A systematic review and meta-analysis of pathologic complete response rates for patients with cholangiocarcinoma treated on liver transplant protocols.

BACKGROUND AND OBJECTIVES: Many heterogenous orthotopic liver transplant (OLT) protocols exist for patients with unresectable cholangiocarcinoma. Little is known about the incidence, predictors for, and the significance of achieving a pathologic complete response (pCR). METHODS: We performed a systematic review through September 2022 of the PubMed, Embase, and Web of Science databases. A random-effect meta-analysis was conducted to pool data across studies with reported pCR rates. Heterogeneity between treatment protocols was assessed via subgroup analysis. The pCR and 1-, 3-, and 5-year recurrence-free survival (RFS) and overall survival (OS) rates were extracted as outcomes of interest. RESULTS: A total of 15 studies reported pCR rates and were grouped by use of the Mayo protocol (4/15), stereotactic body radiation therapy (2/15), and an Other category (9/15). The pooled pCR rate among all studies was 32%. Both radiation technique and duration of CHT showed no significant association with pCR (p = 0.05 and 0.13, respectively). Pooled 1-year RFS and OS after any neoadjuvant therapy and OLT was 80% (95% confidence interval [CI], 0.61-0.91), and 91% (95% CI, 0.87-0.94), respectively. There was no 1-year OS difference detected among the three groups. pCR was not associated with OS in the meta-regression. Pooled 3- and 5-year OS among all studies was 72% and 61%, respectively. CONCLUSIONS: The pooled incidence of pCR was 32%. Differences in radiation technique did not appear to influence pCR rates and upon meta-regression, pCR was not a surrogate marker for survival.

Utility of ultrasound in managing acute medical conditions in space: a scoping review.

BACKGROUND: In long-distance spaceflight, the challenges of communication delays and the impracticality of rapid evacuation necessitate the management of medical emergencies by onboard physicians. Consequently, these physicians must be proficient in tools, such as ultrasound, which has proven itself a strong diagnostic imaging tool in space. Yet, there remains a notable gap in the discourse surrounding its efficacy in handling acute medical scenarios. This scoping review aims to present an updated analysis of the evidence supporting the role of ultrasound in diagnosing acute conditions within microgravity environments. METHODS: A systematic search was executed across three bibliographic databases: PubMed, EMBASE (Embase.com), and the Web of Science Core Collection. We considered articles published up to February 25, 2023, that highlighted the application of ultrasound in diagnosing acute medical conditions in either microgravity or microgravity-simulated settings. Exclusions were made for review papers, abstracts, and in-vitro studies. RESULTS: After removing duplicates, and filtering papers by pre-determined criteria, a total of 15 articles were identified that discuss the potential use of ultrasound in managing acute medical conditions in space. The publication date of these studies ranged from 1999 to 2020. A relatively similar proportion of these studies were conducted either on the International Space Station or in parabolic flight, with one performed in supine positioning to simulate weightlessness. The included studies discuss acute pathologies, such as abdominal emergencies, decompression sickness, deep venous thrombosis, acute lung pathologies, sinusitis, musculoskeletal trauma, genitourinary emergencies, and ocular emergencies. CONCLUSIONS: While ultrasound has shown promise in addressing various acute conditions, significant knowledge gaps remain, especially in gastrointestinal, cardiac, vascular, and reproductive emergencies. As we venture further into space, expanding our medical expertise becomes vital to ensure astronaut safety and mission success.

Transitioning from One Electronic Health Record to Another: A Systematic Review.

