bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual orexin/hypocretin receptor antagonism attenuates attentional impairments in an NMDA receptor hypofunction model of schizophrenia
Authors: Maness Eden B. , Blumenthal Sarah A. , Burk Joshua A.
Published: February 2023

Schizophrenia is a neuropsychiatric condition that is associated with impaired attentional processing and performance. Failure to support increasing attentional load may result, in part, from abnormally overactive basal forebrain projections to the prefrontal cortex, and available antipsychotics often fail to address this issue. Orexin/hypocretin receptors are expressed on corticopetal cholinergic neurons, and their blockade has been shown to decrease the activity of cortical basal forebrain outputs and prefrontal cortical cholinergic neurotransmission. In the present experiment, rats (N = 14) trained in a visual sustained attention task that required discrimination of trials which presented a visual signal from trials during which no signal was presented. Once trained, rats were then co-administered the psychotomimetic N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801: 0 or 0.1 mg/kg, intraperitoneal injections) and the dual orexin receptor antagonist filorexant (MK-6096: 0, 0.1, or 1 mM, intracerebroventricular infusions) prior to task performance across six sessions. Dizocilpine impaired overall accuracy during signal trials, slowed reaction times for correctly-responded trials, and increased the number of omitted trials throughout the task. Dizocilpine-induced increases in signal trial deficits, correct response latencies, and errors of omission were reduced following infusions of the 0.1 mM, but not 1 mM, dose of filorexant. Orexin receptor blockade, perhaps through anticholinergic mechanisms, may improve attentional deficits in a state of NMDA receptor hypofunction.

Highlights

Schizophrenia is associated with attentional deficits that may stem from abnormally reactive BF projections to the prefrontal cortex

Orexin receptor antagonists decrease acetylcholine release and reduce prefrontal cortical activity

The dual orexin receptor antagonist filorexant alleviated impairments of attention following NMDA receptor blockade
A Theory of Hippocampal Theta Correlations: Extrinsic and Intrinsic Sequences
Authors: Yiu Yuk-Hoi , Leibold Christian
Published: February 2023

Hippocampal place cell sequences have been hypothesized to serve as diverse purposes as the induction of synaptic plasticity, formation and consolidation of long-term memories, or navigation and planning. During spatial behaviors of rodents, sequential firing of place cells at the theta timescale (known as theta sequences) encodes running trajectories, which can be considered as 1-dimensional behavioral sequences of traversed locations. In a 2-dimensional space, however, each single location can be visited along arbitrary 1-dimensional running trajectories. Thus, a place cell will generally take part in multiple different theta sequences, raising questions about how this 2-dimensional topology can be reconciled with the idea of hippocampal sequences underlying memory of (1-dimensional) episodes. Here, we propose a computational model of cornu ammonis 3 (CA3) and dentate gyrus (DG), where sensorimotor input drives the direction-dependent (extrinsic) theta sequences within CA3 reflecting the 2-dimensional spatial topology, whereas the in-trahippocampal CA3-DG projections concurrently produce intrinsic sequences that are independent of the specific running trajectory. Consistent with experimental data, these intrinsic theta sequences are less prominent in the theta state, but we show that they can nevertheless be detected during theta activity, thereby serving as running-direction independent landmark cues. We hypothesize that the intrinsic sequences largely reflect replay and preplay activity during non-theta states.
Monitoring oligomerization dynamics of individual human neurotensin receptors 1 in living cells and in SMALP nanodiscs
Authors: Spantzel Lukas , Pérez Iván , Heitkamp Thomas , Westphal Anika , Reuter Stefanie , Mrowka Ralf , Börsch Michael
Published: February 2023

The human neurotensin receptor 1 (NTSR1) is a G protein-coupled receptor. The receptor is activated by a small peptide ligand neurotensin. NTSR1 can be expressed in HEK cells by stable transfection. Previously we used the fluorescent protein markers mRuby3 or mNeonGreen fused to NTSR1 for EMCCD-based structured illumination microscopy (SIM) in living HEK cells. Ligand binding induced conformational changes in NTSR1 which triggered the intracellular signaling processes. Recent single-molecule studies revealed a dynamic monomer/dimer equilibrium of this receptor in artificial lipid bilayers. Here we report on the oligomerization state of human NTSR1 from living cells by trapping them into lipid nanodiscs. Briefly, SMALPs (styrene-maleic acid copolymer lipid nanoparticles) were produced directly from the plasma membranes of living HEK293T FlpIn cells. SMALPs with a diameter of 15 nm were soluble and stable. NTSR1 in SMALPs were analyzed by single-molecule intensity measurements one membrane patch at a time using a custom-built confocal anti-Brownian electrokinetic trap (ABEL trap) microscope. We found oligomerization changes before and after stimulation of the receptor with its ligand neurotensin.
Pramipexole restores behavioral inhibition in highly impulsive rats through a paradoxical modulation of frontostriatal networks
Authors: Magnard Robin , Fouyssac Maxime , Vachez Yvan M. , Cheng Yifeng , Dufourd Thibault , Carcenac Carole , Boulet Sabrina , Janak Patricia H. , Savasta Marc , Belin David , Carnicella Sebastien
Published: February 2023

