bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher expression of denervation‐responsive genes is negatively associated with muscle volume and performance traits in the study of muscle, mobility, and aging (SOMMA)
Authors: Lukasiewicz Cole J. , Tranah Gregory J. , Evans Daniel S. , Coen Paul M. , Barnes Haley N. , Huo Zhiguang , Esser Karyn A. , Zhang Xiping , Wolff Christopher , Wu Kevin , Lane Nancy E. , Kritchevsky Steven B. , Newman Anne B. , Cummings Steven R. , Cawthon Peggy M. , Hepple Russell T.
Published: June 2024

With aging skeletal muscle fibers undergo repeating cycles of denervation and reinnervation. In approximately the 8th decade of life reinnervation no longer keeps pace, resulting in the accumulation of persistently denervated muscle fibers that in turn cause an acceleration of muscle dysfunction. The significance of denervation in important clinical outcomes with aging is poorly studied. The Study of Muscle, Mobility, and Aging (SOMMA) is a large cohort study with the primary objective to assess how aging muscle biology impacts clinically important traits. Using transcriptomics data from vastus lateralis muscle biopsies in 575 participants we have selected 49 denervation‐responsive genes to provide insights to the burden of denervation in SOMMA, to test the hypothesis that greater expression of denervation‐responsive genes negatively associates with SOMMA participant traits that included time to walk 400 meters, fitness (VO2peak), maximal mitochondrial respiration, muscle mass and volume, and leg muscle strength and power. Consistent with our hypothesis, increased transcript levels of: a calciumdependent intercellular adhesion glycoprotein (CDH15), acetylcholine receptor subunits (CHRNA1, CHRND, CHRNE), a glycoprotein promoting reinnervation (NCAM1), a transcription factor regulating aspects of muscle organization (RUNX1), and a sodium channel (SCN5A) were each negatively associated with at least 3 of these traits. VO2peak and maximal respiration had the strongest negative associations with 15 and 19 denervation‐responsive genes, respectively. In conclusion, the abundance of denervationresponsive gene transcripts is a significant determinant of muscle and mobility outcomes in aging humans, supporting the imperative to identify new treatment strategies to restore innervation in advanced age.
Histochemical and immunohistochemical investigation of the number and localization of mast cells in the feline tongue
Authors: Ertuğrul Tuğrul , Tütüncü Şerife , Delice Nurcan , Özdemir Bengül
Published: June 2024

This is the first study to describe the subtypes, number and distribution of mast cells (MC) in cat tongue by histochemical and immunohistochemical methods. Six male adult felines' tongue tissue samples consist of the study's material. Samples were fixed in 10% formaldehyde. MC number and distribution in the feline tongue were assessed using toluidine blue. Also, sections taken from blocks were stained in alcian blue/safranin O (AB/SO) combined dyes to determine the MC subtypes. The Streptavidin biotin complex method using anti‐chymase and anti‐tryptase primary antibodies was used for immunohistochemistry. Metachromatic MCs were mainly observed in the lamina propria close to the multilayered keratinized stratified squamous epithelium. The high number of MCs in this region may be because the dorsal surface of the tongue plays an essential role in the defence system of tongue tissue and, thus, of the body as a whole. Additionally, the number of MCs stained with AB (+) (1.7 ± 0.08) in the feline tongue was statistically higher than those with SO (+) (0.18 ± 0.02). This might be interpreted as an indication that MC heterogeneity may be due not only to their staining properties but also to their localization. It is also conceivable that the high histamine content may be a factor in this. Tryptase‐positive MCs were found in the loose connective tissue around blood vessels, between the glands, as solitary cells, or in groups of several cells. Chymase‐positive MCs were observed more individually rather than in groups. Moreover, chymase‐positive MCs were detected to be located in the filiform papillae subepithelial and in the blood vessels' immediate vicinity. Animals often lick themselves to clean themselves and promote healing. For this reason, it is very important to protect the tongue, which is in direct contact with the external environment, against foreign agents. Considering both the functional and protective properties of the tongue, we concluded that MCs may play a role in oral cavity immunity and protective effect.
A systematic review of case–control studies of cytokines in blister fluid and skin tissue of patients with Stevens Johnson syndrome and toxic epidermal necrolysis
Authors: Stewart Thomas Jonathan , Farrell Joshua , Frew John Walter
Published: June 2024

Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions characterised by keratinocyte apoptosis, necroptosis and epidermal detachment. Several cytokines and cytotoxic proteins have been shown to be elevated in the blood and skin of SJS/TEN sufferers and biologics such as intravenous immune globulin and tumour necrosis factor (TNF)‐alpha inhibitors have demonstrated good therapeutic potential. The exact pathogenic model of SJS/TEN however remains elusive. This systematic review aimed to evaluate the case–control studies of cytokines and cytotoxic proteins in the blister fluid and skin of adults with Stevens Johnson syndrome and/or toxic epidermal necrolysis. This review was registered with INPLASY and conducted in accordance with the PRISMA reporting guidelines. Potential bias was assessed using the NIH criteria. Eleven articles describing results from 96 cases and 170 controls were included. Fas, Fas ligand, Interleukin (IL)‐8 and B‐cell lymphoma (Bcl)‐2 were elevated in SJS/TEN blister fluid and skin tissue, compared with healthy controls. IL‐2, IL‐6, TNF‐alpha, tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL), interferon‐gamma and matrix metalloproteinase‐2 were elevated in SJS/TEN blister fluid compared with fluid sampled from lesional controls. Granulysin, IL‐33, TGF‐beta‐1 and IL‐13 were elevated in SJS/TEN skin tissue compared with lesional lichen planus tissue, as was IL‐13, IFN‐gamma, IL‐2 and IL‐5, when compared with erythema multiforme tissue. A wide array of cytokines and cytotoxic proteins are present at higher concentrations in the blister fluid and skin tissue of SJS/TEN patients compared with healthy and lesional controls. Our findings suggest that these proteins may be pathogenic, as well as possibly markers for diagnosis, disease severity and course. They may also prove to be useful therapeutic targets. More research is needed.
Evaluating the Baby@Home program: Early discharge strategies for (pre)term infants are safe and benefit health outcomes
Authors: Stekelenburg Iza , van den Hoogen Agnes , de Lange Wendela , Peels Barbara , Vijlbrief Daniel C.
Published: June 2024

