bluuebunny/crossref_metadata_2025 huggingface dataset:
BI15 (P048) Immunosuppression and vaccination: a cross-specialty survey on current practices
Authors: Lim Chris Puo Nen , Maliampurakal Akash , Saunders Jayne , Paton Elaine , Drummond Angela
Published: June 2024

According to the 2018 General Medical Services contract in Scotland, the responsibility for vaccination delivery has shifted from general practitioners to secondary care. Dermatologists working in NHS Scotland now have an active role in recommending vaccinations for their patients who are on immunosuppressants. This recommendation is outlined in the Green Book published by the UK Health Security Agency. Currently, dermatology patients on immunosuppressants are required to receive the pneumococcal vaccine before starting treatment and every 5 years thereafter. However, this requirement is not included in the patient group direction produced by Public Health Scotland. As a result, individual prescriptions for the vaccination are needed, which adds to the workload on the services. Our objective was to assess current vaccination practices for patients on systemic medications across multiple specialties (dermatology, rheumatology, gastroenterology) in our local health board. We developed an online questionnaire, which was iteratively refined and distributed between June and August 2023 to clinicians working in dermatology, rheumatology and gastroenterology locally, as well as other dermatology units in Scotland through the Scottish Dermatological Society. The questionnaire aimed to gather information on clinicians’ recommendations regarding influenza, pneumococcal and COVID-19 vaccines for patients taking various immunosuppressants, including methotrexate, ciclosporin, azathioprine, mycophenolate mofetil, fumaric acid esters, apremilast, biologics, and Janus kinase inhibitors. In total, 64 responses were obtained from dermatology (44 of 64, 69%), rheumatology (8 of 64, 13%) and gastroenterology (12 of 64, 19%). Most respondents in dermatology (68%) and rheumatology (88%) were consultants or associate specialists, while 50% of the respondents in gastroenterology were specialist trainees. Almost all respondents across the three specialties recommended vaccinations routinely in their clinical practice. The majority of respondents recommended yearly vaccinations against influenza. There were mixed responses on recommendations regarding pneumococcal vaccinations, with varying frequencies between yearly and 5-year intervals. A significant proportion of respondents were unsure of the latest COVID-19 vaccine recommendations. Free-text comments revealed an interest in the project and the need for standardization of vaccination recommendations. A review of the Green Book highlighted the following recommendations for patients on immunosuppressants: annual influenza vaccine, one-off pneumococcal vaccine unless in high-risk groups (asplenia, splenic dysfunction, and chronic kidney disease) and booster COVID-19 vaccines during seasonal campaigns. In conclusion, we highlight the variations in vaccination practices among these three specialties, and the importance of standardization in vaccination recommendations.
BI25 Crusted scabies in a patient with Down syndrome on risankizumab: a complex interaction of biologics, neurological background and immunodeficiency in psoriasis management
Authors: Bajwa Dalvir Singh , Jassal-Prior Pooja , Reynolds Nick J
Published: June 2024

Scabies, caused by Sarcoptes scabiei, presents a significant global health challenge and is primarily transmitted through skin-to-skin contact. Despite the remarkable advances in the use of biologics to treat psoriasis, a concerning trend of increased susceptibility to infections and infestations has emerged. In this comprehensive case study, we report the complex clinical scenario of a patient with a neurological disorder and psoriasis undergoing biologic treatment who was subsequently diagnosed with crusted scabies predominantly localized to her psoriatic plaques. A 37-year-old female patient with Down syndrome undergoing risankizumab biologic therapy for psoriasis was reviewed in the biologics clinic on a routine appointment. The patient exhibited a notable escalation in her Psoriasis Area and Severity Index (PASI) score, increasing from 11.4 to 30.6, accompanied by crusted plaques resembling the distribution of her psoriasis. Dermoscopic examination revealed distinctive burrows and mites, with microscopic confirmation of three scabies mites. A scabies outbreak in the patient’s care facility prompted a comprehensive treatment regimen involving topical permethrin and oral ivermectin, resulting in nearly complete clearance. However, residual crust necessitated additional topical treatments for resolution. Crusted scabies, prevalent in individuals with immunodeficiencies and neurological disorders such as Down syndrome, is intricately linked to cognitive impairment, altering itch perception and fostering parasite proliferation despite elevated IgE and eosinophils. Notably, crusted scabies demonstrates elevated interleukin (IL)-17 levels, potentially indicating T helper (Th)17 dysregulation. Risankizumab, an IL-23 inhibitor, influences the inflammatory function of CD4+ helper T cells, particularly Th17 cells, which produce cytokines such as IL-17A and IL-17F. The pathogenesis of psoriasis involves a positive feedback loop wherein IL-17 stimulates keratinocytes to produce inflammatory mediators, exacerbating inflammation and keratinocyte proliferation. Our hypothesis suggests that risankizumab-induced downregulation of Th17, combined with the patient’s Down syndrome background, heightened the risk of scabies infestation, leading to crusted scabies development in specific areas. This comprehensive case study highlights the importance of considering crusted scabies in immunosuppressed or neurologically affected patients with refractory psoriasis, providing valuable insights into the intricate interplay between biologics, patient characteristics and cutaneous manifestations.
BI26 HIV-associated sarcoidosis as a manifestation of immune reconstitution inflammatory syndrome
Authors: Diong Sophie , Gnanamoorthy Pranav , O’Rourke Michéal , Byrne Joanne , Bergin Colm , McMenamin Mairin , Wynne Bairbre
Published: June 2024

