bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of acute mechanical revascularization in minor stroke (NIHSS score ⩽ 5) and large vessel occlusion: The MOSTE multicenter, randomized, clinical trial protocol
Authors: Arquizan Caroline , Lapergue Bertrand , Gory Benjamin , Labreuche Julien , Henon Hilde , Albucher Jean-François , Sibon Igor , Turc Guillaume , Richard Sebastien , Nouri Nasreddine , Cognard Christophe , Marnat Gauthier , Naggara Olivier , Di Maria Federico , Duhamel Alain , Jovin Tudor , Costalat Vincent ,   for the MOSTE Trial Investigators
Published: June 2023

Rationale:

Mechanical thrombectomy (MT) has become the standard of care for patients with acute ischemic stroke secondary to large vessel occlusion (LVO) of the anterior circulation. Conversely, its benefit in patients with National Institutes of Health Stroke Scale (NIHSS) score ⩽ 5 is unproven.

Aim:

To demonstrate the superiority of immediate MT plus best medical treatment (BMT) compared to BMT (with secondary MT in case of deterioration) for increasing the rate of modified Rankin Scale (mRS) score ⩽ 1 at 90 days after minor stroke (NIHSS score ⩽ 5) and anterior circulation LVO.

Sample size estimates:

To detect an absolute increase of 10% (80% power) in the 90-day mRS score = 0–1 rate in the MT + BMT group, by assuming an mRS score = 0–1 rate of 60% in the BMT group and by considering two interim efficacy/futility analyses (after study completion by 274 and 548 patients), 824 patients must be included by 36 centers in France, Spain, and the USA.

Methods and design:

MOSTE is an international, multicenter, prospectively randomized into two parallel (1:1) arms, open-label, with blinded endpoint trial. Eligibility criteria are diagnosis of acute ischemic stroke within 23 h of last-seen-well, NIHSS score ⩽ 5, and LVO in the anterior circulation (intracranial internal carotid artery, M1 or M1-M2 segment of the middle cerebral artery).

Study outcomes:

The primary endpoint is the rate of excellent outcome at day 90 (mRS score = 0–1). Secondary endpoints include the rates of 90-day mRS score = 0–2 and score = 0, NIHSS score change, secondary MT, revascularization and infarct volume growth at 24 h, and quality of life and cognitive function at day 90. Safety outcomes (90-day all-cause mortality, procedural complications, symptomatic intracerebral hemorrhage, and rapid NIHSS score worsening) are recorded.

Discussion:

The MOSTE trial will determine MT efficacy and safety in patients with minor stroke and LVO in the anterior circulation.

Trial registration:

MOSTE Trial. NCT 03796468
Factors associated with potentially inappropriate prescribing among older persons in primary care settings: Systematic review
Authors: Lee Cia Sin , Tan Ngiap Chuan , Goh Kuan Liang Shawn , Chang Zi Ying , Liew Tau Ming
Published: June 2023

Background

Potentially inappropriate prescribing (PIP) is common in primary care and is associated with adverse outcomes. Knowledge of the risk factors of PIP can be critical in designing PIP interventions, especially in guiding our understanding on how PIP occurs in primary care.

Objective

This systematic review examined factors associated with PIP, specific to primary care.

Methods

We searched PubMed, Embase, CINAHL, Web of Science, Scopus and PsycINFO for studies related to ‘older persons’, ‘primary care’ and ‘inappropriate prescribing’. Two reviewers conducted study selection, data extraction and quality appraisal. Factors associated with PIP were narratively synthesized.

Results

Of the 1017 articles identified, we included 25 articles and a total of 2,893,925 participants, with average age of 70.4–84.0 years. Risk factors of PIP could be classified into patient, physician and system factors. Patient factors were related to patient demographics (advanced age, lower education level and lower socioeconomic status), medical comorbidities (polypharmacy and multimorbidity) and lifestyle factors (unhealthy habits and use of over-the-counter medications). Physician and system factors included older, male, solo general practitioner (GP), higher number of visits of pharmaceutical sales representatives to GP, centrally located GP practice, and smaller number of older patients following up with GP, and medication source from public health system.

Conclusions

The findings provide contextual information to guide our understanding of PIP in primary care. Factors identified in this review can inform the design of complex interventions for PIP, as well as be used to develop risk prediction tools to identify high-risk groups who may require further interventions related to PIP.
Nordic approaches to evaluation and assessment in early childhood education and care
Authors: Urban Mathias , Reikerås Elin , Eidsvåg Gunnar Magnus , Guevara Jennifer , Saebø Janken , Semmoloni Carolina
Published: June 2023