Aim

Prolonged hospitalisation in the neonatal intensive care unit (NICU) can emotionally tax newborn infants and their families, resulting in developmental adversities and inadequate parent–infant bonding. This study aimed to assess the feasibility and value of the Baby@Home program in reducing prolonged hospital stays.

Methods

This is a retrospective cohort study of 26 infants from a tertiary neonatology department, using qualitative data (gathered through interviews with parents (n = 15) and professionals (n = 5)) and quantitative data (retrieved from medical records and the Luscii application).

Results

Our study included 26 newborn infants. 76% were premature, born at an average term of 35 weeks and 2 days. During the study period, all infants thrived, and only two adverse events occurred (an allergic reaction and respiratory incident necessitating readmission). Interviews were conducted based on six major themes concerning the feasibility and value of the program. Despite the challenges of application utilisation, the program's overall value was evident.

Conclusion

The Baby@Home program effectively facilitated early discharge, promoted family reunification, and yielded favourable safety and health outcomes. Innovative solutions such as Baby@Home have the potential to pave the way for more sustainable and patient‐centred care models.
Clinical course of ulcerative colitis: Frequent use of biologics and low colectomy rate first year after diagnosis—results from the IBSEN III inception cohort
Authors: Strande Vibeke , Lund Charlotte , Hagen Milada , Bengtson May‐Bente , Cetinkaya Raziye Boyar , Detlie Trond Espen , Frigstad Svein Oskar , Høie Ole , Medhus Asle W. , Henriksen Magne , Aass Holten Kristina I. , Hovde Øistein , Huppertz‐Hauss Gert , Johansen Ingunn , Olsen Bjørn Christian , Opheim Randi , Ricanek Petr , Torp Roald , Tønnessen Tor , Vatn Simen , Aabrekk Tone Bergene , Høivik Marte Lie , Kristensen Vendel A.
Published: June 2024

Background

The introduction of biologic therapies and the ‘treat‐to‐target’ treatment strategy may have changed the disease course of ulcerative colitis (UC).

Aims

To describe the early disease course and disease outcome at 1‐year follow‐up in a population‐based inception cohort of adult patients with newly diagnosed UC.

Methods

The Inflammatory Bowel Disease in South‐Eastern Norway (IBSEN) III study is a population‐based inception cohort study with prospective follow‐up. Patients newly diagnosed with inflammatory bowel disease during 2017–2019 were included. Patients ≥18 years at diagnosis of UC who attended the 1‐year follow‐up were investigated. We registered clinical, endoscopic and demographic data at diagnosis and 1‐year follow‐up.

Results

We included 877 patients with UC (median age 36 years (range: 18–84), 45.8% female). At diagnosis, 39.2% presented with proctitis, 24.7% left‐sided colitis and 36.0% extensive colitis. At the 1‐year follow‐up, 13.9% experienced disease progression, and 14.5% had received one or more biologic therapies. The colectomy rate was 0.9%. Steroid‐free clinical remission was observed in 76.6%, and steroid‐free endoscopic remission in 68.7%. Anaemia and initiation of systemic steroid treatment at diagnosis were associated with biologic therapy within the first year after diagnosis.

Conclusion

In this population‐based inception cohort, colectomy rate in the first year after diagnosis was low, and a high proportion of patients were in remission at 1‐year follow‐up. The use of biologic therapy increases, consistent with findings from previous studies.
The aging gastrointestinal tract: Epidemiology and clinical significance of disorders of gut‐brain interaction in the older general population
Authors: Sperber Ami D. , Freud Tamar , Palsson Olafur S. , Bangdiwala Shrikant I. , Simren Magnus
Published: June 2024

Background

Most previous reports on the prevalence of disorders of gut‐brain interaction (DGBI) show higher rates in younger individuals. Exceptions are faecal incontinence and functional constipation.

Aim

To compare prevalence rates for 22 DGBI and 24 primary symptoms, by age, using the Rome Foundation Global Epidemiology (RFGES) study dataset.

Methods

The RFGES dataset enables diagnosis of 22 DGBI among 54,127 participants (≥18 years) in 26 countries. Older age was defined as ≥65 years. We assessed differences between age groups by sex, geographic region, somatisation, abnormal anxiety and depression scores, quality of life (QoL), individual gastrointestinal symptoms and disease severity for irritable bowel syndrome (IBS).

Results

Rates for any DGBI were 41.9% and 31.9% in the <65 and ≥65 age groups, respectively. For all Rome IV diagnoses except faecal incontinence, rates were higher in the younger group. The older group had lower scores for any DGBI by geographic region, non‐gastrointestinal somatic symptoms, abnormal anxiety and depression scores, and IBS severity, and better scores for QoL. The mean number of endorsed symptoms and their frequency were higher in the younger group.

