bluuebunny/crossref_metadata_2025 huggingface dataset:
An
Azospirillum brasilense
chemoreceptor that mediates nitrate chemotaxis has conditional roles in the colonization of plant roots
Authors: Ganusova Elena E. , Russell Matthew H. , Patel Siddhi , Seats Terry , Alexandre Gladys
Published: May 2024

Motile plant-associated bacteria use chemotaxis and dedicated chemoreceptors to navigate gradients in their surroundings and to colonize host plant surfaces. Here, we characterize a chemoreceptor that we named Tlp2 in the soil alphaproteobacterium
Azospirillum brasilense
. We show that the Tlp2 ligand-binding domain is related to the 4-helix bundle family and is conserved in chemoreceptors found in the genomes of many soil- and sediment-dwelling alphaproteobacteria. The promoter of
tlp2
is regulated in an NtrC- and RpoN-dependent manner and is most upregulated under conditions of nitrogen fixation or in the presence of nitrate. Using fluorescently tagged Tlp2 (Tlp2-YFP), we show that this chemoreceptor is present in low abundance in chemotaxis-signaling clusters and is prone to degradation. We also obtained evidence that the presence of ammonium rapidly disrupts Tlp2-YFP localization. Behavioral experiments using a strain lacking Tlp2 and variants of Tlp2 lacking conserved arginine residues suggest that Tlp2 mediates chemotaxis in gradients of nitrate and nitrite, with the R159 residue being essential for Tlp2 function. We also provide evidence that Tlp2 is essential for root surface colonization of some plants (teff, red clover, and cowpea) but not others (wheat, sorghum, alfalfa, and pea). These results highlight the selective role of nitrate sensing and chemotaxis in plant root surface colonization and illustrate the relative contribution of chemoreceptors to chemotaxis and root surface colonization.

IMPORTANCE

Bacterial chemotaxis mediates host-microbe associations, including the association of beneficial bacteria with the roots of host plants. Dedicated chemoreceptors specify sensory preferences during chemotaxis. Here, we show that a chemoreceptor mediating chemotaxis to nitrate is important in the beneficial soil bacterium colonization of some but not all plant hosts tested. Nitrate is the preferred nitrogen source for plant nutrition, and plants sense and tightly control nitrate transport, resulting in varying nitrate uptake rates depending on the plant and its physiological state. Nitrate is thus a limiting nutrient in the rhizosphere. Chemotaxis and dedicated chemoreceptors for nitrate likely provide motile bacteria with a competitive advantage to access this nutrient in the rhizosphere.
Immune restoration by TIGIT blockade is insufficient to control chronic SIV infection
Authors: Webb Gabriela M. , Pessoa Cleiton T. , McCullen Allyson J. , Hwang Joseph M. , Humkey Matthew C. , Thormin-Odum Raymond , Kukula Kaitlyn A. , Smedley Jeremy , Fischer Miranda , Sciurba Joseph , Bochart Rachele M. , Shriver-Munsch Christine , Ndhlovu Lishomwa C. , Sacha Jonah B.
Published: May 2024

TIGIT is a negative immune checkpoint receptor associated with T cell exhaustion in cancer and HIV. TIGIT upregulation in virus-specific CD8
+
T cells and NK cells during HIV/SIV infection results in dysfunctional effector capabilities.
In vitro
studies targeting TIGIT on CD8
+
T cells suggest TIGIT blockade as a viable strategy to restore SIV-specific T cell responses. Here, we extend these studies
in vivo
using TIGIT blockage in nonhuman primates in an effort to reverse T cell and NK cell exhaustion in the setting of SIV infection. We demonstrate that
in vivo
administration of a humanized anti-TIGIT monoclonal antibody (mAb) is well tolerated in both cynomolgus macaques and rhesus macaques. Despite sustained plasma concentrations of anti-TIGIT mAb, we observed no consistent improvement in NK or T cell cytolytic capacity. TIGIT blockade minimally enhanced T cell proliferation and virus-specific T cell responses in both magnitude and breadth though plasma viral loads in treated animals remained stable indicating that anti-TIGIT mAb treatment alone was insufficient to increase anti-SIV CD8
+
T cell function. The enhancement of virus-specific T cell proliferative responses observed
in vitro
with single or dual blockade of TIGIT and/or PD-1 highlights TIGIT as a potential target to reverse T cell dysfunction. Our studies, however, reveal that targeting the TIGIT pathway alone may be insufficient in the setting of viremia and that combining immune checkpoint blockade with other immunotherapeutics may be a future path forward for improved viral control or elimination of HIV.

