bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for anti‐inflammatory effects of firocoxib administered to mares with experimentally induced placentitis
Authors: Macpherson Margo L. , Giguère Steeve , Pozor Malgorzata A. , Burden Chelsie A. , Berghaus Londa J. , Berghaus Roy D. , Varner Jennifer C. , Hayna Justin T. , Benson Susanne M. , Randell Sarah A. , Lyle Sara K. , Kelleman Audrey A. , Hart Kelsey A. , Mallicote Martha F. , Horohov David W.
Published: February 2021

Problem

Minimal evidence exists supporting therapeutic selections for equine placentitis. The goal of this study was to characterize the anti‐inflammatory effects of firocoxib when administered to mares with placentitis.

Methods

Mares (gestation D270‐300) were assigned to: INFECT (n = 6; placentitis, no treatment), FIRO (n = 6; placentitis, firocoxib, 0.1 mg/kg, PO, daily), and NORM (n = 6; no infection/treatment). Allantoic fluid (8 hours, 24 hours, birth) and amniotic fluid (birth) were collected from mares after infection. Concentrations of IL‐1β, IL‐6, TNF‐α, IL‐10, PGF2α, and PGE2in fluids were measured by ELISA. mRNA expression of IL‐1β, IL‐6, TNF‐α, IL‐8, IL‐10, matrix metalloproteinases (MMPs) −1, 3, and 9 in fetal membranes/fetuses was quantified using real‐time PCR.

Results

Allantoic TNF‐α concentrations were lowest in FIRO at 8 hours and 24 hours post‐infection; IL‐6 concentrations were lower in FIRO than NORM at 8 hours, lower in FIRO than INFECT at 24 hours post‐inoculation, and lower in NORM than FIRO or INFECT at birth. Marginal mean allantoic IL‐β and IL‐10 concentrations were lower in FIRO and NORM than INFECT. Amniotic fluid cytokines were lowest in NORM with all measurements in that group being below the limit of detection. Allantoic PGF2αconcentrations were lower in FIRO and INFECT than NORM at 8 hours post‐inoculation, and lower in FIRO than INFECT or NORM at 24 hours post‐inoculation. Allantoic PGE2concentrations were lower in FIRO than INFECT. Amniotic PGF2αand PGE2concentrations were lower in NORM than INFECT. In fetal membranes, group differences with respect to IL‐1β, IL‐6, IL‐8, and MMP1 were dependent on tissue type.

Conclusions

Data suggest a suppressive effect of firocoxib administration on cytokine and prostaglandin production in mares with placentitis.
Transcriptomics‐determined chemokine‐cytokine pathway presents a common pathogenic mechanism in pregnancy loss and spontaneous preterm birth
Authors: Wang Peirong , Pan Jing , Tian Xiujuan , Dong Xiaoyan , Ju Weina , Wang Yong , Zhong Nanbert
Published: February 2021

Problem

Various etiological factors, such as infection and inflammation, may induce the adverse outcomes of pregnancy of miscarriage, stillbirth, or preterm birth. The pathogenic mechanisms associated with these adverse pregnancies are yet unclear. We hypothesized that a common pathogenic mechanism may underlie variant adverse outcomes of pregnancy, which are induced by genetic‐environmental factors. The specific objective of the current study is to uncover the common molecular mechanism(s) by identifying the specific transcripts that are present in variant subtypes of pregnancy loss and preterm birth.

Method of Study

Transcriptomic profiling was performed with RNA expression microarray or RNA sequencing of placentas derived from pregnancy loss (which includes spontaneous miscarriage, recurrent miscarriage, and stillbirth) and spontaneous preterm birth, followed by bioinformatic analysis of multi‐omic integration to identify pathogenic molecules and pathways involved in pathological pregnancies.

Results

The enrichment of common differentially expressed genes between full‐term birth and preterm birth and pregnancy loss of miscarriage and stillbirth revealed different pathophysiological pathway(s), including cytokine signaling dysregulated in spontaneous preterm birth, defense response, graft‐versus‐host disease, antigen processing and presentation, and T help cell differentiation in spontaneous miscarriage. Thirty‐three genes shared between spontaneous preterm birth and spontaneous miscarriage were engaged in pathways of interferon gamma–mediated signaling and of antigen processing and presentation. For spontaneous miscarriage, immune response was enriched in the fetal tissue of chorionic villi and in the maternal facet of the placental sac. The transcript of nerve growth factor receptor was identified as the common molecule that is differentially expressed in all adverse pregnancies: spontaneous preterm birth, stillbirth, spontaneous miscarriage, and recurrent miscarriage. Superoxide dismutase 2 was up‐regulated in all adverse outcomes of pregnancy except for recurrent miscarriage. Cytokine‐cytokine receptor interaction was the common pathway in spontaneous preterm birth and spontaneous miscarriage. Defense response was enriched in the fetal tissue of miscarriage and in the maternal tissue in spontaneous miscarriage.

Conclusions

Our results indicated that the chemokine‐cytokine pathway may play important roles in and function as a common pathogenic mechanism associated with, the different adverse outcomes of pregnancy, which demonstrated that differentially expressed transcripts could result from a common pathogenic mechanism associated with pregnancy loss and spontaneous preterm birth, although individual pregnancy outcomes may differ from each other phenotypically.
Profile and rural exposure for nursing and allied health students at two Australian Universities: A retrospective cohort study
Authors: Smith Tony , Sutton Keith , Beauchamp Alison , Depczynski Julie , Brown Leanne , Fisher Karin , Waller Susan , Wakely Luke , Maybery Darryl , Versace Vincent L.
Published: February 2021

Objective

Linking enrolment and professional placement data for students' from 2 universities, this study compares characteristics across universities and health disciplines. The study explores associations between students' location of origin and frequency, duration and type of placements.

