Background: The clearance or transcriptional silencing of integrated HBV DNA is crucial for achieving a functional cure in patients with chronic hepatitis B (CHB) and reducing the risk of hepatocellular carcinoma (HCC) development. The PLC/PRF/5 cell line is commonly used as an in vitro model for studying HBV integration. In this study, we employed a range of multi-omics techniques to gain a panoramic understanding of the characteristics of HBV integration in PLC/PRF/5 cells and to reveal the transcriptional regulatory mechanisms of integrated HBV DNA.Methods: Transcriptome long-read sequencing (ONT) was conducted to analyze and characterize the transcriptional activity of different HBV DNA integration sites in PLC/PRF/5 cells. Additionally, we collected data related to epigenetic regulation, including whole-genome bisulfite sequencing (WGBS), histone chromatin immunoprecipitation sequencing (ChIP-seq), and assays for transposase-accessible chromatin using sequencing (ATAC-seq), to explore the potential mechanisms involved in the transcriptional regulation of integrated HBV DNA.Result: Long-read RNA sequencing analysis revealed significant transcriptional differences at various integration sites in the PLC/PRF/5 cell line, with higher HBV DNA transcription levels at integration sites on chr11, chr13, and the chr13/chr5 fusion chromosome t (13:5). Combining long-read DNA and RNA sequencing results, we found that transcription of integrated HBV DNA generally starts downstream of the SP1, SP2, or XP promoters. ATAC-seq data confirmed that chromatin accessibility has limited influence on the transcription of integrated HBV DNA in the PLC/PRF/5 cell line. Analysis of whole-genome bisulfite sequencing data showed that the methylation intensity of integrated HBV DNA was highly negatively correlated with its transcription level (r = -0.8929, p = 0.0123). After AzaD treatment, the transcription level of integrated HBV DNA significantly increased, especially for the integration chr17, which had the highest level of methylation. Through ChIP-seq data, we observed the association between histone modification of H3K4me3 and H3K9me3 with the transcription of integrated HBV DNA.

Objective: The aim of this investigation was to explore the potential correlation between signal intensity ratio (SIR) at internal auditory canal (IAC) bottom and hearing impairment in MD, thereby providing a foundation for further comprehension of the underlying mechanisms contributing to hearing loss. Design: Fifty patients diagnosed with unilateral definited MD were enrolled in the study. 3D-FLAIR MRI was conducted four hours after intravenous administration of gadobutrol to determine the SIR of bilateral IAC bottom. The difference of SIR of IAC bottom was assessed between affected and unaffected sides, followed by an analysis of its correlation with low-, middle-, and high-tone hearing thresholds. Additionally, correlation analysis was conducted between the degree of EH in vestibular and cochlea and the SIR on the affected side. Results: The degree of EH in MD can be clearly visualized through 3D-FLAIR MRI. The SIR on the affected side was significantly higher than that on the unaffected side (P=0.000). Furthermore, a positive correlation was observed between the SIR at the affected and low (r=0.692, P=0.000), middle (r=0.615, P=0.000) and high-tone (r=0.440, P=0.001); the SIR showed no significant correlation with cochlear (r=0.315, P=0.088) or vestibular hydrops (r=0.215, P=0.244). Conclusion: 3D-FLAIR MRI can observe the degree of EH in MD; impairment of the internal auditory barrier may be one of the factors of hearing loss in MD.

Fluvial hazards of river mobility and flooding are often problematic for road infrastructure and need to be considered in the planning process. The extent of river and road infrastructure networks and their tendency to be close to each other creates a need to be able to identify the most dangerous areas quickly and cost-effectively. In this study we propose a novel methodology using random forest (RF) machine learning methods to provide easily interpretable fine-scale fluvial hazard predictions for large river systems. The tools developed provide predictions for three models: presence of flooding (PFM), presence of mobility (PMM) and type of erosion model (TEM, lateral migration, or incision) at reference points every 100 meters along the fluvial network of three watersheds within the province of Quebec, Canada. The RF models uses variables focused on river conditions and hydrogeomorphological processes such as confinement, sinuosity, and upstream slope. Training/validation data included field observations, results from hydraulic and erosion models, government infrastructure databases, and hydro- geomorphological assessments using 1-m DEM and satellite/historical imagery. A total of 1,807 reference points were classified for flooding, 1,542 for mobility, and 847 for the type of erosion out of the 11,452 reference points for the 1,145 km of rivers included in the study. These were divided into training (75%) and validation (25%) datasets, with the training dataset used to train supervised RF models. The validation dataset indicated the models were capable of accurately predicting the potential for fluvial hazards to occur, with precision results for the three models ranging from 83% to 94% of points accurately predicted. The results of this study suggest that RF models are a cost-effective tool to quickly evaluate the potential for fluvial hazards to occur at the watershed scale.

