bluuebunny/crossref_metadata_2025 huggingface dataset:
Haemophilia, the journey in search of a cure. 1960–2020
Authors: Nathwani Amit C. , Tuddenham Edward G. D.
Published: September 2023

The single most important step on the path to our modern understanding of blood coagulation and haemophilia in the 20th century was taken by British pathologist Robert Gwyn Macfarlane with his 1964 publication ‘An enzyme cascade in the blood clotting mechanism, and its function as a biochemical amplifier’. In the same year, Ratnoff and Davie in the USA reached the same conclusion. Macfarlane and Rosemary Biggs had previously, in 1952, discovered factor IX as the factor deficient in haemophilia B. In 1973, Arthur Bloom defined the distinct role of Factor VIII and von Willebrand factor in haemophilia A and von Willebrand’s disease respectively. This inspired the efforts of Tuddenham and his group towards the purification of Factor VIII which reached homogeneity in 1982, leading to the cloning of the Factor VIII gene in 1984 in collaboration with US scientists at Genentech, which in turn enabled development of safe recombinant factor concentrates for patients with haemophilia. Brownlee cloned the factor IX gene in 1982 at the Sir William Dunn Institute of Pathology in Oxford. This led eventually to the first successful trial of gene therapy for haemophilia B in 2011 by the Nathwani group at UCL, which built on pioneering work of US groups and was partnered with St Jude in Memphis where Nathwani started the project. This trial has fuelled the current quest for a functional cure of haemophilia A and B. The UK has, therefore, made a rich contribution to advances in haemostasis over the last 60 years, often in partnership with other groups across the world.
Hairy Cell Leukaemia: From Hairy Beginnings to a BRAF New World
Authors: Dearden Claire , Iyengar Sunil
Published: September 2023

For a disease initially described in 1958 as a leukaemic reticulo‐endotheliosis associated with poor outcomes, we have come a long way in our understanding of Hairy cell leukaemia. The vast majority of patients diagnosed with this rare, often diagnostically challenging, leukaemia can now expect a lifespan that is similar to the general population. This article covers some of the highlights from the last 6 decades that have led to our current understanding of this fascinating leukaemia ‐ from elucidation of its B‐cell origin to discovery of the almost universal occurrence of the BRAF V600E mutation; from the initial successes reported with splenectomy to the more recent development of targeted therapies such as Vemurafenib and Moxetumomab Pasudotox. It also pays tribute to some of the outstanding research in this field focusing particularly on the significant contributions made by the clinical and scientific community in the UK.
Acute lymphoblastic leukaemia (ALL) things come to those who wait: 60 years of progress in the treatment of adult ALL
Authors: Fielding Adele K. , Goldstone Anthony H.
Published: September 2023

The UK has made a well‐recognised contribution to the international effort to understand and treat acute lymphoblastic leukaemia (ALL) in adults. Work done in the UK by numerous personnel over many years has been instrumental in developing novel risk stratifications, evaluating treatment strategies for adult patients with de novo and relapsed disease and in making novel scientific contributions. The UK has championed and achieved very high levels of recruitment to clinical trials and, in particular, is known for success in large, investigator‐initiated randomised controlled trials. This historical review charts the progress of clinical research in adult ALL from its inception to the present day.
BSH 2020 Student Essay Prize ‐ ‘How are you inspired by haematology and how will you inspire others to become haematologists?’
Authors: Girard Louis‐Pierre
Published: September 2023

All medical personnel ponder their future career, and students perhaps more so than professionals. Indeed, there are many old and famous specialties in which we might envision ourselves forging a path, each competing for our attention. Far‐off from the clamour and glamour of venerable medicine and surgery, however, there lies younger specialties that reward quiet curiosity and stolid perseverance. Chief amongst them, in my eyes, is the speciality of haematology. Often misunderstood or otherwise unheard of, the subject of haematology and those practice it have steadily plotted a course through the maelstrom of blood disease and unremittingly turned its tide back in favour of the patients, for whom they labour. As the British Society for Haematology celebrates its 60th anniversary, the question rightly posed this year to interested students is, based on our own personal reflections, how should we continue to nourish the buds of enthusiasm and interest for this still‐blossoming specialty? In this essay, I put forth those intellectual and historical facets of haematology which have given me great inspiration, and I reflect on how we, as practitioners or as aspirants, can best cultivate the passion we feel for our subject in the hearts of others.
Retrospective first‐in‐human use of the LithoVue™ Elite ureteroscope to measure intrarenal pressure
Authors: Bhojani Naeem , Koo Kyo Chul , Bensaadi Kahina , Halawani Abdulghafour , Wong Victor KF. , Chew Ben H.
Published: September 2023

Objective

To report on our first‐in‐human experience using the LithoVue Elite™ ureteroscope (Boston Scientific Corp., Marlborough, MA, USA) to measure intrarenal pressure (IRP) during flexible ureteroscopy.

Patients and Methods

A single‐arm retrospective observational analysis was performed in 50 consecutive patients undergoing ureteroscopic lithotripsy using the LithoVue Elite™ system with pressure sensing capability between April 2022 and February 2023 at two centres. A pressure bag set at 150 mmHg or hand irrigation with a 60‐mL syringe was used for irrigation and a ureteric access sheath (UAS) was placed at the physician's discretion. Median and maximum IRPs, and relative cumulative time exceeding 20, 40, 60, 80, 100, 120, 140, 160, and 200 mmHg per total procedure time were analysed. The two‐sample Mann–Whitney U‐test was used, with statistical significance set at P < 0.05.

