bluuebunny/crossref_metadata_2025 huggingface dataset:
H14 Francois Henri Hallopeau: pulling out the hair and picking out the spots
Authors: Yip Alphonsus , Roy Nandini , Natkunarajah Janakan
Published: June 2024

Francois Henri Hallopeau was born in Paris in 1842. He entered the Paris medical school aged 24, studying under Alfred Vulpian and Sigismond Jaccoud, eventually ranking second among a large cohort of candidates for medical internships. He received his doctorate aged 29, after submission of his thesis on convulsive symptoms in disorders of the spinal cord. Francois was affiliated with the hospitals of Tenon and St Antoine, before becoming a physician at the Hôpital Saint Louis in 1884, where he remained until he retired in 1907. At the Hôpital Saint Louis, he initially practised as a neurologist, before exclusively focusing his efforts on dermatology. The variety of the patients who he cared for enabled him to report a number of important descriptions on cutaneous diseases, which formed the basis of the first edition of his Practical Treatise on Dermatology. Hallopeau was the first to describe acrodermatitis continua of Hallopeau, a painful acral pustular disease characterized by sterile pustules on erythematous skin of the distal fingers and toes, in 1890. He is also credited as being the first to describe lichens planus atrophique, now known as lichen planus sclerosus et atrophicus sclerosis, in a clinical lecture in 1887. Since then, World Lichens Sclerosis Awareness Day is celebrated on his birthday – 17 January. Hair pulling has been widely described throughout history, first documented by Aristotle (4th century Bc), when he referenced plucking out hair in the context of self-control and vices in Nicomachean Ethics. In 1889, after encountering a young male patient who had torn out tufts of his hair, Hallopeau was the first to coin the term trichotillomania, derived from the Greek thrix (hair), tillein (pulling) and mania (madness). In 1890, he cofounded the French Society of Dermatology and Syphiligraphy, of which he eventually became secretary general in 1893. He also remained an established member of the Academy of Medicine from this point. In 1907, after his retirement from Saint Louis due to the age rule, he continued working as the consulting physician at the Maison Départmentale of Nanterre until 1918, when his sight among other comorbidities led him to fully retire. Francois Henri Hallopeau’s impact in the field of dermatology persists to this day, and he continues to be remembered for his descriptions featured in his collection of over 800 publications.
H23 A sailor went to C
Authors: Murphy Lisa
Published: June 2024

As modern fad diets and chronic illnesses have led to a re-emergence in the presentation of scurvy to dermatology services, we aimed to review the original cohort of patients that gave this condition notoriety – sailors. Scurvy is a disease process secondary to vitamin C deficiency. It has a number of dermatological manifestations, including petechiae, perifollicular haemorrhage, bruising and gingivitis. These presentations occur as vitamin C (ascorbic acid) plays a fundamental role in collagen synthesis. When this process is defective, impaired wound healing is seen. This condition became synonymous with the British and European sailing community during the age of exploration, and it is estimated that 2 million sailors died as a result between the 16th and 18th centuries alone. As ascorbic acid is not naturally produced by humans, we are reliant on external sources of vitamin C to replenish stores. Key sources of vitamin C include fresh fruit and vegetables, such as citrus fruits, spinach, potatoes, berries and tomatoes. Given that there were generally only nonperishable foods available on board these sailing ships, thousands of sailors fell victim to scurvy. James Lind played a notable role in the discovery of vitamin C as a therapeutic agent in the treatment of scurvy and is credited with being the father of the modern-day clinical trial as we know it. The first authenticated example of a therapeutic experiment with controls appears to have been James Lind’s trial in 1747 of the value of citrus fruits in treating scurvy in sailors. (Thomas DP. Sailors, scurvy and science. J R Soc Med 1997; 90: 50–4). Captain James Cook, the eminent sailor, was also one of the first to establish that the provision of fresh vegetables on board could prevent scurvy from developing while on long voyages of exploration. Even in the most severe and end-stage cases of scurvy, it was discovered that the disease process could be reversed with sufficient vitamin C supplementation. While this condition is often considered to be a historical disease, having once been referred to as the ‘plague of the seas’, it is one that dermatologists should continue to be cognizant of when treating patients in modern society.
PS03 Psychiatric comorbidity in patients with hidradenitis suppurativa: a retrospective review of a tertiary centre clinic
Authors: Webber Lucy , Clark Emma , King Natalie , Wainman Hannah , Sinha Aparna
Published: June 2024