A document by Josef Mana. Click on the document to view its contents.

Wintering birds serve as vital climate sentinels, yet they are often underrepresented in comprehensive surveys and overlooked in studies of avian diversity change. Here, we provide a continental-scale characterization of change in multiple facets of wintering avifauna and examine the effects of climate change on these dynamics. We reveal a strong functional reorganization of wintering bird communities marked by a distinct east-west gradient in functional diversity change, along with a superimposed north-south gradient in trait composition change. Assemblages in the eastern US saw an expansion of the functional space and increases in functional originality, evenness, and divergence, while the western US saw contractions of the functional space. Shifts in functional diversity were underlined by significant reshuffling in trait composition, particularly pronounced in the northern US. Finally, we find strong contributions of climate change to this functional reorganization, underscoring the importance of wintering birds in tracking climate change impacts on biodiversity.

Ctenostomes are a group of gymnolaemate bryozoans with an uncalcified chitinous body wall having few external, skeletal characters. Hence, species identification is challenging and their systematics remain poorly understood, even more so when they exhibit an endolithic (boring) lifestyle. Currently, there are four Recent families of endolithic bryozoans that live inside in mineralized substrates like mollusk shells. In particular, Penetrantiidae Silén, 1946 has received considerable attention and its systematic affinity to either cheilostomes or ctenostomes has been debated. Species delimitation of penetrantiids remains difficult, owing to a high degree of colonial and zooidal plasticity. Consequently, an additional molecular approach is essential to unravel the systematics of penetrantiids, their phylogenetic placement and their species diversity. We therefore sequenced the mitochondrial (mt) genomes and two nuclear markers of 27 ctenostome species including nine penetrantiids. Our phylogeny supports the Penetrantiidae as a monophyletic group placed as sister taxa to the remaining ctenostomes alongside paludicellids and arachnoidids. Our results also suggest that the endolithic lifestyle evolved at least twice independently within ctenostomes, since the boring families Terebriporidae d’Orbigny, 1847 and Penetrantiidae are well separated. Ctenostome paraphyly is supported by our data, as the cheilostomes nest within them. A Multiporata clade is also well supported, including the former victorelloid genus Sundanella. Altogether, this study provides new insights into ctenostome systematics, assists with species delimitation and contributes to our understanding of the bryozoan tree of life.

Computing protein structure from amino acid sequence information has been a long-standing grand challenge. CASP (Critical Assessment of Structure Prediction) conducts community experiments aimed at advancing solutions to this and related problems. Experiments are conducted every two years. The 2020 experiment (CASP14) saw major progress, with the second generation of deep learning methods delivering accuracy comparable with experiment for many single proteins. There is an expectation that these methods will have much wider application in computational structural biology. Here we summarize results from the most recent experiment, CASP15, in 2022, with an emphasis on new deep learning-driven progress. Other papers in this special issue of Proteins provide more detailed analysis. For single protein structures, the AlphaFold2 deep learning method is still superior to other approaches, but there are two points of note. First, although AlphaFold2 was the core of all the most successful methods, there was a wide variety of implementation and combination with other methods. Second, using the standard AlphaFold2 protocol and default parameters only produces the highest quality result for about two thirds of the targets, and more extensive sampling is required for the others. The major advance in this CASP is the enormous increase in the accuracy of computed protein complexes, achieved by the use of deep learning methods, although overall these do not fully match the performance for single proteins. Here too, AlphaFold2 based method perform best, and again more extensive sampling than the defaults is often required. Also of note are the encouraging early results on the use of deep learning to compute ensembles of macromolecular structures. Critically for the usability of computed structures, for both single proteins and protein complexes, deep learning derived estimates of both local and global accuracy are of high quality, however the estimates in interface regions are slightly less reliable. CASP15 also included computation of RNA structures for the first time. Here, the classical approaches produced better agreement with experiment than the new deep learning ones, and accuracy is limited. Also, for the first time, CASP included the computation of protein-ligand complexes, an area of special interest for drug design. Here too, classical methods were still superior to deep learning ones. Many new approaches were discussed at the CASP conference, and it is clear methods will continue to advance.