Results

The median (interquartile range [IQR]) patient age and body mass index (BMI) was 62.5 (46.7–68.2) years and 27.6 (23.3–32.1) kg/m2, respectively. During the median (IQR) total procedure time of 31.9 (17.4–44.9) min, the median and maximum IRPs were 28.5 (20.0–47.5) and 174.0 (133.5–266.0) mmHg, respectively. IRP remained at <60 mmHg during 92% of the procedure times. Patients with Asian ethnicity, and those without pre‐stenting or UAS use exhibited longer cumulative/total durations exceeding pre‐defined IRP cut‐off values. The smaller 10/12‐F UAS did not lower pressures as much as the 11/13‐F or 12/14‐F UAS (P < 0.001). Age, diabetes, hypertension, preoperative α‐blockade, stone size, and BMI did not show any statistically significant associations with IRP.

Conclusions

The IRP can now be routinely measured during ureteroscopy. Patients had a median IRP of 28.5 mmHg and a maximum of 174 mmHg. Using a smaller UAS (10/12 F), Asian ethnicity, and tight ureters were found to have higher IRPs.
Geomorphological record of the glacial to periglacial transition from the Bølling–Allerød to the Holocene in the Central Pyrenees: the Lòcampo cirque in the regional context
Authors: Fernandes Marcelo , Oliva Marc , Fernández‐Fernández José María , Vieira Gonçalo , Palacios David  , Garcia‐Oteyza Julia , Ventura Josep , Schimmelpfennig Irene ,   ASTER Team
Published: September 2023

In the highest tributaries of the Upper Garonne Basin, Central Pyrenees, cirques up to 2600 m a.s.l. were already deglaciated by 15–14 ka. The long‐term deglaciation during Termination‐1 (T‐1) was interrupted by glacial advances within the cirques during the Bølling–Allerød (B‐A) interstadial and the Younger Dryas stadial. The cirques preserve a variety of glacial and periglacial landforms whose chronologies are poorly known. This study is focused on the Lòcampo cirque (42°38′06″N and 0°59′10″E), Upper Garonne Basin, where a detailed geomorphological map and 10Be terrestrial cosmic ray exposure (CRE) dating allowed us to constrain the chrono‐sequence between the glacial and periglacial domains. In the small Lòcampo cirque, a glacier formed a cirque moraine between 2200 and 2300 m a.s.l., which surrounds a relict rock glacier encompassing several transversal ridges. Additionally, longitudinal ridges typically observed in debris‐covered glaciers are preserved between the moraine and the rock glacier. The eight‐sample data set of CRE ages indicates the formation of the cirque moraine during the second half of the B‐A, by 13.2±1.1 ka. Exposure ages from the rock glacier boulders show a range between 13.6±0.9 and 11.9±0.7 ka, which did not allow its formation to be chronologically constrained. Therefore, the environmental evolution following the moraine stabilization could follow the formation of a debris‐covered glacier at the bottom of the Lòcampo cirque, with the subsequent formation of the rock glacier. After the rock glacier formation, its front rapidly ceased at 13.6±0.9 ka, while the upper ridges gradually stabilized until it became definitively relict at 11.9±0.7 ka or afterwards. These results show evidence of the complex glacial to periglacial transition that needs more robust chronological data sets to better understand the role of climate forcing and local topography during the deglaciation in mid‐latitude mountain environments.
The role of systematicity in early referent selection
Authors: Sia Ming Yean , Mather Emily , Crocker Matthew W. , Mani Nivedita
Published: September 2023

Previous studies showed that word learning is affected by children's existing knowledge. For instance, knowledge of semantic category aids word learning, whereas a dense phonological neighbourhood impedes learning of similar‐sounding words. Here, we examined to what extent children associate similar‐sounding words (e.g., rat and cat) with objects of the same semantic category (e.g., both are animals), that is, to what extent children assume meaning overlap given form overlap between two words. We tested this by first presenting children (N = 93, Mage = 22.4 months) with novel word‐object associations. Then, we examined the extent to which children assume that a similar sounding novel label, that is, a phonological neighbour, refers to a similar looking object, that is, a likely semantic neighbour, as opposed to a dissimilar looking object. Were children to preferentially fixate the similar‐looking novel object, it would suggest that systematic word form‐meaning relations aid referent selection in young children. While we did not find any evidence for such word form‐meaning systematicity, we demonstrated that children showed robust learning for the trained novel word‐object associations, and were able to discriminate between similar‐sounding labels and also similar‐looking objects. Thus, we argue that unlike iconicity which appears early in vocabulary development, we find no evidence for systematicity in early referent selection.
Attention and motor profiles in children with developmental coordination disorder: A neuropsychological and neuroimaging investigation
Authors: Bonthrone Alexandra F. , Green Dido , Morgan Angela T. , Mankad Kshitij , Clark Christopher A. , Liégeois Frédérique J.
Published: September 2023

Aim

This study aimed to (1) quantify attention and executive functioning in children with developmental coordination disorder (DCD), (2) assess whether some children with DCD are more likely to show attention difficulties, and (3) characterize brain correlates of motor and attention deficits.

