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We investigated which parts of the cerebellum are involved in formulating and articulating sentences using (i) a sentence production task that involved describing simple events in pictures; (ii) an auditory sentence repetition task involving the same sentence articulation but not sentence formulation; and (iii) an auditory sentence-to-picture matching task that involved the same pictorial events and no overt articulation. Activation for each of these tasks was compared to the equivalent word processing tasks: noun production, verb production, auditory noun repetition, and auditory noun-to-picture matching. We associate activation in bilateral cerebellum lobule VIIb with sequencing words into sentences because it increased for sentence production compared to all other conditions and was also activated by word production compared to word matching. We associate a paravermal part of right cerebellar lobule VIIIb with overt motor execution of speech, because activation was higher during (i) production and repetition of sentences compared to the corresponding noun conditions and (ii) noun and verb production compared to all matching tasks, with no activation relative to fixation during any silent (nonspeaking) matching task. We associate activation within right cerebellar Crus II with covert articulatory activity because it activated for (i) all speech production more than matching tasks and (ii) sentences compared to nouns during silent (nonspeaking) matching as well as sentence production and sentence repetition. Our study serendipitously segregated, for the first time, three distinct functional roles for the cerebellum in generic speech production, and it demonstrated how sentence production enhanced the demands on these cerebellar regions., Competing Interests: Competing Interests: The authors have declared that no competing interests exist., (© 2024 Massachusetts Institute of Technology.)

Culture-acquired variants in human pluripotent stem cells (hPSCs) hinder their applications in research and clinic. However, the mechanisms that underpin selection of variants remain unclear. Here, through analysis of comprehensive karyotyping datasets from over 23,000 hPSC cultures of more than 1,500 lines, we explored how culture conditions shape variant selection. Strikingly, we identified an association of chromosome 1q gains with feeder-free cultures and noted a rise in its prevalence in recent years, coinciding with increased usage of feeder-free regimens. Competition experiments of multiple isogenic lines with and without a chromosome 1q gain confirmed that 1q variants have an advantage in feeder-free (E8/vitronectin), but not feeder-based, culture. Mechanistically, we show that overexpression of MDM4, located on chromosome 1q, drives variants' advantage in E8/vitronectin by alleviating genome damage-induced apoptosis, which is lower in feeder-based conditions. Our study explains condition-dependent patterns of hPSC aberrations and offers insights into the mechanisms of variant selection., Competing Interests: Declaration of interests T.E.L. is a co-inventor and receives a share of royalties on various hPSC media- and culture-related patents currently owned and licensed by the Wisconsin Alumni Research Foundation (WARF). I.B. is a member of the scientific advisory board of WiCell. U.B.-D. received consulting fees from Accent Therapeutics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The relationships between opioid use disorder (OUD), chronic pain, and mental health distress are complex and multidirectional. The objective of this exploratory study was to examine the relationship between mental health conditions and Chronic pain severity and interference among patients stabilized on either buprenorphine or methadone., Methods: We report baseline data from a randomized trial of a mind-body intervention conducted at 5 outpatient clinics that provided either buprenorphine or methadone treatment. Validated scales were used to measure substance use, mental health distress, and pain severity and interference. Statistical analyses examined the relationship between mental health conditions and pain severity and interference., Results: Of 303 participants, 57% (n = 172) reported Chronic pain. A total of 88% (n = 268) were prescribed buprenorphine. Mental health conditions were common, with one-quarter of the sample screening positive for all 3 mental health conditions (anxiety, depression, and posttraumatic stress disorder [PTSD]). Compared to participants without Chronic pain, participants with Chronic pain were more likely to screen positive for moderate-severe anxiety (47% vs 31%); moderate-severe depression (54% vs 41%); and the combination of anxiety, depression, and PTSD (31% vs 18%). Among participants with Chronic pain, mental health conditions were associated with higher pain interference. Pain severity was higher among participants with mental health conditions, but only reached statistical significance for depression. Pain interference scores increased with a higher number of co-occurring mental health conditions., Conclusions: Among individuals stabilized on either buprenorphine or methadone, highly symptomatic and comorbid mental health distress is common and is associated with increased pain interference. Adequate screening for, and treatment of, mental health conditions in patients with OUD and Chronic pain is needed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Systematic evidence syntheses (systematic reviews and maps) summarize knowledge and are used to support decisions and policies in a variety of applied fields, from medicine and public health to biodiversity conservation. However, conducting these exercises in conservation is often expensive and slow, which can impede their use and hamper progress in addressing the current biodiversity crisis. With the explosive growth of large language models (LLMs) and other forms of artificial intelligence (AI), we discuss here the promise and perils associated with their use. We conclude that, when judiciously used, AI has the potential to speed up and hopefully improve the process of evidence synthesis, which can be particularly useful for underfunded applied fields, such as conservation science., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: There is little study of lifetime trauma exposure among individuals engaged in medication treatment for opioid use disorder (MOUD). A multisite study provided the opportunity to examine the prevalence of lifetime trauma and differences by gender, PTSD status, and chronic pain., Methods: A cross-sectional study examined baseline data from participants (N = 303) enrolled in a randomized controlled trial of a mind-body intervention as an adjunct to MOUD. All participants were stabilized on MOUD. Measures included the Trauma Life Events Questionnaire (TLEQ), the Brief Pain Inventory (BPI), and the Posttraumatic Stress Disorder Checklist (PCL-5). Analyses involved descriptive statistics, independent sample t-tests, and linear and logistic regression., Results: Participants were self-identified as women (n = 157), men (n = 144), and non-binary (n = 2). Fifty-seven percent (n = 172) self-reported chronic pain, and 41% (n = 124) scored above the screening cut-off for PTSD. Women reported significantly more intimate partner violence (85%) vs 73%) and adult sexual assault (57% vs 13%), while men reported more physical assault (81% vs 61%) and witnessing trauma (66% vs 48%). Men and women experienced substantial childhood physical abuse, witnessed intimate partner violence as children, and reported an equivalent exposure to accidents as adults. The number of traumatic events predicted PTSD symptom severity and PTSD diagnostic status. Participants with chronic pain, compared to those without chronic pain, had significantly more traumatic events in childhood (85% vs 75%)., Conclusion: The study found a high prevalence of lifetime trauma among people in MOUD. Results highlight the need for comprehensive assessment and mental health services to address trauma among those in MOUD treatment., Trial Registration: NCT04082637., (© 2024. The Author(s).)

