan IP, Teubner-Rhodes S, Drummey AB, Nutile L, Krupa L, Novick JM 2013
Cognition
129
, 637–651) which test congruency sequence effect between very different domains: from a syntactic to a non-syntactic domain (Experiment 1), and from a perceptual to a verbal domain (Experiments 2 and 3). Despite all our efforts, we found only partial support for the claims of the original study. With a single exception, we could not replicate the original findings; the data remained inconclusive or went against the theoretical hypothesis. We discuss the compatibility of the results with alternative theoretical frameworks.
A comparative test of the gamete dynamics theory for the evolution of anisogamy in Bryopsidales green algae
Authors: Togashi Tatsuya , Horinouchi Yusuke , Parker Geoff A.
Published: March 2021

Gamete dynamics theory proposes that anisogamy arises by disruptive selection for gamete numbers versus gamete size and predicts that female/male gamete size (anisogamy ratio) increases with adult size and complexity. Evidence has been that in volvocine green algae, the anisogamy ratio correlates positively with haploid colony size. However, green algae show notable exceptions. We focus on Bryopsidales green algae. While some taxa have a diplontic life cycle in which a diploid adult (=fully grown) stage arises directly from the zygote, many taxa have a haplodiplontic life cycle in which haploid adults develop indirectly: the zygote first develops into a diploid adult (sporophyte) which later undergoes meiosis and releases zoospores, each growing into a haploid adult gametophyte. Our comparative analyses suggest that, as theory predicts: (i) male gametes are minimized, (ii) female gamete sizes vary, probably optimized by number versus survival as zygotes, and (iii) the anisogamy ratio correlates positively with diploid (but not haploid) stage complexity. However, there was no correlation between the anisogamy ratio and diploid adult stage size. Increased environmental severity (water depth) appears to drive increased diploid adult stage complexity and anisogamy ratio: gamete dynamics theory correctly predicts that anisogamy evolves with the (diploid) stage directly provisioned by the zygote.
Generative models of network dynamics provide insight into the effects of trade on endemic livestock disease
Authors: Knight Martin A. , White Piran C. L. , Hutchings Michael R. , Davidson Ross S. , Marion Glenn
Published: March 2021

We develop and apply analytically tractable generative models of livestock movements at national scale. These go beyond current models through mechanistic modelling of heterogeneous trade partnership network dynamics and the trade events that occur on them. Linking resulting animal movements to disease transmission between farms yields analytical expressions for the basic reproduction number
R
0
. We show how these novel modelling tools enable systems approaches to disease control, using
R
0
to explore impacts of changes in trading practices on between-farm prevalence levels. Using the Scottish cattle trade network as a case study, we show our approach captures critical complexities of real-world trade networks at the national scale for a broad range of endemic diseases. Changes in trading patterns that minimize disruption to business by maintaining in-flow of animals for each individual farm reduce
R
0
, with the largest reductions for diseases that are most challenging to eradicate. Incentivizing high-risk farms to adopt such changes exploits ‘scale-free’ properties of the system and is likely to be particularly effective in reducing national livestock disease burden and incursion risk. Encouragingly, gains made by such targeted modification of trade practices scale much more favourably than comparably targeted improvements to more commonly adopted farm-level biosecurity.
Leaky barriers: leaky enough for fish to pass?
Authors: Müller Stephanie , Wilson Catherine A. M. E. , Ouro Pablo , Cable Joanne
Published: March 2021

Perceived as environmental-friendly hydraulic structures, leaky barriers used for natural flood management are introduced into rivers, potentially creating migration barriers for fish. Using sustainable, local materials to construct wooden barriers across river channels in upper catchments, these barriers aim to slow down the flow, reduce flood peaks and attenuate the flow reaching downstream communities. Yet little is known about their impact on hydrodynamics and fish passage. Here, we examined two model barrier designs under 100% and 80% bankfull flow conditions in an open channel flume. These barriers included a porous and a non-porous design, with the latter emulating the natural accumulation of brush, sediment and leaf material between logs over time. Flow visualization and velocity measurements recorded with acoustic Doppler velocimetry characterized the flow field upstream and downstream of the barriers. Our fish behavioural studies revealed that juvenile salmon (
Salmo salar
) movement between downstream and upstream sections of the flume was inhibited by barrier design rather than discharge, influencing upstream fish passage and their spatial preference, indicating the importance of barrier design criteria to facilitate fish movement.
Ecomorphological diversification of squamates in the Cretaceous
Authors: Herrera-Flores Jorge A. , Stubbs Thomas L. , Benton Michael J.
Published: March 2021

