bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biallelic TUFT1 variants cause woolly hair, superficial skin fragility and desmosomal defects
Authors: Jackson Adam , Moss Celia , Chandler Kate E , Balboa Pablo Lopez , Bageta Maria L , Petrof Gabriela , Martinez Anna E , Liu Lu , Guy Alyson , Mellerio Jemima E , Lee John Y W , Ogboli Malobi , Ryan Gavin ,   Genomics England Research Consortium, McGrath John A , Banka Siddharth 
Published: January 2023

Abstract

Background
Desmosomes are complex cell junction structures that connect intermediate filaments providing strong cell-to-cell adhesion in tissues exposed to mechanical stress.

Objectives
To identify causal variants in individuals with woolly hair and skin fragility of unknown genetic cause.

Methods
This research was conducted using whole-genome sequencing, whole-exome sequencing, clinical phenotyping, haplotype analysis, single-cell RNA sequencing data analysis, immunofluorescence microscopy and transmission electron microscopy.

Results
We identified homozygous predicted loss-of-function tuftelin-1 (TUFT1) variants in nine individuals, from three families, with woolly hair and skin fragility. One donor splice-site variant, c.60+1G&gt;A, was present in two families, while a frameshift variant, p.Gln189Asnfs*49, was found in the third family. Haplotype analysis showed the c.60+1G&gt;A substitution to be a founder variant in the Irish population that likely arose approximately 20 generations ago. Human and mouse single-cell RNA sequencing data showed TUFT1 expression to be enriched in the hair dermal sheath and keratinocytes. TUFT1 expression was highly correlated with genes encoding desmosomal components implicated in diseases with phenotypes that overlap with the cohort presented here. Immunofluorescence showed tuftelin-1 to be mainly localized to the peripheral cell membranes of keratinocytes in normal skin. Skin samples from individuals with TUFT1 variants showed markedly reduced immunoreactivity for tuftelin-1, with a loss of the keratinocyte cell membrane labelling. Light microscopy revealed keratinocyte adhesion, mild hyperkeratosis and areas of superficial peeling. Transmission electron microscopy showed panepidermal acantholysis with widening of intercellular spaces throughout the epidermis and desmosomal detachment through the inner plaques.

Conclusions
Biallelic loss-of-function TUFT1 variants cause a new autosomal recessive skin/hair disorder characterized by woolly hair texture and early-onset skin fragility. Tuftelin-1 has a role in desmosomal integrity and function.
A homozygous p.Leu813Pro gain-of-function NLRP1 variant causes phenotypes of different severity in two siblings
Authors: Li Mingfeng , Lay Kenneth , Zimmer Andreas , Technau-Hafsi Kristin , Wong Jasmine , Reimer-Taschenbrecker Antonia , Rohr Jan , Abdalla Ebtesam , Fischer Judith , Reversade Bruno , Has Cristina 
Published: January 2023

Abstract

Background
A trio exome sequencing study identified a previously unreported NLRP1 gene variant resulting in a p.Leu813Pro substitution of the LRR (leucine-rich repeats) domain of the NLRP1 protein (NACHT, LRR and PYD domains-containing protein 1). This homozygous mutation was shared by two sisters with different clinical presentation: the younger sister had generalized inflammatory nodules with keratotic plugs, clinically resembling multiple keratoacanthomas, while the older had manifestations of familial keratosis lichenoides chronica.

Objectives
To analyse the consequences of this NLRP1 variant in two siblings with a different clinical spectrum of severity.

Methods
To demonstrate the pathogenicity, p.Leu813Pro was recombinantly expressed, and its effect on inflammasome assembly was assessed. Exome sequencing and RNA-Seq were performed to identify factors with potentially modifying effects on the severity of the skin manifestation between each sibling.

Results
The variant p.Leu813Pro triggered activation of the NLRP1 inflammasome leading to ASC (apoptosis-associated speck-like protein containing a CARD) speck formation and interleukin (IL)-1β release. The more severely affected sister had several additional genomic variants associated with atopy and psoriasis that were not present in her sibling. IL-5 and IL-17 emerged as dominant cytokines driving prominent inflammation in the skin of the severely affected sibling.