Method

Fifty‐three children (36 with DCD and 17 without) aged 8 to 10 years underwent T1‐weighted and diffusion‐weighted magnetic resonance imaging, and standardized attention and motor assessments. Parents completed questionnaires of executive functioning and symptoms of inattention and hyperactivity. We assessed regional cortical thickness and surface area, and cerebellar, callosal, and primary motor tract structure.

Results

Analyses of covariance and one‐sample t‐tests identified impaired attention, non‐motor processing speed, and executive functioning in children with DCD, yet partial Spearman's rank correlation coefficients revealed these were unrelated to one another or the type or severity of the motor deficit. Robust regression analyses revealed that cortical morphology in the posterior cingulate was associated with both gross motor skills and inattentive symptoms in children with DCD, while gross motor skills were also associated with left corticospinal tract (CST) morphology.

Interpretation

Children with DCD may benefit from routine attention and hyperactivity assessments. Alterations in the posterior cingulate and CST may be linked to impaired forward modelling during movements in children with DCD. Overall, alterations in these regions may explain the high rate of non‐motor impairments in children with DCD.

What this paper adds

Children with developmental coordination disorder have difficulties in attention, processing speed, and executive functioning.

Non‐motor impairments were not interrelated or correlated with the type or severity of motor deficit.

Posterior cingulate morphology was associated with gross motor skills and inattention.

Gross motor skills were also associated with left corticospinal tract morphology.
Pre‐play promises, threats and commitments under partial credibility
Authors: Melkonyan Tigran , Chakravarty Surajeet
Published: September 2023

The paper examines how pre‐play communication between players with partial credibility affects the ensuing strategic interaction. We consider an environment where players are uncertain about the economic and psychological costs of reneging on promises but learn these at the time of their implementation. We demonstrate that in the equilibrium both players make promises. The latter are partially effective in terms of achieving collusive outcomes and improving the players' payoffs under strategic complementarity, where promises are used to signal future collusive behavior. In contrast, under strategic substitutability the ability to make a promise can be used to signal future aggressive behavior and one of the players may even get a lower expected (before the type is revealed) payoff than in the game without communication.
First report of Ceratocystis fimbriata causing wilt on Gmelina arborea in Costa Rica
Authors: Méndez‐Álvarez Dawa , de Souza Cândido Tonimara , Couto Alfenas Acelino , Murillo Olman , Badilla Yorleny , Ferreira Alfenas Rafael
Published: September 2023

Increased diseases outbreaks in Gmelina arborea (melina) are a threat to sustainability of commercial plantations. One main disease, known as 'melina sudden death', limits the growth and development of trees, causing losses of up to 40% in commercial plantation. However, the main cause of this disease was unknown, until now. Proof of Ceratocystis fimbriata as the aetiological agent of 'melina sudden death' is provided based on field records of disease symptoms, histopathological observation of infected tissue, morphological features of the fungus, maximum‐likelihood phylogenetic inference of the ITS rDNA sequences and pathogenicity test conducted on GENFORES elite melina genotypes. Thus, the appropriate name for the disease should be Ceratocystis wilt. As far as we know, this is the first report of Ceratocystis wilt in melina caused by Ceratocystis fimbriata in Central America. This disease represents a serious threat to Costa Rica's forest industry, as well as in other Latin American countries.
Decay fungi associated with cavity excavation by a large South American woodpecker
Authors: Pozzi Carla , Rajchenberg Mario , Ojeda Valeria
Published: September 2023

In temperate systems of the Northern Hemisphere, wood‐decay fungi are known to facilitate cavity excavation by woodpeckers. For South America, woodpecker–fungi interactions have not been explored. The aim of this work was to identify wood‐decay fungi associated with the process of cavity excavation by the Magellanic woodpecker (Campephilus magellanicus), a large South American picid that excavates on living trees. The survey was conducted in old‐growth Nothofagus pumilio forests of Patagonia. For freshly excavated cavities, wood condition was assessed, adjacent basidiocarps were collected, and fungal cultures were obtained from wood samples taken to the laboratory. All cavities exhibited softened wood. Four Agaricomycotina were isolated in cultures: Stereum hirsutum was the most frequent, followed by Postia pelliculosa, Nothophellinus andinopatagonicus and Aurantiporus albidus. Basidiocarps around cavities were of two species that did not develop in cultures: Laetiporus portentosus and Macrohyporia dictyopora. Excavations were slightly more frequent in white rot colonized than brown rot colonized wood, but this may be an artefact of differential success in fungal isolation and culturing, since several cavities that showed visual symptoms of brown wood rots did not yield mycelia of those wood‐decay fungi. As shown by research elsewhere, basidiocarps underestimated heart rot on cavity walls and revealed additional wood‐decay species living on the same trees; therefore, assessments of fungal diversity in substrates used for cavity excavation should be based on culturing and/or DNA extraction. Because fungal communities in the southern Andes are poorly known, decay fungi and their roles in ecosystem development should be studied across different forest areas, where samples from non‐cavity‐bearing (control) trees should also be taken in order to determine excavation‐site selection.
A computational model of current control mechanism for long‐term potentiation (LTP) in human episodic memory based on gene–gene interaction
Authors: Tripathi Sudhakar , Mishra Ravi Bhushan , Bihari Anand , Agrawal Sanjay , Joshi Puneet
Published: September 2023

