bluuebunny/crossref_metadata_2025 huggingface dataset:
Disparities and barriers to the access of biologics in moderate‐to‐severe adult psoriasis
Authors: Wan Vincent , Habibi Alireza , Mija Lorena A. , Abdi Parsa , Selvakumar Rishika , Mukovozov Ilya
Published: June 2024

Psoriasis is a chronic, relapsing inflammatory skin disorder that is associated with substantial physical and psychosocial comorbidity. Although biologic agents have offered transformative therapeutic advantages to those unresponsive to traditional treatments, data from recent literature indicate significant undertreatment of certain populations, highlighting potential barriers to access. This review aims to comprehensively elucidate barriers to biological therapy, addressing a recognized gap in the current literature. A search was conducted using MEDLINE, Embase, and Web of Science to investigate the obstacles and disparities that prevent access to biologic treatments in biologic‐naïve psoriatic patients. Emergent themes were then systematically categorized into five primary domains: patient‐level, prescriber‐level, medicine‐level, organizational‐, and external environment‐level factors. Our results demonstrate pronounced barriers and disparities encompassing increased age, race, socioeconomic status, rural location, cost and insurance, and insufficient knowledge that may hinder access to biologic treatments among psoriatic patients. Further research on how these barriers can be effectively addressed is needed to optimize treatment outcomes.
Loving and Letting: A Constructive Reading of Genesis 1
Authors: Olson J. W.
Published: June 2024

This essay evaluates possible meanings of God's creative ‘let’ in Genesis 1 in order to evaluate how God's generative love of creation forms a paradigm for human love. Beginning with the work of philosopher John Haugeland, who gives four possible meanings of letting‐be in his reading of Heidegger, this essay argues that creation is best understood in terms of Haugeland's model of letting‐be as enabling, in which what is created are conditions of possibility rather than determined outcomes. Understanding God's relationship to creation as making‐possible then sets the stage for characterizing right human relations as superabundantly generative rather than simply the absence of conflict.
The RNA interference response to alphanodavirus replication in Phlebotomus papatasi sand fly cells
Authors: Alexander Akira J. T. , Parry Rhys H. , Ratinier Maxime , Arnaud Frédérick , Kohl Alain
Published: June 2024

In this study, we identified and assembled a strain of American nodavirus (ANV) in the Phlebotomus papatasi‐derived PP9ad cell line. This strain most closely resembles Flock House virus and ANV identified in the Drosophila melanogaster S2/S2R cell line. Through small RNA sequencing and analysis, we demonstrate that ANV replication in PP9ad cells is primarily targeted by the exogenous small interfering RNA (exo‐siRNA) pathway, with minimal engagement from the PIWI‐interacting RNA (piRNA) pathway. In mosquitoes such as Aedes and Culex, the PIWI pathway is expanded and specialised, which actively limits virus replication. This is unlike in Drosophila spp., where the piRNA pathway does not restrict viral replication. In Lutzomyia sandflies (family Psychodidae), close relatives of Phlebotomus species and Drosophila, there appears to be an absence of virus‐derived piRNAs. To investigate whether this absence is due to a lack of PIWI pathway proteins, we analysed the piRNA and siRNA diversity and repertoire in PP9ad cells. Previous assemblies of P. papatasi genome (Ppap_1.0) have revealed a patchy repertoire of the siRNA and piRNA pathways. Our analysis of the updated P. papatasi genome (Ppap_2.1) has shown no PIWI protein expansion in sandflies. We found that both siRNA and piRNA pathways are transcriptionally active in PP9ad cells, with genomic mapping of small RNAs generating typical piRNA signatures. Our results suggest that the piRNA pathway may not respond to virus replication in these cells, but an antiviral response is mounted via the exo‐siRNA pathway.
Combinations of Energy‐based Devices plus isotretinoin for management of acne and acne scars: A systematic review
Authors: Xu Yidan , Wang Hao , Guo Linghong , Hamblin Michael R. , Wen Xiang
Published: June 2024

Background and Objective

A 6‐month interval between systemic isotretinoin (ISO) and the initiation of energy‐based interventions has been recommended, due to concerns about keloid formation and delayed wound healing. While this postponement goes against the current trend of early intervention for acne scarring. This systematic review evaluates the efficacy, safety, and patient satisfaction of combinations of ISO with energy‐based devices (EBD).

Study Design/Methods and Materials

PubMed, Embase, Web of Science, Cochrane Library, and Cochrane Central Register of Controlled Trials were comprehensively searched up to April 2023 according to PRISMA guidelines. Two independent reviewers screened the titles and abstracts to select articles. The quality of the literature was assessed for each study design.

Results

A total of 16 studies addressing the efficacy and safety of energy‐based modalities combined with ISO were identified, including six randomized controlled trials (RCTs), two case series, seven cohort studies, and one case report. ISO combinations with intense pulsed light (IPL), fractional ablative CO2 laser, pulsed dye laser (PDL), non‐ablative fractional laser (NAFL) and fractional microneedle radiofrequency (FMRF) have been tested for improving acne severity, acne scarring and erythema.

