The Negative Impact of Prolonged Desiccation on the Recovery of Selaginella bryopteris: Insights Into Autophagy and Cellular Protection Strategies.

Desiccation tolerance is a complex biological phenomenon that allows certain plants to survive extreme dehydration and revive upon rehydration. Although significant progress has been made in understanding the physiological and molecular mechanisms involved in desiccation tolerance, recovery mechanisms after prolonged desiccation periods are enigmatic. Combining physiological, biochemical, transcriptomic and metabolomic approaches, we investigated the role of prolonged desiccation on recovery of Selaginella bryopteris. Prolonged desiccation causes a decline in the antioxidant system, leading to accumulation of ROS that hinder recovery by inducing cellular damage. Transcriptome and WGCNA analysis revealed the significance of protective proteins, alternative respiration and protein homeostasis in cellular protection and recovery after short and long-term desiccation. Metabolomic analysis exhibited an increased accumulation of antioxidant compounds, which can be substituted for antioxidant enzymes to maintain cellular protection during prolonged desiccation. The significant role of autophagy and autophagic components was evaluated by H2O2 treatment and phylogenetic analysis of ATG4 and ATG8, which unveiled their substantial role in desiccation tolerance and remarkable conservation of the autophagy-related genes across plant species. Our data demonstrated that prolonged desiccation leads to ROS-induced cell death by extensive autophagy due to enormous loss of protective proteins, antioxidant enzymes and energy resources during desiccation.

Status and Depth of Mastoid Antrum and the Pattern of Mastoid Pneumatization in Cases of Large, Subtotal Perforations and Posterosuperior Retraction Pockets (PSRP).

The present study aimed to evaluate the pneumatization status of the mastoid air cells in general with the depth and status of mastoid antrum in particular, in patients of chronic otitis media (COM). This is an observational cross-sectional study in sample size of 60 participants with large, subtotal perforation and posterosuperior retraction pocket (PSRP). Mean age with large central and subtotal perforation combined was 35.78 years, compared to 32.13 years in PSRP. Granulations seen in antrum in 71.6% and cholesteatoma observed in 15%. Mean depth of the mastoid antrum was 17.27 mm. A well pneumatized mastoid in 21.6%, diploic 28.3% and sclerotic in 50% was noted in this study. Chronic otitis media affects temporal bone pneumatization, particularly the mastoid antrum. Our findings indicate that the depth of the mastoid antrum is slightly greater in cholesteatoma cases due to bone erosion. As early intervention enhances postoperative quality of life by preserving or restoring auditory function, understanding the mastoid pneumatization and antrum depth is crucial for managing chronic otitis media effectively.

Assessing the Co-relation between Mandibular Flare and Thickness of Lingual Cortex in Relation to the Third Molars: A Retrospective Cross-sectional Study.

Aim: To assess the co-relation between mandibular flare and thickness of lingual cortex in relation to the third molars. Materials and Methods: Retrospectively obtained computed tomography (CT) data of 26 patients was used after classifying them into respective skeletal malocclusion groups (classes I, II, and III). Thickness of lingual cortex was measured at crestal, middle, and apical levels in mandibular third molar region. Two angular and two linear measurements were used to measure mandibular flare. Angular measurements included the angle between condylion (Co) and menton (Me), and between gonion (Go) and menton (Me). Linear measurements included bigonial and bicondylion widths. Results: The two angular measurements did not differ significantly among the three skeletal malocclusion groups. Contrastingly, bicondylion width differed significantly among the three groups. Class II group showed no significant correlation between mandibular flare and lingual cortical thickness. Class III group demonstrated a significant negative correlation of linear and angular measurements with cortical bone thickness. Bicondylion width was significantly more in Class III group than in other skeletal groups, which proved an increased mandibular flare in patients with Class III malocclusion. Conclusion: Increase in mandibular flare was associated with decreased thickness of lingual cortical bone.

Comparative Study of Endoscopic Transcanal Tympanoplasty and Tympanoplasty by Conventional Postaural Approach in a Tertiary Care Hospital in Central India.