Aims: The initial phase of multiple sclerosis (MS), often known as clinically isolated syndrome (CIS), is a critical period for identifying individuals at high risk of progressing to full-blown MS and initiating timely treatment. In this study, we aimed to evaluate the prognostic value of CXCL13 and IL-8 as potential markers for CIS patients’ conversion to MS. Methods: Our study encompassed patients with CIS, those with relapsing-remitting MS (RRMS), and control subjects, with sample analysis conducted on both cerebrospinal fluid (CSF) and serum. Patients were categorized into four groups: CIS-CIS (no MS development within two years), CIS-RRMS (conversion to RRMS within two years), RRMS (already diagnosed), and a control group (CG) with non-inflammatory CNS disorders. Results: Results showed significantly elevated levels of CXCL13 in CSF across all patient groups compared to the CG (p < 0.0001, Kruskal-Wallis test). Although CXCL13 concentrations were slightly higher in the CIS-RRMS group, statistical significance was not reached. Similarly, significantly higher levels of IL-8 were detected in CSF samples from all patient groups compared to the CG (p < 0.0001, Kruskal-Wallis test), with comparable levels among patient groups. ROC analysis in the CIS-RRMS group identified both CXCL13 (AUC = 0.959) and IL-8 (AUC = 0.939) in CSF as significant predictors of CIS to RRMS conversion. Conclusion: In conclusion, our study suggests a trend toward elevated CXCL13 levels in CIS patients progressing to RRMS. These findings emphasize the importance of identifying prognostic markers to guide appropriate treatment strategies for individuals in the early stages of MS.

Across its Holarctic range, Arctic charr (Salvelinus alpinus) populations have diverged into distinct trophic specialists across independent replicate lakes. The major aspect of divergence between ecomorphs is in head shape and body shape, which are ecomorphological traits reflecting niche use. However, whether the genomic underpinnings of these parallel divergences are consistent across replicates was unknown but key for resolving the substrate of parallel evolution. We investigated the genomic basis of head shape and body shape morphology across four benthivore-planktivore ecomorph pairs of Arctic charr in Scotland. Through genome-wide association analyses, we found genomic regions associated with head shape (89 SNPs) or body shape (180 SNPs) separately and 50 of these SNPs were strongly associated with both body and head shape morphology. For each trait separately, only a small number of SNPs were shared across all ecomorph pairs (3 SNPs for head shape and 10 SNPs for body shape). Signs of selection on the associated genomic regions varied across pairs, consistent with evolutionary demography differing considerably across lakes. Using a comprehensive database of salmonid QTLs newly augmented and mapped to a charr genome, we found several of the head and body shape associated SNPs were within or near morphology QTLs from other salmonid species, reflecting a shared genetic basis for these phenotypes across species. Overall, our results demonstrate how parallel ecotype divergences can have both population-specific and deeply shared genomic underpinnings across replicates, influenced by differences in their environments and demographic histories.

Background: There remains limited knowledge about the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-COV2) vaccination in pediatric oncology patients, which is essential to provide counseling and risk adaptation in this vulnerable population. The goal of this study was to understand immunogenicity after vaccination in pediatric oncology patients and determine if certain clinical factors impacted response. Methods: Patients 0-25 years of age with a diagnosis of cancer and actively receiving therapy were enrolled on study. We excluded patients who were completely vaccinated prior to their cancer diagnosis. Blood samples were collected pre-vaccination, as well as 2, 4-6, and 8-12 weeks after vaccination. Healthy children who were fully vaccinated enrolled as controls. Clinical data and complete blood counts around time of vaccination were collected. To study B and T cell immunity, we measured neutralizing antibodies by enzyme-linked immunoassay and interferon gamma secretion by enzyme-linked immunospot, respectively. Results: 26 patients enrolled on study, for which 11 were evaluable oncology patients and 7 were healthy controls. Adequate B cell response was seen in 36.4% of patients and adequate T cell response in 77.8% of patients. Numbers were too small to detect differences based on malignancy type. There was no differences in immunity based on absolute lymphocyte count (ALC) or intensity of therapy. Conclusion: Pediatric oncology patients have a suboptimal immune response to SARS-COV2 vaccination. Booster doses will be imperative to provide optimal protection against COVID-19, however blood counts may not be a useful guide to optimize the time of administration.