In up to 30% of patients with HIV treated with highly active antiretroviral therapy (HAART), paradoxical reactions occur following immune system recovery, with improvements in CD4 counts and resultant T-helper responses to inflammation – a process known as immune reconstitution inflammatory syndrome (IRIS). Sarcoidosis, a T-helper-cell-mediated disease, has been associated with this state. We present a case of HIV-associated sarcoidosis as a manifestation of IRIS. A 47-year-old South African female patient with HIV and pulmonary sarcoidosis reported a 3-month history of a new rash. She acknowledged intermittent compliance with HAART 8 months prior. Examination revealed an erythematous papular eruption affecting her face and upper extremities. Interferon-γ release assay was negative. Serum angiotensin-converting enzyme was elevated. Serum soluble interleukin-2 receptor was normal, perhaps due to underlying HIV diagnosis. Initial biopsy highlighted non-necrotizing granulomas in keeping with sarcoidosis. Five months later, following a further period of poor HAART compliance, the eruption was more florid, associated with nasal congestion and xerophthalmia. Examination revealed multiple erythematous indurated nodulopapular lesions affecting her nasal bridge, bilateral cheeks and glabella, with scattered erythematous indurated papules affecting the patient’s trunk, neck and limbs. Similar lesions in the scalp were observed, with associated alopecia. Mucous membrane involvement was present with nasal asymmetry, hard palate plaques and florid erythematous conjunctival nodules. No further multisystem involvement was noted on cardiovascular and endocrinology investigations. Treatment has been challenging due to underlying comorbidities and aggressive mucocutaneous disease. Cutaneous features responded to a combination of weaning oral prednisolone, hydroxychloroquine and methotrexate, healing with scarring. Flares have been exacerbated by cutaneous bacterial superinfection with Streptococcus pyogenes. Ocular disease remains recalcitrant, requiring lesional steroids. It has been four decades since the onset of the HIV/AIDS epidemic. Due to advances in pharmacotherapeutics, HIV has transitioned from a life-threatening infection to a chronic condition, bringing comorbidities into focus. Dermatological conditions are extremely common in HIV infection, and cutaneous IRIS manifestations account for up to 75% of all IRIS events. This IRIS manifestation is unique in its latent presentation, occurring months to years after HAART introduction – hypothesized to correlate with recovery of naive T cells. Clinically and histologically, presentations are similar to those of sarcoidosis occurring in patients with no HIV infection. However, comorbidities compounded with side-effects from immunosuppressants pose significant therapeutic obstacles in managing this challenging condition.
BI33 A case of disseminated herpes zoster in a patient on abrocitinib
Authors: Doolan Brent , Drummond Sarah , Pink Andrew , Smith Catherine , Agius Elaine
Published: June 2024

Janus kinase (JAK) inhibitors are disease-modifying agents with efficacy in treating a spectrum of burdensome dermatological conditions. Abrocitinib, which is a JAK1 selective inhibitor, has recently been approved for the treatment of moderate-to-severe atopic dermatitis in adults and young people. Data from randomized controlled trials and real-world analyses have shown herpes zoster to be one of the most frequent serious infections. We present a rare case of disseminated herpes zoster infection with lumbar plexopathy. A 62-year-old White woman was commenced on 200 mg of daily abrocitinib after failure of multiple systemic agents for treatment of her severe atopic dermatitis. After 12 months of treatment, she awoke with spontaneous left-sided ­lower-limb pain that was worse on ambulation. She was given a presumed diagnosis of sciatica and provided with analgesia. The following day the pain remained and she developed pruritic, ulcerated lesions on her face and chest and within her mouth, with periorbital oedema. She attended her local district hospital and was considered to have had a reaction to the analgesia and given oral corticosteroids. She was then reviewed 1 week later and was confined to a wheelchair as she was unable to bear weight on her left leg secondary to hip pain. Neurological examination revealed marked weakness to ankle plantar and dorsiflexion, and loss of sensation. Skin examination showed haemorrhagic crusted papules on the face, abdomen, back and lower limbs, with some intact vesicles on her thigh. Skin swabs confirmed varicella zoster virus infection and she was diagnosed with disseminated herpes zoster. In light of the neurological deficits, she was referred to the neurological team. A lumbosacral magnetic resonance imaging scan showed oedema, thickening and contrast enhancement of the left L4, L5 and S1 nerve roots, in keeping with lumbar plexopathy. She was commenced on high-dose intravenous antiviral therapy, with ongoing, significant neurological impairment to her left leg. Potential risk factors for treatment-emergent herpes zoster have been noted to include abrocitinib dose, baseline age, past history of herpes zoster and absolute lymphocyte count prior to infection. For patients with atopic dermatitis who have achieved acceptable control of their disease, abrocitinib dose reduction should be considered. Patients should be counselled on these serious infections, have their risk factors assessed and have the shingles vaccination recommended for those at risk, prior to commencing treatment.
BI41 Azacitidine-induced neutrophilic dermatosis
Authors: Oldham Jaimie , Goldsmith Portia
Published: June 2024