Background Chronic otitis media (COM) often necessitates tympanoplasty to repair the tympanic membrane. While conventional postaural tympanoplasty (PA) is well-established, endoscopic transcanal tympanoplasty (ET) is gaining traction for its minimally invasive benefits. This study aims to compare these two surgical techniques regarding their anatomical and functional outcomes and assess the role of platelet-rich plasma (PRP) in improving these outcomes. Material and methods This prospective comparative study was conducted at Acharya Vinoba Bhave Rural Hospital, involving 60 patients with COM. Participants were randomly assigned to receive either ET or PA, with each group further subdivided based on PRP use. Preoperative evaluations included auditory function tests and diagnostic endoscopy. Postoperative assessments were performed at seven days, one month, and three months to evaluate graft acceptance and hearing improvement using pure tone audiometry (PTA). Statistical analyses included the chi-square test, t-test, ANOVA, and paired t-test. Results The study included patients with a mean age of 38.1 years, predominantly female (71.67%). ET demonstrated superior anatomical outcomes compared to PA, with higher graft acceptance rates and better hearing improvements. The average hearing gain was 10.4 dB in the ET group versus 8.1 dB in the PA group. PRP uses enhanced graft acceptance and hearing restoration across both surgical approaches, contributing to better overall outcomes. Conclusion ET offers significant advantages over conventional postaural tympanoplasty in terms of anatomical and functional results. PRP further improves surgical outcomes, making ET a preferable option for tympanoplasty in COM patients. These findings support the broader adoption of ET and PRP to enhance patient outcomes in tympanoplasty procedures.

Artificial Intelligence in Otology, Rhinology, and Laryngology: A Narrative Review of Its Current and Evolving Picture.

With technological advancements, artificial intelligence (AI) has progressed to become a ubiquitous part of human life. Its aspects in otorhinolaryngology are varied and are continuously evolving. Currently, AI has applications in hearing aids, imaging technologies, interpretation of auditory brain stem systems, and many more in otology. In rhinology, AI is seen to impact navigation, robotic surgeries, and the determination of various anomalies. Detection of voice pathologies and imaging are some areas of laryngology where AI is being used. This review gives an outlook on the diverse elements, applications, and advancements of AI in otorhinolaryngology. The various subfields of AI including machine learning, neural networks, and deep learning are also discussed. Clinical integration of AI and otorhinolaryngology has immense potential to revolutionize the healthcare system and improve the standards of patient care. The current applications of AI and its future scopes in developing this field are highlighted in this review.

Molecular interaction studies of L-proline in water and ethanol at different temperatures using dielectric relaxation, refractive index and DFT methods.

The complex dielectric permittivity of L-Proline in water and ethanol solutions with molar concentrations ranging from 0.025 M to 0.15 M was measured by open-ended coaxial probe technique. The measurements were carried out across a frequency span of 0.02 < ν/GHz < 20 and temperatures varying from 298.15 K to 323.15 K. The densities (ρ) and refractive index (nD) of the L-proline in aqueous and ethanol solutions were also determined to provide insights into the solute-solvent interactions in the system. The Havriliak-Negami equation was employed to compute the dielectric relaxation time of the mixtures. The relaxation time of L-Proline in an ethanol medium was found to be higher than that of L-Proline in an aqueous medium due to the greater degree of self-association of ethanol molecules. Additionally, the relaxation time of the mixtures lengthened with rising molar concentration, which is attributed to the presence of hydrogen bonds among L-Proline and aqueous/ethanol molecules. The strength of the hydrogen bond interaction of L-Proline in both mediums was calculated using single-point energy calculations employing IEFPCM/PCM solvation models through DFT/B3LYP and MP2 approaches with a 6-311 G ++ (d, p) basis set. The results were correlated with the hydrogen bond strength, Gibbs' free energy of activation parameter, and dipole-dipole interactions.Communicated by Ramaswamy H. Sarma.

Study of molecular interaction between L-proline with water/ethanol mixturesDielectric relaxation studies of aqueous and ethanol mixtures at various temperaturesCorrelate relaxation time in terms of contribution of hydration/bound waterEffect of H- bonding on dipole moment, relaxation and polarizability valuesPositive values of ΔG* confirms the presence of multimers in the solution.

A Case Report of Neurofibroma of the Tongue Presented as a Solitary Lesion.

Neurofibroma are rare occurrences in the oral cavity with the tongue as the most common location in the oral cavity being affected by neurofibroma. Neurofibroma are usually asymptomatic, irregular tissue masses of benign nature with a small rate of malignant conversion. Recurrence rates are also low in the neurofibromas of the oral cavity. It is rare in India with only a few cases reported to date. Hence, we report this case of a 63-year-old female with a tissue mass present on the right side of her tongue for the last five years, with a progressive nature. The mass was associated with pain during chewing food for the last three months. She was managed by a wide local incision and was reported well recovering at a three-month follow-up.