Rationale: Increasing demand for fish and seafood means that traceability of marine products is becoming ever more important for consumers, producers and regulators. Highly complex and globalised supply networks create challenges for verifying the claimed catch region. Atlantic cod is one of the most commercially important species in the northeast Atlantic. Several regional fisheries supply cod into the trade network, of which some are at more risk of overexploitation than others. Tools allowing retrospective testing of spatial origin for traded cod products would significantly assist sustainable harvesting of wild fish, reducing incentives for illegal fishing and fraud. Methods: Here we investigate whether stable isotope ratios of carbon, nitrogen and sulfur in muscle tissue can be used to identify the catch region of Atlantic cod ( Gadus morhua). We measured the isotopic composition of muscle tissue from 377 cod from ten known catch regions across the Northeast Atlantic and Northeast Arctic, and then applied three different assignment methods to classify cod to their region of most likely origin. The assignment method developed was subsequently tested using independent known-origin samples. Results: Individual cod could be traced back to their true origin with an average assignment accuracy of 70-79% and over 90% accuracy for certain regions. Assignment success rates comparable to those using genetic techniques were achieved when the same origin regions were selected. However, assignment accuracy estimated from independent samples averaged c25% overall. Conclusion: Stable isotope techniques can provide effective tools to test for origin in Atlantic cod. However not all catch regions are isotopically distinct. Stable isotopes could be used in conjunction with genetic techniques to result in higher assignment accuracy than could be achieved using either method independently. Assignment potential can be estimated from reference datasets, but estimates of realistic assignment accuracy require independently collected data.

Background/Aim: The present study aimed to develop detailed parameters for prediction of prognosis for patients with unresectable hepatocellular carcinoma (uHCC) receiving Atezolizumab plus Bevacizumab (Atez/Bev). Methods: Between September 2020 and January 2023, the patients treated with Atez/Bev were enrolled (n=719, males 577, median age 74 years). Factors involved in overall survival (OS) were extracted and a prognostic scoring system based on hazard ratio (HR) was created. OS and progression-free survival (PFS) were examined retrospectively, and the prognostic ability of the newly system was compared to CRAFITY score using concordance index (c-index) and Akaike Information Criterion (AIC) results. Results: Cox-hazards multivariate analysis showed BCLC classification C/D (HR 1.4; 1 point), AFP ≥100 ng/mL (HR 1.4; 1 point), mALBI 2a (HR 1.7; 1 point), mALBI 2b/3 (HR 2.8; 2 points), and DCP ≥100 mAU/mL (HR 1.6; 1 point) as significant factors. The assigned points were added and used for IMnunotherapy with AFP, BCLC staging, mALBI, and DCP evaluation (IMABALI-De) scoring. For IMABALI-De scores of 0/1/2/3/4/5, OS was not applicable (NA)/NA/26.11/18.79/14.07/8.32 months (P<0.001; AIC 2788.67, c-index 0.699), while for CRAFITY scores of 0/1/2, OS was 26.11/20.29/11.32 months (p<0.001; AIC 2864.54, c-index 0.606). PFS for those IMABALI-De scores was 21.75/12.89/9.18/8.0/5.0/3.75 months (P<0.001; AIC 5203.32, c-index 0.623) and for the CRAFITY scores was10.32/7.68/3.57 months (p<0.001; AIC 5246.61, c-index 0.574). IMABALI-De score had better AIC and c-index results as compared to CRAFITY score for both OS and PFS. Conclusion: The proposed IMABALI-De score may have a favorable prognostic predictive ability for uHCC patients with Atez/Bev.