Conclusion

The current evidence does not justify delaying the use of EBDs for patients who have recently undergone or are currently receiving ISO treatment. Evidence‐based treatments such as PDL, NAFL, and FMRF etc. are suggested relatively safe and effective in treating acne and acne scarring.
What is the Strategy of Strategy to Tackle Climate Change?
Authors: Wickert Christopher , Muzio Daniel
Published: June 2024

To effectively tackle climate change, the strategic management enterprise needs to fundamentally reinvent itself. In their Point, Bansal, Durand, Kreutzer, Kunisch and McGahan forcefully argue for such a turnaround and outline a ‘new strategy’ paradigm that integrates the constraints of planetary boundaries and Earth systems not as an afterthought, but as the basis of inquiry. This, however, doesn't come without fierce contestation, as shown by the Counterpoint by Foss and Klein and the further Counterpoint by Davis and DeWitt. In this introduction to the Point‐Counterpoint debate on strategic management and climate change, we argue that this contestation is largely due to what we call three epistemic fault lines that cut through how strategy scholars understand climate change, devise possible solutions, and assume the relationship between theories and reality. We specify these fault lines and connect them to important avenues for future research that expand the strategic management conversation about climate change.
Links between socioeconomic position and cognitive and behavioral regulation in adolescence: The role of pubertal development
Authors: Chaku Natasha , Waters Nicholas E. , Ahmed Sammy F.
Published: June 2024

Adolescent cognitive and behavioral regulation is influenced by multidimensional and multidirectional processes within and across biological and contextual systems that shift throughout development. Key among these influences are distal processes such as early life socioeconomic position (SEP), and proximal processes such as pubertal development, but questions remain concerning how links between SEP, pubertal development, and cognitive and behavioral regulation accumulate and unfold over adolescence. In the current study, and in line with Dr. John Schulenberg's foundational work, direct associations between SEP, puberty, and adolescent cognitive and behavioral regulation were examined; then pubertal timing and tempo were considered as moderators and mediators of links between SEP and adolescent cognitive and behavioral regulation. Data were drawn from the NICHD Study of Early Child Care and Youth Development, a longitudinal study of 970 youth (52% male; 80% White, 13% Black, and 7% another race/ethnicity). Cognitive and behavioral regulation was measured using direct assessments of working memory, planning, risky decision‐making, and impulse control at age 15. SEP included maternal education and family income‐to‐needs and was averaged from birth to 54 months old; estimates of pubertal timing and tempo were derived using logistic growth curve models from age 9 to age 15. SEP was directly associated with cognitive and behavioral regulation. Pubertal development tended to moderate those links, but rarely mediated them. Specifically, socioeconomic disadvantage along with earlier timing or faster tempo tended to be associated with worse cognitive and behavioral regulation. Overall, findings suggest that pubertal timing and tempo may exacerbate existing environmental constraints.
Definition of refractory migraine and their evolution
Authors: Kikui Shoji , Danno Daisuke , Takeshima Takao
Published: June 2024

Introduction

The term ‘refractory migraine’ (RM) is commonly used in clinical settings; however, it is not recognized in the International Classification of Headache Disorders, third edition. A growing need for a shared definition of refractoriness has been highlighted by a multidisciplinary expert group. Although definitions for RM currently exist, the key parameters for the definition of refractoriness (e.g., unresponsiveness to treatment, high frequency, severe disability, or all of these features) remain contentious. Thus, a consensus on the definition of RM is crucial.

Methods

Calcitonin gene‐related peptide (CGRP) is a neuropeptide that plays an important role in migraine pathophysiology and is a target for migraine preventive therapies. Monoclonal antibodies targeting the CGRP (i.e., galcanezumab, fremanezumab, and eptinezumab) and its receptor (erenumab) have shown consistent efficacy for migraine prophylaxis with excellent safety profiles. Their effect on refractory cases has also been reported, offering promise to the many patients who have not found relief with existing treatments. Therefore, we anticipate a paradigm shift in migraine treatment.

Results

Following the widespread use of monoclonal antibodies targeting the CGRP and its receptor, the European Headache Federation proposed a definition for two subsets of difficult‐to‐treat migraine—resistant and refractory migraine—that considers both the frequency and disability caused by single and frequent attacks.

Conclusion

We expect that this definition will help resolve previous conflicts that have limited the use of earlier definitions.
H7 modulation of the L3 auditory neuron and phonotaxis in the cricket Acheta domesticus
Authors: Navia Benjamin , Widdicombe Lilly , Kim Lauren , Rim Jessica , Olivares Ana , Oster Zoe , Mbungu David
Published: June 2024

Several studies have implicated the L3 auditory interneuron in the regulation of syllable period selective phonotaxis in female cricket Acheta domesticus. The L3's response to model calls of conspecific males comprises of an immediate and a prolonged response. The kinetics of activation of these electrical activities are consistent with sequential activation of ionotropic and metabotropic mechanisms. In this study, we used electrophysiological and pharmacological tools to investigate the cellular mechanisms underlying L3's response. Bath application of the synthetic protein kinase inhibitor 1‐(5‐isoquinolinesul‐fonyl)‐2‐methylpiperazine (H7), results in the suppression of L3's spiking response, and this effect can be reversed by saline wash. Additionally, when female A. domesticus that were previously nano‐injected with H7 were tested for phonotaxis on a non‐compensating treadmill, they demonstrated suppression of syllable period‐dependent phonotaxis. These findings implicate protein kinase in the regulation of L3's spiking rhythm and the associated phonotaxis in A. domesticus.
Danish citizens' perspectives on the preventive medication recommended after screen‐detected cardiovascular disease: A qualitative study
Authors: Højgaard Helen Gräs , Frederiksen Kirsten , Høgh Annete Langager , Rasmussen Bodil , Dahl Marie
Published: June 2024