BACKGROUND: Transitioning to a new electronic health record (EHR) presents different challenges than transitions from paper to electronic records. We synthesized the body of peer-reviewed literature on EHR-to-EHR transitions to evaluate the generalizability of published work and identify knowledge gaps where more evidence is needed. METHODS: We conducted a broad search in PubMed through July 2022 and collected all publications from two prior reviews. Peer-reviewed publications reporting on data from an EHR-to-EHR transition were included. We extracted data on study design, setting, sample size, EHR systems involved, dates of transition and data collection, outcomes reported, and key findings. RESULTS: The 40 included publications were grouped into thematic categories for narrative synthesis: clinical care outcomes (n = 15), provider perspectives (n = 11), data migration (n = 8), patient experience (n = 4), and other topics (n = 5). Many studies described single sites that are early adopters of technology with robust research resources, switching from a homegrown system to a commercial system, and emphasized the dynamic effect of transitioning on important clinical care and other outcomes over time. DISCUSSION: The published literature represents a heterogeneous mix of study designs and outcome measures, and while some of the stronger studies in this review used longitudinal approaches to compare outcomes across more sites, the current literature is primarily descriptive and is not designed to offer recommendations that can guide future EHR transitions. Transitioning from one EHR to another constitutes a major organizational change that requires nearly every person in the organization to change how they do their work. Future research should include human factors as well as diverse methodological approaches such as mixed methods and implementation science.

Antiaging Effects of Topical Defensins.

Topical defensins have recently gained attention as agents to improve skin composition. This study aimed to aggregate and synthesize studies in the literature assessing the effects of topical defensins on skin composition in the context of its ability to combat signs of aging.

Assessing the publishing priorities and preferences among STEM researchers at a large R1 institution.

The cost of academic publishing has increased substantially despite the ease with which information can be shared on the web. Open Access publishing is a key mechanism for amplifying research access, inclusivity, and impact. Despite this, shifting to a free-to-read publishing environment requires navigating complex barriers that vary by career status and publishing expectations. In this article, we investigate the motivations and preferences of researchers situated within our large research institution as a case study for publishing attitudes at similar institutions. We surveyed the publishing priorities and preferences of researchers at various career stages in STEM fields as they relate to openness, data practices, and assessment of research impact. Our results indicate that publishing preferences, data management experience and research impact assessment vary by career status and departmental approaches to promotion. We find that open access publishing is widely appreciated regardless of career status, but financial limitations and publishing expectations were common barriers to publishing in Open Access journals. Our findings shed light on publishing attitudes and preferences among researchers at a major R1 research institution, and offer insight into advocacy strategies that incentivize open access publishing.

Completeness and Spin of medRxiv Preprint and Associated Published Abstracts of COVID-19 Randomized Clinical Trials.

This study examines publication timelines, completeness, and spin in the abstracts of all randomized clinical trials related to COVID-19 posted to medRxiv during the first 2 years of the pandemic and compared the latter 2 with their published counterparts.

Factors Associated With Open Access Publishing Costs in Oncology Journals: Cross-sectional Observational Study.

BACKGROUND: Open access (OA) publishing represents an exciting opportunity to facilitate the dissemination of scientific information to global audiences. However, OA publishing is often associated with significant article processing charges (APCs) for authors, which may thus serve as a barrier to publication. OBJECTIVE: In this observational cohort study, we aimed to characterize the landscape of OA publishing in oncology and, further, identify characteristics of oncology journals that are predictive of APCs. METHODS: We identified oncology journals using the SCImago Journal & Country Rank database. All journals with an OA publication option and APC data openly available were included. We searched journal websites and tabulated journal characteristics, including APC amount (in US dollars), OA model (hybrid vs full), 2-year impact factor (IF), H-index, number of citable documents, modality/treatment specific (if applicable), and continent of origin. All APCs were converted to US-dollar equivalents for final analyses. Selecting variables with significant associations in the univariable analysis, we generated a multiple regression model to identify journal characteristics independently associated with OA APC amount. An audit of a random 10% sample of the data was independently performed by 2 authors to ensure data accuracy, precision, and reproducibility. RESULTS: Of 367 oncology journals screened, 251 met the final inclusion criteria. The median APC was US $2957 (IQR 1958-3450). The majority of journals (n=156, 62%) adopted the hybrid OA publication model and were based in Europe (n=119, 47%) or North America (n=87, 35%). The median (IQR) APC for all journals was US $2957 (1958-3540). Twenty-five (10%) journals had APCs greater than US $4000. There were 10 (4%) journals that offered OA publication with no publication charge. Univariable testing showed that journals with a greater number of citable documents (P<.001), higher 2-year IF (P<.001), higher H-index (P<.001), and those using the hybrid OA model (P<.001), or originating in Europe or North America (P<.001) tended to have higher APCs. In our multivariable model, the number of citable documents (ß=US $367, SD US $133; P=.006), 2-year IF (US $1144, SD US $177; P<.001), hybrid OA publishing model (US $991, SD US $189; P<.001), and North American origin (US $838, SD US $186; P<.001) persisted as significant predictors of processing charges. CONCLUSIONS: OA publication costs are greater in oncology journals that publish more citable articles, use the hybrid OA model, have a higher IF, and are based in North America or Europe. These findings may inform targeted action to help the oncology community fully appreciate the benefits of open science.