IMPORTANCE

Upregulation of the immune checkpoint receptor TIGIT is associated with HIV-mediated T cell dysfunction and correlates with HIV disease progression. Compelling evidence exists for targeting immune checkpoint receptor pathways that would potentially enhance immunity and refocus effector cell efforts toward viral clearance. In this report, we investigate TIGIT blockade as an immunotherapeutic approach to reverse immune exhaustion during chronic SIV/SHIV infection in a nonhuman primate model of HIV infection. We show that interfering with the TIGIT signaling axis alone is insufficient to improve viral control despite modest improvement in T cell immunity. Our data substantiate the use of targeting multiple immune checkpoint receptors to promote synergy and ultimately eliminate HIV-infected cells.
The 12 dimensions of health impacts of war (the 12-D framework): a novel framework to conceptualise impacts of war on social and environmental determinants of health and public health
Authors: Jayasinghe Saroj
Published: May 2024

Global rates of armed conflicts have shown an alarming increase since 2008. These conflicts have devastating and long-term cumulative impacts on health. The overriding aim in these conflicts is to achieve military or political goals by harming human life, which is the antithesis of the moral underpinnings of the health professions. However, the profession has rarely taken on a global advocacy role to prevent and eliminate conflicts and wars. To assume such a role, the health profession needs to be aware of the extensive and multiple impacts that wars have on population health. To facilitate this discourse, the author proposes a novel framework called ‘The Twelve Dimensions of Health Impacts of War’ (or the 12-D framework). The framework is based on the concepts of social and environmental determinants of population health. It has 12 interconnected ‘dimensions’ beginning with the letter D, capturing the adverse impacts on health (n=5), its social (n=4) and environmental determinants (n=3). For health, the indices are Deaths, Disabilities, Diseases, Dependency and Deformities. For social determinants of health, there are Disparities in socioeconomic status, Displacements of populations, Disruptions to the social fabric and Development reversals. For environmental determinants, there is Destruction of infrastructure, Devastation of the environment and Depletion of natural resources. A relatively simple framework could help researchers and lay public to understand the magnitude and quantify the widespread health, social and environmental impacts of war, comprehensively. Further validation and development of this framework are necessary to establish it as a universal metric for quantifying the horrific impacts of war on the planet and garner support for initiatives to promote global peace.
Patterns of cytotoxic T-cell densities in immunogenic endometrial cancers reveal a potential mechanism for differences in immunotherapy efficacy
Authors: Ryan Neil , Glaire Mark , Walker Thomas , ter Haar Natalja , Ijsselsteijn Marieke , Bolton James , de Miranda Noel , Evans Gareth , Church David N , Bosse Tjalling , Crosbie Emma
Published: May 2024

Objective

To explore the impact of molecular subtype in endometrial cancer (EC) on CD8+T cell densities. Furthermore, this work will test the assumption that all mismatch repair deficient (MMRd) tumours are immunologically similar which would enable current trial data to be generalised to all MMRd ECs.

Methods and analysis

All tumours were characterised into the four clinical molecular subtypes. For analysis, theTP53mutant and no-specific molecular profile tumours were grouped together and described as the low mutational burden (LMB) cohort. CD8+T cell counts were taken from four regions of interest which sampled the tumour-stromal interface and the tumour core. CD8+T cell counts were analysed as mean averages.

Results

In total, 607 ECs contributed to the analysis. CD8+T cell counts in confirmed Lynch syndrome (LS) ECs were significantly higher thanMLH1-methylated ECs in all tumour locations excluding the tumour stroma. Confirmed LS and path_POLEECs had significantly higher CD8+T cell counts across all tumour locations when compared with LMB ECs. There were limited significant differences in CD8+T cell counts between path_POLEversus confirmed LS ECs. There was no significant difference in the CD8+T cells counts and gene (MLH1,MSH2,MSH6,PMS2) in which the LS pathogenic variant was found; however, this analysis was limited by small numbers.

Conclusion

These data indicate that CD8+T cell numbers and distribution is not equal betweenMLH1-methylated and confirmed LS ECs. This is relevant when interpreting current trial data looking to the application of checkpoint inhibition treatments in MMRd cancers.
General practitioner workforce sustainability to maximise effective and equitable patient care: a realist review protocol
Authors: Park Sophie , Owen-Boukra Emily , Burford Bryan , Cohen Tanya , Duddy Claire , Dunn Harry , Fadia Vacha , Goodman Claire , Henry Cecily , Lamb Elizabeth I , Ogden Margaret , Rapley Tim , Rees Eliot , Vance Gillian , Wong Geoff
Published: May 2024

Introduction

There are not enough general practitioners (GPs) in the UK National Health Service. This problem is worse in areas of the country where poverty and underinvestment in health and social care mean patients experience poorer health compared with wealthier regions. Encouraging more doctors to choose and continue in a GP career is a government priority. This review will examine which aspects of the healthcare system affect GP workforce sustainability, how, why and for whom.

Methods and analysis

A realist review is a theory-driven interpretive approach to evidence synthesis, that brings together qualitative, quantitative, mixed-methods research and grey literature. We will use a realist approach to synthesise data from the available published literature to refine an evidence-based programme theory that will identify the important contextual factors and underlying mechanisms that underpin observed outcomes relating to GP workforce sustainability. Our review will follow Pawson’s five iterative stages: (1) finding existing theories, (2) searching for evidence, (3) article selection, (4) data extraction and (5) synthesising evidence and drawing conclusions. We will work closely with key stakeholders and embed patient and public involvement throughout the review process to refine the focus of the review and enhance the impact and relevance of our research.

Ethics and dissemination

This review does not require formal ethical approval as it draws on secondary data from published articles and grey literature. Findings will be disseminated through multiple channels, including publication in peer-reviewed journals, at national and international conferences, and other digital scholarly communication tools such as video summaries, X and blog posts.