This paper presents and discusses the findings of a collaborative investigation into Nordic approaches to evaluation and assessment in early childhood education and care. The project explored values and principles that underpin and guide evaluation in ECEC systems and practices in five Nordic countries: Denmark, Finland, Iceland, Norway and Sweden. The qualitative study combined documentary analysis with interviews with early childhood educators, academics and policy makers. The study was commissioned by the Nordic Council of Ministers in order to shed light on the values and principles that have guided the evaluation and assessment of the quality of early childhood education and care in the various Nordic countries, the ways in which evaluation and quality assessment has been developed in the Nordic countries and the parties responsible for carrying out the evaluation and assessment. Central to our exploration was whether a coherent Nordic approach exists and what characteristics distinguish it from other possible models of ECEC system evaluation. This question has gained relevance in global contexts of International Large-scale Standardised Assessments in ECEC, promoted most prominently the Organisation for Economic Co-operation and Development (OECD). Our findings confirm the existence of a Nordic approach, consisting of a shared and coherent understanding of the underpinning values, the purpose and the appropriate methodologies across several dimensions of comparison between countries as well as within countries. Shared values and principles include well-being, child-centredness, play, learning, professionalism and reducing inequalities. Shared purpose of evaluation is to provide relevant information to improve the quality of the ECEC system. In consequence, the focus is on evaluating settings and systems that enable children to thrive, rather than assessing individual children. Nonetheless, the Nordic model must be carefully interpreted in its specific contexts. Much responsibility is delegated to the municipality level, leading to local variations and influences. More generally, we found the Nordic approaches to evaluation and assessment in ECEC firmly situated in a Nordic model of governance that emphasises decentralisation and values local democracy. We discuss the implications of this for international comparative research in ECEC, for further research into the relationship between the central and the local in ECEC and for the possibility of an explicit Nordic contribution to informing the global ECEC policy debate.
Influence of menopausal status on physical function and performance: A cross-sectional study
Authors: Walankar Prachita , Kini Raveena , Panhale Vrushali , Desai Nidhi
Published: June 2023

Objective

To compare the physical function and performance in pre-, peri-, and postmenopausal women.

Study design

A cross sectional study using convenience sampling method was conducted in 210 women categorized into premenopausal, perimenopausal, and postmenopausal.

Main outcome measures

Flexibility, muscle strength, muscle endurance, cardiovascular endurance, static balance, dynamic balance, and gait speed.

Results

The mean age of the premenopausal, perimenopausal, and postmenopausal women was 46.55 ± 1.77, 49.54 ± 3.38 and 54.85 ± 3.77 years respectively. There is significant difference observed between premenopausal, perimenopausal, and postmenopausal women in muscle strength, upper limb endurance, lower limb endurance, static balance, dynamic balance, gait speed, and cardiovascular endurance ( p < .05) using Kruskal Wallis test. There is no significant difference observed between the groups for flexibility ( p > .05).

Conclusion

It was observed that physical function and performance was impaired in postmenopausal women when compared to pre- and perimenopausal women. Hence, these components should be included during assessment which will provide a holistic and multimodal approach toward the understanding, planning and management of postmenopausal women in community settings.
The Impact of Meetings on the Network Governance and Mobility of UN Policy Programs on Environment and Education
Authors: Stahelin Nicolas , McKenzie Marcia
Published: June 2023

Purpose

This paper adds to the understandings of how face-to-face meetings contribute to the network governance and global mobility of United Nations (UN) policy programs on environmental and sustainability education (ESE).

Design/Approach/Methods

Data from interviews with 13 international ESE policy leaders were transcribed, coded, and analyzed for key themes related to the research purpose.

Findings

The findings indicate that meetings provide an arena for collaboration and influence on UN ESE policy programs, as well as facilitating the impact of the policy programs on UN member country policy. In addition, attending meetings enables the production of network relations that bind ESE policy communities together across distant locations. They are also a venue for the networking labor involved in forging new relationships and facilitating the social learning that supports global policy mobility.

Originality/Value

This pilot study enriches understanding of face-to-face meetings as a key vector of policy mobility and a significant factor in the overall network governance of UN organizations and their policy programs. We hope the study contributes to the fields of critical policy studies and ESE, as well as to informing policy actors on how important their participation in meetings can be for the network governance and mobility of UN policy programs.
Motivation for the Choice of the Teaching Profession: The Role of Prospective Teachers’ Personality Traits, Emotional Competence, and Life-Satisfaction
Authors: Pavin Ivanec Tea , Defar Ana
Published: June 2023

Interest in the motivation for the choice of the teaching profession has been growing in the last few decades. Although the literature recognizes the importance of exploring non-academic factors that affect the quality of teaching and teachers’ well-being, studies exploring these factors within the context of the teaching career choice are rather underrepresented. The aim of this study was to explore the predictive value of personality traits, emotional competence, and life-satisfaction of prospective teachers in explaining prospective teachers’ motivation for the choice of the teaching profession. A total of 591 prospective teachers participated in this study. The data were analyzed by the hierarchical regression analyses, and the results indicated that almost all personality traits and the ability to regulate and manage emotions predicted the importance of intrinsic value and the social utility value of teaching, whereby neuroticism was a negative predictor of these motives. Also, life-satisfaction was predictive of the importance of both of these motives and the importance of the personal utility value of teaching.
Emerging Adults’ Experience of Mindful Parenting: Distinct Associations With Their Dispositional and Interpersonal Mindfulness, Self-Compassion, and Adjustment
Authors: Mera Samira , Zimmer-Gembeck Melanie J. , Conlon Elizabeth G.
Published: June 2023