INTRODUCTIONMycosis fungoides: Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma. It represents the most common type of extranodal non-Hodgkin lymphomas 12. Follicular or folliculotropic MF (F-MF, also known as follicular T-cell lymphoma, follicular MF, MF-associated mucinosis, or pleiotropic MF) is an under-recognized subtype of MF. It is characterized histologically by folliculotropism (histologically analogous to epidermotropism) with malignant T cells, with or without associated follicular mucinosis3. In 2005, The WHO/EORTC considered F-MF as a variant of MF in their classification4-7.Mycosis fungoides in the Kingdom of Saudi Arabia: In the Kingdom of Saudi Arabia, few studies are available about MF and F-MF1,8-12. AlGhamdi et al examined the clinicopathologic features of MF in 43 cases of immunohistologically confirmed MF. The average age was 33.5 years was reviewed. The male-to-female ratio was 2:1. Most of the cases presented in an early-stage (I and II) MF. Most of the patients had classic MF and other subtypes included hypopigmented MF and other variants. The patients were followed up for a duration of 27.6 months. The follow-up data indicated that few patients recovered (9.5%) patients recovered; whereas the majority (83.3%) had persistent MF skin lesions. A single patient had the extracutaneous disease; whereas only two patients died of MF 8.Al-Dawsari et al examined the surgical pathology records of Saudi patients from 1995 to 2014 at the Johns Hopkins Aramco Healthcare Center (Eastern Province of KSA). This medical facility is the healthcare provider for the employees working at Saudi Aramco company and their dependents in the Eastern Province of Saudi Arabia. The total number of primary skin tumors was 204 and out of them 22 cases were MF10. Albasri et al examined the pattern of skin cancer in the Madinah region of KSA. Among the 202 cancer cases examined in their series, there were 14 (6.8%) cases of MF. The mean age of the patients was 30.7 years with a male-to-female ratio of 11:3. The distribution of the MF skin lesions included: 4 cases (head and neck), 3 cases (upper limb), and 7 cases (lower limb) 11.Alsaif et al described the Leser-Trelat sign (sudden appearance of seborrheic keratosis) in a 60-year-old Saudi male patient with MF. The lesions appeared on the face and back 12. Alojail et reported the clinical features and treatment regimens in 34 cases of MF in KSA. The cases included both hyperpigmented (11 cases) and hypopigmented (21 cases) MF, poikilodermatous MF, and pagetoid reticulosis (a single, each). The treatment regimens included phototherapy Narrowband UVB (NB-UVB) in combination with topical corticosteroids, phototherapy NB-UVB in combination with the topical corticosteroid, and phototherapy NB-UVB with topical corticosteroid and systemic acitretin 1.Alghubaywi et al examined all MF cases diagnosed at King Abdulaziz Medical City in KSA (January 2016 to July 2022). A total of 73 patients were included in their study. The incidence of MF was slightly higher in females (male to female ratio: 1: 1.3). The average age was 44 years. The most common MF subtypes included classic MF, followed by hypopigmented MF. Most of the cases were presented at an early-stage MF (IA, IB, and IIA). The treatment option was mainly in the form of topical steroids. Immunohistological staining of CD4+/CD8+ with CD8 predominance was common and this may reason for the favorable disease outcome 13. These authors also indicated that MF was under-recognized with 20% of the patients with MF initially misdiagnosed as atopic dermatitis. The correct diagnosis of MF was rendered within a mean of 33 months from the time of presentation to the Dermatology clinics. The authors reasoned the delay in the diagnosis of MF the fact that chronic dermatitis and MF share several clinical manifestations such as the presence of pruritic, erythematous, scaly plaques 13. A summary of the previous studies is shown in Table 1.Follicular mucinosis: Follicular mucinosis, i.e. accumulation of mucin in the epithelium of the hair follicles can be either a primary idiopathic disorder or an associated event with several inflammatory conditions (such as chronic spongiotic dermatitis), benign or malignant neoplasms14-16. In 1957, Pinkus first described mucin deposits in the follicular epithelium (alopecia mucinosa) that are associated with folliculotropism, i.e., infiltration of the epithelial cells of the outer hair sheath by atypical lymphocytes17. In 1959, the term follicular mucinosis was introduced by Jablonska 18. There are two clinical types of follicular mucinosis: idiopathic follicular mucinosis and lymphoma-related follicular mucinosis, i.e., F-MF. The latter can be separated from the classical MF on a clinical and histological basis2,19,20. Currently, there is no specific therapy for idiopathic follicular mucinosis and the skin lesions can resolve spontaneously within a period of 2 to 24. Some therapeutic options include steroids (topical, intralesional, and systemic steroids), photodynamic therapy, antimalarials, interferon, and dapson21,22.Folliculotropic mycosis fungoides: F-MF represents the most common non-classic variant of MF, representing approximately 10% of the cases of MF 