Design

Retrospective cohort data linkage.

Setting

Two Australian universities, Monash University and the University of Newcastle.

Participants

Students who completed medical radiation science, nursing, occupational therapy, pharmacy or physiotherapy at either university between 2 February 2017 and 28 February 2018.

Interventions

Location of origin, university and discipline of enrolment.

Main outcome measure(s)

Main measures were whether graduates had multiple rural placements, number of rural placements and cumulative rural placement days. Location of origin, discipline and university of enrolment were the main explanatory variables. Secondary dependent variables were age, sex, socio‐economic indices for location of origin, and available placements.

Results

A total of 1,315 students were included, of which 22.1% were of rural origin. The odds of rural origin students undertaking a rural placement was more than 4.5 times greater than for urban origin students. A higher proportion of rural origin students had multiple rural placement (56.0% vs 14.9%), with a higher mean number of rural placement days. Public hospitals were the most common placement type, with fewer in primary care, mental health or aged care.

Conclusions

There is a positive association between rural origin and rural placements in nursing and allied health. To help strengthen recruitment and retention of graduates this association could be further exploited, while being inclusive of non‐rural students
Long‐acting muscarinic antagonists and small airways in asthma: Which link?
Authors: Cazzola Mario , Calzetta Luigino , Matera Maria Gabriella
Published: February 2021

Involvement of small airways, those of <2 mm in internal diameter, is present in all stages of asthma and contributes substantially to its pathophysiologic expression. Therefore, small airways are a potential target to achieve optimal asthma control. Airway tone, which is increased in asthma, is mainly controlled by the vagus nerve that releases acetylcholine (ACh) and activates muscarinic ACh receptors (mAChRs) post‐synaptically on airway smooth muscle (ASM). In small airways, M3 mAChRs are expressed, but there is no vagal innervation. Non‐neuronal ACh released from the epithelial cells that may express choline acetyltransferase in response to inflammatory stimuli, as well as from other structural cells in the airways, including fibroblasts and mast cells, can activate mAChRs. By antagonizing M3 mAChR, the contraction of the ASM is prevented and, potentially, local inflammation can be reduced and the progression of remodeling may be averted. In fact, ACh also contributes to inflammation and remodeling of the airways and regulates the growth of ASM. Several experimental studies have demonstrated the potential benefit derived from the use of mAChR antagonists, mainly long‐acting mAChR antagonists (LAMAs), on small airways in asthma. However, there are several confounding factors that may cause a wrong estimation of the relationship between LAMAs and small airways in asthma. Further studies are needed to differentiate broncholytic and anti‐inflammatory effects of LAMAs and to better understand the interaction between LAMAs and corticosteroids, also in the context of a triple therapy that includes a β2‐AR agonist, at different levels of the bronchial tree.
Open‐globe wounds in operation Iraqi Freedom and Operation Enduring Freedom: risk factors for poor visual outcomes and enucleation
Authors: Harris Justin P. , Justin Grant A. , Brooks Daniel I. , Woreta Fasika A. , Agrawal Rupesh V. , Ryan Denise S. , Weichel Eric D. , Colyer Marcus H.
Published: February 2021

Purpose

To determine the rates and types of open‐globe wounds in soldiers admitted to Walter Reed Army Medical Center from 2001 to 2011 after sustaining combat injuries.

Methods

Data were collected in the Walter Reed Ocular Trauma Database. Inclusion criteria were patients who suffered open‐globe injuries. Open‐globe injuries were classified by type of wound: corneal, corneo‐scleral or scleral, or type of open‐globe injury: perforating, rupture, penetrating or intraocular foreign body. The primary analysis assessed the effect on final visual acuity (VA) and the risk of enucleation.

Results

In this study, 285 (32.02%) open‐globe injuries were recorded in 890 eyes in the data set. Corneal wounds were noted in 127 (44.56%) eyes, corneo‐scleral wounds in 78 (27.37%) and scleral wounds in 129 (45.26%) eyes. The involvement of both the corneal and sclera was associated with poorer visual outcome (BCVA < 20/200) compared to injuries with an injury confined to either the cornea or scleral alone (p = 0.038). At a wound length of greater than approximately 14 mm, patients had 75% chance of having a poor final VA. Enucleation was performed in 64 (22.46%) eyes of patients with wounds. The type of wound was not found to be predictive of enucleation in multivariate analysis, but rather the type of open‐globe injury was predictive. Perforating (OR: 1.58, 95% CI: 1.43–1.72) and globe rupture injuries (OR: 1.49, 95% CI: 1.33–1.66) were more likely to undergo enucleation.

Conclusions

Open‐globe injuries occur frequently in combat ocular trauma. Poor final VA was noted most with corneo‐scleral wounds with approximately 50% of patients having a final VA less than 20/200.
Ankle contractures are frequent among children with cerebral palsy and associated with lower gross motor function and degree of spasticity
Authors: Krarup Lærke Hartvig , Kristensen Pia Kjær , Strand Louise , Bredtoft Sofie Langbo , Mechlenburg Inger , Nordbye‐Nielsen Kirsten
Published: February 2021

Aim

To estimate yearly prevalence of ankle contractures among children with cerebral palsy (CP). Moreover, to investigate whether age, gross motor function or spasticity are associated with ankle contracture.

