bluuebunny/crossref_metadata_2025_split huggingface dataset:
O10 Multifocal congenital haemangiomas: expanding our understanding of “neonatal haemangiomatosis” – case series
Authors: Peeva Daniela , Petrof Gabriela , Solman Lea 
Published: January 2024

Abstract

Background
Congenital haemangiomas are benign vascular tumours, typically solitary, categorised by their postnatal behaviour as rapidly involuting, non-involuting, or partially involuting. Histologically, they differ from infantile haemangiomas by the lack of immunostaining for GLUT-1. We present three infants with congenital, small, multifocal, non-progressive haemangiomas on the skin.

Cases
Our first patient was a male, born with 18 small vascular lesions. Abdominal ultrasound showed three vascular lesions in his liver and one in his left kidney, which were not visible on the repeated ultrasound in 3 months. MRI of the thorax showed a vascular lesion in the right hemithorax. He was completely asymptomatic, and the lung lesion was monitored annually with ultrasound.
The second patient was a male, born with eight vascular lesions. He had an abdominal ultrasound, which was clear. He was also asymptomatic, and the lesions disappeared in the first year.
The third patient was a female, born with 24 vascular lesions. Cranial ultrasound was clear; however, MRI head revealed nine punctate white matter lesions suggestive of vascular lesions. She had three small foci in the liver, consistent with haemangiomas, which were not detected after 6 weeks.
All three patients had skin biopsy, which showed thin-walled dilated vessels in the dermis, negative for GLUT1 and D240. None of the patients had coagulopathy.

Conclusion
These three cases expand the diagnosis of congenital haemangioma to include a multifocal phenotype and demonstrate their possible association with visceral and intracranial lesions/abnormalities.
P03 EB or not EB? A report of two neonates with congenital blisters
Authors: Bageta Maria , Miller Catherine , Sivakumar Branavan , Balboa Pablo Lopez , Dodein Razan , Petrof Gabriela , Martinez Anna E 
Published: January 2024

Abstract
Neonatal compartment syndrome (NCS) is extremely rare, with less than 100 cases reported. The affected limb usually presents with significant swelling and sentinel skin changes such as desquamation, blisters and skin necrosis. Risk factors that predispose infants to a hypercoagulable state or trauma have been implicated, but the exact cause remains elusive. We report two neonates with no family history of note, except for oligohydramnios in patient 1, who presented with congenital bullae over the upper extremity which led to an open wound. They were both referred to our service with a provisional diagnosis of epidermolysis bullosa (EB). Patient 1 also presented with a reduction in spontaneous movements of the hand shortly after birth.
The wound took weeks to heal with scaring and subcutaneous tissue and muscle loss resulting in significant ulnar deviation by age 9 weeks. This was managed with stretching exercises, splints and surgical intervention. Despite this there remained noticeable limb length discrepancy and functional limitations to date. Patient 2 had a lack range of motion and restricted passive motion on the affected limb by the age of 4 weeks. Subsequent neurophysiological studies showed evidence of a severe chronic median and ulnar neuropathy with distal axonal loss and a right radial neuropathy at the site of the scar.
Clinically, both cases were in keeping with NCS. A skin biopsy and molecular analysis ruled out EB. NCS requires early recognition and intervention as it can lead to long-term sequelae including Volkmann contracture, limb length discrepancies and permanent nerve damage.
P20 A Rare Case of Hereditary Mucoepithelial Dysplasia With Long Term Follow Up
Authors: Vetsiou Evangelia , Hayes Emily , Holden Simon , Burrows Nigel 
Published: January 2024

Abstract
This 28-year old woman initially presented at 2 years of age with patchy alopecia, perianal erythema and widespread rough skin. Prior to her first birthday she was diagnosed with bilateral corneal ulceration and was treated initially with soft contact lenses. She had no features of ichthyosis or hyperkeratosis and teeth, nails and eyelashes were normal. The hair loss progressed with involvement of the eyebrows. On examination, there was widespread keratosis pilaris, perianal and vulval erythema and angular cheilitis. Light microscopy of the cut hair was essentially normal. A clinical diagnosis of hereditary mucoepithelial dysplasia was made at that time. She recently underwent genetic testing which has confirmed the diagnosis. She is now registered blind and wears a wig. Her IQ is normal.
Hereditary mucoepithelial dysplasia (HMD; OMIM 158310) is a rare autosomal dominant genodermatosis characterised by chronic mucosal lesions associated with keratitis, non-scarring alopecia, keratosis pilaris and psoriasiform perineal intertrigo. A novel causative heterozygous pathogenic variant c.1580G&gt;T (p.Arg527Leu) was identified in our patient in the sterol regulatory element-binding factor 1 (SREBF1) gene. This is involved in promoting the transcription of lipogenes that are associated with epidermal cholesterol and fatty acid biosynthesis.
HMD is allelic with autosomal dominant IFAP showing considerable phenotypic overlap and should be considered in patient with congenital hypotrichosis.
P21 Bi-allelic TUFT1 variants in two siblings with woolly hair and skin fragility
Authors: Balboa Pablo Lopez , Bageta Maria L , McGrath John A , Petrof Gabriela , Martinez Anna E 
Published: January 2024