Conclusions
To the best of our knowledge, this is the first report of a NLRP1 variant that leads to a different clinical spectrum of severity within the same sibship. IL-5 and IL-17 were the main cytokines expressed in the inflammatory lesions of the severely affected patient and might be regarded as disease modifying factors, and therefore may be considered as therapeutic targets.
Long-term oral antibiotic use in people with acne vulgaris in UK primary care: a drug utilization study
Authors: Bhate Ketaki , Mansfield Kathryn E , Sinnott Sarah-Jo , Margolis David J , Adesanya Elizabeth  , Francis Nick , Leyrat Clemence , Hopkins Susan , Stabler Richard , Shallcross Laura , Langan Sinéad M , Mathur Rohini 
Published: January 2023

Abstract

Background
The inappropriate use of antibiotics is understood to contribute to antimicrobial resistance. Oral antibiotics are regularly used to treat moderate-to-severe acne vulgaris. In practice, we do not know the typical length of oral antibiotic treatment courses for acne in routine primary care and what proportion of people receive more than one course of treatment following a new acne diagnosis.

Objectives
To describe how oral antibiotics are prescribed for acne over time in UK primary care.

Methods
We conducted a descriptive longitudinal drug utilization study using routinely collected primary care data from the Clinical Practice Research Datalink GOLD (2004–2019). We included individuals (8–50 years) with a new acne diagnosis recorded between 1 January 2004 and 31 July 2019.

Results
We identified 217 410 people with a new acne diagnosis. The median age was 17 years [interquartile range (IQR) 15–25] and median follow-up was 4.3 years (IQR 1.9–7.6). Among people with a new acne diagnosis, 96 703 (44.5%) received 248 560 prescriptions for long-term oral antibiotics during a median follow-up of 5.3 years (IQR 2.8–8.5). The median number of continuous courses of antibiotic therapy (≥ 28 days) per person was four (IQR 2–6). The majority (n = 59 010, 61.0%) of first oral antibiotic prescriptions in those with a recorded acne diagnosis were between the ages of 12 and 18. Most (n = 71 544, 74.0%) first courses for oral antibiotics were for between 28 and 90 days. The median duration of the first course of treatment was 56 days (IQR 50–93 days) and 18 127 (18.7%) of prescriptions of ≥ 28 days were for &lt; 6 weeks. Among people who received a first course of oral antibiotic for ≥ 28 days, 56 261 (58.2%) received a second course after a treatment gap of ≥ 28 days. The median time between first and second courses was 135 days (IQR 67–302). The cumulative duration of exposure to oral antibiotics during follow-up was 255 days (8.5 months).

Conclusions
Further work is needed to understand the consequences of using antibiotics for shorter periods than recommended. Suboptimal treatment duration may result in reduced clinical effectiveness or repeated exposures, potentially contributing to antimicrobial resistance.
The association of anxiety with granuloma annulare: a case–control study of the National Institutes of Health ‘All of Us’ research programme
Authors: Belzer Annika , Leasure Audrey C , Damsky William , Cohen Jeffrey M 
Published: January 2023

Abstract
Dear Editor, Granuloma annulare (GA) is an inflammatory skin disease that has been associated with diabetes, dyslipidaemia, hypothyroidism and autoimmune disorders.1,2 The annualized incidence and prevalence of GA in the USA are approximately 0.04% and 0.06%, respectively (with a female predominance).3 GA is clinically classified as localized (75% of cases), generalized or subcutaneous.4 There is a body of evidence supporting an association between several inflammatory dermatoses, such as psoriasis, and mental health conditions.5 Improvement of depression and anxiety following treatment of certain inflammatory dermatoses has also been described.5 It has been postulated that this association may, in part, relate to proinflammatory cytokines, which have been proposed to mechanistically connect inflammatory dermatoses and mental health conditions.6 A recent nested case–control study demonstrated a significant association of GA with depression, insomnia, opioid dependence and post-traumatic stress disorder.7 This study aims to investigate whether an association exists between GA and anxiety.
‘Eczema shouldn’t control you; you should control eczema’: qualitative process evaluation of online behavioural interventions to support young people and parents/carers of children with eczema
Authors: Greenwell Kate , Sivyer Katy , Howells Laura , Steele Mary , Ridd Matthew J , Roberts Amanda , Ahmed Amina , Lawton Sandra , Langan Sinéad M , Hooper Julie , Wilczynska Sylvia , Leighton Paul , Griffiths Gareth , Sach Tracey , Little Paul , Williams Hywel C , Thomas Kim S , Yardley Lucy , Santer Miriam , Muller Ingrid 
Published: January 2023