The distribution of initial estimates moderates the effect of social influence on the wisdom of the crowd.

Whether, and under what conditions, groups exhibit "crowd wisdom" has been a major focus of research across the social and computational sciences. Much of this work has focused on the role of social influence in promoting the wisdom of the crowd versus leading the crowd astray and has resulted in conflicting conclusions about how social network structure determines the impact of social influence. Here, we demonstrate that it is not enough to consider the network structure in isolation. Using theoretical analysis, numerical simulation, and reanalysis of four experimental datasets (totaling 2885 human subjects), we find that the wisdom of crowds critically depends on the interaction between (i) the centralization of the social influence network and (ii) the distribution of the initial individual estimates. By adopting a framework that integrates both the structure of the social influence and the distribution of the initial estimates, we bring previously conflicting results under one theoretical framework and clarify the effects of social influence on the wisdom of crowds.

Co-designing a dementia-specific education and training program for home care workers: The 'Promoting Independence Through Quality Dementia Care at Home' project.

Undertaking co-design with the end users of services has rapidly evolved as the best-practice approach to program design, development and implementation. Increased interest in using participatory co-design in dementia care has drawn attention to the need for evidence-informed methods for facilitating the meaningful involvement of people with dementia and their family carers in co-design activities. The aim of this paper is to describe the co-design framework used in the co-design of a dementia specialist training program for home care workers. The Promoting Independence Through quality dementia Care at Home program is a successful example of co-design methodology used across multiple project stages and with various stakeholder groups, including people living with dementia, family carers, home care workers, managers and researchers. Co-design methods were tailored to each stage, purpose, and stakeholder group, and to facilitate the involvement of people living with dementia. Findings provide unique insights into optimising input from co-design partners, including people living with dementia; the methodology, conditions and requirements for participants to co-design and implement ideas; and perspectives on the enablers and challenges of using co-design in this population. In this paper, we present a comprehensive approach for involving people living with dementia as active and equal contributors in inclusive and meaningful participatory co-design.

What constitutes 'good' home care for people with dementia? An investigation of the views of home care service recipients and providers.

BACKGROUND: Our objective was to explore what people receiving and providing care consider to be 'good' in-home care for people living with dementia. METHODS: We conducted 36 in-depth interviews and two focus groups with key stakeholders in Australia in the first quarter of 2018. Participants included those receiving care (4 people living with dementia, 15 family carers) or providing care (9 case managers, 5 service managers, 10 home care workers). Qualitative thematic analysis was guided by Braun and Clarke's six-step approach. RESULTS: Consensus was reached across all groups on five themes considered as important for good in-home dementia care: 1) Home care workers' understanding of dementia and its impact; 2) Home care workers' demonstrating person-centred care and empathy in their care relationship with their client; 3) Good relationships and communication between care worker, person with dementia and family carers; 4) Home care workers' knowing positive practical strategies for changed behaviours; 5) Effective workplace policies and workforce culture. The results contributed to the co-design of a dementia specific training program for home care workers. CONCLUSIONS: It is crucial to consider the views and opinions of each stakeholder group involved in providing/receiving dementia care from home care workers, to inform workforce training, education program design and service design. Results can be used to inform and empower home care providers, policy, and related decision makers to guide the delivery of improved home care services. TRIAL REGISTRATION: ACTRN 12619000251123 .