Abstract
TUFT1 encodes tuftelin-1, a glycoprotein thought to play a major role in mineralization and structural organization of enamel, but it has not been implicated in any monogenic enamel disorders.
Recently, Jackson et al. (2023) identified that tuftelin-1 has a role in desmosomal function. Pathology in desmosomal components causes disorders affecting the skin, hair, and heart. Newly described bi-allelic loss-of-function TUFT1 variants (OMIM600087) cause a novel skin fragility-woolly hair phenotype.
We present two siblings from non-consanguineous parents of Irish and British ancestry. Both had normal skin at birth and developed widespread blisters on day two of life, on the limbs, buttocks area and inside the mouth.
Although their skin fragility had improved with age, they still developed flare-ups with multiple small blisters, mainly on their limbs when viral illness. They had mild palmoplantar keratoderma and skin peeling.
Their most characteristic phenotype was slow-­growing woolly hair that did not need cutting until the age of 5 years old in the older sibling. The eyebrows and eyelashes were unaffected. Recently, the older sibling has developed keratosis pilaris on her arms. The heart was unaffected with normal electrocardiogram and echocardiogram. Whole exome sequencing identified homozygous NM_020127:c.60+1G&gt;A TUFT1 variants in both affected individuals.
These two cases reflect a novel condition. The predominant clinical phenotype is woolly hair and early signs of skin fragility. Despite having a role in desmosomal integrity bi-­allelic loss-of-function TUFT1 variants do not appear to cause cardiac pathology.
P23 Successful Control of Systemic Mastocytosis Symptoms in a Two-Year-Old with Omalizumab
Authors: Ramwani Miteshkumar , Kotsapas Constantinos , Clark Sheila , Bartram Jack , Solman Lea 
Published: January 2024

Abstract
A 6-month-old boy presented to us with diffuse cutaneous mastocytosis, experiencing constant severe pruritus, blistering, urticaria, flushing, diarrhoea, and frequent anaphylaxis episodes. He was found to have hepatosplenomegaly and mast cells in the bone marrow aspirate, confirming systemic mastocytosis. His tryptase was significantly elevated (87 ug/ml). A c-KIT D816V mutation was identified in exon 17 through a skin biopsy and peripheral blood testing.
The patient received concomitant treatment with cetirizine (eightfold dosage), hydroxyzine,
chlorphenamine, cimetidine, ketotifen, sodium cromoglicate, and montelukast in addition to topical treatment. Despite the treatment, he continued to have frequent episodes of flushing, anaphylaxis, blisters, and severe pruritus. He required oral prednisolone on several occasions, which provided little relief.
Treatment with Imatinib was not an option, as patients with mastocytosis who have the c-KIT D816V mutation do not respond to it. Due to his poor quality of life, we initiated monthly injections of omalizumab (150 mg sc). After three doses, his DLQI score decreased from 29/30 to 10/30. He had no further anaphylactic episodes, and he had significant reduction in the episodes of flushing, urticaria and blistering. Unfortunately, there was little improvement in his pruritus, which remains troublesome for him, particularly at night. He had no significant side effects of omalizumab.
Conclusion Omalizumab may provide safe and effective management of symptoms in paediatric patients with systemic mastocytosis, refractory to high-dose conventional therapy, particularly in patients who cannot receive imatinib.
P27 Successful treatment of severe eczema and plane warts with Dupilumab in a child with Dedicator of Cytokinesis 8 (DOCK8) deficiency (Autosomal recessive form of hyper-IgE syndrome)
Authors: Oyedepo Jadesola , Worth Austen , Solman Lea 
Published: January 2024