Methods

We examined yearly prevalence of ankle contractures among 933 children based on data from a national clinical quality database from 2012 to 2019. We used the Gross Motor Function Classification System (GMFCS) and the Modified Ashworth Scale (MAS) to assess gross motor function and spasticity in the plantar flexors. Ankle contracture was defined as dorsiflexion with an extended knee equal to or below 0 degrees. Associations between age, GMFCS, spasticity and ankle contractures were analysed using multivariable regression and presented as odds ratios (OR) with 95% confidence intervals (95%CI).

Results

The prevalence of ankle contracture was 32% and did not change with calendar year. GMFCS IV–V compared to I–III (40.6% vs. 28.9%, OR = 1.5 (95%CI: 1.07–2.11) and MAS 2–4 compared to 0 (44.6% vs. 24.4%, OR = 2.5 (95%CI: 1.59–3.91) were associated with a higher prevalence of ankle contracture. Age was not associated with ankle contracture.

Conclusion

Ankle contractures are frequent among children with CP. Lower gross motor function and severe spasticity were associated with ankle contracture.
Suppurative thyroiditis: Systematic review and clinical guidance
Authors: Lafontaine Nicole , Learoyd Diana , Farrell Stephen , Wong Rosemary
Published: February 2021

Objective

Acute suppurative thyroiditis (AST) is a rare but potentially fatal condition which can initially be difficult to distinguish from the more common subacute thyroiditis (SAT). We aim to update understanding of this medical emergency.

Design

A systematic review over the past 20 years was performed on the epidemiology, clinical features, investigations, management and outcomes of AST. All full‐text cases of microscopy or culture‐ proven AST in the English literature were included.

Results

200 cases of AST have been described in 148 articles from January 2000 – January 2020. Bacterial AST is most common, often presenting with neck pain (89%) and fever (82%). Immunosuppression and pyriform sinus fistula are the most common causes, most often due to gram‐positive aerobes. Transient hyperthyroidism is common (42%). Aspiration and antibiotics are becoming a more common treatment. Overall mortality was 7.8%. Tuberculous and fungal AST are less likely to present with fever and neck pain. Fungal AST is more common in immunosuppressed individuals (31%) and has a high overall mortality (33%). Tuberculous AST is more common in TB endemic areas.

Conclusion

The symptoms and signs of AST commonly overlap with SAT and initially can be hard to diagnose. AST can be rapidly morbid or even fatal. Clinicians need to consider AST when they assess patients with thyroiditis who are systemically unwell, have high fever, high white cell count and c‐reactive protein, tender neck and abnormal neck imaging. An investigative and treatment strategy is described based on a systematic review of the literature.
Solution of intuitionistic fuzzy linear programming problem by dual simplex algorithm and sensitivity analysis
Authors: Mohan Suresh , Kannusamy Arun Prakash , Sidhu Sukhpreet Kaur
Published: February 2021

Sensitivity analysis is designed to study the effect on the optimal solution of changes in model parameters. This analysis is known to be an integral part of any real‐life problem solving. This gives a system a dynamic function that enables a researcher to analyze the behavior of the optimal solution as a result of changing the parameters of the model. In this article, postoptimality analysis for changes in objective functions and constraints is presented with suitable numerical illustrations by dual simplex method using magnitude based ranking of triangular intuitionistic fuzzy numbers. The sensitivity range is determined within which the parameters that exist in intuitionistic fuzzy linear programming problem can vary without affecting the optimality of the solution.
Leukocyte transcriptome indicators of development of infection in kidney transplant recipients
Authors: Schaenman Joanna M. , Rossetti Maura , Liang Emily C. , Lum Erik , Abdalla Basmah , Bunnapradist Suphamai , Pham Phuong Thu , Danovitch Gabriel , Reed Elaine F. , Cole Steve W.
Published: February 2021

After kidney transplantation, infection and death are important clinical complications, especially for the growing numbers of older patients with limited resilience to withstand adverse events. Evaluation of changes in gene expression in immune cells can reveal the underlying mechanisms behind vulnerability to infection. A cohort of 60 kidney transplant recipients was evaluated. Gene expression in peripheral blood mononuclear cells 3 months after kidney transplantation was analyzed to compare differences between patients with infection and those who were infection‐free in the first‐year post‐transplant. Pro‐inflammatory genes such as IL1B, CCL4, and TNF were found to be downregulated in post‐transplant PBMC from patients who developed infection. In contrast, genes involved in metabolism, HLA genes, and transcripts involved in type I interferon innate antiviral responses were found to be upregulated. Promoter‐based bioinformatic analyses implicated increased activity of interferon regulatory factors, erythroid nuclear factor (E2), and CCAAT‐enhancer‐binding protein (C/EBP) in patients who developed infections. Differential patterns of gene expression were observed in patients who developed infection after kidney transplantation, with patterns distinct from changes associated with patient age, suggesting possible mechanisms behind vulnerability to infection. Assessment of gene expression in blood may offer an approach for patient risk stratification and monitoring after transplantation.
Quantitative protein expression of blood‐brain barrier transporters in the vasculature of brain metastases of patients with lung and breast cancer
Authors: Bao Xun , Wu Jianmei , Jiang Jun , Tien An‐Chi , Sanai Nader , Li Jing
Published: February 2021