Impulse control disorders (ICDs), a wide spectrum of maladaptive behaviors which includes pathological gambling, hypersexuality and compulsive buying, have been recently suggested to be triggered or aggravated by treatments with dopamine D2/3receptor agonists, such as pramipexole (PPX). Despite evidence showing that impulsivity is associated with functional alterations in corticostriatal networks, the neural basis of the exacerbation of impulsivity by PPX has not been elucidated. Here we used a hotspot analysis to assess the functional recruitment of several corticostriatal structures by PPX in male rats identified as highly (HI), moderately impulsive (MI) or with low levels of impulsivity (LI) in the 5-choice serial reaction time task (5-CSRTT). PPX dramatically reduced impulsivity in HI rats. Assessment of the expression pattern of the two immediate early genes C-fos and Zif268 byin situhybridization subsequently revealed that PPX resulted in a decrease in Zif268 mRNA levels in different striatal regions of both LI and HI rats accompanied by a high impulsivity specific reduction of Zif268 mRNA levels in prelimbic and cingulate cortices. PPX also decreased C-fos mRNA levels in all striatal regions of LI rats, but only in the dorsolateral striatum and nucleus accumbens core (NAc Core) of HI rats. Structural equation modelling further suggested that the anti-impulsive effect of PPX was mainly attributable to the specific downregulation of Zif268 mRNA in the NAc Core. Altogether, our results show that PPX restores impulse control in highly impulsive rats by modulation of limbic frontostriatal circuits.
Cellular iron governs the host response to malaria
Authors: Wideman Sarah K. , Frost Joe N. , Richter Felix C. , Naylor Caitlin , Lopes José M. , Viveiros Nicole , Teh Megan R. , Preston Alexandra E. , White Natasha , Yusuf Shamsideen , Draper Simon J. , Armitage Andrew E. , Duarte Tiago L. , Drakesmith Hal
Published: February 2023

Malaria and iron deficiency are major global health problems with extensive epidemiological overlap. Iron deficiency-induced anaemia can protect the host from malaria by limiting parasite growth. On the other hand, iron deficiency can significantly disrupt immune cell function. However, the impact of host cell iron scarcity beyond anaemia remains elusive in malaria. To address this, we employed a transgenic mouse model carrying a mutation in the transferrin receptor (TfrcY20H/Y20H), which limits the ability of cells to internalise iron from plasma. At homeostasisTfrcY20H/Y20Hmice appear healthy and are not anaemic. However,TfrcY20H/Y20Hmice infected withPlasmodium chabaudi chabaudi ASshowed significantly higher peak parasitaemia and body weight loss. We found thatTfrcY20H/Y20Hmice displayed a similar trajectory of malaria-induced anaemia as wild-type mice, and elevated circulating iron did not increase peak parasitaemia. Instead,P. chabaudiinfectedTfrcY20H/Y20Hmice had an impaired innate and adaptive immune response, marked by decreased cell proliferation and cytokine production.

Moreover, we demonstrated that these immune cell impairments were cell-intrinsic, asex vivoiron supplementation fully recovered CD4 T cell and B cell function. Despite the inhibited immune response and increased parasitaemia,TfrcY20H/Y20Hmice displayed mitigated liver damage, characterised by decreased parasite sequestration in the liver and an attenuated hepatic immune response. Together, these results show that host cell iron scarcity inhibits the immune response but prevents excessive hepatic tissue damage during malaria infection. These divergent effects shed light on the role of iron in the complex balance between protection and pathology in malaria.
Niche cells regulate primordial germ cell quiescence in response to basement membrane signaling
Authors: McIntyre Daniel C. , Nance Jeremy
Published: February 2023

Stem cell quiescence, proliferation and differentiation are controlled by interactions with niche cells and a specialized extracellular matrix called the basement membrane (BM). Direct interactions with adjacent BM are known to regulate stem cell quiescence; however, it is less clear how niche BM relays signals to stem cells that it does not contact. Here, we examine how niche BM regulatesC. elegansprimordial germ cells (PGCs), which remain quiescent during embryogenesis. Depleting the BM protein laminin causes embryonic PGCs to proliferate, indicating that laminin functions to maintain PGC quiescence. How laminin signals to the PGCs remains unclear, as somatic niche cells enwrap PGCs and physically exclude them from contacting the BM. Here, we show that, following laminin depletion, gonadal niche cells relay proliferation-inducing signals from the gonadal BM to PGCs via integrin receptors. Mutations disrupting the BM proteoglycan perlecan block PGC proliferation when laminin is depleted, suggesting that laminin functions to inhibit a proliferation-inducing signal originating from perlecan. Our results reveal how BM signals can regulate stem cell quiescence indirectly, by activating niche cell integrin receptors.
Overcoming clinical resistance to EZH2 inhibition using rational epigenetic combination therapy
Authors: Kazansky Yaniv , Cameron Daniel , Mueller Helen , Demarest Phillip , Zaffaroni Nadia , Arrighetti Noemi , Zuco Valentina , Kuwahara Yasumichi , Somwar Romel , Ladanyi Marc , Qu Rui , Stanchina Elisa De , Cruz Filemon Dela , Kung Andrew , Gounder Mrinal , Kentsis Alex
Published: February 2023