Otorhinolaryngologic Manifestations of Tuberculosis: A Comprehensive Review of Clinical and Diagnostic Challenges.

Tuberculosis (TB) is a significant global health issue, predominantly affecting the lungs but also capable of involving the otorhinolaryngologic (ear, nose, and throat) regions. This comprehensive review explores the epidemiology, pathophysiology, clinical presentation, diagnostic challenges, management strategies, and public health implications of otorhinolaryngologic TB. The disease's diverse clinical manifestations, such as chronic ear discharge, nasal obstruction, and hoarseness, often mimic other common conditions, complicating diagnosis and delaying treatment. Diagnostic confirmation requires a combination of clinical assessment, laboratory tests, and imaging techniques, each with inherent limitations. Effective management necessitates a multidisciplinary approach, integrating medical and surgical interventions tailored to individual patient needs. Potential complications, including airway obstruction and hearing loss, highlight the importance of timely and appropriate treatment. The review underscores the critical role of public health measures in TB control. It also identifies emerging trends in diagnosis and treatment, emphasizing the need for ongoing research to improve patient outcomes and contribute to the global effort to control and eventually eradicate TB. This review aims to give healthcare providers a deeper understanding of otorhinolaryngologic TB, enhancing diagnostic and therapeutic approaches and improving patient care.

Bio fabricated palladium nano particles using phytochemicals from aqueous cranberry fruit extract for anti-bacterial, cytotoxic activities and photocatalytic degradation of anionic dyes.

The low cost and ecological compatibility of green technology makes it superior to chemical approaches in the generation of metal nanoparticles. The current study shows the use of cranberry fruit extract in the environmentally friendly green production of palladium nanoparticles. It is well known that the fruit extract from cranberries has a rich phytochemical composition that makes it a useful bio reducing agent for the formation of PdNPs. Several spectroscopic techniques, including ultraviolet-visible spectroscopy (UV-vis), X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersive X-ray spectroscopy (EDX), were used to characterize the palladium nanoparticles (PdNPs). The diffractogram of the XRD analysis shows significant reflections at 39.98° (111), 46.49° (200), and 67.95° (220), which indicate the face-centered cubic (FCC) structure of PdNPs and demonstrate the crystallinity of the produced nanoparticles from the green method. The SEM and TEM structural and morphological analyses reveal that the synthesized nanoparticles have a spherical shape with size ranging between 2 nm to 50 nm. In addition, the synthesized PdNPs demonstrated possible antibacterial activity on both Gram-positive and Gram-negative bacteria as well as a cytotoxic effect on the MCF-7 breast cancer cell line. The degradation of Indigo Carmine (IC) and Sunset Yellow (SY) dyes can be effectively catalyzed by biogenic PdNPs, according to the results.

A Giant Vallecular Cyst in an Adult: A Case Report.

Vallecular cysts (VCs) are rare benign lesions arising from the obstruction of mucous gland ducts. VCs are uncommon anomalies found in both pediatric and adult populations. They are also known as mucous-retention cysts, preepiglottic cysts, ductal cysts, base-of-tongue cysts, and epiglottis cysts. VCs are often asymptomatic in adults and may present with nonspecific symptoms such as globus sensation, voice changes, dysphagia, hoarseness, or airway obstruction when symptomatic. This case report details a rare occurrence of a giant VC in an adult male, emphasizing the diagnostic approach and surgical management and highlighting the importance of managing the airway in such cases and the advantages of endoscopic procedures.

Wheat TaNACα18 functions as a positive regulator of high-temperature adaptive responses and improves cell defense machinery.

Global wheat production amounted to >780 MMT during 2022-2023 whose market size are valued at >$128 billion. Wheat is highly susceptible to high-temperature stress (HTS) throughout the life cycle and its yield declines 5-7% with the rise in each degree of temperature. Previously, we reported an array of HTS-response markers from a resilient wheat cv. Unnat Halna and described their putative role in heat acclimation. To complement our previous results and identify the key determinants of thermotolerance, here we examined the cytoplasmic proteome of a sensitive cv. PBW343. The HTS-triggered metabolite reprograming highlighted how proteostasis defects influence the formation of an integrated stress-adaptive response. The proteomic analysis identified several promising HTS-responsive proteins, including a NACα18 protein, designated TaNACα18, whose role in thermotolerance remains unknown. Dual localization of TaNACα18 suggests its crucial functions in the cytoplasm and nucleus. The homodimerization of TaNACα18 anticipated its function as a transcriptional coactivator. The complementation of TaNACα18 in yeast and overexpression in wheat demonstrated its role in thermotolerance across the kingdom. Altogether, our results suggest that TaNACα18 imparts tolerance through tight regulation of gene expression, cell wall remodeling and activation of cell defense responses.

