bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatio-temporal modeling reveals a layer of tunable control circuits for the distribution of cytokines in tissues
Authors: Brunner Patrick , Kiwitz Lukas , Thurley Kevin
Published: March 2022

Cytokines are diffusible mediators of cell-cell communication among immune cells with critical regulatory functions for cell differentiation and proliferation. Previous studies have revealed considerable spatial inhomogeneities in the distribution of cytokine molecules in tissues, potentially shaping the efficacy and range of paracrine cytokine signals. How such cytokine gradients emerge and are controlled within cell populations is incompletely understood. In this work, we employed a spatial reaction-diffusion model to systematically investigate the formation and influence of spatial cytokine gradients. We found the fraction of cytokine secreting cells to be the main source of spatial inhomogeneity and subsequent activation. Positive feedback from local cytokine levels upon cytokine receptor expression leads to further increased spatial cytokine inhomogeneities. By exploring the effect of co-clustering cytokine secreting cells and cells with large amounts of receptor expression, as in the presence of regulatory T cells in the vicinity of antigen-presenting cells, we found that such constrained tissue architecture can have profound effects on the range of paracrine cytokine signals.
Peripheral and central employment of acid-sensing ion channels during early bilaterian evolution
Authors: Martí-Solans Josep , Børve Aina , Bump Paul , Hejnol Andreas , Lynagh Timothy
Published: March 2022

Nervous systems are endowed with rapid chemosensation and intercellular signaling by ligand-gated ion channels (LGICs). While a complex, bilaterally symmetrical nervous system is a major innovation of bilaterian animals, the employment of specific LGICs during early bilaterian evolution is poorly understood. We therefore questioned bilaterian animals’ employment of acid-sensing ion channels (ASICs), LGICs that mediate fast excitatory responses to decreases in extracellular pH in vertebrate neurons. Our phylogenetic analysis identified an earlier emergence of ASICs from the overarching DEG/ENaC superfamily than previously thought and suggests that ASICs were a bilaterian innovation. Our broad examination of ASIC gene expression and biophysical function in each major bilaterian lineage of Xenacoelomorpha, Protostomia, and Deuterostomia, suggests that the earliest bilaterian ASICs were probably expressed in the periphery, before being incorporated into the brain as it emerged independently in certain deuterostomes and xenacoelomorphs. The loss of certain peripheral cells from Ecdysozoa when they split from other protostomes likely explains their loss of ASICs, and thus the absence of ASICs in model organismsDrosophilaandC. elegans. Thus, our use of diverse bilaterians in the investigation of LGIC expression and function offers a unique hypothesis on the employment of LGICs in early bilaterian evolution.
Causal Inference on Neuroimaging Data with Mendelian Randomisation
Authors: Taschler Bernd , Smith Stephen M. , Nichols Thomas E.
Published: March 2022

While population-scale neuroimaging studies offer the promise of discovery and characterisation of subtle risk factors, massive sample sizes increase the power for both meaningful associations and those attributable to confounds. This motivates the need for causal modelling of observational data that goes beyond statements of association and towards deeper understanding of complex relationships between individual traits and phenotypes, clinical biomarkers, genetic variation, and brain-related measures of health. Mendelian randomisation (MR) presents a way to obtain causal inference on the basis of genetic data and explicit assumptions about the relationship between genetic variables, exposure and outcome. In this work, we provide an introduction to and overview of causal inference methods based on Mendelian randomisation, with examples involving imaging-derived phenotypes from UK Biobank to make these methods accessible to neuroimaging researchers. We motivate the use of MR techniques, lay out the underlying assumptions, introduce common MR methods and focus on several scenarios in which modelling assumptions are potentially violated, resulting in biased effect estimates. Importantly, we give a detailed account of necessary steps to increase the reliability of MR results with rigorous sensitivity analyses.
Lack of self-medication by fungus infected Lasius platythorax ants in a multitrophic experiment
Authors: Rissanen Jason , Helanterä Heikki , Will Torsten , Freitak Dalial
Published: March 2022

Ants live in dense colonies with low genetic diversity between nestmates, creating favourable conditions for the spread of diseases. Due to the constant pressure by infectious disease, ants have evolved different mechanisms to cope with it. One way to combat pathogens is via consumption of biologically active compounds, which can inhibit the growth of the microbes or eliminate them. Although ants are known to respond to pathogen infections by altering their foraging to incorporate reactive oxygen species (ROS) into their diet to successfully combat disease under laboratory conditions, it is still unknown how ants would self-medicate in the wild. By designing a multitrophic environment, we try for the first time to identify potential sources of medicinal compounds for ants to use against fungal infections under natural conditions to better understand how the behaviour is expressed in nature. We investigated whether a bean plant suffering from an infestation of Megoura viciae aphids would be a source of ROS which the ant could use for self-medication, and whether the ant Lasius platythorax changes its foraging behaviour on bean plants if exposed to infectious spores of the entomopathogenic fungus Beauveria bassiana. We found no clear evidence that the ants significantly change their foraging behaviour on extrafloral nectaries in response to the pathogen or that the nectar produced by aphid stressed plants contains ROS. The aphids contained ROS in levels which ants could potentially use, however Megoura viciae is considered unpalatable to ants and we saw no evidence of predation on the aphids. Our results mean that the combination of species of the ant – plant – aphid interactions which we studied does result in a detectable self-medication response in ants. Therefore, we suggest that alternative species of aphids as well as other natural sources of ROS should be studied for self-medication.
Complementing machine learning-based structure predictions with native mass spectrometry
Authors: Allison Timothy M. , Degiacomi Matteo T. , Marklund Erik G. , Jovine Luca , Elofsson Arne , Benesch Justin L. P. , Landreh Michael
Published: March 2022