Mammalian herbivores browse palatable plants of ecological and economical value. Undesirable neighbours can reduce browsing to these plants by providing 'associational refuge', but they can also compete for resources. Here we recreated the informative odour emitted by undesirable plants. We then tested whether this odour could act as virtual neighbours, providing browsing refuge to palatable eucalyptus tree seedlings. We found that protection using this method was equivalent to protection provided by real plants. Palatable seedlings were 17-20 times more likely to be eaten by herbivores without virtual, or real, neighbours. Because many herbivores use plant odour to forage, virtual neighbours could provide a useful practical management approach to help protect valued plants., (© 2024. The Author(s).)

Background Aims: The appearance of genetically variant populations in human pluripotent stem cell (hPSC) cultures represents a concern for research and clinical applications. Genetic variations may alter hPSC differentiation potential or cause phenotype variation in differentiated cells. Further, variants may have properties such as proliferative rate, or response to the culture environment, that differ from wild-type cells. As such, understanding the behavior of these variants in culture, and any potential operational impact on manufacturing processes, will be necessary to control quality of putative hPSC-based products that include a proportion of variant threshold in their quality specification., Methods: Here we show a computational model that mathematically describes the growth dynamics between commonly occurring genetically variant hPSCs and their counterpart wild-type cells in culture., Results: We show that our model is capable of representing the growth behaviors of both wild-type and variant hPSCs in individual and co-culture systems., Conclusions: This representation allows us to identify three critical process parameters that drive critical quality attributes when genetically variant cells are present within the system: total culture density, proportion of variant cells within the culture system and variant cell overgrowth. Lastly, we used our model to predict how the variability of these parameters affects the prevalence of both populations in culture., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

Anomia, or difficulty naming common objects, is the most common, acquired impairment of language. Effective therapeutic interventions for anomia typically involve massed practice at high doses. This requires significant investment from patients and therapists. Aphasia researchers have increasingly looked to neurostimulation to accelerate these treatment effects, but the evidence behind this intervention is sparse and inconsistent. Here, we hypothesised that group-level neurostimulation effects might belie a more systematic structure at the individual level. We sought to test the hypothesis by attempting to predict the immediate (online), individual-level behavioural effects of anodal and sham neurostimulation in 36 chronic patients with anomia, performing naming and size judgement tasks. Using clinical, (pre-stimulation) behavioural and MRI data, as well as Partial Least Squares regression, we attempted to predict neurostimulation effects on accuracies and reaction times of both tasks. Model performance was assessed via cross-validation. Predictive performances were compared to that of a null model, which predicted the mean neurostimulation effects for all patients. Models derived from pre-stimulation data consistently outperformed the null model when predicting neurostimulation effects on both tasks' performance. Notably, we could predict behavioural declines just as well as improvements. In conclusion, inter-patient variation in online responses to neurostimulation is, to some extent, systematic and predictable. Since declines in performance were just as predictable as improvements, the behavioural effects of neurostimulation in patients with anomia are unlikely to be driven by placebo effects. However, the online effect of the intervention appears to be as likely to interfere with task performance as to improve it.