Abstract

Background
There is a lack of well-conducted randomized controlled trials evaluating the effectiveness of theory-based online interventions for eczema. To address these deficiencies, we previously developed and demonstrated the effectiveness of two online behavioural interventions: Eczema Care Online for parents/carers of children with eczema, and Eczema Care Online for young people with eczema.

Objectives
To explore the views and experiences of people who have used the Eczema Care Online interventions to provide insights into how the interventions worked and identify contextual factors that may impede users’ engagement with the interventions.

Methods
Qualitative semistructured interviews were conducted with 17 parents/carers of children with eczema and 17 young people with eczema. Participants were purposively sampled from two randomized controlled trials of the interventions and recruited from GP surgeries in England. Transcripts were analysed using inductive thematic analysis, and intervention modifications were identified using the person-based approach table of changes method.

Results
Both young people and parents/carers found the interventions easy to use, relatable and trustworthy, and perceived that they helped them to manage their eczema, thus suggesting that Eczema Care Online may be acceptable to its target groups. Our analysis suggested that the interventions may reduce eczema severity by facilitating empowerment among its users, specifically through improved understanding of, and confidence in, eczema management, reduced treatment concerns, and improved treatment adherence and management of irritants/triggers. Reading about the experiences of others with eczema helped people to feel ‘normal’ and less alone. Some (mainly young people) expressed firmly held negative beliefs about topical corticosteroids, views that were not influenced by the intervention. Minor improvements to the design and navigation of the Eczema Care Online interventions and content changes were identified and made, ready for wider implementation.

Conclusions
People with eczema and their families can benefit from reliable information, specifically information on the best and safest ways to use their eczema treatments early in their eczema journey. Together, our findings from this study and the corresponding trials suggest wider implementation of Eczema Care Online (EczemaCareOnline.org.uk) is justified.
How we treat atopic dermatitis now and how that will change over the next 5 years
Authors: Flohr Carsten 
Published: January 2023

Abstract
We live in exciting times in atopic dermatitis therapeutics, with many novel treatments in the clinical trial pipeline. Frustratingly, most of these trials are vehicle- or placebo-controlled, rather than head-to-head comparisons. Network meta-analyses can rank treatments against each other, even for placebo-controlled studies, aiding evidence-based guideline formulation and clinical decision-making. Treatment registries are an important additional vehicle to collect ‘real-world’ data on the long-term (cost) effectiveness and safety of the new drugs, outside of the stringent and short-term settings of clinical trials. As further agents enter clinical practice, the need for biomarkers of treatment response and drug safety becomes more pressing to move us towards personalized medicine and to avoid wasting healthcare resources. This review takes stock of our current treatment armamentarium for atopic dermatitis, highlights important gaps in our knowledge – including the relatively low number of studies conducted in children – and maps out how our treatment approaches for atopic dermatitis can become more targeted and holistic in the future.
An ostomy baseplate with a skin-protection technology reduces peristomal skin complications: a randomized controlled trial (the ATTRACT study)
Authors: Sætre Ragne , Gotfredsen Johanne L , Nonboe Pernille , Hansen Helle Doré , Mathiesen Ronja , Karlsmark Tonny , Størling Zenia M , Rolfsen Thomas 
Published: January 2023

Abstract

Background
Peristomal skin complications (PSCs) are the predominant complication for people living with a stoma, negatively affecting their health-related quality of life (HRQoL). PSCs may also have an impact on healthcare costs for society with more visits to healthcare professionals and increased consumption of products and treatment strategies, which amplifies the need for new strategies to reduce or prevent PSCs.

