bluuebunny/crossref_metadata_2025 huggingface dataset:
The genomes of chicory, endive, great burdock and yacon provide insights into Asteraceae palaeo‐polyploidization history and plant inulin production
Authors: Fan Wei , Wang Sen , Wang Hengchao , Wang Anqi , Jiang Fan , Liu Hangwei , Zhao Hanbo , Xu Dong , Zhang Yan
Published: June 2022

Inulin is an important reserve polysaccharide in Asteraceae plants, and is also widely used as a sweetener, a source of dietary fibre and prebiotic. Nevertheless, a lack of genomic resources for inulin‐producing plants has hindered extensive studies on inulin metabolism and regulation. Here, we present chromosome‐level reference genomes for four inulin‐producing plants: chicory (Cichorium intybus), endive (Cichorium endivia), great burdock (Arctium lappa) and yacon (Smallanthus sonchifolius), with assembled genome sizes of 1.28, 0.89, 1.73 and 2.72 Gb, respectively. We found that the chicory, endive and great burdock genomes were shaped by whole genome triplication (WGT‐1), and the yacon genome was shaped by WGT‐1 and two subsequent whole genome duplications (WGD‐2 and WGD‐3). A yacon unique whole genome duplication (WGD‐3) occurred 5.6–5.8 million years ago. Our results also showed the genome size difference between chicory and endive is largely due to LTR retrotransposons, and rejected a previous hypothesis that chicory is an ancestor of endive. Furthermore, we identified fructan‐active‐enzyme and transcription‐factor genes, and found there is one copy in chicory, endive and great burdock but two copies in yacon for most of these genes, except for the 1‐FEH II gene which is significantly expanded in chicory. Interestingly, inulin synthesis genes 1‐SST and 1‐FFT are located close to each other, as are the degradation genes 1‐FEH I and 1‐FEH II. Finally, we predicted protein structures for 1‐FFT genes to explore the mechanism determining inulin chain length.
Variation in thermal and hydrotime requirements for seed germination of Chaco seasonally dry forest species in relation to population environmental conditions and seed mass
Authors: Bertuzzi Tania , Pastrana‐Ignes Valeria , Curti Ramiro N. , Batlla Diego , Baskin Carol C. , Sühring Silvia , Galíndez Guadalupe
Published: June 2022

Thermal and hydrotime requirements for seed germination can vary with the species, environment in which the seeds developed and/or seed mass. We investigated seed germination responses to temperature and water potential of Aspidosperma quebracho‐blanco, Bulnesia retama, Parasenegalia visco, Parkinsonia praecox and Tecoma stans, all of which are native tree species of Chaco seasonally dry forests in northwest Argentina. We determined inter‐and intraspecific variability in seed germination through thermal and hydrotime models and correlated model parameters with environmental variables of seed provenance and seed mass. Seeds of all species germinated to high percentage over a range of temperatures. Seeds of A. quebracho‐blanco, P. praecox and T. stans were more tolerant to water stress than those of B. retama and P. visco. Thermal and hydrotime parameters for germination varied amongst species and populations. There was a negative correlation between thermal (θT(50)) and hydrotime (θH) constants and base temperature (Tb) and water potential (Ψb(50)). Seed mass correlated negatively with Tb and positively with θT(50). Species and populations were grouped according to thermal and hydrotime parameters and seed mass but not according to seed provenance. These results suggest that seed germination traits related to temperature, water potential and seed mass are species specific, and the variations within a species are probably due to a high phenotypic plasticity. These species showed a complex set of germination strategies that give them a competitive advantage in different environments, depending on dispersal time, seed mass and local environmental conditions during the germination period.
Interspecific variation in the diet of a native apex predator and invasive mesopredator in an alpine ecosystem
Authors: Thompson Eilysh R. , Driscoll Don A. , Venn Susanna E. , Geary William L. , Ritchie Euan G.
Published: June 2022

Carnivores have key ecological roles in structuring and regulating ecosystems through their impacts on prey populations. When apex‐ and meso‐predators co‐occur in ecosystems, there is the potential for complex interspecific interactions and trophic dynamics that can affect the composition and functioning of ecological communities. Investigating the diet of sympatric carnivores can allow us to better understand their ecological roles (e.g. potential suppression of herbivores) or impacts (e.g. predation of threatened species). Australia's alpine region provides an ideal system in which to explore spatial and temporal variation in predator and prey interactions, using the dingo (Canis dingo) and invasive red fox (Vulpes vulpes) diet. We examined the diet of dingoes and foxes across three different mountains and seasons in Victoria's alpine region, using macroscopic scat analysis. There was little diet overlap between the two carnivores, with foxes having a broader diet than dingoes. Dingoes primarily consumed larger mammal species, including invasive sambar deer (Cervus unicolor, 44%), and the native common wombat (Vombatus ursinus, 34%), whereas foxes typically consumed smaller mammals, including the native bush rat (Rattus fuscipes, 55%), and the invasive European rabbit (Oryctolagus cuniculus, 15%). Dingoes consumed more than thirty times the volume of large invasive mammals (predominantly sambar deer) than did foxes. Foxes consumed close to 15 times as many critical weight range individuals per scat than dingoes. Only one threatened critical weight range mammal species was identified within scats, the broad‐toothed rat (Mastacomys fuscus), found within five fox scats. Our results suggest that the introduction of novel prey may alter predator–predator interactions by causing a reduction in the dietary overlap. Therefore, in the context of integrated wildlife management and biodiversity conservation, any control of novel, invasive prey populations needs to consider possible flow on effects to apex‐ and meso‐predator diets and potential secondary impacts on native prey.
Facilitating inclusive ICT application and e‐Commerce development in rural China
Authors: Huang Jikun , Su Lanlan , Huang Qiwang , Liu Xinyu
Published: June 2022

