bluuebunny/crossref_metadata_2025_split huggingface dataset:
PA33 Mosaic KRAS mutation associated with epidermal naevus and somatic limb overgrowth
Authors: Thu-Ta Flora , Bajwa Dalvir Singh , Leech Suzanne , Dubois Anna , Wilson Brian 
Published: June 2024

Abstract
Mosaic KRAS variants are recognized to cause a range of features including somatic overgrowth, lymphatic and vascular malformations and other anomalies. We present a child with a mosaic variant in this gene and discuss the phenotype of this condition. A 2-year-old boy was noted at birth to have an extensive keratinocytic epidermal naevus and swelling of the left lower limb. The child was born after an uncomplicated pregnancy to unrelated parents. No anomalies had been detected prenatally. The naevus was large, affecting the left side of the body with a central demarcation down the midline of his chest to the left groin. The naevus continued down the volar aspect of the left arm onto the palm of the hand. The left lower limb was hypertrophic throughout, with nonpitting oedema. The perfusion and movement of the limb appeared normal. An infantile haemangioma was noted on the lower back, and later a deeper haemangioma of the anterior neck; neither required treatment. The left testis was undescended initially, with subsequent overgrowth of the skin of the penis and scrotum. Investigations soon after birth revealed a cystic dysplastic left kidney. A magnetic resonance imaging scan of the brain was normal. Initial genetic analysis was performed on blood. Diagnostic testing for a panel of genes associated with segmental overgrowth (R110) detected no pathogenic variant. The mosaic skin disorders deep sequencing panel (R327) showed no pathogenic variant using DNA extracted from blood. This panel was subsequently repeated on DNA extracted from skin, and a mosaic pathogenic KRAS variant c.35G&gt;A, p.Gly12Asp was identified in 30% of next-generation sequencing reads. Mosaic RASopathies affect genes involved in the RAS–mitogen-activated protein kinase signalling pathway. Phenotypes of mosaic RASopathies are often distinct from their germline counterparts. The c.35G&gt;A variant seen in our patient is widely reported, and leads to constitutive overactivation and increased signal transduction in downstream pathways. Epidermal naevi, both keratinocytic and sebaceous, are a common finding resulting from mosaic RAS mutations. Good developmental progress was made; milestones were generally met and although the leg remained enlarged due to lymphatic overgrowth, he was able to walk. No neurological symptoms have been noted, and the eyes have been checked with no anomalies found. The kidneys will be kept under review, as renal tumours have been reported in patients with mosaic KRAS variants. Our patient highlights aspects of the phenotype of a mosaic KRAS variant and adds to the growing knowledge of these conditions.
BI31 Pembrolizumab-induced scleroderma in a patient with nonsmall cell lung cancer
Authors: Kunnumpurath Anamika , Gjorgjievska-Marsh Vesna 
Published: June 2024

Abstract
We present the case of a 59-year-old woman with locally advanced metastatic adenocarcinoma of the lung, who developed skin tightening and thickening following a course of treatment with pembrolizumab. She was commenced on pembrolizumab in September 2021, and in July 2023 she developed the skin changes in the neck, shoulders, stomach and thighs with associated pain, as well as areas of colour change and restriction of movement. Clinical presentation combined with subsequent histopathological confirmation led to a diagnosis of scleroderma. Following a failed trial of high-dose prednisolone, methotrexate was started with beneficial effect. This case highlights that scleroderma is a rare skin-related adverse event that can occur with immune checkpoint inhibitors.
Global Health DermatologyOral presentationsGD01 Comparative efficacy of Mycobacterium indicus pranii and bacille Calmette–Guérin as immunotherapeutic adjuncts in multibacillary leprosy: a clinical and molecular randomized controlled trial
Authors: Jain Sejal , Chhabra Seema , Dogra Sunil , Yadav Rakesh , Chatterjee Debajyoti , Narang Tarun 
Published: June 2024