Experiencing mindful parenting has been positively associated with youth’s dispositional mindfulness and self-compassion, which in turn, relates to better emotional adjustment. However, mindful parenting could also relate to interpersonal mindfulness, which is another form of mindfulness that has had a unique relation with social adjustment. In this study, 458 emerging adults (age of 17–21 years) completed a survey to report their current experience of mindful parenting, dispositional mindfulness, self-compassion, interpersonal mindfulness, emotional (general well-being, social anxiety) and social adjustment (friendship quality, prosocial behavior, conflict negotiation). Regression models testing direct and indirect associations showed that mindful parenting was directly but also indirectly associated with emerging adults’ emotional adjustment via dispositional mindfulness and self-compassion (not interpersonal mindfulness), and indirectly associated with social adjustment via interpersonal mindfulness (not dispositional mindfulness or self-compassion). Findings have implications for theory and practice within the areas of mindfulness, parenting, and emerging adults’ emotion regulation and personal adjustment.
Comparison of Arthroscopic-Assisted Percutaneous Internal Fixation With a Modified Reducer Versus Open Reduction and Internal Fixation for Schatzker Type II and III Tibial Plateau Fractures
Authors: Huang Xingrui , Zhao Song , Jiang Yuanbin , Fang Shuchen , Xu Hao , Li Hanlin , Zhao Jinzhong , Dong Qirong
Published: June 2023

Background:

Tibial plateau fractures require anatomical reduction and stable fixation to achieve satisfactory results. In addition, addressing any related injuries is of paramount importance. Arthroscopic reduction and internal fixation (ARIF) has been promoted as a possible technique to treat tibial plateau fractures.

Purpose:

To compare the effectiveness of ARIF with this modified reducer and open reduction and internal fixation (ORIF) for Schatzker types II and III tibial plateau fractures.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

We retrospectively reviewed 68 patients who were treated for Schatzker type II or III tibial plateau fractures between August 1, 2014, and October 31, 2018. Patients were categorized into the ARIF (n = 33) and ORIF groups (n = 35). The groups were compared regarding intra-articular injuries, duration of hospital stay, complications, and clinical outcomes—including the International Knee Documentation Committee (IKDC) score, the Hospital for Special Surgery (HSS) score, and range of motion (ROM). The paired t test was used to compare preoperative and postoperative data, and the chi-square test was used to compare the IKDC and HSS scores.

Results:

The median follow-up period was 36 months (26-40 months). Additional intra-articular lesions were found in 29 patients—21 in the ARIF group and 8 in the ORIF group ( P = .02). A significant difference was observed in the duration of hospital stay—3.58 ± 1.46 days for the ARIF group and 4.57 ± 1.12 days for the ORIF group ( t = –3.169; P = .002). All fractures healed within 3 months after surgery. The complication rate for all patients was 11%, with no significant difference between the ARIF and ORIF groups ( t = 1.244; P = .265). At the final follow-up, there were no significant differences between the 2 groups in the IKDC score, HSS score, and ROM ( P > .05 for all).

Conclusion:

ARIF with a modified reducer was found to be an effective, reliable, and safe procedure for the treatment of Schatzker types II and III tibial plateau fractures. Both ARIF and ORIF provided equally good results, while ARIF offered a more precise evaluation and reduced the duration of hospital stay.
Development of Complementary Encounter and Patient Decision Aids for Shared Decision Making about Stroke Prevention in Atrial Fibrillation
Authors: Jones Aubrey E. , McCarty Madeleine M. , Cameron Kenzie A. , Cavanaugh Kerri L. , Steinberg Benjamin A. , Passman Rod , Kansal Preeti , Guzman Adriana , Chen Emily , Zhong Lingzi , Fagerlin Angela , Hargraves Ian , Montori Victor M. , Brito Juan P. , Noseworthy Peter A. , Ozanne Elissa M.
Published: June 2023

Introduction

Decision aids (DAs) are helpful instruments used to support shared decision making (SDM). Patients with atrial fibrillation (AF) face complex decisions regarding stroke prevention strategies. While a few DAs have been made for AF stroke prevention, an encounter DA (EDA) and patient DA (PDA) have not been created to be used in conjunction with each other before.

Design

Using iterative user-centered design, we developed 2 DAs for anticoagulation choice and stroke prevention in AF. Prototypes were created, and we elicited feedback from patients and experts via observations of encounters, usability testing, and semistructured interviews.

Results

User testing was done with 33 experts (in AF and SDM) and 51 patients from 6 institutions. The EDA and PDA underwent 1 and 4 major iterations, respectively. Major differences between the DAs included AF pathophysiology and a preparation to meet with the clinician in the PDA as well as different language throughout. Content areas included personalized stroke risk, differences between anticoagulants, and risks of bleeding. Based on user feedback, developers 1) addressed feelings of isolation with AF, 2) improved navigation options, 3) modified content and flow for users new to AF and those experienced with AF, 4) updated stroke risk pictographs, and 5) added structure to the preparation for decision making in the PDA.

Limitations

These DAs focus only on anticoagulation for stroke prevention and are online, which may limit participation for those less comfortable with technology.

Conclusions

Designing complementary DAs for use in tandem or separately is a new method to support SDM between patients and clinicians. Extensive user testing is essential to creating high-quality tools that best meet the needs of those using them.