Application of information and communication technologies (ICTs) in general and e‐commerce development in particular are increasingly becoming one of the important driving forces of transforming rural economy in China. Based on two sets of household survey datasets in 2015–2019, this study documents the overall trends of major ICTs’ and e‐commerce adoption in rural China and farmers’ selling fruits online in more developed e‐commerce villages in two provinces, and examines the enabling and constraining factors for farmers adopting ICTs and using e‐commerce to sell products. The results show that, although the increase has been impressive, there is still plenty of room for the diffusion of ICTs and e‐commerce. Empirical analyses suggest that human capital, social networks, resource endowments, ICT infrastructure and location are the main determinants of a household's or an individual's adoption of ICTs, and the producer's selling his/her fruits through e‐commerce. Moreover, this study provides new and strong evidence of intergenerational support for older and less educated farmers from their children to engage in online sales. However, this study also points out that a new digital divide on the spread of ICTs and e‐commerce has emerged across regions and among farmers in rural China. The article concludes with several policy implications for fostering rapid and inclusive ICT application and e‐commerce development in rural areas in the coming digital era.
Endometriosis and inflammatory immune responses: Indian experience
Authors: Gajbhiye Rahul K
Published: June 2022

Endometriosis is a public health disorder affecting ∼ 247 million women globally and ∼ 42 million women in India. Women with endometriosis suffer from dysmenorrhea, chronic pelvic pain, dyspareunia, dyschezia, fatigue, depression, and infertility leading to significant socioeconomic impact and morbidity. The etiology of endometriosis is not understood well even after 100 years of research. Currently, there is no permanent cure for endometriosis. The inflammatory immune response is one of the important features of etiopathogenesis of endometriosis and therefore understanding the inflammatory immune response would lead to a better understanding of this enigmatic disorder and may also lead to biomarker discovery for diagnosis of endometriosis. We investigated the autoimmune etiology of endometriosis in the Indian population. Using the proteomics approach, anti‐endometrial antibodies (AEAs) were detected in Indian women with endometriosis [anti‐endometrial antibodies ‐ tropomyosin 3 (TPM3), stomatin‐like protein2 (SLP‐2), and tropomodulin 3 (TMOD3)]. The studies on AEAs provided a better understanding of autoimmune mechanisms in endometriosis. All three subtypes of endometriosis; superficial peritoneal, ovarian endometrioma, and deep infiltrating endometriosis were reported in Indian women. In this review, we discuss our experiences of the inflammatory immune response, autoimmunity, comorbidities, and clinical phenotypes in women with endometriosis in India.
Moral bias toward different social classes
Authors: Jiang Ming , Yao Xiaoqiang , Wang Yiwen
Published: June 2022

The influence of social class on prosocial behaviour has long been a focus of intense research interest. The present research involved four studies that covered four moral exemplars (villains, victims, heroes, and beneficiaries) to test whether people of different social classes are treated equally in moral judgements. We described moral events experienced by different agents of varying social classes and asked participants to rate the morality of the events and their emotional responses. The results revealed that compared with the low‐class condition, high‐class individuals had an overall moral disadvantage when they were regarded as villains, victims, and beneficiaries. For the exemplar of hero, the high‐class condition was no different from the low‐class condition except that high‐class heroes evoked less elevation than low‐class heroes. The results reveal that people hold a biased moral attitude toward individuals in different social classes.
Splanchnic venous thrombosis: aetiologies and a review of the literature
Authors: Tan Rebekah , Daneshmand Ali , Parys Simon , Watanabe Yuki , Sieunarine Kishore
Published: June 2022

Background

Splanchnic vein thrombosis (SVT) is an uncommon yet potentially life‐threatening manifestation of venous thromboembolism. The aim of this study was to present a retrospective analysis of a cohort of Western Australian patients diagnosed with SVT on imaging study, and a review of the literature surrounding the aetiology, location, anticoagulation treatment and outcomes of SVT.

Methods

All patients diagnosed with SVT over a five‐year period from 2015 to 2020 in three tertiary hospitals in Western Australia were identified by using an electronic search engine of imaging reports. Collected data included patient demographics and co‐morbidity, presentation data, location of thrombus, aetiology of thrombus, treatment with anti‐coagulation, length of stay and outcome data including mortality.

Results

A total of 164 patients met inclusion criteria. The 90‐day mortality was 20.1%; 64% of whom were those with portal vein thrombosis. Aetiology was grouped into haematological conditions (4 patients), non‐haematological conditions (130 patients), a combination of factors (17 patients) and idiopathic (13 patients). The majority of deaths were due to malignancy, severe pancreatitis or decompensated liver cirrhosis.