The advent of machine learning-based structure prediction algorithms such as AlphaFold2 (AF2) has moved the generation of accurate structural models for the entire cellular protein machinery into the reach of the scientific community. However, structure predictions of protein complexes are based on user-provided input and may therefore require experimental validation. Mass spectrometry (MS) is a versatile, time-effective tool that provides information on post-translational modifications, ligand interactions, conformational changes, and higher-order oligomerization. Using three protein systems, we show that native MS experiments can uncover structural features of ligand interactions, homology models, and point mutations, that are undetectable by AF2 alone. We conclude that machine learning can be complemented with MS to yield more accurate structural models on the small and the large scale.
Tissue-adjusted pathway analysis of cancer (TPAC)
Authors: Frost H. Robert
Published: March 2022

We describe a novel single sample pathway analysis method for cancer transcriptomics data named tissue-adjusted pathway analysis of cancer (TPAC). The TPAC method leverages information about the normal tissue-specificity of human genes to compute a robust multivariate distance score that quantifies pathway dysregulation in each profiled tumor. Because the null distribution of the TPAC scores has an accurate gamma approximation, both population and sample-level inference is supported. As we demonstrate through an analysis of gene expression data from The Cancer Genome Atlas (TCGA), TPAC pathway scores are more strongly associated with both patient prognosis and tumor stage than the scores generated by existing single sample pathway analysis methods. An R package implementing the TPAC method can be found athttps://hrfrost.host.dartmouth.edu/TPAC.
Understandable Multifunctionality Measures Using Hill Numbers
Authors: Byrnes Jarrett E. K. , Roger Fabian , Bagchi Robert
Published: March 2022

In ecology, multifunctionality measures the simultaneous performance of multiple ecosystem functions. If species diversity describes the variety of species that together build the ecosystem, multifunctionality attempts to describe the variety of functions these species perform. A range of methods have been proposed to quantify multifunctionality, successively attempting to alleviate problems that have been identified with the previous methods. This has led to a proliferation of more-or-less closely related metrics which, however, lack an overarching theoretical framework. Here we borrow from the comprehensive framework of species diversity to derive a new metric of multifunctionality. Analogously to the effective number of species used to quantify species diversity, the metric we propose is influenced both by the number of functions as well as, crucially, the evenness of performance levels across functions. In addition, the effective multifunctionality also considers the average level at which the functions are performed. The result is a measure of the cumulative performance of the system were all functions provided equally. The framework allows for the inclusion of the correlation structure among functions, thus allowing it to account for non-independence between functions. We show that the average metric is a special case of the newly proposed metric when all functions are uncorrelated and performed at equal levels. We hope that by providing a new metric of multifunctionality anchored in the rigorous framework of species diversity based on effective numbers, we will overcome the considerable skepticism that the larger community of ecologists has built against indices of multifunctionality. We thereby hope to help popularize this important concept which, as biological diversity, describes a fundamental property of ecosystems and thus lies at the heart of ecology.
Influence of perceptual load on attentional orienting in post-stroke fatigue: a study of auditory evoked potentials
Authors: De Doncker William , Kuppuswamy Annapoorna
Published: March 2022

Objective

Increasing perceptual load alters behavioural outcomes in post-stroke fatigue. While the effect of perceptual load on top-down attentional processing is known, here we investigate if increasing perceptual load modulates bottom-up attentional processing in a fatigue dependent manner.

Methods

In this cross-sectional observational study, in twenty-nine first-time non-depressed stroke survivors, an auditory oddball task consisting of target, standard and novel tones was performed in conditions of low and high perceptual load. Electroencephalography was used to measure auditory evoked potentials. Perceived effort was rated using the visual analog scale at regular intervals during the experiment. Fatigue was measured using the fatigue severity scale. The effect of fatigue and perceptual load on behaviour (response time, accuracy, and effort rating) and auditory evoked potentials (amplitude and latency) was examined using mixed model ANOVAS.

Results

Response time was prolonged with greater perceptual load and fatigue. There was no effect of load or fatigue on accuracy. Greater effort was reported with higher perceptual load both in high and low fatigue. p300a amplitude of auditory evoked potentials (AEP) for novel stimuli was attenuated in high fatigue with increasing load when compared to low fatigue. Latency of p300a was longer in low fatigue with increasing load when compared to high fatigue. There were no effects on p300b components, with smaller N100 in high load conditions.