Objectives
To evaluate the performance of an ostomy baseplate with a skin-protection technology. The target group comprised people living with a stoma with liquid faecal effluent, who struggled with PSCs.

Methods
A randomized, controlled, open-labelled, cross-over trial was conducted from September 2021 to February 2022 in five different countries. Each participant tested the investigational product against a comparator product (SenSura® Mio). The Ostomy Skin Tool 2.0 was used to evaluate the peristomal skin and HRQoL was measured using the Dermatology Life Quality Index (DLQI) questionnaire. Data were analysed in mixed repeated-measures models.

Results
A total of 79 adult participants (mean age 54.5 years, female 45.6%) were included in the intention-to-treat (ITT) population. A significant reduction in PSCs (P = 0.015) and HRQoL (P = 0.035) was found for the investigational product when compared with the comparator product. Also, significantly more study participants preferred the investigational product when compared with the comparator product (P = 0.017).

Conclusions
The investigational product, an ostomy baseplate with a skin-protective technology, reduced PSCs and improved the HRQoL of people living with a stoma with liquid faecal effluent. Consequently, the investigational product was the preferred ostomy appliance of the participants. Thus, the product investigated in this study may be a new solution to be included in everyday clinical practice to overcome leakage-induced PSCs for people living with a stoma.
Comparative phylogeography of a restricted and a widespread heather: genetic evidence of multiple independent introductions ofErica mackayanainto Ireland from northern Spain
Authors: Fagúndez Jaime , Díaz-Tapia Pilar 
Published: January 2023

AbstractSpecies of flora and fauna occurring in the west of Ireland and south-west Europe, known as Lusitanian elements, constitute a puzzling case of isolated populations of uncertain origin. Here we studied the population genetic structure of the heather Erica mackayana in Ireland and northern Spain and compared it with its widespread close relative Erica tetralix using single nucleotide polymorphisms (SNPs). We reconstructed phylogenetic relationships using maximum likelihood (ML), inferred population genetic structure using cluster assignment and principal component analysis, and estimated population genetic diversity. The cluster analysis and ML phylogenetic tree showed a geographical pattern for E. tetralix supporting a post-glacial migration from Iberia to Ireland. In contrast, Irish populations of E. mackayana were supported in independent clades in the phylogenetic tree and shared clusters with Iberian populations in the structure analysis, and FST values were lower among Irish and Spanish populations than among Irish ones. This suggests that Irish populations of E. mackayana are the result of recent multiple independent introductions from its native area in northern Spain, probably assisted by humans. However, the origin of the largest Irish population at Roundstone Bog is unclear and should be further investigated. Post-glacial, long-distance dispersal is the most plausible explanation for Lusitanian species distribution in Ireland.
How is oral isotretinoin prescribed for the treatment of acne vulgaris? Results from a UK Dermatology Clinical Trials Network (UKDCTN) and British Dermatological Nursing Group (BDNG) survey of health professionals
Authors: Moledina Zahra , McPhee Margaret , Ravenscroft Jane C , Healy Eugene , Radley Kathy , Thomas Kim S , Burden-Teh Esther ,   Acne-ID Trial Development Team, Burden-Teh Esther , Healy Eugene , Hepburn Trish , Layfield Carron , Layton Alison , Leighton Paul , Leng Simon , Mitchell Miss Eleanor , Northover Guy , Radley Kathy , Ramesh Miss Grishma , Ravenscroft Jane C , Sach Tracey , Santer Miriam , Thomas Kim S , Thompson Andrew , Whitehouse Heather , Williams Hywel C 
Published: January 2023

