bluuebunny/crossref_metadata_2025 huggingface dataset:
BI30 An extensive follicular eruption in a transplant recipient
Authors: Orpin Sid , Patel Bhavnisha
Published: June 2024

A 46-year-old woman, who had been a patient with poorly controlled type 1 diabetes since age 18 years, received a combined pancreas and renal transplant in 2020. She was taking tacrolimus and mycophenolate as an immunosuppression regimen and presented with a 6-month history of an extensive rash. On examination, there was a widespread, symmetrical eruption affecting face, trunk and limbs consisting of folliculocentric pigmented keratinous papules. On the face and trunk in particular, these demonstrated a spiny appearance. Clinically, this was considered to be trichodysplasia spinulosa (TS), a rare dermatological condition first described in 1995 and established to be caused by TS-associated polyomavirus (TSPyV) in 2010. All cases are associated with either immunosuppressive medication or diseases that cause reduced immune function. Biopsies taken from the patient’s trunk and left thigh showed striking features of dilated follicles with prominent dyskeratosis and the follicular wall replaced by cells with grey cytoplasm and vesicular nuclei, alongside numerous homogeneous, eosinophilic intracytoplasmic inclusion bodies. These features have been described in only one case of a form of acquired epidermodysplasia verruciformis (EV) caused by type 49 human papillomavirus (HPV). More often, HPV-3, 4, 5, 8 and 51 are seen in EV. Subsequent use of SV40, an immunohistochemical stain that is a surrogate marker for polyomavirus infection, failed to demonstrate TSPyV, confirming the diagnosis as EV. There are currently no published case reports of acquired EV presenting in this way, simulating the follicle-centred spiculated rash seen exclusively in TS up to this point. EV, whether of inherited or acquired origin, presents either as a spreading eruption of pityriasis versicolor-like scaly macules, flat planar wart-like papules or verrucous seborrhoeic keratosis-like papules and plaques. Although the acquired form of EV does not appear to have the same risks of developing cutaneous squamous cell carcinomas as the inherited type, there is still an increased incidence of such tumours in transplant populations, so treating EV in our patient remains an important goal. Unfortunately, there are no established, effective treatment modalities. With less widespread lesions cryotherapy, topical imiquimod or topical 5-aminolaevulinic acid photodynamic therapy might be considered. In this case, with extensive disease, systemic treatment with oral retinoids, interferons or cimetidine could be considered but the results are unpredictable, and even when this treatment is effective at reducing the number of EV-related lesions, there is a high risk of recurrence upon cessation of therapy. In the first instance, following discussion with the renal team, it has been decided to cautiously reduce the doses of the patient’s immunosuppressive drugs as this is often effective in cases of TS.
BI32 A case of pembrolizumab-induced psoriasiform rash treated with risankizumab
Authors: Agarwal Vani , Chamberlain Georgie , Bala Laksha , Shimy Noha El
Published: June 2024

We present the case of a 77-year-old female patient with a pT3a clear cell renal cell carcinoma who underwent a nephrectomy and adjuvant pembrolizumab therapy. She had a past medical history of hypercholesterolaemia, for which she took atorvastatin. After 11 cycles of pembrolizumab she developed widespread erythematous plaques with overlying scale. The initial clinical diagnosis was a lichenoid drug eruption secondary to immunotherapy. Pembrolizumab was paused for 4 weeks and the rash significantly improved with daily application of 0.1% mometasone ointment. After two further cycles of pembrolizumab, the rash reoccurred with worsening severity. A 4-mm punch biopsy was taken from the right thigh. This showed parakeratotic scales, dense neutrophilic inflammation, hypogranulosis, psoriasiform hyperplasia and a dense dermoepidermal mixed acute and chronic inflammatory infiltrate. This was consistent with a psoriasiform pattern of inflammation. Of note, she did not have a personal or family history of psoriasis. Despite maximum topical therapy and stopping immunotherapy, her Psoriasis Area and Severity Index (PASI) score increased from 10 to 33 over a few weeks. She had a body surface area coverage of 70%. Her Dermatology Life Quality Index (DLQI) score was 24. Owing to the severity of her skin and relative contraindications (history of malignancy) to conventional systemic therapies, the decision was made to commence risankizumab, an interleukin-23 inhibitor. She had an excellent response with an improvement of PASI score to 8.4 and DLQI score to 4, 4 weeks after initial induction. Pembrolizumab is an immune checkpoint inhibitor that inhibits programmed cell death 1. It has been associated with a wide variety of cutaneous adverse events including eczematous, morbilliform and lichenoid dermatoses, as well as vitiligo and pruritus. It has less commonly been associated with psoriasiform dermatoses, bullous disorders and severe cutaneous adverse reactions. In the literature, there have been reported cases of immunotherapy-induced psoriasis that have been successfully treated with apremilast and secukinumab. To our knowledge, this is the second reported such case of successful treatment with risankizumab. As immunotherapy continues to become more widely used for the treatment of malignancies, reporting cases of safe, rapidly responsive and efficacious treatments is of great importance.
BI34 Lung toxicity with methotrexate: fact or fiction?
Authors: Gold Adam , Yesudian Paul D
Published: June 2024