Hidradenitis suppurativa (HS) is closely linked to psychiatric comorbidities, elevated suicide risk, stigmatization and body image impairment (Patel K, Lee, H, Rastogi S et al. Association between hidradenitis suppurativa, depression, anxiety, and suicidality: a systematic review and meta-analysis. J Am Acad Dermatol 2020; 83: 737–44). We conducted a retrospective review of the first 100 patients referred to our tertiary HS service from August 2020 to identify those receiving psychiatric input. We assessed patient characteristics, underlying mental health diagnoses, treatment, mental health and HS severity scores, and referral outcomes. Among the 100 patients, 25 were referred to a tertiary psychodermatology service and 6 were already receiving psychiatric care. Of these 31 patients, 81% were female, the average age was 34 years and the mean body mass index was 35.6 kg m−2. Overall, 60% currently smoked and 93% had Hurley scores of 2 or 3. Compared with those not referred for psychiatric input, these 31 patients exhibited higher baseline abscess and inflammatory nodule (AN) counts of > 5 (50% vs. 28%), severe pain scores > 7 out of 10 (48% vs. 21%), severe General Anxiety Disorder-7 (GAD-7) scores > 15 (44% vs. 37%), severe Patient Health Questionnaire-9 (PHQ-9) scores > 20 (40% vs. 21%) and high Dermatology Life Quality Index (DLQI) scores > 10 (81% vs. 68%). Of those referred for or already receiving psychiatric care, 94% had received a formal mental health diagnosis, with 62% having more than one diagnosis. The most common diagnosis was anxiety and depression, followed by post-traumatic stress disorder, eating disorders and emotionally unstable personality disorder. One-third reported thoughts of suicide or self-harm, with 19% of patients experiencing this on several days and 10% nearly every day. While no significant difference in systemic or biologic therapy usage was observed, treatment led to improved AN counts, and reductions in GAD-7, PHQ-9 and DLQI scores. No change was noted in severe pain scores (47% vs. 48%). Of the 25 patients referred for psychiatric input, 8 were seen, 3 did not attend and 14 await review. Overall, 55% (17 of 31) were encouraged to self-refer for psychological support, including National Health Service talking therapies, cognitive behavioural therapy and bereavement support. Identifying underlying mental health diagnoses and addressing psychological burden alongside medical treatment are essential to comprehensively manage HS. Many HS services do not have links to psychiatry, and the demand for psychological support for patients with HS exceeds available capacity. The introduction of HS-specific community interventions could enhance patients’ access to timely and effective psychological care while increasing our understanding of patients’ needs.
BT23 Artificial intelligence generation of patient information leaflets can have a useful role in the dermatology clinic
Authors: Verran Callum , Ardern-Jones Michael R , Seccombe Ella
Published: June 2024

Provision of information to patients via written patient information leaflets (PILs) is an important component of clinical care. The British Association of Dermatologists (BAD) PILs follow a consistent template and undergo quality testing with input from experts and nonmedical reviewers, and therefore they are time-consuming and costly to generate. Hence, existing PILs cover a limited range of skin conditions and treatments. General-language AI can use existing knowledge to infer, synthesize and summarize information and output this in any number of styles, including lay language. The aim of this study was to evaluate whether AI offers a useful function in generation of new PILs. ChatGPT (v3.5) was tasked to generate eight PILs where a BAD-produced PIL was not available. AI-generated PILs were reviewed by eight dermatologists and five nonmedical reviewers using a five-point Likert scale to assess document structure, accuracy, relevance and utility. Dermatologist responses varied based on PIL subject and were positive for structure, relevance and accuracy in 98%, 88% and 65% of responses, respectively, for condition-related PILs, whereas positive responses were seen in only 81%, 38% and 25% for medication-related PILs. While 64.6% of condition-related PILs were considered acceptable for patient distribution, this was only 12.5% for medication-related PILs. Nonmedical reviewers were more uniformly positive about the AI-generated PILs, with a majority of positive responses to presentation (97%), structure (97%), and language and content (97%) for condition-related PILs, and 70%, 70% and 70% of responses, respectively, for medication-related PILs. Our data show that dermatologists and nonmedical reviewers are positive towards the structure and relevance of condition-related PILs, but less so towards their content accuracy, and to medication-related PILs as a whole. We highlight the potential use of AI in clinical practice for PIL generation but recommend caution on content checking before publication and distribution, especially for medication-related information.
BT24 Pseudonymization for artificial intelligence skin lesion datasets: a real-world feasibility study
Authors: Chin Trisha J M , Chin Gillian X M , Sutherland James , Coon Andrew , Morton Colin , Fleming Colin
Published: June 2024

The use of patient data for artificial intelligence (AI) research should be transparent, rigorous and accountable. In the UK, the General Data Protection Regulation, Data Protection Act 2018 and General Medical Council govern data handling and patients’ rights to privacy. We report on our multistep pseudonymization protocol for real-world skin lesion datasets, in preparation for research within a trusted research environment (TRE). Firstly, patients referred from primary care are triaged for community locality and imaging centre (CLIC) suitability. There, trained healthcare professionals capture lesion images (dermoscopic, macroscopic and regional) and patient information using a mobile application on trust-certified devices. Training is standardized across all CLIC sites, with specific anonymization training on removing in-frame clothing and jewellery, device positioning, and magnification to minimize identifiable features like eyes, nose and ears. Lesion datasets (paired images and clinical information) are subsequently transferred to an image management system (IMS) hosted on our trust-secured network. Within the IMS, images are manually inspected, and those with identifiable tattoos and piercings are excluded. All regional images are also excluded from transfer to the TRE. Before transfer to the TRE, images undergo a further round of review. Data fields are manually checked for identifiable patient information, patient names are removed, and dates of birth are rounded to 3-month granularity. The job ID, patient’s hospital number, date of clinical episode and responsible photographer are replaced with randomly generated project-specific identifiers. In an initial study period, 658 of 963 (68%) captured lesion datasets have undergone IMS manual inspection. Of these, 24 lesion datasets were excluded for identifiable features, 10 (41%) for more than one-third of the face being visible, 9 (38%) for full iris visibility, and 5 (21%) for tattoos. On breakdown by anatomical location these images were of the face (19, 80%), torso (2, 8%), limbs (2, 8%) and neck (1, 4%). The remaining 634 datasets (96%) were securely transferred to the TRE, where a further 5% were excluded due to potential identifiability. Although full anonymization is desirable, it is usually achieved by aggregating patient data. Pseudonymization, which allows for future reidentification in a secured fashion, strikes the balance between patient data privacy and clinical governance, while retaining a level of granularity sufficient for meaningful analysis. Currently, this protocol is manually intensive with room to partly automate. Use of common standardized protocols will strengthen the public trust in clinical AI.
BT30 Artificial intelligence triage is of greater benefit for screening suspected melanoma referrals than squamous cell carcinoma referrals
Authors: Ismail Nor , Barfei Maryam , McLaughlin Hannah , Roberts Elizabeth Jane
Published: June 2024

