bluuebunny/crossref_metadata_2025 huggingface dataset:
Viral load suppression after intensive adherence counselling among adult people living with HIV at Kiswa health centre, Kampala: a retrospective cohort study. Secondary data analysis
Authors: Nakaye Catherine , Mukiza Nelson , Mawanda Denis , Kataike Hajira , Kaganzi Hellen , Ahimbisibwe Grace Miriam , Businge Gerald Bright , Kyambadde Raymonds Crespo , Nakalega Rita
Published: March 2023

Background

The Joint United Nations Programme on HIV/AIDS through the 95-95-95 target requires 95% of people living with HIV (PLHIV) on antiretroviral treatment (ART) to be virally suppressed. Viral Load (VL) non-suppression has been found to be associated with suboptimal ART adherence, and Intensive Adherence Counselling (IAC) has been shown to lead to VL re-suppression by over 70% in PLHIV on ART. Currently, there is data paucity on VL suppression after IAC in adult PLHIV in Uganda. This study aimed to evaluate the proportion of VL suppression after IAC and associated factors among adult PLHIV on ART at Kiswa Health Centre in Kampala, Uganda.

Methods

Study was a retrospective cohort design and employed secondary data analysis to review routine program data. Medical records of adult PLHIV on ART for at least six months with VL non-suppression from January 2018 to June 2020 at Kiswa HIV clinic were examined in May 2021. Descriptive statistics were applied to determine sample characteristics and study outcome proportions. Multivariable modified Poisson regression analysis was employed to assess predictors of VL suppression after IAC.

Results

Analysis included 323 study participants of whom 204 (63.2%) were female, 137 (42.4%) were between the age of 30 and 39 years; and median age was 35 years (interquartile range [IQR] 29–42). Participant linkage to IAC was 100%. Participants who received the first IAC session within 30 days or less after unsuppressed VL result were 48.6% (157/323). Participants who received recommended three or more IAC sessions and achieved VL suppression were 66.4% (202/304). The percentage of participants who completed three IAC sessions in recommended 12 weeks was 34%. Receipt of three IAC sessions (ARR = 1.33, 95%CI: 1.15–1.53, p < 0.001), having baseline VL of 1,000–4,999 copies/ml (ARR = 1.47, 95%CI: 1.25–1.73, p < 0.001) and taking Dolutegravir containing ART regimen were factors significantly associated with VL suppression after IAC.

Conclusion

VL suppression proportion of 66.4% after IAC in this population was comparable to 70%, the percentage over which adherence interventions have been shown to cause VL re-suppression. However, timely IAC intervention is needed from receipt of unsuppressed VL results to IAC process completion.
Untargeted metabolomic analysis of ischemic injury in human umbilical vein endothelial cells reveals the involvement of arginine metabolism
Authors: Wu Ruihao , Zhong Jiayin , Song Lei , Zhang Min , Chen Lulu , Zhang Li , Qiu Zhaohui
Published: March 2023

Objective

In this study, differentially expressed metabolites of vascular endothelial cells were examined to further understand the metabolic regulation of ischemic injury by untargeted metabolomics.

Method

Human umbilical vein endothelial cells (HUVECs) were selected to construct an ischemia model using oxygen–glucose deprivation (OGD) and 0, 3, 6, and 9 h of treatment. After that, cell survival levels were determined by CCK8 detection. Flow cytometry, ROS detection, JC-1 detection, and western blotting were used to measure apoptosis and oxidative stress in cells. Then, combined with UPLC Orbitrap/MS, we verified the impacted metabolism pathways by western blotting and RT‒PCR.

Results

CCK8 assays showed that the survival of HUVECs was decreased with OGD treatment. Flow cytometry and the expression of cleaved caspase 3 showed that the apoptosis levels of HUVECs increased following OGD treatment. The ROS and JC-1 results further suggested that oxidative stress injury was aggravated. Then, combined with the heatmap, KEGG and IPA, we found that arginine metabolism was differentially altered during different periods of OGD treatment. Furthermore, the expression of four arginine metabolism-related proteins, ASS1, ARG2, ODC1 and SAT1, was found to change during treatment.

Conclusion

Arginine metabolism pathway-related proteins were significantly altered by OGD treatment, which suggests that they may have a potential role in ischemic injury.
A DELPHI study priority setting the remaining challenges for the use of routinely collected data in trials: COMORANT-UK
Authors: Williams Adam D. N. , Davies Gwyneth , Farrin Amanda J. , Mafham Marion , Robling Michael , Sydes Matthew R. , Lugg-Widger Fiona V.
Published: March 2023

Background

Researchers are increasingly seeking to use routinely collected data to support clinical trials. This approach has the potential to transform the way clinical trials are conducted in the future. The availability of routinely collected data for research, whether healthcare or administrative, has increased, and infrastructure funding has enabled much of this. However, challenges remain at all stages of a trial life cycle. This study, COMORANT-UK, aimed to systematically identify, with key stakeholders across the UK, the ongoing challenges related to trials that seek to use routinely collected data.

Methods

This three-step Delphi method consisted of two rounds of anonymous web-based surveys and a virtual consensus meeting. Stakeholders included trialists, data infrastructures, funders of trials, regulators, data providers and the public. Stakeholders identified research questions or challenges that they considered were of particular importance and then selected their top 10 in the second survey. The ranked questions were taken forward to the consensus meeting for discussion with representatives invited from the stakeholder groups.