Methotrexate (MTX) is widely used as a first-line immunomodulator for inflammatory skin diseases. MTX-induced lung toxicity is a rarely reported complication, and its prevalence is unclear. We conducted a survey of UK clinicians on their experiences with MTX lung toxicity. In total, 109 clinicians, including 54 dermatologists (49.5%), 19 radiologists (17.4%), 26 respiratory physicians (23.9%) and 10 respondents not stating their specialty (9.2%), completed an online questionnaire that assessed their experiences with MTX-induced lung toxicity. A total of 12 questions were sent to clinicians across the UK from October 2023 to December 2023. Overall, 93 clinicians (85.3%) reported seeing either no cases (n = 58, 53.2%) or between 1 and 5 cases (n = 35, 32.1%) of MTX-induced lung toxicity. Of these, only four (3.7%) respondents identified MTX-induced lung changes in patients with dermatological indications, in the absence of other causes. One respondent did not answer the question of how many cases they had seen. In the subgroup of clinicians who observed more than 5 cases (n = 15, 13.8%), there were no dermatologists, and none reported MTX use for dermatological indications. All patients had rheumatological/connective tissue diseases (CTDs). Of those who reported seeing more than 5 cases, 10 (67%) were respiratory physicians and 5 (33%) were radiologists. Of those who reported seeing no cases of MTX-related lung changes, 41 (71%) were dermatologists. The main lung complications reported were pulmonary fibrosis and pneumonitis, with variable outcomes regarding improvement. In a 2009 literature review of 3463 patients with rheumatoid arthritis treated with MTX, 84 patients (2%) experienced some form of lung toxicity, with only 15 cases (0.4%) being attributed to MTX. In contrast, in 2015 a review of clinical trials involving patients with psoriasis, psoriatic arthritis or inflammatory bowel disease found no significant increase in respiratory adverse events for MTX users over treatment periods of 16–52 weeks. Of 1630 participants in 7 trials, only 1 MTX-treated patient developed pneumonitis (0.06%). These findings are reassuring and seem to suggest that lung toxicity is more commonly linked to CTD or other conditions rather than to MTX treatment for skin disease.
Poster presentationsPS09 User experiences of Melanotan II injection for tanning
Authors: McKenzie Ning , Gonzalez Nathaly , Huang Cathleen , Barzallo Devin , Ware Olivia , Leslie Kieron
Published: June 2024

Melanotan II (MT2) is an injectable melanocortin agonist advertised as a tanning agent, despite not being approved by the Food and Drug Administration. Sold online as a ‘research peptide’, individuals can purchase and reconstitute the lyophilized (freeze-dried) form with bacteriostatic water to inject with insulin needles. While MT2 has been previously studied for erectile dysfunction treatment, its potential adverse effects (dysplastic naevi, renal infarction) and lack of ongoing clinical trials limit scientific research on its effects (Habbema L, Halk AB, Neumann M, Bergman W. Risks of unregulated use of alpha-melanocyte-stimulating hormone analogues: a review. Int J Dermatol 2017; 56: 975–80; Peters B, Hadimeri H, Wahlberg R, Afghahi H. Melanotan II: a possible cause of renal infarction: review of the literature and case report. CEN Case Rep 2020; 9: 159–61). This study aims to understand MT2 users’ motivations, hesitations, side-­effects and tanning effects, and their relationship with healthcare providers. Participants were recruited for this qualitative study through online forums such as Reddit.com, as well as snowballing via personal contacts. Virtual interview audio was recorded, transcribed into text, and coded using thematic analysis with two coders. Twenty-eight participants have been interviewed, aged 18–64 years (mean 38.4, SD 10.2); gender breakdown is 21 cisgender men, 6 cisgender women, and 1 transgender man. Three participants identify as LGBTQ+. Two of the 28 participants identify as Hispanic; all identify as White, with one who also identifies as Native American. All participants started MT2 for tanning, but some emphasized burn prevention as a motivator. Commonly reported side-effects include nausea, reversible darkening of moles, and an increase in libido or erections. All participants had darkening of skin tone, but their sun-exposure habits varied from none to dedicated, timed sun tanning. Dosage and dosage frequency also vary widely. Common topics that emerged include participants being introduced to MT2 through the bodybuilding community and frustration with the lack of available scientific research or medical knowledge regarding MT2. While physicians have reported dysplastic naevi in people using MT2, some participants perceive that MT2 is protective against skin cancer through preventing sunburns. Many patients regularly visit doctors or even dermatologists, but do not openly discuss their MT2 usage due to general distrust or doubt that their providers are knowledgeable enough to help. This provides an opportunity for dermatologists to build trust with patients and encourage harm reduction.
SG07 Evaluation of the Foot Function Index in pachyonychia congenita
Authors: Oldham Jaimie , Stuart Beth , McCarthy Rebecca , Schwartz Janice , Evans Holly , Hansen David , O’Toole Edel
Published: June 2024