Abstract
We undertook a survey of UK healthcare professionals through the UK Dermatology Clinical Trials Network and British Dermatological Nursing Group to understand clinicians’ routine practice of prescribing oral isotretinoin for treatment of acne vulgaris. We also wanted to understand clinicians’ experiences and views on prescribing low daily dose regimens. Overall, the survey showed that clinicians adopted a patient-centred approach when deciding isotretinoin dosing. The rationale for using a low-dose regimen varied, but was focused on patient wellbeing during treatment. Some clinicians were concerned that use of a low-dose regimen could be less effective and lead to longer treatment durations. The survey results will be useful to inform a clinical trial investigating the effectiveness and safety of low daily dose isotretinoin for the treatment of acne.
Laser treatment of acne scarring in skin of colour
Authors: Havelin Alison , Seukeran Daron C 
Published: January 2023

AbstractAcne vulgaris is a chronic inflammatory skin disorder that affects patients of all skin types. Acne scarring affects up to 95% of patients. Laser treatment is the most effective treatment for acne scarring. Adverse effects (AEs) include pain, infection, erythema, postinflammatory hyperpigmentation (PIH), hypopigmentation and scarring. Patients with darker skin types are more prone to developing PIH, arising as a result of inflammation, which can be intrinsic or extrinsic. There is concern that laser treatment may not be suitable for patients with skin of colour (SOC) due to the risks of AEs. However, the use of appropriate treatment protocols can help to mitigate these risks. Clinicians should consider the type of acne scarring and skin type of the patient when choosing the most appropriate laser. Laser treatments should be offered to patients with SOC, who should be fully informed of the risks before embarking on treatment. It is important to note that no treatment will eliminate scarring completely, but lasers can significantly improve the appearance of acne scars. Laser treatment for acne scarring can be performed safely and effectively when tailored to the patient’s needs and skin type. Further studies are needed to evaluate the use of lasers for patients with SOC.
Dermoscopy in Mycobacterium marinum infection and its correlation with clinical and histopathological features: a prospective observational study
Authors: Yao Qiu-nan , Lu Yu-mo , Fei Wen-min , Xie Chun-tao , Cheng Wen-hao , Ren Hong , Hu Wen-long 
Published: January 2023

Abstract

Background
Mycobacterium marinum is a nontuberculous mycobacterium and a conditional pathogen to humans, which can be inoculated directly and cause chronic skin granulomas. Dermoscopy has been applied to other granulomatous skin diseases, but not to M. marinum infection.

Aim
To explore the dermoscopic features of M. marinum infection, and its correlation with clinical and histopathological features.

Methods
In total, 27 lesions from 27 patients (19 women, 8 men, age range 28–71 years) diagnosed with M. marinum infection were identified by clinical examination, histopathological results, PCR sequencing and mycobacterial culture in the dermatology outpatient department of our hospital from March 2020 to February 2022. The dermoscopy images and pathological characteristics were analysed.

Results
Lesions were located on the hands, forearms and upper arms. The following dermoscopic features were observed: yellowish-orange structureless areas (85·2%), white striped structures (59·3%), follicular plugs (29·6%), yellowish oval clods (14·8%) and reddish or pinkish areas (14·8%). Vessel structures were visible in all cases: long hairpin vessels (81·5%), corkscrew vessels (25·9%), comma-shaped vessels (22·2%) and linear vessels (22·2%).

Conclusion
Yellowish-orange structureless areas, white striped structures and long hairpin vessels are the most common dermoscopic features of M. marinum infection. Thus, dermoscopy could be used as a noninvasive auxiliary diagnostic method to provide a diagnostic basis for this disease.
Environmental management systems and their relevance to dermatology
Authors: Tso Simon 
Published: January 2023

Abstract
The International Organization for Standardization ISO 14000 family of standards and the European Commission Eco-Management and Auditing Scheme are examples of voluntary environmental management systems (EMS). EMS provides a framework to facilitate organizations to incorporate environmental considerations into their governance and operations to improve the use of resources and waste management practices. Organizations with EMS accreditation reported operational efficiency improvements and cost savings. This review article describes EMS and discusses their relevance to the dermatology sustainability.