cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.19877915
title: Novel regulation of the transcription factor ZHX2 by N-terminal methylation

description: N-terminal methylation (Nα-methylation) by the methyltransferase NRMT1 is an important post-translational modification that regulates protein–DNA interactions. Accordingly, its loss impairs functions that are reliant on such interactions, including DNA repair and transcriptional regulation. The global loss of Nα-methylation results in severe developmental and premature aging phenotypes, but given over 300 predicted substrates, it is hard to discern which physiological substrates contribute to each phenotype. One of the most striking phenotypes in NRMT1 knockout (<i>Nrmt1<sup>−/−</sup></i>) mice is early liver degeneration. To identify the disrupted signaling pathways leading to this phenotype and the NRMT1 substrates involved, we performed RNA-sequencing analysis of control and <i>Nrmt1<sup>−/−</sup></i> adult mouse livers. We found both a significant upregulation of transcripts in the cytochrome P450 (CYP) family and downregulation of transcripts in the major urinary protein (MUP) family. Interestingly, transcription of both families is inversely regulated by the transcription factor zinc fingers and homeoboxes 2 (ZHX2). ZHX2 contains a non-canonical NRMT1 consensus sequence, indicating that its function could be directly regulated by Nα-methylation. We confirmed misregulation of CYP and MUP mRNA and protein levels in <i>Nrmt1<sup>−/−</sup></i> livers and verified NRMT1 can methylate ZHX2 <i>in vitro</i>. In addition, we used a mutant of ZHX2 that cannot be methylated to directly demonstrate Nα-methylation promotes ZHX2 transcription factor activity and target promoter occupancy. Finally, we show <i>Nrmt1<sup>−/−</sup></i> mice also exhibit early postnatal de-repression of ZHX2 targets involved in fetal liver development. Taken together, these data implicate ZHX2 misregulation as a driving force behind the liver phenotype seen in <i>Nrmt1<sup>−/−</sup></i> mice.
DOI: 10.6084/m9.figshare.19877915.v1
title: Novel regulation of the transcription factor ZHX2 by N-terminal methylation

description: N-terminal methylation (Nα-methylation) by the methyltransferase NRMT1 is an important post-translational modification that regulates protein–DNA interactions. Accordingly, its loss impairs functions that are reliant on such interactions, including DNA repair and transcriptional regulation. The global loss of Nα-methylation results in severe developmental and premature aging phenotypes, but given over 300 predicted substrates, it is hard to discern which physiological substrates contribute to each phenotype. One of the most striking phenotypes in NRMT1 knockout (<i>Nrmt1<sup>−/−</sup></i>) mice is early liver degeneration. To identify the disrupted signaling pathways leading to this phenotype and the NRMT1 substrates involved, we performed RNA-sequencing analysis of control and <i>Nrmt1<sup>−/−</sup></i> adult mouse livers. We found both a significant upregulation of transcripts in the cytochrome P450 (CYP) family and downregulation of transcripts in the major urinary protein (MUP) family. Interestingly, transcription of both families is inversely regulated by the transcription factor zinc fingers and homeoboxes 2 (ZHX2). ZHX2 contains a non-canonical NRMT1 consensus sequence, indicating that its function could be directly regulated by Nα-methylation. We confirmed misregulation of CYP and MUP mRNA and protein levels in <i>Nrmt1<sup>−/−</sup></i> livers and verified NRMT1 can methylate ZHX2 <i>in vitro</i>. In addition, we used a mutant of ZHX2 that cannot be methylated to directly demonstrate Nα-methylation promotes ZHX2 transcription factor activity and target promoter occupancy. Finally, we show <i>Nrmt1<sup>−/−</sup></i> mice also exhibit early postnatal de-repression of ZHX2 targets involved in fetal liver development. Taken together, these data implicate ZHX2 misregulation as a driving force behind the liver phenotype seen in <i>Nrmt1<sup>−/−</sup></i> mice.
DOI: 10.6084/m9.figshare.14750990
title: Developing a self-management intervention to manage hypermobility spectrum disorders (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS): an analysis informed by behaviour change theory

