bluuebunny/crossref_metadata_2025_split huggingface dataset:
BT36 A cross-sectional study of social media content relating to cutaneous lupus
Authors: Murphy Lisa , Wynne Bairbre 
Published: June 2024

Abstract
Social media is now a well-recognized entity when it comes to accessing information quickly and at minimal cost. If patients could be directed towards reputable social media pages, they could have greater access to reliable information, as well as a forum to reach out to other patients with similar conditions. Systemic lupus erythematosus is a complex disease that can affect a number of organs. Some patients may become overwhelmed with the wealth of information being provided to them at diagnosis. Social media could play a key role in providing patients with more user-friendly information, while equally introducing a more interactive component to information sharing. As a result, the aim of this study was to establish the nature of the content available to patients on popular social media websites. Three popular social media sites were identified and included in this study: Instagram, X (formerly known as Twitter) and Facebook. The search words ‘cutaneous lupus’ were used on all three websites and the top 30 posts were included in data analysis. The content breakdown on Instagram could be stratified into the sharing of patients’ personal photographs, infographics, and the sharing of cutaneous lupus events and resources. Overall, 30% of the posts consisted of infographics with factual medical information for viewers, while 23% of patients posted personal photographs of their cutaneous lupus manifestations. The average number of people who had engaged with posts on Instagram was 1541. In terms of the site X, 47% of posts shared were to disseminate article links and publications in medical journals. Six posts were statements that contained factual medical knowledge, eight posts were images and two posts were infographics. The average number of views for these posts on X was 9797 people. Of the analysed posts on Facebook, 10 were links to article publications, 5 were statements, 5 were members seeking advice, 3 were infographics, 5 were images and 2 were videos. In total, 73% of posts on Facebook contained factual medical information regarding lupus. The average number of people to have engaged with posts on Facebook was 29. Social media has the potential to provide patients with increased access to healthcare information, medical developments, and support from other patients. This study highlights that social media may prove to be a useful adjunct for clinicians to direct their patients towards for further information. While it is important to warn patients of the potential for misinformation, if patients could be counselled on how to use social media sites appropriately, this could be an effective method for patients to garner support and knowledge about cutaneous lupus.
BT40 A case of low-grade angiosarcoma of the face: is teledermatology effective in early diagnosis of rare skin tumours?
Authors: Kubba Faris , Aliyeva-Derraz Pakiza 
Published: June 2024

Abstract
An 87-year-old White man presented with a gradual swelling of the right side of the face. This was clinically diagnosed by his general practitioner via teledermatology as erysipelas refractory to antibiotic treatment, with a clinical course of around 10 months. The differential diagnosis included rosacea. The lesion was gradually involving the cheek and spreading to the left side of the face. The patient was referred to the dermatology clinic and on examination the lesion was found to be indurated, tender and warm with a wet texture. The patient had a previous history of bladder cancer, which was treated 5 years earlier. A 4-mm punch biopsy from the right cheek was taken, which showed a permeative vasoformative tumour within the dermis composed of anastomosing vascular spaces lined by a single layer of plump endothelial cells. Mitotic figures were identified. ERG immunohistochemical stain highlighted the endothelial cells. Human herpesvirus 8 stain was negative. The diagnosis was a grade 1 angiosarcoma. This was also reviewed in the specialized unit and the patient was urgently referred to a sarcoma service. Computed tomography and positron emission tomography scans were performed and he was be referred for chemotherapy. The role of teledermatology for skin lesion assessment has been a recent development, particularly since the COVID-19 pandemic, and has impacted the ability to assess patients in person. In recent research, 22 studies were reviewed to include basal cell carcinoma, squamous cell carcinoma and melanoma. The authors stated that anxiety around missing early curable cases needs to be balanced against inappropriate referral and unnecessary excision of benign lesions. Their results suggest that teledermatology can correctly identify the majority of malignant lesions. In another recent review of 45 publications, the authors concluded that teledermatology offers a comparable standard of effectiveness to in-person assessment. It can save significant time in expediting advice and management. Image quality and inclusion of dermoscopy have a considerable bearing on the overall effectiveness. However, our case shows that the diagnostic accuracy of teledermatology in similar rare tumours needs to be carefully evaluated. Any clinical suspicion about lesions with diffuse growth patterns that mimic dermatoses refractory to medications should be taken seriously and an urgent referral to a dermatologist is to be recommended. In conclusion, we have presented a case of angiosarcoma of the face initially diagnosed as erysipelas, which needed further referral after being refractory to antibiotics. As primary cutaneous angiosarcoma is one of the most aggressive skin tumours and carries a very poor prognosis, further assessment of teledermatology as a reliable diagnostic method needs to be evaluated, and confusion with inflammatory dermatosis remains a serious diagnostic pitfall.
Frontotemporal lobar degeneration targets brain regions linked to expression of recently evolved genes
Authors: Pasquini Lorenzo , Pereira Felipe L , Seddighi Sahba , Zeng Yi , Wei Yongbin , Illán-Gala Ignacio , Vatsavayai Sarat C , Friedberg Adit , Lee Alex J , Brown Jesse A , Spina Salvatore , Grinberg Lea T , Sirkis Daniel W , Bonham Luke W , Yokoyama Jennifer S , Boxer Adam L , Kramer Joel H , Rosen Howard J , Humphrey Jack , Gitler Aaron D , Miller Bruce L , Pollard Katherine S , Ward Michael E , Seeley William W 
Published: June 2024