Squamates (lizards and snakes) are highly successful modern vertebrates, with over 10 000 species. Squamates have a long history, dating back to at least 240 million years ago (Ma), and showing increasing species richness in the Late Cretaceous (84 Ma) and Early Palaeogene (66–55 Ma). We confirm that the major expansion of dietary functional morphology happened before these diversifications, in the mid-Cretaceous, 110–90 Ma. Until that time, squamates had relatively uniform tooth types, which then diversified substantially and ecomorphospace expanded to modern levels. This coincides with the Cretaceous Terrestrial Revolution, when angiosperms began to take over terrestrial ecosystems, providing new roles for plant-eating and pollinating insects, which were, in turn, new sources of food for herbivorous and insectivorous squamates. There was also an early Late Cretaceous (95–90 Ma) rise in jaw size disparity, driven by the diversification of marine squamates, particularly early mosasaurs. These events established modern levels of squamate feeding ecomorphology before the major steps in species diversification, confirming decoupling of diversity and disparity. In fact, squamate feeding ecomorphospace had been partially explored in the Late Jurassic and Early Cretaceous, and jaw innovation in Late Cretaceous squamates involved expansions at the extremes of morphospace.
Rapid characterization of hypanthium and seed in wild and cultivated rosehip: application of Raman microscopy combined with multivariate analysis
Authors: Pećinar Ilinka , Krstić Djurdja , Caruso Gianluca , Popović-Djordjević Jelena B.
Published: March 2021

Rosehip (pseudo-fruit) of dog rose (
Rosa canina
L.) is highly valued, and owing to nutritional and sensory properties it has a significant place in the food industry. This work represents an innovative report focusing on the evaluation of the phytochemical composition of rosehips (hypanthium and seed) grown in different locations in Serbia, using Raman microspectroscopy combined with multivariate data analysis. Some significant differences arose between the analysed rosehip samples with regard to the chemical profile of both hypanthium parenchyma cells and seed, although no evident discrimination was recorded between the samples of wild and cultivated rosehip. The differences between the hypanthium samples compared were mainly determined by the content of carotenoids, phenolic compounds and polysaccharides, whereas phenolics, polysaccharides (pectin, cellulose and hemicellulose) and lipids (to a lower extent) contributed to the seed sample discrimination. The differences observed between the rosehip samples may be attributed to abiotic factors (growing, ripening and storage conditions), which had a significant impact on the carotenoid and polyphenols biosynthesis.
Negative-tone molecular glass photoresist for high-resolution electron beam lithography
Authors: Wang Yafei , Chen Long , Yu Jiating , Guo Xudong , Wang Shuangqing , Yang Guoqiang
Published: March 2021

A low molecular weight organic compound containing bis-phenol A backbone (BPA-6OH) is reported as a negative-tone photoresist. This material has a high glass transition temperature and excellent thermal stability. A good contrast, well-resolved line pattern around 73.4 nm and sensitivity of 52 µC cm−2can be received for negative-tone molecular glass photoresist upon exposure in electron beam lithography system. It indicates that the negative-tone molecular glass photoresist is one of the promising candidates for use in electron beam lithography.
Marine iodine emissions in a changing world
Authors: Carpenter Lucy J. , Chance Rosie J. , Sherwen Tomás , Adams Thomas J. , Ball Stephen M. , Evans Mat J. , Hepach Helmke , Hollis Lloyd D. J. , Hughes Claire , Jickells Timothy D. , Mahajan Anoop , Stevens David P. , Tinel Liselotte , Wadley Martin R.
Published: March 2021

Iodine is a critical trace element involved in many diverse and important processes in the Earth system. The importance of iodine for human health has been known for over a century, with low iodine in the diet being linked to goitre, cretinism and neonatal death. Research over the last few decades has shown that iodine has significant impacts on tropospheric photochemistry, ultimately impacting climate by reducing the radiative forcing of ozone (O3) and air quality by reducing extreme O3concentrations in polluted regions. Iodine is naturally present in the ocean, predominantly as aqueous iodide and iodate. The rapid reaction of sea-surface iodide with O3is believed to be the largest single source of gaseous iodine to the atmosphere. Due to increased anthropogenic O3, this release of iodine is believed to have increased dramatically over the twentieth century, by as much as a factor of 3. Uncertainties in the marine iodine distribution and global cycle are, however, major constraints in the effective prediction of how the emissions of iodine and its biogeochemical cycle may change in the future or have changed in the past. Here, we present a synthesis of recent results by our team and others which bring a fresh perspective to understanding the global iodine biogeochemical cycle. In particular, we suggest that future climate-induced oceanographic changes could result in a significant change in aqueous iodide concentrations in the surface ocean, with implications for atmospheric air quality and climate.
Ocean acidification effects on fish hearing
Authors: Radford C. A. , Collins S. P. , Munday P. L. , Parsons D.
Published: March 2021