Highlights

First-time complementary encounter and patient decision aids have been designed to work together or separately. User feedback led to greater structure and different experiences for patients naïve or experienced with anticoagulants in patient decision aids. Online tools allow for easier dissemination, use in telehealth visits, and updating as new evidence comes out.
Becoming a Synodal Church: Political Charity and Collective Spirituality for Philippine Catholicism
Authors: Itao Alexis Deodato S.
Published: June 2023

This article explores the prospects of Philippine Catholicism, especially in light of Pope Francis’s exhortation to rebrand the Church into a synodal reality. To steer the Philippine Catholic Church towards synodality, I argue that imitating the first Christians is imperative for Filipino Catholics. The early Church was a synodal Church, and if Philippine Catholicism aspires to be such, I further argue that two essential building blocks are necessary so it can tread the path of synodality, namely, political charity and collective spirituality. These two are equally crucial elements for Philippine Catholicism to realize its synodal transformation.
The Rural Missionaries of the Philippines: Prophetic Mission in the Midst of Persecution
Authors: Imbong Jerry D.
Published: June 2023

The Rural Missionaries of the Philippines (RMP), one of the Mission Partners of the Conference of Major Religious Superiors in the Philippines (CMRSP), was founded on August 15, 1969, in the context of brewing social upheaval and agrarian unrest under the late dictator Ferdinand Marcos Sr. For more than fifty years, RMP remained steadfast in its mandate to serve Christ through the rural poor. As a consequence of their unwavering commitment to their prophetic mission, RMP often encountered various forms of harassments and threats from state forces and those in power. With President Rodrigo Duterte’s ascent into power, attacks against progressive groups and individuals, activists, human rights defenders, and church-based NGOs significantly increased. This article aims to shed light on the nature of RMP’s missionary activity in the midst of intensified state repression.
Healing as God’s Intention for Ministers of Reconciliation
Authors: O’Neill Daniel W.
Published: June 2023

There is something missing in our view of the intentions of God and the purposes of the church in global mission. Tracing the historical precedent for the church as a healing agent in the world, and challenging narrow views of what healing means, a biblical healing metanarrative emerges as the primary telos of God, and reconciliation as an essential part of healing. By reconciling salvation and healing, spirit and matter, as well as healing and suffering, the ongoing work of the reconciling Healer is highlighted along with the implication that healing is an indispensable part of collective global mission.
Under lockdown: Remaking “home” through infrastructures of care during COVID-19
Authors: Muñoz Solange , Clark Jordin , Auerbach Jeremy , Hardwig Lily
Published: June 2023

This paper examines how poor urban residents in the Sun Valley public housing community in Denver, CO (US) experienced the pandemic during the first few months of the crisis. Employing a framework that focuses on people, community, housing and home as potential spaces and possibilities of “infrastructures of care”, this research examines the strategies and practices that emerged during the pandemic to address the immediate needs and concerns of the Sun Valley residents. We consider how these practices and the pandemic itself have potentially led to new imaginings and understandings of home and community, both at the intimate and collective scales. Using qualitative methods and photo-voice techniques, we documented residents’ experience during lockdown. Their narratives reveal the many ways the COVID-19 pandemic has affected people’s lives and highlight how community support, services and home are necessary for ensuring that residents can develop resilient infrastructures of care that allow them to overcome public health crises.
Trajectory of external implementation support activities across two states in the United States: A descriptive study
Authors: Aldridge William A. , Roppolo Rebecca H. , Chaplo Shannon D. , Everett Ariel B. , Lawrence Sherra N. , DiSalvo Christina I. , Minch Devon R. , Reed Jessica J. , Boothroyd Renée I.
Published: June 2023

Background

Reporting on strategies to advance implementation outcomes is imperative. The current study reports descriptive information about external implementation support (EIS) provided over 5 years to 13 regions in North Carolina and South Carolina scaling an evidence-based system of parenting and family supports. Regional support teams operating through the Implementation Capacity for Triple P (ICTP) projects employed core practice components (CPCs) for EIS as proposed by Aldridge et al. and further operationalized by members of The Impact Center at FPG Child Development Institute, UNC-Chapel Hill.

Method

Practice activities associated with CPCs were developed and iteratively refined across the study period. ICTP regional support teams systematically tracked their use of CPCs and related activities following each substantive support interaction. Tracking included the duration of time a CPC was employed and the use of specific practice activities associated with that CPC. Data were aggregated by month of the relationship to account for differential start dates across regions.

Results

From November 2016 through December 2021, ICTP support teams tracked 749 support interactions with Triple P regions in North Carolina and South Carolina. Monthly support decreased year over year, though dose varied considerably. Patterns of CPC use indicated a high dose of “foundational” and “co-design” CPCs early, followed by a blended and more diverse use thereafter, with some notable trends. Practice activities considered essential to influencing intended practice outcomes were characterized by higher rates of use. Like CPCs, practice activities were used dynamically across the study period.