Results

In the first survey, 66 respondents yielded over 260 questions or challenges. These were thematically grouped and merged into a list of 40 unique questions. Eighty-eight stakeholders then ranked their top ten from the 40 questions in the second survey. The most common 14 questions were brought to the virtual consensus meeting in which stakeholders agreed a top list of seven questions. We report these seven questions which are within the following domains: trial design, Patient and Public Involvement, trial set-up, trial open and trial data. These questions address both evidence gaps (requiring further methodological research) and implementation gaps (requiring training and/or service re-organisation).

Conclusion

This prioritised list of seven questions should inform the direction of future research in this area and should direct efforts to ensure that the benefits in major infrastructure for routinely collected data are achieved and translated. Without this and future work to address these questions, the potential societal benefits of using routinely collected data to help answer important clinical questions will not be realised.
Molecular characterization of oriental eyeworm (Thelazia callipaeda) detected from raccoon (Procyon lotor) and Japanese raccoon dog (Nyctereutes viverrinus) in Kanto region, Japan
Authors: Doi Kandai , Tokiwa Toshihiro , Imoto Miyu , Chou Shyun , Yamasaki Fumiaki , Kato Takuya , Hayama Shin-ichi
Published: March 2023

Background

The oriental eyeworm Thelazia callipaeda (Spirurida: Thelaziidae) is an emerging parasitic ocular nematode of carnivores and humans. In domestic animals and humans, the infection causes varying degrees of inflammation and lacrimation, and wild carnivores represent an important reservoir. In this study we examined the infection status and molecular characterization of T. callipaeda in two urban carnivores, raccoons Procyon lotor and wild Japanese raccoon dogs Nyctereutes viverrinus, in the Kanto region of Japan.

Methods

From January 2020 to December 2021, 193 carcasses including 178 raccoons and 15 raccoon dogs were examined for the presence of worms in the eye. The worms from infected animals (one worm per host) were morphologically identified as T. callipaeda. Worms (1–5 worms per host) were subjected to genetic analysis using mitochondrial cytochrome c oxidase subunit I gene sequences.

Results

The prevalence of T. callipaeda in raccoons and Japanese raccoon dogs was 20.2% (36/178) and 13.3% (2/15), respectively. The cox1 sequences from 56 worms from 38 animals revealed three haplotypes (h9, h10, and h12). Analysis of multiple worms for five raccoons showed co-infection of two different haplotypes (h9 and h10) in a single host. Comparing our data with published sequences, three sequences obtained from raccoons and raccoon dogs shared the same haplotypes as those reported in humans, dogs, and cats in Japan.

Conclusions

Our findings show a high prevalence of T. callipaeda in raccoons, suggesting that this invasive carnivore species serves as an important natural reservoir of T. callipaeda in the Kanto region of Japan, an area with the highest human population of the country.

Graphical Abstract
Phosphorylated proteomics-based analysis of the effects of semaglutide on hippocampi of high-fat diet-induced-obese mice
Authors: Chen Xiaoyi , Ma Liang , Gan Kexin , Pan Xiaoyu , Chen Shuchun
Published: March 2023

The aim of this paper was to investigate the effects of semaglutide on phosphorylated protein expression, and its neuroprotective mechanism in hippocampi of high-fat-diet-induced obese mice. In total, 16 obese mice were randomly divided into model group (H group) and semaglutide group (S group), with 8 mice in each group. In addition, a control group (C group) was set up comprising 8 C57BL/6J male normal mice. The Morris water maze assay was conducted to detect cognitive function changes in the mice, and to observe and compare body weight and expression levels of serological indicators between groups after the intervention. Phosphorylated proteomic analysis was performed to detect the hippocampal protein profile in mice. Proteins up-regulated twofold or down-regulated 0.5-fold in each group and with t-test p < 0.05 were defined as differentially phosphorylated proteins and were analyzed bioinformatically. The results showed that the high-fat diet-induced obese mice had reduced body weight, improved oxidative stress indexes, significantly increased the percentage of water maze trips and the number of platform crossings, and significantly shortened the water maze platform latency after semaglutide intervention. The phosphorylated proteomics results identified that 44 overlapping proteins among the three experimental groups. Most of the phosphorylated proteins identified were closely associated with pathways of neurodegeneration-multiple diseases. In addition, we identified Huntington, Neurofilament light chain, Neurofilament heavy chain as drug targets. This study demonstrates for the first time that semaglutide exerts neuroprotective effects by reducing HTT Ser1843, NEFH Ser 661 phosphorylation and increasing NEFL Ser 473 phosphorylation in hippocampal tissue of obese mice.
DNA methylation and cardiovascular disease in humans: a systematic review and database of known CpG methylation sites
Authors: Krolevets Mykhailo , Cate Vincent ten , Prochaska Jürgen H. , Schulz Andreas , Rapp Steffen , Tenzer Stefan , Andrade-Navarro Miguel A. , Horvath Steve , Niehrs Christof , Wild Philipp S.
Published: March 2023

Background

Cardiovascular disease (CVD) is the leading cause of death worldwide and considered one of the most environmentally driven diseases. The role of DNA methylation in response to the individual exposure for the development and progression of CVD is still poorly understood and a synthesis of the evidence is lacking.