PROSPERO registration number

CRD42023395583.
Optimising personal continuity for older patients in general practice: a cluster randomised stepped wedge pragmatic trial
Authors: Groot Lex , Schers Henk , Burgers J S , Smalbrugge Martin , Uijen Annemarie A , Hoogland Jeroen , van der Horst Henriëtte E , Maarsingh Otto R
Published: May 2024

Aim

To evaluate the effectiveness, feasibility and acceptability of a multicomponent intervention for improving personal continuity for older patients in general practice.

Design

A cluster randomised three-wedged, pragmatic trial during 18 months.

Setting

32 general practices in the Netherlands.

Participants

221 general practitioners (GPs), practice assistants and other practice staff were included. Practices were instructed to include a random sample of 1050 patients aged 65 or older at baseline and 12-month follow-up.

Intervention

The intervention took place at practice level and included opTimise persOnal cOntinuity for oLder (TOOL)-kit: a toolbox containing 34 strategies to improve personal continuity.

Outcomes

Data were collected at baseline and at six 3-monthly follow-up measurements. Primary outcome measure was experienced continuity of care at the patient level measured by the Nijmegen Continuity Questionnaire (NCQ) with subscales for personal continuity (GP knows me and GP shows commitment) and team/cross-boundary continuity at 12-month follow-up. Secondary outcomes were measured in GPs, practice assistants and other practice staff and included work stress and satisfaction and perceived level of personal continuity. In addition, a process evaluation was undertaken among GPs, practice assistants and other practice staff to assess the acceptability and feasibility of the intervention.

Results

No significant effect of the intervention was observed on NCQ subscales GP knows me (adjusted mean difference: 0.05 (95% CI −0.05 to 0.15), p=0.383), GP shows commitment (0.03 (95% CI −0.08 to 0.14), p=0.668) and team/cross-boundary (0.01 (95% CI −0.06 to 0.08), p=0.911). All secondary outcomes did not change significantly during follow-up. Process evaluation among GPs, practice assistants and other practice staff showed adequate acceptability of the intervention and partial implementation due to the COVID-19 pandemic and a high perceived workload.

Conclusion

Although participants viewed TOOL-kit as a practical and accessible toolbox, it did not improve personal continuity as measured with the NCQ. The absence of an effect may be explained by the incomplete implementation of TOOL-kit into practice and the choice of general outcome measures instead of outcomes more specific for the intervention.

Trial registration number

International Clinical Trials registry Platform (ICTRP), trial NL8132 (URL: ICTRP Search Portal (who.int).
Lived experiences of mothers with postnatal anxiety: a qualitative phenomenology study from Pakistan
Authors: Saeed Qamar , Shafique Kashif , Chaudhry Nasim
Published: May 2024

Objective

The prevalence of postnatal anxiety is high among women during the first year of childbirth globally. Rates are higher in low and middle-income countries (LMICs), that is, 24%. Existing literature on maternal mood and its impact on child development has largely focused on postnatal depression. Postnatal anxiety has been recognised to have significant independent effects similar to those of postnatal depression, including negative effects on various aspects of maternal well-being including quality of life, parent–child interaction and child development. The evidence exploring lived experiences of postnatal anxiety is limited from LMICs. This study explored the lived experiences of anxiety in postnatal mothers in Pakistan.

Design

A phenomenological approach was used for this qualitative study. The audio-recorded interviews were transcribed and analysed using the process of thematic analysis.

Settings

The study was conducted in two community settings in Karachi, Pakistan; the Bin Qasim and Gadap town.

Participants

Women who were 18 years of age or older, had a live childbirth within the previous 12 months and had a score of 10 or higher on the Generalised Anxiety Disorder-7.

Results

In-depth, one-to-one interviews were conducted with 10 participants. The qualitative data comprised of three themes.Theme one: Factors perceived to be associated with postnatal anxiety, Theme two: The perceived impact of postnatal anxietyandTheme three: Support needs. The first theme was further subdivided into two subthemes, that is,Mothers’ perception of navigating domestic responsibilitiesandsociocultural norms of motherhood and financial constraints.

Conclusion

Despite the high prevalence of postnatal anxiety in LMICs there is not any published evidence on exploring this phenomenon through in-depth research in Pakistan. Understanding the lived experiences will help health professionals to identify women at risk of developing postnatal anxiety and to develop effective culturally appropriate interventions for women with anxiety during this postnatal period.
Protocol for cost-effectiveness analysis of a randomised trial of mHealth coaching (Bump2Baby and Me) compared with usual care for healthy gestational weight gain and postnatal outcomes in at-risk women and their offspring in the UK, Australia, Ireland and Spain
Authors: Nørmark Laura Pirhonen , McAuliffe Fionnuala , Maindal Helle Terkildsen , O'Reilly Sharleen , Davies Anna , Burden Christy , Skinner Timothy C , Vrangbæk Karsten , Callander Emily
Published: May 2024

Introduction

Gestational diabetes mellitus and overweight are associated with an increased likelihood of complications during birth and for the newborn baby. These complications lead to increased immediate and long-term healthcare costs as well as reduced health and well-being in women and infants. This protocol presents the health economic evaluation to investigate the cost-effectiveness of Bump2Baby and Me (B2B&Me), which is a health coaching intervention delivered via smartphone to women at risk of gestational diabetes.