Humans are rapidly changing the marine environment through a multitude of effects, including increased greenhouse gas emissions resulting in warmer and acidified oceans. Elevated CO
2
conditions can cause sensory deficits and altered behaviours in marine organisms, either directly by affecting end organ sensitivity or due to likely alterations in brain chemistry. Previous studies show that auditory-associated behaviours of larval and juvenile fishes can be affected by elevated CO
2
(1000 µatm). Here, using auditory evoked potentials (AEP) and micro-computer tomography (microCT) we show that raising juvenile snapper,
Chrysophyrs auratus
, under predicted future CO
2
conditions resulted in significant changes to their hearing ability. Specifically, snapper raised under elevated CO
2
conditions had a significant decrease in low frequency (less than 200 Hz) hearing sensitivity. MicroCT demonstrated that these elevated CO
2
snapper had sacculus otolith's that were significantly larger and had fluctuating asymmetry, which likely explains the difference in hearing sensitivity. We suggest that elevated CO
2
conditions have a dual effect on hearing, directly effecting the sensitivity of the hearing end organs and altering previously described hearing induced behaviours. This is the first time that predicted future CO
2
conditions have been empirically linked through modification of auditory anatomy to changes in fish hearing ability. Given the widespread and well-documented impact of elevated CO
2
on fish auditory anatomy, predictions of how fish life-history functions dependent on hearing may respond to climate change may need to be reassessed.
Tree species richness modulates water supply in the local tree neighbourhood: evidence from woodδ13C signatures in a large-scale forest experiment
Authors: Jansen Kirstin , von Oheimb Goddert , Bruelheide Helge , Härdtle Werner , Fichtner Andreas
Published: March 2021

Biodiversity is considered to mitigate the adverse effects of changing precipitation patterns. However, our understanding of how tree diversity at the local neighbourhood scale modulates the water use and leaf physiology of individual trees remains unclear. We made use of a large-scale tree diversity experiment in subtropical China to study eight tree species along an experimentally manipulated gradient of local neighbourhood tree species richness. Twig wood carbon isotope composition (δ13Cwood) was used as an indicator for immediate leaf-level responses to water availability in relation to local neighbourhood conditions and a target tree's functional traits. Across species, a target tree'sδ13Cwoodsignatures decreased progressively with increasing neighbourhood species richness, with effects being strongest at high neighbourhood shading intensity. Moreover, theδ13Cwood-shading relationship shifted from positive (thin-leaved species) or neutral (thick-leaved species) in conspecific to negative in heterospecific neighbourhoods, most likely owing to a lower interspecific competition for water and microclimate amelioration. This suggests that promoting tree species richness at the local neighbourhood scale may improve a tree's local water supply with potential effects for an optimized water-use efficiency of tree communities during drought. This assumption, however, requires validation by further studies that focus on mechanisms that regulate the water availability in mixtures.
Evolutionary versatility of the avian neck
Authors: Marek Ryan D. , Falkingham Peter L. , Benson Roger B. J. , Gardiner James D. , Maddox Thomas W. , Bates Karl T.
Published: March 2021

Bird necks display unparalleled levels of morphological diversity compared to other vertebrates, yet it is unclear what factors have structured this variation. Using three-dimensional geometric morphometrics and multivariate statistics, we show that the avian cervical column is a hierarchical morpho-functional appendage, with varying magnitudes of ecologically driven osteological variation at different scales of organization. Contrary to expectations given the widely varying ecological functions of necks in different species, we find that regional modularity of the avian neck is highly conserved, with an overall structural blueprint that is significantly altered only by the most mechanically demanding ecological functions. Nevertheless, the morphologies of vertebrae within subregions of the neck show more prominent signals of adaptation to ecological pressures. We also find that both neck length allometry and the nature of neck elongation in birds are different from other vertebrates. In contrast with mammals, neck length scales isometrically with head mass and, contrary to previous work, we show that neck elongation in birds is achieved predominantly by increasing vertebral lengths rather than counts. Birds therefore possess a cervical spine that may be unique in its versatility among extant vertebrates, one that, since the origin of flight, has adapted to function as a surrogate forelimb in varied ecological niches.
Cuttlefish exert self-control in a delay of gratification task
Authors: Schnell Alexandra K. , Boeckle Markus , Rivera Micaela , Clayton Nicola S. , Hanlon Roger T.
Published: March 2021