There has been a rapid expansion in the use of artificial intelligence (AI) models to aid in diagnosis and triage of skin cancer in the UK in the last few years. This has been driven by a need to manage an increasing number of urgent referrals for suspected skin cancer. Our service has been using one such platform to screen out benign lesions, thus reducing the number of patients subsequently requiring a face-to-face appointment with a trust dermatologist. The AI platform assesses the features of a single dermoscopic image to categorize the lesion into benign or malignant. Information from patient history and macroscopic images are not involved. As dermatologists, we recognize the importance of history (pain, rapid growth) and clinical examination (induration, tenderness) as well as dermoscopic assessment in reaching a diagnosis. We suspected that the use of dermoscopy in clinical practice is of greater value for distinguishing benign from malignant pigmented lesions compared with keratotic lesions. When a suspected skin cancer is referred into our service, the general practitioner is required to state whether they suspect melanoma or squamous cell carcinoma (SCC). (Basal cell carcinomas are referred on a separate, routine pathway). We sought to use this information to assess for any differences in outcomes. A retrospective review of patients assessed by the AI platform was conducted between August 2023 and November 2023. In total 800 patients were included in the study (396 melanoma pathway, 404 squamous cell carcinoma pathway). In total 116 referrals were discharged by the AI platform on the melanoma pathway (29.2%) and 32 referrals were discharged by DERM on the SCC pathway (7.9%). These results support our hypothesis that AI is better at recognizing benign pigmented lesions, as 92% of patients referred on the SCC pathway required further assessment by a trust dermatologist compared with 70% of those referred on a melanoma pathway. This information is of importance to commissioners planning to implement skin cancer AI triage models.
BT33 Ethical challenges with skin cancer and artificial intelligence integration
Authors: Chan Sut Mo Zachary , Dubash Faishal
Published: June 2024

The integration of artificial intelligence (AI) in the field of dermatology promises a revolutionary transformation in our approach to this domain. However, the use of AI in dermatology is still in its early stages, and with limited scope of applications. While some of the existing research performed has highlighted the capabilities of AI in diagnosing lesions comparable with those of a dermatologist, the implementation of AI brings about its own ethical challenges that affect both the clinician and the patient. This article aims to explore the ethical issues and prospects surrounding AI implementation in dermatology by drawing insights from the current literature. A qualitative analysis was conducted on articles focusing on AI usage in medical care, with a specific emphasis on dermatology. The analysis unveils several ethical issues that emerge from the implementation of AI in dermatology: the obscure and subjective nature of AI leads to selective bias and unequal treatment based on skin tone differences. It also has the potential to erode patient autonomy by taking on a more paternalistic approach to medicine, increasing the risk of unwarranted harm to patients because of unnecessary biopsies, along with potential misalignment of treatment priorities between AI systems and patients. Issues of accountability arise as AI integration can challenge the epistemic authority and ownership of clinicians over their patients. Finally, the closed-loop system of training algorithms coupled with the lack of an open-access database due to privacy issues further increases the subjectiveness and inaccessibility of each algorithm. While AI’s integration in dermatology promises to streamline the diagnostic process, it also sparks ethical issues that affect the main stakeholders. These findings indicate the need for further development and enhancement of AI systems before they are capable of being implemented. Introduction of a transparent, explainable AI model would alleviate concerns regarding patient autonomy and treatment rationalization. Simultaneously, the establishment of a global open-access database will serve to mitigate selective bias. Furthermore, additional research comparing algorithms would be useful in establishing a standardized validation tool. As it stands, rather than replacing clinicians, AI should be used as a diagnostic adjunct in aiding clinical decisions.
Are Welsh primary schools Sunproofed? Results of a national survey, part 2: sun protection practices in primary schools in Wales
Authors: Abbott Rachel A , Tod Daniel , Lanyon Kirsty , Driscoll Timothy , Prathap Swetha , Watkins Alan , Peconi Julie
Published: June 2024

Background

Skin cancer rates are on the rise globally. School sun safety programmes are recommended by the World Health Organization to reduce the risk of future skin cancer at the population level; however, these are encouraged but not mandated in Wales.

Objectives

To explore current sun protection practices and sun safety education in primary schools in Wales and whether these are linked to the existence of a formal sun safety policy.

Methods

An online survey to all 1241 Welsh primary schools asking about sun safety practices, education and formal policies was undertaken.