Background

The rationale for screening for cardiovascular disease (CVD) is debated as a prevention strategy. However, research shows that when preventive medication is initiated after screening for CVD, mortality rates decrease, especially among men. When implementing screening programmes, facilitating citizens' informed decisions and empowering their autonomy in the decision‐making process are crucial. We therefore aimed to explore citizens' perspectives on and decisions regarding initiating cardiovascular preventive medication for screen‐detected CVD.

Methods

We employed an exploratory qualitative design using semi‐structured interviews to investigate participants' perspectives on and decisions regarding initiating cardiovascular preventive medication for screen‐detected CVD. Twelve interviews were conducted and analysed using thematic analysis following Braun and Clarke's six‐step approach.

Findings

We found one overall theme, Being on a continuum between wellness and illness, with two underlying sub‐themes. Sub‐theme (1) Navigating mixed feelings and pathways reflects participants' perspectives on CVD preventive medication, which were positioned on a continuum with shifting perspectives. The state between wellness and illness was experienced as liminal and characterised by uncertainty and concerns about CVD risk. (2) Navigating medication decisions: a negotiated process. Pivotal medical decisions hinged on trust in authorities or own judgement, influenced by attitudes towards the need for medication, perception of meaningfulness, asymptomatic condition, age, family responsibility and predisposition. Participants' medical decisions were supported and impacted by significant others.

Conclusion

We uncovered a continuum of shifting perspectives ranging from feeling improved health to experiencing fear of CVD. For certain citizens, it is like navigating between these contrasting feelings. The perceived necessity and meaningfulness, in particular, shape medical decisions. Providing support for informed decisions is crucial and includes significant others. Shared decision‐making with healthcare professionals as facilitators is needed. Future research is warranted to investigate how to embrace the various perspectives on initiating CVD preventive medication in clinical practice.
The end of ambivalence. A narrative perspective on ambivalence in the suicidal process
Authors: Galasiński Dariusz , Ziółkowska Justyna
Published: June 2024

Introduction

Suicidal ambivalence is a recognized phenomenon in suicidology, yet not much is known about it in the context of progression from suicidal ideation to action. The current study addresses this gap. We explore narrative dynamics of suicidal ambivalence in stories about transition from suicidal ideation to action.

Methods

We employ an experiential qualitative approach to gain in‐depth understanding of narrated experience of suicidal ambivalence. We conducted semi‐structured interviews with 22 patients hospitalized after a suicide attempt. For a detailed analysis, we selected 11 interviews in which the interviewees' accounts spontaneously referred to their ambivalence about attempting suicide. We used a text‐oriented version of Critical Discourse Studies (CDS) to analyze the semantics and syntax, as well as the functions of what was said within the local context, and the social actions thus accomplished.

Results

Our study shows primarily that ambivalence is not resolved. Rather, it is set aside and removed from the narrative and replaced by an action‐focused narrative with no references to mental activities.

Conclusion

We propose that ambivalence recedes and gives way to action and that qualitative research provides a useful evidence base for conceptualizing and understanding the role of ambivalence in transition from suicidal ideation to action.
Introducing HESSS: Home Economics at Swiss Secondary Schools
Authors: Grob Anja , Binding Garret , Spirig Judith
Published: June 2024

Political science research into the determinants and consequences of who was taught what, when, and how in public schools is rare. One challenge encountered by researchers is that structured and detailed (historical) comparative data about curricula is limited, also in Switzerland. We contribute to closing this gap by introducing HESSS, a novel dataset on the provision of home economics education (“Hauswirtschaftsunterricht”) in Switzerland in ten German‐speaking cantons for vocational‐ and university‐track secondary schools since 1980 and 1991, respectively. Our dataset can help scholars explore variation in home economics education over time and across cantons, and facilitate research on the Swiss educational system. In this research note, we outline the main features of the data and illustrate how they can be used in two applications: (i) tracking the switch from gender‐segregated to co‐educated home economics classes across cantons; and (ii) describing the impact of budget cuts on home economics in the canton of Zurich.
Metallogenic age of the world‐class giant huoshaoyun non‐sulphide Zn–Pb deposit in Karakoram Area, Xinjiang, Northwest China
Authors: Wang Da , Jia Wenbin , Li Yongsheng , Mathur Ryan , Yu Xiaofei , Lu Yvhan , Dai Meng , Yan Guangsheng
Published: June 2024