Conclusions

In this large general population study, the prevalence and impact of DGBI, apart from faecal incontinence, were higher in the younger group. Despite this, DGBI rates are still high in absolute terms in the ≥65 age group and necessitate clinical awareness and, perhaps, an age‐specific treatment approach.
Cardiovascular events of Bruton's tyrosine kinase inhibitors: A real‐world study based on the United States Food and Drug Administration Adverse Event Reporting System database
Authors: Zhao Zeng‐Xiang , Yang Tian‐Yi , Wang Yuan‐Hui , Zhang Li , Li Ji , Su Yu‐Wen
Published: June 2024

Aims

Bruton's tyrosine kinase inhibitors (BTKIs), including first‐generation ibrutinib, second‐generation acalabrutinib and zanubrutinib, may be involved in the mechanisms of action related to adverse events (AEs) of the cardiovascular system. We aimed to characterize the cardiovascular AEs of BTKIs reported in the US Food and Drug Administration (FDA) Adverse Event Reporting System, and to compare the cardiovascular risks of BTKIs.

Methods

Across all indications of three FDA‐approved BTKIs, primary suspect drugs were extracted over two periods: from January 2013 to December 2022 (after the approval of the first BTKI), and from January 2020 to December 2022 (all three BTKIs on the market). Disproportionality was measured by reporting odds ratios (RORs) and information components. Additional analyses were performed without incorporating patients with underlying cardiovascular disease (CVD).

Results

A total of 10 353 cases included the uses of ibrutinib, acalabrutinib and zanubrutinib. Ibrutinib was significantly associated with 47 cardiovascular AEs. Acalabrutinib was associated with new signals, including cardiac failure (ROR = 1.82 [1.13‐2.93]), pulmonary oedema (ROR = 2.15 [1.19‐3.88]), ventricular extrasystoles (ROR = 5.18 [2.15‐12.44]), heart rate irregular (ROR = 3.05 [1.53‐6.11]), angina pectoris (ROR = 3.18 [1.71‐5.91]) and cardiotoxicity (ROR = 25.22 [17.14‐37.10]). In addition, cardiovascular events had an earlier onset in acalabrutinib users. Zanubrutinib was only associated with atrial fibrillation. Acalabrutinib and zanubrutinib had lower ROR values than ibrutinib. The AE signals were generally consistent between the population receiving and not receiving CVD medications.

Conclusions

Potential cardiovascular risks identified in this study were not clearly noted on the label of marketed acalabrutinib. Caution should be paid to the cardiovascular risks of BTKIs having been or being developed.
International consensus panel for transurethral resection of bladder tumours metrics: assessment of face and content validity
Authors: Paciotti Marco , Diana Pietro , Gallioli Andrea , De Groote Ruben , Farinha Rui , Ficarra Vincenzo , Gaston Richard , Gontero Paolo , Hurle Rodolfo , Martínez‐Piñeiro Luis , Minervini Andrea , Pansadoro Vito , Van Cleynenbreugel Ben , Wiklund Peter , Casale Paolo , Lughezzani Giovanni , Uleri Alessandro , Mottrie Alexandre , Palou Joan , Gallagher Anthony G. , Breda Alberto , Buffi Nicolò
Published: June 2024

Objective

To develop performance metrics that objectively define a reference approach to a transurethral resection of bladder tumours (TURBT) procedure, seek consensus on the performance metrics from a group of international experts.

Methods

The characterisation of a reference approach to a TURBT procedure was performed by identifying phases and explicitly defined procedure events (i.e., steps, errors, and critical errors). An international panel of experienced urologists (i.e., Delphi panel) was then assembled to scrutinise the metrics using a modified Delphi process. Based on the panel's feedback, the proposed metrics could be edited, supplemented, or deleted. A voting process was conducted to establish the consensus level on the metrics. Consensus was defined as the panel majority (i.e., >80%) agreeing that the metric definitions were accurate and acceptable. The number of metric units before and after the Delphi meeting were presented.

Results

A core metrics group (i.e., characterisation group) deconstructed the TURBT procedure. The reference case was identified as an elective TURBT on a male patient, diagnosed after full diagnostic evaluation with three or fewer bladder tumours of ≤3 cm. The characterisation group identified six procedure phases, 60 procedure steps, 43 errors, and 40 critical errors. The metrics were presented to the Delphi panel which included 15 experts from six countries. After the Delphi, six procedure phases, 63 procedure steps, 47 errors, and 41 critical errors were identified. The Delphi panel achieved a 100% consensus.

Conclusion

Performance metrics to characterise a reference approach to TURBT were developed and an international panel of experts reached 100% consensus on them. This consensus supports their face and content validity. The metrics can now be used for a proficiency‐based progression training curriculum for TURBT.
Positive allosteric modulation of the cannabinoid CB1 receptor potentiates endocannabinoid signalling and changes ERK1/2 phosphorylation kinetics
Authors: Green Hayley M. , Manning Jamie J. , Greig Ian R. , Ross Ruth A. , Finlay David B. , Glass Michelle
Published: June 2024

Background and Purpose

Activation of CB1 by exogenous agonists causes adverse effects in vivo. Positive allosteric modulation may offer improved therapeutic potential and a reduced on‐target adverse effect profile compared with orthosteric agonists, due to reduced desensitisation/tolerance, but this has not been directly tested. This study investigated the ability of PAMs/ago‐PAMs to induce receptor regulation pathways, including desensitisation and receptor internalisation.