The ability to exert self-control varies within and across taxa. Some species can exert self-control for several seconds whereas others, such as large-brained vertebrates, can tolerate delays of up to several minutes. Advanced self-control has been linked to better performance in cognitive tasks and has been hypothesized to evolve in response to specific socio-ecological pressures. These pressures are difficult to uncouple because previously studied species face similar socio-ecological challenges. Here, we investigate self-control and learning performance in cuttlefish, an invertebrate that is thought to have evolved under partially different pressures to previously studied vertebrates. To test self-control, cuttlefish were presented with a delay maintenance task, which measures an individual's ability to forgo immediate gratification and sustain a delay for a better but delayed reward. Cuttlefish maintained delay durations for up to 50–130 s. To test learning performance, we used a reversal-learning task, whereby cuttlefish were required to learn to associate the reward with one of two stimuli and then subsequently learn to associate the reward with the alternative stimulus. Cuttlefish that delayed gratification for longer had better learning performance. Our results demonstrate that cuttlefish can tolerate delays to obtain food of higher quality comparable to that of some large-brained vertebrates.
The structure and diversity of strain-level variation in vaginal bacteria
Authors: Tortelli Brett A. , Lewis Amanda L. , Fay Justin C.
Published: March 2021

The vaginal microbiome plays an important role in human health and species of vaginal bacteria have been associated with reproductive disease. Strain-level variation is also thought to be important, but the diversity, structure and evolutionary history of vaginal strains is not as well characterized. We developed and validated an approach to measure strain variation from metagenomic data based on SNPs within the core genomes for six species of vaginal bacteria:

Gardnerella vaginalis

,

Lactobacillus crispatus

,

Lactobacillus iners

,

Lactobacillus jensenii

,

Lactobacillus gasseri

and

Atopobium vaginae

. Despite inhabiting the same environment, strain diversity and structure varies across species. All species except

L. iners

are characterized by multiple distinct groups of strains. Even so, strain diversity is lower in the

Lactobacillus

species, consistent with a more recent colonization of the human vaginal microbiome. Both strain diversity and the frequency of multi-strain samples is related to species-level diversity of the microbiome in which they occur, suggesting similar ecological factors influencing diversity within the vaginal niche. We conclude that the structure of strain-level variation provides both the motivation and means of testing whether strain-level differences contribute to the function and health consequences of the vaginal microbiome.
Isolation and characterization of bacteria from activated sludge capable of degrading 17α-ethinylestradiol, a contaminant of high environmental concern
Authors: Palma Tânia Luz , Shylova Anastasiia , Costa Maria Clara
Published: March 2021

The compound 17α-ethinylestradiol (EE2) is a synthetic oestrogen which is classified as a group 1 carcinogen by the World Health Organization. Together with other endocrine disruptor compounds, EE2 has been included in the surface water Watch List by the European Commission, since it causes severe adverse effects in ecosystems. Thus, it became a high priority to find or improve processes such as biodegradation of EE2 to completely remove this drug from the wastewater treatment plants (WWTPs). The present study aimed at the isolation of bacteria capable of degrading EE2 using environmental samples, namely a sludge from the Faro Northwest WWTP. Four isolates with ability to grow in the presence of 50 mg l−1 EE2 were obtained. The analysis of 16SrRNA gene sequences identified the isolated bacteria as Acinetobacter bouvetii, Acinetobacter kookii, Pantoea agglomerans and

