bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-time dynamics and semi-wave of a delayed nonlocal epidemic model with free boundaries
Authors: Chen Qiaoling , Tang Sanyi , Teng Zhidong , Wang Feng
Published: October 2023

This paper is concerned with a nonlocal reaction–diffusion system with double free boundaries and two time delays. The free boundary problem describes the evolution of faecally–orally transmitted diseases. We first show the well-posedness of global solution, and then establish the monotonicity and asymptotic property of basic reproduction number for the epidemic model without delays, which is defined by spectral radius of the next infection operator. By introducing the generalized principal eigenvalue defined in general domain, we obtain an upper bound of the limit value of basic reproduction number. We discuss the spreading and vanishing phenomena in terms of the basic production number. By employing the perturbed approximation method and monotone iteration method, we establish the existence, uniqueness and monotonicity of solution to semi-wave problem. When spreading occurs, we determine the asymptotic spreading speeds of free boundaries by constructing suitable upper and lower solutions from the semi-wave solutions. Moreover, spreading speeds for partially degenerate diffusion case are provided in a similar way.
Ten2Twenty-Ghana: a randomised controlled trial on the efficacy of multiple micronutrient-fortified biscuits on the micronutrient status of adolescent girls
Authors: Azupogo Fusta , Abizari Abdul-Razak , Feskens Edith J. M. , Verhoef Hans , Brouwer Inge D.
Published: October 2023

Adolescent girls are an important target group for micronutrient interventions particularly in Sub-Saharan Africa where adolescent pregnancy and micronutrient deficiencies are common. When consumed in sufficient amounts and at levels appropriate for the population, fortified foods may be a useful strategy for this group, but little is known about their effectiveness and timing (regarding menarche), particularly in resource-poor environments. We evaluated the effect of consuming multiple micronutrient-fortified biscuits (MMB), sold in the Ghanaian market, 5 d/week for 26 weeks compared with unfortified biscuits (UB) on the micronutrient status of female adolescents. We also explored to what extent the intervention effect varied before or after menarche. Ten2Twenty-Ghana was a 26-week double-blind, randomised controlled trial among adolescent girls aged 10–17 years (n621) in the Mion District, Ghana. Biomarkers of micronutrient status included concentrations of Hb, plasma ferritin (PF), soluble transferrin receptor (TfR) and retinol-binding protein (RBP), including body-iron stores. Intention-to-treat analysis was supplemented by protocol-specific analysis. We found no effect of the intervention on PF, TfR and RBP. MMB consumption did not affect anaemia and micronutrient deficiencies at the population level. MMB consumption increased the prevalence of vitamin A deficiency by 6·2 % (95 % CI (0·7, 11·6)) among pre-menarche girls when adjusted for baseline micronutrient status, age and height-for-ageZ-score, but it decreased the prevalence of deficient/low vitamin A status by −9·6 % (95 % CI (−18·9, −0·3)) among post-menarche girls. Consuming MMB available in the market did not increase iron status in our study, but reduced the prevalence of deficient/low vitamin A status in post-menarcheal girls.
THE STATUS OF GAZA AS OCCUPIED TERRITORY UNDER INTERNATIONAL LAW
Authors: Jaber Safaa Sadi , Bantekas Ilias
Published: October 2023

The traditional effective control test for determining the existence of a belligerent occupation requires boots on the ground. However, the evolution of the international law of occupation and the emergence of complex situations, particularly of a technological nature, necessitate a functional approach that protects the rights of occupied populations. The political, historical and geographical conditions of Gaza allow Israel to exert effective remote control. Despite the disengagement of Israel from Gaza in 2005 and the assumption of military and political authority by Hamas, this article argues that Israel nonetheless continues to be in effective occupation of the Gaza Strip on the basis of the following grounds: (1) the relatively small size of Gaza in connection with the technological superiority of the Israeli air force allows Israeli boots to be present in Gaza within a reasonable response time; (2) Hamas's authority and armed resistance do not impede the status of occupation; (3) the long pre-disengagement occupation and close proximity between Israel and Gaza (geography) allow for the remote exercise of effective control; and (4) all imports, exports in and out of Gaza, and any movement of persons are fully controlled and regulated by Israel.
The fragility index: how robust are the outcomes of head and neck cancer randomised, controlled trials?
Authors: Suresh Neeraj V , Go Beatrice C , Fritz Christian G , Harris Jacob , Ahluwalia Vinayak , Xu Katherine , Lu Joseph , Rajasekaran Karthik
Published: October 2023

Background

The fragility index represents the minimum number of patients required to convert an outcome from statistically significant to insignificant. This report assesses the fragility index of head and neck cancer randomised, controlled trials.

Methods

Studies were extracted from PubMed/Medline, Scopus, Embase and Cochrane databases.

Results

Overall, 123 randomised, controlled trials were included. The sample size and fragility index medians (interquartile ranges) were 103 (56–213) and 2 (0–5), respectively. The fragility index exceeded the number of patients lost to follow up in 42.3 per cent (n = 52) of studies. A higher fragility index correlated with higher sample size (r = 0.514, p < 0.001), number of events (r = 0.449, p < 0.001) and statistical significance via p-value (r = −0.367, p < 0.001).