We present the case of a 66-year-old lady with a background of myelofibrosis that had progressed from Janus kinase 2-positive essential thrombocythaemia. She had recently been started on azacitidine and ruxolitinib and had received two cycles of this medication. She was admitted under the care of haematology with progressive pus-filled blisters and had been treated with broad-spectrum intravenous antibiotics for presumed cellulitis with significant deterioration. She was delirious and significantly unwell with a raised respiratory rate, reduced oxygen saturations, hypotension, tachycardia and a temperature. On examination she had tender erythematous, necrotic and exudative areas over both lateral upper arms and her abdomen (which was an injection site for treatment with azacitidine). A skin biopsy was performed and advice was given to start 60 mg of prednisolone (a dose of just under 1 mg per kg) as well as adding in cover for fungal infection. Almost immediately she reported feeling better and by the next day her observations had normalized and she was afebrile so the antifungals and antibiotics were stopped. She was discharged on a weaning course of prednisolone (40 mg for 3 days, 30 mg for 3 days and then weaning by 5 mg every 5 days) and was advised to stop azacitidine. Her skin improved and healed quickly and her symptoms did not return on cessation of steroids. Her biopsy showed a pandermal neutrophilic infiltrate and was negative for all bacterial and fungal stains. Neutrophilic dermatoses have been reported both in patients with underlying myelodysplastic syndrome and with use of azacitidine. The correlation with the drug timeline and the fact that the skin has not worsened since, despite the underlying myelodysplastic syndrome worsening, would lend support to this being a reaction to the medication.
BI43 Sounds fishy: a case of Mycobacterium marinum infection secondary to infliximab infusion
Authors: Khan Attam , Jain Dimple
Published: June 2024

Mycobacterium marinum is a waterborne, atypical mycobacterium that is known to cause infection in fish, mice and bats. M. marinum in humans is rare and can manifest as a skin/soft tissue infection following exposure of damaged skin to polluted water from aqueous environments such as swimming pools, wells, rivers and fish tanks. We report the case of a 73-year-old White man with a history of collagenous colitis on treatment with infliximab. He presented with pustules, ulcerated plaques and nodules on his left wrist and left deltoid as well as some nodules on the right forearm in a sporotrichoid distribution following a second infliximab infusion. A skin biopsy revealed prominent dermal abscess formation with extension of acute inflammation into the subcutis with fat necrosis. Small granulomas were also seen at the edges without caseating necrosis. Numerous acid-fast bacilli were present on a Ziehl–Neelsen stain in keeping with mycobacterial infection. He was started empirically on rifampicin, ethambutol and clarithromycin; however, minimal improvement was noted. A subsequent mycobacteria microscopy, culture and sensitivity revealed sensitivity to ciprofloxacin, and fortunately his skin responded well to this. Tumour necrosis factor (TNF)-α inhibitors such as infliximab are widely used treatments in managing chronic inflammatory dermatoses as well as inflammatory bowel disease. These agents increase the risk of granulomatous disease. A diagnosis of M. marinum is challenging and multiple biopsies and tissues cultures may be necessary for identifying the correct diagnosis. Although this case did not have any typical exposures to M. marinum, it highlights the importance of screening and educating patients regarding the risks of certain environmental exposures prior to commencing anti-TNF treatments.
BI44 Latent tuberculosis reactivation in a patient with chronic plaque psoriasis treated with ustekinumab with a review of the literature
Authors: Amini Sylvia , Hamed Fatma , Johnason Kate , Mahmoud Sarah
Published: June 2024