Metallogenic geochronology plays a crucial role in the study of ore genesis and mineralization evolution. Unfortunately, accurately determining the metallogenic age of the non‐sulphide Zn–Pb deposits is difficult. Herein, we employed Rb–Sr dating of smithsonite and Sm–Nd dating of coexisting calcite to explore the mineralization ages of the Huoshaoyun Zn–Pb deposit. The Rb–Sr and Sm–Nd isotopic ratios yield isochron ages of 26.6 ± 1.7 and 27.5 ± 7.6 Ma, respectively. These obtained ages are identified as the metallogenic age of the Huoshaoyun deposit. Moreover, investigations into carbonate‐hosted Zn–Pb deposits in the East Tethys Metallogenic belt suggest they have formed in similar tectonic settings and yielded consistent Cenozoic ages. In sum, our research indicates that carbonate‐hosted Pb–Zn metallogenic ages in the East Tethys Metallogenic belt are principally concentrated in the late Palaeogene, and directly related to the collisional orogeny of the Tibetan Plateau during 40–26 Ma.
Coupling human mobility and social relationships to predict individual socioeconomic status: A graph neural network approach
Authors: Chen Xiao , Pei Tao , Song Ci , Shu Hua , Guo Sihui , Wang Xi , Liu Yaxi , Chen Jie
Published: June 2024

Understanding individual's socioeconomic status (SES) can provide supporting information for designing political and economic policies. Acquiring large‐scale economic survey data is time‐consuming and laborious. The widespread mobile phone data, which can reflect human mobility and social network characteristics, has become a low‐cost data source for researchers to infer SES. However, previous studies often oversimplify human mobility features and social network features extracted from mobile phone data into general statistical features, resulting in discounting some important temporal and relational information. Therefore, we propose a comprehensive framework for individual SES prediction that effectively utilizes a combination of human mobility and social relationships. In this framework, Word2Vec module extracts human mobility features from mobile phone positioning data, and graph neural network (GNN) module GraphSAGE captures social network characteristics constructed from call detail records. We evaluated the effectiveness of our proposed approach by training the model with real‐world data in Beijing. According to the experimental results, our proposed hybrid approach outperformed the other methods evidently, demonstrating that human mobility and social links are complementary in the characterization of SES. Coupling human mobility and social links can further deepen our understanding of cities' economic geography.
Classification of phonation types in singing voice using wavelet scattering network-based features
Authors: Mittapalle Kiran Reddy , Alku Paavo
Published: June 2024

The automatic classification of phonation types in singing voice is essential for tasks such as identification of singing style. In this study, it is proposed to use wavelet scattering network (WSN)-based features for classification of phonation types in singing voice. WSN, which has a close similarity with auditory physiological models, generates acoustic features that greatly characterize the information related to pitch, formants, and timbre. Hence, the WSN-based features can effectively capture the discriminative information across phonation types in singing voice. The experimental results show that the proposed WSN-based features improved phonation classification accuracy by at least 9% compared to state-of-the-art features.
Exploring the Lived Experiences of Physical Activity in Community-Dwelling Adults Living With Dementia and Their Carers
Authors: Blackwell Joanna , Ray Mo
Published: June 2024

People living with dementia have the same right to well-being as anyone else, including physical activity. Yet, physical activity levels among people with dementia are lower than in the general population, and while the physical activity health benefits are well established, little is known about how people living with dementia experience physical activity. To explore these physical activity experiences, we visited six community settings in one English county and conducted informal interviews with 18 people who were either living with dementia and community dwelling (n = 4), caring for or who had cared for someone with dementia (n = 10), or providing a support service for people living with dementia and their carers (n = 4). Findings highlight both the challenges and facilitators presented by organized groups, service provider skills and qualities, and environmental factors. Additionally, these factors were influential in shaping the physical activity experience of people living with dementia. The findings may be relevant for people providing or planning support services, commissioners, policymakers, and researchers.
Reexamining the Association Between Preseason Challenge and Threat States and Performance Across the Season
Authors: Jewiss Matthew , Hodgson Chris , Greenlees Iain
Published: June 2024

Challenge and threat (C/T) states have been shown to predict sport performance under pressure. Nevertheless, only one study has examined whether preseason C/T states are associated with season-long performance, yielding promising findings. Despite promising findings, this work is not without limitations that warrant addressing. We aimed to address these limitations and contribute to the scarce literature which tests the effect of anticipatory C/T states on longer term performance. Thirty-eight amateur cricketers prepared and delivered two counterbalanced speeches: a control speech and a speech about an important cricket batting situation approximately 16 weeks prior to the start of their competitive season. Regression analysis showed that cardiovascular reactivity in anticipation of delivering a speech about an important cricket batting scenario the next season did not predict season-long batting performance. The findings have potential to challenge the role C/T states play in predicting longer term performance in the sport domain.
Somatic mutations associate with clonal expansion of CD8
+
T cells
Authors: Lundgren Sofie , Myllymäki Mikko , Järvinen Timo , Keränen Mikko A. I. , Theodoropoulos Jason , Smolander Johannes , Kim Daehong , Salmenniemi Urpu , Walldin Gunilla , Savola Paula , Kelkka Tiina , Rajala Hanna , Hellström-Lindberg Eva , Itälä-Remes Maija , Kankainen Matti , Mustjoki Satu
Published: June 2024