Essential epigenetic dependencies have become evident in many cancers. Based on the functional antagonism between BAF/SWI/SNF and PRC2 inSMARCB1-deficient sarcomas, we and colleagues recently completed the clinical trial of the EZH2 inhibitor tazemetostat. However, the principles of tumor response to epigenetic therapy in general, and tazemetostat in particular, remain unknown. Using functional genomics of patient tumors and diverse experimental models, we sought to define molecular mechanisms of tazemetostat resistance inSMARCB1-deficient sarcomas and rhabdoid tumors. We found distinct classes of acquired mutations that converge on the RB1/E2F axis and decouple EZH2-dependent differentiation and cell cycle control. This allows tumor cells to escape tazemetostat-induced G1 arrest despite EZH2 inhibition, and suggests a general mechanism for effective EZH2 therapy. This also enables us to develop combination strategies to circumvent tazemetostat resistance using cell cycle bypass targeting via AURKB, and synthetic lethal targeting of PGBD5-dependent DNA damage repair via ATR. This reveals prospective biomarkers for therapy stratification, including PRICKLE1 associated with tazemetostat resistance. In all, this work offers a paradigm for rational epigenetic combination therapy suitable for immediate translation to clinical trials for epithelioid sarcomas, rhabdoid tumors, and other epigenetically dysregulated cancers.

Significance

Genomic studies of patient epithelioid sarcomas, rhabdoid tumors, and their cell lines identify mutations converging on a common pathway that is essential for response to EZH2 inhibition. Resistance mutations decouple drug-induced differentiation from cell cycle control. We identify complementary epigenetic combination strategies to overcome resistance and improve durability of response, supporting their investigation in clinical trials.
Genome-wide mining and comparative analysis of microsatellite markers fromOrientia tsutsugamushigenomes
Authors: Panda Subhasmita , Swain Subrat Kumar , Sahu Basanta Pravas , Sarangi Rachita
Published: February 2023

Microsatellite markers, otherwise known as the simple sequence repeats (SSRs), are being used for molecular identification and characterization as well as estimation of evolution pattern of the organism due to their high polymorphic nature. These are tandemly repeated sequences observed almost all organisms and differentially distributed across the genome. Although the primary genome information ofOrientia tsutsugamushi(OT) suggested the repeats hold the 40% entire of its genome, but lack of characteristic of this repeats increase our interest to study more about it. Thus we investigated a genome-wide presence of microsatellites within nine complete genomes within OT and analyzed their distribution pattern, composition and complexity. Thein-silicostudy revealed the genome of OT enrich with microsatellites having a total of 126187 SSR and 10374 cSSR throughout the genome from which 70% and 30% represented within the coding and non coding region respectively. The relative density (RD) and relative abundance (RA) of SSRs were 42-44.43/kb and 6.25-6.59/kb while for cSSRs this value ranged from 7.06-8.1/kb and 0.50-0.55/kb respectively. However, RA and RD were weakly correlate with genome size and incidence microsatellites. The mononucleotide repeats (54.55%) were prevalent over di- (33.22%), tri- (11.88%), tetra- (0.27%), penta- (0.02%), hexanucleotide (0.04%) repeats, with poly (A/T) richness over poly (G/C). Motif composition of cSSRs revealed that maximum cSSRs were made up of two microsatellites having unique duplication pattern such as AT-x-AT, CG-x-CG. More numbers microsatellites represented within the coding region provides an insight into the genome plasticity that may interfere for gene regulation to mitigate with host-pathogen interaction and evolution of the species.
Innate receptors with high specificity for HLA class I–peptide complexes
Authors: Sim Malcolm J. W. , Brennan Paul , Wahl Katherine L. , Lu Jinghua , Rajagopalan Sumati , Sun Peter D. , Long Eric O.
Published: February 2023

Genetic studies associate killer-cell immunoglobulin-like receptors (KIR) and their HLA class I ligands with a variety of human diseases. The basis for these associations, and the relative contribution of inhibitory and activating KIR to NK cell responses are unclear. As KIR binding to HLA-I is peptide-dependent, we performed systematic screens totaling over 3,500 specific interactions to determine the specificity of five KIR for peptides presented by four HLA-C ligands. Inhibitory KIR2DL1 was largely peptide sequence agnostic, binding approximately 60% of hundreds of HLA-peptide complexes tested. Inhibitory KIR2DL2, KIR2DL3, and activating KIR2DS1 and KIR2DS4 bound only 10%, down to 1% of HLA-peptide complexes tested, respectively. Activating KIR2DS1, previously described as weak, had high binding affinity for HLA-C with high peptide sequence specificity. Our data revealed MHC-restricted peptide recognition by germ-line encoded NK receptors and imply that NK cell responses can be shaped by HLA-I bound immunopeptidomes in the context of disease or infection.
Coherence-based interhemispheric EEG functional connectivity changes in distinct frequency bands during eyes open meditation
Authors: Pradeep Kumar G , Sharma Kanishka , Adarsh A , Manvi Amrutha , Ramajayam G , Ramakrishnan A G
Published: February 2023