The establishment of long‐term potentiation (LTP) is a prime process for the formation of episodic memory. During the establishment of LTP, activations of various components are required in the signaling cascade of the LTP pathway. Past efforts to determine the activation of components relied extensively on the cellular or molecular level. In this paper, we have proposed a computational model based on gene‐level cascading and interaction in LTP signaling for the establishment and control of current signals for achieving the desired level of activation in the formation of episodic memory. This paper also introduces a model for a generalized signaling pathway in episodic memory. A back‐propagation feedback mechanism is used for updating the interaction levels in the signaling cascade starting from the last stage and ending at the start stage of the signaling cascade. Simulation of the proposed model has been performed for the LTP signaling pathway in the context of human episodic memory. We found through simulation that the qualifying genes correction factors of all stages are updated to their maximum limit. The article explains the signaling pathway for episodic memory and proves its effectiveness through simulation results.
Dopaminergic neuronal death via necroptosis in Parkinson's disease: A review of the literature
Authors: Regoni Maria , Valtorta Flavia , Sassone Jenny
Published: September 2023

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive dysfunction and loss of dopaminergic neurons of the substantia nigra pars compacta (SNc). Several pathways of programmed cell death are likely to play a role in dopaminergic neuron death, such as apoptosis, necrosis, pyroptosis and ferroptosis, as well as cell death associated with proteasomal and mitochondrial dysfunction. A better understanding of the molecular mechanisms underlying dopaminergic neuron death could inform the design of drugs that promote neuron survival.

Necroptosis is a recently characterized regulated cell death mechanism that exhibits morphological features common to both apoptosis and necrosis. It requires activation of an intracellular pathway involving receptor‐interacting protein 1 kinase (RIP1 kinase, RIPK1), receptor‐interacting protein 3 kinase (RIP3 kinase, RIPK3) and mixed lineage kinase domain‐like pseudokinase (MLKL). The potential involvement of this programmed cell death pathway in the pathogenesis of PD has been studied by analysing biomarkers for necroptosis, such as the levels and oligomerization of phosphorylated RIPK3 (pRIPK3) and phosphorylated MLKL (pMLKL), in several PD preclinical models and in PD human tissue. Although there is evidence that other types of cell death also have a role in DA neuron death, most studies support the hypothesis that this cell death mechanism is activated in PD tissues. Drugs that prevent or reduce necroptosis may provide neuroprotection for PD. In this review, we summarize the findings from these studies. We also discuss how manipulating necroptosis might open a novel therapeutic approach to reduce neuronal degeneration in PD.
Hepatic steatosis in people older and younger than fifty who are living with HIV and HIV‐negative controls: A cross‐sectional study nested within the POPPY cohort
Authors: Arenas‐Pinto Alejandro , Bakewell Nicholas , Milinkovic Ana , Williams Ian , Vera Jaime , Post Frank A. , Anderson Jane , Beynon Michelle , O'Brien Alastair , Doyle Nicki , Gilson Richard , Pett Sarah L. , Winston Alan , Sabin Caroline A. ,   the Pharmacokinetic and clinical Observations in People over fiftY [POPPY]) study
Published: September 2023

Background

Hepatic steatosis is a major cause of chronic liver disease associated with several negative health outcomes. We compared the prevalence of and factors associated with steatosis in people living with and without HIV.

Methods

Older (>50 years) and younger (<50 years) people with HIV and older HIV‐negative controls (>50 years) underwent liver transient elastography examination with controlled attenuation parameter (steatosis ≥238 dB/m, moderate/severe steatosis ≥280 dB/m, liver fibrosis ≥7.1 kPa). We compared groups using logistic regression/Chi‐squared/Fisher's exact/Kruskal–Wallis tests.

Results

In total, 317 participants (109 older people with HIV; 101 younger people with HIV; 107 HIV‐negative controls) were predominantly white (86%) and male (76%), and 21% were living with obesity (body mass index ≥30 kg/m2). Most (97%) people with HIV had undetectable HIV RNA. The prevalence of fibrosis was 8.4%, 3.0%, and 6.5% in the three groups, respectively (p = 0.26). Fibrosis was predominately (>65%) mild. The prevalence of steatosis was the same in older people with HIV (66.4%) and controls (66.4%) but lower in younger people with HIV (37.4%; p < 0.001). After adjustment, younger people with HIV were less likely to have steatosis (odds ratio [OR] 0.26; 95% confidence interval [CI] 0.14–0.52) than controls, but male sex (OR 2.45; 95% CI 1.20–4.50) and high waist‐to‐hip ratio (OR 3.04; 95% CI 1.74–5.33) were associated with an increased odds of steatosis. We found no association between steatosis and HIV‐related variables.