Angiosarcoma of the Maxillary Sinus: A Case Report.

Angiosarcoma can be defined as a malignant neoplasm arising from the lining of the blood and lymphatic vessels, including the endothelial cells. It can occur in any body part, such as blood vessels, skin, liver, and breast. Its incidence varies based on the site. There are different underlying etiologies associated with the incidence of angiosarcoma. Clinical presentation depends on the site of origin. Angiosarcoma of the sinus or nasal openings can be observed as a tissue mass, lesions, obstructed nasal cavity, facial swelling, proptosis, anosmia, nasal discharge, and epistaxis. These are rare malignancies with very low incidence. Though it has been reported in all age groups, it is more common in adults in their sixth decade and more. Nasal angiosarcoma can be a diagnostic challenge due to its rarity. This is a case of a 56-year-old female with a major complaint of nasal obstruction and face swelling for two months. Physical examination revealed a pinkish polypoidal mass. A contrast-enhanced computed tomography scan showed a heterogeneously arterial enhancing soft-tissue lesion in the left maxillary sinus with significant erosive changes. Histopathological analysis revealed a malignant spindle cell tumor, which was confirmed by a CD34 immunohistology stain. The patient was advised surgical excision for further management, which was denied. The patient is undergoing radiation therapy and is on third cycle as per the last follow-up.

A Comprehensive Review Exploring Allergic Rhinitis With Nasal Polyps: Mechanisms, Management, and Emerging Therapies.

Allergic rhinitis (AR) and nasal polyps (NP) are common inflammatory disorders of the upper airways that often coexist and significantly impact patients' quality of life. This comprehensive review explores the intricate relationship between AR and NP, elucidating the underlying mechanisms, clinical manifestations, and management strategies. Immunological mechanisms, genetic predispositions, and environmental factors contribute to the development and progression of both conditions. Pharmacological therapies, including intranasal corticosteroids and biologic agents, are cornerstone treatments for managing AR with NP. At the same time, surgical interventions such as functional endoscopic sinus surgery (FESS) may be necessary in refractory cases. Emerging therapies, including immunomodulatory agents and precision medicine approaches, hold promise in improving treatment outcomes. A multidisciplinary approach, personalized treatment plans, and patient education are essential for optimizing clinical practice. Future research should focus on identifying novel therapeutic targets, conducting large-scale clinical trials, exploring precision medicine approaches, and investigating the role of the microbiome. Addressing these research priorities and implementing evidence-based treatment strategies can improve outcomes for patients with AR and NP.

A signaling network map of Lipoxin (LXA4): an anti-inflammatory molecule.

Lipoxins (LXs) are a class of endogenous bioactive lipid mediators that are involved in the regulation of inflammation. They exert immunomodulatory effects by regulating the behaviour of various immune cells, including neutrophils, macrophages, and T and B cells, by promoting the clearance of apoptotic neutrophils. This helps to dampen inflammation and promote tissue repair. LXs regulate the expression of many inflammatory genes by modulating the levels of transcription factors, such as nuclear factor κB (NF-κB), activator protein-1 (AP-1), nerve growth factor-regulated factor 1A binding protein 1 (NGF), and peroxisome proliferator activated receptor γ (PPAR-γ), which are elevated in various diseases, such as respiratory tract diseases, renal diseases, cancer, neurodegenerative diseases, and viral infections. Lipoxin-mediated signaling is involved in chronic inflammation, cancer, diabetes-associated kidney disease, lung injury, liver injury, endometriosis, respiratory tract diseases, neurodegenerative diseases, chronic cerebral hypoperfusion, and retinal degeneration. In this study, we systematically investigated the intricate network of lipoxin signaling by analyzing the relevant literature. The resulting map comprised 467 molecules categorized as activation/inhibition, enzyme catalysis, gene and protein expression, molecular associations, and translocation events. This map serves as a valuable resource for understanding the complexity of lipoxin signaling and its impact on various cellular functions.

Comprehensive insights into the impact of bacterial indole-3-acetic acid on sensory preferences in Drosophila melanogaster.