Pachyonychia congenita (PC) is a rare autosomal dominant disorder caused by variants in the keratin genes KRT6A, KRT6B, KRT6C, KRT16 or KRT17 (PC-K6a, PC-K6b, PC-K6c, PC-K16, PC-K17). All subtypes are associated with plantar calluses, and 98% with plantar pain. Our aim was to assess the utility of the Foot Function Index (FFI) in quantifying the impact of painful calluses on function in PC. The FFI is a self-administered questionnaire composed of 23 questions. It produces a total score and three subscale scores (activity limitation, disability and pain), each of which range from 0% (no effect) to 100% (maximum effect). Patients from the International Pachyonychia Congenita Research Registry (IPCRR) with confirmed PC were asked to complete the FFI three times over 3 months. As well as the FFI, respondents were asked to document the peak temperature that day and their sex. Data were collected from the IPCRR for age and gene variants. In total, 389 responses were received from 211 patients with PC (125 female, 69 male, 17 question not answered). Their age ranged from 6 to 85 years. Genotypes included PC-K6a (62), PC-K6b (29), PC-K6C (11), PC-K16 (95) and PC-K17 (14). The mean score across different timepoint observations was consistent, with overall mean scores of 40.2% (SD 19.8), 40.6% (SD 19.0) and 38.1% (SD 17.0) across the first, second and third measurements, respectively. All groups have lower overall scores than the KRT16 group (44.4%, SD 17.9), but that difference is only statistically significant for the KRT6B group [−9.93%, 95% confidence interval (CI) −17.9 to −1.96]. The disability score and the activity limitation score also showed lower scores in the other gene groups compared with KRT16 (disability 45.3%, SD 20.8; activity limitation 25.2%, SD 17.7), but only the KRT6B group showed statistically significantly lower scores: −13.0%, 95% CI −21.7 to −2.22 for disability, and −8.25%, 95% CI −15.7 to −0.82 for activity limitation. For the pain score, all gene groups had a significantly lower score than KRT16 (54.1%, SD 20.3), apart from KRT6C. The values were KRT6A −8.99% (95% CI −15.7 to −2.3), KRT6B −12.5% (95% CI −21.3 to −3.8) and KRT17 −14.1% (95% CI −25.8 to −2.4). There was no clear relationship between age, temperature or sex and any FFI score. Overall, the results show a significant impact of PC on foot function. The results suggest that some genotypes have a bigger impact on foot function than others, particularly KRT16 variants. The FFI may be a suitable patient-reported outcome measure in PC clinical trials.
SG15 A topical matter: iatrogenic adrenal crisis following excessive prescription corticosteroid use
Authors: Khanna Divya , Bardhan Ajoy , Heagerty Adrian , Harper Natasha
Published: June 2024

A 39-year-old man with intermediate junctional epidermolysis bullosa (EB) was admitted with a 2-week history of nausea, vomiting, diarrhoea, weakness, loss of appetite and abdominal pain. He described worsening pain within his chronic wounds, which were widespread, crusted and producing extensive green exudate. On admission, he was hypotensive, tachycardic and pyrexial. Investigations showed anaemia (haemoglobin 86 g L−1), hyponatraemia (132 mmol L−1), hypokalaemia (3.3 mmol L−1), raised lactate (3.29 mmol L−1), raised C-reactive protein (263 mg L−1), and leucocytosis (white cell count 22.2 × 109 L−1, neutrophils 10.5 × 109 L−1, and eosinophils 1.88 × 109 L−1). Despite treatment for sepsis secondary to cutaneous infection, inflammatory markers remained high, and the wounds deteriorated, with continuous production of yellow exudate, increasing pain and new blistering. Additionally, medical interventions failed to resolve persistent abdominal symptoms, haemodynamic compromise and pyrexia. On further review, the dermatology team noted that, unbeknownst to them, the patient had been prescribed 100 g of clobetasol propionate monthly by his general practitioner for at least the last year. Adrenal insufficiency was suspected and subsequently confirmed by a 09.00 h cortisol test (79 nmol L−1). The dermatology team initiated a 100-mg intravenous hydrocortisone bolus, followed by a 6-hourly 50-mg regimen, with consequent resolution of hypotension, tachycardia, pyrexia, hyponatraemia and eosinophilia. Targeted antibiotic therapy (tazobactam and vancomycin), 50 : 50 ointment and wound management improved inflammatory signs. The endocrinology team confirmed secondary adrenal insufficiency and provided a steroid emergency kit and advice on sick day rules at point of discharge. Adrenal crisis in secondary adrenal insufficiency is a life-threatening medical emergency requiring immediate intervention. In this case, adrenal insufficiency was caused by repeated exposure to excessive exogenous topical corticosteroids, and acute wound infection precipitated adrenal crisis. Given the nonspecific presentation, adrenal crisis is frequently overlooked in favour of other more common differential diagnoses. However, eosinophilia, hypotension, unresolving pyrexia and ongoing acute systemic inflammatory response symptoms aid accurate diagnosis. This patient’s hypokalaemia was likely secondary to vomiting, highlighting the importance of clinical context, as hyperkalaemia is more commonly noted during adrenal crisis. Most importantly, this case highlights the importance of clinician-led corticosteroid stewardship and the need for a higher index of suspicion for adrenal insufficiency in patients with a history of significant topical corticosteroid use.
SG16 CBM-opathies for the dermatologist: a rapidly expanding delineated spectrum of heterogeneous phenotypes
Authors: Dubash Faisal , Henderson Louise
Published: June 2024