Results

A systematic review of articles examining measurements of DNA cytosine methylation in CVD was conducted in accordance with PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. The search yielded 5,563 articles from PubMed and CENTRAL databases. From 99 studies with a total of 87,827 individuals eligible for analysis, a database was created combining all CpG-, gene- and study-related information. It contains 74,580 unique CpG sites, of which 1452 CpG sites were mentioned in ≥ 2, and 441 CpG sites in ≥ 3 publications. Two sites were referenced in ≥ 6 publications: cg01656216 (near ZNF438) related to vascular disease and epigenetic age, and cg03636183 (near F2RL3) related to coronary heart disease, myocardial infarction, smoking and air pollution. Of 19,127 mapped genes, 5,807 were reported in ≥ 2 studies. Most frequently reported were TEAD1 (TEA Domain Transcription Factor 1) and PTPRN2 (Protein Tyrosine Phosphatase Receptor Type N2) in association with outcomes ranging from vascular to cardiac disease. Gene set enrichment analysis of 4,532 overlapping genes revealed enrichment for Gene Ontology molecular function “DNA-binding transcription activator activity” (q = 1.65 × 10–11) and biological processes “skeletal system development” (q = 1.89 × 10–23). Gene enrichment demonstrated that general CVD-related terms are shared, while “heart” and “vasculature” specific genes have more disease-specific terms as PR interval for “heart” or platelet distribution width for “vasculature.” STRING analysis revealed significant protein–protein interactions between the products of the differentially methylated genes (p = 0.003) suggesting that dysregulation of the protein interaction network could contribute to CVD. Overlaps with curated gene sets from the Molecular Signatures Database showed enrichment of genes in hemostasis (p = 2.9 × 10–6) and atherosclerosis (p = 4.9 × 10–4).

Conclusion

This review highlights the current state of knowledge on significant relationship between DNA methylation and CVD in humans. An open-access database has been compiled of reported CpG methylation sites, genes and pathways that may play an important role in this relationship.
Suitability of memory aids and strategies for people with posterior cortical atrophy: protocol for a scoping review
Authors: Burbaite A. , Leeworthy S. , Hirst L. , Mioshi E. , Clare L. , Ahmed S.
Published: March 2023

Background

Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterised by progressive visuospatial and visuoperceptual impairment. Recent research shows that memory impairment can also occur as an early symptom of the condition and that the impairment can be ameliorated by providing support in the memory recall phase, for example, by presenting a related cue. In Alzheimer’s disease (AD), which is defined by an amnestic syndrome, memory aids and strategies have been used to help support everyday memory, which in turn can have a positive impact on patient and carer outcomes. Similar support for PCA could be achieved by using memory aids and strategies which help to encode and/or retrieve information, yet there are currently no guidelines for memory strategies that may be suitable in PCA. Due to the central visual disorder that defines PCA, careful consideration is needed when making recommendations.

Methods

A scoping review will be conducted of published studies that have assessed memory aids and strategies in people with AD and related dementias where memory is considered a core or supplementary feature, with the aim of distinguishing those that may be suitable or adaptable for PCA. The systematic search will include the electronic databases MEDLINE, PsycINFO and CINAHL, using search terms for dementia and memory aids and strategies identified in pilot searches. Findings will be mapped and described based on methods used, population, clinical data and memory aids and strategies identified.

Discussion

The scoping review will give an overview of the memory aids and strategies used in people with AD and related dementias and identify characteristics, modality and pragmatics to evaluate their suitability and adaptability for a PCA population. Tailored memory support strategies for people living with PCA could improve memory performance, with knock-on positive effects on patient and carer outcomes.
Effectiveness of eHealth weight management interventions in overweight and obese adults from low socioeconomic groups: a systematic review
Authors: Myers-Ingram Richard , Sampford Jade , Milton-Cole Rhian , Jones Gareth David
Published: March 2023

Background

Low socioeconomic status (SES) is associated with increased rates of overweight and obesity. Proponents of electronic health (eHealth) hypothesise that its inclusion in weight management interventions can improve efficacy by mitigating typical barriers associated with low SES.

Objectives

To establish the scope of eHealth weight management interventions for people with overweight and obesity from a low SES. Secondary objectives were to determine the efficacy of eHealth interventions in facilitating weight loss, physical activity and fitness improvements.

Methods

Four databases and grey literature were systematically searched to identify eligible studies published in English from inception to May 2021. Studies examining an eHealth intervention with low SES participants were included. Outcomes included temporal change in weight and BMI, anthropometry, physiological measures and physical activity levels. The number and heterogeneity of studies precluded any meta-analyses; thus, a narrative review was undertaken.

Results

Four experimental studies with low risk of bias were reviewed. There was variance in how SES was defined. Study aims and eHealth media also varied and included reducing/maintaining weight or increasing physical activity using interactive websites or voice responses, periodic communication and discourse via telephone, social media, text messaging or eNewsletters. Irrespectively, all studies reported short-term weight loss. eHealth interventions also increased short-term physical activity levels where it was assessed, but did not change anthropometry or physiological measures. None reported any effect on physical fitness.

Conclusions

This review revealed short-term effects of eHealth interventions on weight loss and increased physical activity levels for low SES participants. Evidence was limited to a small number of studies, with small to moderate sample sizes. Inter-study comparison is challenging because of considerable variability. Future work should prioritise how to utilise eHealth in the longer term either as a supportive public health measure or by determining its long-term efficacy in engendering volitional health behaviour changes.