Conclusion

Whilst the prevalence of SVT is rising with the increase in accessibility to radiological studies, it remains a diagnostic and therapeutic challenge for clinicians. With no consensus guidelines available to direct treatment, the management of patients with SVT should be individualized and considered carefully. The potential complications of venous thrombosis, SVT recurrence or extension and the risk of bleeding need to be evaluated before the commencement of anticoagulation therapy.
Eyelid sebaceous gland carcinoma, validation of AJCC 8th edition T staging‐ a retrospective study from North India
Authors: Sen Seema , Bhardwaj Mansi , Jayaraj Perumal , Bakhshi Sameer , Pushker Neelam , Kashyap Seema , Bajaj Mandeep S. , Khandpur Sukhanshi
Published: June 2022

Purpose

This study compares the 8th edition staging of AJCC for prognosis of eyelid Sebaceous Gland Carcinoma (SGC) patients with respect to the 7th edition.

Methods

A retrospective study was undertaken over a period of 100 months. Ninety‐nine histopathologically proven cases of eyelid SGC available for follow‐up were recruited. Patients were staged by both the 7th and 8th editions of AJCC and followed up at six monthly intervals after surgery.

Results

Of the 99 eyelid SGC patients recruited, recurrence and orbital invasion developed in 22%, lymph node metastasis in 21% and 4% had distant metastasis and also died. High‐risk features include tumour size>20 mm, orbital invasion, exenteration and staging by both the 7th and 8th editions of AJCC. Cox regression analysis revealed that staging by AJCC 8th edition was associated with greater risk for local recurrence (HR 3.01,95% CI‐1.65–5.51%, p < 0.01) lymph node metastasis (HR 8.26, 95% CI 3.96–17.19%, p < 0.01) and disease‐free survival (HR 4.61, 95% CI 2.81–7.54). The Kaplan–Meir survival curves of eyelid SGC patients by the 8th edition AJCC staging were also significantly associated with lymph node metastasis (p < 0.01), tumour‐related deaths (p < 0.01) and reduced disease‐free survival (p = 0.07). The higher Harrell's values by the 8th edition signify better predictive value for lymph node metastasis and DFS (disease‐free survival). The lower AIC values indicate a better monotonicity of gradients for lymph node metastasis, recurrence and DFS.

Conclusion

Staging by the 8th AJCC edition is, therefore, recommended for eyelid SGC as it gives a better perspective about disease outcome. The orbital extension was the single most important predictor of lymph node metastasis, recurrence and death.
Cost reduction in screening for retinopathy of prematurity in the Netherlands by comparing different screening strategies
Authors: Trzcionkowska Kasia , Schalij‐Delfos Nicoline E. , van den Akker‐van Marle Elske M. E.
Published: June 2022

Purpose

Evaluate possibilities to reduce the number of infants screened for retinopathy of prematurity (ROP) and investigate costs and number of infants detected of current and alternative screening strategies in the Netherlands.

Methods

Prospective population‐based study including clinical data from all infants born in 2017 and referred for ROP screening (NEDROP‐2 study). Cost and effects of screening strategies were evaluated that differed on the criteria gestational age (GA), birth weight (BW) and presence of one or more specific risk factor(s) (RF): mechanical ventilation, sepsis, necrotizing enterocolitis, postnatal corticoids and/or hypotension treated with inotropic agents. RF obtained from the Dutch perinatal registry (Perined).

Results

Of the possible efficient strategies, the annual costs varied from €137 966 (inclusion of BW < 700, 63 infants eligible for screening, detection of 17/39 treated ROP) to €492 689 (GA < 30 weeks and BW < 1250 grams, together with infants with GA 30–32 and BW 1250–1500 grams with presence of one more RF, 744 infants eligible for screening, all treated infants detected). Total annual costs of the current Dutch guideline that detects all infants that need treatment for ROP amount to €552 143).

Conclusion

The current Dutch ROP guideline can be improved by implementing new screening inclusion criteria. The most effective strategy detecting all severe and treated infants, reduces the number of screened infants by 24% compared to the current guideline and the overall annual costs by €59454.
Primary vitrectomy or intravitreal antibiotics followed by early vitrectomy for acute endophthalmitis: A prospective observational study
Authors: Blom Kathrine , Jørstad Øystein Kalsnes , Faber Rowan Thomas , Stene‐Johansen Ingar , Holberg‐Petersen Mona , Hermansen Nils Olav , Bragadóttir Ragnheiður
Published: June 2022

Background/aims

To compare outcomes of acute endophthalmitis (EO) managed with either primary vitrectomy (PV) or primary intravitreal antibiotics (vancomycin and ceftazidime) followed by early vitrectomy (PIAEV) combined with polymerase chain reaction (PCR)‐based diagnostics.

Methods

This was a prospective, comparative observational study of acute EO cases admitted to a regional vitreoretinal service over 18 months. Depending on whether immediate vitrectomy (within 6 h) was achievable, the EO cases were treated with either (1) PV or (2) PIAEV. Microbiology samples were collected either (A) before or (B) after administration of intravitreal antibiotics. The samples were analysed with broad‐range 16S PCR and culture.

Results

The study included 41 EO cases. There were 19 post‐injection EO, 18 post‐cataract EO, three post‐vitrectomy EO, and one blebitis‐related EO. Fifteen of 19 PV cases and 15 of 21 PIAEV had a clinically meaningful improvement in best‐corrected visual acuity (BCVA) of at least 15 letters at 3 months (p = 0.58). One patient was lost to follow‐up. Twenty‐three cases were culture‐ and PCR‐positive, and seven additional cases were culture‐negative but PCR‐positive (p = 0.02). PCR increased the diagnostic yield for samples collected both before and after administration of intravitreal antibiotics.