In this work, we present a first-principles investigation of the properties of superlattices made from transition metal dichalcogenides for use as electrodes in lithium-ion and magnesium-ion batteries. From a study of 50 pairings, we show that, in general, the volumetric expansion, intercalation voltages, and thermodynamic stability of vdW superlattice structures can be well approximated with the average value of the equivalent property for the component layers. We also found that the band gap can be reduced, improving the conductivity. Thus, we conclude that superlattice construction can be used to improve material properties through the tuning of intercalation voltages toward specific values and by increasing the stability of conversion-susceptible materials. For example, we demonstrate how pairing SnS 2 with systems such as MoS 2 can change it from a conversion to an intercalation material, thus opening it up for use in intercalation electrodes., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Extracellular matrices interface with cells to promote cell growth and tissue development. Given this critical role, matrix mimetics are introduced to enable biomedical materials ranging from tissue engineering scaffolds and tumor models to organoids for drug screening and implant surface coatings. Traditional microscopy methods are used to evaluate such materials in their ability to support exploitable cell responses, which are expressed in changes in cell proliferation rates and morphology. However, the physical imaging methods do not capture the chemistry of cells at cell-matrix interfaces. Herein, we report hyperspectral imaging to map the chemistry of human primary and embryonic stem cells grown on matrix materials, both native and artificial. We provide the statistical analysis of changes in lipid and protein content of the cells obtained from infrared spectral maps to conclude matrix morphologies as a major determinant of biochemical cell responses. The study demonstrates an effective methodology for evaluating bespoke matrix materials directly at cell-matrix interfaces.

In our study, we examined nine transition metal dichalcogenide (TMDC)-graphene superlattices as potential Li-ion intercalation electrodes. We determined their voltages, with ScS 2 -graphene in T- and R-phases showing the highest at around 3 V, while the others ranged from 0 to 1.5 V. Most superlattices exhibited minimal volumetric expansion (5 to 10%), similar to NMC (8%), except for SnS 2 -T and NiS 2 -T, which expanded up to nearly 20%. We evaluated their capacities using a stability metric, E IS , and found that ScS 2 -T, ScS 2 -R, and TiS 2 -T could be intercalated up to two Li ions per MX 2 unit without decomposing to Li 2 S, yielding capacities of 306.77 mA h/g for both ScS 2 phases and 310.84 mA h/g for TiS 2 -T, roughly equivalent to LiC 2 . MoS 2 -T could accept Li up to a limit of a = 15/16 in Li a MoS 2 C b , corresponding to a capacity of 121.29 mA h/g (equivalent to LiC 4 ). Examining the influence of graphene layers on MoS 2 -T, we observed a voltage decrease and an initial E IS decrease before effectively flat lining, which is due to charge donation to the middle graphene layer, reducing the electron concentration near the TMDC layer. As graphene layers increased, overall volume expansion decreased with Li intercalation, which is attributed to the in-plane expansion changing. Our results underscore the potential of TMDC-graphene superlattices as Li-ion intercalation electrodes, offering low volumetric expansions, high capacities, and a wide voltage range. These superlattices all show an increase in the capacity of the graphene., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Machine learning offers great potential for automated prediction of post-stroke symptoms and their response to rehabilitation. Major challenges for this endeavour include the very high dimensionality of neuroimaging data, the relatively small size of the datasets available for learning and interpreting the predictive features, as well as, how to effectively combine neuroimaging and tabular data (e.g. demographic information and clinical characteristics). This paper evaluates several solutions based on two strategies. The first is to use 2D images that summarise MRI scans. The second is to select key features that improve classification accuracy. Additionally, we introduce the novel approach of training a convolutional neural network (CNN) on images that combine regions-of-interests (ROIs) extracted from MRIs, with symbolic representations of tabular data. We evaluate a series of CNN architectures (both 2D and a 3D) that are trained on different representations of MRI and tabular data, to predict whether a composite measure of post-stroke spoken picture description ability is in the aphasic or non-aphasic range. MRI and tabular data were acquired from 758 English speaking stroke survivors who participated in the PLORAS study. Each participant was assigned to one of five different groups that were matched for initial severity of symptoms, recovery time, left lesion size and the months or years post-stroke that spoken description scores were collected. Training and validation were carried out on the first four groups. The fifth (lock-box/test set) group was used to test how well model accuracy generalises to new (unseen) data. The classification accuracy for a baseline logistic regression was 0.678 based on lesion size alone, rising to 0.757 and 0.813 when initial symptom severity and recovery time were successively added. The highest classification accuracy (0.854), area under the curve (0.899) and F1 score (0.901) were observed when 8 regions of interest were extracted from each MRI scan and combined with lesion size, initial severity and recovery time in a 2D Residual Neural Network (ResNet). This was also the best model when data were limited to the 286 participants with moderate or severe initial aphasia (with area under curve = 0.865), a group that would be considered more difficult to classify. Our findings demonstrate how imaging and tabular data can be combined to achieve high post-stroke classification accuracy, even when the dataset is small in machine learning terms. We conclude by proposing how the current models could be improved to achieve even higher levels of accuracy using images from hospital scanners., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Both classic and contemporary models of auditory word repetition involve at least four left hemisphere regions: primary auditory cortex for processing sounds; pSTS (within Wernicke's area) for processing auditory images of speech; pOp (within Broca's area) for processing motor images of speech; and primary motor cortex for overt speech articulation. Previous functional-MRI (fMRI) studies confirm that auditory repetition activates these regions, in addition to many others. Crucially, however, contemporary models do not specify how regions interact and drive each other during auditory repetition. Here, we used dynamic causal modelling, to test the functional interplay among the four core brain regions during single auditory word and pseudoword repetition. Our analysis is grounded in the principle of degeneracy-i.e., many-to-one structure-function relationships-where multiple neural pathways can execute the same function. Contrary to expectation, we found that, for both word and pseudoword repetition, (i) the effective connectivity between pSTS and pOp was predominantly bidirectional and inhibitory; (ii) activity in the motor cortex could be driven by either pSTS or pOp; and (iii) the latter varied both within and between individuals. These results suggest that different neural pathways can support auditory speech repetition. This degeneracy may explain resilience to functional loss after brain damage., (© 2023. The Author(s).)