Conclusions

The prevalence of hepatic steatosis and fibrosis was similar between older participants regardless of HIV status. Age, sex, and abdominal obesity, but not HIV‐related variables, were associated with steatosis. Interventions for controlling obesity should be integrated into routine HIV care.
Type I interferon and cancer
Authors: Holicek Peter , Guilbaud Emma , Klapp Vanessa , Truxova Iva , Spisek Radek , Galluzzi Lorenzo , Fucikova Jitka
Published: September 2023

Type I interferon (IFN) is a class of proinflammatory cytokines with a dual role on malignant transformation, tumor progression, and response to therapy. On the one hand, robust, acute, and resolving type I IFN responses have been shown to mediate prominent anticancer effects, reflecting not only their direct cytostatic/cytotoxic activity on (at least some) malignant cells, but also their pronounced immunostimulatory functions. In line with this notion, type I IFN signaling has been implicated in the antineoplastic effects of various immunogenic therapeutics, including (but not limited to) immunogenic cell death (ICD)‐inducing agents and immune checkpoint inhibitors (ICIs). On the other hand, weak, indolent, and non‐resolving type I IFN responses have been demonstrated to support tumor progression and resistance to therapy, reflecting the ability of suboptimal type I IFN signaling to mediate cytoprotective activity, promote stemness, favor tolerance to chromosomal instability, and facilitate the establishment of an immunologically exhausted tumor microenvironment. Here, we review fundamental aspects of type I IFN signaling and their context‐dependent impact on malignant transformation, tumor progression, and response to therapy.
Short‐term fix or remedy for market failure? Immigration policy as a distinct source of skills
Authors: Wright Chris F. , McLaughlin Colm
Published: September 2023

This article analyses the role of immigration policy as a distinct source of skills supply in liberal market economies. It draws upon interviews with representatives of employer associations and trade unions in the Australian construction and hospitality industries to identify how labour market actors make sense of the function of immigration policy. Rather than ‘complementing’ or ‘undermining’ training and other domestic labour market institutions, as is often assumed, immigration policy can serve to remedy the systemic failures of these institutions to supply skills in the short term. However, overreliance on immigration can disincentivise reform of the labour market institutions necessary to generate adequate skills supply in the long term. The findings suggest the need to reconceptualise the function of immigration policy in terms of its distinct rather than equivalent functions to labour market institutions.
Integrating factors associated with complex wound healing into a mobile application: Findings from a cohort study
Authors: Marques Raquel , de Lopes Marcos Venícios Oliveira , Neves‐Amado João Daniel , Ramos Paulo Alexandre Silva , de Sá Luís Octávio , da Oliveira Irene Maria Silva , da Amado João Manuel Costa , de Vasconcelos Maria João Medeiros , Salgado Pedro Miguel Faria , Alves Paulo Jorge Pereira
Published: September 2023

Complex, chronic or hard‐to‐heal wounds are a prevalent health problem worldwide, with significant physical, psychological and social consequences. This study aims to identify factors associated with the healing process of these wounds and develop a mobile application for wound care that incorporates these factors. A prospective multicentre cohort study was conducted in nine health units in Portugal, involving data collection through a mobile application by nurses from April to October 2022. The study followed 46 patients with 57 wounds for up to 5 weeks, conducting six evaluations. Healing time was the main outcome measure, analysed using the Mann–Whitney test and three Cox regression models to calculate risk ratios. The study sample comprised various wound types, with pressure ulcers being the most common (61.4%), followed by venous leg ulcers (17.5%) and diabetic foot ulcers (8.8%). Factors that were found to impair the wound healing process included chronic kidney disease (U = 13.50; p = 0.046), obesity (U = 18.0; p = 0.021), non‐adherence to treatment (U = 1.0; p = 0.029) and interference of the wound with daily routines (U = 11.0; p = 0.028). Risk factors for delayed healing over time were identified as bone involvement (RR 3.91; p < 0.001), presence of odour (RR 3.36; p = 0.007), presence of neuropathy (RR 2.49; p = 0.002), use of anti‐inflammatory drugs (RR 2.45; p = 0.011), stalled wound (RR 2.26; p = 0.022), greater width (RR 2.03; p = 0.002), greater depth (RR 1.72; p = 0.036) and a high score on the healing scale (RR 1.21; p = 0.001). Integrating the identified risk factors for delayed healing into the assessment of patients and incorporating them into a mobile application can enhance decision‐making in wound care.
Development and validation of a nomogram for arterial stiffness
Authors: Wang Tingjun , Cai Xiaoqi , Zhang Lingyu , Yang Ting , Ye Chaoyi , Xu Guoyan , Xie Liangdi
Published: September 2023

Even though as a gold standard for noninvasive measurement of arterial stiffness, carotid‐femoral pulse wave velocity (cfPWV) is not widely used in primary healthcare institutions due to time‐consuming and unavailable equipment. The aim of this study was to develop a convenient and low‐cost nomogram model for arterial stiffness screening. A cross‐sectional study was undertaken in the department of general practice, the First Affiliated Hospital of Fujian Medical University. Arterial stiffness was defined as cfPWV ≥ 10 m/s. A total of 2717 participants were recruited to construct the nomogram using the least absolute shrinkage and selection operator and logistic regressions. Receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis, clinical impact curve were used to evaluate the performance of the model. The model was validated internally and externally (399 participants) by bootstrap method. Arterial stiffness was identified in 913 participants (33.60%). Age, sex, waist to hip ratio, systolic blood pressure, duration of diabetes, heart rate were selected to construct the nomogram model. Good discrimination and accuracy were exhibited with area under curve of 0.820 (95% CI 0.803–0.837) in ROC curve and mean absolute error = 0.005 in calibration curve. A positive net benefit was shown in decision curve analysis and clinical impact curve. A satisfactory agreement was displayed in internal validation and external validation. The low cost and user‐friendly nomogram is suitable for arterial stiffness screening in primary healthcare institutions.
Translating the nuanced risk for substance use among adolescents treated for attention‐deficit/hyperactivity disorder (ADHD) into clinical practice: a commentary on McCabe et al. (2023)
Authors: Kennedy Traci M. , Molina Brooke S. G.
Published: September 2023