Several bacteria of environmental and clinical origins, including some human-associated strains secrete a cross-kingdom signaling molecule indole-3-acetic acid (IAA). IAA is a tryptophan (trp) derivative mainly known for regulating plant growth and development as a hormone. However, the nutritional sources that boost IAA secretion in bacteria and the impact of secreted IAA on non-plant eukaryotic hosts remained less explored. Here, we demonstrate significant trp-dependent IAA production in Pseudomonas juntendi NEEL19 when provided with ethanol as a carbon source in liquid cultures. IAA was further characterized to modulate the odor discrimination, motility and survivability in Drosophila melanogaster. A detailed analysis of IAA-fed fly brain proteome using high-resolution mass spectrometry showed significant (fold change, ± 2; p ≤ 0.05) alteration in the proteins governing neuromuscular features, audio-visual perception and energy metabolism as compared to IAA-unfed controls. Sex-wise variations in differentially regulated proteins were witnessed despite having similar visible changes in chemo perception and psychomotor responses in IAA-fed flies. This study not only revealed ethanol-specific enhancement in trp-dependent IAA production in P. juntendi, but also showed marked behavioral alterations in flies for which variations in an array of proteins governing odor discrimination, psychomotor responses, and energy metabolism are held responsible. Our study provided novel insights into disruptive attributes of bacterial IAA that can potentially influence the eukaryotic gut-brain axis having broad environmental and clinical implications.

Level and correlates of physical activity among children and adolescents with juvenile idiopathic arthritis compared to controls: results from a German nationwide prospective observational cohort study.

BACKGROUND: Physical active lifestyles are essential throughout growth and maturation and may offer potential preventive and therapeutic benefit in patients with juvenile idiopathic arthritis (JIA). Insufficient physical activity (PA), in contrast, can lead to aggravation of disease-related symptoms. This study aimed to i) examine PA levels in children and adolescents with JIA compared to general population controls and ii) investigate correlates of pronounced physical inactivity in order to identify risk groups for sedentary behaviour. METHODS: Data from children and adolescents with JIA and population controls aged 3 to 17 years documented in the National Pediatric Rheumatologic Database (NPRD) and the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) were used. Self-reported PA was collected from parents/guardians of children up to 11 years of age or adolescents 12 years of age and older. To compare PA-related data, age- and sex-specific pairwise analyses were conducted considering NPRD/KiGGS participants' data from 2017. Correlates of physical inactivity among patients were identified using a linear regression model. RESULTS: Data of 6,297 matched-pairs (mean age 11.2 ± 4.2 years, female 67%, patients' disease duration 4.5 ± 3.7 years, persistent oligoarthritis 43%) were available for evaluation. Almost 36% of patients aged 3-17 years (vs. 20% of controls) achieved the WHO recommended amount of PA, while PA steadily decreased with age (18% of patients aged ≥ 12 years) and varied between JIA categories. Female adolescents and patients with enthesitis-related arthritis were least likely to achieve the minimum recommended level of PA. Physical inactivity was associated with female sex, higher age at disease onset, longer disease duration, more functional disability (C-HAQ) and higher disease activity (cJADAS-10). CONCLUSIONS: Depending on JIA category, children and adolescents with JIA were similarly or even more likely to achieve the WHO recommended minimum level of PA compared to general population controls. However, since a large proportion of young JIA patients appear to be insufficiently physically active, engagement in targeted efforts to promote PA is urgently needed.

Immunomodulation of streptozotocin induced Type 1 diabetes mellitus in mouse model by Macrophage migration inhibitory factor-2 (MIF-2) homologue of human lymphatic filarial parasite, Wuchereria bancrofti.

Helminth parasites modulate the host immune system to ensure a long-lasting asymptomatic form of infection generally, mediated by the secretion of immunomodulatory molecules and one such molecule is a homologue of human host cytokine, Macrophage migratory Inhibitory Factor (hMIF). In this study, we sought to understand the role of homologue of hMIF from the lymphatic filarial parasite, Wuchereria bancrofti (Wba-MIF2), in the immunomodulation of the Streptozotocin (STZ)-induced Type1 Diabetes Mellitus (T1DM) animal model. Full-length recombinant Wba-MIF2 was expressed and found to have both oxidoreductase and tautomerase activities. Wba-MIF2 recombinant protein was treated to STZ induced T1DM animals, and after 5 weeks pro-inflammatory (IL-1, IL-2, IL-6, TNF-α, IFN-γ) and anti-inflammatory (IL-4, IL-10) cytokines and gene expressions were determined in sera samples and spleen respectively. Pro-inflammatory and anti-inflammatory cytokine levels were significantly (p<0.05) up-regulated and down-regulated respectively, in the STZ-T1DM animals, as compared to treated groups. Histopathology showed macrophage infiltration and greater damage of islets of beta cells in the pancreatic tissue of STZ-T1DM animals, than Wba-MIF2 treated STZ-T1DM animals. The present study clearly showed the potential of Wba-MIF2 as an immunomodulatory molecule, which could modulate the host immune system in the STZ-T1DM mice model from a pro-inflammatory to anti-inflammatory milieu.