CBM [Caspase recruitment domain (CARD) protein–B cell lymphoma/leukaemia 10 (BCL10)–MALT1 paracaspase (MALT1)] complex proteins regulate critical signalling of innate and adaptive immunity. They cause a spectrum of primary immunodeficiency disorders, primary atopic disorders and immunodysregulatory syndromes. Germline mutations associated with CBM-opathies can cause antifungal immunodeficiency, CADINS, BENTA, atopic dermatitis, psoriasis, pityriasis rubra pilaris, and CARD14-associated papulosquamous eruption. Genes related to human germline CBM-opathies include CARD9, CARD11, CARD14, BCL10 and MALT1. We have reviewed key dermatological phenotypes related to human germline CBM-opathies. A notable example includes autosomal dominant hypomorphic CARD14 mutations associated with severe atopic dermatitis. Patients tend to be in their first year of life (between 3 and 12 months) with severe atopy, recurrent pyogenic and viral skin infections, and chest infections, as a consequence. CARD14 mutations may impair nuclear factor-κB activation, decreasing inflammatory gene expression, and impact epidermal secretion of antimicrobial peptides. Although hypomorphic mutations in CARD11 and CARD14 cause atopic dermatitis, gain of function mutations are associated with BENTA and inflammatory psoriatic skin disease. Psoriasis or pityriasis rubra pilaris diagnosed in individuals with earlier onset may warrant a high suspicion for sequencing of CARD14 in patients and families to aid therapeutic decisions. Genetic diagnoses can be made using next-generation sequencing techniques, such as whole-exome sequencing, whole-genome sequencing, or an immunodeficiency gene panel. For diagnostic confirmation, novel variants for CBM-opathies may be identified using methods to assess expression of proteins such as CARD11, phosphorylation of nuclear factor-κB, and degradation of IkBa.
BT21 Teledermatology pathway performance for detection of all skin cancer categories
Authors: Walls Joseph , Hall Per , Mills Louise , Kilford Claire , Wishart Gordon
Published: June 2024

The aim of this study was to audit the performance of a UK nurse-led teledermatology pathway for private patients with skin lesions suspicious of melanoma, basal cell carcinoma (BCC) or squamous cell carcinoma (SCC). Patients with suspicious skin lesion symptoms (change in colour, shape or size; > 7 mm; inflamed or oozing) access the teledermatology pathway without general practitioner referral and are initially seen in private, community clinics by specialist skin cancer nurses trained in lesion detection and dermoscopy. Following a detailed lesion history, digital and dermoscopic images are taken then uploaded to the electronic patient management system for telemedicine reporting by experienced teledermatology specialists. Following telemedicine review, patients are either reassured or advised to attend a consultation with a skin cancer specialist for face-to-face examination with or without biopsy on the same day. Between 1 January 2018 and 31 December 2022, a total of 14 790 patients (6089 male, 8701 female; mean age 42 years, range 18–92) entered the diagnostic pathway. In total, 83% were offered a nurse appointment within 5 working days and 94% within 10 working days. Following telemedicine triage, 12 070 (81.6%) were reassured, and the remaining 2720 (18.4%) were advised to attend a consultant appointment. Of these 2720 patients, 2525 accepted this appointment, with the remaining 195 (0.01% of the total) attending the National Health Service (NHS) or alternative private provider. Of the 2525 who attended for further examination, 1634 underwent biopsy (11.0%) and 550 were diagnosed with skin cancer (cancer detection rate of 3.7%). Of the 550 skin cancers detected, there were 88 melanomas, 439 BCCs, 22 SCCs and one cutaneous B-cell lymphoma. Stage at diagnosis was available for 81 melanomas, with 78 (96%) of these patients diagnosed at American Joint Committee on Cancer (version 8) stage 1 or 2. There were no missed cancers documented during (or since) the audit period, giving a sensitivity of 100%, a specificity of 87.7% and an overall accuracy of 86.5% for the teledermatology cancer pathway. This audit confirms that a community-based and nurse-led teledermatology service for patients with one or more suspicious skin lesions can provide short waiting times to lesion assessment and diagnosis, with 81.6% reassured following telemedicine triage and only 18.4% attending a hospital appointment for further assessment and possible biopsy. The cancer detection rate is lower than in the NHS, but commensurate with the younger demographic of private patients. The early-stage melanoma diagnosis rate of 96% is well above the equivalent rates reported by NHS Digital for men (85%) and women (89%) in 2020. All authors are employed by the pathway provider.
BT22 Online dermatological surveys: are your participants who you think they are?
Authors: Stokes Natalie King , McCusker Sarah , Daly Aoife , Hunjan Manrup , Lowe Ashima , Charman Carolyn , George Susannah , Solman Lea , Burden-Teh Esther
Published: June 2024