Systematic review registration

PROSPERO CRD42021243973
Alcohol, the overlooked drug: clinical pharmacist perspectives on addressing alcohol in primary care
Authors: Madden Mary , Stewart Duncan , Mills Thomas , McCambridge Jim
Published: March 2023

Background

Attempts to routinely embed brief interventions in health systems have long been challenging, with healthcare professionals concerned about role adequacy, legitimacy, and support. This is the first study to explore clinical pharmacists’ experiences of discussing alcohol with patients in their new role in UK primary care, in developing a novel approach to brief intervention. It investigates their confidence with the subject of alcohol in routine practice and explores views on a new approach, integrating alcohol into the medication review as another drug directly linked to the patient’s health conditions and medicines, rather than a separated ‘healthy living’ issue. The study forms part of wider efforts to repurpose and reimagine the potential application of brief interventions and to rework their contents.

Methods

Longitudinal qualitative study of 10 recruits to the new clinical pharmacist role in English primary care, involving three semi-structured interviews over approximately 16 months, supplemented by 10 one-off interviews with pharmacists already established in general practice.

Results

When raised at all, enquiring about alcohol in medication reviews was described in terms of calculating dose and level of consumption, leading to crude advice to reduce drinking. The idea was that those who appeared dependent should be referred to specialist services, though few such referrals were recalled. Pharmacists acknowledged that they were not currently considering alcohol as a drug in their practice and were interested in learning more about this concept and the approach it entailed, particularly in relation to polypharmacy. Some recognised a linked need to enhance consultation skills.

Conclusions

Alcohol complicates routine clinical care and adversely impacts patient outcomes, even for those drinking at seemingly unremarkable levels. Changing clinical practice on alcohol requires engaging with, and supportively challenging, routine practices and entrenched ideas of different kinds. Framing alcohol as a drug may help shift the focus from patients with alcohol problems to problems caused for patients by alcohol. This is less stigmatising and provides role legitimacy for pharmacists to address alcohol clinically in medication reviews, thus providing one element in the formation of a new prevention paradigm. This approach invites further innovations tailored to other healthcare professional roles.
N7-methylguanosin regulators-mediated methylation modification patterns and characterization of the immune microenvironment in lower-grade glioma
Authors: Maimaiti Aierpati , Feng Zhaohai , Liu Yanwen , Turhon Mirzat , Xie Zhihao , Baihetiyaer Yilimire , Wang Xixian , Kasimu Maimaitijiang , Jiang Lei , Wang Yongxin , Wang Zengliang , Pei Yinan
Published: March 2023

N7-methylguanosine (m7G) modification signature has recently emerged as a crucial regulator of tumor progression and treatment in cancer. However, there is limited information available on the genomic profile of lower-grade gliomas (LGGs) related to m7G methylation modification genes’ function in tumorigenesis and progression. In this study, we employed bioinformatics methods to characterize m7G modifications in individuals with LGG from The Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA). We used gene set enrichment analysis (GSEA), single sample GSEA (ssGSEA), CIBERSORT algorithm, ESTIMATE algorithm, and TIDE to evaluate the association between m7G modification patterns, tumor microenvironment (TME) cell infiltration properties, and immune infiltration markers. The m7G scoring scheme using principal component analysis (PCA) was employed to investigate the m7G modification patterns quantitatively. We examined the m7G modification hub genes' expression levels in normal samples, refractory epilepsy samples, and LGG samples using immunohistochemistry, western-blotting, and qRT-PCR. Our findings revealed that individuals with LGG could be categorized into two groups based on m7G scores (high and low) according to the properties of m7G. Moreover, we observed that high m7G score was associated with significant clinical benefit and prolonged survival duration in the anti-PD-1 cohort, while low m7G score was associated with improved prognostic outcomes and increased likelihood of complete or partial response in the anti-PD-L1 cohort. Different m7G subtypes also showed varying Tumor Mutational Burden (TMB) and immune profiles and might have distinct responses to immunotherapy. Furthermore, we identified five potential genetic markers that were highly correlated with the m7G score signature index. These findings provide insight into the features and classification associated with m7G methylation modifications and may aid in improving the clinical outcome of LGG.
Examining the effect of safety climate on accident risk through job stress: a path analysis
Authors: Khoshakhlagh Amir Hossein , Sulaie Saleh Al , Yazdanirad Saeid , Park JeeWoong
Published: March 2023

Background

Job stress is a probable mediator of the relationship between safety climate and accident occurrence. To demonstrate this, this study investigates the relationship between safety climate, job stress, and accident risk using a large number of surveys. The study will use structural equation modeling (SEM) to analyze the data collected from the surveys to examine the effect of safety climate on accident risk through job stress.

Methods

The study is a cross-sectional study that was conducted on 1,530 male workers of a petrochemical company. The subjects were asked to complete several questionnaires during rest periods, which included demographic information, the Nordic safety climate questionnaire (NOSACQ-50), and the generic job stress questionnaire (GJSQ). Additionally, data on the frequency and intensity of accidents among participants were gathered from the health unit of the company. Path analysis was conducted by structural equation modeling (SEM) in Analysis of Moment Structures (AMOS) software.