This study determined absolute transporter protein abundances in isolated microvessels of human noncancerous cerebral cortex as well as brain metastases of patients with lung and breast cancer, using a validated targeted proteomics approach. As compared with those in microvessels of noncancerous cerebral cortex, the median protein abundances of glucose transporter 1 (a brain endothelial marker) and sodium‐potassium pump (Na/K ATPase, a plasma membrane marker) were decreased by ~ 80% in brain metastasis microvessels. The major efflux transporters (ABCB1 and ABCG2) fell to undetectable in microvessels of more than 80% of brain metastasis specimens. Monocarboxylate transporter 1 was undetectable in microvessels of more than 80% of brain metastases, whereas large neutral amino acid transporter 1 levels remained unchanged. In conclusion, the integrity of the physical and biochemical barrier with respect to transporter protein expression is largely disrupted in brain metastasis tumor vasculatures. Differential transporter protein abundances at the blood‐brain barrier and blood‐brain tumor barrier provided mechanistic and quantitative basis for prediction of heterogeneous drug penetration into human brain and brain tumors, which is critical not only to the understanding of the success or failure of systemic chemotherapy in the treatment of brain tumors but also to the development of more effective therapeutic strategies.
Bouncing the network: A dynamical systems model of auditory–vestibular interactions underlying infants’ perception of musical rhythm
Authors: Tichko Parker , Kim Ji Chul , Large Edward W.
Published: February 2021

Previous work suggests that auditory–vestibular interactions, which emerge during bodily movement to music, can influence the perception of musical rhythm. In a seminal study on the ontogeny of musical rhythm, Phillips‐Silver and Trainor (2005) found that bouncing infants to an unaccented rhythm influenced infants’ perceptual preferences for accented rhythms that matched the rate of bouncing. In the current study, we ask whether nascent, diffuse coupling between auditory and motor systems is sufficient to bootstrap short‐term Hebbian plasticity in the auditory system and explain infants’ preferences for accented rhythms thought to arise from auditory–vestibular interactions. First, we specify a nonlinear, dynamical system in which two oscillatory neural networks, representing developmentally nascent auditory and motor systems, interact through weak, non‐specific coupling. The auditory network was equipped with short‐term Hebbian plasticity, allowing the auditory network to tune its intrinsic resonant properties. Next, we simulate the effect of vestibular input (e.g., infant bouncing) on infants’ perceptual preferences for accented rhythms. We found that simultaneous auditory–vestibular training shaped the model's response to musical rhythm, enhancing vestibular‐related frequencies in auditory‐network activity. Moreover, simultaneous auditory–vestibular training, relative to auditory‐ or vestibular‐only training, facilitated short‐term auditory plasticity in the model, producing stronger oscillator connections in the auditory network. Finally, when tested on a musical rhythm, models which received simultaneous auditory–vestibular training, but not models that received auditory‐ or vestibular‐only training, resonated strongly at frequencies related to their “bouncing,” a finding qualitatively similar to infants’ preferences for accented rhythms that matched the rate of infant bouncing.
The use of attention to maintain information in working memory: A developmental investigation of spontaneous refreshing in school‐aged children
Authors: Vergauwe Evie , Besch Vincent , Latrèche Caren , Langerock Naomi
Published: February 2021

The capacity of working memory is limited and undergoes important developmental changes during childhood. One proposed reason for the expansion of working memory capacity during childhood is the emergence and increased efficiency of active maintenance mechanisms, such as that of refreshing. Refreshing is a proposed mechanism to keep information active in working memory by bringing memory items back into the focus of attention. One prevalent view is that the spontaneous use of refreshing emerges around the age of 7 and becomes more efficient during middle childhood and beyond. Using a novel approach to examine refreshing in children in Experiment 1, we show, against common conceptions, that simply giving free time in a basic working memory task does not lead to spontaneous refreshing in 9–12‐year‐old children. Instead, their focus of attention appears to linger on the last‐presented memory item, even when ample time for refreshing is provided. Experimentally imposing the use of refreshing in Experiment 2, however, showed that children in this age range are able to switch their focus of attention away from the last‐presented item in switch to another memory item. Thus, the current study uncovers that children in middle childhood do not always spontaneously switch attention away from the last‐presented memory item to refresh the entire list, even though they are able to switch attention away from the last‐presented memory item when instructed to do so. The theoretical implications of these findings are discussed.
Kidney organoids: Research in developmental biology and emerging applications
Authors: Shimizu Tatsuya , Yamagata Kunihiro , Osafune Kenji
Published: February 2021