Surveys are a valuable research method in dermatology. They have a multitude of applications, particularly in understanding the impacts of skin disease, treatments and services on patients. Increasingly researchers are utilizing online surveys and using social media to advertise. We describe our experience conducting an online survey to explore the experiences of parents and adolescents having teleconsultations for eczema in the UK. The survey was distributed through the Jisc online survey platform and advertised via social media platforms including Facebook, Instagram and Twitter in November 2022. As with many patient surveys, there was a prize draw incentive to win a £50 shopping voucher. Within 24 h, 138 responses were received, a higher response rate than expected. On review of the data, only six responses appeared genuine, with the rest fraudulent or suspicious for being fraudulent (95.7%). Red flags for fraudulent responses included the following: 94 responses had supplied an email address containing a name that did not match the participant’s name, while 30 responses gave an email address consisting of a random combination of letters and numbers. Clusters of survey responses appeared to have been started and completed at the same time, with duplicate answers in free-text boxes. In total, 105 responses contained a duplicate free-text response. Fraudulent responses were inconsistent and illogical; for example, 41 respondents selected that they only had experience of face-to-face appointments, despite having previously selected that they did have experience of a teleconsultation in the survey eligibility screening question. Several aspects of the overall results did not fit with expected demographics; for example, a high proportion of patients had had private appointments (42.8%), a high proportion of children were on systemic treatment (29%) and only 20.3% had been prescribed emollients. Immediate action was taken to close the survey. On review of the literature, fraudulent participation in online research is an increasing problem, which threatens the integrity of data, in addition to wasting time and funding. We discuss measures that researchers can take to prevent fraudulent responses, such as use of CAPTCHA to stop bots and not offering monetary incentives. Researchers should include measures to identify and deal with fraudulent responses in the study protocol, for example including an instruction question (such as select answer ‘b’), free-text questions and repeated questions that can be checked for consistency and logic. We hope that our experience will raise awareness among researchers conducting online surveys in dermatology, to be able to prevent and identify fraudulent data, to protect data validity.
Social inequalities in medical appointment cancellations and reschedulings at the onset of the COVID-19 epidemic in France
Authors: Pousson Jeanna-eve , Jusot Florence , Silberzan Léna , Bajos Nathalie ,   EpiCov Study Group, Bagein Guillaume , Counil Emilie , Jusot Florence , Lydie Nathalie , Meyer Laurence , Raynaud Philippe , Rouquette Alexandra , Pailhé Ariane , Rahib Delphine , Sillard Patrick , Spire Alexis
Published: June 2024

Inconsistent results are found regarding social inequalities related to healthcare appointment cancellations during the COVID-19 crisis. Whether rescheduling was associated with social status is unknown. By studying both cancellations and rescheduling, we comprehensively describe which social groups were affected by care disruption. First follow-up of a random population-based cohort was used, including 95 118 people aged 18 or older at baseline and who live in France. Poisson and multinomial regressions were used to study social factors associated with experiencing both medical appointment cancellation by health professionals during the first COVID-19 lockdown, and rescheduling within six months. Among all individuals (including those without scheduled appointment), 21.1% reported cancellations initiated by healthcare professionals. Women, the richest, and those with a chronic disease were the most affected by these cancellations. Although 78.1% who had their appointment cancelled obtained a new appointment within six months, 6.6% failed to reschedule and 15.2% did not want to reschedule. While the oldest were more likely to reschedule, regardless of their health status, the poorest and those with multiple chronic diseases were less likely to do so. Difficulties in rescheduling revealed certain social groups were ultimately more penalized by the restriction of access to care during the first wave of the COVID-19 pandemic. Given that the poorest people, a social group that is in poorer health condition compared to other groups, were the most affected, our results raise questions about the ability of the healthcare system to reduce social health inequalities during a major health crisis.
The Semantics of Beauty in Spanish Adjectives: Conceptual Structure and Implications for Folk Aesthetics
Authors: Wong García Ernesto
Published: June 2024

This article presents an analysis of Spanish adjectives that express positive aesthetic evaluation, framed in terms of Conceptual Semantics. The sample of ninety-six adjectives (with one hundred and forty-eight individual meanings) was taken from the Diccionario ideográfico y semántico de la valoración estética positiva en español. Semantic analysis of dictionary definitions showed that beauty is ascribed by way of three distinct conceptual structures, with beauty seen respectively as an intrinsic quality, as cause or effect or as a resemblance. It further showed a clear prevalence of visual attributes and part structure as targets of aesthetic evaluation, with other secondary qualities (like daintiness, perfection, effort, grace, taste and uniqueness) also being ascribed. A quantitative analysis yielded informative correlations between some of these pieces of semantic information, in the form of asymmetries between human and non-human beauty, which point to some interesting implications and questions for Spanish folk aesthetics.
Tetraploid interspecific hybrids between Asian and African rice species restore fertility depending on killer–protector loci for hybrid sterility
Authors: Kuniyoshi Daichi , Ishihara Megumi , Yamamori Koichi , Koide Yohei , Kishima Yuji
Published: June 2024

Interspecific F1 hybrids between Asian (Oryza sativa) and African rice (Oryza glaberrima) exhibit severe sterility caused by the accumulation of hybrid sterility genes/loci at 15 or more loci. The mechanisms underlying the hybrid sterility genes are largely unknown; however, a few genes associated with the killer–protector system, which is the system most frequently associated with hybrid sterility genes, have been identified. We previously produced fertile plants as tetraploids derived from diploid interspecific F1 hybrids through anther culture; therefore, it was suggested that hybrid sterility could be overcome following tetraploidization. We investigated whether tetraploid interspecific plants produced by crossing are fertile and tested the involvement of hybrid sterility genes in the process. Fertile tetraploid interspecific F1 hybrid plants were obtained by crossing 2 tetraploids of O. sativa and O. glaberrima. To elucidate the relationships between pollen fertility and the hybrid sterility loci in the tetraploid F1 microspores, we performed genetic analyses of the tetraploid F2 hybrids and diploid plants obtained from the microspores of tetraploid interspecific hybrids by anther culture. The result suggested that the tetraploid interspecific hybrids overcame pollen and seed infertility based on the proportion of loci with the killer–protector system present in the tetraploids. The heterozygous hybrid sterility loci with the killer–protector system in the tetraploid segregate the homozygous killed allele (16.7–21.4%), with more than three-quarters of the gametes surviving. We theoretically and experimentally demonstrated that fertile rice progenies can be grown from tetraploid interspecific hybrids.
Globalization, Competition and the Transformation of German Universities since the 1970s
Authors: Mayer Alexander
Published: June 2024