Results

In total, 471 (38.0%) schools responded. A minority (22/469, 4.7%) of responding schools reported they had sufficient shade for most activities. In the spring and summer terms, almost two-thirds of schools encourage hat wearing (304/469, 64.8%) and sunscreen (296/468, 63.2%). Although nearly all schools reported that parents were encouraged to apply sunscreen to students before school (449/469, 95.7%), there was wide variation in other sunscreen application practices. Less than one-third of schools (129/445, 29.0%) reported that they include sun protection education in the curriculum in every year group, with 11.7% (52/445) including this in certain years only. Schools with a formal policy were more likely to report more comprehensive sun protection practices, including having sufficient shade [odds ratio (OR) 1.51, 95% confidence interval (CI) 1.04–2.19; P = 0.03], having spare hats for pupils to wear (OR 1.59, 95% CI 1.07–2.37; P = 0.02), providing guidance for staff (OR 5.87, 95% CI 3.05–11.28; P < 0.001), encouraging them to model sun safe behaviours (OR 1.82, 95% CI 1.18–2.80; P = 0.007) and teaching sun protection education as part of the curriculum in every year group (OR 2.56, 95% CI 1.76–3.71; P < 0.001). With respect to sunscreen, the existence of a formal policy did not seem to affect a school’s practice.

Conclusions

Although in most cases, the existence of a formal policy suggests more comprehensive sun protection practices and education in schools, sun protection measures and education need improvement across the primary school sector in Wales to reverse rising skin cancer rates.
Solvated Ba2+ with square antiprismatic and cubic coordination geometries
Authors: Umakoshi Ayano , Minato Takuo , Kanematsu Yusuke , Sadakane Masahiro
Published: June 2024

Solvated metal cations represent fundamental and crucial mononuclear species in various research fields, including chemical, physical, and biochemical studies. However, controlling their coordination geometry poses a significant challenge. In this study, we successfully synthesized and structurally characterized solvated Ba2+ complexes. The coordination geometry of [Ba(CH3CN)8]2+ was a thermodynamically stable square antiprism, while that of [Ba{(CH3)2CO}8]2+ exhibited a rare cubic structure, demonstrating a unique approach to controlling coordination geometry solely by altering crystallization solvents.
The Role of N6-methyladenosine Modification in Gametogenesis and Embryogenesis: Impact on Fertility
Authors: Wang Yujie , Yang Chen , Sun Hanxiao , Jiang Hui , Zhang Pin , Huang Yue , Liu Zhenran , Yu Yaru , Xu Zuying , Xiang Huifen , Yi Chengqi
Published: June 2024

The most common epigenetic modification of messenger RNAs (mRNAs) is N6-methyladenosine (m6A), which is mainly located near the 3′ untranslated region of mRNAs, near the stop codons, and within internal exons. The biological effect of m6A is dynamically modulated by methyltransferases (writers), demethylases (erasers), and m6A-binding proteins (readers). By controlling post-transcriptional gene expression, m6A has a significant impact on numerous biological functions, including RNA transcription, translation, splicing, transport, and degradation. Hence, m6A influences various physiological and pathological processes, such as spermatogenesis, oogenesis, embryogenesis, placental function, and human reproductive system diseases. During gametogenesis and embryogenesis, genetic material undergoes significant changes, including epigenomic modifications such as m6A. From spermatogenesis and oogenesis to the formation of an oosperm and early embryogenesis, m6A changes occur at every step. m6A abnormalities can lead to gamete abnormalities, developmental delays, impaired fertilization, and maternal-to-zygotic transition blockage. Both mice and humans with abnormal m6A modifications exhibit impaired fertility. In this review, we discuss the dynamic biological effects of m6A and its regulators on gamete and embryonic development and review the possible mechanisms of infertility caused by m6A changes. We also discuss the drugs currently used to manipulate m6A and provide prospects for the prevention and treatment of infertility at the epigenetic level.
Individuals, Disaggregation of the State, and Negotiation Tactics: Evidence from the European Union
Authors: Chelotti Nicola
Published: June 2024

This article intends to investigate to what extent, how, and when individuals who are below the leader’s level affect the processes and outputs of international politics. It does so by analyzing one group of below-leader actors—diplomatic negotiators in EU foreign policy. It first shows how, despite all the bureaucratic layers they are embedded in, individual negotiators have de facto acquired ultimate policymaking responsibilities, most prominently in the selection of tactics. This empowerment of individual diplomats occurs through a process of double state disaggregation: Policymaking responsibilities have shifted from the political to the bureaucratic level; then, within the latter, from the capital-based administration to the officials involved, often in single capacity, in negotiations. Next, it tests three individual characteristics (experience, style, and identity) against an original dataset of 138 questionnaires completed by EU diplomats and 17 interviews. It shows that negotiators’ personal traits explain the use of some, but not all, tactics. Specifically, they are less likely to matter when negotiators have to commit the state in significant and explicit ways, e.g., when threatening/exercising veto. When this does not happen (e.g., showing flexibility in the delegation’s position or using persuasion), the influence of individual characteristics is instead strong.
Organizational Bricolage and Insurgent Group Effectiveness in Cities: The Formation and Initial Urban Campaign of the Movement of the 19th of April in Colombia (1973–1980)
Authors: Boulanger Martel Simon Pierre
Published: June 2024