Methods and analysis

Using data from the B2B&Me randomised controlled trial, this economic evaluation compares costs and health effects between the intervention and control group as an incremental cost-effectiveness ratio. Direct healthcare costs, costs of pharmaceuticals and intervention costs will be included in the analysis, body weight and quality-adjusted life-years for the mother will serve as the effect outcomes. To investigate the long-term cost-effectiveness of the trial, a Markov model will be employed. Deterministic and probabilistic sensitivity analysis will be employed.

Ethics and dissemination

The National Maternity Hospital Human Research and Ethics Committee was the primary approval site (EC18.2020) with approvals from University College Dublin HREC-Sciences (LS-E-20-150-OReilly), Junta de Andalucia CEIM/CEI Provincial de Granada (2087-M1-22), Monash Health HREC (RES-20-0000-892A) and National Health Service Health Research Authority and Health and Care Research Wales (HCRW) (21/WA/0022). The results from the analysis will be disseminated in scientific papers, through conference presentations and through different channels for communication within the project.

Trial registration number

ACTRN12620001240932.
Coproducing a physical activity referral scheme in Germany: a qualitative analysis of stakeholder experiences
Authors: Klamroth Sarah , Mino Eriselda , Naber Inga , Weissenfels Anja , Geidl Wolfgang , Gelius Peter , Abu-Omar Karim , Pfeifer Klaus
Published: May 2024

Objectives

This study evaluated stakeholders’ experiences of participating in a coproduction process to develop a physical activity referral scheme (PARS) in the German healthcare system. The focus was on examining facilitators and challenges, along with gathering insights on potential modifications to the joint development process, all from the viewpoint of stakeholders.

Design

This qualitative study employed one-to-one semi-structured interviews, and the findings were analysed using summarising qualitative content analysis.

Setting

The study focused on the German healthcare system.

Participants

Seven stakeholders from the coproduction process were purposefully selected for interviews using maximum variation sampling. The interviewees represented different sectors (physician associations, physical activity professionals’ associations, health insurance companies and patient organisations), various positions within their organisations, and different levels of attendance during the coproduction process.

Results

In almost all interviews, the following factors were highlighted as facilitators of the development process: coproduction approach, process of coproduction, multi-sector stakeholder group, possibility of active participation, coordinating role of researchers, communication, atmosphere and interaction. In contrast, differences in roles and hierarchy, merging of different perspectives, clarification of intervention costs, and competition and conflicting interests were pointed out as challenges. Only a few suggestions regarding adaptations in terms of group composition and cooperation among stakeholders were mentioned.

Conclusions

Stakeholder experiences with the joint development process were predominantly positive, indicating that coproduction is a beneficial approach for the development of PARS intended for integration into healthcare systems. The effective management of power differences among stakeholders is intricately tied to the coproduction method; therefore, it should be selected carefully. The research team plays a pivotal role in coordinating and negotiating the process, and the team should be equipped with a diverse set of skills and knowledge, particularly to understand the intricacies of the healthcare system where the PARS is intended for implementation.

Trial registration number

NCT04947787.
Care for the caregiver: an exploration of caregiver burden of children with chronic medical conditions at a tertiary care hospital in Karachi, Pakistan – a mixed-methods study
Authors: Saeed Sana , Malik Marib Ghulam Rasool , Khan Maryam Hameed , Malik Shahzil Abdur Rehman , Aziz Bisma
Published: May 2024

Objectives

Caregiver burden often goes unrecognised and can substantially affect caregivers’ physical, psychological and financial well-being, thereby impacting quality of care. This study investigates burden among caregivers of children with chronic medical conditions in a tertiary care hospital in Pakistan. The study aims to assess the extent of burden, explore influencing factors and recommendations for interventions.

Design

Mixed-methods study, comprising of an in-person paper-based survey, employing the Zarit Burden Interview scale to assess burden scores. Qualitative component included thematic analysis of semi-structured in-depth interviews with caregivers.

Participants

383 caregivers of children admitted to the inpatient paediatric services at our tertiary care centre were surveyed. In-depth interviews were conducted with 19 caregivers.

Results

The survey revealed a mean burden score of 35.35±15.14, with nearly half of the participants (46%, n=177) experiencing mild burden, while 37% (n=140) reporting moderate-to-severe burden. The most common diagnosis was cancer (24%, n=92), while the highest burden (42.97±15.47) was noted for congenital cardiac disease. Greater burden was significantly associated with lower caregiver education, young age of the child at diagnosis and increased number of hospital visits (p<0.05). Caregivers highlighted financial strain, psychosocial effects and impact on lifestyle and relationships as key challenges. They emphasised the need for improved medical coordination, financial support and enhanced hospital services.