Interoception, the representation of the body's internal state, is increasingly recognized for informing subjective wellbeing and promoting regulatory behavior. However, few empirical reports characterize interoceptive neural networks, and fewer demonstrate changes to these networks in response to an efficacious intervention. Using a two-group randomized controlled trial, this pilot study explored within-participant neural plasticity in interoceptive networks following Mindful Awareness in Body-oriented Therapy (MABT). Participants (N = 22) were assigned to either 8 weeks of MABT or to a no-treatment control and completed baseline and post-intervention assessments that included subjective interoceptive awareness (MAIA) and neuroimaging of an interoceptive awareness task. MABT was uniquely associated with insula deactivation, increased functional connectivity between the dorsal attention network and the somatomotor cortex, and connectivity changes correlated positively with changes in subjective interoception. Within the MABT group, changes in subjective interoception interacted with changes in a predefined anterior cingulate seed region to predict changes in right middle insula activity, a putative primary interoceptive representation region. While the small sample size requires the replication of findings, results suggest that interoceptive training enhances sensory-prefrontal connectivity, and that such changes are commensurate with enhanced interoceptive awareness.

Conservation behaviour is a growing field that applies insights from the study of animal behaviour to address challenges in wildlife conservation and management. Conservation behaviour interventions often aim to manage specific behaviours of a species to solve conservation challenges. The field is often viewed as offering approaches that are less intrusive or harmful to animals than, for example, managing the impact of a problematic species by reducing its population size (frequently through lethal control). However, intervening in animal behaviour, even for conservation purposes, may still raise important ethical considerations. We discuss these issues and develop a framework and a decision support tool, to aid managers and researchers in evaluating the ethical considerations of conservation behaviour interventions against other options., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Agglomeration is an issue that causes many problems during secondary processing for pharmaceutical companies, causing material to need further processing and costing additional time and resources to ensure a satisfactory outcome. A potential source of agglomeration arises from the particle contacts established during filtration that lead to robust agglomerates forming during drying, so that a necessary first step toward understanding agglomeration is to study the packing properties of filtration beds. Here, we present two and three-dimensional models simulating the formation of packed bed structures during filtration. The models use circular and spherical particles of different sizes, mimicking the bimodal particle size distributions sometimes encountered in industrial practice. The statistics of packing and void formation, along with the distribution of interparticle contacts and percolation structures, are presented and discussed in the context of filtration, drying, and agglomeration. The model paves the way for predictive capabilities that can lead to the rational design of processes to minimize the impact of agglomeration., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Interoception, the representation of the body's internal state, plays a central role in emotion, motivation and wellbeing. Interoceptive sensibility, the ability to engage in sustained interoceptive awareness, is particularly relevant for mental health but is exclusively measured via self-report, without methods for objective measurement. We used machine learning to classify interoceptive sensibility by contrasting using data from a randomized control trial of interoceptive training, with functional magnetic resonance imaging assessment before and after an 8-week intervention (N = 44 scans). The neuroimaging paradigm manipulated attention targets (breath vs. visual stimuli) and reporting demands (active reporting vs. passive monitoring). Machine learning achieved high accuracy in distinguishing between interoceptive and exteroceptive attention, both for within-session classification (~80% accuracy) and out-of-sample classification (~70% accuracy), revealing the reliability of the predictions. We then explored the classifier potential for 'reading out' mental states in a 3-min sustained interoceptive attention task. Participants were classified as actively engaged about half of the time, during which interoceptive training enhanced their ability to sustain interoceptive attention. These findings demonstrate that interoceptive and exteroceptive attention is distinguishable at the neural level; these classifiers may help to demarcate periods of interoceptive focus, with implications for developing an objective marker for interoceptive sensibility in mental health research., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Interoception, the representation of the body's internal state, serves as a foundation for emotion, motivation, and wellbeing. Yet despite its centrality in human experience, the neural mechanisms of interoceptive attention are poorly understood. The Interoceptive/Exteroceptive Attention Task (IEAT) is a novel neuroimaging paradigm that compares behavioral tracking of the respiratory cycle (Active Interoception) to tracking of a visual stimulus (Active Exteroception). Twenty-two healthy participants completed the IEAT during two separate scanning sessions ( N  = 44) as part of a randomized control trial of mindful awareness in body-oriented therapy (MABT). Compared with Active Exteroception, Active Interoception deactivated somatomotor and prefrontal regions. Greater self-reported interoceptive sensibility (MAIA scale) predicted sparing from deactivation within the anterior cingulate cortex (ACC) and left-lateralized language regions. The right insula, typically described as a primary interoceptive cortex, was only specifically implicated by its deactivation during an exogenously paced respiration condition (Active Matching) relative to self-paced Active Interoception. Psychophysiological interaction (PPI) analysis characterized Active Interoception as promoting greater ACC connectivity with lateral prefrontal and parietal regions commonly referred to as the dorsal attention network (DAN). In contrast to evidence relating accurate detection of liminal interoceptive signals such as the heartbeat to anterior insula activity, interoceptive attention toward salient signals such as the respiratory cycle may involve reduced cortical activity but greater ACC-DAN connectivity, with greater sensibility linked to reduced deactivation within the ACC and language-processing regions., Competing Interests: The authors declare no competing financial interests., (Copyright © 2023 Farb et al.)