Abstracts

How do rebel groups form in cities? What makes urban-based insurgent organizations effective? Urban armed conflicts have become an important subject of research due to the political, economic, and demographic significance of cities. Yet, we know little about the mechanisms of insurgent group formation and effectiveness in urban contexts. Building on the case of the formation and initial urban campaign of M-19 in Colombia (1973–1980), this article argues that rebel leaders originating from multiple organizations and confronted with intramovement competition have strong motives to employ organizational bricolage to form their organization. Organizational bricolage shapes insurgent effectiveness by producing structures that are fit for achieving certain objectives but not others. M-19’s organizational bricolage combined the armed vanguard, intellectual collective, and populist party forms. This structure was effective to foster public support but ineffective to establish a robust social base and maintain urban operations under repression. The research employs the analysis of organizational repertoires and process tracing to retrace M-19’s formation and initial urban campaign. Empirical material includes an original dataset comprising M-19 founders’ biographical data, archival documents, and interviews with ex-combatants. Studying how rebel leaders employ organizational bricolage sheds light on how insurgent organizations form, behave, and transform after war.
Morphological and biological characteristics of Eriborus sp. (Hymenoptera: Ichneumonidae), a parasitoid wasp of Cydalima perspectalis (Lepidoptera: Crambidae)
Authors: Kim Byung-Chan , Sul Sung-Gum , Park Il-Kwon
Published: June 2024

The box tree moth (BTM), Cydalima perspectalis Walker, is a pest that infests various plants within the Buxus genus. Although a specific parasitoid wasp species associated with the BTM has been observed in the Republic of Korea, no research on this species has been published. Here, we describe the fundamental morphological and biological characteristics of this parasitoid. We have identified the wasp as belonging to the genus Eriborus (Hymenoptera: Ichneumonidae: Campopleginae). Eriborus sp. parasitizes within the living host body, with 1 wasp emerging from each host. The parasitism rate observed in collected BTM populations was 33.1%. The emergence rate was 87.1%, with all emerging adults being females, resulting in a sex ratio of 0. The pupal period avg 9.5 days, and the adult lifespan avg 10.5 days. Eriborus sp. parasitized BTM larvae from the first to the fourth instar and reproduced by thelytokous parthenogenesis. Eriborus sp. exhibited morphological differences compared with previously reported Eriborus species in Korea, particularly in the length of the ovipositor sheath. Additionally, the proportion of the highest similarity in nucleotide sequences of mitochondrial cytochrome oxidase I DNA was only 94.53%, rendering species identification using GenBank’s mt cytochrome c oxidase 1 DNA sequences unfeasible. These data suggest that Eriborus sp. could be used as a biological control agent for managing BTM infestations.
Predicting the potential distribution and coexistence of Chagas disease vectors in the Americas
Authors: Altamiranda-Saavedra Mariano , Montaño Contreras Sandra Carolina , Rivera Pacheco Juan Camilo , Bernal Contreras Karen Andrea , López Clara Roció Galvis , Vasquez Trujillo Adolfo , Moo-Llanes David A
Published: June 2024

Predicting the potential distribution and coexistence of suitable geographic areas for Chagas disease vectors in the Americas is a crucial task for understanding the eco-epidemiological dynamics of this disease. The potential distribution and coexistence of 3 species—Rhodnius prolixus (Hemiptera: Reduviidae), Cavernicola pilosa (Hemiptera: Reduviidae), and Rhodnius pictipes (Hemiptera: Reduviidae) were modeled. Presence records were obtained and environmental variables were selected based on correlation analysis, Jackknife analysis and knowledge of the biology and natural history of the species. The MaxEnt algorithm included in the kuenm package of R software was used for modeling the potential distribution, and various scenarios of the BAM diagram (Biotic, Abiotic, and Movement variables) were evaluated. The variables contributing to the final models were different for each species. Rhodnius pictipes showed a potential distribution in South America, particularly in Brazil, Bolivia, Peru, Colombia, Venezuela, Guyana, and Suriname. Areas with environmentally suitable conditions for R. prolixus were located in southern Brazil, Peru, Colombia, southern Mexico, Guatemala, El Salvador, and Honduras, whereas for C. pilosa they were in southeastern Brazil, southeastern Central America, Peru, Ecuador, Colombia, Venezuela, Guyana, Suriname, and French Guiana. Co-occurrence analysis revealed distinct patterns in the neotropical region, with some areas indicating the potential distribution of 1 or more species. In Brazil, occurrence and co-occurrence areas were concentrated in the northwest and southeast regions. Overall, this study provides valuable information on the potential distribution and coexistence of vectors, which can inform targeted vector control strategies and contribute to global efforts in combating Chagas disease.
Enhanced axon guidance and synaptic markers in rat brains using ferric–tannic nanoparticles
Authors: Sanit Jantira , Intakhad Jannarong , Kittilukkana Aiyarin , Vachiraarunwong Arpamas , Wongpoomchai Rawiwan , Pilapong Chalermchai
Published: June 2024