Meditation is a self-regulatory process practiced primarily to reduce stress, manage emotions and mental health. The objective was to study the information exchange between symmetric electrodes across the hemispheres during meditation using functional connectivity (FC) measures. We investigate the changes in the coherence between EEG electrode pairs during the meditation practiced by long-term Brahmakumaris Rajyoga meditators with open eyes and during listening to music by controls as the comparable task. Two distinct FC measures derived from coherency, namely, magnitude squared coherence (MSC) and imaginary part of coherency (ICoh) are used to study the changes in interhemispheric coherence. During baseline conditions, higher MSC is found in meditators in frontocentral and centroparietal regions and higher |ICoh| globally in higher beta and gamma bands than controls. Further, in meditators, the MSC significantly increases in higher theta and alpha bands in the frontal and parietal regions and |ICoh| significantly decreases across all regions and bands except in the alpha band during meditation. However, the control subjects with no knowledge of meditation show no change in theta or alpha MSC or |ICoh| during the music session. Distinct patterns of changes are observed with the two FC measures in different frequency bands during meditation in the meditators and music-listening session in the control subjects indicating varied information processing between the right and left hemispheres and differences in the FC measures used. We found increased MSC and decreased |ICoh| between the frontal electrodes implying increased self-awareness in meditators. The MSC between the occipital electrodes in meditators is less than the controls in baseline condition indicating a possible modified visual information processing in Rajyoga meditators due to the long-term practice of meditation with open eyes. Overall, the changes in MSC indicate increased functional integration during meditation supporting the hypothesis of cortical integration theory.
Plain language in Mauritius: an empirical study of legal communication in Mauritius
Authors: Beebeejaun Ambareen
Published: February 2023

Purpose

Irrespective of various forms of language existent worldwide, it is still imperative that recipients of professional legal advice be communicated in clear terms to avoid a chaotic situation and to better fulfil obligations and enjoy the rights to which they are entitled to appropriately. As such, the objectives of this paper are twofold: firstly, this paper aims to assess the extent to which clients of the legal profession prefer plain over traditional legal language in Mauritius, a country using a myriad of languages, and secondly, to suggest recommendations for the legal stakeholders in Mauritius regarding guidelines and mechanisms on plain language provisions.

Design/methodology/approach

This study will use a desk-based research methodology by analysing existing literature on the importance of plain language in legal writing. In addition, an empirical study will be conducted to gather information on clients’ preferences in legal communication.

Findings

The responses were received on a complete anonymous basis, and it was found that in general, clients of the legal profession in Mauritius are more at ease when law practitioners use simple, direct and straightforward terms, sentences structured in active voice rather than passive voice or the use of legal jargons or complicated words. These clients also prefer when their legal advisers explain the legal meaning or interpretation in a document or agreement even if these advices may be longer than shorter sentences with only the legal jargons.

Originality/value

At present, there are few literature on the researched topic and this study will be among the first academic writings on the effectiveness of using plain language in legal documentation in Mauritius. The study is carried out with the aim of combining a large amount of empirical, theoretical and factual information that can be of use to various stakeholders and not only to academics.
Application of income capitalization approach for emerging rental income cash flow in Enugu metropolis property market
Authors: Ifeanacho Kenechi Peter , Egbenta Idu Robert
Published: February 2023

Purpose

The purpose of this research is to ascertain the extent to which the income capitalization approach reflects the pattern of emerging rental income in Enugu property market.

Design/methodology/approach

The survey research design was used in this study. Data from the field was gathered through a data collection pro forma administered to 40 valuers in Enugu metropolis in the manner of conducting interviews. This study used key valuation details of 54 sampled income generating properties valued by the respondent valuers between 2015 and 2022 using the income capitalization approach. The same sampled properties were then revalued by the researchers using annuity due assumption/formulas of the income capitalization approach. Descriptive and inferential statistics were used to analyze the data.

Findings

The study revealed that the income capitalization approach used by most valuers in Enugu does not reflect the property rental income pattern prevailing in Enugu property market where rents are paid in advance. The study further shows that the application of the income capitalization approach for valuation of annually in-advance property rental income cash flow results in a higher capital value of 3.49% in Enugu property market.

Research limitations/implications

The limitations to this study are that past valuation done by valuers were used in the analysis instead of actual property sales and a relatively small number of sampled valuers and properties are used in the study The implication of the study is that ordinary annuity assumptions or formulas is inaccurate and not suitable for valuation of income generating property in an emerging market like Nigerian where timing of cash flow is annually in advance. Based on the result of this study it seems that ordinary annuity approach negate the principle of estimating value using income capitalization method by converting future cash flow from income generating property into an estimate of property value.

Practical implications

The study advocates the adoption of the use of annuity due formulas in the valuation of income generating properties in Nigeria as its practice standard to avoid undervaluation as this assumption is logical and provides more accurate value due to prevailing lease structure and rent payments patterns in the country. The implication of the study is that the use of ordinary annuity assumptions or formulas is inaccurate and not suitable for the valuation of income generating property in an emerging market like Nigerian where timing of cash flow is annually in advance.