Somatic mutations in T cells can cause cancer but also have implications for immunological diseases and cell therapies. The mutation spectrum in nonmalignant T cells is unclear. Here, we examined somatic mutations in CD4
+
and CD8
+
T cells from 90 patients with hematological and immunological disorders and used T cell receptor (TCR) and single-cell sequencing to link mutations with T cell expansions and phenotypes. CD8
+
cells had a higher mutation burden than CD4
+
cells. Notably, the biggest variant allele frequency (VAF) of non-synonymous variants was higher than synonymous variants in CD8
+
T cells, indicating non-random occurrence. The non-synonymous VAF in CD8
+
T cells strongly correlated with the TCR frequency, but not age. We identified mutations in pathways essential for T cell function and often affected lymphoid neoplasia. Single-cell sequencing revealed cytotoxic T
EMRA
phenotypes of mutated T cells. Our findings suggest that somatic mutations contribute to CD8
+
T cell expansions without malignant transformation.
Phase-changing citrate macromolecule combats oxidative pancreatic islet damage, enables islet engraftment and function in the omentum
Authors: Burke Jacqueline A. , Zhu Yunxiao , Zhang Xiaomin , Rios Peter D. , Joshi Ira , Lopez Daisy , Nasir Hafsa , Roberts Sharon , Rodriguez Quetzalli , McGarrigle James , Cook David , Oberholzer Jose , Luo Xunrong , Ameer Guillermo A.
Published: June 2024

Clinical outcomes for total-pancreatectomy followed by intraportal islet autotransplantation (TP-IAT) to treat chronic pancreatitis (CP) are suboptimal due to pancreas inflammation, oxidative stress during islet isolation, and harsh engraftment conditions in the liver’s vasculature. We describe a thermoresponsive, antioxidant macromolecule poly(polyethylene glycol citrate-
co
-
N
-isopropylacrylamide) (PPCN) to protect islet redox status and function and to enable extrahepatic omentum islet engraftment. PPCN solution transitions from a liquid to a hydrogel at body temperature. Islets entrapped in PPCN and exposed to oxidative stress remain functional and support long-term euglycemia, in contrast to islets entrapped in a plasma-thrombin biologic scaffold. In the nonhuman primate (NHP) omentum, PPCN is well-tolerated and mostly resorbed without fibrosis at 3 months after implantation. In NHPs, autologous omentum islet transplantation using PPCN restores normoglycemia with minimal exogenous insulin requirements for >100 days. This preclinical study supports TP-IAT with PPCN in patients with CP and highlights antioxidant properties as a mechanism for islet function preservation.
Subducting plate structure and megathrust morphology from deep seismic imaging linked to earthquake rupture segmentation at Cascadia
Authors: Carbotte Suzanne M. , Boston Brian , Han Shuoshuo , Shuck Brandon , Beeson Jeffrey , Canales J. Pablo , Tobin Harold , Miller Nathan , Nedimovic Mladen , Tréhu Anne , Lee Michelle , Lucas Madelaine , Jian Hanchao , Jiang Danqi , Moser Liam , Anderson Chris , Judd Darren , Fernandez Jaime , Campbell Chuck , Goswami Antara , Gahlawat Rajendra
Published: June 2024

The origin of rupture segmentation along subduction zone megathrusts and linkages to the structural evolution of the subduction zone are poorly understood. Here, regional-scale seismic imaging of the Cascadia margin is used to characterize the megathrust spanning ~900 km from Vancouver Island to the California border, across the seismogenic zone to a few tens of kilometers from the coast. Discrete domains in lower plate geometry and sediment underthrusting are identified, not evident in prior regional plate models, which align with changes in lithology and structure of the upper plate and interpreted paleo-rupture patches. Strike-slip faults in the lower plate associated with oblique subduction mark boundaries between regions of distinct lower plate geometry. Their formation may be linked to changes in upper plate structure across long-lived upper plate faults. The Juan de Fuca plate is fragmenting within the seismogenic zone at Cascadia as the young plate bends beneath the heterogeneous upper plate resulting in structural domains that coincide with paleo-rupture segmentation.
Lymphatic vessel transit seeds cytotoxic resident memory T cells in skin draining lymph nodes
Authors: Heim Taylor A. , Schultz Austin C. , Delclaux Ines , Cristaldi Vanessa , Churchill Madeline J. , Ventre Katherine S. , Lund Amanda W.
Published: June 2024

Lymphatic transport shapes the homeostatic immune repertoire of lymph nodes (LNs). LN-resident memory T cells (T
RMs
) play an important role in site-specific immune memory, yet how LN T
RMs
form de novo after viral infection remains unclear. Here, we tracked the anatomical distribution of antiviral CD8
+
T cells as they seeded skin and LN T
RMs
using a model of vaccinia virus–induced skin infection. LN T
RMs
localized to the draining LNs (dLNs) of infected skin, and their formation depended on the lymphatic egress of effector CD8
+
T cells from the skin, already poised for residence. Effector CD8
+
T cell transit through skin was required to populate LN T
RMs
in dLNs, a process reinforced by antigen encounter in skin. Furthermore, LN T
RMs
were protective against viral rechallenge in the absence of circulating memory T cells. These data suggest that a subset of tissue-infiltrating CD8
+
T cells egress from tissues during viral clearance and establish a layer of regional protection in the dLN basin.
Considerations for viral co-infection studies in human populations
Authors: Chin Taylor , Foxman Ellen F. , Watkins Timothy A. , Lipsitch Marc
Published: June 2024