Abstract
In frontotemporal lobar degeneration (FTLD), pathological protein aggregation in specific brain regions is associated with declines in human-specialized social-emotional and language functions. In most patients, disease protein aggregates contain either TDP-43 (FTLD-TDP) or tau (FTLD-tau). Here, we explored whether FTLD-associated regional degeneration patterns relate to regional gene expression of human accelerated regions (HARs), conserved sequences that have undergone positive selection during recent human evolution.
To this end, we used structural neuroimaging from patients with FTLD and human brain regional transcriptomic data from controls to identify genes expressed in FTLD-targeted brain regions. We then integrated primate comparative genomic data to test our hypothesis that FTLD targets brain regions linked to expression levels of recently evolved genes. In addition, we asked whether genes whose expression correlates with FTLD atrophy are enriched for genes that undergo cryptic splicing when TDP-43 function is impaired.
We found that FTLD-TDP and FTLD-tau subtypes target brain regions with overlapping and distinct gene expression correlates, highlighting many genes linked to neuromodulatory functions. FTLD atrophy-correlated genes were strongly enriched for HARs. Atrophy-correlated genes in FTLD-TDP showed greater overlap with TDP-43 cryptic splicing genes and genes with more numerous TDP-43 binding sites compared with atrophy-correlated genes in FTLD-tau. Cryptic splicing genes were enriched for HAR genes, and vice versa, but this effect was due to the confounding influence of gene length. Analyses performed at the individual-patient level revealed that the expression of HAR genes and cryptically spliced genes within putative regions of disease onset differed across FTLD-TDP subtypes.
Overall, our findings suggest that FTLD targets brain regions that have undergone recent evolutionary specialization and provide intriguing potential leads regarding the transcriptomic basis for selective vulnerability in distinct FTLD molecular-anatomical subtypes.
Nav1.2 channel mutations preventing fast inactivation lead to SCN2A encephalopathy
Authors: Berecki Géza , Tao Elaine , Howell Katherine B , Coorg Rohini K , Andersen Erik , Kahlig Kris , Wolff Markus , Corry Ben , Petrou Steven 
Published: June 2024