Ustekinumab, a monoclonal antibody against interleukin (IL)-12 and IL-23, is used for the treatment of psoriasis and psoriatic arthritis. The IL-12 pathway also plays an important role in regulating immunity to Mycobacterium tuberculosis. A multicentre, double-blind, randomized clinical trial study of 121 Korean patients with moderate-to-severe psoriasis revealed at least 75% improvement in Psoriasis Area and Severity Index (PASI) score after 12 weeks of ustekinumab treatment. Ten cases of latent tuberculosis infection (LTBI) were reported. Lupea-Chilom et al. [Lupea-Chilom DS, Solovan CS, Farcas SS et al. Latent tuberculosis in psoriasis patients on biologic therapies: real-world data from a care center in Romania. Medicina (Kaunas) 2023; 59: 1015] conducted a retrospective observational study on a total of 97 patients with severe psoriasis who were on different biologics. That study showed that two of seven patients on monotherapy ustekinumab developed LTBI. In this abstract, we present the case of a 49-year-old White woman with resistant moderate-to-severe chronic psoriasis without psoriatic arthritis who developed LTBI while on ustekinumab. She was diagnosed with psoriasis in 2012 with involvement of the scalp, flexural, vulval and gluteal regions as well as the nails. She was started on ustekinumab in October 2013 following a satisfactory prebiologics screen (including a negative QuantiFERON test). Her PASI score was zero at week 12. In 2017, she developed a malar rash and positive antinuclear antibody test, which was not tested prior to starting biologics. As lupus is a potential adverse effect of this medication, the ustekinumab was stopped in April 2017. Further rheumatological investigations ruled out lupus and ustekinumab was restarted in November 2017. As part of the screening process prior to restarting treatment, she had a repeat QuantiFERON test, which was positive. The respiratory team reviewed the patient and issued a 3-month course of rifampicin and isoniazid to treat LTBI. Following a few months of monitoring, it was deemed safe to restart ustekinumab in December 2018 and her PASI improved. In February 2020, due to the COVID pandemic, this medication had to be stopped. She was started on acitretin as an alternative in 2021 with a resulting worsening of her condition. In December 2021, the patient was restarted on ustekinumab. In this abstract, we illustrate that ustekinumab has the potential to reactivate latent tuberculosis, a phenomenon that is infrequently reported and attributed to its impact on the IL-12 pathway. To address this concern, we recommend conducting repeated annual screening during treatment in addition to a comprehensive baseline evaluation, including a chest X-ray and QuantiFERON test. Additionally, it is advisable to consider initiating isoniazid chemoprophylaxis concurrently with ustekinumab treatment as a precautionary measure.
GD04 Erythroderma: uncovering the culprit
Authors: Damani Namiz , Gold Adam , Krishnakumar S , Yesudian Paul Devakar
Published: June 2024

A middle-aged man presented to clinic in South India with a 1-year history of a widespread rash involving his whole body. There was no pre-existing skin condition. It appeared to be a possible inflammatory dermatosis and he was prescribed fixed-dose combination topical agents, including topical steroids (clobetasol propionate), topical antibiotics (gentamicin and neomycin), and a combination of an oral antifungal (terbinafine) and topical antifungals (clotrimazole and miconazole). On examination, there were numerous large, scaly plaques coalescing to an erythrodermic morphology. He was reviewed by two dermatologists, who commenced him on a reducing course of prednisolone. Due to nonresponse he was then started on ciclosporin 2.5 mg kg−1 per day. However, the condition continued to worsen. A skin biopsy was taken; this demonstrated hyperkeratosis with multiple fungal filaments consistent with extensive dermatophytosis. Over the past decade, there has been a significant increase in recalcitrant dermatophytosis seen in India. A recent multicentre study notes that the inaccessibility of adequate antifungal susceptibility testing results in excessively long treatment durations with poorly selected drugs and experimentation in medication dosage and frequency, which in turn contribute to drug resistance and the emergence of new strains (Ebert A, Monod M, Salamin K et al. Alarming India-wide phenomenon of antifungal resistance in dermatophytes: a multicentre study. Mycoses 2020; 63: 717–28). Trichophyton indotineae (previously known as Trichophyton mentagrophytes genotype VIII) is a newly identified dermatophyte species and has outpaced Trichophyton rubrum as the major causative agent of tinea cruris, tinea corporis and tinea faciei in India (Uhrlaß S, Verma SB, Gräser Y et al. Trichophyton indotineae – an emerging pathogen causing recalcitrant dermatophytoses in India and worldwide – a multidimensional perspective. J Fungi 2022; 8: 757). It has since spread to many countries globally. It is particularly problematic due to its resistance to terbinafine as a result of point mutations within the squalene epoxidase gene. Clinically, T. indotineae infections are extensive, involving multiple sites with symptoms of pain, pruritis and localized burning. Infection characteristically follows a chronic and relapsing clinical course, with an average duration of 9 months. The drug of choice is itraconazole 100 mg twice daily for 4–8 weeks, with fluconazole and griseofulvin as second-line options. Adequate hygiene measures are crucial to avert transmission and reinfection. This case highlights the issue of recalcitrant dermatophytosis in the subcontinent, emphasizing the need for improved antifungal susceptibility testing and judicious use of medications to curb drug resistance.
GD06 An observational study of the impact of the Ukraine war in our dermatology department
Authors: Hegazy Sherok , Byrne Berbie , Laing Mary
Published: June 2024