Results

The results revealed that the latent variable of safety climate with an effect coefficient of – 0.112 did not have a direct effect on accident risk (P = 0.343). However, safety climate with an effect coefficient of − 0.633 had an indirect effect on accident risk through job stress (P < 0.001). The total score of job stress had a significant direct effect (0.649) on accident risk (P < 0.001). Among the dimensions of safety climate, the variables of management’s safety priority, commitment, and competence (− 0.108) and workers’ safety commitment (− 0.107) had the highest indirect effect coefficients on accident risk. Among the dimensions of job stress, the highest indirect effects belonged to the variables of conflict at work (0.636), physical environment (0.631), and workload and responsibility (0.631), respectively.

Conclusion

The results of the study revealed that job stress mediates the relationship between safety climate and accident risk. This finding suggests that organizations can potentially decrease accidents in industries by addressing and managing job stress in the workplace.
Association between baseline dissociation levels and stress-induced state dissociation in patients with posttraumatic-stress disorder, borderline personality disorder, and major depressive disorder
Authors: Graumann Livia , Heekerens Johannes Bodo , Duesenberg Moritz , Metz Sophie , Spitzer Carsten , Otte Christian , Roepke Stefan , Wingenfeld Katja
Published: March 2023

Introduction

Dissociative symptoms are highly prevalent in patients with trauma-related disorders such as borderline personality disorder (BPD) and posttraumatic-stress disorder (PTSD), and also occur in patients with depressive disorders. Acute dissociative states are theorized to be stress-related, and some individuals experience recurring patterns of dissociation. The relationship between the intensity of dissociative episodes (trait-like dissociation) and acute dissociative states, however, is incompletely understood. In the present study, we investigated how levels of baseline (trait-like) dissociation relate to changes in dissociative states during a laboratory stress induction.

Methods

Our female sample comprised 65 patients with BPD and/or PTSD, 84 patients with major depressive disorder (MDD) and 44 non-clinical controls (NCC). Baseline dissociation was assessed at the start of the study using the Dissociation Tension Scale past week version (DSS-7). All participants underwent the Trier Social Stress Test (TSST) and a placebo version (P-TSST). Before and after the TSST or P-TSST, state dissociation was assessed using the Dissociation Tension Scale acute (DSS-4). We used structural equation models to estimate changes in state dissociation items (somatoform dissociation, derealization, depersonalization, analgesia), and to test whether these changes relate to levels of baseline dissociation.

Results

We found significant increases in all state dissociation items in response to the TSST in patients with BPD and/or PTSD and patients with MDD, but not in NCCs. Increases in somatoform dissociation and derealization during the TSST were significantly related to higher levels of baseline dissociation in patients with BPD and/or PTSD, but not in patients with MDD or NCCs. Results indicate no significant changes in state dissociation during the P-TSST.

Conclusion

Our results replicate earlier findings that patients with BPD and/or PTSD report higher levels of stress-related state dissociation than NCC and extend them to patients with MDD. In addition, our findings indicate that baseline levels of dissociation relate to stress-induced changes in state dissociation among patients with BPD and PTSD, but not patients with MDD. In clinical applications, measures of baseline dissociation could be used to facilitate the prediction and treatment of stress-related dissociative states in patients with BPD and/or PTSD.
Online comic-based art workshops as an innovative patient and public involvement and engagement approach for people with chronic breathlessness
Authors: Harrison Samantha L. , Lawrence Julian , Suri Sophie , Rapley Tim , Loughran Kirsti , Edwards James , Roberts Louise , Martin Denis , Lally Joanne E.
Published: March 2023

Background

Talking about breathlessness can be emotionally challenging. People can feel a sense of illegitimacy and discomfort in some research contexts. Comic-based illustration (cartooning) offers an opportunity to communicate in a more creative and inclusive way. We used cartooning in patient and public involvement and engagement (PPIE) work to explore symptoms of breathlessness and their impact on peoples’ everyday lives.

Main body

Five, 90-min cartooning workshops were delivered online to members of Breathe Easy Darlington (UK). The workshop series involved 5–10 Breathe Easy members and were facilitated by a professional cartoonist supported by three researchers. The experience of living with breathlessness was represented via illustrations of cartoon characters and ideas explored in subsequent conversations. Cartooning was fun and the majority found it a nostalgic experience. Sharing the experience helped the research team develop new understandings of breathlessness and fostered relationships with the Breathe Easy members. The illustrations showed characters leaning against objects, sweating and sitting down, demonstrating living with the sensation of not being in control.

Conclusion

Comic-based art, as a fun and innovative PPIE approach. It facilitated the research team becoming embedded in an existing group who will act as PPIE members on a long-term research programme. Illustrations enabled storytelling and fostered novel insights into the lived experiences of people with breathlessness including sensations of a loss of control, disorientation, and unsteadiness. This will impact on work investigating balance in people with chronic obstructive pulmonary disease. This model has potential to be applied in a range of PPIE and research contexts.
A review article of inflammatory bowel disease treatment and pharmacogenomics
Authors: Eltantawy Nashwa , El-Zayyadi Islam Abd El-Hamid , Elberry Ahmed A. , Salah Layla M. , Abdelrahim Mohamed E. A. , Kassem Amira B.
Published: March 2023