23. It usually shows a male predominance and most of the cases occur in adults 24. Its clinical findings include follicle-based infiltrated erythematous grouped papules resembling acne or keratosis pilaris, patches, plaques, and tumor-like lesions with follicular accentuation 2,20,25. Other clinical presentations include prurigo-like lesions, pseudotumors, lichen spinulosus-like lesions, rosacea-like lesions, and lupus tumidus-like plaques 26. Pruritis is a common complaint and it is aggravated by superinfection by staphylococcus auras resulting in pyoderma 25. The lesions of F-MF vary from solitary lesions to extensive lesions giving the appearance of a leonine face 23. The head and neck region is the most commonly affected site. Other sites include the trunk, and the extremities 17. The features of F-MF are seen in nearly 10% of the patients with MF 2,20,25. The salient histological features of F-MF include perivascular and peri‑adnexal dermal lymphocytic infiltrates with variable infiltration and destruction of the follicular epithelium by small, medium‑sized, or large-sized lymphocytes with hyperconvoluted nuclei (cerebriformnuclei). The epidermis is usually spared. Other histological findings include follicular mucinosis, Pautrier’s Micro-abscess, follicular plugging, tagging of the atypical lymphocytes along the follicular epithelium, peri-eccrine infiltrate of atypical lymphocytes23,26. Immunohistochemistry usually reveals prominent CD3 positive infiltrate, witha predominance of CD4 positive lymphocytes over rare CD8 positive T-cells. CD7 expression is reduced or completely lost. Molecular analysis (T-cell receptor-γ gene rearrangement) reveals a monoclonal T-cell population23,26-28. The therapeutic options in F-MF include photochemotherapy combined with interferon alpha-2a and retinoids. Other options include local radiotherapy, topical imiquimod, and total body electron beam irradiation 23.Several F-MF case reports were presented in the literature. Monopoli et al described two adult patients with F-MF. The clinical manifestations included alopecia and follicular erythematous papules, and comedones and cysts, respectively. The histological findings included folliculotropic atypical T-cell infiltrate that extends to the epidermis. There was no associated mucinosis. Clonality analyses revealed the oligo/monoclonal nature of the T-cell lymphocytic infiltrate 27.Rajalakshmi et al examined four cases of F-MF affecting the skin of the face. The mean age of the patients was 17.5 years and there were no differences in gender distribution. The lesions were in the form of hypopigmented patches or erythematous plaques. Two patients had associated alopecia. The salient histological finding included folliculotropism, mucin deposition around the hair follicles, lymphocyte tagging with haloes, atypical lymphocytes with hyperconvoluted/cerebriform nuclei, and infiltration of the eccrine and sebaceous glands by atypical lymphocytes. Other histological features included the presence of epithelioid cells, parakeratosis, and a prominent infiltrate of eosinophils 29. Magro et al reported 6 cases of unilesional follicular MF. All the patients were males with a mean age of 28 years. The patients were presented with a solitary lesion on the face and scalp (five patients) and trunk (a single patient) that persisted for a few months. There were follicular prominence and alopecia. On histology, there was an atypical folliculotropic lymphocytic infiltrate associated with follicular mucinosis. Immunohistology revealed a high CD4: CD8 ratio and loss of CD7 expression. A single untreated case developed similar lesions over the skin of the thigh and buttock after 3-4 years 28. F-MF usually occurs in adults with an average age at the time of diagnosis of 60 years 30. F-MF is exceptionally rare in children and adolescents. Mantri et al reported a case of F-MF in a 16-year-old boy who presented with 6x7 cm plaque on the forehead for a 2-month duration. Immunohistological examination revealed dense atypical T-cell lymphocytes invading and destroying the hair follicles. Follicular mucinosis was also seen. Most of the neoplastic cells were CD4-positive T- T-lymphocytes with scarce CD8-positive T cells around the hair follicles. Treatment was in the form of a spot electron beam and the lesion completely resolved within 2 months 30. Interestingly, Emge et al reported a case of F-MF in a 6-year-old boy. The lymphoma was associated with idiopathic follicular mucinosis31.Taken collectively, these previous reports indicated that F-MF is a rare and aggressive form of MF that has a worse prognosis compared to conventional MF. It usually affects the head and neck region in adults. It has distinct histological features and may or may not be associated with follicular mucinosis. F-MF has several clinical presentations and many histological faces. Therefore, it is often misdiagnosed, or diagnosed with much delay at an advanced stage as compared to the conventional MF.Herein, we report a case of F-MF in a middle-aged male patient. To date and to be best of our knowledge, this is the first case of F-MF to be reported in the Southern region (Asir region) of the KSA. The clinicopathologic features were discussed.