We aimed to assess the cohort of patients attending our dermatology department who have been displaced by the war in Ukraine, to evaluate the impact of the conflict on the continuity of medical care, and to shed light on the challenges faced by political refugees in an unfamiliar medical system. Consenting Ukrainian refugees attending our department over a 3-month period answered questions regarding their displacement, medical history, and reason for referral to the dermatology service. We assessed the impact of their care on our department including translators, treatment plans and further follow-up appointments. We also present a single patient’s story, highlighting the devastating impact political conflict can have on patient care. Seventeen patients participated in the study. Most patients (82%) arrived in Ireland over 1 year ago. Thirteen of the presenting complaints (76%) occurred prior to displacement. Six patients were referred for assessment of a rash and 11 with lesions. Working diagnoses included benign naevi (35%), skin cancers (29%) and inflammatory dermatoses including eczema, psoriasis and tinea (35%). Four patients had translators booked, while the remainder communicated through family members or an online translator service. In total, seven patients required excisions, two required systemic treatment and one required biologic treatment. The remaining 10 patients were discharged from dermatology. We also present a single patient’s story. The patient was a 46-year-old woman referred to dermatology with psoriasis for which she was previously on maintenance treatment with methotrexate in Ukraine. She incidentally had a lesion recently excised in Ukraine, from which she never got the results due to the war. Following her displacement she subsequently developed pain and swelling around her surgical site. Investigation revealed what was likely metastatic melanoma. Political conflict can lead to fractured patient care, catastrophic outcomes and increased pressure on thinly stretched healthcare resources. Our hospital’s immediate catchment area has accommodated just under 10 000 Ukrainian refugees to date and we have seen some of the deleterious effects this conflict has had on patient care as a consequence. Nevertheless, we must continue supporting political refugees to the best of our ability, keeping in mind the impact of displacement on their care.
H03 (P068) A history of mycosis fungoides: from Alibert to mogamulizumab
Authors: Johnson Nicholas A , Venables Zoe C , Mistry Khaylen , Levell Nick J
Published: June 2024

In 1806, French physician Baron Jean-Louis Alibert treated a 56-year-old man with a desquamating rash and skin tumours. Alibert considered this to be a variant of yaws. In 1829 Alibert named the condition mycosis fungoides (MF), meaning ‘mushroom-like fungal disease’. Over 100 years later, French dermatologist Albert Sézary published papers from 1938 to 1949 detailing a mysterious disease that caused erythroderma and ‘cellules monstrueuses’, describing cutaneous ‘monster cells’. In 1961, these clinical findings were collated together into ‘Sézary syndrome’. Over this time there was widespread confusion between these conditions, fungal infections and yaws. In the 1870s English dermatologist William Tilbury Fox published a dermatology atlas detailing cases similar to what we know now as MF, with the name ‘fibroma fungoides’. The atlas described MF as a type of fungus, before giving a description of yaws and painting a clinical picture that differed from that of a lymphoma. In 1975, Pierre-Antoine-Ernest Bazin and associates in suggested the classification system and term we now recognize as cutaneous T-cell lymphoma (CTCL). Neoplastic cells have been thought to arise from chronic activation of T cells via antigen-presenting cells, yet the antigen to trigger this response remains unknown. Several potential bacterial, viral, fungal and iatrogenic causes have been studied, but no reliable triggers have been discovered. In 2018, the World Health Organization and European Organisation for Research and Treatment of Cancer officially recognized four types of MF. These are the classic Alibert–Bazin type (representing 88.6% of cases) and its three subtypes; folliculotropic MF (11.4%), Pagetoid reticulosis, and granulomatous slack skin (both with a combined 1% prevalence). CTCL has an incidence of approximately 0.2–0.6 per 100 000 person-years, with MF being the most common subtype. MF is twice as common in male as in female patients. It is twice as common in those of Black ethnic background than in White and Asian ethnicities. Development of immunohistochemistry and polymerase chain reaction for the T-cell receptor gene in the 1980s improved the diagnosis of CTCL. However, diagnosis of MF remains challenging due to its heterogeneous presentation, often mimicking inflammatory dermatoses. Advanced disease therapies have evolved from cytotoxic chemotherapy in the 1970s to novel monoclonal antibodies such as mogamulizumab, targeting proteins on T-cell lymphoma cells (CCR4). Reflection on the past two centuries from Alibert to mogamulizumab offers insight into the challenges that accompany the aetiology, diagnosis, classification and management of MF.
PS08 Exploring the health inequality gap in atopic dermatitis among LGBTQ+ and minority ethnicity communities
Authors: Ho Bernard , Aftab Yousaf , Wright Owen , Moloney Susan , Corner Lynne
Published: June 2024

Research evidence suggests inequities in access to specialist atopic dermatitis (AD) care for LGBTQ+ and minority ethnicity groups, who can experience poorer outcomes and higher consultation rates with a general practitioner before being referred to a specialist. Understanding of why such inequities exist is limited. The research that exists is largely quantitative and lacks both patient and professional perspectives. This study aimed to address this gap through in-depth exploration of the patient journey and generation of novel insight. We used qualitative methods involving one-to-one interviews and focus groups with members of LGBTQ+ and minority ethnicity groups aged ≥ 18 years and living in the UK with a medical diagnosis of AD. People registered their interest in the study via Voice, a public engagement platform, followed by purposive sampling and selection of 20 patient participants (10 LGBTQ+ and 10 minority ethnic) to maximize diversity and generation of a broad perspective. Five healthcare professionals representing a range of clinical practice were identified from known academic sources, and/or snowball sampling to take part in an interview. Ethical approval and full participant consent were obtained. Interviews and focus groups were conducted remotely via Zoom; they were recorded then transcribed anonymously. Interviews followed a semistructured topic guide covering screening, diagnosis, general views of healthcare professionals, treatment, management and symptoms. Data were analysed thematically and compared for commonalities and differences both across and within groups. To date, 10 interviews have been completed, with six LGBTQ+ participants and four minority ethnic participants (seven female, two male, one nonbinary, one trans-female), age range 24–47 years. Preliminary results suggest that while discrimination-based barriers are not prevalent, the care system can be perceived as lacking empathy and understanding of the patient experience for people living with AD. Participants expressed personal expertise in their condition, with a desire for access to a more holistic approach to AD care that includes preventative measures. However, short consultation times with primary care givers deterred discussion beyond episodic treatment. Participants were unaware of such care options being available through alternative sites of care (pharmacies). This study is ongoing but has already generated deeper insight into the patient journey for people living with AD. Further analysis will illuminate perceived barriers to specialist care for members of LGBTQ+ and minority ethnicity groups and how these might be addressed. The findings will inform general patient-centric recommendations for practice and guide further qualitative work specific to subcommunity needs. Pfizer sponsored and funded this study.
Skin cancer decision-making in people with dementia
Authors: Page Melanie , Asfour Leila , Finlay Andrew Y
Published: June 2024