Inflammatory bowel disease (IBD) involves a variety of conditions, particularly Crohn’s disease (CD) and ulcerative colitis (UC). IBD is characterized by chronic inflammatory process of patient’s gut. This review aims to summarize the pharmacogenetics of biologics approved for IBD and the correlation with azathioprine-metabolizing enzymes and adverse reactions, therefore highlighting a likely relationship between particular polymorphisms and therapeutic response. Therefore, we reviewed and discussed the activities of TDM protocols which use monoclonal antibodies (mABs) with a particular attention on the integration of other actions aimed to exploit the most effective and safest medications for IBD cases. The pharmacotherapy of IBD (CD and UC) has experienced a great advancement with the advent of mABs which have peculiar pharmacokinetic properties differentiating them from chemical agents, like aminosalicylates, antimetabolites (e.g., azathioprine (AZA), 6-mercaptopurine (6MP)), and methotrexate), and immunosuppressant agents (steroids and cyclosporine). But clinical studies showed that biologicals might have pharmacokinetic variability which can affect the anticipated clinical outcomes, beyond primary resistance phenomena. Thus, therapeutic drug monitoring (TDM) protocols are applied to the doses of medications according to the required serum mABs levels. This aims to maximize the favorable effects of mABs and minimizing the toxicity. But, the presence of particular genetic polymorphisms in patients might determine a different outcome in response to treatment, indicating the heterogeneity of the effectiveness among IBD cases. Indeed, many reports demonstrated significant associations between polymorphisms and response to biologics. In conclusion, the improvement of TNF-, TNFR and IL-1 pharmacogenetics could be the best approach toward a targeted treatment for IBD. Pre-therapy genotyping has to be integrated with IBD therapeutic guidelines, as it is the most suitable approach to choose the most appropriate biologicals for each case. Also, the addition of pharmacodynamic markers (including serum, cellular, or tissue concentrations of TNF-alpha and IL-8) might boost the predictive performance of models and, eventually, control the disease with a significant improvement in quality of life (QOL).
Fluorescence strip sensor for sensitive determination of prometryn in foods
Authors: Gu Weifang , Suryoprabowo Steven , Guo Lingling , Wu Aihong , Liu Liqiang , Xu Chuanlai
Published: March 2023

We report the development of a sensitive, fast, and simple method for the detection of prometryn (PRO) in potato and celery using a lateral flow immunochromatographic assay (LFIA). A monoclonal antibody (mAb) against PRO was prepared under optimized conditions, and the 50% inhibition concentration (IC50) for use in ELISA was determined to be 0.6 ng mL−1. Moreover, the cut-off value for use in an LFIA was 50 ng mL−1. To validate the reliability of the developed LFIA strip, real samples were used, and the recovery rate was found to be 99.3–104.3%. The assays were completed within 8 min, demonstrating the suitability of our developed methods for the detection of PRO in potato and celery.
Current status and trends of antimicrobial resistance among clinical isolates in China: a retrospective study of CHINET from 2018 to 2022
Authors: Yang Weiwei , Ding Li , Han Renru , Yin Dandan , Wu Shi , Yang Yang , Zhu Demei , Guo Yan , Hu Fupin ,   on behalf of the China Antimicrobial Surveillance Network (CHINET) Study Group, Xu Yingchun , Zhang Xiaojiang , Zhang Zhaoxia , Ji Ping , Kang Mei , He Chao , Wang Chuanqing , Fu Pan , Xu Yuanhong , Huang Ying , Chen Zhongju , Sun Ziyong , Ni Yuxing , Sun Jingyong , Chu Yunzhuo , Tian Sufei , Hu Zhidong , Li Jin , Yu Yunsong , Lin Jie , Shan Bin , Du Yan , Guo Sufang , Wang Yanyan , Wei Lianhua , Wang Xin , Zhang Hong , Wang Chun , Hu Yunjian , Ai Xiaoman , Zhuo Chao , Su Danhong , Wang Ruizhong , Fang Hua , Yu Bixia , Gong Ping , Song Miao , Guo Dawen , Zhao Jinying , Liu Wen’en , Li Yanming , Jin Yan , Wang Yueling , Weng Kaizhen , Zhang Yirong , Xu Xuesong , Yan Chao , Huang Xiangning , Yu Hua , Li Yi , Wang Shanmei , Zhang Lixia , Ma Juan , Zhou Shuping , Ke Jiangwei , Zhu Lei , Meng Jinhua , Shen Han , Zhou Wanqing , Li Gang , Jia Wei , Wu Jinsong , Lu Yuemei , Li Jihong , Liu Jiangshan , Liao Longfeng , Gu Hongqin , Jiang Lin , He Wen , Xue Shunhong , Feng Jiao , Dou Rui , Yue Chunlei , Guo Ruyi , Jin Yan , Ma Xiaobo , Zheng Yanping , Hu Fangfang , Chen Yunsheng , Meng Qing , Xia Yun , Sun Shan
Published: March 2023