Responding to the perceived challenges of globalization, German politicians have sought to transform German universities into competitive ‘entrepreneurial universities’. Based on archival material from six German universities, this article shows how reforms of university governance and new modes of funding have changed power relations within universities as well as within the German scientific community. Even though the breakthrough of ‘New Public Management’ must be situated in the 1990s, some causes of these transformations can be traced back to the 1970s, when the end of the postwar boom, educational expansion and discontent with the democratization of universities gave rise to new visions of the university’s role in society. Even though neoliberal ideas did play a part in the transformation of German universities, this process was more complex than the often-used label ‘neoliberal university’ suggests. International comparisons are applied to assess the scope of change and to highlight some of the peculiarities of the German developments.
Genome evolution and transcriptome plasticity is associated with adaptation to monocot and dicot plants in Colletotrichum fungi
Authors: Baroncelli Riccardo , Cobo-Díaz José F , Benocci Tiziano , Peng Mao , Battaglia Evy , Haridas Sajeet , Andreopoulos William , LaButti Kurt , Pangilinan Jasmyn , Lipzen Anna , Koriabine Maxim , Bauer Diane , Le Floch Gaetan , Mäkelä Miia R , Drula Elodie , Henrissat Bernard , Grigoriev Igor V , Crouch Jo Anne , de Vries Ronald P , Sukno Serenella A , Thon Michael R
Published: June 2024

Background

Colletotrichum fungi infect a wide diversity of monocot and dicot hosts, causing diseases on almost all economically important plants worldwide. Colletotrichum is also a suitable model for studying gene family evolution on a fine scale to uncover events in the genome associated with biological changes.

Results

Here we present the genome sequences of 30 Colletotrichum species covering the diversity within the genus. Evolutionary analyses revealed that the Colletotrichum ancestor diverged in the late Cretaceous in parallel with the diversification of flowering plants. We provide evidence of independent host jumps from dicots to monocots during the evolution of Colletotrichum, coinciding with a progressive shrinking of the plant cell wall degradative arsenal and expansions in lineage-specific gene families. Comparative transcriptomics of 4 species adapted to different hosts revealed similarity in gene content but high diversity in the modulation of their transcription profiles on different plant substrates. Combining genomics and transcriptomics, we identified a set of core genes such as specific transcription factors, putatively involved in plant cell wall degradation.

Conclusions

These results indicate that the ancestral Colletotrichum were associated with dicot plants and certain branches progressively adapted to different monocot hosts, reshaping the gene content and its regulation.
How Bureaucrats Represent Economic Interests: Partisan Control over Trade Adjustment Assistance
Authors: KIM Minju
Published: June 2024

Embedded liberalism prescribes compensating workers hurt by globalization, but government compensation programs are often criticized for their lack of responsiveness. I explain the lack of responsiveness by illuminating bureaucrats who approve the compensation programs in the frontline. I examine how career bureaucrats distribute Trade Adjustment Assistance (TAA) benefits, the single largest federal program in the United States that compensates workers displaced by international trade. Exploiting the quasi-random assignment of TAA petitions to individual investigators at different stages of their careers, I find that career bureaucrats are less likely to certify TAA petitions and are more likely to delay investigations during Republican presidencies relative to Democratic presidencies. This partisan performance, however, applies uniquely to career bureaucrats who are not tenured and increases in magnitude during periods of high alignment between labor and the Democratic Party. The political sustainability of globalization depends on an institutional design that shapes the career incentives of bureaucrats.
Development of a Stability-Indicating Purity Method for Ubrogepant Through Stress Degradation Analysis, Extraction, and Characterization of Unidentified Degradation Products Using Flash Chromatography, NMR, IR, and LC–MS
Authors: Vanga Nagavardhana Reddy , K. Venkata Ratnam , Ummiti Kumarswamy , Ratnakaram Venkata Nadh
Published: June 2024

Background

Ubrogepant is a prescription medication used to prevent migraine headaches. It is currently available in tablet form.

Objective

The goal of this work is to investigate the drug degradation profile of ubrogepant, as well as to isolate and characterize undiscovered ubrogepant degradation products by utilizing LC–MS, NMR, and IR spectroscopic analytical techniques and, furthermore, to develop a high-resolution, sensitive, stability-indicating analytical approach for detecting and quantifying ubrogepant degradation products in its pharmaceutical formulation.

Methods

To identify and quantify the degradation products of ubrogepant in pharmaceutical products, a novel gradient reverse-phase HPLC (RP-HPLC) technique with a photo diode array (PDA) detector was developed by utilizing a C18 stationary phase column. The eluent comprised a mixture of acetonitrile and water with 0.1% (v/v) ortho-phosphoric acid. To establish the intrinsic stability of the ubrogepant pharmaceutical product, it was stress-tested under various degradation conditions, including water, alkaline, acid hydrolysis, photolytic, oxidative, and thermal. Flash chromatography was used to isolate the two major degradants, and the structures were determined using NMR (1H, 13C, distortionless enhancement by polarisation transfer-DEPT-135), IR, and LC–MS methods.