Conclusion

Primary vitrectomy or PIAEV allowed for vitrectomy for all cases of acute EO in a large region. Most eyes in both groups achieved a clinically meaningful improvement in BCVA. By combining culture with PCR in connection with the vitrectomy procedure, intravitreal antibiotics could be injected before microbiological sampling, thereby improving the door‐to‐treatment time without sacrificing microbial identification.
Biomarkers for iron metabolism among patients hospitalized with community‐acquired pneumonia caused by infection with SARS‐CoV‐2, bacteria, and influenza
Authors: Hegelund Maria Hein , Glenthøj Andreas , Ryrsø Camilla Koch , Ritz Christian , Dungu Arnold Matovu , Sejdic Adin , List Karoline Cecilie Knudsen , Krogh‐Madsen Rikke , Lindegaard Birgitte , Kurtzhals Jørgen Anders Lindholm , Faurholt‐Jepsen Daniel
Published: June 2022

Ferritin, the central iron storage protein, has attracted attention as a biomarker of severe COVID‐19. Few studies have investigated regulators of iron metabolism in the context of COVID‐19. The aim was to evaluate biomarkers for iron metabolism in the acute phase response to community‐acquired pneumonia (CAP) caused by SARS‐CoV‐2 compared with CAP caused by bacteria or influenza virus in hospitalized patients. A cross‐sectional study of 164 patients from the Surviving Pneumonia Cohort recruited between January 8, 2019 and May 26, 2020. Blood samples were collected at admission and analyzed for levels of C‐reactive protein (CRP), ferritin, soluble transferrin receptor, erythroferrone, and hepcidin. Median (IQR) hepcidin was higher in SARS‐CoV‐2 with 143.8 (100.7–180.7) ng/mL compared with bacterial and influenza infection with 78.8 (40.1–125.4) and 53.5 (25.2–125.8) ng/mL, respectively. The median ferritin level was more than 2‐fold higher in patients with SARS‐CoV‐2 compared with the other etiologies (p < 0.001). Patients with SARS‐CoV‐2 had lower levels of erythroferrone and CRP compared with those infected with bacteria. Higher levels of hepcidin and lower levels of erythroferrone despite lower CRP levels among patients with SARS‐CoV‐2 compared with those infected with bacteria indicate alterations in iron metabolism in patients with SARS‐CoV‐2 infection.
Studies on the mode of action of synthetic diindolylmethane derivatives against triple negative breast cancer cells
Authors: Shilpa Ganesan , Lakshmi Sreerenjini , Jamsheena Vellekkatt , Lankalapalli Ravi Shankar , Prakash Ved , Anbumani Sadasivam , Priya Sulochana
Published: June 2022

Diindolylmethane (DIM) is a metabolic product of indole‐3‐carbinol (I3C), the major phytochemicals present in cruciferous vegetables, which can modulate multiple signalling pathways in cancer. The present study deals with the mechanism of action of two synthetic biaryl conjugates of DIM in triple negative breast cancer cells. Out of 12 DIM derivatives tested, two compounds, DIM‐1 and DIM‐4, exhibit cytotoxicity with GI50 values of 9.83 ± 0.2195 μM and 8.726 ± 0.5234 μM, respectively, in 2D culture. In 3D culture, DIM‐1 and DIM‐4 show GI50 values of 24.000 ± 0.7240 μM and 19.230 ± 0.3754 μM, respectively. The non‐toxic nature of the compounds was also established by the toxicity studies using the zebrafish model system. The two compounds induced apoptosis and anoikis in the cancer cells, which was confirmed by morphological analysis, nuclear fragmentation, membrane integrity assay, caspase activity measurements and modulation of pro/anti‐apoptotic proteins. The compounds inhibited cell migration and MMP‐2 and MMP‐9 activities indicating their anti‐metastatic property. They also reduced the expression of active Ras, phosphorylated forms of PI3K, Akt and mTOR. Immunofluorescence studies revealed the reduced expression of EGFR and pEGFR in treated cells. To conclude, DIM‐1 and DIM‐4 induced anti‐breast cancer effects by blocking EGF receptor and subsequently inhibiting Ras‐mediated PI3K‐Akt–mTOR signalling pathway.
Parental warmth predicts more child pro‐social behaviour in children with better emotion regulation
Authors: Yavuz H. Melis , Colasante Tyler , Malti Tina
Published: June 2022

Parental warmth and child emotion regulation have each been implicated in the development of child pro‐social behaviours; however, their interactive benefits remain unclear. In this multi‐method, multi‐cohort longitudinal study, we examined the effect of parental warmth on child pro‐social behaviours at different levels of child emotion regulation. We collected data from 6‐ and 10‐year‐olds in Canada (NT1 = 233; Mage = 8.41; SD = 2.08) and their parents. Parental warmth, child emotion regulation, and child pro‐social behaviours were assessed via parent report. Children's baseline respiratory sinus arrhythmia (RSA; an indicator of cardiac regulatory capacity) was assessed as a correlate of emotion regulation. Child pro‐social behaviours were assessed concurrently and 1 year later. Results showed that higher parental warmth was related to higher concurrent prosocial behaviours and greater increases in prosocial behaviours over 1 year. These effects were strengthened for children with higher emotion regulation whether measured by parent report or RSA. We discuss implications for understanding pro‐social development in middle childhood from a strengths‐based perspective.
Contribution of haemodynamic side effects and associated autonomic reflexes to ventricular arrhythmias triggering by torsadogenic hERG blocking drugs
Authors: Champéroux Pascal , Fares Raafat , Bastogne Thierry , Richard Serge , Le Guennec Jean‐Yves , Thireau Jérôme
Published: June 2022

Background and Purpose

HERG blocking drugs known for their propensity to trigger Torsades de Pointes (TdP) were reported to induce a sympatho‐vagal coactivation and to enhance High Frequency heart rate (HFHR) and QT oscillations (HFQT) in telemetric data. The present work aimed to characterize the underlying mechanism(s) leading to these autonomic changes.