Interpretation

High fatigue specific modulation of p300a component of AEP with increasing load is indicative of distractor driven alteration in orienting response, suggestive of compromise in bottom-up selective attention in post-stroke fatigue.
Heterocyclic aromatic amines (HAAs) target mitochondrial physiology
Authors: Sammi Shreesh Raj , Syeda Tauqeerunnisa , Foguth Rachel , Cannon Jason
Published: March 2022

Heterocyclic aromatic amines (HAA) may be found naturally in plants or are formed through the Maillard reaction when meat is cooked at high temperatures. Previous studies have indicated HAAs are especially toxic to dopaminergic neurons, whereas specific exposures may also affect other neuronal populations such as cholinergic neurons. Biochemical mechanisms of neurotoxic action implicate elevated oxidative stress and afflicted mitochondria. Notably, these mechanisms are of importance in Alzheimer’s disease (AD) and Parkinson’s disease (PD). Most neurodegenerative disease cases are sporadic, where environmental and dietary factors may modulate risk. To further investigate HAA neurotoxicity, we tested the effect of common HAA (harmane, harmine, norharmane, PhIP, and HONH-PhIP) exposure on mitochondrial physiology, a key pathogenic target in AD and PD. Upon assessing mitochondrial bioenergetics, we observed a significant reduction in basal respiration, ATP production, maximal respiratory capacity, and non-mitochondrial respiration, indicating that HAA negatively impacts mitochondrial respiration. Followed by more specific studies on individual mitochondrial complexes, it was found that harmane, harmine, norharmane specifically inhibit complex I enzyme activity, whereas HONH-PhiP, a reactive metabolite of PhIP, inhibits Complex III enzyme activity. Our findings provide significant advancement with respect to underlying mechanisms of toxicity, though also validating HAA exposure as a potential risk factor for AD and PD.
Maternal separation induces autism spectrum disorder in young rhesus monkeys
Authors: Ren Xiao-Feng , Wu Shi-Hao , Zhou Hui , Lv Long-Bao , Qiu Zi-Long , Feng Xiao-Li , Hu Xin-Tian
Published: March 2022

Autism spectrum disorder (ASD) is a class of severe neurodevelopmental disorders with a high incidence in young children, and its pathogenesis remains elusive. There is no effective treatment, and ASD children usually have a hard time in integrating into society and leading a normal life, which places a heavy burden on the families and society. Studies have shown that in addition to genetic factors, environmental factors are another important risk contributing to the pathogenesis of ASD. Early environmental adversity, which can lead to abnormal brain development and affect cognition and behavior, greatly increases the incidence of a variety of brain developmental diseases including ASD. However, studies on this aspect are inadequate at present, and no clear conclusions can be drawn. We explored whether early adversity could trigger ASD core clinical symptoms in macaques by modeling early adversity through maternal separation. In this study, we conducted a rigorous behavioral analysis of 12 male macaques (1.5-2 years old) that underwent maternal separation and 9 male normal macaques of the same age that had been mother raised, and found that maternal separation could induce a small number of the young individuals to develop three core symptoms of ASD, including social impairment, stereotyped behaviors, and restricted interest simultaneously. According to DSM-V and ASD clinical diagnostic criteria, these individuals should be ASD macaques for having all the three core ASD symptoms at the same time., For the first time, this study reveals that early environmental adversity can lead to ASD pathogenesis in monkeys, and provides a new approach for future ASD studies and modeling ASD monkeys.
Behavioral and dopaminergic signatures of resilience
Authors: Willmore Lindsay , Cameron Courtney , Yang John , Witten Ilana , Falkner Annegret
Published: March 2022

Chronic stress can have lasting adverse consequences in some individuals, yet others are resilient to the same stressor1,2. While previous work found differences in the intrinsic properties of mesolimbic dopamine (DA) neurons in susceptible and resilient individuals after stress was over;3–10 the causal links between DA activity during stress, dynamic stress-evoked behavior, and individual differences in susceptibility and resilience are not known. Here, we record behavior and neural activity in DA projections to the nucleus accumbens (NAc, signals reward11–14) and to the tail striatum (TS, signals threat15–18) during a multiday chronic social defeat paradigm and discover behavioral and neural signatures of resilience. Using supervised and unsupervised behavioral quantification, we find that resilient and susceptible individuals employ different behavioral strategies during stress. In addition, NAc-DA (but not TS-DA) activity is higher in the proximity of the aggressor in resilient mice, consistent with a greater subjective value of the aggressor. Moreover, NAc-DA tends to be elevated at the onset of fighting back in resilient mice and at the offset of attacks in susceptible mice. To test whether DA activation during defeat can generate resilience, and if its timing with respect to behavior is critical, we performed optogenetic stimulation of NAc-DA in open-loop (randomly timed) during defeat or timed to specific behaviors using real-time pose-tracking and behavioral classification. We find that both open-loop DA activation and fighting-back-timed activation promote resilience, in both cases reorganizing behavior during defeat toward resilience-associated patterns. Attack offset-timed activation promotes avoidance during defeat but does not promote susceptibility afterwards. Together, these data suggest a model whereby, during stress, DA in the NAc can increase resilience primarily by elevating the subjective value of the stressor rather than by reinforcing particular stress-responsive behaviors.
Molecular determinants of the Bacillus subtilis chromosome origin basal unwinding system
Authors: Pelliciari Simone , Burnham Daniel R. , Merces George , Yardimci Hasan , Murray Heath
Published: March 2022