Conclusions

The study elucidates the multifaceted nature of caregiver burden in the context of paediatric chronic illnesses in Pakistan. Interventions should emphasise financial aid, educational support and development of system-level changes to improve access to resources and medical care coordination. These insights call for policy and practice integration to support caregivers effectively.
Exploration of registration and the risk of bias in acupuncture randomised controlled trials: a systematic review protocol
Authors: Duan Yuting , Deng Yuening , Tang Binbin , Xu Zhirui , Ye Xiaolin , Lu Manyi , Liu Shujuan , Xiong Linghui , Zhu Weifeng , Yu Lin , Zhao Pinge
Published: May 2024

Background

Randomised controlled trials (RCTs) are the predominant type in acupuncture clinical research, and the publications have increased rapidly in recent years, but there is a prevalence of the high risk of bias and poor methodological design in acupuncture RCTs. Clinical trial registration can improve the transparency and credibility of studies by disclosing key information in advance. However, the registration in acupuncture RCTs is not satisfactory, as there is widespread of the under-registration, inconsistency with published studies and insufficient disclosure of key methodological information. Whether registration can reduce the risk of bias in acupuncture RCTs and improve data transparency has not been fully explored. Therefore, we constructed this study to investigate the association between registration and risk of bias and data sharing level in acupuncture RCTs.

Methods

Seven databases including MEDLINE, EMBASE, CENTRAL, CBM, CNKI, Wanfang and VIP databases will be systematically searched between 1 January 2014 and 31 March 2024, for acupuncture RCTs. Two reviewers will independently extract data using a predefined standardised format and perform secondary validation. The characteristics and data sharing level of the included studies will be summarised. The risk of bias of included RCTs will be assessed by the revised Cochrane risk-of-bias tool for randomised trials. The risk of bias and registration in acupuncture RCTs will be analysed by logistic or quantile regression analyses (depending on the number of minimum events). The data sharing level and registration will be analysed by quantile regression analyses.

Ethics and dissemination

As the systematic review aims to consolidate info from published sources, ethical approval is not necessary for this study. The study’s findings will be submitted to a peer-reviewed academic journal and disseminated via conference presentations. This protocol has been registered in Open Science Framework Registries.
Cross-sectional examination of commercial milk formula industry funding of international, regional and national healthcare professional associations: protocol
Authors: Henke-Ciążyńska Katarzyna , Fober Iwo , Munblit Daniel , Fabbri Alice , Grundy Quinn , Bero Lisa , Boyle Robert J , Helfer Bartosz
Published: May 2024

Introduction

Commercial milk formula manufacturers often emphasise their role in supporting infant and young child nutrition and breastfeeding, but their commercial goals to increase volume and profit margin of formula sales conflict with these declarations. Healthcare professional associations have an important role in healthcare worker education, shaping clinical practice. When healthcare professional associations enter into financial relationships with formula manufacturers, conflicts of interest arise, which may undermine education and practice that promotes optimal infant and young child feeding. The World Health Assembly calls on all parties to avoid such conflicts of interest, but it is uncertain how often this recommendation is followed. This protocol documents a systematic method to identify funding from the commercial milk formula industry among international, regional and national associations of healthcare professionals.

Methods and analysis

Using systematic search strategies in the Gale Directory Library and Google, we will identify international healthcare professional associations relevant to maternal and child health. Data regarding funding relationships with the commercial milk formula industry over the past 24 months will be extracted from the official websites or, in their absence, social media accounts by two independent analysts. The analysis will focus on the presence of conflict of interest or sponsorship policies and type of funding, such as sponsorship or payment for services.

Ethics and dissemination

This study does not require ethical approval and will use data available in the public domain. The results will be disseminated through peer-reviewed journal articles, at conferences and among the healthcare professional associations.
Comorbidities among adult patients with psoriasis in Tianjin: a cross-sectional analysis of the Health Database study
Authors: Zhang Yiming , Guo Yali , Zhang Kaiyue , Fan Liyun , Ma Jingyue , Li Yan , Zhou Quan , Zhao Qian , Hou Shuping , Wang Huiping
Published: May 2024

Objectives

This study aims to examine the prevalence of comorbidities in adult patients with psoriasis and compare them with those in control subjects without psoriasis in Tianjin, China.

Design

The study is a cross-sectionalanalysis.

Participants

The participants were established by identifying all patients (age ≥18 years) who visited hospitals and clinics in Tianjin between 1 January 2016 and 31 October 2019.

Setting

The study group consisted of 20 678 adult patients with psoriasis, and a comparison group was created after 1:1 propensity score matching. Logistic regression analyses were conducted to examine the risk of 22 comorbidities for these two groups.

Results

Patients with psoriasis had a significantly higher prevalence of 11 comorbidities and a lower prevalence of 2 comorbidities within 12 months of follow-up. Our results also showed that the proportion of psoriatic arthritis might account for approximately 2% of all patients with psoriasis. This psoriatic arthritis group had a higher average age and CCI (Charlson Comorbidity Index) index score (2.27 >1.62, p <0.001) than the non-arthritis group.

Conclusions

This study showed that psoriasis in Tianjin is associated with various comorbidities. It also emphasises the importance of clinical treatment in improving therapeutic effects and reducing the burden of psoriasis in China.
Compassionate Communication and Advance Care Planning to improve End-of-life Care in Treatment of Haematological Disease ‘ACT’: Study Protocol for a Cluster-randomized trial
Authors: Borregaard Myrhøj Cæcilie , Clemmensen Stine Novrup , Jarden Mary , Johansen Christoffer , von Heymann Annika
Published: May 2024

Introduction

To support the implementation of advance care planning and serious illness conversations in haematology, a previously developed conversation intervention titled ‘Advance Consultations Concerning your Life and Treatment’ (ACT) was found feasible. This study aims to investigate the effect of ACT on the quality of end-of-life care in patients with haematological malignancy and their informal caregivers.