Long-term safety and effectiveness of canakinumab in patients with monogenic autoinflammatory diseases: results from the interim analysis of the RELIANCE registry.

OBJECTIVE: Interim analysis of the RELIANCE registry, an on-going, non-interventional, open-label, multicentre, prospective study evaluating the long-term safety, dosing regimens and effectiveness of canakinumab in patients with cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF), tumour-necrosis factor receptor-associated periodic syndrome (TRAPS) or mevalonate-kinase deficiency (MKD)/hyperimmunoglobulin-D syndrome (HIDS). METHODS: From September 2017 for patients with CAPS, and June 2018 for patients with FMF, TRAPS or MKD/HIDS, the registry enrolled paediatric (aged ≥2 years) and adult patients (aged ≥18 years) receiving canakinumab as part of their routine medical care. Safety, canakinumab dose, disease activity and quality of life outcome measures were evaluated at baseline and every 6 months until end of study visit. RESULTS: At the analysis cut-off date (December 2020), 168 patients (91 CAPS, 54 FMF, 16 TRAPS and 7 MKD/HIDS) were enrolled. 85 (50.9%) patients were female and 72 (43.1%) were children (<18 years). The median patient age was 20.0 years (range 2.0-79.0 years). In the CAPS cohort, serious infections and serious adverse drug-reactions were more common in patients receiving higher than the recommended starting dose (SD) of canakinumab. A trend to receive >SD of canakinumab was observed in the pooled population. The majority of patients were reported as having either absent or mild/moderate disease activity (physician's global assessment) from baseline to Month 30, with a stable proportion of patients (~70%) in remission under canakinumab treatment. Patient-reported disease activity (Visual Analogue Scale (VAS), Autoinflammatory Disease Activity Index), fatigue (VAS); markers of inflammation (C-reactive protein, serum amyloid A and erythrocyte sedimentation rate) remained well-controlled throughout. CONCLUSION: Data from this analysis confirm the long-term safety and effectiveness of canakinumab for the treatment of CAPS, FMF, TRAPS and MKD/HIDS.

Development of pathophysiologically relevant models of sickle cell disease and ß-thalassemia for therapeutic studies.

Ex vivo cellular system that accurately replicates sickle cell disease and ß-thalassemia characteristics is a highly sought-after goal in the field of erythroid biology. In this study, we present the generation of erythroid progenitor lines with sickle cell disease and ß-thalassemia mutation using CRISPR/Cas9. The disease cellular models exhibit similar differentiation profiles, globin expression and proteome dynamics as patient-derived hematopoietic stem/progenitor cells. Additionally, these cellular models recapitulate pathological conditions associated with both the diseases. Hydroxyurea and pomalidomide treatment enhanced fetal hemoglobin levels. Notably, we introduce a therapeutic strategy for the above diseases by recapitulating the HPFH3 genotype, which reactivates fetal hemoglobin levels and rescues the disease phenotypes, thus making these lines a valuable platform for studying and developing new therapeutic strategies. Altogether, we demonstrate our disease cellular systems are physiologically relevant and could prove to be indispensable tools for disease modeling, drug screenings and cell and gene therapy-based applications.

[Society for Pediatric and Adolescent Rheumatology (GKJR) diagnosis and treatment optimization board-New ways to the diagnosis and treatment of complex diseases : An analysis after 2 years testing in practice]. / GKJR(Gesellschaft für Kinder- und Jugendrheumatologie)-Diagnose- und Therapieoptimierungsboard ­ neue Wege zu Diagnose und Therapie komplexer Erkrankungen : Eine Analyse nach 2 Jahren Praxistest.

With the diagnosis and treatment optimization board, the Society for Pediatric and Adolescent Rheumatology (GKJR) has developed a new format for expert-based discussion of rare and complex diseases. So far, 32 cases, predominantly from the areas of hyperinflammation, systemic lupus erythematosus, myositis and nonbacterial osteomyelitis, could be discussed in 8 conferences. The digital format enabled a high number of participants and the involvement of national and international experts. Rare diseases increasingly present modern medicine with challenges, which the GKJR meets with the new format.