Genome duplication is essential for cell proliferation and DNA synthesis is generally initiated by dedicated replication proteins at specific loci termed origins. During DNA replication initiation in bacteria, the ubiquitous DnaA protein engages both double-strand DNA (dsDNA) and single-stranded DNA (ssDNA) at the chromosome origin (oriC) to promote DNA duplex unwinding. While the molecular basis for DnaA binding to a specific dsDNA element (“DnaA-box”) has been established, the mechanism for DnaA binding to a specific ssDNA motif (“DnaA-trio”) is unclear. Here we define specific steps of DnaA-trio engagement by Bacillus subtilis DnaA. Single-molecule total internal reflection fluorescence microscopy indicates that DnaA proteins are loaded onto DnaA-trios using DnaA-boxes located on a shared DNA polymer. Chemical modification of either the phosphodiester backbone or the nucleobases revealed that three DnaA-trio repeats proximal to DnaA-boxes are necessary and sufficient to promote DnaA-dependent strand separation, and that the amino group from the central nucleobase of the DnaA-trio is critical for this reaction. Finally, based on electrophoretic mobility shift assays, we propose that during replication initiation DnaA progresses from DnaA-boxes to nucleobase recognition at DnaA-trios before engaging the phosphodiester backbone and destabilizing the DNA duplex. These results provide new molecular insight into DnaA-dependent Bacterial Unwinding System (BUS) activity at a bacterial chromosome origin.
Novel repertoire of tau biosensors to monitor pathological tau transformation and seeding activity in living cells
Authors: Cecon Erika , Oishi Atsuro , Luka Marine , Ndiaye-Lobry Delphine , François Arnaud , Lescuyer Mathias , Panayi Fany , Dam Julie , Machado Patricia , Jockers Ralf
Published: March 2022

Aggregates of the tau protein are a well-known hallmark of several neurodegenerative diseases, collectively referred as tauopathies, including frontal temporal dementia and Alzheimer’s disease (AD). Monitoring the transformation process of tau from physiological monomers into pathological oligomers or aggregates in a high-throughput, quantitative manner and in a cellular context is still a major challenge in the field. Identifying molecules able to interfere with those processes is of high therapeutic interest. Here, we developed a series of inter- and intramolecular tau biosensors based on the highly sensitive Nanoluciferase (Nluc) binary technology (NanoBiT) able to monitor the pathological conformational change and self-interaction of tau in living cells. Our repertoire of tau biosensors reliably reporti.molecular proximity of physiological full-length tau at microtubules;ii.changes in tau conformation and self-interaction associated with tau phosphorylation, as well asiii.tau interaction induced by seeds of recombinant tau or from mouse brain lysates of a mouse model of tau pathology. By comparing biosensors comprising different tau forms (i.e.full-length or short fragments, wild-type or the disease-associated tau(P301L) variant) further insights in the tau transformation process are obtained. Proof-of-concept data for the high-throughput suitability and identification of molecules interfering with the pathological tau transformation processes are presented. This novel repertoire of tau biosensors is aimed to boost the disclosure of molecular mechanisms underlying pathological tau transformation in living cells and to discover new drug candidates for tau-related neurodegenerative diseases.
Mitochondrial Matrix Protease ClpP Agonists inhibit Cancer Stem Cell Function in Breast Cancer Cells by Disrupting Mitochondrial Homeostasis
Authors: Greer Yoshimi E. , Hernandez Lidia , Fennell Emily M. J. , Voeller Donna , Chari Raj , Gilbert Sam , Tang Binwu , Hafner Markus , Annunziata Christina M. , Iwanowicz Edwin , Graves Lee M. , Lipkowitz Stanley
Published: March 2022

Mitochondria are multifaceted organelles which are important for bioenergetics, biosynthesis and signaling in metazoans. Mitochondrial functions are frequently altered in cancer to promote both the energy and the necessary metabolic intermediates for biosynthesis required for tumor growth. Cancer stem cells (CSCs) contribute to chemotherapy resistance, relapse, and metastasis. Recent studies have shown that while non-stem, bulk cancer cells utilize glycolysis, breast CSCs are more dependent on oxidative phosphorylation (OxPhos) and therefore targeting mitochondria may inhibit CSC function. We previously reported that small molecule ONC201, which is an agonist for the mitochondrial caseinolytic protease (ClpP), induces mitochondrial dysfunction in breast cancer cells. In this study, we report that ClpP agonists inhibit breast cancer CSC functionin vitroandin vivo. Mechanistically, we found that OxPhos inhibition downregulates multiple pathways required for CSC function, such as the mevalonate pathway, YAP, Myc, and the HIF pathway. ClpP agonists showed significantly greater inhibitory effect on CSC functions compared with other mitochondria-targeting drugs. Further studies showed that ClpP agonists deplete NAD(P)+ and NAD(P)H and induce redox imbalance, and dysregulate one-carbon metabolism and proline biosynthesis. Downregulation of these pathways by ClpP agonists further contribute to the inhibition of CSC function. In conclusion, ClpP agonists inhibit breast CSC functions by disrupting mitochondrial homeostasis in breast cancer cells and inhibiting multiple pathways critical to CSC function.
Functional analysis of the N-terminal region of Vibrio FlhG, a MinD-type ATPase in flagellar number control
Authors: Homma Michio , Mizuno Akira , Hao Yuxi , Kojima Seiji
Published: March 2022