Methods and analysis

The study is a nationwide 2-arm cluster randomised trial randomising 40 physician–nurse clusters across seven haematological departments in Denmark to provide standard care or ACT intervention. A total of 400 patients with haematological malignancies and their informal caregivers will be included. The ACT intervention includes an ACT conversation that centres on discussing the patient’s prognosis, worries, hopes and preferences for future treatment. The intervention is supported by clinician training and supervision, preparatory materials for patients and informal caregivers, and system changes including dedicated ACT-conversation timeslots and templates for documentation in medical records.

This study includes two primary outcomes: (1) the proportion of patients receiving chemotherapy within the last 30 days of death and (2) patients’ and informal caregivers’ symptoms of anxiety (General Anxiety Disorder-7) at 3 6, 9, 12 and 18 months follow-up. Mixed effects models accounting for clusters will be used.

Ethics and dissemination

The Declaration of Helsinki and the European GDPR regulations as practised in Denmark are followed through all aspects of the study. Findings will be made available to the participants, patient organisations, funding bodies, healthcare professionals and researchers at national and international conferences and through publication in peer-reviewed international journals.

Registration details

The study is registered at ClinicalTrials.gov (NCT05444348). The Regional Ethics Committee of the Capital Region of Denmark (record no: 21067634) has decided that approval is not necessary as per Danish legislation. Study approval has been obtained from The Capital Region of Denmark Data Protection Agency (record no: P-2022-93).

Trial registration number

NCT05444348.
Immunosuppressive therapy in elderly patients with neuromyelitis optica spectrum disorder: a retrospective multicentre study
Authors: Kim Ki Hoon , Chung Yeon Hak , Min Ju-Hong , Han Hee Jo , Kim Seung Woo , Shin Ha Young , Kwon Young Nam , Kim Sung-Min , Lim Young-Min , Kim Hyunjin , Lee Eun-Jae , Jeong Seong Ho , Hyun Jae-Won , Kim Su-Hyun , Kim Ho Jin
Published: May 2024

Background

The risk–benefit relationship of immunosuppressive therapies (ISTs) for elderly patients with neuromyelitis optica spectrum disorder (NMOSD) is not well established. This study aimed to investigate the safety and efficacy of IST in elderly patients with NMOSD.

Methods

This retrospective study analysed IST efficacy and safety in 101 patients with aquaporin-4 antibody-positive NMOSD aged over 65 years, treated for at least 6 months at five Korean referral centres, focusing on relapse rates, infection events and discontinuation due to adverse outcomes.

Results

The mean age at disease onset was 59.8 years, and female-to-male ratio was 4:1. Concomitant comorbidities at NMOSD diagnosis were found in 87 patients (86%). The median Expanded Disability Status Scale score at the initiation of IST was 3.5. The administered ISTs included azathioprine (n=61, 60%), mycophenolate mofetil (MMF) (n=48, 48%) and rituximab (n=41, 41%). Over a median of 5.8 years of IST, 58% of patients were relapse-free. The median annualised relapse rate decreased from 0.76 to 0 (p<0.001), and 81% experienced improved or stabilised disability. Patients treated with rituximab had a higher relapse-free rate than those treated with azathioprine or MMF (p=0.022). During IST, 21 patients experienced 25 severe infection events (SIEs) over the age of 65 years, and 3 died from pneumonia. 14 patients (14%) experienced 17 adverse events that led to switching or discontinuation of IST. When comparing the incidence rates of SIEs and adverse events, no differences were observed among patients receiving azathioprine, MMF and rituximab.

Conclusion

In elderly patients with NMOSD, IST offers potential benefits in reducing relapse rates alongside a tolerable risk of adverse events.
Cost of sterility: probe covers should not be mandated for single-shot peripheral nerve blocks
Authors: Gerner Philipp , Graff Veena , Herman Melody , Stone Alexander B
Published: May 2024

Ultrasound guidance has become ubiquitous with regional anesthesia, but little consistency exists on necessary ultrasound probe hygiene and sterility barriers. Fear of possible infection has led to calls for universal use of sterile ultrasound probe covers. Available data seems to suggest that single-shot peripheral nerve blocks have a low infectious risk. The widespread use of single-use disposable probe covers would carry an associated cost, increased environmental impact, and little evidence to suggest that they are effective at preventing infection if proper technique is used. While various parties have labeled single-shot nerve blocks as a sterile procedure, in practice, it is a clean technique. In this article, we argue that mandating the use of probe covers is unnecessary and that it should be left to the anesthesiologist to determine what type of anti-infection equipment is necessary for single-shot nerve blocks based on their practice situation and expertize.
Hospice care and the value of a statistical life year (VSLY)
Authors: Sweis Nadia J
Published: May 2024

Introduction

In this study, we aim to refine the value of a statistical life (VSL) framework to align with hospice care’s focus on quality over quantity of life, recognising the necessity for age-sensitive economic assessments.