This paper considers the steps needed to generate pragmatic and interpretable lesion-symptom mappings that can be used for clinically reliable prognoses. The novel contributions are 3-fold. We first define and inter-relate five neurobiological and five methodological constraints that need to be accounted for when interpreting lesion-symptom associations and generating synthetic lesion data. The first implication is that, because of these constraints, lesion-symptom mapping needs to focus on probabilistic relationships between Lesion and Symptom, with Lesion as a multivariate spatial pattern, Symptom as a time-dependent behavioural profile and evidence that Lesion raises the probability of Symptom. The second implication is that in order to assess the strength of probabilistic causality, we need to distinguish between causal lesion sites, incidental lesion sites, spared but dysfunctional sites and intact sites, all of which might affect the accuracy of the predictions and prognoses generated. We then formulate lesion-symptom mappings in logical notations, including combinatorial rules, that are then used to evaluate and better understand complex brain-behaviour relationships. The logical and theoretical framework presented applies to any type of neurological disorder but is primarily discussed in relationship to stroke damage. Accommodating the identified constraints, we discuss how the 1965 Bradford Hill criteria for inferring probabilistic causality, post hoc , from observed correlations in epidemiology-can be applied to lesion-symptom mapping in stroke survivors. Finally, we propose that rather than rely on post hoc evaluation of how well the causality criteria have been met, the neurobiological and methodological constraints should be addressed, a priori , by changing the experimental design of lesion-symptom mappings and setting up an open platform to share and validate the discovery of reliable and accurate lesion rules that are clinically useful., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Functional imaging studies of neurotypical adults report activation in the left putamen during speech production. The current study asked how stroke survivors with left putamen damage are able to produce correct spoken responses during a range of speech production tasks. Using functional magnetic resonance imaging, activation during correct speech production responses was assessed in 5 stroke patients with circumscribed left dorsal striatal lesions, 66 stroke patient controls who did not have focal left dorsal striatal lesions, and 54 neurotypical adults. As a group, patients with left dorsal striatal damage (our patients of interest) showed higher activation than neurotypical controls in the left superior parietal cortex during successful speech production. This effect was not specific to patients with left dorsal striatal lesions as we observed enhanced activation in the same region in some patient controls and also in more error-prone neurotypical participants. Our results strongly suggest that enhanced left superior parietal activation supports speech production in diverse challenging circumstances, including those caused by stroke damage. They add to a growing body of literature indicating how upregulation within undamaged parts of the neural systems already recruited by neurotypical adults contributes to recovery after stroke., (© The Author(s) 2022. Published by Oxford University Press.)

The growing demand for high efficiency portable batteries has prompted a deeper exploration for alternative cathode materials. Due to low Earth abundance, scandium has not received much attention, however its low atomic mass makes it ideal for high gravimetric capacity electrodes. Here we have performed a comprehensive first-principles study to assess the performance of layered ScS 2 as a potential cathode for lithium-ion and beyond-lithium-ion batteries. We have explored the configuration space of ScS 2 and its intercalated compounds using a mix of machine learning and ab initio techniques, finding the ground state geometry to be layered in nature. This layered structure is found to have a high voltage, reaching above 4.5 V for Group I intercalants, ideal volume expansions below 10% for lithium and magnesium intercalation, is electronically conductive, and is ductile once intercalated. Of the intercalants considered, we find that lithium is the best choice for cathode applications, for which we have used a combination of thermodynamic phase diagrams, ab intio phonon calculations, and evaluation of the elastic tensor to conclude that ScS 2 possesses a reversible capacity of 182.99 mA h g -1 , on par with current state of the art cathode materials such as LiCoO 2 , NMC, and NCA. Finally, we substitute foreign metal species into the ScS 2 material to determine their effect on key cathode properties, but find that these are overall detrimental to the performance of ScS 2 . This does, however, highlight the potential for improvement if scandium were mixed into other layered systems such as the layered transition metal oxides.