Conclusion

Head and neck cancer randomised, controlled trials demonstrated low fragility index values, in which statistically significant results could be nullified by altering the outcomes of just two patients, on average. Future head and neck oncology randomised, controlled trials should report the fragility index in order to provide insight into statistical robustness.
Impact of Sharing Dance Older Adults on Physical and Psychosocial Outcomes
Authors: Sodums Devin J. , Kim Sophia , Gallucci Christina E. , Natadiria Marsha , Bar Rachel , Gardner Sandra , Tafler Melissa
Published: October 2023

Dance for older adults is increasingly being used to support health and well-being. While dance may be enjoyable for many, understanding its benefits for those with limited physical and cognitive abilities may provide further support for how dance may be used in these contexts. This was a study of Sharing Dance Older Adults, a dance program with remotely streamed sessions. Data were collected from 48 older adults who took part in the On Your Feet version of the program, and from 38 who took part in the In Your Seat version. Measures included interviews, physical fitness tests and surveys on mood, quality of life, and program satisfaction. Physical fitness significantly improved for both groups, unlike for mood, social well-being, or quality of life. This contrasts with qualitative findings, with participants reporting how the program enhanced their mood, social interactions, and quality of life.
Enhancing domestic consumption to deliver food security in a volatile world
Authors: Willer David F. , Aldridge David C.
Published: October 2023

Non-technical summary

Global conflicts and the pandemic reveal the risks of food import reliance. In the UK, pandemic, Brexit, and Ukraine war caused food price spikes. To bolster food security, the UK needs to produce and consume more domestically, including nutrient-rich bivalve mollusks. Current mollusk exports hinder domestic food sources. Promoting domestic consumption through convenient, attractive products and taxing unhealthy processed foods can help. Reducing reliance on food trade is crucial amid global instability and climate change. The UK's mollusk export issues illustrate food security risks of excessive reliance on international trade.

Technical summary

Here we examine the critical issue of food security in the context of international volatility, emphasizing the risks associated with an excessive reliance on food trade. The UK's experience with disruptions caused by the pandemic, Brexit, and the Ukraine war, resulting in a significant surge in food prices, serves as a pertinent case study. The research underscores the potential benefits of increasing domestic food production and consumption to enhance resilience against global events. The UK's current production, export, and import statistics are analyzed, with a particular focus on the fish and seafood sector. The study highlights the bivalve mollusk industry, such as blue mussels, as an example of an underutilized domestic resource. Bivalve mollusks are rich in essential micronutrients, yet their consumption in the UK is low compared to other countries. We propose strategies to boost domestic demand, including incorporating bivalve meat into processed food products, utilizing advanced technologies to improve taste and texture, and government intervention through taxes on unhealthy processed foods to promote better nutritional profiles. In summary, the study emphasizes the need for greater self-sufficiency in food production to mitigate vulnerabilities resulting from an overreliance on food trade in the context of international conflicts and climate change.

Social media summary

Failure to effectively utilize domestic food resources and overreliance on trade threatens food security in an increasingly volatile world.
Exploring chemical control of 2,4-D–resistant wild radish (Raphanus raphanistrum) with auxin-related compounds
Authors: Goggin Danica , Taylor Candy , Busi Roberto , Sayer Chad , Wells Andrew , Slatter Mark , Flower Ken
Published: October 2023

Synthetic auxin herbicides were developed and commercialized 60 yr before their mode of action was definitively elucidated. Although evolution of resistance to auxinic herbicides proceeded more slowly than for some other herbicide chemistries, it has become a major problem in the dicotyledonous weeds of many cropping areas of the world. With the molecular characterization of the auxin perception and signaling pathway in the mid-2000s came a greater understanding of how auxinic herbicides work, and how resistance may develop in weeds subjected to repeated selection with these herbicides. In wild radish (Raphanus raphanistrum L.) populations in southern Australia, resistance to multiple herbicides, including synthetic auxins such as 2,4-D, has reduced the number of chemical control options available. The aim of this study was to determine whether compounds involved in auxin biosynthesis, transport, and signaling are able to synergize with 2,4-D and increase its ability to control 2,4-D–resistant R. raphanistrum populations. Although some mild synergism was observed with a few compounds (abscisic acid, cyclanilide, tryptamine), the response was not large or consistent enough to warrant further study. Similarly, alternative auxinic herbicides applied pre- or postemergence were no more effective than 2,4-D. Therefore, while use of auxinic herbicides continues to increase due to the adoption of transgenic resistant crops, nonchemical control techniques will become more important, and chemical control of 2,4-D–resistant R. raphanistrum should be undertaken with alternative modes of action, using mixtures and good stewardship to delay the development of resistance for as long as possible.
Dynamic functional connectivity changes associated with psychiatric traits and cognitive deficits in Cushing’s disease
Authors: Feng Zhebin , Zhang Haitao , Zhou Tao , Yu Xinguang , Zhang Yanyang , Yan Xinyuan
Published: October 2023