When respiratory viruses co-circulate in a population, individuals may be infected with multiple pathogens and experience possible virus–virus interactions, where concurrent or recent prior infection with one virus affects the infection process of another virus. While experimental studies have provided convincing evidence for within-host mechanisms of virus–virus interactions, evaluating evidence for viral interference or potentiation using population-level data has proven more difficult. Recent studies have quantified the prevalence of co-detections using populations drawn from clinical settings. Here, we focus on selection bias issues associated with this study design. We provide a quantitative account of the conditions under which selection bias arises in these studies, review previous attempts to address this bias, and propose unbiased study designs with sample size estimates needed to ascertain viral interference. We show that selection bias is expected in cross-sectional co-detection prevalence studies conducted in clinical settings, except under a strict set of assumptions regarding the relative probabilities of being included in a study limited to individuals with clinical disease under different viral states. Population-wide studies that collect samples from participants irrespective of their clinical status would meanwhile require large sample sizes to be sufficiently powered to detect viral interference, suggesting that a study’s timing, inclusion criteria, and the expected magnitude of interference are instrumental in determining feasibility.
Draft genome sequence of
Bacillus thuringiensis
strain V-AB8.18, a novel isolate with potential nematicidal activity
Authors: Palma Leopoldo , Bel Yolanda , Escriche Baltasar
Published: June 2024

We report the draft genome of
Bacillus thuringiensis
strain V-AB8.18, comprising 308 contigs totaling 6,182,614 bp, with 35% G + C content. It contains 6,151 putative protein-coding genes, including App6 and Cry5-like crystal proteins, exhibiting 99% pairwise identity to nematicidal proteins App6Aa2 and Cry5Ba2, active against
Meloidogyne incognita
and
Meloidogyne hapla
.
Trace fossils, paleosalinity, and depositional environment of the Northview Formation, southwest Missouri, USA
Authors: Rovey Charles W. , Bassett Damon J. , Schuette* Jaren , Michelfelder Gary S.
Published: June 2024

The Early Mississippian Northview Formation is a siliciclastic deposit reaching 25 m in thickness along an east-west trend in southwest Missouri, USA. Along this trend, the formation coarsens upward from shale to coarse siltstone with shaley interbeds and channel fills. The siltstones have high concentrations of two trace fossils: Nereites missouriensis and Zoophycos. Thus, the ichnofauna is dominated by namesake genera of the two deepest marine ichnofacies. Nevertheless, the Northview was deposited on a shallow carbonate platform.

The vertical succession of trace fossils is consistent with deltaic deposition. The lowest shale is dominated by common elements of the Phycosiphon prodelta ichnofacies, and the lowest overlying siltstone is dominated by elements of the Rosselia delta-front ichnofacies. N. missouriensis occurs abundantly and dominates the overlying siltstones, with Zoophycos covering bedding planes near the top, a pattern found within the lower plain of other Paleozoic deltas. Geochemical proxy measurements indicate paleosalinity decreasing upward through the formation and an approaching freshwater (fluvial) source, raising questions about Early Mississippian source areas and tectonics.
Misoprostol for non-alcoholic steatohepatitis: a randomised control trial
Authors: Siyal Mehreen , Abbas Zaigham , Qadeer Muhammad Ali , Saeed Alina , Ali Usman , Khatoon Ambrina
Published: June 2024

Introduction

The management of non-alcoholic steatohepatitis (NASH) is an unmet clinical need. Misoprostol, a structural analogue of naturally occurring prostaglandin E1, has been reported to decrease proinflammatory cytokine production and may have a potential role in treating NASH. We aimed to evaluate the efficacy and safety of misoprostol in treating patients with NASH.

Methods

In this phase 2, double-blind, randomised, placebo-controlled trial, patients with NASH were randomly assigned in a 1:1 ratio to receive 200 µg of misoprostol or placebo thrice daily for 2 months. The primary endpoint was an improvement in liver function tests (LFTs), interleukin-6 (IL-6) and endotoxin levels. The secondary endpoint was improvement in insulin resistance, dyslipidaemia, hepatic fibrosis and hepatic steatosis.

Results

A total of 50 patients underwent randomisation, of whom 44 (88%) were males. The age range was 25–64 years (mean±SE of mean (SEM) 38.1±1.4). 19 (38%) patients had concomitant type 2 diabetes mellitus. 32 (64%) patients were either overweight or obese. At the end of 2 months’ treatment, a reduction in total leucocyte count (TLC) (p=0.005), alanine aminotransferase (ALT) (p<0.001), aspartate aminotransferase (AST) (p=0.002) and controlled attenuation parameter (CAP) (p=0.003) was observed in the misoprostol group, whereas placebo ensued a decline in ALT (p<0.001), AST (p=0.018), gamma-glutamyl transferase (GGT) (p=0.003), CAP (p=0.010) and triglycerides (p=0.048). There was no diminution in insulin resistance, hepatic fibrosis (elastography) and dyslipidaemia in both groups. However, misoprostol resulted in a significant reduction in CAP as compared with the placebo group (p=0.039). Moreover, in the misoprostol group, pretreatment and post-treatment IL-6 and endotoxin levels remained stable, while in the placebo group, an increase in the IL-6 levels was noted (p=0.049). Six (12%) patients had at least one adverse event in the misoprostol group, as did five (10%) in the placebo group. The most common adverse event in the misoprostol group was diarrhoea. No life-threatening events or treatment-related deaths occurred in each group.