Originality/value

This is one of the very few empirical studies carried out in Nigeria to ascertain the extent to which the income capitalization approach used by valuers reflects the rental income pattern that prevails in the Nigeria property market.
‘He knows he is safe; you are the safety net’. Key adult intervention with children with attachment difficulties: the TAs perspective
Authors: Blackwood Lisa , Farrow Brenna
Published: February 2023

Children and young adults who are ‘looked after’ can present teachers and teaching assistants with a variety of day‐to‐day classroom challenges and a range of complex behaviours due to adverse childhood environments. This group of vulnerable young people have very complex social and emotional behaviours that require a considered approach of support and interventions. The types of interventions deployed in schools, however, may depend on staff knowledge, staff self‐confidence, and interpersonal skills to support the child's learning and complex behaviours. An example of an intervention is the key adult intervention programme, which is purported to develop staff knowledge and self‐confidence when working with looked after children. training in key adult intervention occurred at a special school, which had a high percentage of looked after children, situated in an East Midlands town. The purpose of the study was firstly to support the children through in‐depth knowledge development for supporting staff, and secondly to investigate staff confidence and understanding of the needs of looked after children. In addition, supporting factors of the key adult intervention and a discovery of any barriers to its implementation were sought. Using a mixed methods approach, data were collected from participating staff using questionnaires and focused conversations. Qualitative data were analysed using Cresswells six‐step process. Findings suggest that the key adult intervention is an effective means to support staff confidence and understanding and offer support for looked after children. Recommendations for future practice include increased training and support for teaching assistants, teachers and the school community as a whole. In addition, targeted professional and emotional support for the teaching assistants deployed, and increased communication between senior leaders and teaching assistants is crucial. The current research, therefore, adds to existing literature by providing an evaluation of the key adult intervention within a special school setting with evidence gathered from teaching assistants.
Universal two‐dimensional labelled probe‐mediated melting curve analysis based on multiplex PCR for rapid typing of Plasmodium in a single closed tube
Authors: Xu Haipo , Sun Yupeng , Zhang Xiaolong , Chen Ronghua , Cai Zhixiong , Zhao Bixing , Liu Xiaolong , Liu Jingfeng
Published: February 2023

Currently, malaria is still one of the major public health problems commonly caused by the four Plasmodium species. The similar symptoms of malaria and the COVID‐19 epidemic of fever or fatigue lead to frequent misdiagnosis. The disadvantages of existing detection methods, such as time‐consuming, costly, complicated operation, need for experienced technicians, and indistinguishable typing, lead to difficulties in meeting the clinical requirements of rapid, easy, and accurate typing of common Plasmodium species. In this study, we developed and optimized a universal two‐dimensional labelled probe‐mediated melting curve analysis (UP‐MCA) assay based on multiplex and asymmetric PCR for rapid and accurate typing of five Plasmodium species, including novel human Plasmodium, Plasmodium knowlesi (Pk), in a single closed tube following genome extraction. The assay showed a limit of detection (LOD) of 10 copies per reaction and could accurately distinguish Plasmodium species from intra‐plasmodium and other pathogens. Additionally, we proposed and validated different methods of fluorescence quenching and tag design for probes that are suitable for UP‐MCA assays. Moreover, the clinical performance of the Plasmodium UP‐MCA assay using a base‐quenched universal probe was evaluated using 226 samples and showed a sensitivity of 100% (164/164) and specificity of 100% (62/62) at a 99% confidence interval, with the microscopy method as the gold standard. In summary, the UP‐MCA assay showed excellent sensitivity, specificity, and accuracy for genotyping Plasmodium species spp. Additionally, it facilitates convenient and rapid Plasmodium detection in routine clinical practice and has great potential for clinical translation.
The proof is in the poo: Non‐invasive method to detect endoparasitic infection
Authors: Doherty Jean‐François , Bhattarai Upendra R. , Ferreira Sara , Poulin Robert , Gemmell Neil J. , Dowle Eddy J.
Published: February 2023

Almost every animal trait is strongly associated with parasitic infection or the potential exposure to parasites. Despite this importance, one of the greatest challenges that researchers still face is to accurately determine the status and severity of the endoparasitic infection without killing and dissecting the host. Thus, the precise detection of infection with minimal handling of the individual will improve experimental designs in live animal research. Here, we quantified extracellular DNA from two species of endoparasitic worm that grow within the host body cavity, hairworms (phylum Nematomorpha) and mermithids (phylum Nematoda), from the frass of their insect host, a cave wētā (Orthoptera: Rhaphidophoridae) and an earwig (Dermaptera: Forficulidae), respectively. Frass collection was done at two successive time periods, to test if parasitic growth correlated with relative DNA quantity in the frass. We developed and optimized two highly specific TaqMan assays, one for each parasite‐specific DNA amplification. We were able to detect infection prevalence with 100% accuracy in individuals identified as infected through post‐study dissections. An additional infection in earwigs was detected with the TaqMan assay alone, probably because some worms were either too small or degraded to observe during dissection. No difference in DNA quantity was detected between sampling periods, although future protocols could be refined to support such a trend. This study demonstrates that a noninvasive and minimally stressful method can be used to detect endoparasitic infection with greater accuracy than dissection alone, helping improve protocols for live animal studies.
Efficacy and safety of Extrapleural block in patients with coronary artery disease after thoracoscopic surgery
Authors: Qu Tianfang , Han Tian , Yang Wenqu , Wei Zhihui , He Huizhen , Yuan Xin
Published: February 2023

Objective

This study aimed to investigate the efficacy and safety of extrapleural block (EPB) application in patients with coronary artery disease after thoracoscopic surgery.