Experimental Approach

Bioluminescence resonance energy transfer (BRET) assays in HEK293 cells were performed to investigate G protein dissociation, ERK1/2 phosphorylation and β‐arrestin 2 translocation, while immunocytochemistry was performed to measure internalisation of CB1 in response to the PAMs ZCZ011, GAT229 and ABD1236 alone and in combination with the orthosteric agonists AEA, 2‐AG, and AMB‐FUBINACA.

Key Results

ZCZ011, GAT229 and ABD1236 were allosteric agonists in all pathways tested. The ago‐PAM ZCZ011 induced a biphasic ERK1/2 phosphorylation time course compared to transient activation by orthosteric agonists. In combination with 2‐AG but not AEA or AMB‐FUBINACA, ZCZ011 and ABD1236 caused the transient peak of ERK1/2 phosphorylation to become sustained. All PAMs increased the potency and efficacy of AEA‐induced signalling in all pathways tested; however, no notable potentiation of 2‐AG or AMB‐FUBINACA was observed.

Conclusion and Implications

Ago‐PAMs can potentiate endocannabinoid CB1 agonism by AEA to a larger extent compared with 2‐AG. However, all compounds were found to be allosteric agonists and induce activation of CB1 in the absence of endocannabinoid, including β‐arrestin 2 recruitment and internalisation. Thus, the spatiotemporal signalling of endogenous cannabinoids will not be retained in vivo.
Association between plasma proteome and pulmonary heart disease: A two‐stage Mendelian randomization analysis
Authors: Li Shiyang , Ding Haifeng , Li Qi , Zeng Xiaobin , Zhang Yanyu , Lai Chengyi , Xie Xiaoshuang , Tang Yongjiang , Lan Jianjun
Published: June 2024

Pulmonary heart disease (PHD) involves altered structure and function of the right ventricle caused by an abnormal respiratory system that causes pulmonary hypertension. However, the association between changes in plasma proteomics and PHD remains unclear. Hence, we aimed to identify causal associations between genetically predicted plasma protein levels and PHD. Mendelian randomization was performed to test the target proteins associated with PHD. Summary statistics for the human plasma proteome and pulmonary heart disease were acquired from the UK Biobank (6038 cases and 426 977 controls) and the FinnGen study (6753 cases and 302 401 controls). Publicly available pQTLs datasets for human plasma proteins were obtained from a largescale genome‐wide association study in the INTERVAL study. The results were validated using a case–control cohort. We first enrolled 3622 plasma proteins with conditionally independent genetic variants; three proteins (histo‐blood group ABO system transferase, activating signal cointegration 1 complex subunit 1, and calcium/calmodulin‐dependent protein kinase I [CAMK1]) were significantly associated with the risk of pulmonary heart disease in the UK Biobank cohort. Only CAMK1 was successfully replicated (odds ratio: 1.1056, 95% confidence interval: 1.019–1.095, p = 0.0029) in the FinnGen population. In addition, the level of CAMK1 in 40 patients with PHD was significantly higher (p = 0.023) than that in the control group. This work proposes that CAMK1 is associated with PHD, underscoring the importance of the calcium signaling pathway in the pathophysiology to improve therapies for PHD.
Utilizing synchronous care to improve cardiovascular and renal health among patients with type 2 diabetes: Proof‐of‐concept results from the DECIDE‐CV clinical programme
Authors: Marques Pedro , Mavrakanas Thomas A. , Guida Julian , Gédéon Tara , Emami Anahita , Alaamiri Abdulkhaliq , Ho Daniel , Possik Elite , Zhang Guang , Tsoukas Michael A. , Sharma Abhinav
Published: June 2024

Aim

The management of patients with type 2 diabetes is asynchronous, i.e. not coordinated in time, resulting in delayed access to care and low use of guideline‐directed medical therapy (GDMT).

Methods

We retrospectively analysed consecutive patients assessed in the ‘synchronized’ DECIDE‐CV clinic. In this outpatient clinic, patients with type 2 diabetes and cardiovascular or chronic kidney disease are simultaneously assessed by an endocrinologist, cardiologist and nephrologist in the same visit. The primary outcome was use of GDMT before and after the assessment in the clinic, including sodium‐glucose cotransporter 2 inhibitors, glucagon‐like peptide 1 receptor agonists, renin‐angiotensin system blockers and mineralocorticoid receptor antagonists. Secondary outcomes included the baseline‐to‐last‐visit change in surrogate laboratory biomarkers.

Results

The first 232 patients evaluated in the clinic were included. The mean age was 67 ± 12 years, 69% were men and 92% had diabetes. In total, 73% of patients had atherosclerotic cardiovascular disease, 65% heart failure, 56% chronic kidney disease and 59% had a urinary albumin‐to‐creatinine ratio ≥30 mg/g. There was a significant increase in the use of GDMT:sodium‐glucose cotransporter 2 inhibitors (from 44% to 87% of patients), glucagon‐like peptide 1 receptor agonists (from 8% to 45%), renin‐angiotensin system blockers (from 77% to 91%) and mineralocorticoid receptor antagonists (from 25% to 45%) (p < .01 for all). Among patients with paired laboratory data, glycated haemoglobin, urinary albumin‐to‐creatinine ratio and N‐terminal proB‐type natriuretic peptide levels significantly dropped from baseline (p < .05 for all).