Gene function conservation is crucial in molecular ecology, especially for key traits like growth and maturation in teleost fish. The vgll3 and six6 genes are known to influence age-at-maturity in Atlantic salmon, but their impact on other fish species is poorly understood. Here, we investigated the association of vgll3 and six6 in the domestication of gilthead seabream and European seabass, both undergoing selective breeding for growth-related traits in the Mediterranean. We analysed two different sets of samples using two different genotyping approaches. The first dataset comprised farmed and wild populations from Greece, genotyped for SNPs within the genomic range of the two genes (“gene-level genotyping”). The second dataset examined 300k to 600k SNPs located in the chromosomes of the two genes, derived from a meta-analysis of a Pool-Seq experiment involving farmed and wild populations distributed widely across the Mediterranean (“chromosome-level genotyping”). The gene-level analysis revealed a significant effect of domestication on both genes in each species. This finding was partially supported by the chromosome-level analysis, identifying highly differentiated regions associated with domestication at varying distances from the candidate genes. Noteworthy genomic features were found, such as a CpG island in gilthead seabream and novel candidate genes in European seabream, warranting further investigation. These findings support a putative role of vgll3 and six6 in the maturation and growth of gilthead seabream and European seabass, emphasizing the need for further research on their conserved function.

Telehealth is an emerging approach that uses technology to provide healthcare remotely. Recent publications have outlined the importance of supporting the transition to self-management of adolescents with allergic conditions. However, no synthesis of the evidence base on the use and impact of telehealth interventions for this purpose has been conducted to date. This review achieves these aims, in addition to exploring the language use surrounding these interventions, and their implementation. Four databases were searched systematically. References were independently screened by two reviewers. Methodological quality was assessed using the Mixed Methods Appraisal Tool. A narrative synthesis was undertaken. Eighteen papers were included, reporting on fifteen telehealth interventions. 86% targeted adolescents with asthma. Mobile applications were the most common telehealth modality used, followed by video-conferencing, web-based, virtual reality and artificial intelligence Five intervention content categories were identified; educational, monitoring, behavioural, psychosocial and healthcare navigational. Peer and/or healthcare professional interaction, gamification and tailoring may increase engagement. The studies showed positive effects of the interventions or no difference from active controls, in self-management outcomes such as knowledge, health outcomes such as quality-of-life, and economic outcomes such as healthcare utilisation. The most common implementation outcomes reported were acceptability, appropriateness, feasibility and fidelity.

Sexual violence is a world-wide health problem that has begun to escalate in online and virtual spaces. One form of technology-facilitated sexual violence that has escalated in recent years is image-based sexual abuse (IBSA), or the nonconsensual creation, distribution, and/or threat of distribution of nude or sexual images. Using a trauma-informed and victim-centered framework, we asked victim-survivors for structural solutions to IBSA based on their own experiences. Using thematic analysis on 36 semi-structured interviews with adult U.S. victim-survivors of IBSA, we found that victim-survivors proposed structural solutions to IBSA along 5 general dimensions: legal (creating/strengthening laws, enforcing laws, facilitating legal navigation), corporate (corporate responsibility/activism and solutions for employers), educational (IBSA education, outreach and advocacy, and developing communities of support), technological (more platform accountability, improved procedures for uploading images, better avenues for reporting and removing images, and enhanced platform policies), and cultural. Many solutions built on existing structures (e.g., sexual education in schools) and frameworks (e.g., creating support groups like those for people in recovery from alcohol abuse), enabling educational professionals, policy makers, victim-support service providers, and corporations to readily implement them.