Kidney organoids generated from human pluripotent stem cells (hPSCs) have drastically changed the field of stem cell research on human kidneys within a few years. They are self‐organizing multicellular structures that contain nephron components such as glomeruli and renal tubules in most cases, but hPSC‐derived ureteric buds, the progenitors of collecting ducts and ureters, can also form three‐dimensional organoids. Today's challenges facing human kidney organoids are further maturation and anatomical integrity in order to achieve a complete model of the developing kidneys and ultimately a complete adult organ. Since chronic kidney disease (CKD) and impaired kidney function are an increasing burden on public health worldwide, there is an urgent need to develop effective treatments for various renal conditions. In this regard, hPSC‐derived kidney organoids may impact medicine by providing new translational approaches. The unique ability of kidney organoids derived from disease‐specific hPSCs to reproduce human diseases caused by genetic alterations may help provide the next generation of kidney disease models. Recent advances in the field of kidney organoid research have been generally accompanied by progress in developmental biology and other technological breakthroughs. In this review, we consider the current trends in kidney organoid technology, especially focusing on the relationship to the study of human kidney development, and discuss the remaining hurdles and prospects in regenerating human kidney structures beyond organoids.
Fenfluramine as antiseizure medication for epilepsy
Authors: Gogou Maria , Cross J Helen
Published: February 2021

Fenfluramine hydrochloride has classically been described as acting pharmacologically through a serotonergic mechanism. Therefore, it was initially used as an anorectic drug, given that impaired serotonin homeostasis may be associated with increased food intake. Although positive results were documented, cardiovascular concerns resulted in its temporary withdrawal. Nevertheless, a novel role in patients with epilepsy was later suggested by isolated clinical observations. The wide application of genetic testing allowed the classification (predominantly as Dravet syndrome) of patients in whom benefit was seen, while with the development of zebrafish models, its antiepileptic properties were confirmed at a molecular level. Data from randomized clinical trials have shown a beneficial effect of fenfluramine, as an adjunct therapy, on seizure control for children with Dravet syndrome, though there is still uncertainty about the impact on neurodevelopment in these patients. No signs of heart valve disease have been documented to date. Long‐term and appropriately designed clinical studies will verify whether fenfluramine is a therapeutic agent of high importance, living up to the promise shown so far.

What this paper adds

Fenfluramine is a very promising repurposed therapy specifically for seizures in Dravet syndrome.

The long‐term effect of fenfluramine on neurodevelopmental prognosis requires further investigation.
Gastric emptying of solutions containing the natural sweetener erythritol and effects on gut hormone secretion in humans: A pilot dose‐ranging study
Authors: Wölnerhanssen Bettina K. , Drewe Jürgen , Verbeure Wout , le Roux Carel W. , Dellatorre‐Teixeira Ludmilla , Rehfeld Jens F. , Holst Jens J. , Hartmann Bolette , Tack Jan , Peterli Ralph , Beglinger Christoph , Meyer‐Gerspach Anne C.
Published: February 2021

Aim

To determine whether a dose‐dependent effect in the stimulation of gut hormone release (plasma cholecystokinin [CCK], active glucagon‐like peptide‐1 [aGLP‐1] and peptide tyrosine tyrosine [PYY]) is found for the natural sweetener erythritol.

Materials and Methods

Twelve healthy, lean volunteers received solutions with 10, 25 or 50 g erythritol, or tap water enriched with 13C‐sodium acetate on four study days via a nasogastric tube in this randomized (active treatments), placebo‐controlled, double‐blind, cross‐over trial. Blood samples and breath samples (13C‐sodium acetate method for measurement of gastric emptying [GE]) were taken at regular intervals, and sensations of appetite and gastrointestinal symptoms were rated.

Results

We found (a) a dose‐dependent stimulation of CCK, aGLP‐1 and PYY, and slowing of GE, (b) no effect on blood glucose, insulin, motilin, glucagon or glucose‐dependent insulinotropic polypeptide, (c) no effect on blood lipids and uric acid, and (d) no abdominal pain, nausea or vomiting.

Conclusions

Solutions with 10 and 50 g of erythritol stimulated gut hormone release. Emptying of erythritol‐containing solutions from the stomach was slower compared with placebo. There was no effect on plasma glucose, insulin, glucagon, blood lipids or uric acid. All doses were well tolerated.
Global analysis reveals an environmentally driven latitudinal pattern in mushroom size across fungal species
Authors: Bässler Claus , Brandl Roland , Müller Jörg , Krah Franz S. , Reinelt Arthur , Halbwachs Hans
Published: February 2021

Although macroecology is a well‐established field, much remains to be learned about the large‐scale variation of fungal traits. We conducted a global analysis of mean fruit body size of 59 geographical regions worldwide, comprising 5340 fungal species exploring the response of fruit body size to latitude, resource availability and temperature. The results showed a hump‐shaped relationship between mean fruit body size and distance to the equator. Areas with large fruit bodies were characterised by a high seasonality and an intermediate mean temperature. The responses of mutualistic species and saprotrophs were similar. These findings support the resource availability hypothesis, predicting large fruit bodies due to a seasonal resource surplus, and the thermoregulation hypothesis, according to which small fruit bodies offer a strategy to avoid heat and cold stress and therefore occur at temperature extremes. Fruit body size may thus be an adaptive trait driving the large‐scale distribution of fungal species.
Paternal age negatively affects sperm production of the progeny
Authors: Vuarin Pauline , Lesobre Loïc , Levêque Gwènaëlle , Saint Jalme Michel , Lacroix Frédéric , Hingrat Yves , Sorci Gabriele
Published: February 2021