More than memory: A qualitative analysis of carer-reported psychosocial benefits of Memory Cafés.

ISSUE ADDRESSED: Memory Cafés are a psychosocial intervention that aims to provide socialisation and interpersonal support for those living with dementia and their carers. This study explores the Memory Café model and determines the impact of the peer-to-peer Memory Café model on the psychosocial well-being of those living with dementia and their carers. METHODS: Participants were informal carers of those living with dementia, recruited from four Memory Café's located in metropolitan Perth, Western Australia. Demographic information was collected from participants. Eleven semi-structured interviews were conducted. The data were transcribed and analysed thematically. RESULTS: The benefits of participation are described under four themes; sharing experiences and reduction of stigma, a place to feel joy and be yourself, a time to socialise and build friendships and improvements in life outside the Memory Café. The positive attributes of the Memory Cafés that contributed to the benefits were also identified. Concerns about Memory Cafés were limited to it becoming a carers-only group. CONCLUSIONS: Memory Cafés contribute significantly to the psychosocial well-being of carers of those living with dementia and provide a positive outlet for carers to build social networks and become active in their community. The effect on the psychosocial well-being of those living with dementia may be more limited but is still described positively. SO WHAT?: Dementia is a condition with significant impacts on carers and families. Successful peer-based social interventions such as Memory Cafés can lead to further development of dementia-friendly communities aimed at providing joy as well as support.

Optimism where there is none: Asymmetric belief updating observed with valence-neutral life events.

How people update their beliefs when faced with new information is integral to everyday life. A sizeable body of literature suggests that people's belief updating is optimistically biased, such that their beliefs are updated more in response to good news than bad news. However, recent research demonstrates that findings previously interpreted as evidence of optimistic belief updating may be the result of flaws in experimental design, rather than motivated reasoning. In light of this controversy, we conduct three pre-registered variations of the standard belief updating paradigm (combined N = 300) in which we test for asymmetric belief updating with neutral, non-valenced stimuli using analytic approaches found in previous research. We find evidence of seemingly biased belief updating with neutral stimuli - results that cannot be attributed to a motivational, valence-based, optimism account - and further show that there is uninterpretable variability across samples and analytic techniques. Jointly, these results serve to highlight the methodological flaws in current optimistic belief updating research.

Promoting Independence Through quality dementia Care at Home (PITCH): a research protocol for a stepped-wedge cluster-randomised controlled trial.

BACKGROUND: Home care service providers are increasingly supporting clients living with dementia. Targeted and comprehensive dementia-specific training for home care staff is necessary to meet this need. This study evaluates a training programme delivered to care staff (paid personal carers) of clients living with dementia at home. METHODS: This study is a pragmatic stepped-wedge cluster-randomised controlled trial (SW-CRT). Home care workers (HCWs) from seven home care service providers are grouped into 18 geographical clusters. Clusters are randomly assigned to intervention or control groups. The intervention group receives 7 h of a dementia education and upskilling programme (Promoting Independence Through quality dementia Care at Home [PITCH]) after baseline measures. The control group receives PITCH training 6 months after baseline measures. This approach will ensure that all participants are offered the program. Home care clients living with dementia are also invited to participate, as well as their family carers. The primary outcome measure is HCWs' sense of competence in dementia care provision. DISCUSSION: Upskilling home care staff is needed to support the increasing numbers of people living with dementia who choose to remain at home. This study uses a stepped-wedge cluster-randomised trial to evaluate a training programme (PITCH) for dementia care that is delivered to front-line HCWs. TRIAL REGISTRATION: anzctr.org.au ; ACTRN12619000251123. Registered on 20 February 2019.

Multiple Sclerosis Progression Discussion Tool Usability and Usefulness in Clinical Practice: Cross-sectional, Web-Based Survey.