In their recent examination of the Monitoring the Future (MTF) data, McCabe et al. (Journal of Child Psychology and Psychiatry, 2023) address the complex, longstanding, and clinically valuable questions of whether and how stimulant medication treatment for adolescents with ADHD relates to their risk for substance use. Here, we expand on the authors' interpretations of their nuanced findings of increased risk for illicit stimulant use and non‐prescribed stimulant medication use for youth with later age of medication treatment initiation and shorter treatment duration. We particularly focus on highlighting tangible clinical implications, and we recommend ways future research can build on the authors' findings to further clarify this important issue.
Keyword network analysis of changes in the image of nurses pre‐ and post‐COVID‐19 in the media environment
Authors: Kim Doo Ree , Lee Gi Ran
Published: September 2023

Aims and objectives

To analyse and describe the changes in the image of nurses perceived by the public pre‐ and post‐COVID‐19 in Korea.

Background

Nurses play an important role in disaster situations such as COVID‐19. In such disaster situations, we aim to confirm the image of nurses projected in the mass media and promote the professionalism of nurses through the image of nurses as professionals.

Design

Qualitative media keyword networks analysis.

Methods

To understand the change in the image of nurses pre‐ and post‐COVID‐19, the big data program TEXTOM was used to collect data. From 19 January to 31 May 2020, data were set as ‘post‐COVID‐19’, and 1 year before 18 January 2020, data were set as ‘pre‐COVID‐19’. The keywords from 9533 articles were refined, frequency analysed and social networks analysed using TEXTOM and MS office excel, and the analysis results were visualised using UCINET 6 and the NetDraw program.

Results

As for keywords related to nurses pre‐COVID‐19, those with the most frequent appearance and the highest networking degree in centrality were ‘work’, ‘older adults’, ‘care’, ‘time’, ‘care worker’, ‘caring labor’. As for keywords related to nurses post‐COVID‐19, those that appeared most often and had the highest degree of centrality networking were ‘COVID‐19’, ‘USA’, ‘China’, ‘check’, ‘patient’, ‘work’.

Conclusion

This study shows that the public image of nurses has changed more positively after COVID‐19 due to the media. Individual nurses and nursing organizations should pay attention to the deficiency in the image of nurses and provide a way to reform the public image of professional nurses.

Relevance to clinical practice

The effects of global crises such as COVID‐19 on nurses were confirmed, and information delivered through the media was an important way to improve the nursing profession.
Are HPV‐negative lesions concerned for the introduction of primary HPV testing for cervical cancer screening in Japan?
Authors: Hideshima Misako , Hashiguchi Mariko , Honda Atsuko , Umezaki Yasushi , Okuma Ryoichi , Hikari Takako , Fukuda Asako , Okugawa Kaoru , Yokoyama Masatoshi
Published: September 2023

Aim

In Japan, primary human papilloma virus (HPV) testing has not been introduced for cervical cancer screening due to concerns that HPV‐negative lesions may be missed and a lack of Japanese data. The purpose of this study was to evaluate the validity of primary HPV testing in Japan by analyzing cervical intraepithelial neoplasia 2 (CIN2) or more/high‐risk HPV− (CIN2+/hrHPV−) cases in cervical cancer screening.

Methods

Data from 35 525 cervical cancer screenings with HPV testing and cervical cytology from 2011 to 2019 in Saga City, Japan, were reviewed. The cases with low‐grade squamous intraepithelial lesion (LSIL+)/hrHPV− were analyzed in detail.

Results

The results of the 35 525 examinees were as follows: 31 123 were negative for intraepithelial lesion or malignancy (NILM)/hrHPV–, 2612 were NILM/hrHPV+, 262 were atypical squamous cells of undetermined significance (ASC‐US)/hrHPV–, 213 were ASC‐US/hrHPV+, 291 were LSIL+/hrHPV−, and 1024 were LSIL+/hrHPV+. Of the 256 LSIL+/hrHPV− examinees for whom histology was available, CIN2+ were CIN2 9.4% (24/256), CIN3 3.9% (10/256), cervical adenocarcinoma 0.4% (1/256), uterine corpus cancer 1.2% (3/256), and uterine sarcoma 0.4% (1/256). Overall, the rate of LSIL+/hrHPV− was 0.82% (291/35.525), 0.1% (36/35525) of which were cervical lesions with CIN2+. Only one cervical adenocarcinoma was detected, but gastric‐type adenocarcinoma was not included.

Conclusion

HPV‐negative CIN2+ or cervical adenocarcinoma is not a concern for the introduction of primary HPV screening in Japan. Primary HPV testing in cervical cancer screening is considered a feasible method that can be used in Japan, although an algorithm suitable for Japan and a national‐level management system need to be established.
Conservation of beneficial microbes between the rhizosphere and the cyanosphere
Authors: Zheng Qing , Hu Yuntao , Kosina Suzanne M. , Van Goethem Marc W. , Tringe Susannah G. , Bowen Benjamin P. , Northen Trent R.
Published: September 2023

Biocrusts are phototroph‐driven communities inhabiting arid soil surfaces. Like plants, most photoautotrophs (largely cyanobacteria) in biocrusts are thought to exchange fixed carbon for essential nutrients like nitrogen with cyanosphere bacteria. Here, we aim to compare beneficial interactions in rhizosphere and cyanosphere environments, including finding growth‐promoting strains for hosts from both environments.