Parental age has profound consequences for offspring’s phenotype. However, whether patrilineal age affects offspring sperm production remains unknown, despite the importance of sperm production for male reproductive success in species facing post‐copulatory sexual selection. Using a longitudinal dataset on ejaculate attributes of the houbara bustard, we showed that offspring sired by old fathers had different age‐dependent trajectories of sperm production compared to offspring sired by young fathers. Specifically, they produced less sperm (−48%) in their first year of life, and 14% less during their lifetime. Paternal age had the strongest effect, with weak evidence for grandpaternal or great grandpaternal age effects. These results show that paternal age can affect offspring reproductive success by reducing sperm production, establishing an intergenerational link between ageing and sexual selection.
Drawing on Subjective Knowledge and Information Receptivity to Examine an Environmental Sustainability Policy: Insights from the UK's Bag Charge Policy
Authors: Manika Danae , Papagiannidis Savvas , Bourlakis Michael , Clarke Richard M.
Published: February 2021

Drawing on the notions of subjective knowledge (what someone thinks he/she knows about a topic) and receptivity (someone's ability, inclination, and willingness to take in information, ideas, impressions or suggestions), we extend the knowledge‐attitudes‐practice (KAP) model within an environmental sustainability policy (ESP) context: the UK's single‐use bag charge policy, specifically. Based on a cross‐sectional survey with 568 British participants, we illustrate the key role of objective knowledge for ESP compliance/behavioural intentions, whilst subjective knowledge is key for ESP information receptivity. The need for different marketing tactics to promote ‘policy products’ for sustainable success is illustrated by identifying three distinct segments: the Knowledgeable and Compliant (first to comply, need to maintain information receptivity); the Unknowledgeable But Compliant (need to reduce subjective knowledge); and the Unknowledgeable, Non‐compliant, but Receptive (need objective information the most). Contributing to current and future ESP making, this paper provides multiple avenues for future research.
Detection of covert lesions in focal epilepsy using computational analysis of multimodal magnetic resonance imaging data
Authors: Kanber Baris , Vos Sjoerd B. , de Tisi Jane , Wood Tobias C. , Barker Gareth J. , Rodionov Roman , Chowdhury Fahmida Amin , Thom Maria , Alexander Daniel C. , Duncan John S. , Winston Gavin P.
Published: February 2021

Objective

To compare the location of suspect lesions detected by computational analysis of multimodal magnetic resonance imaging data with areas of seizure onset, early propagation, and interictal epileptiform discharges (IEDs) identified with stereoelectroencephalography (SEEG) in a cohort of patients with medically refractory focal epilepsy and radiologically normal magnetic resonance imaging (MRI) scans.

Methods

We developed a method of lesion detection using computational analysis of multimodal MRI data in a cohort of 62 control subjects, and 42 patients with focal epilepsy and MRI‐visible lesions. We then applied it to detect covert lesions in 27 focal epilepsy patients with radiologically normal MRI scans, comparing our findings with the areas of seizure onset, early propagation, and IEDs identified at SEEG.

Results

Seizure‐onset zones (SoZs) were identified at SEEG in 18 of the 27 patients (67%) with radiologically normal MRI scans. In 11 of these 18 cases (61%), concordant abnormalities were detected by our method. In the remaining seven cases, either early seizure propagation or IEDs were observed within the abnormalities detected, or there were additional areas of imaging abnormalities found by our method that were not sampled at SEEG. In one of the nine patients (11%) in whom SEEG was inconclusive, an abnormality, which may have been involved in seizures, was identified by our method and was not sampled at SEEG.

Significance

Computational analysis of multimodal MRI data revealed covert abnormalities in the majority of patients with refractory focal epilepsy and radiologically normal MRI that co‐located with SEEG defined zones of seizure onset. The method could help identify areas that should be targeted with SEEG when considering epilepsy surgery.
The long and narrow path for novel cell‐based seafood to reduce fishing pressure for marine ecosystem recovery
Authors: Halpern Benjamin S. , Maier Jason , Lahr Heather J. , Blasco Gordon , Costello Christopher , Cottrell Richard S. , Deschenes Olivier , Ferraro Danielle M. , Froehlich Halley E. , McDonald Gavin G. , Millage Katherine D. , Weir Michael J.
Published: February 2021

Cell‐based seafood is an emerging novel food, with many start‐up companies aspiring for ocean conservation benefits through expanded market share that displaces wild‐caught seafood. However, the ability for cell‐based seafood to achieve this conservation outcome is often oversimplified and will rely on an extensive, and we find somewhat tenuous, chain of events. Here, we outline the technological, behavioural, market and ecological changes that must occur along this pathway, and conclude that fisheries recoveries and collateral ocean benefits are unlikely to result from cell‐based seafood technology. In particular, we detail nine necessary steps and argue that failure at any one step could hinder or even eliminate cell‐based seafood's conservation effects. We additionally draw comparisons to aquaculture and share broader lessons for other demand‐driven product interventions.
Cryptogamic ground covers as analogues for early terrestrial biospheres: Initiation and evolution of biologically mediated proto‐soils
Authors: Mitchell Ria L. , Strullu‐Derrien Christine , Sykes Dan , Pressel Silvia , Duckett Jeffrey G. , Kenrick Paul
Published: February 2021