BACKGROUND: A digital tool, Multiple Sclerosis Progression Discussion Tool (MSProDiscuss), was developed to facilitate discussions between health care professionals (HCPs) and patients in evaluating early, subtle signs of multiple sclerosis (MS) disease progression. OBJECTIVE: The aim of this study is to report the findings on the usability and usefulness of MSProDiscuss in a real-world clinical setting. METHODS: In this cross-sectional, web-based survey, HCPs across 34 countries completed an initial individual questionnaire (comprising 7 questions on comprehensibility, usability, and usefulness after using MSProDiscuss during each patient consultation) and a final questionnaire (comprising 13 questions on comprehensibility, usability, usefulness, and integration and adoption into clinical practice to capture the HCPs' overall experience of using the tool). The responses were provided on a 5-point Likert scale. All analyses were descriptive, and no statistical comparisons were made. RESULTS: In total, 301 HCPs tested the tool in 6974 people with MS, of whom 77% (5370/6974) had relapsing-remitting MS, including those suspected to be transitioning to secondary progressive MS. The time taken to complete MSProDiscuss was reported to be in the range of 1 to 4 minutes in 97.3% (6786/6974; initial) to 98.2% (269/274; final) of the cases. In 93.54% (6524/6974; initial) to 97.1% (266/274; final) of the cases, the HCPs agreed (4 or 5 on the Likert scale) that patients were able to comprehend the questions in the tool. The HCPs were willing to use the tool again in the same patient, 90.47% (6310/6974; initial) of the cases. The HCPs reported MSProDiscuss to be useful in discussing MS symptoms and their impact on daily activities (6121/6974, 87.76% initial and 252/274, 92% final) and cognitive function (5482/6974, 78.61% initial and 271/274, 79.2% final), as well as in discussing progression in general (6102/6974, 87.49% initial and 246/274, 89.8% final). While completing the final questionnaire, 94.9% (260/274) of the HCPs agreed that the questions were similar to those asked in regular consultation, and the tool helped to better understand the impact of MS symptoms on daily activities (249/274, 90.9%) and cognitive function (220/274, 80.3%). Overall, 92% (252/274) of the HCPs reported that they would recommend MSProDiscuss to a colleague, and 85.8% (235/274) were willing to integrate it into their clinical practice. CONCLUSIONS: MSProDiscuss is a usable and useful tool to facilitate a physician-patient discussion on MS disease progression in daily clinical practice. Most of the HCPs agreed that the tool is easy to use and were willing to integrate MSProDiscuss into their daily clinical practice.

Reconsidering evidence of moral contagion in online social networks.

The ubiquity of social media use and the digital data traces it produces has triggered a potential methodological shift in the psychological sciences away from traditional, laboratory-based experimentation. The hope is that, by using computational social science methods to analyse large-scale observational data from social media, human behaviour can be studied with greater statistical power and ecological validity. However, current standards of null hypothesis significance testing and correlational statistics seem ill-suited to markedly noisy, high-dimensional social media datasets. We explore this point by probing the moral contagion phenomenon, whereby the use of moral-emotional language increases the probability of message spread. Through out-of-sample prediction, model comparisons and specification curve analyses, we find that the moral contagion model performs no better than an implausible XYZ contagion model. This highlights the risks of using purely correlational evidence from large observational datasets and sounds a cautionary note for psychology's merge with big data.

Depletion of essential isoprenoids and ER stress induction following acute liver-specific deletion of HMG-CoA reductase.