Cushing’s disease is a rare neuroendocrine disorder with excessive endogenous cortisol, impaired cognition, and psychiatric symptoms. Evidence from resting-state fMRI revealed the abnormalities of static brain connectivity in patients with Cushing’s disease (CD patients). However, it is unknown whether the CD patients’ dynamic functional connectivity would be abnormal and whether the dynamic features are associated with deficits in cognition and psychopathological symptoms. Here, we evaluated 50 patients with Cushing’s disease and 57 healthy participants by using resting-state fMRI and dynamic functional connectivity (dFNC) approach. We focused on the dynamic features of default mode network (DMN), salience network (SN), and central executive network (CEN) because these are binding sites for the cognitive-affective process, as well as vital in understanding the pathophysiology of psychiatric disorders. The dFNC was further clustered into four states by k-mean clustering. CD patients showed more dwell time in State 1 but less time in State 4. Intriguingly, group differences in dwell time in these two states can explain the cognitive deficits of CD patients. Moreover, the inter-network connections between DMN and SN and the engagement time in State 4 negatively correlated with anxiety and depression but positively correlated with cognitive performance. Finally, the classifier trained by the dynamic features of these networks successfully classified CD patients from healthy participants. Together, our study revealed the dynamic features of CD patients’ brains and found their associations with impaired cognition and emotional symptoms, which may open new avenues for understanding the cognitive and affective deficits induced by Cushing’s disease.
The proton channel OTOP1 is a sensor for the taste of ammonium chloride
Authors: Liang Ziyu , Wilson Courtney E. , Teng Bochuan , Kinnamon Sue C. , Liman Emily R.
Published: October 2023

Ammonium (NH4+), a breakdown product of amino acids that can be toxic at high levels, is detected by taste systems of organisms ranging from C. elegans to humans and has been used for decades in vertebrate taste research. Here we report that OTOP1, a proton-selective ion channel expressed in sour (Type III) taste receptor cells (TRCs), functions as sensor for ammonium chloride (NH4Cl). Extracellular NH4Cl evoked large dose-dependent inward currents in HEK-293 cells expressing murine OTOP1 (mOTOP1), human OTOP1 and other species variants of OTOP1, that correlated with its ability to alkalinize the cell cytosol. Mutation of a conserved intracellular arginine residue (R292) in the mOTOP1 tm 6-tm 7 linker specifically decreased responses to NH4Cl relative to acid stimuli. Taste responses to NH4Cl measured from isolated Type III TRCs, or gustatory nerves were strongly attenuated or eliminated in an Otop1−/− mouse strain. Behavioral aversion of mice to NH4Cl, reduced in Skn-1a−/− mice lacking Type II TRCs, was entirely abolished in a double knockout with Otop1. These data together reveal an unexpected role for the proton channel OTOP1 in mediating a major component of the taste of NH4Cl and a previously undescribed channel activation mechanism.
The USP46 deubiquitylase complex increases Wingless/Wnt signaling strength by stabilizing Arrow/LRP6
Authors: Spencer Zachary T. , Ng Victoria H. , Benchabane Hassina , Siddiqui Ghalia Saad , Duwadi Deepesh , Maines Ben , Bryant Jamal M. , Schwarzkopf Anna , Yuan Kai , Kassel Sara N. , Mishra Anant , Pimentel Ashley , Lebensohn Andres M. , Rohatgi Rajat , Gerber Scott A. , Robbins David J. , Lee Ethan , Ahmed Yashi
Published: October 2023

The control of Wnt receptor abundance is critical for animal development and to prevent tumorigenesis, but the mechanisms that mediate receptor stabilization remain uncertain. We demonstrate that stabilization of the essential Wingless/Wnt receptor Arrow/LRP6 by the evolutionarily conserved Usp46-Uaf1-Wdr20 deubiquitylase complex controls signaling strength in Drosophila. By reducing Arrow ubiquitylation and turnover, the Usp46 complex increases cell surface levels of Arrow and enhances the sensitivity of target cells to stimulation by the Wingless morphogen, thereby increasing the amplitude and spatial range of signaling responses. Usp46 inactivation in Wingless-responding cells destabilizes Arrow, reduces cytoplasmic accumulation of the transcriptional coactivator Armadillo/β-catenin, and attenuates or abolishes Wingless target gene activation, which prevents the concentration-dependent regulation of signaling strength. Consequently, Wingless-dependent developmental patterning and tissue homeostasis are disrupted. These results reveal an evolutionarily conserved mechanism that mediates Wnt/Wingless receptor stabilization and underlies the precise activation of signaling throughout the spatial range of the morphogen gradient.
Viral kinetics of sequential SARS-CoV-2 infections
Authors: Kissler Stephen M. , Hay James A. , Fauver Joseph R. , Mack Christina , Tai Caroline G. , Anderson Deverick J. , Ho David D. , Grubaugh Nathan D. , Grad Yonatan H.
Published: October 2023