Ferric–tannic nanoparticles (FTs) are now considered to be new pharmaceuticals appropriate for the prevention of brain aging and related diseases. We have previously shown that FTs could activate axon guidance pathways and cellular clearance functioning in neuronal cell lines. Herein, we further investigated whether FTs could activate the two coordinated neuronal functions of axon guidance and synaptic function in rat brains and neuronal cell lines. A single intravenous injection of a safe dose of FTs has been shown to activate a protein expression of axon attractant Netrin-1 and neurotransmitter receptor GABRA4 in the cerebral cortexes of male Wistar rats. According to RNA-seq with targeted analysis, axon guidance and synapses have been enriched and Ephrin membered genes have been identified as coordinating a network of genes for such processes. In vitro, as expected, FTs are also found to activate axon guidance markers and promote neuronal tubes in neuronal cell lines. At the same time, pre-synaptic markers (synaptophysin), post-synaptic markers (synapsin), and GABRA4 neurotransmitter receptors have been found to be activated by FTs. Interestingly, synaptophysin has been found to localize along the promoted neuronal tubes, suggesting that enhanced axon guidance is associated with the formation and transportation of pre-synaptic vesicles. Preliminarily, repeated injection of FTs into adult rats every 3 days for 10 times could enhance an expression of synaptophysin in the cerebral cortex, as compared to control rats. This work demonstrates that FTs can be used for activating brain function associated with axon guidance and synaptic function.
PCAF promotes R-loop resolution via histone acetylation
Authors: Lee Seo Yun , Lee Soo Hyeon , Choi Nak Hun , Kim Ja Young , Kweon Jun Hee , Miller Kyle M , Kim Jae Jin
Published: June 2024

R-loops cause genome instability, disrupting normal cellular functions. Histone acetylation, particularly by p300/CBP-associated factor (PCAF), is essential for maintaining genome stability and regulating cellular processes. Understanding how R-loop formation and resolution are regulated is important because dysregulation of these processes can lead to multiple diseases, including cancer. This study explores the role of PCAF in maintaining genome stability, specifically for R-loop resolution. We found that PCAF depletion promotes the generation of R-loop structures, especially during ongoing transcription, thereby compromising genome stability. Mechanistically, we found that PCAF facilitates histone H4K8 acetylation, leading to recruitment of the a double-strand break repair protein (MRE11) and exonuclease 1 (EXO1) to R-loop sites. These in turn recruit Fanconi anemia (FA) proteins, including FANCM and BLM, to resolve the R-loop structure. Our findings suggest that PCAF, histone acetylation, and FA proteins collaborate to resolve R-loops and ensure genome stability. This study therefore provides novel mechanistic insights into the dynamics of R-loops as well as the role of PCAF in preserving genome stability. These results may help develop therapeutic strategies to target diseases associated with genome instability.
Phosphorylation of the nuclear poly(A) binding protein (PABPN1) during mitosis protects mRNA from hyperadenylation and maintains transcriptome dynamics
Authors: Gordon Jackson M , Phizicky David V , Schärfen Leonard , Brown Courtney L , Arias Escayola Dahyana , Kanyo Jean , Lam TuKiet T , Simon Matthew D , Neugebauer Karla M
Published: June 2024

Polyadenylation controls mRNA biogenesis, nucleo-cytoplasmic export, translation and decay. These processes are interdependent and coordinately regulated by poly(A)-binding proteins (PABPs), yet how PABPs are themselves regulated is not fully understood. Here, we report the discovery that human nuclear PABPN1 is phosphorylated by mitotic kinases at four specific sites during mitosis, a time when nucleoplasm and cytoplasm mix. To understand the functional consequences of phosphorylation, we generated a panel of stable cell lines inducibly over-expressing PABPN1 with point mutations at these sites. Phospho-inhibitory mutations decreased cell proliferation, highlighting the importance of PABPN1 phosphorylation in cycling cells. Dynamic regulation of poly(A) tail length and RNA stability have emerged as important modes of gene regulation. We therefore employed long-read sequencing to determine how PABPN1 phospho-site mutants affected poly(A) tails lengths and TimeLapse-seq to monitor mRNA synthesis and decay. Widespread poly(A) tail lengthening was observed for phospho-inhibitory PABPN1 mutants. In contrast, expression of phospho-mimetic PABPN1 resulted in shorter poly(A) tails with increased non-A nucleotides, in addition to increased transcription and reduced stability of a distinct cohort of mRNAs. Taken together, PABPN1 phosphorylation remodels poly(A) tails and increases mRNA turnover, supporting the model that enhanced transcriptome dynamics reset gene expression programs across the cell cycle.
Alternative splicing of a potato disease resistance gene maintains homeostasis between growth and immunity
Authors: Sun Biying , Huang Jie , Kong Liang , Gao Chuyun , Zhao Fei , Shen Jiayong , Wang Tian , Li Kangping , Wang Luyao , Wang Yuanchao , Halterman Dennis A , Dong Suomeng
Published: June 2024