description: Hypermobility Spectrum Disorders (HSD) and Hypermobile Ehlers-Danlos Syndrome (hEDS) are heritable connective tissue disorders associated with joint instability and pain, but with scant guidance for supporting patients. The aim was to determine recommendations for an HSD/hEDS self-management intervention. Barriers to self-management were mapped onto the Theoretical Domains Framework (TDF) and Capability, Opportunity, Motivation-Behaviour (COM-B) model in a behavioural analysis. A modified Nominal Group Technique was used to prioritise behaviour change technique (BCT) interventions (<i>n</i> = 9 women). Possible BCTs incorporated: Incorporating self-help strategies, education to improve their knowledge of HSD/hEDS, and how to judge information about HSD/hEDS. In activity pacing, assertiveness and communication skills, plus what to expect during pregnancy, when symptoms can worsen. Support from occupational therapists to maintain independence at work and home. That illustrates how other people with HSD/hEDS have coped with the psychosocial impact. This study is the first to apply theoretically-informed approaches to the management of HSD/hEDS. Participants indicated poor access to psychological support, occupational therapy and a lack of knowledge about HSD/hEDS. Future research should evaluate which intervention options would be most acceptable and feasible.Implications for rehabilitationPatients with Hypermobility Spectrum Disorders or Hypermobile Ehlers-Danlos Syndrome can be active partners in the co-design of behaviour change interventions.Behaviour change interventions should target psychological support and patient education, particularly patient information.Additional behaviour change interventions included environmental restructuring and enablement; adaptations to participants’ environment with input from occupational therapy.Participants were keen to suggest opportunities for behavioural modelling; positive fist-person modelling narratives, written by those with HSD/hEDS, which addressed how they coped with the psychosocial impact of their condition. Patients with Hypermobility Spectrum Disorders or Hypermobile Ehlers-Danlos Syndrome can be active partners in the co-design of behaviour change interventions. Behaviour change interventions should target psychological support and patient education, particularly patient information. Additional behaviour change interventions included environmental restructuring and enablement; adaptations to participants’ environment with input from occupational therapy. Participants were keen to suggest opportunities for behavioural modelling; positive fist-person modelling narratives, written by those with HSD/hEDS, which addressed how they coped with the psychosocial impact of their condition.
DOI: 10.6084/m9.figshare.14750990.v1
title: Developing a self-management intervention to manage hypermobility spectrum disorders (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS): an analysis informed by behaviour change theory

description: Hypermobility Spectrum Disorders (HSD) and Hypermobile Ehlers-Danlos Syndrome (hEDS) are heritable connective tissue disorders associated with joint instability and pain, but with scant guidance for supporting patients. The aim was to determine recommendations for an HSD/hEDS self-management intervention. Barriers to self-management were mapped onto the Theoretical Domains Framework (TDF) and Capability, Opportunity, Motivation-Behaviour (COM-B) model in a behavioural analysis. A modified Nominal Group Technique was used to prioritise behaviour change technique (BCT) interventions (<i>n</i> = 9 women). Possible BCTs incorporated: Incorporating self-help strategies, education to improve their knowledge of HSD/hEDS, and how to judge information about HSD/hEDS. In activity pacing, assertiveness and communication skills, plus what to expect during pregnancy, when symptoms can worsen. Support from occupational therapists to maintain independence at work and home. That illustrates how other people with HSD/hEDS have coped with the psychosocial impact. This study is the first to apply theoretically-informed approaches to the management of HSD/hEDS. Participants indicated poor access to psychological support, occupational therapy and a lack of knowledge about HSD/hEDS. Future research should evaluate which intervention options would be most acceptable and feasible.Implications for rehabilitationPatients with Hypermobility Spectrum Disorders or Hypermobile Ehlers-Danlos Syndrome can be active partners in the co-design of behaviour change interventions.Behaviour change interventions should target psychological support and patient education, particularly patient information.Additional behaviour change interventions included environmental restructuring and enablement; adaptations to participants’ environment with input from occupational therapy.Participants were keen to suggest opportunities for behavioural modelling; positive fist-person modelling narratives, written by those with HSD/hEDS, which addressed how they coped with the psychosocial impact of their condition. Patients with Hypermobility Spectrum Disorders or Hypermobile Ehlers-Danlos Syndrome can be active partners in the co-design of behaviour change interventions. Behaviour change interventions should target psychological support and patient education, particularly patient information. Additional behaviour change interventions included environmental restructuring and enablement; adaptations to participants’ environment with input from occupational therapy. Participants were keen to suggest opportunities for behavioural modelling; positive fist-person modelling narratives, written by those with HSD/hEDS, which addressed how they coped with the psychosocial impact of their condition.
DOI: 10.6084/m9.figshare.14843018
title: Systematic review of the effectiveness of caregiver training with functional mobility tasks for informal caregivers assisting patients with neurological diagnoses