Conclusions

Joint assessment of patients with diabetes in a synchronized cardiometabolic clinic holds promise for enhancing GDMT use and has led to significant reductions in surrogate cardiovascular and renal laboratory biomarkers.
Institutionalizing foresight in science, technology, and innovation in sub‐Saharan Africa
Authors: Ouma‐Mugabe John , Botha Anthon , Letaba Petrus
Published: June 2024

Motivation

Foresight is increasingly being institutionalized and used in science, technology and innovation (STI) policy processes around the world. Foresight is a toolbox to help decision‐makers generate intelligence about future scientific and technological advances and to frame long‐term STI policy goals and rationales. Foresight can be used to inform policy to steer research and innovation (R&I) towards attaining sustainable development goals. Yet, foresight is not institutionalized and used in sub‐Saharan Africa (SSA) at a time when many governments are formulating new STI policies and some of their science granting councils (SGCs) are setting R&I priorities.

Purpose

This exploratory study is about challenges and opportunities of institutionalizing STI foresight in SSA. It identifies ways of institutionalizing and using STI foresight.

Methods and approach

A literature review, bibliometric analysis, interviews, an online survey, and focus group discussions were conducted to identify challenges to, and lessons for, institutionalizing STI foresight in SSA. The literature identified good practices for institutionalizing STI foresight in selected developed countries, to draw lessons for SSA.

Findings

While academic research on STI foresight and related topics is increasing, there is very limited foresight practice in STI policy processes in SSA. This is mainly owing to low awareness of STI foresight, weak technical capacity, and generally a lack of foresight culture in STI policy‐making in the region.

Policy implications

Building capacity within governments and establishing a community of practice in STI foresight may help improve the quality and effectiveness of STI policy in SSA. It may enable institutions such as science granting councils (SGCs) to make informed funding decisions, targeting scarce resources at priority research and innovation. Overall, building STI foresight literacy and skills, as well as establishing designated offices for STI foresight, supported by the knowledge to select and adapt foresight tools, will result in improved STI policy‐making in SSA.
To move or not to move: Dispersal of Orius insidiosus in strawberry plants
Authors: Alonso Mariángeles , Guisoni Nara , Rocca Margarita , Greco Nancy
Published: June 2024

Spatial and temporal distribution of food resources influences predatory insects' foraging and dispersal behavior. Orius insidiosus (Say) (Hemiptera: Anthocoridae) is a good biological control agent of western flower thrips (WFT), Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), in the strawberry crop and consumes two‐spotted spider mite (TSSM), Tetranychus urticae Koch (Acari: Tetranychidae), and pollen as well. Augmentative biological control programs may fail if, following release, predators disperse from the crop. We studied the dispersal of O. insidiosus as a function of pollen availability, density of their main prey WFT, and the presence of the alternative prey TSSM, within and between strawberry plants. We found that O. insidiosus remained on the flowers during the 24 h of the assay. The dispersal of predators to a neighboring flower with thrips was approximately six times greater from a flower without pollen than from a flower with pollen. When TSSM was the only prey available, O. insidiosus colonized the leaves, and its dispersal within the plant was greater. At the plot scale, the predator dispersal from the release plant to other plants also depended on the presence of flowering plants and prey. Our results highlight the importance of flowering plants and pollen availability in enhancing the persistence of O. insidiosus in strawberry plants. Releases of this predator in the strawberry crop should be after the beginning of flowering, even at low WFT densities.
Reviewing the impact of hydroxyurea on DNA methylation and its potential clinical implications in sickle cell disease
Authors: Lewis Jasmine , Guilcher Gregory M. T. , Greenway Steven C.
Published: June 2024

Hydroxyurea (HU) is the most common drug therapy for sickle cell disease (SCD). The clinical benefits of HU derive from its upregulation of fetal hemoglobin (HbF), which reduces aggregation of the mutated sickle hemoglobin protein (HbS) and reduces SCD symptoms and complications. However, some individuals do not respond to HU, or stop responding over time. Unfortunately, current understanding of the mechanism of action of HU is limited, hindering the ability of clinicians to identify those patients who will respond to HU and to optimize treatment for those receiving HU. Given that epigenetic modifications are essential to erythropoiesis and HbF expression, we hypothesize that some effects of HU may be mediated by epigenetic modifications, specifically DNA methylation. However, few studies have investigated this possibility and the effects of HU on DNA methylation remain relatively understudied. In this review, we discuss the evidence linking HU treatment to DNA methylation changes and associated gene expression changes, with an emphasis on studies that were performed in individuals with SCD. Overall, although HU can affect DNA methylation, research on these changes and their clinical effects remains limited. Further study is likely to contribute to our understanding of hematopoiesis and benefit patients suffering from SCD.
Early effect of onabotulinumtoxinA on EEG‐based functional connectivity in patients with chronic migraine: A pilot study
Authors: Conti Matteo , Bovenzi Roberta , Palmieri Maria Giuseppina , Placidi Fabio , Stefani Alessandro , Mercuri Nicola Biagio , Albanese Maria
Published: June 2024

Objective

In this pilot prospective cohort study, we aimed to evaluate, using high‐density electroencephalography (HD‐EEG), the longitudinal changes in functional connectivity (FC) in patients with chronic migraine (CM) treated with onabotulinumtoxinA (OBTA).

Background

OBTA is a treatment for CM. Several studies have shown the modulatory action of OBTA on the central nervous system; however, research on migraine is limited.