Conclusions

This descriptive study offers a case study for how EIS might be operationalized, tracked, and employed. Findings suggest several interpretations that might refine our understanding and use of EIS. Although the nature of this practical report precludes generalizability of findings, directions for future research and practice are discussed.
Mechanisms of change in external implementation support: A conceptual model and case examples to guide research and practice
Authors: Aldridge William A. , Roppolo Rebecca H. , Brown Jacquie , Bumbarger Brian K. , Boothroyd Renée I.
Published: June 2023

Background

External implementation support (EIS) is a well-recognized feature of implementation science and practice, often under related terms such as technical assistance and implementation facilitation. Existing models of EIS have gaps related to addressing practice outcomes at both individual and organizational levels, connecting practice activities to intended outcomes, or grounding in well-established theories of behavior and organization change. Moreover, there have been calls to clarify the mechanisms of change through which EIS influences related outcomes.

Method

In this article, we theorize about mechanisms of change within EIS. Our theorizing process aligns with the approach advocated by Kislov et al. We aim to consolidate prior EIS literature, combining related constructs from previous empirical and conceptual work while drawing on our extensive EIS experience to develop a higher-order, midrange theory of change.

Results

Our theory of change is empirically and practically informed, conceptually situated within an established grand theory of change, and guided by eight practice principles and social cognitive theory. The theory of change proposes 10 core practice components as mechanisms of change within EIS. When used according to underlying theory and principles, they are believed to contribute to favorable practice outcomes at individual, team, organizational, and system levels. The model offers flexibility by recognizing the need for sequential support processes and the demand to practice in dynamic and responsive ways. Case examples are presented to illustrate major themes and patterns of the model in action.

Conclusions

The proposed model is intended to support prospective EIS studies by conceptualizing discernable practice components with hypothesized relationships to proximal and distal practice outcomes. The model can be behaviorally operationalized to compliment and extend competency-based approaches to implementation support practitioner (ISP) training and coaching. Over time, the model should be refined based on new empirical findings and contributions from ISPs across the field.
The Effectiveness and Adverse Events of Cannabidiol and Tetrahydrocannabinol Used in the Treatment of Anxiety Disorders in a PTSD Subpopulation: An Interim Analysis of an Observational Study
Authors: Stack Sophie K. , Wheate Nial J. , Moloney Niamh C. , Abelev Sarah V. , Barlow John W. , Schubert Elise A.
Published: June 2023

Background: Anxiety is a condition for which current treatments are often limited by adverse events (AEs). Components of medicinal cannabis, cannabidiol (CBD) and tetrahydrocannabinol (THC), have been proposed as potential treatments for anxiety disorders, specifically posttraumatic stress disorder (PTSD). Objective: To evaluate quality-of-life outcomes after treatment with various cannabis formulations to determine the effectiveness and associated AEs. Methods: An interim analysis of data collected between September 2018 and June 2021 from the CA Clinics Observational Study. Patient-Reported Outcomes Measurement Information System-29 survey scores of 198 participants with an anxiety disorder were compared at baseline and after treatment with medicinal cannabis. The data of 568 anxiety participants were also analyzed to examine the AEs they experienced by the Medical Dictionary for Regulatory Activities organ system class. Results: The median doses taken were 50.0 mg/day for CBD and 4.4 mg/day for THC. The total participant sample reported significantly improved anxiety, depression, fatigue, and ability to take part in social roles and activities. Those who were diagnosed with PTSD (n = 57) reported significantly improved anxiety, depression, fatigue, and social abilities. The most common AEs reported across the whole participant cohort were dry mouth (32.6%), somnolence (31.3%), and fatigue (18.5%), but incidence varied with different cannabis formulations. The inclusion of THC in a formulation was significantly associated with experiencing gastrointestinal AEs; specifically dry mouth and nausea. Conclusions: Formulations of cannabis significantly improved anxiety, depression, fatigue, and the ability to participate in social activities in participants with anxiety disorders. The AEs experienced by participants are consistent with those in other studies.
The Challenges of Educating a Cardiac Sonography Workforce
Authors: Hagen-Ansert Sandra , Billick Kristen
Published: June 2023

Objective:

Cardiac sonographers are challenged on a daily basis to provide excellent frontline care for a variety of patients. They face challenges of promoting quality over quantity and continued support for education and training efforts. Echocardiography requires an operator-dependent sonographer with independent judgement and critical thinking skills to obtain and integrate diagnostic information during the echo examination. The growth of echocardiographic procedures has increased the demand for qualified cardiac sonographers to cover the workload.

Materials and Methods:

Occupational employment and wage statistics, educational opportunities, simulation labs and clinical sites, national registries, and ASE standards for a quality echo educational environment are discussed.

Results:

The national curriculum for echocardiography is extensive and requires adequate clinical hands-on training to promote an opportunity for the student to become a competent cardiac sonographer. Credentialing in echocardiography demonstrates to the patients, healthcare professionals, and employers of medical facilities that the cardiac sonographer is a dedicated professional in their respective field.