To examine this, we performed a retrospective analysis of 16S rRNA gene sequencing datasets, host–microbe co‐culture experiments between biocrust communities/biocrust isolates and a model grass (Brachypodium distachyon) or a dominant biocrust cyanobacterium (Microcoleus vaginatus), and metabolomic analysis.

All 18 microbial phyla in the cyanosphere were also present in the rhizosphere, with additional 17 phyla uniquely found in the rhizosphere. The biocrust microbes promoted the growth of the model grass, and three biocrust isolates (Boseasp._L1B56,Pseudarthrobactersp._L1D14 andPseudarthrobacter picheli_L1D33) significantly promoted the growth of both hosts. Moreover, pantothenic acid was produced byPseudarthrobactersp._L1D14 when grown onB.distachyonexudates, and supplementation of plant growth medium with this metabolite increasedB.distachyonbiomass by over 60%.

These findings suggest that cyanobacteria and other diverse photoautotrophic hosts can be a source for new plant growth‐promoting microbes and metabolites.
A Glu209Lys substitution in DRG1/TaACT7, which disturbs F‐actin organization, reduces plant height and grain length in bread wheat
Authors: Xie Zhencheng , Zhang Lichao , Zhang Qiang , Lu Yan , Dong Chunhao , Li Danping , Liu Xu , Xia Chuan , Kong Xiuying
Published: September 2023

Plant height and grain size are two important agronomic traits that are closely related to crop yield. Numerous dwarf and grain‐shape mutants have been studied to identify genes that can be used to increase crop yield and improve breeding programs.

In this study, we characterized a dominant mutant, dwarf and round grain 1 (drg1‐D), in bread wheat (Triticum aestivum L.). drg1‐D plants exhibit multiple phenotypic changes, including dwarfism, round grains, and insensitivity to brassinosteroids (BR). Cell structure observation in drg1‐D mutant plants showed that the reduced organ size is due to irregular cell shape.

Using map‐based cloning and verification in transgenic plants, we found that a Glu209Lys substitution in the DRG1 protein is responsible for the irregular cell size and arrangement in the drg1‐D mutant. DRG1/TaACT7 encodes an actin family protein that is essential for polymerization stability and microfilament (MF) formation. In addition, the BR response and vesicular transport were altered by the abnormal actin cytoskeleton in drg1‐D mutant plants.

Our study demonstrates that DRG1/TaACT7 plays an important role in wheat cell shape determination by modulating actin organization and intracellular material transport, which could in the longer term provide tools to better understand the polymerization of actin and its assembly into filaments and arrays.
Design, analysis, and interpretation of treatment response heterogeneity in personalized nutrition and obesity treatment research
Authors: Zoh Roger S. , Esteves Bridget H. , Yu Xiaoxin , Fairchild Amanda J. , Vazquez Ana I. , Chapple Andrew G. , Brown Andrew W. , George Brandon , Gordon Derek , Landsittel Douglas , Gadbury Gary L. , Pavela Greg , de los Campos Gustavo , Mestre Luis M. , Allison David B.
Published: September 2023

It is increasingly assumed that there is no one‐size‐fits‐all approach to dietary recommendations for the management and treatment of chronic diseases such as obesity. This phenomenon that not all individuals respond uniformly to a given treatment has become an area of research interest given the rise of personalized and precision medicine. To conduct, interpret, and disseminate this research rigorously and with scientific accuracy, however, requires an understanding of treatment response heterogeneity. Here, we define treatment response heterogeneity as it relates to clinical trials, provide statistical guidance for measuring treatment response heterogeneity, and highlight study designs that can quantify treatment response heterogeneity in nutrition and obesity research. Our goal is to educate nutrition and obesity researchers in how to correctly identify and consider treatment response heterogeneity when analyzing data and interpreting results, leading to rigorous and accurate advancements in the field of personalized medicine.
Effect of vertical pump position on start‐up fluid delivery of syringe pumps used for microinfusion
Authors: Weiss Markus , Wendel‐Garcia Pedro David , Grass Beate , Buehler Philipp Karl , Kleine‐Brueggeney Maren
Published: September 2023

Background

Connection and opening a syringe infusion pump to a central venous line can lead to acute anterograde or retrograde fluid shifts depending on the level of central venous pressure. This may lead to bolus events or to prolonged lag times of intravenous drug delivery, being particularly relevant when administering vasoactive or inotropic drugs in critically ill patients using microinfusion. The aim of this study was to assess the effect of syringe pump positioning at different vertical heights on start‐up fluid delivery before versus after purging and connection the pump to the central venous catheter.

Methods

This in vitro study measured ante‐ and retrograde infusion volumes delivered to the central venous line after starting the syringe pump at a set infusion rate of 1 mL/h. In setup one, the pump was first positioned to vertical levels of +43 cm or –43 cm and then purged and connected to a central venous catheter. In setup two, the pump was first purged and connected at zero level and secondarily positioned to a vertical level of +43 cm or –43 cm. Central venous pressure was adjusted to 10 mmHg in both setups.