Abstract
Immunotherapy may be a useful tool in the management of leprosy, especially in highly bacillated patients because of immunological memory. This open-label randomized controlled trial assessed changes in the molecular viability assay (esxA and hsp18 transcript expression) and serology (anti-ND-O-BSA levels) in patients with multibacillary leprosy treated with multibacillary multidrug therapy (MB-MDT) with Mycobacterium indicus pranii (MIP) vaccine or MB-MDT with bacille Calmette–Guérin (BCG) vaccine. Secondary outcomes were changes in histopathological parameters (granuloma fraction and bacillary index of the granuloma), differences in the incidences of type 1 and type 2 lepra reactions, and incidence of immunotherapy-associated adverse drugs reactions among the two groups. The study included 40 patients with multibacillary leprosy randomized into the MIP + MB-MDT and BCG + MB-MDT groups. Thirty patients (15 in each group) completed the 12-month follow-up. Molecular viability assays based on esxA and hsp18 transcript expression, and anti-NO-O-BSA levels were measured in 23 of 30 patients (13 in the MIP group and 10 in the BCG group). In the MIP group, 77% of patients (10 of 13) and in the BCG group, 50% (5 of 10) showed decreased esxA (P = 0.09) and hsp18 transcript expression (P = 0.4). The median decrease in bacteriological index was 1 (interquartile range 0–2) in the MIP group and 1 (interquartile range 0–1) in the BCG group (P = 0.9). A decrease in IgM anti-ND-O-BSA levels was seen in 77% of patients (10 of 13) in the MIP group and 80% (8 of 10) in the BCG group (P = 0.9). Histopathological upgrading was noted in 85% of patients (11 of 13) in the MIP group and 90% (9 of 10) in the BCG group (P = 0.3). Most of the patients had clinical improvement (26 of 30, 87%), which was comparable between the two groups (P = 0.5). None of these patients had primary drug resistance to the first-line MDT drugs. Two patients in the MIP group (13%) and five in the BCG group (33%) had reactional episodes, but only one had an increase in disability. The adverse effect profiles of both vaccines were similar, the majority being injection-site reactions. BCG was associated with neuritis in two patients (12%). This study demonstrates the usefulness of immunotherapy in reducing bacillary viability, improving histopathological and serological markers, and potentially preventing lepra reactions and associated disability. The comparability of MIP and BCG is noteworthy, especially considering BCG’s wider availability and lower cost. The use of molecular viability assays and anti-ND-O-BSA enzyme-linked immunosorbent assay as diagnostic and predictive tools for reactions and/or relapse could advance future research in leprosy.
BT31 The dermatology department without walls: how teledermatology unmasks unmet need in coastal ‘deserts of provision’
Authors: Farooki Roopa , Halpern Saul 
Published: June 2024

Abstract
Dermatology departments actively use digital solutions to provide services remotely, particularly to supplement overbooked face-to-face clinics. In coastal areas, there are additional challenges regarding provision of access to dermatology, with few centres offering dermatology appointments, and with patients not always having the means to travel. This paper discusses how the teledermatology service in one of the coastal ‘deserts of provision’ both widens access to secondary care and unmasks unmet need in these communities. The methods used involve direct comparison of the number of dermatology referrals from primary care, both before the establishment of the teledermatology service and afterwards. The teledermatology service examined has been established in coastal locations, offering photography and dermoscopic images of lesions, submitted with a standardized patient history form. The main focus of the service is to identify skin cancers and provide reassurance of benign lesions, without recourse to 2-week-wait appointments, although other skin conditions suitable for general clinics are also referred. Interestingly, the results show that the teledermatology service has had no impact on mitigating traditional referrals to routine or 2-week-wait clinics, which have continued to increase, on average by 18% in the 2-year period ending January 2024, across 24 surgeries in the region. For one surgery located in one of the most isolated areas, weekly referrals have increased by 142%, representing an increase from three to seven referrals per week. This centre also made an additional eight referrals to teledermatology per week, mainly for single lesions that general practitioners felt did not merit the 2 week wait, but that required timely dermatological opinion. Of 97 referrals examined across a 12-week period (November 2023 to January 2024), five lesions were listed directly for surgical excision, eight for biopsy and eight for further clinical evaluation. It seems evident that in providing this additional path of access, the teledermatology service has unmasked an unmet need in the coastal community. It offers a ‘dermatology department without walls’, where expert secondary care advice with consultant insight can be obtained locally, and surgical follow-up or further clinical management can be organized directly by the advising dermatology team. Further study is needed to confirm that this increased access also leads to improved patient outcomes, which is predicated on appropriate referrals to teledermatology by primary care, and assessment of the diagnostic accuracy of teledermatology compared with traditional in-person clinics. The hope is that effective dermatology specialty care is being brought to the patient more directly in coastal communities than has previously been possible.
BT38 Patient satisfaction of teledermoscopy service in a UK university health board: a service evaluation
Authors: Hughes Anna , Abbott Rachel 
Published: June 2024