Methods

We developed an adapted VSL model that incorporates patient and family preferences, which may guide resource distribution and policymaking in end-of-life care. Methods include a multidisciplinary analysis that merges economic and humanistic perspectives to advocate for policies that support adequate funding and compassionate care.

Results

Results indicate that our adjusted VSL model promotes a more equitable assessment of hospice care, advocating for enhanced patient dignity and comfort.

Conclusions

This paper presents a novel, ethically and economically balanced approach to evaluating hospice care, emphasising dignity and comfort in terminal care.
Evaluating the effects of red osier dogwood extract and grape pomace on growth performance, plasma biochemistry, intestinal morphology and microbiota, and immune and antioxidant status of broiler chickens challenged with heat stress
Authors: Oretomiloye Fisayo , Adewole Deborah
Published: May 2024

A total of 288 1-day-old Ross 308 broiler chicks were randomly allotted into four dietary treatments: (1) Control (CON; corn–wheat–soybean-based diet), (2) CON + 0.05% bacitracin methylene disalicylate (BMD), (3) CON + 0.3% red osier dogwood extract (ROD), and (4) CON + 2.5% grape pomace (GP) and raised for 28 days. On days 21–27, birds were exposed to either a thermoneutral (TN; 24 ± 1 °C) or heat stress (HS; 32–34 °C for 8 h/day) environment. On day 28, 12 male birds per treatment/temperature group were euthanized for measuring blood and intestinal health parameters. 0.05% BMD and 0.3% ROD inclusion improved (P ≤ 0.05) the average body weight gain and feed conversion ratio, compared to CON. HS reduced ( P ≤ 0.05) average feed intake, bursa and spleen weights, plasma alanine transferase, lipase, and creatinine kinase but increased ( P ≤ 0.05) alanine phosphatase and serum immunoglobulins compared to TN birds. HS further reduced ( P ≤ 0.05) duodenal villus height (VH):crypt depth (CD), jejunal VH, and VH:CD but this was reversed by ROD and GP, and 0.05% BMD and 2.5% GP increased ( P < 0.001) the relative abundance of Blautia and Sellimonas compared to the CON diet. ROD increased ( P = 0.010) the relative abundance of Faecalibacterium compared to the BMD diet. The results suggest that 0.3% ROD extract may function as an alternative to antibiotics in improving broiler growth performance and intestinal health.
Comparison of the economic performance of organic and conventional corn–soybean–winter wheat rotations in southwestern Ontario, Canada
Authors: Yang Xueming , Drury Craig F. , Reynolds W. Daniel , Reeb Mary-Anne
Published: May 2024

The economic viability of using summer-seeded legume cover crops (crimson clover, red clover, and hairy vetch) as a primary nitrogen (N) source for an organic corn ( Zea mays L.)–soybean ( Glycine max (L.) Merr.)–winter wheat ( Triticum aestivum L.) rotation was determined on a sandy loam soil in southwestern Ontario, Canada, by comparing gross profit for organic production (organic sources of N and phosphorus, no herbicides) to conventional production (no cover crops, synthetic fertilizers and herbicides added). Profits were determined for the initial 3-year transition period from conventional to organic production (2015–2017), and for 5 years of certified organic production (2018–2022). During the transition period when conventional crop prices applied to both production systems, organic production profits (CAD $1148–$1869 ha−1 per rotation) were lower than conventional profits (CAD $2126 ha−1 per rotation). During the certified organic period when price premiums were applied, organic soybean and corn profits (CAD $1995–$2274 ha−1 and $2819–$3195 ha−1 per year, respectively) were significantly greater than conventional soybean and corn profits (CAD $536 ha−1 and $1926 per ha−1, respectively). Winter wheat profits were slightly higher for organic production (CAD $426–$825 ha−1 per year) than for conventional production (CAD $371 ha−1 per year). During the certified organic production period, profits from the 3-year rotations were CAD $5533–$6153 ha−1 for organic production, and CAD $2860 ha−1 for conventional production. It was concluded that an organic rotation of corn–soybean–winter wheat/legume cover crop can be economically viable and more profitable than conventional production on sandy loam soil in southwestern Ontario.
(De/Re)-Composition of Data-Parallel Computations via Multi-Dimensional Homomorphisms
Authors: Rasch Ari
Published: May 2024

Data-parallel computations, such as linear algebra routines and stencil computations, constitute one of the most relevant classes in parallel computing, e.g., due to their importance for deep learning. Efficiently de-composing such computations for the memory and core hierarchies of modern architectures and re-composing the computed intermediate results back to the final result—we say
(de/re)-composition
for short—is key to achieve high performance for these computations on, e.g., GPU and CPU. Current high-level approaches to generating data-parallel code are often restricted to a particular subclass of data-parallel computations and architectures (e.g., only linear algebra routines on only GPU or only stencil computations), and/or the approaches rely on a user-guided optimization process for a well-performing (de/re)-composition of computations, which is complex and error prone for the user.