Conclusion

Improvement in the biochemical profile was seen in both misoprostol and placebo groups without any statistically significant difference. However, there was more improvement in steatosis, as depicted by CAP, in the misoprostol group and worsening of IL-6 levels in the placebo group.

Trial registration number

NCT05804305.
Automatic three-dimensional reconstruction of the oesophagus in achalasia patients undergoing POEM: an innovative approach for evaluating treatment outcomes
Authors: Grünherz Vivian , Ebigbo Alanna , Elia Miriam , Brunner Alessandra , Krafft Tamara , Pöller Leo , Schneider Pia , Stieler Fabian , Bauer Bernhard , Muzalyova Anna , Messmann Helmut , Nagl Sandra
Published: June 2024

Background and aims

Peroral endoscopic myotomy (POEM) is a standard treatment option for achalasia patients. Treatment response varies due to factors such as achalasia type, degree of dilatation, pressure and distensibility indices. We present an innovative approach for treatment response prediction based on an automatic three-dimensional (3-D) reconstruction of the tubular oesophagus (TE) and the lower oesophageal sphincter (LES) in patients undergoing POEM for achalasia.

Methods

A software was developed, integrating data from high-resolution manometry, timed barium oesophagogram and endoscopic images to automatically generate 3-D reconstructions of the TE and LES. Novel normative indices for TE (volume×pressure) and LES (volume/pressure) were automatically integrated, facilitating pre-POEM and post-POEM comparisons. Treatment response was evaluated by changes in volumetric and pressure indices for the TE and the LES before as well as 3 and 12 months after POEM. In addition, these values were compared with normal value indices of non-achalasia patients.

Results

50 treatment-naive achalasia patients were enrolled prospectively. The mean TE index decreased significantly (p<0.0001) and the mean LES index increased significantly 3 months post-POEM (p<0.0001). In the 12-month follow-up, no further significant change of value indices between 3 and 12 months post-POEM was seen. 3 months post-POEM mean LES index approached the mean LES of the healthy control group (p=0.077).

Conclusion

3-D reconstruction provides an interactive, dynamic visualisation of the oesophagus, serving as a comprehensive tool for evaluating treatment response. It may contribute to refining our approach to achalasia treatment and optimising treatment outcomes.

Trial registration number

22-0149.
Toward a more systematic understanding of water insecurity coping strategies: insights from 11 global sites
Authors: Collins Shalean M , Mock Nancy , Chaparro M Pia , Rose Donald , Watkins Benjamin , Wutich Amber , Young Sera L
Published: June 2024

Introduction

Water insecurity–the inability to access and benefit from affordable, reliable and safe water for basic needs–is a considerable global health threat. With the urgent need to target interventions to the most vulnerable, accurate and meaningful measurement is a priority. Households use diverse strategies to cope with water insecurity; however, these have not been systematically characterised nor measured. The Food Insecurity Coping Strategies Index has been insightful for targeting nutrition interventions to the most vulnerable. As a first step towards creating an analogous scale for water, this study characterises the largest empirical data set on water insecurity coping strategies and proposes guidance on measuring it using a novel toolkit.

Methods

Open-ended responses on water insecurity coping (n=2301) were collected across 11 sites in 10 low- and middle-income countries in the Household Water InSecurity Experiences (HWISE) Scale validation study. Responses were characterised and compared with behaviours identified in the literature to construct an instrument to systematically assess coping.

Results

We identified 19 distinct strategies that households used when experiencing water insecurity. These findings, paired with prior literature, were used to develop a Water Insecurity Coping Strategies Assessment Toolkit with guidance on its piloting to assess coping prevalence, frequency and severity.

Conclusions

The widespread occurrence of water insecurity coping strategies underscores the importance of understanding their prevalence and severity. The Water Insecurity Coping Strategies Assessment Toolkit offers a comprehensive approach to evaluate these strategies and inform the design and monitoring of interventions targeting those most vulnerable to water insecurity.
Urgent support mechanism: saving millions of COVID-19 vaccines from expiry in Africa
Authors: Fallah Mosoka Papa , Sembuche Senga , Kabwe Patrick Chanda , Dereje Nebiyu , Abubakar Tijani , Chipendo Tendai , Ojo John , Bamutura Moses , Shaweno Tamrat , Ramakhunoane Susan , Ts'oeu Silane , Ndoula Shalom Tchokfe , Agoambin Nelly , Kangbai Desmond Maada , Jalloh Mohammad B , Tinuga Florian , Mutayoba Rita , Jalang'o Rose E , Kiarie Jakeline , Legge George Awzenio , David Victoria , Clarke Adolphus T , Kamara Patricia S , Kalangwa Kalangwa , Sakanga Viviane , Ndembi Nicaise , Raji Tajudeen , Abdulaziz Mohammed
Published: June 2024