Abstract
A six-year-old girl first presented with severe eczema at the age of 6 months, which was difficult to control with topical treatments. She was found to have severely elevated total IgE and multiple food allergies. Due to recurrent ear and chest infections, and persistent varicella zoster, she was screened for a primary immunodeficiency and found to have a homozygous exon 29-46 deletion in the DOCK8 gene. Her eczema remained challenging, with coalescing warts on her limbs. She started Methotrexate with an initial good response; however, the frequency of infections and hospitalizations increased. After the diagnosis of DOCK8 deficiency was confirmed, she started Dupilumab, resulting in the complete resolution of her eczema and warts. She is awaiting haematopoietic stem cell transplant (HSCT) .
DOCK8 deficiency is an autosomal recessive hyper-IgE syndrome that presents early in life with severe eczema, skin abscesses, multiple food allergies, recurrent respiratory tract infections, and severe viral (including skin) infections. Older patients invariably develop bronchiectasis and are at high risk of malignancy. Patients have a combined immunodeficiency, with T-cell lymphopenia, reduced thymic output and T-cell skewing to a Th2 response. Children with this condition often present to dermatologists because of severe eczema, which is usually difficult to treat with standard topical treatments. The decision to treat with systemic immunosuppression is often challenging due to recurrent infections. Although HSCT is the curative treatment for DOCK8 deficiency, Dupilumab can be used to reduce inflammation and infections, and improve quality of life in patients awaiting HSCT.
P29 Erosive and vesicular dermatitis
Authors: Stavrou Christiana , Leech Suzy 
Published: January 2024

Abstract
We present a case of a 3 year old girl, born at term via normal vaginal delivery, with significant erosive lesions present from birth. Finger and toenails were small and she was systemically well. At day three, there was already evidence of healing and by week two, the erosions had almost fully healed with residual scaling. Once fully resolved, areas of hypopigmented, reticulate scarring remained.
Investigations included swabs for bacterial, fungal and viral infections were negative. There was no concern regarding perinatal infection and apart from oligohydramnios, there were no other issues in pregnancy. She was managed on the burns unit with nutritional support, antibiotics, emollients and dressings.
She subsequently developed a left micro-ophthalmia and cataract, right severe myopia and a mild developmental delay with microcephaly. Older siblings aged 7 and 5 had a history of mild developmental delay and microcephaly. Parents had no relevant medical issues and were both of Jewish background.
Genetic testing was carried out which did not identify a genetic cause with normal microarrays of her siblings.
A diagnosis of vesicular and pustular dermatosis was made, a rare condition, first described in 1985 by Cohen et al. Lesions typically consist of erythema, erosions, crusting, vesicles and fissures which start to heal within 10 days with residual reticulate scarring. Most cases occur in premature infants, making our case less typical. Nail, ophthalmological abnormalities and developmental delay are other associations, seen in our case.
P32 Bullous Pemphigoid in Childhood and Infancy. A case of a 4-months old post vaccination
Authors: Hassanin Sondos , Katira Arnav , Hardcastle Nicola 
Published: January 2024

Abstract
The first case of bullous pemphigoid was reported in 1970, however, this remains a mystery. Two peaks of incidences of BP in childhood have been reported in the first year of life (infantile BP) and around the age of 8 years old. Bullous pemphigoid is characterized by circulating autoantibodies that attack basal skin membrane antigens.
Increasing numbers of cases have recently increased the suspicion around the link to immunization. We present the case of a 4-month-old male born at full term with no family history of skin diseases and progressive blistering disease manifesting as a papulovesicular eruption on the face, acral sites, and the trunk while sparing the back, who also recently received a 12-week vaccination.
He was treated with Steroids, Intravenous immunoglobulin, and Erythromycin. However, management has been challenging due to limited evidence regarding treatment. He responded well with no relapse.
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CD1a and skin T cells: a pathway for therapeutic intervention
Authors: Ye John H , Chen Yi-Ling , Ogg Graham 
Published: January 2024

Abstract
The CD1 and MR1 protein families present lipid antigens and small molecules to T cells, complementing well-studied major histocompatibility complex–peptide mechanisms. The CD1a subtype is highly and continuously expressed within the skin, most notably on Langerhans cells, and has been demonstrated to present self and foreign lipids to T cells, highlighting its cutaneous sentinel role. Alteration of CD1a-dependent T-cell responses has recently been discovered to contribute to the pathogenesis of several inflammatory skin diseases. In this review, we overview the structure and role of CD1a and outline the current evidence implicating CD1a in the development of psoriasis, atopic dermatitis and allergic contact dermatitis.
Transgressive segregation, hopeful monsters, and phenotypic selection drove rapid genetic gains and breakthroughs in predictive breeding for quantitative resistance to Macrophomina in strawberry
Authors: Knapp Steven J , Cole Glenn S , Pincot Dominique D A , Dilla-Ermita Christine Jade , Bjornson Marta , Famula Randi A , Gordon Thomas R , Harshman Julia M , Henry Peter M , Feldmann Mitchell J 
Published: January 2024