HMG-CoA reductase (Hmgcr) is the rate-limiting enzyme in the mevalonate pathway and is inhibited by statins. In addition to cholesterol, Hmgcr activity is also required for synthesizing nonsterol isoprenoids, such as dolichol, ubiquinone, and farnesylated and geranylgeranylated proteins. Here, we investigated the effects of Hmgcr inhibition on nonsterol isoprenoids in the liver. We have generated new genetic models to acutely delete genes in the mevalonate pathway in the liver using AAV-mediated delivery of Cre-recombinase (AAV-Cre) or CRISPR/Cas9 (AAV-CRISPR). The genetic deletion of Hmgcr by AAV-Cre resulted in extensive hepatocyte apoptosis and compensatory liver regeneration. At the biochemical level, we observed decreased levels of sterols and depletion of the nonsterol isoprenoids, dolichol and ubiquinone. At the cellular level, Hmgcr-null hepatocytes showed ER stress and impaired N-glycosylation. We further hypothesized that the depletion of dolichol, essential for N-glycosylation, could be responsible for ER stress. Using AAV-CRISPR, we somatically disrupted dehydrodolichyl diphosphate synthase subunit (Dhdds), encoding a branch point enzyme required for dolichol biosynthesis. Dhdds-null livers showed ER stress and impaired N-glycosylation, along with apoptosis and regeneration. Finally, the combined deletion of Hmgcr and Dhdds synergistically exacerbated hepatocyte ER stress. Our data show a critical role for mevalonate-derived dolichol in the liver and suggest that dolichol depletion is at least partially responsible for ER stress and apoptosis upon potent Hmgcr inhibition.

Natural history of benign multiple sclerosis: Clinical and HLA correlates in a Western Australian cohort.

BACKGROUND: Benign multiple sclerosis (BMS) is a controversial term that has been used for MS patients with minimal disability decades after disease onset. Herein, we evaluated disease status after 20 years in a Western Australian cohort defined as BMS based on an Expanded Disability Status Scale (EDSS) score ≤ 3.0 at 10 years from onset. METHODS: MS patients with an EDSS score ≤ 3.0 at 10 years from onset and minimum of 20 years follow up were included in the study. The 20-year EDSS score was considered the primary outcome. Associations with demographic and clinical characteristics and HLA-DRB1 genotype were investigated. RESULTS: Among 120 patients with a benign course at 10 years, 78 (65%) remained benign at the 20-year follow up, but patients with an EDSS ≥ 2.5 were more likely to go on to develop more severe disability in the next decade. When considering factors associated with an increase in EDSS score ≤ 1 from 10 to 20 years, indicating limited progression, apart from the EDSS score at 10 years, poly-symptomatic presentation (p = 0.004) and cerebellar/brainstem mono-symptomatic presentation (p = 0.016) were independently associated with more rapid progression compared with other mono-symptomatic presentations. Carriage of the high risk HLA-DRB1*1501 allele was marginally associated with slower progression. CONCLUSIONS: In this geographically isolated MS cohort of predominantly Anglo-Celtic origin clinical progression in the benign MS group was similar to that in other published series from Western countries. These results are in keeping with the view that patients labeled as benign MS are part of a heterogeneous continuum of disease progression and do not possess unique clinical characteristics. Possible genetic determinants of a benign course warrant further investigation.

Small Molecules Revealed in a Screen Targeting Epithelial Scattering Are Inhibitors of Microtubule Polymerization.

Stimulation of cultured epithelial cells with scatter factor/hepatocyte growth factor (HGF) results in the detachment of cell-cell junctions and initiation of cell migration. Instead of coordinating collective cell behavior within a tissue, cells become solitary and have few cell-cell interactions. Since epithelial scattering is recapitulated in cancer progression and since HGF signaling drives cancer metastasis in many cases, inhibitors of HGF signaling have been proposed to act as anticancer agents. We previously sought to better understand critical components required for HGF-induced epithelial scattering by performing a forward chemical genetics screen, which resulted in the identification of compounds with no previously reported biological activity that we report here. In efforts to determine the mechanism of these compounds, we find that many compounds have broad antiproliferative effects on cancer cell lines by arrest of cell division in G2/M with minimal induction of apoptosis. This effect is reminiscent of microtubule-targeting agents, and we find that several of these scaffolds directly inhibit microtubule polymerization. Compounds are assessed for their toxicity and pharmacokinetics in vivo. The identification of novel small-molecule inhibitors of microtubule polymerization highlights the role of the microtubule cytoskeleton in HGF-induced epithelial scattering.