Results

Positioning of the pump prior to purging and connection to the central venous catheter resulted in a better start‐up performance with delivered fluid closer to programmed and expected infusion volumes when compared to the pump first purged, connected, and then positioned. Significant backflow volumes were observed with the pump purged and connected first and then positioned below zero level. No backflow was measured with the pump positioned first below zero level and then purged and connected.

Conclusions

Syringe infusion pump assemblies should be positioned prior to purging and connection to a central venous catheter line when starting a new drug, particularly when administering highly concentrated vasoactive or inotropic drugs delivered at low flow rates.
Increased activity of core photorespiratory enzymes and CO2 transfer conductances are associated with higher and more optimal photosynthetic rates under elevated temperatures in the extremophile Rhazya stricta
Authors: Gregory Luke M. , Roze Ludmila V. , Walker Berkley J.
Published: September 2023

Increase photorespiration and optimising intrinsic water use efficiency are unique challenges to photosynthetic carbon fixation at elevated temperatures. To determine how plants can adapt to facilitate high rates of photorespiration at elevated temperatures while also maintaining water‐use efficiency, we performed in‐depth gas exchange and biochemical assays of the C3 extremophile, Rhazya stricta. These results demonstrate that R. stricta supports higher rates of photorespiration under elevated temperatures and that these higher rates of photorespiration correlate with increased activity of key photorespiratory enzymes; phosphoglycolate phosphatase and catalase. The increased photorespiratory enzyme activities may increase the overall capacity of photorespiration by reducing enzymatic bottlenecks and allowing minimal inhibitor accumulation under high photorespiratory rates. Additionally, we found the CO2 transfer conductances (stomatal and mesophyll) are re‐allocated to increase the water‐use efficiency in R. stricta but not necessarily the photosynthetic response to temperature. These results suggest important adaptive strategies in R. stricta that maintain photosynthetic rates under elevated temperatures with optimal water loss. The strategies found in R. stricta may inform breeding and engineering efforts in other C3 species to improve photosynthetic efficiency at high temperatures.
Non‐invasive monitoring of cardiac contractility: Trans‐radial electrical bioimpedance velocimetry (TREV)
Authors: Stump Alexandra , Gregory Caitlin , Babenko Viktoriya , Rizor Elizabeth , Bullock Tom , Macy Alan , Giesbrecht Barry , Grafton Scott T. , Dundon Neil M.
Published: September 2023

We describe methods and software resources for a bioimpedance measurement technique, ‘trans‐radial electrical bioimpedance velocimetry’ (TREV) that allows for the non‐invasive monitoring of relative cardiac contractility and stroke volume. After reviewing the relationship between the measurement and cardiac contractility, we describe the general recording methodology, which requires impedance measurements of the forearm. We provide open‐source Jupyter‐based software (operable on most computers) for deriving cardiac contractility from the impedance measurements. The software includes tools for removing variance associated with heart rate and respiration. We demonstrate the ability of this bioimpedance measurement for tracking beat‐to‐beat changes of contractility in a maximal grip force production task. Critically, the results demonstrate both a reactive increase in contractility with force production, and suggest there is a learned increase in contractility prior to grip onset, consistent with anticipatory allostatic autonomic regulation mediated by sympathetic inotropy. The method and software should be of broad utility for investigations of event‐related cardiac dynamics in psychophysical studies.
Chemical changes during endoskarn and porphyry‐style alteration and Cu—Fe exoskarn mineralization in the Tonglushan system, eastern China
Authors: Zhang Fei , Williamson Ben J. , Ullmann Clemens V. , Hughes Hannah S. R.
Published: September 2023

Element mobility and chemical mass transfer are evaluated in the formation of Cu—Fe exoskarn deposits and endoskarn and minor porphyry‐style alteration in the Tonglushan quartz monzodiorite (QMD) system, eastern China. Endoskarn formation involved the migration of Ca into the QMD from the exoskarnification of carbonates (now marble) xenoliths and wall rocks, addition of Fe and Mn by magmatic‐hydrothermal fluids emanating from the interior of the QMD, and removal of alkali elements due to the replacement of feldspars and mica by prograde skarn minerals. Zirconium, Hf, U, and rare earth elements (REE) were added by hydrothermal fluids which were able to carry these often poorly mobile high field strength elements (HFSE) due to elevated F activity. Additions of Al were likely from Na‐rich fluids that also caused sodic alteration. Several factors favored mineralization within the exoskarns rather than endoskarns and QMD. The endoskarns were relatively oxidizing, as evidenced by a significant addition of Fe3+, which caused Cu to remain in magmatic‐hydrothermal fluids until they entered and precipitated sulphides in the more reducing environment of the exoskarns. Fluid migration from the QMD through the endoskarns and into the exoskarns was favored due to decarbonation of wall rock carbonates and related upwards migration of CO2 to produce a self‐sustaining chimney effect, which drew further fluids towards the carbonates to form, alter and mineralize the exoskarns. The higher porosity and permeability of the endoskarns compared with the QMD further promoted the lateral flow of Cu‐bearing fluids towards the exoskarns and limited porphyry‐style alteration and mineralization within the QMD. This proposed mechanism is only likely to be relevant for porphyry‐type systems developed predominantly within carbonate host rocks. Its significance for exploration models is that relatively poorly mineralized porphyry stocks in this setting may be associated with more substantive exoskarn deposits on their margins.