To facilitate integrated end-to-end pharmaceutical manufacturing using digital design, a model capable of transferring material property information between operations to predict product attributes in integrated purification processes has been developed. The focus of the work reported here combines filtration and washing operations used in active pharmaceutical ingredient (API) purification and isolation to predict isolation performance without the need of extensive experimental work. A fixed Carman-Kozeny filtration model is integrated with several washing mechanisms (displacement, dilution, and axial dispersion). Two limiting cases are considered: case 1 where there is no change in the solid phase during isolation (no particle dissolution and/or growth), and case 2 where the liquid and solid phases are equilibrated over the course of isolation. In reality, all actual manufacturing conditions would be bracketed by these two limiting cases, so consideration of these two scenarios provides rigorous theoretical bounds for assessing isolation performance. This modeling approach aims to facilitate the selection of most appropriate models suitable for different isolation scenarios, without the requirement to use overly complex models for straightforward isolation processes. Mefenamic acid and paracetamol were selected as representative model compounds to assess a range of isolation scenarios. In each case, the objective of the models was to identify the purity of the product reached with a fixed wash ratio and minimize the changes to the crystalline particle attributes that occur during the isolation process. This was undertaken with the aim of identifying suitable criteria for the selection of appropriate filtration and washing models corresponding to relevant processing conditions, and ultimately developing guidelines for the digital design of filtration and washing processes., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Establishing whether speech and language therapy after stroke has beneficial effects on speaking ability is challenging because of the need to control for multiple non-therapy factors known to influence recovery. We investigated how speaking ability at three time points post-stroke differed in patients who received varying amounts of clinical therapy in the first month post-stroke. In contrast to prior studies, we factored out variance from: initial severity of speaking impairment, amount of later therapy, and left and right hemisphere lesion size and site. We found that speaking ability at one month post-stroke was significantly better in patients who received early therapy ( n  = 79), versus those who did not ( n  = 64), and the number of hours of early therapy was positively related to recovery at one year post-stroke. We offer two non-mutually exclusive interpretations of these data: (1) patients may benefit from the early provision of self-management strategies; (2) therapy is more likely to be provided to patients who have a better chance of recovery (e.g., poor physical and/or mental health may impact suitability for therapy and chance of recovery). Both interpretations have implications for future studies aiming to predict individual patients' speech outcomes after stroke, and their response to therapy.

Finding a material with all the desired properties for a photocatalytic water splitter is a challenge yet to be overcome, requiring both a surface with ideal energetics for all steps in the hydrogen and oxygen evolution reactions (HER and OER) and a bulk band gap large enough to mediate said steps. We have instead examined separating these challenges by investigating the energetic properties of two-dimensional transition metal dichalcogenides (TMDCs) that could be used as a surface coating to a material with a large enough bulk band gap. First we investigated the energetics of monolayer MoS 2 and PdSe 2 using density functional theory and then investigated how these energetics changed when they were combined into a heterostructure. Our results show that the surface properties were practically (<0.2 eV) unchanged when combined and the MoS 2 layer aligns well with the OER and HER. This work highlights the potential of TMDC monolayers as surface coatings for bulk materials that have sufficient band gaps for photocatalytic applications., (Creative Commons Attribution license.)

Purpose: The purpose of this measurement study was to examine the Scale of Body Connection (SBC) sensitivity to change among mind-body or bodywork interventions and to explore the concurrent validity in relation to emotion dysregulation and mindfulness skills. Methods: This study was based on multiple clinical trials that had used the SBC to evaluate changes in body awareness (BA) and bodily dissociation (BD) in response to a mind-body or bodywork intervention. To test for sensitivity to change, t tests were used to examine change and estimate effect sizes. To explore convergent validity, Pearson's product-moment correlations between the SBC subscales and Five-Facet Mindfulness Questionnaire (FFMQ) and Difficulties in Emotion Regulation Scale (DERS) were calculated among a subset of the studies, which also included these measures. Results: The BA and BD scales consistently detected significant positive responses to a range of intervention types (yoga, mindfulness meditation, BA, multimodal therapy, and bodywork), demonstrating SBC sensitivity to change. With a few exceptions, the effect sizes across studies for BA were above 0.35, indicating near moderate-to-large effect sizes. The effect sizes for BD, as a measure of responsiveness, were much smaller than for BA; however, four of the studies had effect sizes between 0.54 and 0.86. Concurrent validity with the DERS was supported by moderate-to-large correlations, and with the FFMQ, it was significant with the BA scale in one included study. Conclusions: The results of this study further establish SBC validity and sensitivity to change across a range of mind-body therapies and confirm prior findings of moderate-to-strong internal consistency reliability. The findings support the use of this brief scale to assess key dimensions of BA and BD in practice and research.