Abstract
Two decades have passed since the strawberry (Fragaria x ananassa) disease caused by Macrophomina phaseolina, a necrotrophic soilborne fungal pathogen, began surfacing in California, Florida, and elsewhere. This disease has since become one of the most common causes of plant death and yield losses in strawberry. The Macrophomina problem emerged and expanded in the wake of the global phase-out of soil fumigation with methyl bromide and appears to have been aggravated by an increase in climate change-associated abiotic stresses. Here we show that sources of resistance to this pathogen are rare in gene banks and that the favorable alleles they carry are phenotypically unobvious. The latter were exposed by transgressive segregation and selection in populations phenotyped for resistance to Macrophomina under heat and drought stress. The genetic gains were immediate and dramatic. The frequency of highly resistant individuals increased from 1% in selection cycle 0 to 74% in selection cycle 2. Using GWAS and survival analysis, we found that phenotypic selection had increased the frequencies of favorable alleles among 10 loci associated with resistance and that favorable alleles had to be accumulated among four or more of these loci for an individual to acquire resistance. An unexpectedly straightforward solution to the Macrophomina disease resistance breeding problem emerged from our studies, which showed that highly resistant cultivars can be developed by genomic selection per se or marker-assisted stacking of favorable alleles among a comparatively small number of large-effect loci.
RtNAC055 promotes drought tolerance via a stomatal closure pathway linked to methyl jasmonate/hydrogen peroxide signaling in Reaumuria trigyna
Authors: Ma Binjie , Zhang Jie , Guo Shuyu , Xie Xinlei , Yan Lang , Chen Huijing , Zhang Hongyi , Bu Xiangqi , Zheng Linlin , Wang Yingchun 
Published: January 2024

Abstract
The stomata regulate CO2 uptake and efficient water usage, thereby promoting drought stress tolerance. NAC proteins (NAM, ATAF1/2, and CUC2) participate in plant reactions following drought stress, but the molecular mechanisms underlying NAC-mediated regulation of stomatal movement are unclear. In this study, a novel NAC gene from Reaumuria trigyna, RtNAC055, was found to enhance drought tolerance via a stomatal closure pathway. It was regulated by RtMYC2 and integrated with jasmonic acid signaling and was predominantly expressed in stomata and root. The suppression of RtNAC055 could improve jasmonic acid and H2O2 production and increase the drought tolerance of transgenic R. trigyna callus. Ectopic expression of RtNAC055 in the Arabidopsis atnac055 mutant rescued its drought-sensitive phenotype by decreasing stomatal aperture. Under drought stress, overexpression of RtNAC055 in poplar promoted ROS (H2O2) accumulation in stomata, which accelerated stomatal closure and maintained a high photosynthetic rate. Drought upregulated the expression of PtRbohD/F, PtP5CS2, and PtDREB1.1, as well as antioxidant enzyme activities in heterologous expression poplars. RtNAC055 promoted H2O2 production in guard cells by directly binding to the promoter of RtRbohE, thus regulating stomatal closure. The stress-related genes RtDREB1.1/P5CS1 were directly regulated by RtNAC055. These results indicate that RtNAC055 regulates stomatal closure by maintaining the balance between the antioxidant system and H2O2 level, reducing the transpiration rate and water loss, and improving photosynthetic efficiency and drought resistance.
Global Nonlinear Stability of Traveling Wave Solution to Time-Like Extremal Hypersurface in Minkowski Space
Authors: Liu Jianli , Zhou Yi 
Published: January 2024

Abstract
There are a few results about the global nonlinear stability of nontrivial large solution to quasilinear wave equations. Time-like extremal surface in Minkowski space is an important model of quasilinear wave equation. There are two folds in this paper. Firstly, we get the existence of traveling wave solution to the time-like extremal hypersurface in $\mathbb {R}^{1+(n+1)}$, which can be considered as the generalized Bernstein theorem. For $n=2$, we are also concerned with global stability of traveling wave solutions with speed of light to time-like extremal hypersurface equation in $1+(2+1)$ dimensional Minkowski space, which is corresponding with quasilinear wave equation in two space dimensions.
Protected Beliefs Under the Equality Act: Grainger Questioned
Authors: Patten Keith 
Published: January 2024