GTPase FlhF and ATPase FlhG are two key factors involved in regulating the flagellum number in Vibrio alginolyticus. FlhG is a paralog of the Escherichia coli cell division regulator MinD, which has a longer N-terminal region. Deleting the N-terminal region of FlhG results in cells with multiple flagella. The Q9A mutation in the DQAxxLR motif of the N-terminal region prevents it from activating the GTPase activity of FlhF in vitro and results in a multi-flagellation phenotype. The mutant FlhG protein was remarkably reduced compared to that of the wild-type protein in vivo. When the mutant FlhG was expressed at the same level as the wild-type FlhG, the number of flagella was restored to the wild-type level. Once synthesized in Vibrio cells, the N-terminal region mutation in FlhG seems not to affect the protein stability. We speculated that the flhG translation efficiency is decreased by N-terminal mutation. Our results suggest that the N-terminal region of FlhG controls the number of flagella by adjusting the FlhF activity and the amount of FlhG in vivo. We speculate that the regulation by FlhG, achieved through transcription by the master regulator FlaK, is affected by the mutations, resulting in reduced flagellar formation by FlhF.
SUMO monoclonal antibodies vary in sensitivity, specificity, and ability to detect SUMO conjugate types
Authors: Garvin Alexander J. , Lanz Alexander J. , Morris Joanna R.
Published: March 2022

Monoclonal antibodies (MAb) to members of the Small Ubiquitin-like modifier (SUMO) family are essential tools in the study of cellular SUMOylation. However, many reagents are poorly validated, and the choice of which antibody to use for which detection format is without an evidence base. Here we test twenty-four anti-SUMO monoclonal antibodies for sensitivity and specificity to SUMO1-4 in monomeric and polymeric states in dot-blots, immunoblots, immunofluorescence and immunoprecipitation. We find substantial variability between SUMO MAbs for different conjugation states, detection of increased SUMOylation in response to thirteen different stress agents and as enrichment reagents for analysis of SUMOylated RanGAP1 or KAP1. All four anti-SUMO4 monoclonal antibodies tested cross-reacted with SUMO2/3, and several SUMO2/3 monoclonal antibodies cross-reacted with SUMO4. ~10% of tested monoclonal antibodies produced specific results across multiple applications.
Fragmentation and entanglement limit vimentin intermediate filament assembly
Authors: Tran Quang D. , Sorichetti Valerio , Pehau-Arnaudet Gerard , Lenz Martin , Leduc Cécile
Published: March 2022

Networks of intermediate filaments (IFs) need to constantly reorganize to fulfil their functions at different locations within the cell. The mechanism of IF assembly is well described and involves filament end-to-end annealing. By contrast, the mechanisms involved in IF disassembly are far less understood.In vitro, IFs are assumed to be very stable and their disassembly negligible. IF fragmentation has been observed in many cell types, but it has been suggested to be associated with active processes such as IF post-translational modifications. In this article, we uncover the contribution of filament spontaneous fragmentation in the assembly dynamics of type III vimentin IF using a combination ofin vitroreconstitution probed by fluorescence imaging and theoretical modeling. We first show that vimentin assembly at low concentrations results in an equilibrium between filament annealing and fragmentation at times ≥24 hours. At higher concentrations, entanglements kinetically trap the system out of equilibrium, and we show that this trapping is reversible upon dilution. Taking into account both fragmentation and entanglement, we estimate that the mean bond breaking time is ∼18 hours. This translates into a mean breaking time of ∼ 5 hours for a 1 μm long filament, which is a relevant time scale for IF reorganization in live cells. Finally, we provide direct evidence through dual-color imaging that filament fragmentation and annealing coexist during assembly. By showing that IF fragmentation can occur without cofactors or post-translational modifications, our study provides new insights into the physical understanding of the IF length regulation.
A systematized review and qualitative synthesis of potential risk factors associated with the occurrence of non‐O157 Shiga toxin‐producing Escherichia coli (STEC) in the primary production of cattle
Authors: Withenshaw Susan M. , Smith Richard P. , Davies Rob , Smith Alice E. O. , Gray Elizabeth , Rodgers John
Published: March 2022

Human infection with Shiga toxin‐producing Escherichia coli (STEC) causes an estimated 2.8 million cases of acute illness worldwide each year. Serogroup O157 is the most commonly diagnosed STEC in humans, but cases linked to non‐O157 STEC serogroups have increased recently due to increased surveillance and improvements to detection methods. Cattle are an important reservoir for STEC O157 and the same may be true for non‐O157 STEC; therefore, reducing the occurrence of these pathogens in cattle could mitigate human infection risk. A systematized literature review of articles published within the Scopus database since 2010 (employing a partially systematic approach) was therefore conducted followed by qualitative synthesis of evidence to provide a structured overview of potential risk factors for non‐O157 STEC in primary cattle production. Overall, few relevant studies were identified (n = 22), highlighting that more studies are needed. Consistently significant associations were only identified with respect to cattle age (broadly higher rate of isolation from young animals compared to adults) and season of sampling (generally increased isolation of non‐O157 STEC in summer). However, wide variation in study designs, including notable differences in laboratory detection methods, means drawing more general conclusions is currently not possible based on the results of this review. However, it is likely that the development of more sensitive methods for non‐O157 STEC detection in potential livestock reservoirs and increased standardization across statistically sound epidemiological investigations are required to identify pertinent risk factors.
Preventable presentations of older adults to emergency departments: General practitioners' perspectives
Authors: Baskaran Radheshan , Gonski Peter N , Metz Colin
Published: March 2022

Objective

To describe general practitioners' (GP) perspectives of older patients presenting to the ED, reasons they would refer to the ED and how they utilise community services to help manage older adults.