Using fMRI, we investigated how right temporal lobe gliomas affecting the posterior superior temporal sulcus alter neural processing observed during speech perception and production tasks. Behavioural language testing showed that three pre-operative neurosurgical patients with grade 2, grade 3 or grade 4 tumours had the same pattern of mild language impairment in the domains of object naming and written word comprehension. When matching heard words for semantic relatedness (a speech perception task), these patients showed under-activation in the tumour infiltrated right superior temporal lobe compared to 61 neurotypical participants and 16 patients with tumours that preserved the right postero-superior temporal lobe, with enhanced activation within the (tumour-free) contralateral left superior temporal lobe. In contrast, when correctly naming objects (a speech production task), the patients with right postero-superior temporal lobe tumours showed higher activation than both control groups in the same right postero-superior temporal lobe region that was under-activated during auditory semantic matching. The task dependent pattern of under-activation during the auditory speech task and over-activation during object naming was also observed in eight stroke patients with right hemisphere infarcts that affected the right postero-superior temporal lobe compared to eight stroke patients with right hemisphere infarcts that spared it. These task-specific and site-specific cross-pathology effects highlight the importance of the right temporal lobe for language processing and motivate further study of how right temporal lobe tumours affect language performance and neural reorganisation. These findings may have important implications for surgical management of these patients, as knowledge of the regions showing functional reorganisation may help to avoid their inadvertent damage during neurosurgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yamamoto, Sanjuán, Pope, Parker Jones, Hope, Prejawa, Oberhuber, Mancini, Ekert, Garjardo-Vidal, Creasey, Yousry, Green and Price.)

Cell-cell interactions are required for development and homeostasis in multicellular organisms from insects to mammals. A critical process governed by these interactions is cell competition, which functions throughout development to control tissue composition by eliminating cells that possess a lower fitness status than their neighbors. Human pluripotent stem cells (hPSCs) are a key biological tool in modeling human development and offer further potential as a source of clinically relevant cell populations for regenerative medicine applications. Recently, cell competition has been demonstrated in hPSC cultures and during induced pluripotent stem cell reprogramming. In turn, these findings suggest that hPSCs can be used as a tool to study and model cell-cell interactions during different stages of development and disease. Here, we provide a panel of protocols optimized for hPSCs to investigate the potential role that cell competition may have in determining the fate and composition of cell populations during culture. The protocols entail assessment of the competitive phenotype and the mode through which cell competition may lead to elimination of less-fit cells from mosaic cultures with fitter counterparts. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Electroporation of hPSCs to establish a fluorescent reference cell line Support Protocol 1: Single-cell dissociation of hPSCs Support Protocol 2: Single-cell cloning of fluorescently labeled hPSCs Basic Protocol 2: Separate culture and co-culture proliferation assays Basic Protocol 3: Assessing levels of apoptosis in hPSC cultures using flow cytometry Basic Protocol 4: Transwell assay Support Protocol 3: Immunohistochemistry and image quantification of cleaved caspase-3 Basic Protocol 5: Cell confrontation assay Basic Protocol 6: Cell compression assay Basic Protocol 7: Time-lapse imaging to assess mechanical extrusion., (© 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.)

Prior studies have shown that the left posterior superior temporal sulcus (pSTS) and left temporo-parietal junction (TPJ) both contribute to phonological short-term memory, speech perception and speech production. Here, by conducting a within-subjects multi-factorial fMRI study, we dissociate the response profiles of these regions and a third region - the anterior ascending terminal branch of the left superior temporal sulcus (atSTS), which lies dorsal to pSTS and ventral to TPJ. First, we show that each region was more activated by (i) 1-back matching on visually presented verbal stimuli (words or pseudowords) compared to 1-back matching on visually presented non-verbal stimuli (pictures of objects or non-objects), and (ii) overt speech production than 1-back matching, across 8 types of stimuli (visually presented words, pseudowords, objects and non-objects and aurally presented words, pseudowords, object sounds and meaningless hums). The response properties of the three regions dissociated within the auditory modality. In left TPJ, activation was higher for auditory stimuli that were non-verbal (sounds of objects or meaningless hums) compared to verbal (words and pseudowords), irrespective of task (speech production or 1-back matching). In left pSTS, activation was higher for non-semantic stimuli (pseudowords and hums) than semantic stimuli (words and object sounds) on the dorsal pSTS surface (dpSTS), irrespective of task. In left atSTS, activation was not sensitive to either semantic or verbal content. The contrasting response properties of left TPJ, dpSTS and atSTS was cross-validated in an independent sample of 59 participants, using region-by-condition interactions. We also show that each region participates in non-overlapping networks of frontal, parietal and cerebellar regions. Our results challenge previous claims about functional specialisation in the left posterior superior temporal lobe and motivate future studies to determine the timing and directionality of information flow in the brain networks involved in speech perception and production., (Copyright © 2021. Published by Elsevier Inc.)