The impact of a prior SARS-CoV-2 infection on the progression of subsequent infections has been unclear. Using a convenience sample of 94,812 longitudinal RT-qPCR measurements from anterior nares and oropharyngeal swabs, we identified 71 individuals with two well-sampled SARS-CoV-2 infections between March 11th, 2020, and July 28th, 2022. We compared the SARS-CoV-2 viral kinetics of first vs. second infections in this group, adjusting for viral variant, vaccination status, and age. Relative to first infections, second infections usually featured a faster clearance time. Furthermore, a person’s relative (rank-order) viral clearance time, compared to others infected with the same variant, was roughly conserved across first and second infections, so that individuals who had a relatively fast clearance time in their first infection also tended to have a relatively fast clearance time in their second infection (Spearman correlation coefficient: 0.30, 95% credible interval (0.12, 0.46)). These findings provide evidence that, like vaccination, immunity from a prior SARS-CoV-2 infection shortens the duration of subsequent acute SARS-CoV-2 infections principally by reducing viral clearance time. Additionally, there appears to be an inherent element of the immune response, or some other host factor, that shapes a person’s relative ability to clear SARS-CoV-2 infection that persists across sequential infections.
Autoantibody binding and unique enzyme-substrate intermediate conformation of human transglutaminase 3
Authors: Heggelund Julie Elisabeth , Das Saykat , Stamnaes Jorunn , Iversen Rasmus , Sollid Ludvig M.
Published: October 2023

Transglutaminase 3 (TG3), the autoantigen of dermatitis herpetiformis (DH), is a calcium dependent enzyme that targets glutamine residues in polypeptides for either transamidation or deamidation modifications. To become catalytically active TG3 requires proteolytic cleavage between the core domain and two C-terminal β-barrels (C1C2). Here, we report four X-ray crystal structures representing inactive and active conformations of human TG3 in complex with a TG3-specific Fab fragment of a DH patient derived antibody. We demonstrate that cleaved TG3, upon binding of a substrate-mimicking inhibitor, undergoes a large conformational change as a β-sheet in the catalytic core domain moves and C1C2 detaches. The unique enzyme-substrate conformation of TG3 without C1C2 is recognized by DH autoantibodies. The findings support a model where B-cell receptors of TG3-specific B cells bind and internalize TG3-gluten enzyme-substrate complexes thereby facilitating gluten-antigen presentation, T-cell help and autoantibody production.
Warming indirectly simplifies food webs through effects on apex predators
Authors: O’Gorman Eoin J. , Zhao Lei , Kordas Rebecca L. , Dudgeon Steve , Woodward Guy
Published: October 2023

Warming alters ecosystems through direct physiological effects on organisms and indirect effects via biotic interactions, but their relative impacts in the wild are unknown due to the difficulty in warming natural environments. Here we bridge this gap by embedding manipulative field experiments within a natural stream temperature gradient to test whether warming and apex fish predators have interactive effects on freshwater ecosystems. Fish exerted cascading effects on algal production and microbial decomposition via both green and brown pathways in the food web, but only under warming. Neither temperature nor the presence of fish altered food web structure alone, but connectance and mean trophic level declined as consumer species were lost when both drivers acted together. A mechanistic model indicates that this temperature-induced trophic cascade is determined primarily by altered interactions, which cautions against extrapolating the impacts of warming from reductionist approaches that do not consider the wider food web.
Hippocampal neurons code individual episodic memories in humans
Authors: Kolibius Luca D. , Roux Frederic , Parish George , Ter Wal Marije , Van Der Plas Mircea , Chelvarajah Ramesh , Sawlani Vijay , Rollings David T. , Lang Johannes D. , Gollwitzer Stephanie , Walther Katrin , Hopfengärtner Rüdiger , Kreiselmeyer Gernot , Hamer Hajo , Staresina Bernhard P. , Wimber Maria , Bowman Howard , Hanslmayr Simon
Published: October 2023

The hippocampus is an essential hub for episodic memory processing. However, how human hippocampal single neurons code multi-element associations remains unknown. In particular, it is debated whether each hippocampal neuron represents an invariant element within an episode or whether single neurons bind together all the elements of a discrete episodic memory. Here we provide evidence for the latter hypothesis. Using single-neuron recordings from a total of 30 participants, we show that individual neurons, which we term episode-specific neurons, code discrete episodic memories using either a rate code or a temporal firing code. These neurons were observed exclusively in the hippocampus. Importantly, these episode-specific neurons do not reflect the coding of a particular element in the episode (that is, concept or time). Instead, they code for the conjunction of the different elements that make up the episode.
Audience synchronies in live concerts illustrate the embodiment of music experience
Authors: Tschacher Wolfgang , Greenwood Steven , Ramakrishnan Sekhar , Tröndle Martin , Wald-Fuhrmann Melanie , Seibert Christoph , Weining Christian , Meier Deborah
Published: October 2023

A study of 132 audience members of three classical public concerts (all three staged the same chamber music pieces by Ludwig van Beethoven, Brett Dean, and Johannes Brahms) had the goal of analyzing the physiological and motor responses of audiences. It was assumed that the music would induce synchronous physiology and movement in listeners (induction synchrony). In addition to hypothesizing that such synchronies would be present, we expected that they were linked to participants’ aesthetic experiences, their affect and personality traits, which were assessed by questionnaires before and after the concerts. Clear evidence was found of physiological synchrony (heart rate, respiration rate, skin conductance response) as well as movement synchrony of the audiences, whereas breathing behavior was not synchronized. Thus the audiences of the three concerts resonated with the music, their music perception was embodied. There were links between the bodily synchrony and aesthetic experiences: synchrony, especially heart-rate synchrony, was higher when listeners felt moved emotionally and inspired by a piece, and were immersed in the music. Personality traits were also associated with the individual contributions to induction synchrony.
Environmental influences on induction of itching and scratching using immersive virtual reality
Authors: van de Burgt Emmy W. T. , van der Mijn Robbert , Fabbri Sara , Lorist Monicque M.
Published: October 2023