Methods

A descriptive study conducted in the Sutherland Shire, Sydney. Case files were compiled using electronic medical records for 50 patients over 70 years old who presented to the ED of The Sutherland Hospital, a teaching hospital in Sydney. Surveys were provided to 10 GPs who each analysed five patients' presentations. Primary outcome was whether the GP would refer the patient to the ED. Secondary outcomes included reasons GPs referred to the ED, and their referral patterns of local community services.

Results

Of the 50 patients who presented to the ED, GPs would have referred 21 (42%) to the ED and managed 29 (58%) in the community. The most common reasons GPs would have referred to the ED was that they were ‘too unwell’, or needed ‘urgent imaging or blood tests’. In 26 (52%) of the patients, GPs were aware of a local service that could help manage the patient and would have made that referral in 21 (42%) patients. Rapid Access Diagnosis and Intervention Unit and Geriatric Flying Squad are two of the local aged care services GPs would have referred to most commonly.

Conclusion

GPs reported they would have been able to manage a significant proportion of older adults who presented to the ED in the community without referring to the ED. Severe and acute illness requiring urgent evaluation and intervention was the main reason GPs would refer to the ED.
Re‐infection in COVID‐19: Do we exaggerate our worries?
Authors: Arslan Yusuf , Akgul Fethiye , Sevim Bunyamin , Varol Zeynep Sedef , Tekin Suda
Published: March 2022

Background

Protective long‐term immunity following coronavirus disease 2019 (COVID‐19) is unclear. The study evaluated the relationship between the vaccination status and risk factors in the re‐infection of patients with a diagnosis of COVID‐19 who reported to the Public Health Management System in a province in south‐eastern Turkey.

Methods

Patients with positive results for the severe acute respiratory syndrome coronavirus 2 by the real‐time reverse transcription polymerase chain reaction (RT‐PCR) test in respiratory samples were defined as confirmed cases. Reinfection was diagnosed in cases with COVID‐19 real‐time RT‐PCR positivity, with or without COVID‐19–like symptoms, in at least 90 days after the first infection/disease.

Results

A total of 58 811 patients with the diagnosis of COVID‐19 from March 11, 2020, to August 31, 2021, were included in the study. Re‐infection was detected in 421 (0.7%) of all patients. The mean age of the cases was 38.0±16.0 years, and 51% of them were female. Eight (2.0%) of the cases resulted in death due to re‐infection. No hospitalization or mortality was observed in fully vaccinated patients. Additionally, none of the mortal cases had completed the vaccination schedule.

Conclusions

We are concerned that the re‐infection rates and mortality may increase due to new variant strains. Vaccination is the greatest weapon against progression to critical illness in re‐infections, even with existing mutations. Therefore, it is important for those without a full vaccination schedule to be vaccinated, even if they have been previously infected.
Bone metabolism parameters and their relation to cytogenetics in multiple myeloma
Authors: Krhovska Petra , Pika Tomas , Proskova Jitka , Balcarkova Jana , Zapletalova Jana , Bacovsky Jaroslav , Minarik Jiri
Published: March 2022

Objectives

Our aim was to correlate serum levels of selected markers of bone metabolism and bone marrow microenvironment to cytogenetic changes in patients with multiple myeloma (MM).

Methods

We assed cytogenetic changes in 308 patients and correlated them with the following levels of bone marrow metabolism: thymidine kinase (TK), β2‐microglobulin (b‐2‐m), Dickkopf‐1 protein (DKK‐1), C‐terminal telopeptide collagen‐I (ICTP), N‐terminal propeptide of type I procollagen (PINP), receptor for interleukin 6 (rIL‐6), vascular cell adhesive molecule‐1 (VCAM), soluble intercellular adhesion molecule‐1, osteoprotegerin (OPG), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), syndecan‐1 (SYN‐1) and Fas antigen.

Result

Individuals with delRB1 had lower levels of OPG (M = 7.39 vs. 5.46 pmol/L, p = .025) and VEGF (M = 304 vs. 196 pg/ml; p = .036). t(14;16) was associated with higher β2m levels (M = 7.59 vs. 4.13 mg/L; p = .022) and lower DKK‐1 levels (M = 4465 ng/L vs. 12,593). The presence of 1q21 gain was associated with higher levels of TK (M = 100.0 vs. 11.0 IU/L, p = .026) and lower levels of PINP (M = 49.3 vs. 67.4 mg/L, p = .030).

Conclusions

Our analysis has shown, some cytogenetic changes, especially delRB1, t(14;16) and 1q21gain, which affect the components of the cytokine network in multiple myeloma.
Continental United States may lose 1.8 petagrams of soil organic carbon under climate change by 2100
Authors: Gautam Sagar , Mishra Umakant , Scown Corinne D. , Wills Skye A. , Adhikari Kabindra , Drewniak Beth A.
Published: March 2022

Aims

High‐resolution information on soils’ vulnerability to climate‐induced soil organic carbon (SOC) loss can enable environmental scientists, land managers, and policy makers to develop targeted mitigation strategies. This study aims to estimate baseline and decadal changes in continental US surface SOC stocks under future emission scenarios.