Experimental Approach

Effects of 15 torsadogenic hERG blocking drugs (astemizole, chlorpromazine, cisapride, droperidol, ibutilide, dofetilide, haloperidol, moxifloxacin, pimozide, quinidine, risperidone, sotalol, sertindole, terfenadine, and thioridazine) were assessed by telemetry in beagle dogs. Haemodynamic effects on diastolic and systolic arterial pressure were analysed from the first doses causing QTc prolongation and/or HFQT oscillations enhancement. Autonomic control changes were analysed using the high frequency autonomic modulation (HFAM) model.

Key Results

Except for moxifloxacin and quinidine, all torsadogenic hERG blockers induced parasympathetic activation or sympatho‐vagal coactivation combined with enhancement of HFQT oscillations. These autonomic effects result from reflex compensatory mechanisms in response to mild haemodynamic side effects. These haemodynamic mechanisms were characterized by transient HR acceleration during HF oscillations. A phenomenon of concealed QT prolongation was unmasked for several torsadogenic hERG blockers under β‐adrenoceptor blockade with atenolol. Resulting enhancement of HFQT oscillations was shown to contribute directly to triggering dofetilide‐induced ventricular arrhythmias.

Conclusion and Implications

This work supports for the first time a contribution of haemodynamic side properties to ventricular arrhythmias triggered by torsadogenic hERG blocking drugs. These haemodynamic side effects may constitute a second component of their arrhythmic profile, acting as a trigger alongside their intrinsic arrhythmogenic electrophysiological properties.
Geo‐scripts and refugee resettlement in Canada: Designations and destinations
Authors: Hyndman Jennifer
Published: June 2022

Most immigrants to Canada who are not refugees contribute to decisions about where they settle; resettled refugees do not. This paper illustrates how one's designated category of resettlement decisively shapes the place one begins life in Canada, and how each has a specific geographical trajectory—or geo‐script. The geo‐scripts are distinct for each category of resettlement: privately‐sponsored refugees live in the same community as the volunteers who finance and support them; government‐assisted refugees are “destined” to one of more than two dozen cities with federally‐funded refugee‐specific services; and blended visa office‐referred refugees are supported through a shared funding model between government and sponsors near whom they co‐locate. Geo‐scripts are derived from refugee categories that effectively govern the spatial settlement patterns of refugees and, in turn, shape the opportunities and outcomes of the resettlement process. Government data show that 70% of resettled refugees do not move after they arrive in Canada. The geo‐scripts of resettlement thus shape people's lives and livelihoods in Canada in fundamental ways. Drawing on interviews conducted between 2017 and 2021 with formerly resettled refugees living in four provinces who have lived in Canada for more than 20 years, locational decisions to stay or leave one's initial destination are elaborated.
Elementary school children in the online world: Naming and mobilization of rights
Authors: Ben‐Hayun Shiran German , Perry‐Hazan Lotem
Published: June 2022

This study drew on interviews with elementary school children (aged 8–12), parents and teachers to explore whether and how children name online infringements of their rights and mobilize their rights when they experience such infringements. The findings revealed distinctions between rights infringements external to children's social world and infringements internal to this world that are intertwined with children's close relationships. Naming internal infringements proved more complex, particularly when the injuries were masked as pranks or conducted between siblings. The distinction between internal and external rights infringements was also apparent in children's mobilization of their online rights.
The role of Na+‐K+‐ATPasein the epileptic brain
Authors: Sun Jinyi , Zheng Yang , Chen Zhong , Wang Yi
Published: June 2022

Na+‐K+‐ATPase, a P‐type ATP‐powered ion transporter on cell membrane, plays a vital role in cellular excitability. Cellular hyperexcitability, accompanied by hypersynchronous firing, is an important basis for seizures/epilepsy. An increasing number of studies point to a significant contribution of Na+‐K+‐ATPase to epilepsy, although discordant results exist. In this review, we comprehensively summarize the structure and physiological function of Na+‐K+‐ATPase in the central nervous system and critically evaluate the role of Na+‐K+‐ATPase in the epileptic brain. Importantly, we further provide perspectives on some possible research directions and discuss its potential as a therapeutic target for the treatment of epilepsy.
Repeated neurofilament light chain measurements did not capture Riluzole therapeutic effect in amyotrophic lateral sclerosis patients
Authors: Esselin Florence , De la Cruz Elisa , Hirtz Christophe , Tiers Laurent , Alphandery Sébastien , Baudesson Léandra , Taieb Guillaume , Camu William , Lehmann Sylvain
Published: June 2022

Background

Little is known about the influence of Riluzole on serum neurofilament light chain (sNfL) levels, a biomarker of prognosis in amyotrophic lateral sclerosis (ALS), and variations with time of sNfL concentrations are controversial.