Conclusions:

Additional accredited cardiovascular programs with active credentialed clinical sites to fulfill this shortage. The skillset has increased with new procedures requiring training in advanced imaging techniques such as three-dimensional imaging, strain, tissue Doppler, and contrast-enhanced imaging.
Effective treatment with the selective cytokine inhibitor BNZ-1 reveals the cytokine dependency of T-LGL leukemia
Authors: Brammer Jonathan E. , Ballen Karen , Sokol Lubomir , Querfeld Christiane , Nakamura Ryotaro , Mishra Anjali , McLaughlin Eric M. , Feith David , Azimi Nazli , Waldmann Thomas A. , Tagaya Yutaka , Loughran Thomas
Published: June 2023

T-cell large granular lymphocytic leukemia (T-LGLL) is a clonal proliferation of cytotoxic T lymphocytes that can result in severe neutropenia, anemia, and bone marrow failure. Strong evidence from patients and mouse models demonstrate the critical role of interleukin-15 (IL-15) in T-LGLL pathogenesis. BNZ-1 is a pegylated peptide that selectively inhibits the binding of IL-15 and other γc cytokines to their cellular receptor complex, which has demonstrated efficacy in ex vivo T-LGLL cells and transgenic mice in preclinical studies. We conducted a phase 1/2 trial of BNZ-1 in patients with T-LGLL who had hematocytopenias (anemia or neutropenia) and required therapy. Clinical responses were assessed using hematologic parameters (improvement in hematocytopenias) based on response criteria from the Eastern Cooperative Oncology Group 5998 T-LGLL trial. BNZ-1 demonstrated clinical partial responses in 20% of patients with T-LGLL with minimal toxicity and the maximum tolerated dose was not reached. Furthermore, T-LGL leukemic cells showed significantly increased apoptosis in response to BNZ-1 treatment as early as day 2, including in clinical nonresponders, with changes that remained statistically different from baseline throughout treatment (P < .005). We report first-in-human proof that T-LGL leukemic cells are dependent on IL-15 and that intervention with IL-15 inhibition with BNZ-1 in patients with T-LGLL shows therapeutic effects, which carries important implications for the understanding of the pathogenesis of this disease. This trial was registered at www.clinicaltrials.gov as #NCT03239392.
Tacrolimus/methotrexate vs tacrolimus/reduced-dose methotrexate/mycophenolate for graft-versus-host disease prevention
Authors: Hamilton Betty K. , Rybicki Lisa A. , Li Hong , Lucas Taylor , Corrigan Donna , Kalaycio Matt , Sobecks Ronald , Hanna Rabi , Rotz Seth J. , Dean Robert M. , Gerds Aaron T. , Jagadeesh Deepa , Brunstein Claudio , Sauter Craig S. , Copelan Edward A. , Majhail Navneet S.
Published: June 2023

Tacrolimus (Tac)/methotrexate (MTX) is standard graft-versus-host disease (GVHD) prophylaxis; however, is associated with several toxicities. Tac, reduced-dose MTX (mini-MTX), and mycophenolate mofetil (MMF) have been used but never compared with standard MTX. We performed a randomized trial comparing Tac/MTX (full-MTX) with Tac/mini-MTX/MMF (mini-MTX/MMF) for GVHD prevention after allogeneic hematopoietic cell transplantation (HCT). Patients (pts) receiving first myeloablative HCT using an 8/8 HLA-matched donor were eligible. Primary end points were incidence of acute GVHD (aGVHD), mucositis, and engraftment. Secondary end points included chronic GVHD (cGVHD), organ toxicity, infection, relapse, nonrelapse mortality (NRM), and overall survival (OS). Ninety-six pts were randomly assigned to full-MTX (N = 49) or mini-MTX (N = 47). The majority (86%) used bone marrow grafts. There was no significant difference in grade 2-4 aGVHD (28% mini-MTX/MMF vs 27% full-MTX; P = .41); however higher incidence of grade 3-4 aGVHD (13% vs 4%; P = .07) with mini-MTX/MMF. Pts receiving mini-MTX/MMF had lower grade 3 or 4 mucositis and faster engraftment. There were no differences in moderate-to-severe cGVHD at 1 year or infections. Pts receiving mini-MTX/MMF experienced less nephrotoxicity and respiratory failure. There was no difference in the 1-year relapse (19% vs 21%; P = .89) and OS (72% vs 71%; P = .08), and mini-MTX/MMF was associated with lower but nonsignificant NRM (11% vs 22%; P = .06). Compared with full-MTX, mini-MTX/MMF was associated with no difference in grade 2-4 aGVHD and a more favorable toxicity profile. The higher severe aGVHD warrants further study to optimize this regimen. The trial was registered at www.clinicaltrials.gov as #NCT01951885.
Mini-percutaneous nephrolithotomy versus Standard percutaneous nephrolithotomy: outcome and complications
Authors: Refaat Hesham M. , Hassan Mohammed , Salem Tarek , Zaza Mohammed
Published: June 2023

Background

Renal stones are a prevalent urological disorder with various treatment options, including minimally invasive techniques such as Standard-PCNL (S-PCNL) and Mini-percutaneous nephrolithotomy (M-PCNL). This study aims to compare the efficacy and safety outcomes of M-PCNL and S-PCNL for managing renal calculi.

Methods

This randomized study enrolled 60 patients with renal stones, comparing the efficacy and safety of M-PCNL (Group A) and S-PCNL (Group B) procedures. Preoperative assessments, surgical procedures, and postoperative care were conducted, and outcomes such as operating time, stone clearance, analgesic requirement, and hospital stay were evaluated. Data analysis was performed using SPSS software, with comparisons between groups conducted using the Chi-square test and Studentttest.