Methods

This study was conducted at the Neurology Unit of “Policlinico Tor Vergata,” Rome, Italy, and included 12 adult patients with CM treated with OBTA and 15 healthy controls (HC). Patients underwent clinical scales at enrollment (T0) and 3 months (T1) from the start of treatment. HD‐EEG was recorded using a 64‐channel system in patients with CM at T0 and T1. A source reconstruction method was used to identify brain activity. FC in δ‐θ‐α‐β‐low‐γ bands was analyzed using the weighted phase‐lag index. FC changes between HCs and CM at T0 and T1 were assessed using cross‐validation methods to estimate the results’ reliability.

Results

Compared to HCs at T0, patients with CM showed hyperconnected networks in δ (p = 0.046, area under the receiver operating characteristic curve [AUC: 0.76‐0.98], Cohen's κ [0.65‐0.93]) and β (p = 0.031, AUC [0.68‐0.95], Cohen's κ [0.51‐0.84]), mainly involving orbitofrontal, occipital, temporal pole and orbitofrontal, superior temporal, occipital, cingulate areas, and hypoconnected networks in α band (p = 0.029, AUC [0.80‐0.99], Cohen's κ [0.42‐0.77]), predominantly involving cingulate, temporal pole, and precuneus. Patients with CM at T1, compared to T0, showed hypoconnected networks in δ band (p = 0.032, AUC [0.73‐0.99], Cohen's κ [0.53‐0.90]) and hyperconnected networks in α band (p = 0.048, AUC [0.58‐0.93], Cohen's κ [0.37‐0.78]), involving the sensorimotor, orbitofrontal, cingulate, and temporal cortex.

Conclusion

These preliminary results showed that patients with CM presented disrupted EEG‐FC compared to controls restored by a single session of OBTA treatment, suggesting a primary central modulatory action of OBTA.
Hard to reach? Methodological challenges researching vulnerable, gang‐involved, young people
Authors: Barker Rhiannon , Bonell Chris , Melendez‐Torres G. J.
Published: June 2024

Introduction

Research with young people (YP) is ethically challenging and bound in a complex maze of issues relating to power, voice and representation. Such sensitivities mean that the challenges raised in researching marginalised YP are often hard to navigate. This paper reports on research carried out with YP to explore links between mental health, school exclusion and involvement in criminal gangs. It aims to provide a practical guide to negotiating some of the methodological and ethical challenges experienced.

Method

In‐depth interviews conducted with 28 YP (aged 14–24 years) who were gang involved or seen to be at risk of gang involvement. Research was conducted in youth clubs, alternative provision and youth justice settings.

Results: Observations/Reflections

We reflect on how navigating ethics can create barriers to involving YP as primary informants in research. We consider why it is important to overcome these hurdles and how public engagement work with recognised gatekeepers and the use of creative interview methods can facilitate meaningful encounters, where YP feel able to share valuable insights into their lives.

Conclusion

Alongside a number of specific learning points, the paper reflects on theories behind research with YP, including the need for recognition of power imbalances and reflexivity. It concludes with thoughts on the practical realities of achieving meaningful participation or an ‘authentic voice’ with marginalised groups and the importance of this in informing policy and practice.

Patient or Public Contribution

The focus of this work was to collect experiences of YP who are recognised as gang‐involved or at risk of being so, with a view to informing health and education policies. The scoping study for the project involved extensive public engagement work with YP exploring and trialling suitable methods of accessing, recruiting and ultimately interviewing this target group. This is central to the discussion within the body of the paper.
A systematic review on the impact of sub‐epidermal moisture assessments on pressure ulcer/injury care delivery pathways
Authors: Avsar Pinar , Patton Declan , Cuddigan Janet , Moore Zena
Published: June 2024

To assess all published studies which describe what happens to the delivery of pressure ulcer/injury (PI/PU) care pathways as a result of detecting raised sub‐epidermal moisture (SEM) delta (∆ ≥ 0.6). We undertook a systematic review of the literature, and included original research studies using either a prospective or retrospective study design that report the impact that assessment using SEM assessments have on healthcare practitioners' delivery of PI/PU care pathways in adults at risk of developing PI/PUs. The review protocol was registered on PROSPERO (CRD42023416975). A literature search was conducted in May 2023, using PubMed, CINAHL, Scopus, Cochrane, EMBASE, Web of Science and Science Direct databases. Data were extracted using a data extraction tool including elements such as country, setting, sample size, intervention, control and quality appraisal was undertaken using the Evidence‐based Librarianship. We identified nine papers published between 2017 and 2022. The majority of these studies were conducted in England (n = 6; 67%). The systematic review included studies conducted across multiple care settings including acute care, medical‐surgical units, and palliative care, highlighting the importance of PI/PU prevention and management across diverse patient populations. The PI/PU care pathways implemented in the studies varied, but commonly included elements such as the application or increased use of pressure‐redistributing mattresses/cushions, implementation of repositioning plans, management of incontinence and moisture, regular skin inspection, and assessment of patient mobility. Out of the nine studies identified, seven reported PI/PU incidence. A meta‐analysis of seven studies (N = 18 451) demonstrated a statistically significant reduction in visual PI/PU development in favour of SEM‐guided care pathways compared to usual care (the odds ratio = 0.36 [95% confidence interval: 0.24–0.53, p < 0.00001]). This systematic review provides evidence that implementing SEM assessments in patients at risk of developing PI/PUs prompts anatomy‐specific clinical actions. The subsequent implementation of enhanced and targeted skin care interventions leads to consistent and sustained reductions in hospital‐acquired PU incidence. The findings emphasise the importance of incorporating SEM assessments as part of comprehensive PI/PU prevention strategies in all care settings and patient populations. This systematic review is limited by the predominance of observational studies and variable study quality. Future research should focus on randomised trials in different care settings that monitor the efficacy of preventive interventions and their impact in reducing PI/PU incidence when implemented based on SEM assessments.
A pragmatic randomised controlled trial of the effectiveness and cost‐effectiveness of Well Parent Japan in routine care in Japan: The training and nurturing support for mothers (TRANSFORM) study
Authors: Shimabukuro Shizuka , Oshio Takashi , Endo Takahiro , Harada Satoshi , Yamashita Yushiro , Tomoda Akemi , Guo Boliang , Goto Yuko , Ishii Atsuko , Izumi Mio , Nakahara Yukiko , Yamamoto Kazushi , Daley David , Tripp Gail
Published: June 2024