Chronic itching is a serious and uncomfortable condition. The scratch response might result in a vicious cycle of alternating itching and scratching. To develop psychological interventions for people suffering from chronic itching and to break the vicious itch-scratching-itch cycle, it is important to elucidate which environmental factors trigger itch sensations. Virtual reality (VR) techniques provide a useful tool to examine specific content characteristics in a three-dimensional (3D VR) environment and their influences on itch sensations and scratching behaviour. This article describes two experiments in which we focused on the effects of environmental information on itching and scratching behaviour. Additionally, in the second experiment, we examined the influence of having a chronic skin condition on sensitivity to itch induction. We found evidence for the importance of the content of audio–visual materials for the effectiveness in inducing feelings of itch in the observers. In both experiments, we observed significantly higher levels of perceived itch in the itch-inducing conditions than in the control condition. Moreover, the results showed that elevated levels of perceived itch were associated with an increase in scratching behaviours, which was especially salient in the contagious itch condition, in which perceived itch was accompanied by a significant increase in the number of scratches. Experiment 2 additionally showed increased perceived itch levels in participants who reported having a chronic skin condition, reflecting higher sensitivity to itch-inducing audio–visual stimuli in this group than in participants without a chronic skin condition. Based on the results we concluded that directing attention towards itch- or scratch aspects of related information in the environment and to the consequences for one’s own skin are effective tools to induce itch sensations and scratching behaviour. This knowledge provides tools for developing novel strategies in advising and treating people suffering from chronic itching and breaking the vicious itch-scratching-itch cycle.
Modeling the space-time correlation of pulsed twin beams
Authors: Gatti Alessandra , Jedrkiewicz Ottavia , Brambilla Enrico
Published: October 2023

Entangled twin-beams generated by parametric down-conversion are among the favorite sources for imaging-oriented applications, due their multimodal nature in space and time. However, a satisfactory theoretical description is still lacking. In this work we propose a semi-analytic model which aims to bridge the gap between time-consuming numerical simulations and the unrealistic plane-wave pump theory. The model is used to study the quantum correlation and the coherence in the angle-frequency domain of the parametric emission, and demonstrates a $$g^{{1/2}}$$

g

1
/
2

growth of their size as the gain g increases, with a corresponding contraction of the space-time distribution. These predictions are systematically compared with the results of stochastic numerical simulations, performed in the Wigner representation, of the full model equations: an excellent agreement is shown even for parameters well outside the expected limit of validity of the model.
Game-theoretical description of the go-or-grow dichotomy in tumor development for various settings and parameter constellations
Authors: Dwivedi Shalu , Glock Christina , Germerodt Sebastian , Stark Heiko , Schuster Stefan
Published: October 2023

A medically important feature of several types of tumors is their ability to “decide” between staying at a primary site in the body or leaving it and forming metastases. The present theoretical study aims to provide a better understanding of the ultimate reasons for this so-called “go-or-grow” dichotomy. To that end, we use game theory, which has proven to be useful in analyzing the competition between tumors and healthy tissues or among different tumor cells. We begin by determining the game types in the Basanta–Hatzikirou–Deutsch model, depending on the parameter values. Thereafter, we suggest and analyze five modified variants of the model. For example, in the basic model, the deadlock game, Prisoner’s Dilemma, and hawk-dove game can occur. The modified versions lead to several additional game types, such as battle of the sexes, route-choice, and stag-hunt games. For some game types, all cells are predicted to stay on their original site (“grow phenotype”), while for other types, only a certain fraction stay and the other cells migrate away (“go phenotype”). If the nutrient supply at a distant site is high, all the cells are predicted to go. We discuss our predictions in terms of the pros and cons of caloric restriction and limitations of the supply of vitamins or methionine. Our results may help devise treatments to prevent metastasis.
Enhanced spectral resolution for correlated spectroscopic imaging using inner-product and covariance transform: a pilot analysis of metabolites and lipids in breast cancer in vivo
Authors: Joy Ajin , Thomas M. Albert
Published: October 2023

Acquisition duration of correlated spectroscopy in vivo can be longer due to a large number of t1 increments along the indirect (F1) dimension. Limited number of t1 increments on the other hand leads to poor spectral resolution along F1. Covariance transformation (CT) instead of Fourier transform along t1 is an alternative way of increasing the resolution of the 2D COSY spectrum. Prospectively undersampled five-dimensional echo-planar correlated spectroscopic imaging (EP-COSI) data from ten malignant patients and ten healthy women were acquired and reconstructed using compressed sensing. The COSY spectrum at each voxel location was then generated using FFT, CT and a variant of CT called Inner Product (IP). Metabolite and lipid ratios were computed with respect to water from unsuppressed one-dimensional spectrum. The effects of t1-ridging artifacts commonly seen with FFT were not observed with CT/IP. Statistically significant differences were observed in the fat cross peaks measured with CT/IP/FFT. Spectral resolution was increased ~ 8.5 times (~ 19.53 Hz in FFT, ~ 2.32 Hz in CT/IP) without affecting the spectral width along F1 was possible with CT/IP. CT and IP enabled substantially increased F1 resolution effectively with significant gain in scan time and reliable measure of unsaturation index as a biomarker for malignant breast cancer.
New fossil data reveal evolutionary pathways within the genus Trichoneura Loew, 1850 (Diptera, Limoniidae)
Authors: Kopeć Katarzyna , Kania-Kłosok Iwona , Zhang Qingqing , Krzemiński Wiesław
Published: October 2023