Plants possess a robust and sophisticated innate immune system against pathogens and must balance growth with rapid pathogen detection and defense. The intracellular receptors with nucleotide-binding leucine-rich repeat (NLR) motifs recognize pathogen-derived effector proteins and thereby trigger the immune response. The expression of genes encoding NLR receptors is precisely controlled in multifaceted ways. The alternative splicing (AS) of introns in response to infection is recurrently observed but poorly understood. Here we report that the potato (Solanum tuberosum) NLR gene RB undergoes AS of its intron, resulting in 2 transcriptional isoforms, which coordinately regulate plant immunity and growth homeostasis. During normal growth, RB predominantly exists as an intron-retained isoform RB_IR, encoding a truncated protein containing only the N-terminus of the NLR. Upon late blight infection, the pathogen induces intron splicing of RB, increasing the abundance of RB_CDS, which encodes a full-length and active R protein. By deploying the RB splicing isoforms fused with a luciferase reporter system, we identified IPI-O1 (also known as Avrblb1), the RB cognate effector, as a facilitator of RB AS. IPI-O1 directly interacts with potato splicing factor StCWC15, resulting in altered localization of StCWC15 from the nucleoplasm to the nucleolus and nuclear speckles. Mutations in IPI-O1 that eliminate StCWC15 binding also disrupt StCWC15 re-localization and RB intron splicing. Thus, our study reveals that StCWC15 serves as a surveillance facilitator that senses the pathogen-secreted effector and regulates the trade-off between RB-mediated plant immunity and growth, expanding our understanding of molecular plant–microbe interactions.
Is unilateral cerebellum sufficient? Insights from new cases of cerebellar agenesis and literature review
Authors: Deng Dingmei , Tao Bo , Yuan Yizhi , Ao Yongsheng , Qiu Lihua
Published: June 2024

The clinical manifestations of adult-acquired cerebellar diseases often surpass those of congenital cerebellar diseases, suggesting the significant role of the cerebellum in the developing brain. Moreover, emerging evidence from structural and functional magnetic resonance imaging indicates that the cerebellum is implicated not only in motor functions but also in non-motor domains such as cognition, emotion, and language. However, delineating the specific extent of cerebellar development required to prevent deficits in either motor or non-motor functions remains challenging. In this study, we present two new cases of unilateral cerebellar agenesis. One individual leads a nearly normal life, while the other exhibits mild cognitive impairment, mild depression, and severe autism, but maintains normal motor function. Van der Heijden et al. (2023) revealed that the brain can compensate for some, but not all, perturbations to the developing cerebellum, including motor deficits and impairments in social behaviors. Therefore, we hypothesize that comparing structural images from our patients and reviewing pertinent literature may elucidate the reasons for the varied clinical manifestations observed in patients with cerebellar agenesis.
Female education ban by the Taliban: A descriptive survey study on suicidal ideation, mental health, and health-related quality of life among girls in Afghanistan
Authors: Mohammadi Abdul Qadim , Neyazi Ahmad , Habibi Diva , Mehmood Qasim , Neyazi Mehrab , Griffiths Mark D
Published: June 2024

Background

Following the Taliban’s resurgence, Afghan girls were probited from attending school and university, likely causing adverse psychological effects. Therefore, the present study investigated depression, suicidal ideation, and quality of life (QoL) among Afghan girls banned from education by the Taliban.

Methods

A survey study assessed depression, suicidal ideation, and QoL among 426 females prohibited from attending secondary schools, high schools, and universities by the Taliban. The study used the CES-D 20 Scale to assess depression, and the WHOQOL-Bref Questionnaire to assess QoL. Associations between variables were tested with chi-square tests, and predictors of QoL were analyzed through multivariate regression analysis.

Results

Among the 426 participants, 87.6% exhibited depression symptoms and 49.8% reported suicidal thoughts. Significant predictors of overall QoL included monthly family income (B = 0.147, P = 0.001), recent others’ behavior toward participants (B = −0.247, P < 0.001), physical illness (B = 0.110, P = 0.011), experiencing a recent traumatic event (B = 0.108, P = 0.015), depression (B = −0.159, P < 0.001) and suicidal ideation (B = −0.187, P < 0.001).

Conclusions

In Taliban-ruled Afghanistan, the results indicated that female students who have been prohibited from studying in classes have a high prevalence of depression and suicidal ideation. Having depression and suicidal ideation significantly predicted decreased quality of life among female students.
3D printing materials and 3D printed surgical devices in oral and maxillofacial surgery: design, workflow and effectiveness
Authors: Wang Xiaoxiao , Mu Min , Yan Jiazhen , Han Bo , Ye Rui , Guo Gang
Published: June 2024

Oral and maxillofacial surgery is a specialized surgical field devoted to diagnosing and managing conditions affecting the oral cavity, jaws, face and related structures. In recent years, the integration of 3D printing technology has revolutionized this field, offering a range of innovative surgical devices such as patient-specific implants, surgical guides, splints, bone models and regenerative scaffolds. In this comprehensive review, we primarily focus on examining the utility of 3D-printed surgical devices in the context of oral and maxillofacial surgery and evaluating their efficiency. Initially, we provide an insightful overview of commonly utilized 3D-printed surgical devices, discussing their innovations and clinical applications. Recognizing the pivotal role of materials, we give consideration to suitable biomaterials and printing technology of each device, while also introducing the emerging fields of regenerative scaffolds and bioprinting. Furthermore, we delve into the transformative impact of 3D-printed surgical devices within specific subdivisions of oral and maxillofacial surgery, placing particular emphasis on their rejuvenating effects in bone reconstruction, orthognathic surgery, temporomandibular joint treatment and other applications. Additionally, we elucidate how the integration of 3D printing technology has reshaped clinical workflows and influenced treatment outcomes in oral and maxillofacial surgery, providing updates on advancements in ensuring accuracy and cost-effectiveness in 3D printing-based procedures.
Do quality of life and work productivity change in early axial spondyloarthritis and non-axial spondyloarthritis patients after 2 years?
Authors: Bento da Silva Ana , Ramiro Sofia , Boel Anne , van Lunteren Miranda , Marques Mary Lucy , van de Sande Marleen , Fongen Camilla , Exarchou Sofia , Ramonda Roberta , van der Heijde Désirée , van Gaalen Floris
Published: June 2024

Objective

The objective of this study was to compare health-related quality of life (HRQoL) and work productivity in axial SpA (axSpA) and non-axSpA patients with chronic back pain of <2 years.