This is an ethical scenario around the decision-making process in patients with skin cancer who lack capacity. It explores how to assess capacity, the legal rights of family members, GMC recommendations and how best to support and care for these patients.
The 2022 ICJ Judgment in Nicaragua v. Colombia: Towards a Theory of Exclusivity in Allocating Rights and Jurisdiction between the Coastal and Other States?
Authors: Zhang Xinjun , Chen Xidi
Published: June 2024

In Alleged Violations of Sovereign Rights and Maritime Spaces in the Caribbean Sea (Nicaragua v. Colombia), the International Court of Justice delves into the matter of exclusivity when assessing alleged violations committed by foreign States within an Exclusive Economic Zone. Additionally, the Court examines the legality of legislative acts concerning the contiguous zone and outlines criteria for the drawing of straight baselines. The Court’s aim seems to be establishing a comprehensive theory of exclusivity, seeking to allocate and balance the rights and jurisdiction of coastal States and other States involved. In this context, it becomes apparent that the abstract notion of freedom of navigation imposes limitations on coastal States, preventing them from enacting legislation that expands the scope of their jurisdiction or adopts a liberal interpretation of permissible conditions within relevant regulatory frameworks. The implications of this theory for the evolution of the legal order pertaining to maritime spaces warrant significant attention.
Clinical and imaging presentations are associated with function in incidental adrenocortical adenomas: a retrospective cohort study
Authors: Hamidi Oksana , Shah Muhammad , Zhang Catherine D , Lazik Natalia , Li Dingfeng , Singh Sumitabh , Iñiguez-Ariza Nicole M , Raman Ram , Hurtado Maria D , Carafone Lindsay , Khanna Aakanksha , Yan Qi , Natt Neena , Hartman Robert P , McKenzie Travis , Young William F , Bancos Irina
Published: June 2024

Objective

The aim of this study is to assess whether clinical and imaging characteristics are associated with the hormonal subtype, growth, and adrenalectomy for incidental adrenal cortical adenomas (ACAs).

Design

This is a single-center cohort study.

Methods

Consecutive adult patients with incidental ACA were diagnosed between 2000 and 2016.

Results

Of the 1516 patients with incidental ACA (median age 59 years, 62% women), 699 (46%) had nonfunctioning adenomas (NFAs), 482 (31%) had mild autonomous cortisol secretion (MACS), 62 (4%) had primary aldosteronism (PA), 39 (3%) had Cushing syndrome, 18 (1%) had PA and MACS, and 226 (15%) had incomplete work-up. Age, sex, tumor size, and tumor laterality, but not unenhanced computed tomography Hounsfield units (HU), were associated with hormonal subtypes. In a multivariable analysis, ≥1 cm growth was associated with younger age (odds ratio [OR] = 0.8 per 5-year increase, P = .0047) and longer imaging follow-up (OR = 1.2 per year, P < .0001). Adrenalectomy was performed in 355 (23%) patients, including 38% of MACS and 15% of NFA. Adrenalectomy for NFA and MACS was more common in younger patients (OR = 0.79 per 5-year increase, P = .002), larger initial tumor size (OR = 2.3 per 1 cm increase, P < .0001), ≥1 cm growth (OR = 15.3, P < .0001), and higher postdexamethasone cortisol (OR = 6.6 for >5 vs <1.8 μg/dL, P = .002).

Conclusions

Age, sex, tumor size, and laterality were associated with ACA hormonal subtype and can guide diagnosis and management. Tumor growth was more common with younger age and longer follow-up. Unenhanced HU did not predict hormonal subtype or growth. Adrenalectomy for MACS and NFA was mainly performed in younger patients with larger tumor size, growth, and elevated postdexamethasone cortisol.
Re-examining the adaptive function of nausea and vomiting in pregnancy
Authors: Emmott Emily H
Published: July 2024