Results

M-PCNL had a longer operation time (133.73 ± 29.18 min) than S-PCNL (48.6 ± 17.88 min,p = 0.009) but a lower mean drop in hemoglobin levels (0.14 ± 0.01 g/dL vs. 0.82 ± 0.05 g/dL,p = 0.032). The success rates (stone-free rate) were significantly different, with 100% in the M-PCNL group and 86.7% in the S-PCNL group (p = 0.040). Complications were generally fewer in the M-PCNL group, including postoperative fever in 2 cases (M-PCNL) vs. 8 cases (S-PCNL) and mild collection in 4 cases (M-PCNL) vs. 26 cases (S-PCNL).

Conclusions

M-PCNL is an effective and safer method for managing renal calculi smaller than 3 cm, offering a higher stone-free rate, lower postoperative pain, and shorter hospital stays compared to S-PCNL. Despite longer operation times due to stone fragmentation, M-PCNL has fewer complications, including lower bleeding rates, hemoglobin drop, and leakage, and can be performed using an ureteroscope when a miniperc scope is unavailable.
Fast and accurate genome-wide predictions and structural modeling of protein–protein interactions using Galaxy
Authors: Guerler Aysam , Baker Dannon , van den Beek Marius , Gruening Bjoern , Bouvier Dave , Coraor Nate , Shank Stephen D. , Zehr Jordan D. , Schatz Michael C. , Nekrutenko Anton
Published: June 2023

Background

Protein–protein interactions play a crucial role in almost all cellular processes. Identifying interacting proteins reveals insight into living organisms and yields novel drug targets for disease treatment. Here, we present a publicly available, automated pipeline to predict genome-wide protein–protein interactions and produce high-quality multimeric structural models.

Results

Application of our method to the Human and Yeast genomes yield protein–protein interaction networks similar in quality to common experimental methods. We identified and modeled Human proteins likely to interact with the papain-like protease of SARS-CoV2’s non-structural protein 3. We also produced models of SARS-CoV2’s spike protein (S) interacting with myelin-oligodendrocyte glycoprotein receptor and dipeptidyl peptidase-4.

Conclusions

The presented method is capable of confidently identifying interactions while providing high-quality multimeric structural models for experimental validation. The interactome modeling pipeline is available at usegalaxy.org and usegalaxy.eu.
Genome-wide identification and immune response analysis of mitogen-activated protein kinase cascades in tea geometrid, Ectropis grisescens Warren (Geometridae, Lepidoptera)
Authors: Wu Xiaozhu , Zhou Chenghua , Li Xiaofang , Lin Jingyi , Aguila Luis Carlos Ramos , Wen Feng , Wang Liande
Published: June 2023

Background

Tea geometrid Ectropis grisescens (Geometridae: Lepidoptera), is one of the most destructive defoliators in tea plantations in China. The MAPK cascade is known to be an evolutionarily conserved signaling module, acting as pivotal cores of host–pathogen interactions. Although the chromosome-level reference genome of E. grisescens was published, the whole MAPK cascade gene family has not been fully identified yet, especially the expression patterns of MAPK cascade gene family members upon an ecological biopesticide, Metarhizium anisopliae, remains to be understood.

Results

In this study, we have identified 19 MAPK cascade gene family members in E. grisescens, including 5 MAPKs, 4 MAP2Ks, 8 MAP3Ks, and 2 MAP4Ks. The molecular evolution characteristics of the whole Eg-MAPK cascade gene family, including gene structures, protein structural organization, chromosomal localization, orthologs construction and gene duplication, were systematically investigated. Our results showed that the members of Eg-MAPK cascade gene family were unevenly distributed in 13 chromosomes, and the clustered members in each group shared similar structures of the genes and proteins. Gene expression data revealed that MAPK cascade genes were expressed in all four developmental stages of E. grisescens and were fairly and evenly distributed in four different larva tissues. Importantly, most of the MAPK cascade genes were induced or constitutively expressed upon M. anisopliae infection.

Conclusions

In summary, the present study was one of few studies on MAPK cascade gene in E. grisescens. The characterization and expression profiles of Eg-MAPK cascades genes might help develop new ecofriendly biological insecticides to protect tea trees.
PagMYB151 facilitates proline accumulation to enhance salt tolerance of poplar
Authors: Hu Jia , Zou Shengqiang , Huang Juanjuan , Huan Xuhui , Jin Xia , Zhou Lieding , Zhao Kai , Han Youzhi , Wang Shengji
Published: June 2023