Methods

Sera from ALS patients (n = 141) and controls (n = 33) were collected at inclusion (sNfL1) and second visit (sNfL2, mean delay 10.4 ± 8.7 months). sNfL levels, determined by single‐molecule array, were compared between ALS and controls at both time points. sNfL concentration changes were compared between patients with Riluzole (w/Ril) at inclusion in the study and those who were treated by Riluzole following inclusion (w/o Ril). The factors influencing sNfL concentrations and changes were studied using linear regression and multivariate analysis.

Results

sNfL levels were higher in ALS patients than in controls at the two time points (p < 0.00001). In ALS patients, sNfL concentrations were higher in females for both sNfL1 (p = 0.014) and sNfL2 (p < 0.001). In the whole ALS group, sNfL levels were higher at sNfL2 than at sNfL1 (p < 0.001). sNfL1 and sNfL2 concentrations were similar between the two ALS subgroups (w/ and w/o Ril). ALS functional rating scale‐revised rate of decline and gender were the two main factors significantly influencing both sNfL1 and sNfL2 levels (p < 0.01). However, only gender was shown to significantly influence sNfL changes with time (p = 0.003).

Conclusions

In this study, sNfL levels increased with time in ALS patients and there was no difference between subjects already treated by Riluzole and those treated after sNfL1. Further studies with larger population samples and different sampling intervals are warranted to better determine the real potential of sNfL measurement as a tool to monitor treatment response in ALS.
Phagocytic microglia and macrophages in brain injury and repair
Authors: Yu Fang , Wang Yangfan , Stetler Anne R. , Leak Rehana K. , Hu Xiaoming , Chen Jun
Published: June 2022

Aims

Phagocytosis is the cellular digestion of extracellular particles, such as pathogens and dying cells, and is a key element in the evolution of central nervous system (CNS) disorders. Microglia and macrophages are the professional phagocytes of the CNS. By clearing toxic cellular debris and reshaping the extracellular matrix, microglia/macrophages help pilot the brain repair and functional recovery process. However, CNS resident and invading immune cells can also magnify tissue damage by igniting runaway inflammation and phagocytosing stressed—but viable—neurons.

Discussion

Microglia/macrophages help mediate intercellular communication and react quickly to the “find‐me” signals expressed by dead/dying neurons. The activated microglia/macrophages then migrate to the injury site to initiate the phagocytic process upon encountering “eat‐me” signals on the surfaces of endangered cells. Thus, healthy cells attempt to avoid inappropriate engulfment by expressing “do not‐eat‐me” signals. Microglia/macrophages also have the capacity to phagocytose immune cells that invade the injured brain (e.g., neutrophils) and to regulate their pro‐inflammatory properties. During brain recovery, microglia/macrophages engulf myelin debris, initiate synaptogenesis and neurogenesis, and sculpt a favorable extracellular matrix to support network rewiring, among other favorable roles. Here, we review the multilayered nature of phagocytotic microglia/macrophages, including the molecular and cellular mechanisms that govern microglia/macrophage‐induced phagocytosis in acute brain injury, and discuss strategies that tap into the therapeutic potential of this engulfment process.

Conclusion

Identification of biological targets that can temper neuroinflammation after brain injury without hindering the essential phagocytic functions of microglia/macrophages will expedite better medical management of the stroke recovery stage.
Spatial distribution of fibropapillomatosis in green turtles along the Queensland coast and an investigation into the influence of water quality on prevalence
Authors: Jones Karina , Limpus Colin J. , Brodie Jon , Jones Rhondda , Read Mark , Shum Edith , Bell Ian P. , Ariel Ellen
Published: June 2022

Fibropapillomatosis (FP) is a tumor‐forming disease which affects all species of marine turtle, but predominantly the green turtle (Chelonia mydas). Expression of this disease is thought to be precipitated by poor environmental conditions and often linked to anthropogenically induced environmental changes. Although FP is a globally distributed disease, targeted studies on the spatial distribution of the disease in Australia are limited. Here, we present the first comprehensive report of FP prevalence in Queensland, Australia. A retrospective analysis of 25,645 capture records for 15 sites along the Queensland coast were used to determine FP prevalence and trends in foraging green turtles. Within this data set, 791 turtles (3.1%) with FP tumors were recorded. Our analysis showed that prevalence varies between sites and years, with juvenile turtles being the most frequently affected by the disease. We found that survey method has a significant influence on the apparent FP prevalence detected at each site. That is, surveys which were explicitly FP‐targeted detected higher numbers of individual turtles with FP, and therefore generated higher prevalence rates than comprehensive population surveys. We also report the first attempt at developing water quality indices (WQIs) to compare with FP prevalence data in foraging green turtles. The WQIs were built from metrics published in a range of peer‐reviewed papers, reports, and based on expert opinion. Despite utilizing an extensive data set, a relationship between FP prevalence and WQI rankings at each site could not be quantified. The analysis was confounded by a range of limitations, including data gaps, varying temporal scales and data capture methods in the FP prevalence, and water quality data sets. This study has significant implications for management as it highlights the benefits of designing and collecting centralized data that can be integrated and used across multiple projects or programs.
Estimation of glomerular filtration rate for drug dosing in patients with very high or low body mass index
Authors: Donker Erik M. , Bet Pierre , Nurmohamed Azam , Serné Erik , Burchell George Louis , Friedman Allon N. , Bouquegneau Antoine , Lemoine Sandrine , Ebert Natalie , Cirillo Massimo , van Agtmael Michiel A. , Bartelink Imke H.
Published: June 2022