New inclusions of Trichoneura preserved in Upper Cretaceous (Cenomanian) Kachin amber allow the description of a new subgenus, Burmania subgen. nov., and four new species: Trichoneura (Burmania) burmitensis subgen. et sp. nov., Trichoneura (Burmania) chungkuni subgen. et sp. nov., Trichoneura (Burmania) sevciki subgen. et sp. nov. and Trichoneura (Burmania) wangi subgen. et sp. nov. The species differ mainly by the morphology of the hypopygium or wing venation but also the construction of the antenna. Based on a comparison of the wing venation and the morphology of the hypopygium it was possible to describe features which are characteristic of the new subgenus, especially the presence of vein R3+4. Moreover, it was possible to elucidate the evolutionary pattern of Trichoneura with two distinct extant and extinct branches. Trichoneura (Trichoneura) canadensis from Upper Cretaceous Canadian amber is transferred to the new subgenus Burmania.
Climate warming accelerates somatic growth of an Arctic fish species in high-latitude lakes
Authors: Kotowych Nicholas , Smalås Aslak , Amundsen Per-Arne , Primicerio Raul
Published: October 2023

High-latitude aquatic ecosystems are responding to rapid climate warming. A longer ice-free season with higher water temperatures may accelerate somatic growth in lake ectotherms, leading to widespread ecological implications. In fish, rising temperatures are expected to boost rates of food intake and conversion, and predictions based on empirical relationships between temperature and growth suggest a substantial increase in fish growth rates during the last decades. Fish abundance negatively affects growth by limiting food availability. This field study addresses the effects of climate warming on growth of a subarctic population of Arctic charr (Salvelinus alpinus (L.) over nearly 40 years. Juvenile growth of 680 individuals of Arctic charr, was reconstructed by sclerochronological analysis using sagittal otoliths sampled annually from the early 1980s to 2016. Statistical modelling revealed a positive effect of water temperature, and a negative effect of abundance on somatic growth in juvenile individuals. Temperature dependence in growth was significant for average and fast-growing individuals across all investigated age classes. These findings suggest that, as temperatures rise, somatic growth of Arctic charr will increase in high latitude lakes. Climate warming will thus influence cold water fish life history and size-structured interactions, with important consequences for their populations and ecosystems.
Temporal serum metabolomic and lipidomic analyses distinguish patients with access-related hand disability following arteriovenous fistula creation
Authors: Khattri Ram B. , Louis Lauryn Z. , Kim Kyoungrae , Anderson Erik M. , Fazzone Brian , Harland Kenneth C. , Hu Qiongyao , O’Malley Kerri A. , Berceli Scott A. , Wymer James , Ryan Terence E. , Scali Salvatore T.
Published: October 2023

For end-stage kidney disease (ESKD) patients, hemodialysis requires durable vascular access which is often surgically created using an arteriovenous fistula (AVF). However, some ESKD patients that undergo AVF placement develop access-related hand dysfunction (ARHD) through unknown mechanisms. In this study, we sought to determine if changes in the serum metabolome could distinguish ESKD patients that develop ARHD from those that have normal hand function following AVF creation. Forty-five ESKD patients that underwent first-time AVF creation were included in this study. Blood samples were obtained pre-operatively and 6-weeks post-operatively and metabolites were extracted and analyzed using nuclear magnetic resonance spectroscopy. Patients underwent thorough examination of hand function at both timepoints using the following assessments: grip strength manometry, dexterity, sensation, motor and sensory nerve conduction testing, hemodynamics, and the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. Nineteen of the forty-five patients displayed overt weakness using grip strength manometry (P < 0.0001). Unfortunately, the serum metabolome was indistinguishable between patients with and without weakness following AVF surgery. However, a significant correlation was found between the change in tryptophan levels and the change in grip strength suggesting a possible role of tryptophan-derived uremic metabolites in post-AVF hand-associated weakness. Compared to grip strength, changes in dexterity and sensation were smaller than those observed in grip strength, however, post-operative decreases in phenylalanine, glycine, and alanine were unique to patients that developed signs of motor or sensory disability following AVF creation.
The potential of UAV and very high-resolution satellite imagery for yellow and stem rust detection and phenotyping in Ethiopia
Authors: Blasch Gerald , Anberbir Tadesse , Negash Tamirat , Tilahun Lidiya , Belayineh Fikrte Yirga , Alemayehu Yoseph , Mamo Girma , Hodson David P. , Rodrigues Francelino A.
Published: October 2023