Abstract
Around 20 000 teledermatology referrals are reviewed by dermatology consultants in our UK university health board each year, including urgent suspected cancer referrals. More recently, an additional ‘teledermoscopy service’ was introduced so that dermatology consultants can request dermoscopy photos – in addition to standard clinical photos – for remote review. With the rising incidence of skin cancer in the UK, and a backlog of referrals created by the COVID-19 pandemic, the demand for access to dermatological care heightens the need for teledermatology services, including teledermoscopy. This service evaluation sought to evaluate the patient satisfaction of the new teledermoscopy service. Over 3 weeks, patient satisfaction of the teledermoscopy service was assessed via a 14-question survey that was developed and piloted in a neighbouring health board. The survey was offered to patients after their appointment in the medical illustration teledermoscopy clinic. Waiting times, hospital accessibility, preappointment information and appointment experience were evaluated using Likert scaling, a five-point scale using the terms; ‘strongly agree’, ‘agree’, ‘don’t know’, ‘disagree’ and ‘strongly disagree’. Overall experience was assessed on a scale of 1–10, and the final question of the survey allowed for free writing of any comments the participants had. In total, 100 patients (mean age 55 years, range 16–90; 42% male) responded to the survey. Overall, 84 of 100 respondents replied to the question asking them to rate their overall experience from 1 to 10: 83 of 84 (99%) rated the service ≥ 8 out of 10, and 62 of 84 (74%) respondents rated the service 10 out of 10. With regards to patient experiences of the appointment, the responses were very positive: 98 of 100 respondents (98%) ‘agreed’ or ‘strongly agreed’ that the procedure was clearly explained to them, and 99% of respondents ‘agreed’ or ‘strongly agreed’ that the photographer acted professionally, and the photographic environment was appropriate. Contrastingly, the responses regarding the preappointment information were less positive: 35 of 99 patients (35%) ‘disagreed’ or ‘strongly disagreed’ that they were given sufficient information about the teledermatology service prior to their appointment. Importantly, 9 of the 100 (9%) reported that they thought their appointment was to see a dermatologist, not a medical photographer. In total, 85 of 100 patients (85%) agreed that the hospital was easy to attend, while 6 of the 100 (6%) expressed a preference for a closer hospital. Finally, 18 of the 100 respondents answered the open-ended ‘further comments’ question. The written feedback provided was mostly positive. The majority of patients were highly satisfied with the teledermoscopy service; however, over one-third felt that more information was needed prior to their appointment.
Social Workers’ Perceptions of the Nature of Child Neglect: A Systematic Literature Review
Authors: Gibbs Jennifer , Coughlan Barry , Morgan Tessa , Mikushnica Arbenita , Phippard Samantha , Crozier-Roche Francesca , Drayak Taliah , Graham David , Smith Jack , Duschinsky Robbie 
Published: June 2024

Abstract
Neglect is the most common form of child maltreatment in the UK and the USA. This article reviews research about how child neglect is perceived by social workers. We conducted a systematic review and identified fifty relevant studies, using a range of methodologies, published since the 1989 Children Act. The themes were identified iteratively and synthesised using a narrative method. The review found that despite evidence that neglect is associated with several adverse outcomes, neglect is a lower priority for social work intervention compared to other forms of maltreatment. This is particularly true for emotional neglect and neglect of older children. The review found that social workers conceptualise poverty and neglect as being distinctly different and try to address poverty through practical, non-punitive interventions. However, assessments could better recognise how deprivation exacerbates other risk factors for neglect. The review found a lack of knowledge about perceptions of neglect in adolescents and children with a disability and about the threshold for intervention when neglect is cumulative. Practice may be improved by better recognising and addressing the societal context to neglect allegations and the risk of long-term harm. Achieving this may have resource and training implications.
Putaminal dopamine modulates movement motivation in Parkinson’s disease
Authors: Banwinkler Magdalena , Dzialas Verena , Rigoux Lionel , Asendorf Adrian L , Theis Hendrik , Giehl Kathrin , Tittgemeyer Marc , Hoenig Merle C , van Eimeren Thilo 
Published: June 2024