Methods

Patients with typical symptoms of angina and myocardial ischemia who underwent thoracoscopic surgery at our institution between December 2018 and December 2020 were screened for eligibility and they received paravertebral blocking (PVB), EPB, and patient‐controlled intravenous analgesia (PCIA). Visual analog scale (VAS) scores were used to assess the analgesic effect and safety outcomes included heart rate, incidence of postoperative rescue analgesics, cardiac complications, and adverse reactions such as nausea and vomiting.

Results

In total, 76 patients (age: 66.5 [61.3, 71] years; male: 63.2%) were eligible, including the PVB group (n = 22), EPB group (n = 25), and PVIA group (n = 29) with comparable baseline characteristics. There was a significantly higher proportion of patients with a VAS score of 1 in the EPB group compared with the other groups at 4 h (88.0% vs. 10.3% for PCIA and 45.5% for PVB; p < .001) and 6 h after the surgery (32.0% vs. 3.4% for PCIA and 13.6% for PVB; p = .012). The preoperative heart rate in the EPB group (81 [71, 94] beats/min) was slightly higher than those in the PVB (76 [70, 85] beats/min) and PCIA groups (76 [69, 84 beats/min]) but without significant difference (p = .193). There was no significant difference in the incidence of rescue analgesia, adverse events, and cardiac complications among the three groups (p = .296, .808, and .669, respectively.)

Conclusion

Compared with PVB and PCIA, the EPB could more effectively relieve acute pain after thoracoscopic surgery in patients with coronary artery disease and offer comparable safety benefits in the management of postoperative heart rate, adverse events, and cardiac complications.
Acquisition of new arithmetic skills based on prior arithmetic skills: A cross‐sectional study in primary school from grade 2 to grade 5
Authors: Thevenot Catherine , Tazouti Youssef , Billard Catherine , Dewi Jasinta , Fayol Michel
Published: February 2023

Background

In several countries, children's math skills have been declining at an alarming rate in recent years and decades, and one of the explanations for this alarming situation is that children have difficulties in establishing the relations between arithmetical operations.

Aim

In order to address this question, our goal was to determine the predictive power of previously taught operations on newly taught ones above general cognitive skills and basic numerical skills.

Samples

More than one hundred children in each school level from Grades 2 to 5 from various socio‐cultural environments (N = 435, 229 girls) were tested.

Methods

Children were assessed on their abilities to solve the four basic arithmetic operations. They were also tested on their general cognitive abilities, including working memory, executive functions (i.e., inhibition and flexibility), visual attention and language. Finally, their basic numerical skills were measured through a matching task between symbolic and nonsymbolic numerosity representations. Additions and subtractions were presented to children from Grade 2, multiplications from Grade 3 and divisions from Grade 4.

Results and Conclusions

We show that addition predicts subtraction and multiplication performance in all grades. Moreover, multiplication predicts division performance in both Grades 4 and 5. Finally, addition predicts division in Grade 4 but not in Grade 5 and subtraction and division are not related whatever the school grade. These results are examined considering the existing literature, and their implications in terms of instruction are discussed.
Neuroimaging biomarkers of small vessel disease in cerebral amyloid angiopathy‐related intracerebral hemorrhage
Authors: Zhang Mengke , Che Ruiwen , Zhao Wenbo , Sun Hailiang , Ren Changhong , Ma Jin , Hu Wenbo , Jia Milan , Wu Chuanjie , Liu Xin , Ji Xunming
Published: February 2023

Aims

The significance of the correlation of computed tomography (CT)–based cerebral small vessel disease (SVD) markers with the clinical outcomes in patients with cerebral amyloid angiopathy (CAA)‐related intracerebral hemorrhage (ICH) remains uncertain. Thus, this study aimed to explore the relationship between SVD markers and short‐term outcomes of CAA‐ICH.

Methods

A total of 183 patients with CAA‐ICH admitted to the Xuanwu Hospital, and Beijing Fengtai You'anmen Hospital, from 2014 to 2021 were included. The multivariate logistic regression analysis was performed to identify the correlation between SVD markers based on CT and clinical outcomes at 7‐day and 90‐day.

Results

Of the 183 included patients, 66 (36%) were identified with severe SVD burden. The multivariate analysis showed that the total SVD burden, white matter lesion (WML) grade, and brain atrophy indicator were independent risk factors for unfavorable outcomes at 90‐day. The brain atrophy indicator was independently associated with mortality at 90‐day. Severe cortical atrophy was significantly associated with early neurological deterioration.

Conclusions

The neuroimaging profiles of SVD based on CT in patients with CAA‐ICH might predict the short‐term outcome more effectively. Further studies are required to validate these findings and identify modifiable factors for preventing CAA‐ICH development.
The Binding Problem 2.0: Beyond Perceptual Features
Authors: Yu Xinchi , Lau Ellen
Published: February 2023

The “binding problem” has been a central question in vision science for some 30 years: When encoding multiple objects or maintaining them in working memory, how are we able to represent the correspondence between a specific feature and its corresponding object correctly? In this letter we argue that the boundaries of this research program in fact extend far beyond vision, and we call for coordinated pursuit across the broader cognitive science community of this central question for cognition, which we dub “Binding Problem 2.0”.
Cognition: A Study in Mental Economy
Authors: Wojtowicz Zachary , Loewenstein George
Published: February 2023