Location

Continental United States.

Time period

2014–2100.

Methods

We used recent SOC field observations (n = 6,213 sites), environmental factors (n = 32), and an ensemble machine learning (ML) approach to estimate baseline SOC stocks in surface soils across the continental United States at 100‐m spatial resolution, and decadal changes under the projected climate scenarios of Coupled Model Intercomparison Project Phase Six (CMIP6) earth system models (ESMs).

Results

Baseline SOC projections from ML approaches captured more than 50% of variability in SOC observations, whereas ESMs represented only 6–16% of observed SOC variability. ML estimates showed a mean total loss of 1.8 Pg C from US surface soils under the high‐emission scenario by 2100, whereas ESMs showed no significant change in SOC stocks with wide variation among ESMs. Both ML and ESM predictions agree on the direction of SOC change (net emissions or sequestration) across 46–51% of continental US land area. These differences are attributable to the high‐resolution site‐specific data used in the ML models compared to the relatively coarse grid represented in CMIP6 ESMs.

Main conclusions

Our high‐resolution estimates of baseline SOC stocks, identification of key environmental controllers, and projection of SOC changes from US land cover types under future climate scenarios suggest the need for high‐resolution simulations of SOC in ESMs to represent the heterogeneity of SOC. We found that the SOC change is sensitive to key soil related factors (e.g. soil drainage and soil order) that have not been historically considered as input parameters in ESMs, because currently more than 95% variability in the SOC of CMIP6 ESMs is controlled by net primary productivity, temperature, and precipitation. Using additional environmental factors to estimate the baseline SOC stocks and predict the future trajectory of SOC change can provide more accurate results.
ReptIslands: Mediterranean islands and the distribution of their reptile fauna
Authors: Bonardi Anna , Ficetola Gentile Francesco , Razzetti Edoardo , Canedoli Claudia , Falaschi Mattia , Lo Parrino Elia , Rota Noemi , Padoa‐Schioppa Emilio , Sindaco Roberto
Published: March 2022

Aim

Analyses of biogeographical patterns and macroecology of islands require large datasets reporting the occurrence of species. The Mediterranean region is a biodiversity hotspot, which hosts a large number of reptile species and has been the focus of many studies. Nevertheless, comprehensive inventories describing the features and biodiversity of these environments are lacking. We gathered a dataset summarizing data on reptile distribution on islands of the Mediterranean basin and Macaronesia, also including detailed information on the geographical features.

Location

Islands from the Mediterranean Basin, the Atlantic Ocean within the Mediterranean biogeographical region, and Macaronesia (Canary and Savage Islands, Azores, Madeira and Cape Verde).

Time period

Present.

Taxon

Reptiles (squamates and turtles).

Methods

Initially, we developed a geographical database describing islands of the study region, then gathered information on reptile occurrences from 757 bibliographical sources, including atlases, published papers and the grey literature. Through a critical review of these sources, we also obtained information on the status of populations (native, island endemic or non‐native) and on the reliability of occurrence data.

Results

We obtained basic geographical information from 1875 islands covering the whole study region and with a very broad range of geographical features. We gathered >4150 records of reptile occurrence on islands, referring to 198 taxonomic units (species or species complexes); information on population status was available for 84.9% of records. Data are provided as comma‐delimited text files.

Main conclusions

The database provides a key resource for biogeographical analyses and can also serve as a backbone for conservation studies. The availability of a large database on island features can also be useful for biogeographers working on other taxonomic groups. Nevertheless, more data are required for some geographical areas, in order to ascertain the status (e.g., native vs. non‐native) of many populations and to understand the interplay between natural and human‐driven processes.
Urethroplasty for chordee with a paper‐thin hypoplastic urethra: A long‐term study
Authors: Zhou Guanglun , Yin Jianchun , Sun Junjie , Liu Xiaodong , Su Jiahong , Li Shoulin
Published: March 2022

Objectives

To establish a standard surgical procedure for children with chordee with a paper‐thin hypoplastic urethra, which was based on the degree of curvature and urethral plate quality. To guidelines for the management of this disorder.

Methods

We reviewed 58 cases of chordee with a paper‐thin hypoplastic urethra, managed between March 2006 and September 2020. The age of the patients ranged from 23 to 89 months. Operative details and postoperative complications were analyzed.

Results

Mild‐moderate chordee with a paper‐thin hypoplastic urethra correction was performed using a tubularized incised plate (13 cases) or onlay island flap (five cases) technique after penile degloving. Severe chordee with a paper‐thin hypoplastic urethra required transection of the urethra and underwent a Duckett (11 cases) or staged (29 cases) urethroplasty. Complications in the tubularized incised plate and onlay island flap groups were 7.7% and 20%, respectively. The overall complication rate was 10.3% in the staged group and 27.3% in the Duckett group.