TITLE PAGEArticle TypeClinical pictureTitlePenile Injury Caused by Neodymium MagnetsAuthorsYuki Akiyama1, Ryo Ichibayashi2Affiliations1. Department of Orthopaedic Surgery, Toho University Medical Center, Sakura Hospital, Chiba, Japan2. Division of Emergency Medicine Department of Internal Medicine, Toho University Medical Center, Sakura Hospital, Chiba, JapanCorresponding AuthorRyo Ichibayashi, MD, PhDORCID iD https://orcid.org/0000-0002-1273-4875Division of Emergency Medicine Department of Internal MedicineToho University Medical Center, Sakura Hospital564-1 ShimosizuSakura-shi, Chiba 285-8741, JapanPhone: +81-43-462-8811Fax: +81-43-462-8835e-mail: [email protected] titleDamage caused by neodymium magnetsKeywordsNeodymium magnet, Penile foreign body, Emergency, TreatmentConflict of interestThe authors have no conflict of interest to disclose.Financial supportThe author(s) received no financial support for this article’s research, authorship, and publication.Patient consentWritten informed consent was obtained from the patient to publish this report by the journal’s patient consent policy.Author contributionYA wrote and drafted the manuscript. RI helped draft the manuscript. All authors read and approved the final manuscript.Data availability statementThe data presented in this study are available on request from the corresponding author. The data are not publicly available due to privacy and ethical considerations.AcknowledgmentsNone.Key clinical messageMultiple neodymium magnets can pinch tissue and cause barotrauma. Be careful if the tissue of the penis or foreskin is pinched, as this may cause foreskin necrosis or damage to the urethra.Clinical picture11-year-old boy. He has no history of developmental disabilities or mental illness. The boy played with a neodymium magnet attached to his penis in the bathroom out of curiosity. However, the neodymium magnet remained attached to his penis and could not be removed, and he was transported to our hospital by ambulance with the chief complaint of penile pain. Emergency crews tried to remove it, but it was impossible because it was painful, and there were concerns that it might damage the foreskin. Two hours had passed since he was transferred to our hospital because he was refused admission by multiple medical institutions. At the time of his visit, his penis had two circular neodymium magnets, each approximately 1 cm in diameter, placed against the foreskin of his penis (Figure 1A). Although it was difficult to remove it by pulling it in the opposite direction, it was possible to remove it by shifting the ground surface. After the foreskin was released, there was a crushed wound, so ointment was applied（Figure 1B）. After confirming that there was no problem with the color tone of his glasses, he returned home. The next day, he returned to the outpatient clinic and confirmed that the color of his glans was standard and that he could urinate. Neodymium magnets were developed in Japan in 1982 and have become famous worldwide due to their effectiveness. It is said to be the strongest magnet currently in use. Neodymium magnets are used in various fields and children’s toys [1]. For this reason, accidents such as accidental ingestion by children and insertion into the urinary tract or anus due to sexual preference are problems in the medical field. Accidents caused by multiple neodymium magnets, especially when accidentally swallowed or inserted with a foreign object, are dangerous because they adhere to each other and pinch tissue, resulting in pressure necrosis [2]. This case also had a crush injury to the foreskin. A month later, the scar remained on my foreskin. Barotrauma caused by neodymium magnets often involves damage to thin tissues, including the intestinal tract and mucous membranes. The structures of the corpus cavernosum and the corpus cavernosum of the urethra, which form the penis, are spongy and soft tissues. This tissue becomes rigid as it fills with blood. For this reason, if not only the foreskin but also the corpus cavernosum of the penis is pinched, there is a possibility that blood flow to the corpus cavernosum and damage to the urethra may occur. After removing the neodymium magnet, it is necessary to observe the color of the glans and foreskin and the state of urination.References1. Taylor MA, Spanos SP, Fenton SJ, Russell KW. Ball Magnets Clicked Together on the Epiglottis. Cureus . 2020. 12(5): e8181. doi: 10.7759/cureus.81812. Yuksel C, Ankarali S, Aslan Yuksel N. The use of neodymium magnets in healthcare and their effects on health. North Clin Istanb . 2018; 5(3): 268-273. doi:10.14744/nci.2017.00483Figure 1A　Neodymium magnet that pinches the foreskin of the penisB　 Foreskin with a crush injury

Understanding the diet preferences and prey selection of invasive species is crucial to better predict their impact on community structure and ecosystem functioning. Limnomysis benedeni, a Ponto-Caspian invasive mysid shrimp, is one of the most successful invaders in numerous European river and lake ecosystems. While existing studies suggest potentially strong trophic impact due to high predation pressure on invaded plankton communities, little is known of its prey selectivity between phyto- and zooplankton, under different prey concentrations. Here, we therefore investigated the feeding selectivity of L. benedeni on two commonly occurring prey organisms in freshwaters, the small rotifer zooplankton Brachionus calyciflorus together with the microphytoplankton Cryptomonas sp. present in increasing densities. Our results demonstrated a clear shift in diet selection, with L. benedeni switching from B. calyciflorus to Cryptomonas sp. already when the two prey species were provided in equal biomasses. Different functional responses were observed for each prey type, indicating somewhat different foraging mechanisms for each prey type. These findings provide experimental evidence on the feeding flexibility of invasive mysid shrimps and potential implications for trophic interactions in invaded ecosystems.