In this letter, we argue that an economic perspective on the mind has played—and should continue to play—a central role in the development of cognitive science. Viewing cognition as the productive application of mental resources puts cognitive science and economics on a common conceptual footing, paving the way for closer collaboration between the two disciplines. This will enable cognitive scientists to more readily repurpose economic concepts and analytical tools for the study of mental phenomena, while at the same time, enriching our understanding of the modern economy, which is increasingly driven by mental, rather than physical, production.
Implications of exceeding the Paris Agreement for mammalian biodiversity
Authors: Mendez Angarita Valeria Y. , Maiorano Luigi , Dragonetti Chiara , Di Marco Moreno
Published: February 2023

The Paris Agreement settled to limit global warming to 2°C and possibly 1.5°C from pre‐industrial times. However, little is known about the implications of such climatic goals for biodiversity once species' adaptability to new climatic conditions is accounted for. Here, we projected the bioclimatic space loss for mammalian communities across terrestrial biomes, under four alternative emission scenarios to year 2050, and evaluated the risk for taxonomic, phylogenetic, and functional biodiversity in each biome. The high‐emission scenario (largely overshooting Paris limits) will lead to an average 34% bioclimatic space loss across biomes, surpassing critical levels in half of them (31 out of 63), including six biomes with high biodiversity content. Overall, these biomes account for an area at risk which is 10 times larger compared to that identified under low‐emission scenarios. Under intermediate‐emission scenario the loss is reduced to 28%, but two biomes with high biodiversity content will still be at risk. Achieving the 1.5°C target would reduce the average bioclimatic space loss to 19%, with only eight biomes facing critical levels of loss, none of which hosts high biodiversity content. These results highlight the biological risk of climate inaction and the consequences of exceeding Paris Agreement's climatic goals.
Balancing Conflicting Types of Authenticity in the Reconstruction of Sound and Music in the Installation Work Blikk (1970)
Authors: Rudi Jøran
Published: February 2023

This article describes the quest for authenticity in the reconstruction of music, sound, light and logic in the installation work Blikk (The Gaze) by Irma Salo Jæger, Sigurd Berge and Jan Erik Vold. My work on this installation was undertaken at the behest of the National Museum for Art and Architecture in Oslo, Norway, who planned for the installation to be part of the exhibition when the doors opened to their new building in June 2022, following several years of construction. Blikk is described here in context with other works from the same period with which it shares some characteristics, and also with a view on the commissioning institution that represented and promoted radical artistic and curatorial innovation at the time. This frames my discussion of the different authenticity concerns that emerged during the restoration and reconstruction process. In fact, as the project grew from relatively trivial restoration to more involved reconstruction, weighing different authenticity types became the central element of the effort. I have used written, visual and sounding sources in descriptions on how I have balanced these concerns, and the discussion has been supplemented with information on the music technology available to the artists in 1970.
Chronic pain interference assessment tools for children and adults who are unable to self‐report: A systematic review of psychometric properties
Authors: Smith Meredith G. , Farrar Lucy C. , Gibson Rachel J. , Russo Remo N. , Harvey Adrienne R.
Published: February 2023

Aim

To identify and evaluate psychometric properties of assessment tools for assessing pain interference in children, adolescents, and adults with chronic pain and the inability to self‐report.

Method

The protocol was registered with PROSPERO (CRD42022310102). A search was run in MEDLINE, Embase, and PsycInfo (29th March 2022) to identify articles reporting psychometric properties of pain interference assessment tools for children, adolescents, and adults with chronic pain and the inability to objectively self‐report pain. Retrieved studies were reviewed by two authors (MGS, LCF) and study quality was assessed using COSMIN.

Results

Psychometric properties of 10 pain interference tools were assessed from 33 studies. The Paediatric Pain Profile (PPP) had low‐quality evidence for content validity and internal consistency with children and adolescents who are unable to self‐report. No tools for adults had evidence for content validity and internal consistency. No tool had evidence for all nine psychometric properties.

Interpretation

The PPP is recommended for pain interference assessment in children and adolescents with chronic pain and the inability to self‐report. Few tools are available for adults. Three tools for children (Patient‐Reported Outcome Measurement Information System Pediatric Proxy Pain Interference Scale; Bath Adolescent Pain Questionnaire for Parents; modified Brief Pain Inventory‐Proxy [mBPI]) and three tools for adults (Doloplus‐2; Patient‐Reported Outcome Measurement Information System Pain Interference Scale‐proxy; Brief Pain Inventory‐proxy) are promising but require further investigation.
Does intrathecal baclofen alter the natural history of hip displacement?
Authors: Gormley Mark
Published: February 2023

This commentary is on the original article by Asma et al. on pages 1112–1117 of this issue.
A phase 1 open‐label trial evaluating focused ultrasound unilateral anterior thalamotomy for focal onset epilepsy
Authors: Krishna Vibhor , Mindel Jesse , Sammartino Francesco , Block Cady , Dwivedi Alok Kumar , Van Gompel Jamie J. , Fountain Nathan , Fisher Robert
Published: February 2023

Objective

Focused ultrasound ablation (FUSA) is an emerging treatment for neurological and psychiatric diseases. We describe the initial experience from a pilot, open‐label, single‐center clinical trial of unilateral anterior nucleus of the thalamus (ANT) FUSA in patients with treatment‐refractory epilepsy.