Very high (spatial and temporal) resolution satellite (VHRS) and high-resolution unmanned aerial vehicle (UAV) imagery provides the opportunity to develop new crop disease detection methods at early growth stages with utility for early warning systems. The capability of multispectral UAV, SkySat and Pleiades imagery as a high throughput phenotyping (HTP) and rapid disease detection tool for wheat rusts is assessed. In a randomized trial with and without fungicide control, six bread wheat varieties with differing rust resistance were monitored using UAV and VHRS. In total, 18 spectral features served as predictors for stem and yellow rust disease progression and associated yield loss. Several spectral features demonstrated strong predictive power for the detection of combined wheat rust diseases and the estimation of varieties’ response to disease stress and grain yield. Visible spectral (VIS) bands (Green, Red) were more useful at booting, shifting to VIS–NIR (near-infrared) vegetation indices (e.g., NDVI, RVI) at heading. The top-performing spectral features for disease progression and grain yield were the Red band and UAV-derived RVI and NDVI. Our findings provide valuable insight into the upscaling capability of multispectral sensors for disease detection, demonstrating the possibility of upscaling disease detection from plot to regional scales at early growth stages.
Risk of incident autoimmune diseases in patients with newly diagnosed psoriatic disease: a nationwide population-based study
Authors: Jung Joon Min , Kim Ye-Jee , Lee Woo Jin , Won Chong Hyun , Lee Mi Woo , Chang Sung Eun
Published: October 2023

There are limited large population-based cohort studies on the risk of incident autoimmune diseases among patients with newly diagnosed psoriatic disease. The objective of this study was to assess the risk of autoimmune diseases in patients with newly diagnosed psoriatic disease. Using the Korean National Health Insurance Service database, patients with newly diagnosed psoriatic disease between 2007 and 2019 were included. Comparators were randomly selected and matched according to age and sex. A total of 321,354 patients with psoriatic disease and 321,354 matched comparators were included in this study. Patients with psoriatic disease had a significantly higher risk of Crohn’s disease [adjusted hazard ratio (aHR), 1.95; 95% confidence interval (CI) 1.42–2.67], ulcerative colitis (aHR, 1.65; 95% CI 1.39–1.96), systemic lupus erythematosus (aHR, 1.86; 95% CI 1.34–2.57), rheumatoid arthritis (aHR, 1.63; 95% CI 1.52–1.76), ankylosing spondylitis (aHR, 2.32; 95% CI 1.95–2.77), alopecia areata (aHR, 1.41; 95% CI 1.35–1.46), and type 1 diabetes (aHR, 1.23; 95% CI 1.11–1.37). However, the risk of Graves’ disease, Hashimoto’s disease, Sjögren’s syndrome, and systemic sclerosis was not significantly different between the groups. In conclusion, patients with newly diagnosed psoriatic disease may have a significantly increased risk of incident autoimmune diseases.
Evaluation and validation of reference genes for RT-qPCR gene expression in Naegleria gruberi
Authors: Martín-Pérez Tania , Köhsler Martina , Walochnik Julia
Published: October 2023

Naegleria gruberi is a free-living amoeboflagellate commonly found in freshwater and in soils around the world. It is a non-pathogenic relative of Naegleria fowleri, which is the etiologic agent of Primary Amoebic Meningoencephalitis (PAM). PAM occurs world-wide and it is considered a rare disease, but its fatality rate is high (96%) mainly because of delay in initiation of treatment due to misdiagnosis and lack of a specific treatment. The analysis of gene expression by quantitative real-time PCR in N. gruberi could be a highly efficient means to understand the pathogenicity of N. fowleri and also to find drug targets. Accurate RT-qPCR analysis requires correct normalization of gene expression data using reference genes (RG), whose expression should be constant under different experimental conditions. In this study, six genes, representing the most frequently used housekeeping genes, were selected for evaluation as reference genes in N. gruberi. The expression and stability of these genes was evaluated employing four algorithms (geNorm, NormFinder, BestKeeper and RefFinder). This work shows significant variations of the stability of RGs depending on the algorithms employed and on the experimental conditions (i.e. logarithmic, stationary, heat-shock and oxidative stress). The geNorm, NormFinder and RefFinder analysis of all the experimental conditions in combination revealed that ACT and G6PD were the most stable RGs. While BestKeeper analysis showed that 18S and TBP were the most stable RGs. Moreover, normalization of HSP90 gene expression with the most stable RGs resulted in an upregulation whereas when the normalization was done with the unstable RGs, the gene expression was not reliable. Hence, the implications of this study are relevant to gene expression studies in N. gruberi.
Elucidation of lipid nanoparticle surface structure in mRNA vaccines
Authors: Wang Mingzhang Maple , Wappelhorst Caitlin N. , Jensen Erika L. , Chi Ying-Chih Thomas , Rouse Jason C. , Zou Qin
Published: October 2023

Lipid nanoparticles (LNPs) have been used as a carrier for messenger RNA (mRNA) vaccines. Surface properties of LNPs are important to the stability and function of mRNA vaccines. Polyethylene-glycol (PEG) is a functional lipid at the surface of LNPs that improves colloidal stability, increases circulation time, and impacts cellular uptake. In this study, we explore in-depth lipid composition at the surface of mRNA-LNPs using high-field nuclear magnetic resonance (NMR) spectroscopy. Our results provide a unique surface lipid profile of intact LNPs identifying PEG chains and partial ionizable lipids are present with quantification capability. The surface PEG density is determined to reveal the brush-like conformation on the surface of mRNA-LNPs. Furthermore, we implement a diffusion NMR strategy for routine testing of formulated drug products during drug development. Comparative NMR analysis of different vaccine preparations and stability samples provides a global view of the mRNA-LNP surface structure for enhanced product knowledge.
Quantification of expected information gain in visual acuity and contrast sensitivity tests
Authors: Lu Zhong-Lin , Zhao Yukai , Lesmes Luis Andres , Dorr Michael
Published: October 2023