Results

The ubrogepant medication was relatively more degradable in alkaline and acidic conditions, and two unique degradation products were discovered. Based on spectroscopic and chromatographic evidence, it was conclusively demonstrated that these unique compounds were ubrogepant hydrolysis products. All degradation products were separated with a resolution greater than 2.0. The peak purity data showed that the ubrogepant peak in all of the stress samples examined was pure. Under all stress environments, ubrogepant achieved a minimum mass balance of 95%. The validated approach developed was sensitive enough to quantify ubrogepant degradation products at 0.03% of the ubrogepant test concentration.

Conclusion

The proposed method was found to be stability-indicating since it fits all of the regulatory authorities' typical requirements. This method is highly efficient for detecting and quantifying impurities in ubrogepant drug substances and drug products in QC laboratories.

Highlights

Two new degradation products of ubrogepant were successfully extracted and characterized using NMR, IR, and LC–MS spectroscopic methods. The proposed HPLC method can accurately quantify the degradation products of ubrogepant in pharmaceutical products and is sensitive enough to detect degradation products of ubrogepant as low as 0.17 µg/mL.
Comparison of ethanol-baited trap designs for ambrosia beetles in orchards in the eastern United States
Authors: Tobin Kelsey N , Lizarraga Sandra , Acharya Rajendra , Barman Apurba K , Short Brent D , Acebes-Doria Angelita L , Rivera Monique J
Published: June 2024

Ambrosia beetles (Coleoptera: Curculionidae: Scolytinae) are among the most devastating pests of orchards, nurseries, and forests. Improving trap design and ethanol lures for capturing ambrosia beetles is necessary to develop effective monitoring and management strategies. In this 2-year study, we assessed 4 trap designs and 3 commercially formulated ethanol lures to refine trapping methods tailored for orchard environments in the eastern United States. Our investigation included orchards in 2 regions, Georgia (pecan orchards) and New York (apple orchards), targeting major ambrosia beetle (Coleoptera: Curculionidae) pest species such as Xylosandrus crassiusculus (Motschulsky), X. compactus (Eichhoff), X. germanus (Blandford), and Anisandrus maiche (Stark). Among the trap designs evaluated, clear sticky cards were most effective for capturing ambrosia beetles across orchard locations. Notably, in Georgia, sticky cards paired with specific low-release ethanol lures demonstrated enhanced capture of X. crassiusculus and X. compactus, 2 key ambrosia beetle pests found infesting young pecan trees. Similarly, in New York, sticky cards baited with low-release ethanol lures captured the highest rates of X. germanus and A. maiche, thus indicating its suitability for diverse ambrosia beetle populations. Overall, our study provides practical implications for tailoring trapping protocols to optimize ambrosia beetle management strategies in orchard settings.
Stochastic inversion based on spectral simulation of non-stationary statistical characteristic parameters
Authors: Wang Baoli , Liu Longdong , Lin Ying , Zhang Guangzhi , Yin Xingyao
Published: June 2024

The traditional method of constructing the prior model for stochastic inversion mainly uses well-logging data to obtain the stationary range from the variogram to characterize the complex non-stationary spatial tectonic features of the subsurface layers. Unfortunately, it is hard for the stationary range to precisely describe the complex non-stationary spatial tectonic features of the subsurface layers. The established prior model is also difficult to use to describe the real spatial tectonic features of the subsurface media; thus, it cannot provide reliable prior information for the inversion. Therefore, according to the theory of random media, we extract the non-stationary statistical characteristic parameters that change with spatial coordinates from the known information such as seismic and well-logging data, to accurately and reliably characterize the non-stationary spatial tectonic of the subsurface media. Then, combined with fast Fourier transform-moving average spectral simulation, a spectral simulation method based on non-stationary statistical characteristic parameters is built to construct the spectral simulation results that can more accurately conform to the spatial tectonic features of the subsurface media, to provide reliable and reasonable geostatistical prior information for a better inversion result.
Biology, ecology, and management of redbanded stink bug (Hemiptera: Pentatomidae)
Authors: Okosun Olabimpe O , George Justin , Portilla Maribel , Glover James P , Parys Katherine A , Reddy Gadi V P
Published: June 2024

The redbanded stink bug (RBSB), Piezodorus guildinii (Westwood) (Hemiptera: Pentatomidae) is an invasive stink bug species and a polyphagous pest of cultivated crops and non-cultivated wild plants. The increase in soybean cultivation during the 1960s–1970s led to the spread of RBSB as an economic pest of soybean throughout South America, especially in Brazil, Argentina, and Uruguay. In the early 2000s, RBSB became an economic concern to US agriculture and is currently a key species in a stink bug complex that damages soybean in many mid-southern states. RBSB causes extensive damage to soybeans and other economically important leguminous crops by feeding on sap from stems, flowers, and foliage with a preference for pods and seeds, which causes flat pods, reduced seed weight, and germination. Infestation by RBSB may lead to more crop loss per capita than other stink bug species. RBSBs are less susceptible to commonly used agrochemicals than other stink bug species and have developed resistance to many commonly used insecticides. Several alternative control strategies based on a wide variety of methods have been reported in recent years. This review will discuss the distribution, biology, ecology, and various control strategies for integrated management of RBSB in the last 2 decades.
A Structural Break in the Aggregate Earnings–Returns Relation
Authors: Curtis Asher , Kim Chang-Jin , Oh Hyung Il
Published: June 2024