Nausea and vomiting in pregnancy (NVP) have been proposed to have a prophylactic function. In this review, I re-examine NVP from an evolutionary perspective in light of new research on NVP. First, current evidence suggests that the observed characteristics of NVP does not align well with a prophylactic function. Further, NVP is typically associated with high costs for pregnant women, while moderate-to-severe NVP is associated with increased risks of poorer foetal/birth outcomes. In contrast, mild NVP limited to early pregnancy may associate with improved foetal outcomes—indicating a potential evolutionary benefit. Second, researchers have recently identified growth differentiation factor 15 (GDF15) to cause NVP, with implications that low-levels of pre-conception GDF15 (associated with lower cellular stress/inflammation) may increase risks/symptoms of NVP. If so, NVP in contemporary post-industrialized populations may be more severe due to environmental mismatch, and the current symptomology of NVP in such populations should not be viewed as a typical experience of pregnancy.
Comparative Genomic Analysis of the Pattern of Evolution of Male and Female Reproductive Proteins in Seed Beetles
Authors: Papachristos Konstantinos , Sayadi Ahmed , Arnqvist Göran
Published: June 2024

Male seminal fluid proteins often show signs of positive selection and divergent evolution, believed to reflect male–female coevolution. Yet, our understanding of the predicted concerted evolution of seminal fluid proteins and female reproductive proteins is limited. We sequenced, assembled, and annotated the genome of two species of seed beetles allowing a comparative analysis of four closely related species of these herbivorous insects. We compare the general pattern of evolution in genes encoding seminal fluid proteins and female reproductive proteins with those in digestive protein genes and well-conserved reference genes. We found that female reproductive proteins showed an overall ratio of nonsynonymous to synonymous substitutions (ω) similar to that of conserved genes, while seminal fluid proteins and digestive proteins exhibited higher overall ω values. Further, seminal fluid proteins and digestive proteins showed a higher proportion of sites putatively under positive selection, and explicit tests showed no difference in relaxed selection between protein types. Evolutionary rate covariation analyses showed that evolutionary rates among seminal fluid proteins were on average more closely correlated with those in female reproductive proteins than with either digestive or conserved genes. Gene expression showed the expected negative covariation with ω values, except for male-biased genes where this negative relationship was reversed. In conclusion, seminal fluid proteins showed relatively rapid evolution and signs of positive selection. In contrast, female reproductive proteins evolved at a lower rate under selective constraints, on par with genes known to be well conserved. Although our findings provide support for concerted evolution of seminal fluid proteins and female reproductive proteins, they also suggest that these two classes of proteins evolve under partly distinct selective regimes.
National Identity and the Limits of Platform Power in the Global Economy
Authors: Girard Tyler
Published: June 2024

Among the defining features of the contemporary global economy are the digital disruption of economic sectors and the accompanying political and regulatory conflicts. Across the world, multinational technology firms have mobilized consumers as a key ally in these conflicts, a critical element of the platform power they wield. In this article, I examine how non-consumer identities can limit the exercise of platform power by such firms. By synthesizing the concept of platform power with research on political consumerism and national identity, I argue that activating national identity can generate opposition to policies favorable to multinational technology firms and, in turn, curtail their ability to appeal to public support. Empirically, this article uses an online, nationally representative survey fielded in Canada. I explore the determinants of support for global regulatory cooperation and the domestic policy status quo, as well as the causal effect of consumer and national identity framing using vignette experiments across three issue areas: banking, telecommunications, and taxation. The findings reveal that activating consumer identities consistently shifts support but the effect of national identity is more variable. This article thus contributes to scholarship on the digital economic transformation and the exercise of business power in the global economy.
Itaconate and dimethyl itaconate upregulate IL-6 production in the LPS-induced inflammation in mice
Authors: Nosenko Maxim , Anisov Denis , Gubernatorova Ekaterina , Gorshkova Ekaterina , Zeng Yi-Rong , Ye Dan , Wang Pu , Finlay David , Drutskaya Marina , Nedospasov Sergei
Published: June 2024

Itaconate is one of the most studied immunometabolites produced by myeloid cells during inflammatory response. It mediates a wide range of anti-inflammatory and immunoregulatory effects and plays a role in a number of pathological states, including autoimmunity and cancer. Itaconate and its derivatives are considered potential therapeutic agents for the treatment of inflammatory diseases. While immunoregulatory effects of itaconate have been extensively studied in vitro and using knockout mouse models, less is known about how therapeutic administration of this metabolite regulates inflammatory response in vivo. Here, we investigate the immunoregulatory properties of exogenous administration of itaconate and its derivative dimethyl itaconate in a mouse model of lipopolysaccharide-induced inflammation. The data show that administration of itaconate or dimethyl itaconate controls systemic production of multiple cytokines, including increased IL-10 production. However, only dimethyl itaconate was able to suppress systemic production of IFNγ and IL-1β. In contrast to in vitro data, administration of itaconate or dimethyl itaconate in vivo resulted in systemic upregulation of IL-6 in the blood. Electrophilic stress due to itaconate or dimethyl itaconate was not responsible for IL-6 upregulation. However, inhibition of succinate dehydrogenase with dimethyl malonate also resulted in elevated systemic levels of IL-6 and IL-10. Taken together, our study reports a novel effect of exogenous itaconate and its derivative dimethyl itaconate on the production of IL-6 in vivo, with important implications for the development of itaconate-based anti-inflammatory therapies.
Activity responses of a mammal community to a 17-year cicada emergence event
Authors: Proudman Alexis S , Jones Landon R , Watkins Morgan O , Flaherty Elizabeth A
Published: June 2024