Modern cryptogamic ground covers (CGCs), comprising assemblages of bryophytes (hornworts, liverworts, mosses), fungi, bacteria, lichens and algae, are thought to resemble early divergent terrestrial communities. However, limited in situ plant and other fossils in the rock record, and a lack of CGC‐like soils reported in the pre‐Silurian sedimentological record, have hindered understanding of the structure, composition and interactions within the earliest CGCs. A key question is how the earliest CGC‐like organisms drove weathering on primordial terrestrial surfaces (regolith), leading to the early stages of soil development as proto‐soils, and subsequently contributing to large‐scale biogeochemical shifts in the Earth System. Here, we employed a novel qualitative, quantitative and multi‐dimensional imaging approach through X‐ray micro‐computed tomography, scanning electron, and optical microscopy to investigate whether different combinations of modern CGC organisms from primordial‐like settings in Iceland develop organism‐specific soil forming features at the macro‐ and micro‐scales. Additionally, we analysed CGCs growing on hard rocky substrates to investigate the initiation of weathering processes non‐destructively in 3D. We show that thalloid CGC organisms (liverworts, hornworts) develop thin organic layers at the surface (<1 cm) with limited subsurface structural development, whereas leafy mosses and communities of mixed organisms form profiles that are thicker (up to ~ 7 cm), structurally more complex, and more organic‐rich. We term these thin layers and profiles proto‐soils. Component analyses from X‐ray micro‐computed tomography data show that thickness and structure of these proto‐soils are determined by the type of colonising organism(s), suggesting that the evolution of more complex soils through the Palaeozoic may have been driven by a shift in body plan of CGC‐like organisms from flattened and appressed to upright and leafy. Our results provide a framework for identifying CGC‐like proto‐soils in the rock record and a new proxy for understanding organism–soil interactions in ancient terrestrial biospheres and their contribution to the early stages of soil formation.
Body stoichiometry of heterotrophs: Assessing drivers of interspecific variations in elemental composition
Authors: Andrieux Benjamin , Signor Juliette , Guillou Vincent , Danger Michael , Jabot Franck
Published: February 2021

Aim

The aim was to document how body stoichiometry of heterotrophs varies globally and to assess phylogenetic, trophic, habitat and body mass drivers of this interspecific variation in elemental composition, focusing on carbon (C), nitrogen (N) and phosphorus (P).

Location

World‐wide.

Time period

1930–2019.

Major taxa studied

Amphibians, fishes (Actinopterygii), invertebrates, mammals, microbes and sauropsids (birds and reptiles).

Methods

We compiled from the scientific literature a global database of body elemental composition of heterotrophs in marine, freshwater and terrestrial realms. We used model selection and ANCOVAs to investigate the proportion of variance in elemental composition explained by taxonomic groups, diet, habitat and body mass. We assessed the phylogenetic signal in body stoichiometry using Blomberg's K and Pagel's λ statistics. We assessed the phylogenetic structure of interspecific variation in body stoichiometry using mixed models, with nested taxonomic levels as random factors. We finally assessed the covariations in elemental composition.

Results

Our database gathered 31,371 observations on 1,512 species. Body elemental composition was widely variable among species, with the four assessed drivers contributing significantly to this variation. Taxonomic group was the strongest contributor to interspecific variance for the stoichiometric traits studied, followed by habitat, diet and body mass. More precisely, C, N and P contents and C:N ratio were generally structured among classes, whereas the largest variations in C:P and N:P ratios were among families. This resulted in a significant but relatively modest phylogenetic signal. Finally, we found significant covariation among the three body elemental contents, resulting in taxonomic group‐specific C:N:P spectra.

Main conclusions

Our global synthesis of body stoichiometry of heterotrophs revealed a strong interspecific variability that was only modestly explained by the species attributes investigated (body mass, habitat and diet). It also revealed that this taxonomically structured residual variation in body stoichiometry seemed to be constrained along taxonomic group‐specific elemental spectra.
Oropharyngeal squamous cell carcinoma: p16/p53 immunohistochemistry as a strong predictor of HPV tumour status
Authors: Benzerdjeb Nazim , Tantot Juliet , Blanchet Christophe , Philouze Pierre , Mekki Yahia , Lopez Jonathan , Devouassoux‐Shisheboran Mojgan
Published: February 2021

Aims

Oropharyngeal squamous cell carcinomas (OPSCC) related to human papillomavirus (HPV) infection have a better prognosis than those without HPV infection. Although p16INK4a overexpression is used as a surrogate marker for HPV infection, 5–20% of p16‐positive OPSCC are described as being unrelated to HPV infection, with worse overall survival compared to OPSCC‐related HPV. There is therefore a risk of undertreating a proportion of OPSCC patients falsely considered to be HPV‐driven because of p16 positivity. TP53 mutations are highly prevalent in OPSCC driven by mutagens in tobacco and alcohol. We describe herein a combined p16/p53 algorithm to predict HPV tumour status in OPSCC.

Methods and results

A total of 110 OPSCC were identified in the database of the pathology department and were studied using p16 and p53 immunohistochemistry. For p16‐positive or p16‐negative/wild‐type patterns‐p53 (WT‐p53) cases (n = 63), DNA in‐situ hybridisation for high‐risk HPV was performed, and if negative the HPV status was controlled by HPV DNA polymerase chain reaction (PCR) (n = 19). A significant association between TP53 mutation and pattern of p53 expression was found (WT‐p53, seven of 16, P < 0.001). The p16‐positive/WT‐p53 was significantly associated with HPV+ tumour status (p16‐positive/WT‐p53, 50 of 110, P < 0.001). Interestingly, a subset of p16‐positive OPSCC was unrelated to HPV (13.5%, eight of 59), and showed mutant‐type staining of p53 expression.