Abstract
The relative inability to produce effortful movements is the most specific motor sign of Parkinson’s disease, which is primarily characterized by loss of dopaminergic terminals in the putamen. The motor motivation hypothesis suggests that this motor deficit may not reflect a deficiency in motor control per se, but a deficiency in cost-benefit considerations for motor effort. For the first time, we investigated the quantitative effect of dopamine depletion on the motivation of motor effort in Parkinson’s disease.
A total of 21 early-stage, unmedicated patients with Parkinson’s disease and 26 healthy controls were included. An incentivized force task was used to capture the amount of effort participants were willing to invest for different monetary incentive levels and dopamine transporter depletion in the bilateral putamen was assessed.
Our results demonstrate that patients with Parkinson’s disease applied significantly less grip force than healthy controls, especially for low incentive levels. Congruously, decrease of motor effort with greater loss of putaminal dopaminergic terminals was most pronounced for low incentive levels. This signifies that putaminal dopamine is most critical to motor effort when the trade-off with the benefit is poor.
Taken together, we provide direct evidence that the reduction of effortful movements in Parkinson’s disease depends on motivation and that this effect is associated with putaminal dopaminergic degeneration.
Identification of angiogenesis-related genes and molecular subtypes for psoriasis based on random forest algorithm
Authors: Zhang Meng-Jie , Xue Ting-Ting , Fei Xiao-Ya , Zhang Ying , Luo Ying , Ru Yi , Jiang Jing-Si , Song Jian-Kun , Kuai Le , Luo Yue , Wang Rui-Ping , Li Bin 
Published: June 2024

Abstract
Psoriasis is a chronic immune-mediated recurrent skin disease causing systemic damage. Increased angiogenesis has been reported to participate in the progression of psoriasis. However, angiogenesis-related genes (ARGs) in psoriasis have not been systematically elucidated. Therefore, we aim to identify potential biomarkers and subtypes using two algorithmsr. Transcriptome sequencing data of patients with psoriasis were obtained, in which differentially expressed genes were assessed by principal component analysis. A diagnostic model was developed using random forest algorithm and validated by receiver operating characteristic (ROC) curves. Subsequently, we performed consensus clustering to calculate angiogenesis-associated molecular subtypes of psoriasis. Additionally, a correlation analysis was conducted between ARGs and immune cell infiltration. Finally, validation of potential ARG genes was performed by quantitative real-time PCR (qRT-PCR). We identified 29 differentially expressed ARGs, including 13 increased and 16 decreased. Ten ARGs, CXCL8, ANG, EGF, HTATIP2, ANGPTL4, TNFSF12, RHOB, PML, FOXO4, and EMCN were subsequently sifted by the diagnostic model based on a random forest algorithm. Analysis of the ROC curve (area under the curve [AUC] = 1.0) indicated high diagnostic performance in internal validation. The correlation analysis suggested that CXCL8 has a high positive correlation with neutrophil (R =0.8, P &lt; 0.0001) and interleukins pathway (R = 0.79, P &lt; 0.0001). Furthermore, two ARG-mediated subtypes were obtained, indicating potential heterogeneity. Finally, the qRT-PCR demonstrated that the mRNA expression levels of CXCL8 and ANGPTL4 were elevated in psoriasis patients, with a reduced expression of EMCN observed. The current paper indicated potential ARG-related biomarkers of psoriasis, including CXCL8, ANGPTL4, and EMCN, with two molecular subtypes.
Simultaneous cortical, subcortical, and brainstem mapping of sensory activation
Authors: Reddy Neha A , Clements Rebecca G , Brooks Jonathan C W , Bright Molly G 
Published: June 2024