Methods

Two adult subjects with treatment‐refractory, focal onset epilepsy were recruited. The subjects received ANT FUSA using the Exablate Neuro (Insightec) system. We determined the safety and feasibility (primary outcomes), and changes in seizure frequency (secondary outcome) at 3, 6, and 12 months. Safety was assessed by the absence of side effects, that is, new onset neurological deficits or performance deterioration on neuropsychological testing. Feasibility was defined as the ability to create a lesion within the anterior nucleus. The monthly seizure frequency was compared between baseline and postthalamotomy.

Results

The patients tolerated the procedure well, without neurological deficits or serious adverse events. One patient experienced a decline in verbal fluency, attention/working memory, and immediate verbal memory. Seizure frequency reduced significantly in both patients; one patient was seizure‐free at 12 months, and in the second patient, the frequency reduced from 90–100 seizures per month to 3–6 seizures per month.

Significance

This is the first known clinical trial to assess the safety, feasibility, and preliminary efficacy of ANT FUSA in adult patients with treatment‐refractory focal onset epilepsy.
Seeing, being seen, and the semiotics of perspective
Authors: Nakassis Constantine V.
Published: February 2023

Building upon work in visual studies and art history on symbolic perspective, film studies on structures of looking, and linguistic anthropology on entextualization and ideology, this article explores the semiotics of vision/visibility and perspective. In particular, I focus on ethnographic data from the cinema of Tamil Nadu, India, wherein (being seen) seeing a film image and being seen in a film image emerge as pragmatically problematic for those party to the image. In doing so, the article asks: what does it mean and do to see and be seen by, look away from and be effaced by the film image and, further, see or be seen vis‐à‐vis the above (seeing someone being seen in a film image, be seen looking away, etc.)?
Silenced Conflict: Surveillance and Normalization UsingWhatsAppGroups at School
Authors: Moyano Dávila Camila , Rojas‐Navarro Sebastián , Domenech Raúl
Published: February 2023

Objective

To understand the particularities of the surveillance produced by parents' WhatsApp groups and the consequences they have for schools and families.

Background

The literature on the use of these groups and platforms for online communication has contended that teachers and parents feel that they are under constant surveillance when they are using them. The advantages and disadvantages of these platforms are presented, as well as recommendations for good practices.

Method

Qualitative analysis of two WhatsApp chats of parents from two schools in Chile, one public and one private, using a grounded theory approach.

Results

Using a theoretical framework of science, technology, and society studies, we examine the particularities of this surveillance observed in three dimensions: conflicts as smoke bombs, operational surveillance, and affective surveillance. In this respect, we argue that in these groups, intimate surveillance leads to the normalization of certain behaviors that cause conflict to be silenced.

Conclusion

We argue that silencing of conflict is problematic in that it does not allow the emergence of different ways of being a teacher or parent, which has significant consequences for families and their relationship with the school, especially in locations similar to the one we studied, where communication between families and schools has relied heavily on messaging apps such as WhatsApp.

Implications

WhatsApp groups appear to offer opportunities to subvert the surveillance of digital platforms, as long as conflicts are allowed to be sustained when differences emerge.
Pressure does not affect fibrotic function of dermal fibroblast through an in vitro 3D hydrogel culture model
Authors: Wei Yating , Deng Jiawen , Yin Meifang , Xu Guangchao , He Jinqing , Wang Xiaoyan , Zhang Lijun , Li Zhibin , Huang Guangtao , Wu Jun
Published: February 2023

Pressure therapy has been used for the prevention and treatment of hypertrophic scars for decades. However, the cellular and molecular mechanisms of this treatment modality have not been fully elaborated, leading to long‐lasting controversies regarding its clinical effectiveness. In this current study, we adopted an in vitro 3D culture and compression model to explore the effect of pressure force on fibroblasts, in order to further explain the working mechanism of compression force during pressure treatment. Human dermal fibroblasts were cultured in the 3D culture hydrogel and treated with 1.5 atm of external compression force through a syringe tube device, for 4, 8, and 20 h respectively. RNA‐seq identified 437 differentially regulated genes after an 8‐h compression intervention compared with control cells, among which 256 genes were up‐regulated and 181 genes were down‐regulated. Further q‐PCR analysis confirmed that early growth response 1(EGR1) and c‐fos were down‐regulated after an 8‐h compression intervention. However, the down‐regulation of EGR1 and c‐fos at the mRNA level does not lead to altered protein synthesis through western blot, for both 8 and 20‐h time points after pressure intervention. Genes closely related to the fibrotic function of fibroblasts including type I collagen (COL1), type III collagen (COL3), transforming growth factor β1(TGF‐β1), matrix metallopeptidase 1 (MMP1), matrix metallopeptidase 1 (TIMP1), connective tissue growth factor (CTGF), α smooth muscle actin (α‐SMA), and fibronectin 1 (FN1), were also unaffected after pressure treatment for 8 h. The current study indicated that in our 3D hydrogel culture model, pressure does not directly affect the fibrotic function of dermal fibroblast in vitro. Indirect regulation including reducing oedema, blood perfusion, and tension could be a more possible mechanism of pressure therapy.