Abstract
SCN2A gene-related early-infantile developmental and epileptic encephalopathy (EI-DEE) is a rare and severe disorder that manifests in early infancy. SCN2A mutations affecting the fast inactivation gating mechanism can result in altered voltage dependence and incomplete inactivation of the encoded neuronal Nav1.2 channel and lead to abnormal neuronal excitability.
In this study, we evaluated clinical data of seven missense Nav1.2 variants associated with DEE and performed molecular dynamics simulations, patch-clamp electrophysiology and dynamic clamp real-time neuronal modelling to elucidate the molecular and neuron-scale phenotypic consequences of the mutations.
The N1662D mutation almost completely prevented fast inactivation without affecting activation. The comparison of wild-type and N1662D channel structures suggested that the ambifunctional hydrogen bond formation between residues N1662 and Q1494 is essential for fast inactivation. Fast inactivation could also be prevented with engineered Q1494A or Q1494L Nav1.2 channel variants, whereas Q1494E or Q149K variants resulted in incomplete inactivation and persistent current. Molecular dynamics simulations revealed a reduced affinity of the hydrophobic IFM-motif to its receptor site with N1662D and Q1494L variants relative to wild-type. These results demonstrate that the interactions between N1662 and Q1494 underpin the stability and the orientation of the inactivation gate and are essential for the development of fast inactivation. Six DEE-associated Nav1.2 variants, with mutations mapped to channel segments known to be implicated in fast inactivation were also evaluated. Remarkably, the L1657P variant also prevented fast inactivation and produced biophysical characteristics that were similar to those of N1662D, whereas the M1501V, M1501T, F1651C, P1658S and A1659V variants resulted in biophysical properties that were consistent with gain-of-function and enhanced action potential firing of hybrid neurons in dynamic action potential clamp experiments. Paradoxically, low densities of N1662D or L1657P currents potentiated action potential firing, whereas increased densities resulted in sustained depolarization.
Our results provide novel structural insights into the molecular mechanism of Nav1.2 channel fast inactivation and inform treatment strategies for SCN2A-related EI-DEE. The contribution of non-inactivating Nav1.2 channels to neuronal excitability may constitute a distinct cellular mechanism in the pathogenesis of SCN2A-related DEE.
Automatic classification and segmentation of multiclass jaw lesions in cone-beam CT using deep learning
Authors: Liu Wei , Li Xiang , Liu Chang , Gao Ge , Xiong Yutao , Zhu Tao , Zeng Wei , Guo Jixiang , Tang Wei 
Published: June 2024

Abstract

Objectives
To develop and validate a modified deep learning (DL) model based on nnU-Net for classifying and segmenting five-class jaw lesions using cone-beam CT (CBCT).

Methods
A total of 368 CBCT scans (37 168 slices) were used to train a multi-class segmentation model. The data underwent manual annotation by two oral and maxillofacial surgeons (OMSs) to serve as ground truth. Sensitivity, specificity, precision, F1-score, and accuracy were used to evaluate the classification ability of the model and doctors, with or without artificial intelligence assistance. The dice similarity coefficient (DSC), average symmetric surface distance (ASSD), and segmentation time were used to evaluate the segmentation effect of the model.

Results
The model achieved the dual task of classifying and segmenting jaw lesions in CBCT. For classification, the sensitivity, specificity, precision, and accuracy of the model were 0.871, 0.974, 0.874, and 0.891, respectively, surpassing oral and maxillofacial radiologists (OMFRs) and OMSs, approaching the specialist. With the model's assistance, the classification performance of OMFRs and OMSs improved, particularly for odontogenic keratocyst (OKC) and ameloblastoma (AM), with F1-score improvements ranging from 6.2% to 12.7%. For segmentation, the DSC was 87.2% and the ASSD was 1.359 mm. The model's average segmentation time was 40 ± 9.9 s, contrasting with 25 ± 7.2 min for OMSs.

Conclusions
The proposed DL model accurately and efficiently classified and segmented five classes of jaw lesions using CBCT. In addition, it could assist doctors in improving classification accuracy and segmentation efficiency, particularly in distinguishing confusing lesions (eg, AM and OKC).
A Deeper Understanding of the Constitutional Status of Māori and Their Rights Required: A Reply to Christian Riffel
Authors: Charters Claire 
Published: June 2024

Abstract
In his recent article, Christian Riffel makes the important argument that New Zealand’s free trade agreements (FTAs) with the European Union and the United Kingdom constitute a form of constitutional law-making. However, in my view, Riffel misconstrues Māori rights under domestic and international law and associated context and law. He does not take sufficiently seriously the unique right of Indigenous peoples to self-determination and, in relation to Māori specifically, to tino rangatiratanga under New Zealand’s founding constitutional document, te Tiriti o Waitangi. This means that Indigenous peoples have rights to exercise public and governance power alongside a state. In this way, Indigenous peoples’ rights are fundamentally and qualitatively different from other minorities or groups in New Zealand and must not be conflated. There are several consequences that result from Riffel’s omission. For example, Riffel’s argument that Indigenous peoples’ rights under the FTAs challenge democracy does not adequately address Indigenous peoples’ rights to govern or the state’s legally questionable claim to sovereignty. I have some other less fundamental gripes. For example, Riffel’s comments on whether Māori in this field have considered the importance of the ‘Māori provisions’ is somewhat condescending.
Acute myocardial infarction and ischaemic stroke: differences and similarities in reperfusion therapies—a review
Authors: Scheldeman Lauranne , Sinnaeve Peter , Albers Gregory W , Lemmens Robin , Van de Werf Frans 
Published: June 2024