Background

Well Parent Japan (WPJ) is a new hybrid group parent training programme combining sessions to improve mothers' psychological well‐being with a culturally adapted version of the New Forest Parenting Programme (NFPP). This study investigates the effectiveness and cost‐effectiveness of WPJ against treatment as usual (TAU) within Japanese child mental health services.

Methods

TRANSFORM was a pragmatic multi‐site randomised controlled trial (RCT) with two parallel arms. Altogether 124 mothers of 6–12‐year‐old children with DSM‐5 ADHD were randomised to WPJ (n = 65) or TAU (n = 59). Participants were assessed at baseline, post‐treatment and three‐month follow‐up. The primary outcome was parent‐domain stress following intervention. Secondary outcomes included maternal reports of child‐domain stress, parenting practices, parenting efficacy, mood, family strain, child behaviour and impairment. Objective measures of the parent–child relationship were collected at baseline and post‐treatment. Data analysis was intention to treat (ITT) with treatment effects quantified through analysis of covariance (ANCOVA) via multilevel modelling. An incremental cost‐effectiveness ratio (ICER) assessed WPJ's cost‐effectiveness.

Results

WPJ was superior to TAU in reducing parent‐domain stress post‐treatment (adjusted mean difference = 5.05, 95% CI 0.33 to 9.81, p = .036) and at follow‐up (adjusted mean difference 4.82, 95% CI 0.09 to 9.55, p = .046). Significant WPJ intervention effects were also observed for parenting practices, parenting efficacy and family strain. WPJ and TAU were not significantly different post‐intervention or at follow‐up for the other secondary outcomes. The incremental cost of WPJ was 34,202 JPY (315.81 USD). The probability that WPJ is cost‐effective is 74% at 10,000 JPY (USD 108.30) per one‐point improvement in parenting stress, 92% at 20,000 JPY (216.60 USD). The programme was delivered with high fidelity and excellent retention.

Conclusions

WPJ can be delivered in routine clinical care at modest cost with positive effects on self‐reported well‐being of the mothers, parenting practices and family coping. WPJ is a promising addition to psychosocial interventions for ADHD in Japan.
Changes in emotion regulation strategies during the pandemic: prospective pathways to adolescent depressive symptoms
Authors: Liu Sihan , Xu Jianjie , Cao Huiting , An Ye , Li Yijia , Li Zhuangyang , Gao Mengyu (Miranda) , Han Zhuo Rachel
Published: June 2024

Background

Emotion regulation (ER) is considered central in adolescent psychopathology, and ER strategies may change during challenging times, such as a global pandemic. Despite this, there remains a limited understanding of individual differences in ER mechanisms and their associations with psychopathology. This study examined whether and how cognitive reappraisal, expressive suppression, and self‐compassion changed over COVID‐19 and how these changes uniquely predicted adolescents' depressive symptoms.

Methods

A total of 2,411 adolescents (58.6% females; Mage = 18.51, SD = 0.80) completed the Emotional Regulation Questionnaire, the Self‐compassion Scale, and the Symptom Checklist‐90 before COVID‐19 (in 2019) and during COVID‐19 (in 2020). The predictive associations between each ER strategy and depressive symptoms were tested with latent change score models.

Results

Adolescents' use of expressive suppression and self‐compassion strategies both increased during COVID‐19. More increases in expressive suppression predicted more depressive symptoms, whereas more increases in self‐compassion predicted fewer depressive symptoms. Although, on average, cognitive reappraisal did not change, it did show significant variations within the sample – increases (vs. decreases) in cognitive appraisal predicted fewer depressive symptoms.

Conclusions

The study indicates how adolescents' ER strategies changed during the unprecedented global pandemic. It underscores protective roles of increased cognitive reappraisal and self‐compassion, as well as the adverse consequence of heightened expressive suppression on adolescents' depressive symptoms. Findings offer insights for targeted interventions aimed at addressing specific ER strategies.
Adherence to medication, dietary and physical activity recommendations: Findings from a multicenter cross‐sectional study among adults with diabetes in rural South Africa
Authors: Owolabi Eyitayo O. , Ajayi Anthony Idowu
Published: June 2024

Background

Diabetes is a complex health condition requiring medical therapy and lifestyle modifications to attain treatment targets. Previous studies have not fully explored factors associated with adherence to medication, diets and physical activity recommendations among individuals living with diabetes in rural South Africa. We examined the association between knowledge, health belief and adherence to medication, dietary, and physical activity recommendations and explored self‐reported reasons for non‐adherence.