Controversy surrounds the interpretation of higher activation for pseudoword compared to word reading in the left precentral gyrus and pars opercularis. Specifically, does activation in these regions reflect: (1) the demands on sublexical assembly of articulatory codes, or (2) retrieval effort because the combinations of articulatory codes are unfamiliar? Using fMRI, in 84 neurologically intact participants, we addressed this issue by comparing reading and repetition of words (W) and pseudowords (P) to naming objects (O) from pictures or sounds. As objects do not provide sublexical articulatory cues, we hypothesis that retrieval effort will be greater for object naming than word repetition/reading (which benefits from both lexical and sublexical cues); while the demands on sublexical assembly will be higher for pseudoword production than object naming. We found that activation was: (i) highest for pseudoword reading [P>O&W in the visual modality] in the anterior part of the ventral precentral gyrus bordering the precentral sulcus (vPCg/vPCs), consistent with the sublexical assembly of articulatory codes; but (ii) as high for object naming as pseudoword production [P&O>W] in dorsal precentral gyrus (dPCg) and the left inferior frontal junction (IFJ), consistent with retrieval demands and cognitive control. In addition, we dissociate the response properties of vPCg/vPCs, dPCg and IFJ from other left frontal lobe regions that are activated during single word speech production. Specifically, in both auditory and visual modalities: a central part of vPCg (head and face area) was more activated for verbal than nonverbal stimuli [P&W>O]; and the pars orbitalis and inferior frontal sulcus were most activated during object naming [O>W&P]. Our findings help to resolve a previous discrepancy in the literature, dissociate three functionally distinct parts of the precentral gyrus, and refine our knowledge of the functional anatomy of speech production in the left frontal lobe., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Pre- and intra-operative language mapping in neurosurgery patients frequently involves an object naming task. The choice of the optimal object naming paradigm remains challenging due to lack of normative data and standardization in mapping practices. The aim of this study was to identify object naming paradigms that robustly and consistently activate classical language regions and could therefore be used to improve the sensitivity of language mapping in brain tumor and epilepsy patients. Methods: Functional magnetic resonance imaging (fMRI) data from two independent groups of healthy controls (total = 79) were used to generate threshold-weighted voxel-based consistency maps. This novel approach allowed us to compare inter-subject consistency of activation for naming single objects in the visual and auditory modality and naming two objects in a phrase or a sentence. Results: We found that the consistency of activation in language regions was greater for naming two objects per picture than one object per picture, even when controlling for the number of names produced in 5 s. Conclusion: More consistent activation in language areas for naming two objects compared to one object suggests that two-object naming tasks may be more suitable for delimiting language eloquent regions with pre- and intra-operative language testing. More broadly, we propose that the functional specificity of brain mapping paradigms for a whole range of different linguistic and non-linguistic functions could be enhanced by referring to databased models of inter-subject consistency and variability in typical and atypical brain responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ekert, Kirkman, Seghier, Green and Price.)

Broca's area in the posterior half of the left inferior frontal gyrus has traditionally been considered an important node in the speech production network. Nevertheless, recovery of speech production has been reported, to different degrees, within a few months of damage to Broca's area. Importantly, contemporary evidence suggests that, within Broca's area, its posterior part (i.e. pars opercularis) plays a more prominent role in speech production than its anterior part (i.e. pars triangularis). In this study, we therefore investigated the brain activation patterns that underlie accurate speech production following stroke damage to the opercular part of Broca's area. By combining functional MRI and 13 tasks that place varying demands on speech production, brain activation was compared in (i) seven patients of interest with damage to the opercular part of Broca's area; (ii) 55 neurologically intact controls; and (iii) 28 patient controls with left-hemisphere damage that spared Broca's area. When producing accurate overt speech responses, the patients with damage to the left pars opercularis activated a substantial portion of the normal bilaterally distributed system. Within this system, there was a lesion-site-dependent effect in a specific part of the right cerebellar Crus I where activation was significantly higher in the patients with damage to the left pars opercularis compared to both neurologically intact and patient controls. In addition, activation in the right pars opercularis was significantly higher in the patients with damage to the left pars opercularis relative to neurologically intact controls but not patient controls (after adjusting for differences in lesion size). By further examining how right Crus I and right pars opercularis responded across a range of conditions in the neurologically intact controls, we suggest that these regions play distinct roles in domain-general cognitive control. Finally, we show that enhanced activation in the right pars opercularis cannot be explained by release from an inhibitory relationship with the left pars opercularis (i.e. dis-inhibition) because right pars opercularis activation was positively related to left pars opercularis activation in neurologically intact controls. Our findings motivate and guide future studies to investigate (i) how exactly right Crus I and right pars opercularis support accurate speech production after damage to the opercular part of Broca's area and (ii) whether non-invasive neurostimulation to one or both of these regions boosts speech production recovery after damage to the opercular part of Broca's area., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)