Abstract
Acute ST-elevation myocardial infarction (STEMI) and acute ischaemic stroke (AIS) share a number of similarities. However, important differences in pathophysiology demand a disease-tailored approach. In both conditions, fast treatment plays a crucial role as ischaemia and eventually infarction develop rapidly. Furthermore, in both fields, the introduction of fibrinolytic treatments historically preceded the implementation of endovascular techniques. However, in contrast to STEMI, only a minority of AIS patients will eventually be considered eligible for reperfusion treatment. Non-invasive cerebral imaging always precedes cerebral angiography and thrombectomy, whereas coronary angiography is not routinely preceded by non-invasive cardiac imaging in patients with STEMI. In the late or unknown time window, the presence of specific patterns on brain imaging may help identify AIS patients who benefit most from reperfusion treatment. For STEMI, a uniform time window for reperfusion up to 12 h after symptom onset, based on old placebo-controlled trials, is still recommended in guidelines and generally applied. Bridging fibrinolysis preceding endovascular treatment still remains the mainstay of reperfusion treatment in AIS, while primary percutaneous coronary intervention is the strategy of choice in STEMI. Shortening ischaemic times by fine-tuning collaboration networks between ambulances, community hospitals, and tertiary care hospitals, optimizing bridging fibrinolysis, and reducing ischaemia–reperfusion injury are important topics for further research. The aim of this review is to provide insights into the common as well as diverging pathophysiology behind current reperfusion strategies and to explore new ways to enhance their clinical benefit.
Closed loop stimulation reduces the incidence of atrial high-rate episodes compared with conventional rate-adaptive pacing in patients with sinus node dysfunctions
Authors: Pisanò Ennio C L , Calvi Valeria , Viscusi Miguel , Rapacciuolo Antonio , Lazzari Ludovico , Bontempi Luca , Pelargonio Gemma , Arena Giuseppe , Caccavo Vincenzo , Wang Chun-Chieh , Merkely Béla , Lin Lian-Yu , Oh Il-young , Bertaglia Emanuele , Saporito Davide , Menichelli Maurizio , Nicosia Antonino , Carretta Domenico M , Coppolino Aldo , Ching Chi Keong , del Castillo Álvaro Marco , Su Xi , Del Maestro Martina , Giacopelli Daniele , Gargaro Alessio , Botto Giovanni L 
Published: June 2024

Abstract

Aims
Subclinical atrial fibrillation (AF) is associated with increased risk of progression to clinical AF, stroke, and cardiovascular death. We hypothesized that in pacemaker patients requiring dual-chamber rate-adaptive (DDDR) pacing, closed loop stimulation (CLS) integrated into the circulatory control system through intra-cardiac impedance monitoring would reduce the occurrence of atrial high-rate episodes (AHREs) compared with conventional DDDR pacing.

Methods and results
Patients with sinus node dysfunctions (SNDs) and an implanted pacemaker or defibrillator were randomly allocated to dual-chamber CLS (n = 612) or accelerometer-based DDDR pacing (n = 598) and followed for 3 years. The primary endpoint was time to the composite endpoint of the first AHRE lasting ≥6 min, stroke, or transient ischaemic attack (TIA). All AHREs were independently adjudicated using intra-cardiac electrograms. The incidence of the primary endpoint was lower in the CLS arm (50.6%) than in the DDDR arm (55.7%), primarily due to the reduction in AHREs lasting between 6 h and 7 days. Unadjusted site-stratified hazard ratio (HR) for CLS vs. DDDR was 0.84 [95% confidence interval (CI), 0.72–0.99; P = 0.035]. After adjusting for CHA2DS2-VASc score, the HR remained 0.84 (95% CI, 0.71–0.99; P = 0.033). In subgroup analyses of AHRE incidence, the incremental benefit of CLS was greatest in patients without atrioventricular block (HR, 0.77; P = 0.008) and in patients without AF history (HR, 0.73; P = 0.009). The contribution of stroke/TIA to the primary endpoint (1.3%) was low and not statistically different between study arms.