description: To complete a systematic review to identify evidence of the effectiveness of informal caregiver training with functional mobility tasks for patients with neurological diagnoses routinely completed by physical therapists (PTs). Databases searched: PubMed, PEDro, CINAHL, Web of Science, Proquest Health and Medical, and Scopus. Authors included studies with adult patients requiring assistance with functional mobility due to a neurological diagnosis, with the care provided by informal caregivers. Authors excluded studies with paid caregivers, or patient diagnoses of human immunodeficiency virus, dementia, or cancer. Data extracted included type of study, methodological quality review (using Downs and Black scale), number of subjects, outcome measures, interventions, and main results. Of 2372 total articles screened, 36 full-text articles were analyzed, with seven articles identified for inclusion in the review. All studies showed variability in number of subjects, methods, interventions, outcome measures, and results. Four of the studies showed positive results from the training of informal caregivers. While there is initial evidence that training informal caregivers in physical mobility tasks may help to lessen caregiver burden, further investigation is warranted. The topics typically addressed by PTs with informal caregiver training, such as transfers and ambulation, have not been extensively studied in the literature.Implications for rehabilitationPhysical therapists routinely complete training for caregivers on functional mobility tasks, with some initial evidence of the effectiveness of this training.Training for informal caregivers assisting individuals with neurological conditions has the potential to reduce injuries and decrease caregiver burden.Rehabilitation professionals should implement effective training methods for caregivers, resulting in a safer home environment for individuals with neurological diagnoses. Physical therapists routinely complete training for caregivers on functional mobility tasks, with some initial evidence of the effectiveness of this training. Training for informal caregivers assisting individuals with neurological conditions has the potential to reduce injuries and decrease caregiver burden. Rehabilitation professionals should implement effective training methods for caregivers, resulting in a safer home environment for individuals with neurological diagnoses.
DOI: 10.6084/m9.figshare.14843018.v1
title: Systematic review of the effectiveness of caregiver training with functional mobility tasks for informal caregivers assisting patients with neurological diagnoses

description: To complete a systematic review to identify evidence of the effectiveness of informal caregiver training with functional mobility tasks for patients with neurological diagnoses routinely completed by physical therapists (PTs). Databases searched: PubMed, PEDro, CINAHL, Web of Science, Proquest Health and Medical, and Scopus. Authors included studies with adult patients requiring assistance with functional mobility due to a neurological diagnosis, with the care provided by informal caregivers. Authors excluded studies with paid caregivers, or patient diagnoses of human immunodeficiency virus, dementia, or cancer. Data extracted included type of study, methodological quality review (using Downs and Black scale), number of subjects, outcome measures, interventions, and main results. Of 2372 total articles screened, 36 full-text articles were analyzed, with seven articles identified for inclusion in the review. All studies showed variability in number of subjects, methods, interventions, outcome measures, and results. Four of the studies showed positive results from the training of informal caregivers. While there is initial evidence that training informal caregivers in physical mobility tasks may help to lessen caregiver burden, further investigation is warranted. The topics typically addressed by PTs with informal caregiver training, such as transfers and ambulation, have not been extensively studied in the literature.Implications for rehabilitationPhysical therapists routinely complete training for caregivers on functional mobility tasks, with some initial evidence of the effectiveness of this training.Training for informal caregivers assisting individuals with neurological conditions has the potential to reduce injuries and decrease caregiver burden.Rehabilitation professionals should implement effective training methods for caregivers, resulting in a safer home environment for individuals with neurological diagnoses. Physical therapists routinely complete training for caregivers on functional mobility tasks, with some initial evidence of the effectiveness of this training. Training for informal caregivers assisting individuals with neurological conditions has the potential to reduce injuries and decrease caregiver burden. Rehabilitation professionals should implement effective training methods for caregivers, resulting in a safer home environment for individuals with neurological diagnoses.
DOI: 10.6084/m9.figshare.14714038
title: “I’ve learned to look at things in a different way”: exploring patients’ perspectives on participation in physiotherapist delivered integrated stress inoculation training and exercise for acute whiplash

description: To explore patient perspectives of the integrated intervention (intervention arm) of a recent randomised clinical trial that found clinically relevant and sustained benefits of a physiotherapist delivered integrated stress inoculation training (SIT) and exercise for people with acute whiplash-associated disorders (WAD) and at risk of poor recovery. Twelve patients from the 53 who participated in the SIT and exercise arm of a randomised controlled trial (StressModex RCT) participated in semi-structured interviews. Data were analysed using inductive thematic analysis. Five main themes were identified: “balance between the physical and psychological components,” “dealing with stress,” “coping with the injury,” “pain relief and return to function,” and “elements enhancing therapeutic alliance.” The majority of patients found the SIT techniques to be helpful in managing stress and pain, coping with their injury, and returning to function. The patients also found the exercises useful and acknowledged the importance of both the physical and the psychological aspects of whiplash injury.IMPLICATIONS FOR REHABILITATIONPatients with acute WAD at risk of poor recovery welcomed the inclusion of psychological strategies as part of physiotherapy treatment.The patients nominated both the psychological (SIT) component and exercise as assisting them with their stress, pain, and recovery.Physiotherapists could consider including strategies targeting early stress responses in their management of patients with acute WAD. Patients with acute WAD at risk of poor recovery welcomed the inclusion of psychological strategies as part of physiotherapy treatment. The patients nominated both the psychological (SIT) component and exercise as assisting them with their stress, pain, and recovery. Physiotherapists could consider including strategies targeting early stress responses in their management of patients with acute WAD.
DOI: 10.6084/m9.figshare.14773572.v1
title: A systematic review of non-drug interventions to prevent and treat anxiety in people with aphasia after stroke