During a limited period in the summer of 2021, 17-year cicada species (Magicicada cassini, M. septendecula, M. septendecim) represented a large pulse of easily accessible food unique to forest ecosystems in the eastern United States. Using trail cameras and acoustic recorders, we tested whether the activity levels of 8 mammal species in northwestern Indiana shifted in response to spatial and temporal variation in cicada densities from 18 May to 20 June 2021. Cicada densities varied temporally and spatially across all study sites. Most mammal species with sufficient data showed no response to cicada emergence, including 2 tree squirrel species, Peromyscus mice, Eastern Chipmunks (Tamias striatus), and 2 species of bats. Raccoons (Procyon lotor), likely cicada predators, showed a quadratic or more complex activity response to cicada abundance, indicating a potential saturation point at densities near 1 cicada per m2. Surprisingly, White-tailed Deer (Odocoileus virginianus) activity decreased to almost 0 at the same cicada densities when we expected no change in activity. While size or accessibility may exclude cicadas as prey for small and volant mammals, our results suggest predation and satiation by Raccoons. In contrast, deer may be avoiding areas of cicada abundance due to other stimuli, such as high noise output, which may decrease their ability to detect predators.
Coyote use of prairie dog colonies is most frequent in areas used by American badgers
Authors: Windell Rebecca M , Bailey Larissa L , Livieri Travis M , Eads David A , Biggins Dean E , Breck Stewart W
Published: June 2024

The consequences of intraguild predation on vulnerable subordinate species are an important consideration in the recovery of endangered species. In prairie ecosystems, coyotes (Canis latrans) are the primary predator of endangered black-footed ferrets (Mustela nigripes; hereafter, ferrets) and presumably compete for prairie dog (Cynomys spp.) prey. Coyote predation of ferrets is thought to occur at night when ferrets are active aboveground; however, the apparent source of competition, diurnal prairie dogs, are belowground and inaccessible to coyotes at this time, presenting a perplexing temporal mismatch between actual and expected times that coyotes and ferrets come into conflict. Our study used remote wildlife cameras, occupancy models, and overlap of circadian activity patterns to investigate how landscape features, prairie dog colony attributes, and attraction to sympatric species, i.e., American badgers (Taxidea taxus; hereafter, badgers) and lagomorphs (cottontail rabbits and jackrabbits) influence Coyote use of prairie dog colonies and potential Coyote–ferret interactions. We first evaluated Coyote use (i.e., occupancy) between prairie dog colonies and surrounding available grasslands, finding that coyotes whose home ranges include prairie dog colonies used colonies nearly twice as much as surrounding grasslands. Next, we investigated biotic and abiotic factors that may influence Coyote use and frequency of use (i.e., detection probability) on prairie dog colonies. We found high Coyote use across all areas on prairie dog colonies; however, their frequency of use increased in areas that were also used by badgers. High overlap between Coyote and badger activity patterns (81%) further supports the spatial use patterns revealed by our occupancy analysis, and badgers and coyotes are known to form hunting associations. Interspecific competition and overlapping patterns of resource use between badgers and ferrets have been documented in previous studies; our study supports these findings and suggests that Coyote attraction to badger activity may influence Coyote–ferret interactions.
Scalar field dark matter: impact of supernova-driven blowouts on the soliton structure of low-mass dark matter haloes
Authors: Robles Victor H , Zagorac J Luna , Padmanabhan Nikhil
Published: June 2024

We present the first study on the gravitational impact of supernova feedback in an isolated soliton and a spherically symmetric dwarf scalar field dark matter (SFDM) halo of virial mass $1\times 10^{10}\,\mathrm{M_\odot }$. We use a boson mass $m=10^{-22}\,\mathrm{eV\,c^{-2}}$ and a soliton core $r_\mathrm{ c} \approx 0.7$ kpc, comparable to typical half-light radii of Local Group dwarf galaxies. We simulate the rapid gas removal from the centre of the soliton by a concentric external time-dependent Hernquist potential. We explore two scenarios of feedback blowouts: (i) a massive single burst and (ii) multiple consecutive blowouts injecting the same total energy to the system, including various magnitudes for the blowouts in both scenarios. In all cases, we find one single blowout has a stronger effect on reducing the soliton central density. Feedback leads to central soliton densities that oscillate quasi-periodically for an isolated soliton and stochastically for an SFDM halo. The range in the density amplitude depends on the strength of the blowout; however, we observe typical variations of a factor of $\geqslant$2. One important consequence of the stochastic fluctuating densities is that, if we had no prior knowledge of the system evolution, we can only know the configuration profile at a specific time within some accuracy. By fitting soliton profiles at different times to our simulated structures, we found the (1$\sigma$) scatter of their time-dependent density profiles. For configurations within the 1$\sigma$ range, we find the inferred boson mass is typically less than 20 per cent different from the real value used in our simulations. Finally, we compare the observed dynamical masses of field dwarf galaxies in our Local Group with the implied range of viable solitons from our simulations and find good agreement.