Abstract
The definition of what is a ‘protected belief’ for the purpose of the Equality Act 2010 is of significant practical importance. This is because it determines whether people have the right not to be discriminated against and, correspondingly, whether others have the obligation not to discriminate. As such it determines how people can act. Despite this the statute itself offers little assistance in relation to this definition, instead preferring to leave the matter to tribunals to develop. This article looks at the way in which that definition has developed and at the practical difficulties this may give tribunals (both at first instance and on appeal) in deciding whether a particular belief falls to be protected or not.
Tafenoquine-Atovaquone Combination Achieves Radical Cure and Confers Sterile Immunity in Experimental Models of Human Babesiosis
Authors: Vydyam Pratap , Pal Anasuya C , Renard Isaline , Chand Meenal , Kumari Vandana , Gennaro Joseph C , Mamoun Choukri Ben 
Published: January 2024

Abstract
Human babesiosis is a potentially fatal tick-borne disease caused by intraerythrocytic Babesia parasites. The emergence of resistance to recommended therapies highlights the need for new and more effective treatments. Here we demonstrate that the 8-aminoquinoline antimalarial drug tafenoquine inhibits the growth of different Babesia species in vitro, is highly effective against Babesia microti and Babesia duncani in mice and protects animals from lethal infection caused by atovaquone-sensitive and -resistant B. duncani strains. We further show that a combination of tafenoquine and atovaquone achieves cure with no recrudescence in both models of human babesiosis. Interestingly, elimination of B. duncani infection in animals following drug treatment also confers immunity to subsequent challenge. Altogether, the data demonstrate superior efficacy of tafenoquine plus atovaquone combination over current therapies for the treatment of human babesiosis and highlight its potential in providing protective immunity against Babesia following parasite clearance.
Association of piperacillin/tazobactam MIC and mortality in a cohort of ceftriaxone-resistant Escherichia coli bloodstream infections treated with piperacillin/tazobactam and carbapenems: a multicentric propensity score-weighted observational cohort study
Authors: Rando Emanuele , Salvati Federica , Sangiorgi Flavio , Catania Francesca , Leone Elisa , Oliva Alessandra , Di Gennaro Francesco , Fiori Barbara , Cancelli Francesca , Figliomeni Sara , Bobbio Francesca , Sacco Federica , Bavaro Davide Fiore , Diella Lucia , Belati Alessandra , Saracino Annalisa , Mastroianni Claudio Maria , Fantoni Massimo , Murri Rita 
Published: January 2024

Abstract

Objectives
To assess the impact of piperacillin/tazobactam MICs on in-hospital 30 day mortality in patients with third-generation cephalosporin-resistant Escherichia coli bloodstream infection treated with piperacillin/tazobactam, compared with those treated with carbapenems.

Methods
A multicentre retrospective cohort study was conducted in three large academic hospitals in Italy between 2018 and 2022. The study population comprised patients with monomicrobial third-generation cephalosporin-resistant E. coli bloodstream infection, who received either piperacillin/tazobactam or carbapenem therapy within 48 h of blood culture collection. The primary outcome was in-hospital 30 day all-cause mortality. A propensity score was used to estimate the likelihood of receiving empirical piperacillin/tazobactam treatment. Cox regression models were performed to ascertain risk factors independently associated with in-hospital 30 day mortality.

Results
Of the 412 consecutive patients included in the study, 51% received empirical therapy with piperacillin/tazobactam, while 49% received carbapenem therapy. In the propensity-adjusted multiple Cox model, the Pitt bacteraemia score [HR 1.38 (95% CI, 0.85–2.16)] and piperacillin/tazobactam MICs of 8 mg/L [HR 2.35 (95% CI, 1.35–3.95)] and ≥16 mg/L [HR 3.69 (95% CI, 1.86–6.91)] were significantly associated with increased in-hospital 30 day mortality, while the empirical use of piperacillin/tazobactam was not found to predict in-hospital 30 day mortality [HR 1.38 (95% CI, 0.85–2.16)].

Conclusions
Piperacillin/tazobactam use might not be associated with increased mortality in treating third-generation cephalosporin-resistant E. coli bloodstream infections when the MIC is &lt;8 mg/L.