Conclusion
Dual-chamber CLS in patients with SND is associated with a significantly lower AHRE incidence than conventional DDDR pacing.
Academic orientation and cannabis use—findings from a population-based study of Swedish adolescents in upper secondary school
Authors: Gripe Isabella , Ramstedt Mats , Karlsson Patrik , Thor Siri 
Published: June 2024

Abstract

Aim
To examine the association between academic orientation and frequent cannabis use among Swedish adolescents in upper secondary school and include pupils from introductory programs (IPs), a large group of adolescents previously overlooked in research on adolescent cannabis use.

Methods
We used cross-sectional data from two anonymous school surveys carried out in upper secondary school in 2021. The samples consisted of pupils from all academic orientations, and the analysis included 3151 pupils in higher education preparatory programs (HEPs), 1010 pupils in vocational programs (VPs), and 819 pupils in IPs. The association between the exposure academic orientation and the outcome frequent (21+ times) cannabis was analyzed using multi-level mixed-effects Poisson regression.

Results
Estimates from the first model showed a significant (P &lt; 0.05) 2.45 times higher risk of frequent cannabis use among pupils in IPs compared with in HEPs [incidence rate ratio (IRR) 2.45, 95% confidence interval (CI) 1.28–4.66] and 82% higher in VPs (IRR 1.82, 95% CI 1.09–3.04) compared with in HEPs. However, the associations between academic orientation and frequent (21+ times) cannabis use were attenuated and no longer significant when socioeconomic status, truancy, school dissatisfaction, and early onset of substance use were adjusted for.

Conclusions
There was a higher risk of frequent (21+ times) cannabis use among pupils in IPs, and this differential was explained by higher exposure to risk factors in this group. This result is important from a policy perspective as it provides knowledge of a previously neglected risk group for frequent cannabis use.
DNA Methylation Mediates the Association Between Cardiometabolic Risk Factors and Cognition: Findings From the Health and Retirement Study
Authors: Wan Zengyi , Chibnik Lori B , Valeri Linda , Hughes Timothy M , Blacker Deborah , Ma Yuan 
Published: June 2024

Abstract
The association between cardiometabolic risk factors and cognitive function has been well documented, but the underlying mechanisms are not fully understood. This longitudinal study aimed to investigate the potential mediating role of DNA methylation in this association. We conducted the analyses in 3 708 participants (mean [standard deviation {SD}] age: 67.3 [9.5], women: 57.9%) from the Health and Retirement Study who were assessed in the 2014–2020 waves, had Infinium Methylation EPIC BeadChip methylation assays from the 2016 Venous Blood Study, and had cognitive assessment between 2016 and 2020. Causal mediation analyses were used to test the mediation role of DNA methylation in the associations between cardiometabolic risk factors and cognition, adjusting for demographic, socioeconomic, and lifestyle factors. Hypertension (−0.061 in composite cognitive z-score; 95% confidence interval [CI: −0.119, −0.004]) and diabetes (−0.134; 95% CI: [−0.198, −0.071]) were significantly associated with worse cognitive function while abnormal body weight and hypercholesterolemia were not. An increased number of cardiometabolic risk factors was associated with worse cognitive function (p = .002). DNA methylation significantly mediated the association of hypertension (mediated effect on composite cognitive z-score: −0.023; 95% CI: −0.033, −0.014), diabetes (−0.022; 95% CI: −0.032, −0.014), and obesity (−0.021; 95% CI: −0.033, −0.011) with cognitive function, whereas the mediation effect was not observed for having hypercholesterolemia. The estimated proportions mediated were 37.4% for hypertension and 16.7% for diabetes. DNA methylation may be an important mediator linking cardiometabolic risk factors to worse cognition and might even provide a potential target for dementia prevention.