We make use of expected information gain to quantify the amount of knowledge obtained from measurements in a population. In the first application, we compared the expected information gain in the Snellen, ETDRS, and qVA visual acuity (VA) tests, as well as in the Pelli–Robson, CSV-1000, and qCSF contrast sensitivity (CS) tests. For the VA tests, ETDRS generated more expected information gain than Snellen. Additionally, the qVA test with 15 rows (or 45 optotypes) generated more expected information gain than ETDRS, whether scored with VA threshold alone or with both VA threshold and VA range. Regarding the CS tests, CSV-1000 generated more expected information gain than Pelli–Robson, and the qCSF test with 25 trials generated more expected information gain than CSV-1000, whether scored with AULCSF or with CSF at six spatial frequencies. The active learning-based qVA and qCSF tests have the potential to generate more expected information gain than traditional paper chart tests. Although we have specifically applied it to compare VA and CS tests, expected information gain is a general concept that can be used to compare measurements in any domain.
Data-driven networking of global transcriptomics and male sexual development in the main malaria vector, Anopheles funestus
Authors: Koekemoer L. L. , Hajkazemian M. , Zawada J. W. , Mirzaie M. , Dahan-Moss Y. L. , Emami S. N.
Published: October 2023

Deaths from malaria remain staggering despite global support that drives research into new territories. One major gap is our understanding of the sexual biological aspects of the male mosquito, which maintain the vector population solidity. Although Anopheles funestus s.s. is an extremely efficient African vector, little is known about the network between its sexual physiology and gene expression. The Culicidae male’s sexual maturity involves a suite of physiological changes, such as genitalia rotation that is necessary for successful mating to occur. We show that mating success is guided by genes and physiological plasticity. Transcriptome analysis between newly emerged males (immature) versus males with rotating genitalia (maturing) provides insight into possible molecular mechanisms regulating male sexual behaviour. Putative transcripts that were associated with male sexual maturation were identified and validated. The discovery of the functions of these transcripts could lead to identifying potential targets for innovative vector control interventions, and mosquito population suppression.
Pan-tissue mitochondrial phenotyping reveals lower OXPHOS expression and function across cancer types
Authors: Boykov Ilya N. , Montgomery McLane M. , Hagen James T. , Aruleba Raphael T. , McLaughlin Kelsey L. , Coalson Hannah S. , Nelson Margaret A. , Pereyra Andrea S. , Ellis Jessica M. , Zeczycki Tonya N. , Vohra Nasreen A. , Tan Su-Fern , Cabot Myles C. , Fisher-Wellman Kelsey H.
Published: October 2023

Targeting mitochondrial oxidative phosphorylation (OXPHOS) to treat cancer has been hampered due to serious side-effects potentially arising from the inability to discriminate between non-cancerous and cancerous mitochondria. Herein, comprehensive mitochondrial phenotyping was leveraged to define both the composition and function of OXPHOS across various murine cancers and compared to both matched normal tissues and other organs. When compared to both matched normal tissues, as well as high OXPHOS reliant organs like heart, intrinsic expression of the OXPHOS complexes, as well as OXPHOS flux were discovered to be consistently lower across distinct cancer types. Assuming intrinsic OXPHOS expression/function predicts OXPHOS reliance in vivo, these data suggest that pharmacologic blockade of mitochondrial OXPHOS likely compromises bioenergetic homeostasis in healthy oxidative organs prior to impacting tumor mitochondrial flux in a clinically meaningful way. Although these data caution against the use of indiscriminate mitochondrial inhibitors for cancer treatment, considerable heterogeneity was observed across cancer types with respect to both mitochondrial proteome composition and substrate-specific flux, highlighting the possibility for targeting discrete mitochondrial proteins or pathways unique to a given cancer type.
Tipping point arises earlier under a multiple-stressor scenario
Authors: Carrier-Belleau Charlotte , Pascal Ludovic , Tiegs Scott D. , Nozais Christian , Archambault Philippe
Published: October 2023

Anthropogenic impacts and global changes have profound implications for natural ecosystems and may lead to their modification, degradation or collapse. Increases in the intensity of single stressors may create abrupt shifts in biotic responses (i.e. thresholds). The effects of multiple interacting stressors may create non-additive responses, known as synergistic or antagonistic interactions. Here we combine both concepts—ecological thresholds and interactions between multiple stressors—to understand the effects of multiple interacting stressors along environmental gradients, and how this can affect the occurrence of thresholds. Using an experimental approach to investigate the effect of nutrient enrichment and saltwater intrusion on mortality in the zebra mussel, Dreissena polymorpha, we show that multiple stressors can create thresholds at lower levels of an environmental gradient. Our results reveal a major shortcoming in how we currently investigate these two ecological concepts, as considering them separately may be causing underestimation of thresholds and stressor-interaction impacts.