Conclusions

Reconstruction of the entire hypoplastic urethra should be recommended in the management of chordee with a paper‐thin hypoplastic urethra. We propose an algorithm based on the degree of curvature and urethral plate quality. The tubularized incised plate or onlay island flap technique can be used for mild to moderate chordee with a paper‐thin hypoplastic urethra, and the outcome of the tubularized incised plate technique tends to be better than that of the onlay island flap technique. Duckett or staged urethroplasty is suitable for severe chordee with a paper‐thin hypoplastic urethra, and the staged technique can improve the overall success rate.
Do different adverse childhood experiences lead to specific symptoms of psychosis in adulthood? A systematic review of the current literature
Authors: Grindey Ashleigh , Bradshaw Tim
Published: March 2022

Previous research has demonstrated significant associations between adverse childhood experiences (ACEs) and risks of psychosis. Further research has examined underlying mechanisms to understand the relationship between these variables. This review aimed to explore the associations between various ACEs and the development of different psychotic symptoms in adulthood. The Cochrane Library, Cinahl, PsychINFO, Medline, Embase, and Web of Science were searched from January 1980 to November 2021 to ensure a systematic review of relevant literature. Poverty, fostering, adoption, childhood emotional and physical neglect, and childhood physical (CPA), sexual (CSA), and emotional abuse (CEA) significantly correlated with delusions. Significant relationships were found between hallucinations and CSA and CPA. Paranoia correlated with violent adversities including CPA, assault, and witnessing killing. Limited associations were identified for thought disorder and negative symptoms. The findings of this review indicate that there may be a degree of specificity between various ACEs and psychotic symptoms, but these findings are subject to some limitations. The findings also demonstrate the importance of inquiring about and addressing ACE in clinical practice to develop formulations and treatment plans for individuals with psychosis.
Safety and efficacy for hair removal in dark skin types III and IV with a high‐powered, combined wavelength (810, 940 and 1060 nm) diode laser: A single‐site pilot study
Authors: Gold Michael H. , Biron Julie , Wilson April , Viera‐Mármol Gregorio , Lamas Reyna E. Vargas , Castillejos‐Pallàs Marta , Ferrández‐Martínez Jose A.
Published: March 2022

Background

Previous studies have demonstrated the superior efficacy of a high‐power diode laser (4800 W) with a wavelength of 810 nm over others with less power and the same wavelength, while also being safe and comfortable for the patient. However, the use of this laser is limited on dark skin.

Objectives

This study aims to compare the efficacy, safety, and comfort of a 4800 W diode laser (810 nm) with that of the new Blend diode laser (810 nm, 940 nm, and 1064 nm). Furthermore, the study aims to demonstrate that the Blend diode laser delivers better results on darker skin.

Materials and methods

A 810 nm diode laser was compared with the Blend diode laser (810, 940 and 1064 nm) (Primelase, Cocoon Medical). A side‐by‐side comparative study was carried out over three sessions involving fourteen participants with skin types III and IV, with evaluation of the results 6 months after treatment. The study was performed at the Tennessee Clinical Research Center, Nashville, Tennessee, USA. This evaluation was based on efficacy, safety, comfort, and participant satisfaction.

Results

Blend diode laser treatments were performed with fluences 40% (SE = 0.04%) higher than those of the 810 nm. Besides mild‐to‐moderate transient discomfort during the procedure, the Blend diode laser also produced an increased pricking sensation that was 1.8 points higher on a 10‐point scale (p < 0.05), due to the higher fluence used. Hair reduction was 12% higher with the Blend diode laser, with a confidence level of 70%. Moreover, participants were more satisfied with the results of the Blend diode laser than with the diode laser (50% very satisfied vs. 36%, respectively). No long‐term adverse effects were observed.

Conclusions

The new Blend diode laser has been shown to be more effective and satisfactory than 810 nm diode laser on dark skin types III and IV, while also being safe and comfortable for participants.
Ancient mitochondrial genomes recovered from small vertebrate bones through minimally destructive DNA extraction: Phylogeography of the New Zealand gecko genus Hoplodactylus
Authors: Scarsbrook Lachie , Verry Alexander J. F. , Walton Kerry , Hitchmough Rodney A. , Rawlence Nicolas J.
Published: March 2022

Methodological and technological improvements are continually revolutionizing the field of ancient DNA. Most ancient DNA extraction methods require the partial (or complete) destruction of finite museum specimens, which disproportionately impacts small or fragmentary subfossil remains, and future analyses. We present a minimally destructive ancient DNA extraction method optimized for small vertebrate remains. We applied this method to detect lost mainland genetic diversity in the large New Zealand diplodactylid gecko genus Hoplodactylus, which is presently restricted to predator‐free island and mainland sanctuaries. We present the first mitochondrial genomes for New Zealand diplodactylid geckos, recovered from 19 modern, six historical/archival (1898–2011) and 16 Holocene Hoplodactylus duvaucelii sensu latu specimens, and one modern Woodworthia sp. specimen. No obvious damage was observed in post‐extraction micro‐computed tomography reconstructions. All “large gecko” specimens examined from extinct populations were found to be conspecific with extant Hoplodactylus species, suggesting their large relative size evolved only once in the New Zealand diplodactylid radiation. Phylogenetic analyses of Hoplodactylus samples recovered two genetically (and morphologically) distinct North and South Island clades, probably corresponding to distinct species. Finer phylogeographical structuring within Hoplodactylus spp. highlighted the impacts of Late Cenozoic biogeographical barriers, including the opening and closure of Pliocene marine straits, fluctuations in the size and suitability of glacial refugia, and eustatic sea‐level change. Recent mainland extinction obscured these signals from the modern tissue‐derived data. These results highlight the utility of minimally destructive DNA extraction in genomic analyses of less well studied small vertebrate taxa, and the conservation of natural history collections.