Methods

Baseline and 2-year data for patients included in the SPondyloArthritis Caught Early cohort were analysed. HRQoL was assessed by the physical (PCS) and mental component summary (MCS) scores of the 36-Item Short-Form Health Survey, and presenteeism, absenteeism, work productivity loss (WPL) and activity impairment (AI) by the Work Productivity and Activity Impairment questionnaire. Linear or zero-inflated negative binomial regression was conducted to compare 2-year outcomes between groups (axSpA and non-axSpA), adjusting for the baseline value, sex, age and use of NSAIDs.

Results

There were 265 axSpA and 108 non-axSpA patients: males 52% vs 26%, mean age 29 vs 31 years, respectively. At baseline, non-axSpA patients showed worse PCS (mean 28.6 axSpA vs 26.6 non-axSpA), presenteeism (31.1% vs 37.3%), absenteeism (8.2% vs 10.3%), WPL (34.7% vs 44.1%) and AI (39.6% vs 48.5%). MCS was not impaired in either group. After 2 years, PCS, presenteeism, WPL and AI significantly improved in both groups; absenteeism only improved in axSpA. In multivariable analysis, axSpA (vs non-axSpA) was associated with 22% less WPL [incidence rate ratio (95% CI): 0.78 (0.62; 0.98)] and 18% less AI [0.82 (0.69; 0.97)].

Conclusion

HRQoL and work productivity are more impaired in non-axSpA (vs axSpA) at baseline and also after 2 years. Although most outcomes improve in both groups, axSpA is associated with larger reductions in WPL and AI.
Linoleic acid‐derived diol 12,13‐DiHOME enhances NLRP3 inflammasome activation in macrophages
Authors: Valencia Robert , Kranrod Joshua W. , Fang Liye , Soliman Amro M. , Azer Brandon , Clemente‐Casares Xavier , Seubert John M.
Published: June 2024

12,13‐dihydroxy‐9z‐octadecenoic acid (12,13‐DiHOME) is a linoleic acid diol derived from cytochrome P‐450 (CYP) epoxygenase and epoxide hydrolase (EH) metabolism. 12,13‐DiHOME is associated with inflammation and mitochondrial damage in the innate immune response, but how 12,13‐DiHOME contributes to these effects is unclear. We hypothesized that 12,13‐DiHOME enhances macrophage inflammation through effects on NOD‐like receptor protein 3 (NLRP3) inflammasome activation. To test this hypothesis, we utilized human monocytic THP1 cells differentiated into macrophage‐like cells with phorbol myristate acetate (PMA). 12,13‐DiHOME present during lipopolysaccharide (LPS)‐priming of THP1 macrophages exacerbated nigericin‐induced NLRP3 inflammasome activation. Using high‐resolution respirometry, we observed that priming with LPS+12,13‐DiHOME altered mitochondrial respiratory function. Mitophagy, measured using mito‐Keima, was also modulated by 12,13‐DiHOME present during priming. These mitochondrial effects were associated with increased sensitivity to nigericin‐induced mitochondrial depolarization and reactive oxygen species production in LPS+12,13‐DiHOME‐primed macrophages. Nigericin‐induced mitochondrial damage and NLRP3 inflammasome activation in LPS+12,13‐DiHOME‐primed macrophages were ablated by the mitochondrial calcium uniporter (MCU) inhibitor, Ru265. 12,13‐DiHOME present during LPS‐priming also enhanced nigericin‐induced NLRP3 inflammasome activation in primary murine bone marrow‐derived macrophages. In summary, these data demonstrate a pro‐inflammatory role for 12,13‐DiHOME by enhancing NLRP3 inflammasome activation in macrophages.
Comprehensive pan‐cancer analysis of the C2ORF40 expression: Infiltration associations and prognostic implications
Authors: Liu Yuxi , Hou Jiaxin , Zhao Yunrong , Zhou Jiangshan , Bai Shuhua , Ding Yi
Published: June 2024

In recent years, C2ORF40 has been identified as a tumor suppressor gene with multiple functions, including roles in cell proliferation, migration, and senescence. To explore the role of the C2ORF40 gene in different tumors, we used multiple databases for analysis. Compared to adjacent normal tissues, C2ORF40 is downregulated in a variety of malignant tumors, including tumors such as breast cancer, colorectal cancer, bladder cancer, hepatocellular carcinoma and prostate cancer. Notably, low expression of the gene is significantly associated with poor overall survival and relapse‐free survival rates. In specific cancers including colon cancer and prostate cancer, the expression of C2ORF40 is correlated with the infiltration of CAFs. C2ORF40 is also involved in biological processes such as cell apoptosis and regulation of protein stability. In conclusion, C2ORF40 can hold promise as a prognostic marker for pan‐cancer analysis.