Methods

This cross‐sectional study was conducted among 399 individuals living with diabetes recruited over 12 weeks from six randomly selected primary healthcare centres in rural South Africa. Sociodemographic and clinical data were obtained by self‐report. Health beliefs, knowledge, and adherence were assessed using validated measures. Descriptive and inferential statistics were carried out.

Results

The majority (81.7%) of the participants were females, with a mean age of 62 ± 11 years. Only 39% reported adhering to their prescribed medication regimen, 25% reported adhering to dietary recommendations, and 32% reported adhering to physical activity recommendations. The most cited reasons for non‐adherence were lack of access to (n = 64) and cost of drugs (n = 50), perceived high costs of healthy diets (n = 243), and lack of time (n = 181) for physical activity. Level of education was an independent predictor of medication adherence [odds ratio, OR = 2.02 (95% confidence interval, CI: 1.20–3.40)] while diabetes knowledge was independently associated with both medications [OR = 3.04 (95% CI: 1.78–45.12)]; and physical activity adherence [OR = 2.92 (95% CI: 1.04–2.96). Positive health belief was independently associated with adherence to medications [OR = 1.72 (95% CI: 1.15–2.57) and dietary recommendations [OR = 1.75 (95% CI: 1.04–2.96)].

Conclusion

Adherence to three important self‐care practices, medication, diet, and physical activity, was suboptimal in this study setting. Socioeconomic reasons and access barriers were significant drivers of non‐adherence, while increased knowledge and positive health beliefs were potential facilitators. Efforts to improve medication adherence and foster engagement in healthy lifestyle behaviours must consider patients’ knowledge and health beliefs. Primary healthcare providers should create awareness on the importance of adherence on health outcomes for people with diabetes. Likewise, efforts to increase the availability and affordability of medications for socioeconomically disadvantaged populations should be prioritised by the key health stakeholders.
Assessing future urban flood hazard: A comprehensive approach to estimating the implications of future rainfall scenarios
Authors: Moon Hyeon‐Tae , Yoon Sun‐Kwon , Kim Jong‐Suk , Moon Young‐Il
Published: June 2024

Estimating potential changes in future flood patterns based on anticipated changes in hydrological characteristics within the basin is crucial for mitigating flood damage and managing flood risk. In this study, nonparametric probability models are used to estimate future rainfall patterns in Seoul under the GCM‐based climate change scenarios (CCS), and the estimated future daily rainfall data was temporally downscaled to hourly units using the KNNR‐GA technique. Changes in flood hazard and runoff characteristics of the target area based on the estimated future rainfall data are quantitatively assessed. The results highlight that under CCS, flood runoff may increase further into the future, resulting in more significant changes in flood patterns and accelerating the increase in flood hazard. The delta change factor of flood risk indicators increased relatively significantly in more severe CCS. This study also proposed a process to estimate future flood runoff and mitigation effects according to CCS by reflecting various flood mitigation measures in the urban drainage system model. These findings can offer valuable insights for setting the direction of current and future mitigation measures.
The Associations Between Health‐Related Knowledge and Health Beliefs Regarding Risk for Gestational Diabetes in American Indian and Alaska Native Female Adolescents and Young Adults at Risk for Gestational Diabetes and Their Female Caregivers: A Cross‐Sectional Dyadic Analysis
Authors: Sereika Susan M. , Moore Kelly R. , Stotz Sarah , Chalmers Laura J. , Garrow Heather , Gonzales Kelly , O'Banion Nancy , Powell Jeffrey , Knoki‐Wilson Ursula , Charron‐Prochownik Denise ,   For The Stopping GDM Study Group
Published: June 2024

Introduction

Research on associations between knowledge and health beliefs for women at risk for gestational diabetes mellitus (GDM) has focused on adults at risk for or having GDM. Gaps also exist in examining interpersonal associations with family members or peers. We examined dyadic associations between knowledge and health beliefs about the risk for GDM between and within American Indian and Alaska Native (AIAN) female adolescents and young adults (FAYAs) at risk for GDM and their mothers or adult female caregivers (FCs).

Methods

Grounded in the Expanded Health Belief Model, we employed a cross‐sectional design using baseline data from 147 dyads of AIAN FAYAs at risk for GDM and their FCs who participated in the Stopping GDM in Daughters and Mothers trial. FAYAs were 12.0 to 24.5 years of age, and 89.1% were students. FCs had a mean (SD) age of 44.0 (9.3) years, 87.0% were AIAN, 44.9% were college educated, 19.7% had ever had GDM, and 81.0% were the FAYA's mother. FAYAs and FCs completed surveys about knowledge and health beliefs (benefits, barriers, severity, susceptibility) regarding GDM risk and prevention. Bivariate correlational analyses were performed to examine associations between and within dyad members. Dyadic associations were investigated using actor‐partner interdependence modeling (APIM) assuming distinguishable dyad members.

Results

Compared with their FCs, FAYAs had lower health‐related knowledge and perceived benefits of GDM prevention and susceptibility regarding GDM risk. APIM revealed actor and partner effects of health‐related knowledge on health beliefs for dyads. In particular, positive actor effects were found for FAYAs and FCs for GDM‐related knowledge with perceived benefits (P < .001), and positive partner effects of GDM‐related knowledge for FCs were related to perceived susceptibility and severity for FAYAs (P < .05).

Discussion

As shown in these AIAN dyads, FAYAs and their FCs, as members of one another's social network, may influence each other's health beliefs regarding GDM risk and prevention.