This study empirically estimates the date of the structural change in the aggregate earnings–returns relation and reports it as the fourth quarter of 1991. We identify three sources of the structural change: (i) an increase in the relative importance of cash flow news contained in stock returns; (ii) a decrease in the importance of discount rate news contained in aggregate earnings; and (iii) a decrease in the persistence or the predictability of aggregate earnings and returns. Next, we examine the components of aggregate earnings and find that the change in the aggregate earnings–returns relation is largely driven by intertemporal changes in aggregate inventory accruals, suggesting the structural change is attributable to improved inventory management systems.
Comparison of mutation spectra induced by gamma-rays and carbon ion beams
Authors: Tokuyama Yuka , Mori Kanae , Isobe Midori , Terato Hiroaki
Published: June 2024

The ionizing radiation with high linear energy transfer (LET), such as a heavy ion beam, induces more serious biological effects than low LET ones, such as gamma- and X-rays. This indicates a difference in the DNA damage produced by low and high LET radiations and their biological effects. We have been studying the differences in DNA damage produced by gamma-rays and carbon ion beams. Therefore, we analyze mutations induced by both ionizing radiations to discuss the differences in their biological effects in this study. pUC19 plasmid DNA was irradiated by carbon ion beams in the solution containing 1M dimethyl sulfoxide to mimic a cellular condition. The irradiated DNA was cloned in competent cells of Escherichia coli. The clones harboring some mutations in the region of lacZα were selected, and the sequence alterations were analyzed. A one-deletion mutation is significant in the carbon-irradiated DNA, and the C:G↔T:A transition is minor. On the other hand, the gamma-irradiated DNA shows mainly G:C↔T:A transversion. These results suggest that carbon ion beams produce complex DNA damage, and gamma-rays are prone to single oxidative base damage, such as 8-oxoguanine. Carbon ion beams can also introduce oxidative base damage, and the damage species is 5-hydroxycytosine. This was consistent with our previous results of DNA damage caused by heavy ion beams. We confirmed the causal DNA damage by mass spectrometry for these mutations.
Calcified amorphous tumor attached to the membranous septum: a rare clinical entity
Authors: Spencer Dean , Gysbers Josh T , Raghavan Ravi , Tanwangco-Barker Krizzette M , Cullom Chris J , Siddiqui Danish , Sakr Antoine , Kherlopian Alec G , Chung Josh S , Rabkin David G
Published: June 2024

We report a rare case of a pedunculated calcified amorphous tumor (CAT) of the left ventricle attached by a stalk to the membranous septum in a 74-year-old woman who presented with a cerebrovascular accident. We believe this is the first report of a CAT attached to the membranous septum.
Why are non-radial solar eruptions less frequent than radial ones?
Authors: Liu Qingjun , Jiang Chaowei , Feng Xuesheng , Zuo Pingbing , Wang Yi
Published: June 2024

Coronal mass ejections from the Sun are not always initiated along a radial trajectory; such non-radial eruptions are well known to be caused by the asymmetry of the pre-eruption magnetic configuration, which is primarily determined by the uneven distribution of magnetic flux at the photosphere. Therefore, it is naturally expected that the non-radial eruptions should be rather common, at least as frequent as radial ones, given the typically asymmetrical nature of photospheric magnetic flux. However, statistical studies have shown that only a small fraction of eruptions display non-radial behaviour. Here we aim to shed light on this counterintuitive fact, based on a series of numerical simulations of eruption initiation in bipolar fields with different asymmetric flux distributions. As the asymmetry of the flux distribution increases, the eruption direction tends to deviate further away from the radial path, accompanied by a decrease in eruption intensity. In case of too strong asymmetry, no eruption is triggered, indicating that excessively inclined eruptions cannot occur. Therefore, our simulations suggest that asymmetry plays a negative role in producing eruption, potentially explaining the lesser frequency of non-radial solar eruptions compared to radial ones. With increasing asymmetry, the degree of non-potentiality the field can attain is reduced. Consequently, the intensity of the pre-eruption current sheet decreases, and reconnection becomes less efficient, resulting in weaker eruptions.
Formation of the inner Oort cloud in the presence of an early solar binary
Authors: Raush Dennis , Batygin Konstantin
Published: June 2024

Consistent with the notion that most Sun-like stars form in multistellar systems, this study explores the impact of a temporarily bound stellar binary companion on the early dynamical evolution of the Solar system. Using N-body simulations, we illustrate how such a companion markedly enhances the trapping of scattered bodies on inner Oort cloud-like orbits, with perihelion distances exceeding $q \gt 40$ au. We further find that the orbital geometry of the Sun-binary system plays a central role in regulating the efficiency of small-body implantation on to high-perihelion orbits, and demonstrate that this process is driven by the von Zeipel–Kozai–Lidov mechanism. Incorporating the transiency of stellar clusters and the eventual Sun-binary pair dissociation due to passing stars, we show how the binary can be stripped away by an approximately solar-mass ejector star, with only a modest impact on the generated inner Oort cloud population. Collectively, our results highlight a previously underappreciated process that could have contributed to the formation of the inner Oort cloud.