Antimicrobial resistance (AMR) is a pressing issue in China, with antibiotic therapy becoming less effective against bacterial infections. To address this challenge, the China Antimicrobial Surveillance Network (CHINET) was established in 2005 to monitor antimicrobial resistance in the country. This study analyzed the CHINET data from teaching hospitals and evaluated the trends of AMR in China from 2018 to 2022. A range of 163,636 to 301,917 isolates was obtained per year, with the majority being Gram-negative bacilli (69.0% to 71.8%). The proportion of important multidrug-resistant pathogens remained stable over the years. While the analysis showed diverse AMR profiles for different bacterial species. Over the five years, generally decreased resistance rates were observed from the majority of the tested species. For example, resistance to ceftriaxone decreased in Escherichia coli and Klebsiella pneumoniae, while resistance to imipenem and meropenem decreased in Pseudomonas aeruginosa. Moreover, resistance to methicillin, gentamicin, fosfomycin, and clindamycin also decreased in clinical Staphylococcus aureus isolates. On the other hand, resistance levels of Acinetobacter baumannii remained stable. Our study provides a comprehensive overview of the AMR profiles of common bacterial species in China and highlights the ongoing efforts to address this challenge.
Measurable Residual Disease and Fusion Partner Independently Predict Survival and Relapse Risk in Childhood KMT2A-Rearranged Acute Myeloid Leukemia: A Study by the International Berlin-Frankfurt-Münster Study Group
Authors: van Weelderen Romy E. , Klein Kim , Harrison Christine J. , Jiang Yilin , Abrahamsson Jonas , Arad-Cohen Nira , Bart-Delabesse Emmanuelle , Buldini Barbara , De Moerloose Barbara , Dworzak Michael N. , Elitzur Sarah , Fernández Navarro José M. , Gerbing Robert B. , Goemans Bianca F. , de Groot-Kruseman Hester A. , Guest Erin , Ha Shau-Yin , Hasle Henrik , Kelaidi Charikleia , Lapillonne Hélène , Leverger Guy , Locatelli Franco , Masetti Riccardo , Miyamura Takako , Norén-Nyström Ulrika , Polychronopoulou Sophia , Rasche Mareike , Rubnitz Jeffrey E. , Stary Jan , Tierens Anne , Tomizawa Daisuke , Zwaan C. Michel , Kaspers Gertjan J.L.
Published: March 2023

PURPOSE

A previous study by the International Berlin-Frankfurt-Münster Study Group (I-BFM-SG) on childhood KMT2A-rearranged ( KMT2A-r) AML demonstrated the prognostic value of the fusion partner. This I-BFM-SG study investigated the value of flow cytometry-based measurable residual disease (flow-MRD) and evaluated the benefit of allogeneic stem-cell transplantation (allo-SCT) in first complete remission (CR1) in this disease.

METHODS

A total of 1,130 children with KMT2A-r AML, diagnosed between January 2005 and December 2016, were assigned to high-risk (n = 402; 35.6%) or non–high-risk (n = 728; 64.4%) fusion partner-based groups. Flow-MRD levels at both end of induction 1 (EOI1) and 2 (EOI2) were available for 456 patients and were considered negative (<0.1%) or positive (≥0.1%). End points were 5-year event-free survival (EFS), cumulative incidence of relapse (CIR), and overall survival (OS).

RESULTS

The high-risk group had inferior EFS (30.3% high risk v 54.0% non-high risk; P < .0001), CIR (59.7% v 35.2%; P < .0001), and OS (49.2% v 70.5%; P < .0001). EOI2 MRD negativity was associated with superior EFS (n = 413; 47.6% MRD negativity v n = 43; 16.3% MRD positivity; P < .0001) and OS (n = 413; 66.0% v n = 43; 27.9%; P < .0001), and showed a trend toward lower CIR (n = 392; 46.1% v n = 26; 65.4%; P = .016). Similar results were obtained for patients with EOI2 MRD negativity within both risk groups, except that within the non–high-risk group, CIR was comparable with that of patients with EOI2 MRD positivity. Allo-SCT in CR1 only reduced CIR (hazard ratio, 0.5 [95% CI, 0.4 to 0.8]; P = .00096) within the high-risk group but did not improve OS. In multivariable analyses, EOI2 MRD positivity and high-risk group were independently associated with inferior EFS, CIR, and OS.

CONCLUSION

EOI2 flow-MRD is an independent prognostic factor and should be included as risk stratification factor in childhood KMT2A-r AML. Treatment approaches other than allo-SCT in CR1 are needed to improve prognosis.
PD-1/PD-L1 Inhibitor Plus Chemotherapy Versus PD-1/PD-L1 Inhibitor in Microsatellite Instability Gastrointestinal Cancers: A Multicenter Retrospective Study
Authors: Chen Mifen , Wang Zhenghang , Liu Zimin , Deng Ting , Wang Xiaodong , Chang Zhiwei , Zhang Qi , Yang Wenlei , Liu Ning , Ji Zhi , Zhang Xiaotian , Wang Xicheng , Peng Zhi , Li Yi , Cao Yujuan , Jin Xuan , Lu Hongxia , Qu Huajun , Tang Yong , Xu Chunlei , Fang Weijia , Zhang Hangyu , Yan Dong , Wang Li , Li Jiayi , Zhang Jingdong , Wang Qiwei , Xue Liying , Yin Fei , Han Guangjie , Cheng Zhiqiang , Liu Qing , Jin Yongdong , Zhang Yinjie , Li Lanxing , Cao Baoshan , Yao Yanhong , Chen Zhiyu , Zou Jianling , Ying Jieer , Wei Qing , Tian Tiantian , Zhao Weifeng , Li Longmei , Zhang Tong , Song Fanghua , Ba Ya-er , Li Na , Gao Hui , Ji Yinghua , Bao Liying , Zhao Xiaochen , Cai Jinping , Yuan Zheping , Shen Lin , Li Jian
Published: March 2023

PURPOSE

To investigate the efficacy of PD-1/PD-L1 inhibitors plus chemotherapy versus anti–PD-1/PD-L1 monotherapy in advanced microsatellite instability (MSI)/mismatch repair-deficient (dMMR) gastrointestinal cancers.