We formally introduce a systematic (de/re)-composition approach, based on the algebraic formalism of Multi-Dimensional Homomorphisms (MDHs). Our approach is designed as general enough to be applicable to a wide range of data-parallel computations and for various kinds of target parallel architectures. To efficiently target the deep and complex memory and core hierarchies of contemporary architectures, we exploit our introduced (de/re)-composition approach for a correct-by-construction, parametrized cache blocking, and parallelization strategy. We show that our approach is powerful enough to express, in the same formalism, the (de/re)-composition strategies of different classes of state-of-the-art approaches (scheduling-based, polyhedral, etc.), and we demonstrate that the parameters of our strategies enable systematically generating code that can be fully automatically optimized (auto-tuned) for the particular target architecture and characteristics of the input and output data (e.g., their sizes and memory layouts). Particularly, our experiments confirm that via auto-tuning, we achieve higher performance than state-of-the-art approaches, including hand-optimized solutions provided by vendors (such as NVIDIA cuBLAS/cuDNN and Intel oneMKL/oneDNN), on real-world datasets and for a variety of data-parallel computations, including linear algebra routines, stencil and quantum chemistry computations, data mining algorithms, and computations that recently gained high attention due to their relevance for deep learning.
A Combinatorial Optimization Framework for Probability-Based Algorithms by Means of Generative Models
Authors: Malagón Mikel , Irurozki Ekhine , Ceberio Josu
Published: May 2024

Probability-based algorithms have proven to be a solid alternative for approaching optimization problems. Nevertheless, in many cases, using probabilistic models that efficiently exploit the characteristics of the problem involves large computational overheads, and therefore, lower complexity models such as those that are univariate are usually employed within approximation algorithms. With the motivation to address such an issue, in this article, we aim to introduce an iterative optimization framework that employs generative models to efficiently estimate the parameters of probability models for optimization problems. This allows the use of complex probabilistic models (or those that are appropriate for each problem) in a way that is feasible to apply them iteratively. Specifically, the framework is composed of three elements: a generative model, a probability model whose probability rule is differentiable, and a loss function. The possibility of modifying any of the three elements of the framework offers the flexibility to design algorithms that best adapt to the problem at hand. Experiments conducted on two case studies reveal that the presented approach has strong performance in terms of objective value and execution time when compared to other probability-based algorithms. Moreover, the experimental analysis demonstrates that the convergence of the algorithms is controllable by adjusting the components of the framework. For the sake of reproducibility, the source code, results, scripts, figures, and other material related to the manuscript are available at
https://github.com/mikelma/nnco_lib
.
The hormonal profile in women using combined monophasic oral contraceptive pills varies across the pill cycle: a temporal analysis of serum endogenous and exogenous hormones using liquid chromatography with tandem mass spectroscopy
Authors: Rodriguez Luis A. , Casey Ellen , Crossley Eric , Williams Noelle , Dhaher Yasin Y.
Published: May 2024

The results from this study have wide-ranging implications for research and treatment in women’s health including considerations in research design and interpretation for studies including women taking oral contraceptives, the potential for more precise and personalized methods of dosing to reduce unwanted side effects and adverse events, and the potential treatment of a variety of disorders ranging from musculoskeletal to neurological with exogenous hormones.
Electromechanical coupling and anatomy of the in vivo gastroduodenal junction
Authors: Simmonds Sam , Matthee Ashton , Dowrick Jarrah M. , Taberner Andrew J. , Du Peng , Angeli-Gordon Timothy R.
Published: May 2024

This study applies electrical mapping, impedance planimetry, and histological techniques to the gastroduodenal junction to elucidate electromechanical coupling in vivo. Contractions of the terminal antrum and pyloric sphincter were associated with gastric slow waves. In the duodenum, bursts of spike activity triggered oscillating contractions. The relative sparsity of myenteric interstitial cells of Cajal in the pylorus, compared with the adjacent antrum and duodenum, is hypothesized to prevent coupling between antral and duodenal slow waves.
Neutrophil reduction attenuates the severity of lung injury in the early phase of pneumococcal pneumonia in mice
Authors: Taenaka Hiroki , Fang Xiaohui , Maishan Mazharul , Trivedi Alpa , Wick Katherine D. , Gotts Jeffrey E. , Martin Thomas R. , Calfee Carolyn S. , Matthay Michael A.
Published: May 2024

Neutrophil accumulation is a key feature of ARDS, but their contribution to the pathogenesis is still uncertain. We investigated the effect of reducing neutrophils in a clinically relevant mouse model of pneumococcal pneumonia treated with antibiotics. When appropriate antibiotics were administered, neutrophil reduction with Ly6G antibody markedly attenuated lung injury and improved oxygenation. In the early phase of bacterial pneumonia, neutrophils contribute to the severity of lung injury, although they also participate in host defense.
Stimulus-specific enhancement in mouse visual cortex requires GABA but not VIP-peptide release from VIP interneurons
Authors: Kaneko Megumi , Hoseini Mahmood S. , Waschek James A. , Stryker Michael P.
Published: May 2024

Many neurons package and release a peptide along with a conventional neurotransmitter. The conventional view is that such peptides exert late, slow effects on plasticity. We studied a form of cortical plasticity that depends on the activity of neurons that express both vasoactive intestinal peptide (VIP) and the inhibitory neurotransmitter GABA. GABA release accounted for their action on plasticity, with no effect of deleting the peptide on this phenomenon.