description: To investigate the effectiveness of non-drug interventions for people with aphasia in the prevention and/or treatment of anxiety post-stroke as either a primary or secondary outcome. A systematic search of Medline, CINAHL, PsycINFO and Cochrane Library up to March 2021 was carried out. Studies of stroke populations were included if people with aphasia represented 25% or more of the enrolled participants. Quality of the evidence was assessed. A narrative synthesis of results is presented. The PROSPERO record ID for this study is 106451. Ten studies were included: five randomised controlled trials (RCTs), a single case experimental design, and four pre-post studies. The quality of the RCT trials was at least adequate but none demonstrated a benefit to anxiety outcomes. Those studies that reported benefit were of lower-level evidence with respect to National Health and Medical Research Classifications. No studies were found that evaluated the prevention of anxiety after stroke for people with aphasia. Definitive conclusions about the effectiveness of non-drug interventions for the prevention and/or treatment of anxiety in people with aphasia post-stroke cannot be made. Interventions that may show promise for those with aphasia and symptoms of anxiety include mindfulness meditation, modified cognitive behaviour therapy, unilateral nostril breathing, and the “Enhance Psychological Coping after Stroke” programme. Further high-quality research with better reporting of the inclusion of participants with aphasia and their specific sub-group results are required.Implications for RehabilitationIt is important for rehabilitation professionals to consider prevention of anxiety post-stroke as well as treatment.Mindfulness meditation, modified cognitive behavioural therapy, unilateral nostril breathing, and the and the “Enhance Psychological Coping after Stroke” programme may be of benefit to people with aphasia post-stroke.Adapting intervention protocols to be more communicatively accessible and training health professionals in supported communication may help people with aphasia engage in psychological therapies. It is important for rehabilitation professionals to consider prevention of anxiety post-stroke as well as treatment. Mindfulness meditation, modified cognitive behavioural therapy, unilateral nostril breathing, and the and the “Enhance Psychological Coping after Stroke” programme may be of benefit to people with aphasia post-stroke. Adapting intervention protocols to be more communicatively accessible and training health professionals in supported communication may help people with aphasia engage in psychological therapies.
DOI: 10.6084/m9.figshare.14773572
title: A systematic review of non-drug interventions to prevent and treat anxiety in people with aphasia after stroke

description: To investigate the effectiveness of non-drug interventions for people with aphasia in the prevention and/or treatment of anxiety post-stroke as either a primary or secondary outcome. A systematic search of Medline, CINAHL, PsycINFO and Cochrane Library up to March 2021 was carried out. Studies of stroke populations were included if people with aphasia represented 25% or more of the enrolled participants. Quality of the evidence was assessed. A narrative synthesis of results is presented. The PROSPERO record ID for this study is 106451. Ten studies were included: five randomised controlled trials (RCTs), a single case experimental design, and four pre-post studies. The quality of the RCT trials was at least adequate but none demonstrated a benefit to anxiety outcomes. Those studies that reported benefit were of lower-level evidence with respect to National Health and Medical Research Classifications. No studies were found that evaluated the prevention of anxiety after stroke for people with aphasia. Definitive conclusions about the effectiveness of non-drug interventions for the prevention and/or treatment of anxiety in people with aphasia post-stroke cannot be made. Interventions that may show promise for those with aphasia and symptoms of anxiety include mindfulness meditation, modified cognitive behaviour therapy, unilateral nostril breathing, and the “Enhance Psychological Coping after Stroke” programme. Further high-quality research with better reporting of the inclusion of participants with aphasia and their specific sub-group results are required.Implications for RehabilitationIt is important for rehabilitation professionals to consider prevention of anxiety post-stroke as well as treatment.Mindfulness meditation, modified cognitive behavioural therapy, unilateral nostril breathing, and the and the “Enhance Psychological Coping after Stroke” programme may be of benefit to people with aphasia post-stroke.Adapting intervention protocols to be more communicatively accessible and training health professionals in supported communication may help people with aphasia engage in psychological therapies. It is important for rehabilitation professionals to consider prevention of anxiety post-stroke as well as treatment. Mindfulness meditation, modified cognitive behavioural therapy, unilateral nostril breathing, and the and the “Enhance Psychological Coping after Stroke” programme may be of benefit to people with aphasia post-stroke. Adapting intervention protocols to be more communicatively accessible and training health professionals in supported communication may help people with aphasia engage in psychological therapies.