Shinella zoogloeoides

. The results of biodegradation assays showed that

Acinetobacter bouvetii

,

Acinetobacter kookii

,

Pantoea agglomerans

and

Shinella zoogloeoides

were able to degrade 47±4 %, 55±3 %, 64±4% and 35±4 %, respectively of 13 mg l−1 EE2 after 168 h at 28 °C. To the best of our knowledge, these bacterial isolates were identified as EE2 degraders for the first time. In a preliminary experiment on the identification of metabolic products resulting from EE2 degradation products such as estrone (E1), γ-lactone compounds, 2-pentanedioic acid and 2-butenedioic acid an intermediate metabolite of the TCA cycle, were detected.
Inflammatory Bowel Disease Risk Variants Are Associated with an Increased Risk of Skin Cancer
Authors: Cushing Kelly C. , Du Xiaomeng , Chen Yanhua , Stetson LC , Kuppa Annapurna , Chen Vincent L. , Kahlenberg J Michelle , Gudjonsson Johann E. , Higgins Peter DR , Speliotes Elizabeth
Published: March 2021

Background and Aims

Inflammatory bowel disease is associated with an increased risk of skin cancer. The aims of this study were to determine whether genomic variants associated with IBD susceptibility are also associated with skin cancer susceptibility and if such risk is augmented by the use of immune-suppressive therapy.

Methods

The discovery cohort included participants in the UK Biobank (n=408,381). The validation cohort included participants in the Michigan Genomics Initiative (n=51,405). The primary outcome of interest was skin cancer, sub-grouped into non-melanoma (NMSC) and melanoma skin cancers (MSC). Multivariable logistic regression was performed to identify genomic predictors of skin malignancy. Validated SNPs were evaluated for effect modification by immune-suppressive medication.

Results

The discovery cohort included 11,079 cases of NMSC and 2,054 cases of MSC. The validation cohort included 7,334 cases of NMSC and 3,304 cases of MSC. Thirty variants were associated with risk of NMSC in the discovery cohort, of which six replicated in the validation cohort [Increased risk: rs7773324-A (DUSP22; IRF4), rs2476601-G (PTPN22), rs1847472-C (BACH2), rs72810983-A (CPEB4); Decreased risk: rs6088765-G (PROCR; MMP24), rs11229555-G (ZFP91-CNTF; GLYAT)]. Twelve variants were associated with risk of MSC in the discovery cohort, of which three replicated in the validation cohort (Increased risk: rs61839660-T (IL2RA); Decreased risk: rs17391694-C (GIPC2; MGC27382), rs6088765-G (PROCR; MMP24)]. No effect modification was observed.

Conclusion

The results of this study highlight shared genetic susceptibility across IBD and skin cancer, with increased risk of NMSC in those who carry risk variants in IRF4, PTPN22, CPEB4, and BACH2 and increased risk of MSC in those who carry a risk variant in IL2RA.
Development and validation of decision rules models to stratify coronary artery disease, diabetes, and hypertension risk in preventive care: cohort study of returning UK Biobank participants
Authors: Forte José Castela , Folkertsma Pytrik , Gannamani Rahul , Kumaraswamy Sridhar , Mount Sarah , de Koning Tom J. , van Dam Sipko , Wolffenbuttel Bruce H. R.
Published: March 2021

Background

A wide range of predictive models exist that predict risk of common lifestyle conditions. However, these have not focused on identifying pre-clinical higher risk groups that would benefit from lifestyle interventions and do not include genetic risk scores.

Objective

To develop, validate, and compare the performance of three decision rule algorithms including biomarkers, physical measurements and genetic risk scores for incident coronary artery disease (CAD), diabetes (T2D), and hypertension in the general population against commonly used clinical risk scoring tools.

Methods

We identified 60782 individuals in the UK Biobank study with available follow-up data. Three decision rules models were developed and tested for an association with incident disease. Hazard ratios (with 95% confidence interval) for incident CAD, T2D, and hypertension were calculated from survival models. Model performance in discriminating between higher risk individuals suitable for lifestyle intervention and individuals at low risk was assessed using the area under the receiver operating characteristic curve (AUROC).

Results

We ascertained 500 incident CAD cases, 1005 incident T2D cases, and 2379 incident cases of hypertension. The higher risk group in the decision rules model had a 40-, 40.9-, and 21.6-fold increase in risk of CAD, T2D, and hypertension, respectively (P < 0.001 for all). Risk increased significantly between the three strata for all three conditions (P < 0.05). Risk stratification based on decision rules identified both a low-risk group (only 1.3% incident disease across all models), as well as a high-risk group where at least 72% of those developing disease within 8 years would have been recommended lifestyle intervention. Based on genetic risk alone, we identified not only a high-risk group, but also a group at elevated risk for all health conditions.