Poplar is one of the main urban and rural greening and shade tree species in the northern hemisphere, but its growth and development is always restricted by salt stress. R2R3-MYB transcription factor family is commonly involved in many biological processes during plant growth and stress endurance. In this study, PagMYB151 (Potri.014G035100) one of R2R3-MYB members related to salt stress and expressed in both nucleus and cell membrane was cloned from Populus alba × P. glandulosa to perfect the salt tolerance mechanism. Morphological and physiological indexes regulated by PagMYB151 were detected using the PagMYB151 overexpression (OX) and RNA interference (RNAi) transgenic poplar lines. Under salt stress conditions, compared with RNAi and the non-transgenic wild-type (WT) plants, the plant height, both aboveground and underground part fresh weight of OX was significantly increased. In addition, OX has a longer and finer root structure and a larger root surface area. The root activity of OX was also enhanced, which was significantly different from RNAi but not from WT under salt treatment. Under normal conditions, the stomatal aperture of OX was larger than WT, whereas this phenotype was not obvious after salt stress treatment. In terms of physiological indices, OX enhanced the accumulation of proline but reduced the toxicity of malondialdehyde to plants under salt stress. Combing with the transcriptome sequencing data, 6 transcription factors induced by salt stress and co-expressed with PagMYB151 were identified that may cooperate with PagMYB151 to function in salt stress responding process. This study provides a basis for further exploring the molecular mechanism of poplar PagMYB151 transcription factor under abiotic stress.
Unsolved mystery of Fas: mononuclear cells may have trouble dying in patients with Sjögren’s syndrome
Authors: Lindrova Irena , Kolackova Martina , Svadlakova Tereza , Vankova Radka , Chmelarova Marcela , Rosecka Michaela , Jozifkova Eva , Sembera Martin , Krejsek Jan , Slezak Radovan
Published: June 2023

Background

Patients with Sjögren’s syndrome, like other patients with autoimmune disorders, display dysregulation in the function of their immune system. Fas and Fas Ligand (FasL) are among the dysregulated proteins.

Methods

We studied Fas and FasL on IL-2Rα+ cells and in serum of patients with Sjögren’s syndrome (n = 16) and healthy individuals (n = 16); both from same ethnic and geographical background. We used flow cytometry and enzyme-linked immunosorbent for this purpose. We also measured the expression of Bcl-2 and Bax by reverse transcription quantitative real-time PCR (RT-qPCR) and percentage of apoptotic and dead cells using Annexin V and 7-AAD staining in lymphocytes.

Results

FasL was increased in patients’ T and B cells while Fas was increased in patients’ monocytes, T and B cells. No signs of increased apoptosis were found. sFas and sFasL in patients’ serum were increased, although the increase in sFasL was not significant. We suspect an effect of non-steroidal anti-inflammatory therapy on B cells, explaining the decrease of the percentage Fas+ B cells found within our samples. In healthy individuals, there was a noticeable pattern in the expression of FasL which mutually correlated to populations of mononuclear cells; this correlation was absent in the patients with Sjögren’s syndrome.

Conclusions

Mononuclear cells expressing IL-2Rα+ had upregulated Fas in Sjögren’s syndrome. However, the rate of apoptosis based on Annexin V staining and the Bcl-2/Bax expression was not observed in mononuclear cells. We suspect a functional role of abnormal levels of Fas and FasL which has not been cleared yet.
Data quality in an HIV vaccine efficacy clinical trial in South Africa: through natural disasters and with discipline
Authors: Laher Fatima , Malahleha Mookho , Ramirez Shelly , Brumskine William , Otwombe Kennedy , Moodie Zoe , Allen Mary
Published: June 2023

Background

To produce quality data that informs valid clinical trial results and withstands regulatory inspection, trial sites should adhere to many complex and dynamic requirements. Understanding non-conformance to requirements informs the emerging field of improvement science. We describe protocol deviations in South Africa’s largest HIV vaccine efficacy trial.

Methods

We analysed data from the HVTN 702 trial using mixed methods. We obtained descriptive statistics, from protocol deviation case report forms collected from 2016–2022, of deviation by participant, trial site, and time to site awareness. We thematically analysed text narratives of deviation descriptions, corrective and preventive actions, generating categories, codes and themes which emerged from the data.

Results

For 5407 enrollments, 4074 protocol deviations were reported (75 [95% CI: 73.0–77.6] deviations per 100 enrolments). There was a median of 1 protocol deviation per participant (IQR 1–2). Median time from deviation to site awareness was 31 days (IQR 0–146). The most common category of deviation type was omitted data and/or procedures (69%), and 54% of these omissions were stated to have arisen because of the national lockdown at the beginning of the COVID-19 pandemic. The ratio of protocol deviations to cumulative enrolments was highest in the year 2020 (0.34). Major themes of deviations were: COVID-19 and climate disasters giving rise to deviation trends, subroutines introducing an opportunity for deviation, and document fragmentation (such as requirements dispersed across multiple guidance documents) as an obstacle. Preventive action categories were: no preventive measures; discipline, training and/or awareness; quality review, checking and verifying and changing the process and/or implementation tools. Major themes of preventive actions were that systems-based actions are unusual, with people-based actions dominating, and that root cause analysis was rarely mentioned.

Conclusions

In the age of infectious and climate disaster risks, trials may benefit from simple study designs and trial-related documents. To optimise protocol adherence, sponsors and sites should consider ongoing training, and routinely review deviation reports with a view to adjusting processes. These data quality lessons may inform future trial design, training and implementation.

Trial registration

HVTN 702 was registered with the South African National Clinical Trials Register (DOH-27–0916-5327) and ClinicalTrials.gov (NCT02968849).