An accurate estimated glomerular filtration rate (eGFR) is essential in drug dosing. This study demonstrates the limitations of indexed (ml/min/1.73 m2) and de‐indexed (ml/min) eGFR based drug dosing in patients with obesity or underweight. This systematic study aimed to determine the most appropriate approach to estimate the GFR for standardized eGFR based drug dosing in these patients. (Raw) data of 12 studies were selected to investigate the accuracy and bias of both the indexed and de‐indexed estimations of the Modification of Diet in Renal Disease (MDRD) study equation and the Chronic Kidney Disease Epidemiology Collaboration equation (CKD‐EPI), and of the Cockcroft–Gault (CG) in patients with obesity or underweight. Accuracy was calculated as the proportion of eGFR values within 30% of the measured GFR (P30) using an inert tracer (e.g., iohexol, inulin, 51Cr‐EDTA, or iothalamate clearance). An accuracy of at least 80% was considered acceptable. GFR values estimated with the CG, MDRD, and CKD‐EPI differ significantly within a patient with obesity or underweight regardless of whether it is indexed or de‐indexed. All studies, with two exceptions, show that all three equations are inaccurate for patients with underweight or class II obesity (P30: 55%–94%). De‐indexing eGFR improves not or modestly the accuracy, and mostly remains below the 80% (P30: 62%–100%). CG was highly inaccurate in obese and underweight patients (P30: 7%–82%). Although these results show that CG is obsolete, the accuracy of MDRD and CKD‐EPI is low in patients with obesity or underweight and de‐indexing is not the solution. Better education and more accurate methods for appropriate drug dosing (e.g., measured GFR with inert tracer, therapeutic drug monitoring, or 24‐h creatinine clearance) are recommended.
Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion and prominent epidermal involvement: A case report
Authors: Vest Blake E. , Harview Christina L. , Liu Vincent , Swick Brian L. , Berrebi Kristen G. , Olivares Shantel , Stone Mary S. , Sargen Michael R. , Gerami Pedram
Published: June 2022

Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion (CMCT) is a recently described entity with only 13 cases reported in the literature. Histopathologically, the neoplasm consists of atypical epithelioid to spindled cells that form a well‐circumscribed nodule usually confined to the dermis and subcutis with cytological features including large vesicular nuclei with prominent nucleoli and abundant eosinophilic cytoplasm. Immunohistochemistry shows variable expressivity of melanocytic markers. Currently, there are limited data regarding long‐term outcomes of this newly described entity. Most cases have done well, but there is one case reported with an adverse event. Hence, further studies are needed to accurately classify this tumor. Definitive diagnosis is made by laboratory evidence of CMCT. Herein, we report the first case of CMCT with epidermal involvement in the youngest patient known to be affected to date.
Droplet nuclei are generated during colonoscopy and are decreased by the use of carbon dioxide and water immersion technique
Authors: Chan Shannon Melissa , Ma Tsz Wah , Chu Simon , Fei Hon Sok , Futaba Kaori , Yip Hon Chi , Teoh Anthony Yuen Bun , Wong Martin Chi‐Sang , Ng Simon Siu Man , Ng Enders Kwok Wai , Chiu Philip Wai Yan
Published: June 2022

Objectives

The COVID‐19 pandemic has raised concerns on whether colonoscopies (CS) carry a transmission risk. The aim was to determine whether CS are aerosol‐generating procedures.

Methods

This was a prospective observational trial including all patients undergoing CS at the Prince of Wales Hospital from 1 June to 31 July 2020. Three particle counters were placed 10 cm from each patient’s anus and near the mouth of endoscopists and nurses. The particle counter recorded the number of particles of size 0.3, 0.5, 0.7, 1, 5, and 10 μm. Patient demographics, seniority of endoscopists, use of CO2 and water immersion technique, and air particle count (particles/cubic foot, dCF) were recorded. Multilevel modeling was used to test all the hypotheses with a post‐hoc analysis.

Results

A total of 117 patients were recruited. During CS, the level of 5 μm and 10 μm were significantly higher than the baseline period (P = 0.002). Procedures performed by trainees had a higher level of aerosols when compared to specialists (0.3 μm, P < 0.001; 0.5 μm and 0.7 μm, P < 0.001). The use of CO2 and water immersion techniques had significantly lower aerosols generated when compared to air (CO2: 0.3, 0.5, and 0.7 μm: P < 0.001; water immersion: 0.3 μm: P = 0.048; 0.7 μm: P = 0.03). There were no significant increases in any particle sizes during the procedure at the endoscopists' and nurses' mouth. However, 8/117 (6.83%) particle count tracings showed a simultaneous surge of all particle sizes at the patient's anus and endoscopists' and nurses' level during rectal extubation.

Conclusion

Colonoscopy generates droplet nuclei especially during rectal extubation. The use of CO2 and water immersion techniques may mitigate these risks.
The impact of socio‐economic deprivation on access to diabetes technology in adults with type 1 diabetes
Authors: Fallon Ciara , Jones Emma , Oliver Nick , Reddy Monika , Avari Parizad
Published: June 2022

Background

With advances in technology, there is an emerging concern that inequalities exist in provision and diabetes outcomes in areas of greater deprivation. We assess the relationship between socio‐economic status and deprivation with access to diabetes technology and their outcomes in adults with type 1 diabetes.