METHODS

We retrospectively recruited patients with MSI/dMMR gastrointestinal cancer who received anti–PD-1/PD-L1 with or without chemotherapy and compared objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) of PD-1/PD-L1 inhibitor plus chemotherapy (chemo-anti–PD-1/PD-L1 group) and PD-1/PD-L1 inhibitor alone (anti–PD-1/PD-L1 group). Propensity score–based overlap weighting analysis was conducted to adjust the baseline covariable imbalance. Sensitivity analysis was performed to confirm the stability of the results by propensity score matching and multivariable Cox and logistic regression models.

RESULTS

A total of 256 patients were eligible, with 68 and 188 receiving chemo-anti–PD-1/PD-L1 and anti–PD-1/PD-L1, respectively. The chemo-anti–PD-1/PD-L1 group showed significant improvements versus the anti–PD-1/PD-L1 group in ORR (61.8% v 38.8%; P = .001), DCR (92.6% v 74.5%; P = .002), PFS (median PFS [mPFS], not reached [NR] v 27.9 months; P = .004), and OS (median OS [mOS], NR v NR; P = .014). After overlap weighting, the improvements tended to be more significant with chemo-anti–PD-1/PD-L1 versus anti–PD-1/PD-L1 in ORR (62.5% v. 38.3%; P < .001), DCR (93.8% v 74.2%; P < .001), PFS (mPFS, NR v 26.0 months; P = .004), and OS (mOS, NR v NR; P = .010). These results were solidified through sensitivity analysis.

CONCLUSION

Chemo-anti–PD-1/PD-L1 is superior to anti–PD-1/PD-L1 in MSI/dMMR gastrointestinal cancers with improved efficacy.
Extinction Panic: C. S. Lewis and Planetary Nihilism
Authors: Harper Tyler Austin
Published: March 2023

Today figures like Elon Musk and Jeff Bezos have become high-profile evangelists for private space exploration, arguing that interplanetary colonization is necessary to save humanity from extinction. Although they may have the sheen of innovation, however, these ideas are not new. A century ago a coterie of British novelists, scientists, and social theorists writing during the interwar period became preoccupied with the possibility of human extinction and believed that such a fate might be avoided by taking human civilization to the stars. Watching these intellectual developments with a wary eye, a young C. S. Lewis was increasingly skeptical of both the “extinction panic” that gripped his contemporaries and the utilitarian and environmentally exploitative imagination of planetary conquest they championed. In response Lewis penned Out of the Silent Planet (1938), a novel that imagines three sentient species that have the means to prevent their own extinction but choose not to do so. Reading Lewis’s novel as a critique of the rapacious ideologies that defined this strain of interwar speculation, this article suggests that the novel models how the humanities might effectively respond to the extinction panic and cosmic adventurism that grip our own imperiled twenty-first century.
Black Soil
Authors: Bain Kimberly
Published: March 2023

This article turns to the minor Black matter of soil to map a provisional theory of Black alchemy. Black alchemy names an erotic and ethical orientation toward the Dead and dead matter. Sifting the metonymic, metaphysical, and material properties between (Black fleshly) matter and (earthly) matters, the article argues for an attention to the erotic relations among Blackness, soil, and Dead (matter). These relations disrupt and refuse the circuits of racial capitalism that establish both Black bodies and soil as sites of resource depletion and commodification. Turning to the syncretic knowledge system of Obeah and tinctures of grave dirt, cachexia africana and histories of dirt eating, and the 2019 performance and installation Dirt Eater by Kiyan Williams, the article asks, What are the practices of those who have collectively lived the end of the world and therefore are already dreaming the messy, dirty end of this one?
Strategies for promoting sustainable use and conservation of indigenous chicken breeds in Sub-Saharan Africa: Lessons from low-income countries
Authors: Kanyama Christopher .M , Moss Amy .F , Crowley Tamsyn .M
Published: March 2023

This review explores innovative and sustainable strategies for the utilisation and conservation of indigenous chickens (IC) (Gallus domesticus) in Sub-Saharan Africa (SSA), drawing lessons from selected low-income countries. Small-scale farmers (SSF) have kept IC for hundreds of years to meet their households' nutritional needs, incomes, and social-cultural and religious uses. The commitment exhibited by SSF to keeping IC has made them the significant custodians of essential animal genetic resources for food and agriculture (AnGR) in most low-income countries. Between 1991 and 2012, Zambia's private breeders invested over US$95 million in the commercial poultry sector, resulting in over a 100% increase in the annual production of day-old chicks to 65 million. However, high production costs and low market access hindered rural farmers' full participation, hence their continued dependence on IC breeds. The erosion of AnGR poses the biggest threat to livelihoods in SSA. The Food and Agriculture Organisation, an international body of the United Nations, highlighted that over 3.5% (60) of chicken breeds were extinct, 21.3% (368) were at risk of extinction, and nearly 63% (1089) were under unknown risk status. The report stated that 12.3% of the known chicken breeds were not at risk. Poultry diseases, lack of sustainable conservation strategies and poor use have significantly contributed to these losses. In 2012, 60% of IC were reportedly diseased in parts of SSA. The continued loss of IC-AnGR may negatively impact rural livelihoods, and future research and breeding programs in poultry may suffer. This paper reviews the IC sector in parts of SSA, the socioeconomic, cultural and religious roles of IC and lessons on researcher community-stakeholder strategies from selected low-income countries. The paper concludes and outlines some recommendations for future research.