Delivering COVID-19 vaccines with 4–6 weeks shelf life remains one of Africa’s most pressing challenges. The Africa Centres for Disease Control and Prevention (Africa CDC) leadership recognised that COVID-19 vaccines donated to many African countries were at risk of expiry considering the short shelf life on delivery in the Member States and slow vaccine uptake rates. Thus, a streamlined rapid response system, the urgent support mechanism, was developed to assist countries accelerate COVID-19 vaccine uptake. We describe the achievements and lessons learnt during implementation of the urgent support mechanism in eight African countries. An Africa CDC team was rapidly deployed to meet with the Ministry of Health of each country alerted for COVID-19 vaccine expiry and identified national implementing partners to quickly develop operational work plans and strategies to scale up the urgent use of the vaccines. The time between the initiation of alerts to the start of the implementation was typically within 2 weeks. A total of approximately 2.5 million doses of vaccines, costing $900 000, were prevented from expiration. The urgent support has also contributed to the increased COVID-19 vaccination coverage in the Member States from 16.1% at the initiation to 25.3% at the end of the urgent support. Some of the effective strategies used by the urgent support mechanism included coordination between Africa CDC and country vaccine task forces, establishment of vaccination centres, building the capacity of routine and surge health workforce, procurement and distribution of vaccine ancillaries, staff training, advocacy and sensitisation events, and use of trusted religious scriptures and community influencers to support public health messages. The urgent support mechanism demonstrated a highly optimised process and serves as a successful example for acceleration and integration of vaccination into different healthcare delivery points.
Realist process evaluation of occupational performance coaching: protocol
Authors: Graham Fiona , Williman Jonathan , Desha Laura , Snell Deborah , Jones Bernadette , Ingham Tristram , Latu Anna Tiatia Fa'atoese , Ranta Annemarei , Walker Emma , Makasini Salote , Ziviani Jenny
Published: June 2024

Introduction

A cluster randomised controlled trial, the Meaning, Agency and Nurturing Autonomy (MANA) study, is underway comparing the effects of occupational performance coaching (OPC) and usual care on the social participation, health and well-being of children with neurodisability and their caregivers. This protocol presents the realist process evaluation which is occurring in parallel with the trial to allow testing and further refinement of OPC programme theory, as represented in its logic model. The aim of this realist evaluation is to examine what works, for whom, in the implementation of OPC with caregivers of children with neurodisability (in particular, Māori and Pasifika) in current service delivery contexts.

Methods and analysis

Guided by OPC programme theory and realist evaluation processes, mixed-methods data collected from the MANA study OPC group will be analysed to elucidate when OPC works (outcomes), for whom, how (mechanisms) and under what circumstances (contexts). This will culminate in the synthesis of Intervention-Actor Context-Mechanism-Outcome configurations. Descriptive analyses will be reported for quantitative measures of treatment fidelity (OPC-Fidelity Measure), caregiver emotional response to OPC (Session Rating Scale) preintervention emotional state (Depression Stress and Anxiety Scale) and client outcomes (Canadian Occupational Performance Measure). Reflexive thematic analysis will be undertaken to analyse realist interviews with therapists who implemented OPC above and below fidelity thresholds and culturally focused interviews with clients of Māori or Pasifika ethnicity, informing understanding of the contexts influencing therapists’ implementation of OPC with fidelity, and the mechanisms triggered within therapists or caregivers to elicit a response to the intervention. The MANA study trial outcomes will be reported separately.

Ethics and dissemination

Ethical approval for this study was granted by the New Zealand Health and Disability Ethics Committee (20/STH/93). In all participating jurisdictions local area approval was obtained, involving a process of local Māori consultation. Results will be disseminated to all participants, and more broadly to clinicians and policy-makers through conference presentations and peer-reviewed journal publications, which will inform decision-making about resourcing and supporting effective delivery of OPC to optimise outcomes for children and caregivers.

Trial registration number

ACTRN12621000519853.
Long COVID cognitive sequelae 6 months postinfection and beyond: a scoping review protocol
Authors: Monteiro Sara , Dessenne Coralie , Perquin Magali
Published: June 2024

Introduction

The novel and expanding field of long COVID research has undergone diverse methodological approaches in recent years. This protocol lays out the methodological approach, which aims at identifying nuances in current research. It underscores the necessity for a more precise understanding of prolonged cognitive sequelae and their relation to initial disease severity. The findings will add valuable insights for the development of targeted rehabilitation, healthcare interventions and thereby aid patients, clinicians, policymakers and researchers. Our upcoming research is introduced here.

Methods and analysis

To map current research in the field, a scoping review will be conducted and documented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Review Extension standards. A systematic search of scientific databases (PubMed, EMBASE), presented 1409 eligible results, published up to 21 December 2023. After removal of duplicates, 925 articles were extracted for screening. Two independent reviewers will screen for titles, abstracts and full texts, to extract data, which will then be organised using charting software. Data for various variables, that is, journal info, studied population demographics, study design, long COVID related data, cognitive outcomes and neuropsychological tests will be gathered. Descriptive analyses, evidence gap maps, heat map quantifications and narrative synthesis will be conducted for reporting of results.

This scoping review has been registered with the Open Science Framework (https://doi.org/10.17605/OSF.IO/JHFX6).

Ethics and dissemination

Ethical approval is not required, as the study does not involve human participants. The findings will be disseminated through a publication in a scientific journal and within the professional network.