Methods

Retrospective, observational analysis of adults attending a tertiary centre, comprising three urban hospitals in the UK. Socio‐economic deprivation was assessed by the English Indices of Deprivation 2019. Data analysis was performed using one‐way ANOVAs and chi‐squared tests.

Results

In total, 1631 adults aged 44 ± 15 years and 758 (47%) women were included, with 391 (24%) using continuous subcutaneous insulin infusion, 312 (19%) using real‐time continuous glucose monitoring and 558 (34%) using intermittently scanned continuous glucose monitoring. The highest use of diabetes technology was in the least deprived quintile compared to the most deprived quintile (67% vs. 45%, respectively; p < 0.001). HbA1c outcomes were available in 400 participants; no association with deprivation was observed (p = 0.872). Participation in structured education was almost twice as high from the most deprived to the least deprived groups (23% vs. 43%; p < 0.001). Adults with white or mixed ethnicity were more likely to use technology compared to black ethnicity (60% vs. 40%; p < 0.001).

Conclusions

Adults living in the most deprived quintile had less technology use. Irrespective of socio‐economic status or ethnicity, glycaemia was positively affected in all groups. It is imperative that health disparities are further addressed.
Giant coronary aneurysms in an infant: Dilemma of MIS‐C
Authors: Drury Alexandra , Wold Kelsey , Healan Steven , Garg Ashish
Published: June 2022

COVID‐19 related multisystem inflammatory syndrome in children (MIS‐C) can present with cardiovascular complications like shock, arrhythmias, pericardial effusion, and coronary artery dilatation. The majority of MIS‐C associated coronary artery abnormalities are dilation or small aneurysms which are transient and resolve in a few weeks. We present here a case of a 3‐month‐old child who was noted to have giant aneurysms of her coronary arteries (LAD and RCA) 26 days after testing positive for COVID‐19. She was treated with IVIG, infliximab, and glucocorticoids along with aspirin, clopidogrel, and enoxaparin. She did not show any signs of coronary ischemia or cardiac dysfunction but continued to have persistent giant coronary artery aneurysms involving the LAD (z‐score ∼35) and RCA (z‐score ∼30). This study emphasizes the importance of early detection and aggressive management of MIS‐C to prevent potentially life‐threatening consequences.
Prevalance and course of tobacco use among individuals receiving coordinated specialty care for first‐episode psychosis
Authors: Rogers R. Tyler , Marino Leslie , Scodes Jennifer , Wall Melanie , Nossel Ilana , Dixon Lisa
Published: June 2022

Aim

Tobacco use is decreasing among the general population, but persistent use among individuals in treatment for first‐episode psychosis (FEP) remains a problem. This study aimed to measure the prevalence and course of tobacco use and explore the associations between tobacco use and clinical outcomes in a FEP sample located in New York State (NYS).

Methods

Participants (N = 870) were from the OnTrackNY system of coordinated specialty care clinics in NYS. Participant data were collected at admission to the program and at every 3 months of follow‐up using standardized forms based on reports from clients, client families and chart review. Course of tobacco use was categorized into four groups: no‐use, cessation, persistent and initiation over 1 year of follow‐up.

Results

The prevalence of tobacco use was 12.8% at baseline and 19.9% at 1‐year follow‐up. Only 3.8% of tobacco users stopped by 1 year follow‐up, and 4.9% initiated use. Urbanicity of clinic location (p < .001); age at admission (p = .044); gender (p = .015); ethnoracial group (p = .007); baseline education/employment status (p = .004); and baseline use of any non‐tobacco substances (p < .001), including alcohol (p < .001) and cannabis (p < .001), were associated with tobacco course. Findings suggest an association between tobacco use and reduced improvement in symptoms.

Conclusion

Despite a lower prevalence of tobacco use among OnTrack participants than in other comparable samples, tobacco cessation was minimal and more individuals initiated tobacco use than ceased over the course of follow‐up. Efforts to implement tobacco cessation interventions in coordinated specialty care are warranted, since tobacco use is associated with poor health outcomes.
Integrating closed‐loop principles in supply chains in emerging markets: The case of the Russian waste management industry
Authors: Aray Yulia , Veselova Anna , Knatko Dmitri , Levchenko Anna
Published: June 2022

Abstracts

The integration of closed‐loop (CL) principles in supply chain management plays an important role for business and society. The CL supply chain can serve as a good example of an environment‐friendly and sustainable solution because it assumes waste reduction and further usage in production. Hence, the notion of the CL supply chain is premised on the design, control and operation of a system that creates extra value using the entire product life cycle and capture value recovery from various returns over time. In practice, a successful integration of CL principles depends on many contextual factors. This study aimed to identify the factors that support and discourage CL supply chain innovations in emerging markets. The study employed institutional theory as theoretical background and conducted an in‐depth case analysis of a Russian waste management company to present empirical evidence. The results showed that cooperation with an experienced and legitimate partner can drive the introduction of a CL initiative. Meanwhile, a low level of knowledge and trust might become a serious impediment. Thus, investment in knowledge dissemination and reputation building are crucial in an emerging market.