Conclusion

We found that decision rule models comprising blood biomarkers, physical measurements, and polygenic risk scores are superior at identifying individuals likely to benefit from lifestyle intervention for three of the most common lifestyle-related chronic health conditions compared to commonly used clinical risk scores. Their utility as part of digital data or digital therapeutics platforms to support the implementation of lifestyle interventions in preventive and primary care should be further validated.
Lack of lockdown, open borders, and no vaccination in sight: is Bosnia and Herzegovina a control group?
Authors: Fojnica Adnan , Osmanovic Ahmed , Đuzic Nermin , Fejzic Armin , Mekic Ensar , Gromilic Zehra , Muhovic Imer , Kurtovic-Kozaric Amina
Published: March 2021

Bosnia and Herzegovina is among ten countries in the world with the highest mortality rate due to COVID-19 infection. Lack of lockdown, open borders, high mortality rate, no herd immunity, no vaccination plan, and strong domestic anti-vaccination movement present serious COVID-19 concerns in Bosnia and Herzegovina. In such circumstances, we set out to study if the population is willing to receive the vaccine.

A cross-sectional study was conducted among 10,471 adults in Bosnia and Herzegovina to assess the attitude of participants toward COVID-19 vaccination. Using a logistic regression model, we assessed the associations of sociodemographic characteristics with vaccine rejection, reasons for vaccine hesitancy, preferred vaccine manufacturer, and information sources.

Surprisingly, only 25.7% of respondents indicated they would like to get a COVID-19 vaccine, while 74.3% of respondents were either hesitant or completely rejected vaccination. The vaccine acceptance increased with increasing age, education, and income level. Major motivation of pro-vaccination behaviour was intention to achieve collective immunity (30.1%), while the leading incentive for vaccine refusal was deficiency of clinical data (30.2%). The Pfizer-BioNTech vaccine is shown to be eightfold more preferred vaccine compared to the other manufacturers. For the first time, vaccine acceptance among health care professionals has been reported, where only 39.4% of healthcare professionals expressed willingness to get vaccinated.

With the high share of the population unwilling to vaccinate, governmental impotence in securing the vaccines supplies, combined with the lack of any lockdown measures suggests that Bosnia and Herzegovina is unlikely to put COVID-19 pandemic under control in near future.
Estimation of secondary household attack rates for emergent SARS-CoV-2 variants detected by genomic surveillance at a community-based testing site in San Francisco
Authors: Peng James , Mann Sabrina A , Mitchell Anthea M , Liu Jamin , Laurie Matthew T. , Sunshine Sara , Pilarowski Genay , Ayscue Patrick , Kistler Amy , Vanaerschot Manu , Li Lucy M. , McGeever Aaron , Chow Eric D. , Team IDseq , Marquez Carina , Nakamura Robert , Rubio Luis , Chamie Gabriel , Jones Diane , Jacobo Jon , Rojas Susana , Rojas Susy , Tulier-Laiwa Valerie , Black Douglas , Martinez Jackie , Naso Jamie , Schwab Joshua , Petersen Maya , Havlir Diane , DeRisi Joseph
Published: March 2021

Background

Sequencing of the SARS-CoV-2 viral genome from patient samples is an important epidemiological tool for monitoring and responding to the pandemic, including the emergence of new mutations in specific communities.

Methods

SARS-CoV-2 genomic sequences were generated from positive samples collected, along with epidemiological metadata, at a walk-up, rapid testing site in the Mission District of San Francisco, California during November 22-December 2, 2020 and January 10-29, 2021. Secondary household attack rates and mean sample viral load were estimated and compared across observed variants.

Results

A total of 12,124 tests were performed yielding 1,099 positives. From these, 811 high quality genomes were generated. Certain viral lineages bearing spike mutations, defined in part by L452R, S13I, and W152C, comprised 54.9% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to “West Coast” variants were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.357 vs 0.294, RR=1.29; 95% CI:1.01-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020. Viral loads were similar among persons infected with West Coast versus non-West Coast strains, as was the proportion of individuals with symptoms (60.9% vs 64.1%).

Conclusions

The increase in prevalence, relative household attack rates, and reproductive number are consistent with a modest transmissibility increase of the West Coast variants; however, additional laboratory and epidemiological studies are required to better understand differences between these variants.

We observed a growing prevalence and elevated attack rate for “West Coast” SARS-CoV-2 variants in a community testing setting in San Francisco during January 2021, suggesting its modestly higher transmissibility.