Conclusions

The p16 protein immunopositivity in conjunction with the mutant‐type pattern of p53 staining helped to reclassify a subset of p16‐positive OPSCC as OPSCC‐unrelated HPV. This approach could be routinely applied by pathologists involved in the management of OPSCC, because of their potential therapeutic implications.
A laboratory study to test the responses of human dental pulp stem cells to extracts from three dental pulp capping biomaterials
Authors: Abou ElReash A. , Hamama H. , Grawish M. , Saeed M. , Zaen El‐Din A. M. , Shahin M. A. , Zhenhuan W. , Xiaoli X.
Published: February 2021

Aim

This laboratory study aimed to investigate the effects of three endodontic biomaterials; MTA‐HP, iRoot‐BP‐Plus and ACTIVA on the proliferation, adhesion and osteogenic differentiation of human Dental Pulp Stem Cells (hDPSCs).

Methodology

The hDPSCs were isolated from the dental pulps of 21 patients scheduled for surgical extraction of their impacted third molars. The MTT assay was used for assessing cellular proliferation. Ninety‐six‐well plates were used and the experiment was repeated four times under the same condition and the assay was done in triplicate. Four groups were assigned in which the hDPSCs were cultured in complete media only and considered as negative control. Whilst in the 2nd, 3rd and 4th groups, the cells were treated with CM supplemented with 1.5 μl MTA‐HP (CM‐MTA, iRoot‐BP‐Plus (CM‐BP), and ACTIVA(CM‐AC) extracts, respectively. Attachment adhesion and growth morphology of hDPSCs were observed using SEM and the osteogenic differentiation assay was evaluated by Alizarin red stain test (ARS). The data of proliferation and osteogenic differentiation were analysed using two‐way ANOVA followed by Tukey’s post hoc multiple comparison test. A p‐value < 0.05 was considered significant to analyse the differences amongst the means of groups.

Results

Both CM‐MTA and CM‐BP groups were associated with a significant increase in hDPSC proliferation in comparison with CM‐AC and CM groups (p = 0.001). hDPSCs exhibited a greater cellular attachment to iRoot‐BP‐Plus surfaces followed by MTA‐HP, whilst less attachment was observed in the ACTIVA group. Moreover, at day 7 there was a significant difference in formation of mineralizing nodules; CM‐BP, CM‐MTA and CM‐AC groups respectively (p = 0.001). Whilst there was no significance of difference between CM‐AC and CM groups (p > 0.05).

Conclusions

In a laboratory setting, ACTIVA, MTA‐HP and iRoot‐BP‐Plus promoted hDPSCs proliferation, mineralization and attachment, which may explain their in‐situ success as endodontic biomaterials.
Regulation of EAE by spontaneously generated IL‐10‐secreting regulatory T cells in HLA‐DR15/TCR.Ob1A12 double transgenic mice
Authors: Leno‐Durán Ester , Ng Sze‐Ling , Strominger Jack L.
Published: February 2021

Humanized double transgenic mice express both HLA‐DR15 (the MHC gene linked to MS) and TCR.Ob1A12 from a multiple sclerosis patient (that recognizes MBP85‐99 presented by HLA‐DR15), yet they fail to develop autoimmune encephalomyelitis quickly, although 5–10% develop disease at 12 months. These mice were found to express large numbers of IL‐10‐secreting splenocytes as early as 4 weeks of age. These regulatory T cells appeared spontaneously without prior immunization with the autoantigen MBP85‐99. They were of murine origin and had a cytokine secretion profile and surface phenotype similar to that reported for Tr1 cells. Notably, the frequency of disease appeared to increase at 14 months. The diseased mice had small spleens which averaged 47 mg, while the remaining non‐diseased mice in our colony killed at ages 14–15 months had splenocytes that averaged 80 mg (ranging from 47–130 mg). Thus, the appearance of disease was associated with diminution in numbers of IL‐10‐secreting regulatory T cells with age.
Host‐directed therapy to combat mycobacterial infections*
Authors: Kilinç Gül , Saris Anno , Ottenhoff Tom H. M. , Haks Mariëlle C.
Published: February 2021

Upon infection, mycobacteria, such asMycobacterium tuberculosis(Mtb) and nontuberculous mycobacteria (NTM), are recognized by host innate immune cells, triggering a series of intracellular processes that promote mycobacterial killing. Mycobacteria, however, have developed multiple counter‐strategies to persist and survive inside host cells. By manipulating host effector mechanisms, including phagosome maturation, vacuolar escape, autophagy, antigen presentation, and metabolic pathways, pathogenic mycobacteria are able to establish long‐lasting infection. Counteracting these mycobacteria‐induced host modifying mechanisms can be accomplished by host‐directed therapeutic (HDT) strategies. HDTs offer several major advantages compared to conventional antibiotics: (a) HDTs can be effective against both drug‐resistant and drug‐susceptible bacteria, as well as potentially dormant mycobacteria; (b) HDTs are less likely to induce bacterial drug resistance; and (c) HDTs could synergize with, or shorten antibiotic treatment by targeting different pathways. In this review, we will explore host‐pathogen interactions that have been identified forMtbfor which potential HDTs impacting both innate and adaptive immunity are available, and outline those worthy of future research. We will also discuss possibilities to target NTM infection by HDT, although current knowledge regarding host‐pathogen interactions for NTM is limited compared toMtb. Finally, we speculate that combinatorial HDT strategies can potentially synergize to achieve optimal mycobacterial host immune control.