Abstract
Nonpainful tactile sensory stimuli are processed in the cortex, subcortex, and brainstem. Recent functional magnetic resonance imaging studies have highlighted the value of whole-brain, systems-level investigation for examining sensory processing. However, whole-brain functional magnetic resonance imaging studies are uncommon, in part due to challenges with signal to noise when studying the brainstem. Furthermore, differentiation of small sensory brainstem structures such as the cuneate and gracile nuclei necessitates high-resolution imaging. To address this gap in systems-level sensory investigation, we employed a whole-brain, multi-echo functional magnetic resonance imaging acquisition at 3T with multi-echo independent component analysis denoising and brainstem-specific modeling to enable detection of activation across the entire sensory system. In healthy participants, we examined patterns of activity in response to nonpainful brushing of the right hand, left hand, and right foot (n = 10 per location), and found the expected lateralization, with distinct cortical and subcortical responses for upper and lower limb stimulation. At the brainstem level, we differentiated the adjacent cuneate and gracile nuclei, corresponding to hand and foot stimulation respectively. Our findings demonstrate that simultaneous cortical, subcortical, and brainstem mapping at 3T could be a key tool to understand the sensory system in both healthy individuals and clinical cohorts with sensory deficits.
Prevalence, awareness, treatment, and control of hypertension in community-dwelling older adults with chronic kidney disease: the Irish longitudinal study on ageing
Authors: Browne Leonard D , Alamin Mohammed Y , Miri Hamid H , Hall Robert , Tandan Meera , Sexton Donal , Stack Austin G 
Published: June 2024

ABSTRACT

Background
Hypertension is highly prevalent in chronic kidney disease (CKD), posing a significant but modifiable risk for adverse clinical outcomes. This study explored the prevalence, awareness, treatment, and control of hypertension in older Irish adults with CKD.

Methods
Data were analysed from participants in Wave 1 of The Irish Longitudinal Study on Ageing (TILDA) who were aged 50 years and older. CKD was defined as eGFR &lt;60 ml/min/1.72 m2, hypertension defined as systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg and/or self-reported use of antihypertensive medication. Participant awareness and treatment of hypertension was based on self-report and SBP/DBP &lt;140/90 mmHg. Multivariable logistic regression examined relationships with awareness, treatment, and control of hypertension expressed as adjusted odds ratios.

Results
Prevalence of hypertension was significantly higher in participants with CKD than without (81.9% vs 59.7%, P &lt; .001). Among hypertensive individuals, 70.1% (95% CI: 65.8–74.1) were aware, 83.5% (95% CI 80.0–86.6) were on treatment, yet blood pressure control &lt;140/90 mmHg and SBP &lt;120 mmHg were achieved in only 49.3% (CI 44.0–54.7%) and 17.9% (CI 14.4–22.1), respectively. In multivariable analysis, advancing age 1.05 (CI 1.01–1.10), obesity 6.23 (CI 2.51–15.5), diabetes 5.78 (CI 1.55–21.5), and cardiovascular disease 9.89 (CI 3.27–29.9) were associated with higher odds of treatment, while cardiovascular disease 2.35 (CI 1.39–3.99) and combination antihypertensive therapy 1.76 (CI 1.03–3.01) were associated with blood pressure control.

Conclusion
The prevalence of hypertension is substantial in older Irish adults with CKD; however, control is poor. Approximately, one-third of participants were unaware of their hypertensive status and approximately one-fifth were untreated.
Interdependent security games in the Stackelberg style: how first-mover advantage impacts free riding and security (under-)investment
Authors: Huang Ziyuan , Naghizadeh Parinaz , Liu Mingyan 
Published: June 2024

Abstract
Network games are commonly used to capture the strategic interactions among interconnected agents in simultaneous moves. The agents’ actions in a Nash equilibrium must take into account the mutual dependencies connecting them, which is typically obtained by solving a set of fixed point equations. Stackelberg games, on the other hand, model the sequential moves between agents that are categorized as leaders and followers. The corresponding solution concept, the subgame perfect equilibrium, is typically obtained using backward induction. Both game forms enjoy very wide use in the (cyber)security literature, the network game often as a template to study security investment and externality—also referred to as the interdependent security games—and the Stackelberg game as a formalism to model a variety of attacker–defender scenarios. In this study, we examine a model that combines both types of strategic reasoning: the interdependency as well as sequential moves. Specifically, we consider a scenario with a network of interconnected first movers (firms or defenders, whose security efforts and practices collectively determine the security posture of the eco-system) and one or more second movers, the attacker(s), who determine how much effort to exert on attacking the many potential targets. This gives rise to an equilibrium concept that embodies both types of equilibria mentioned above. We will examine how its existence and uniqueness conditions differ from that for a standard network game. Of particular interest are comparisons between the two game forms in terms of effort exerted by the defender(s) and the attacker(s), respectively, and the free-riding behavior among the defenders.