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Abstract Purpose Pain and anxiety-inducing interventions have a major impact on pediatric patients. Pain reduction by virtual reality (VR) during port and vein punctures is well studied. This study investigates peri-interventional reduction of pain, anxiety and distress using VR compared to the standard of care (SOC) in a pediatric oncology outpatient clinic. Methods In a randomized, controlled cross-over design, patients aged 6–18 years experience potentially painful interventions accompanied by VR. Observational instruments include NRS, FPS-r, BAADS, mYPAS-SF, PedsQL and SSKJ3-8R. All patients undergo two observations: SOC (A) and VR (B) in a randomized order. In addition, parents and staff are interviewed. Specific conditions for VR in an outpatient clinic setting derived from interprofessional focus group discussion are being explored. Results Between July 2021 and December 2022 57 eligible patients were included and randomized to the orders A/B (n = 28) and B/A (n = 29). Thirty-eight patients completed both observations. Characteristics in both groups did not differ significantly. More than half of the patients had no previous experience with VR, 5% decided to discontinue VR prematurely. Peri-interventional pain, anxiety and distress were significantly reduced by VR compared with SOC. 71% of patients and 76% of parents perceived punctures with VR to be more relaxed than previous ones. 95% of patients perceived fun with VR goggles. Detailed questionnaires on individual stress and anxiety were returned from 26 of 38 patients. Focus group discussion with staff yielded evidence for successful implementation of VR in an outpatient clinic. Conclusions The present study shows that VR can be used for peri-interventional reduction of pain, anxiety, and distress in the special environment of a pediatric outpatient clinic. Specific conditions must be met for successful implementation. Further studies are needed to identify particularly susceptible patients and to illuminate alternatives for distraction that are feasible to implement with limited resources. Trial registration number (ClinicalTrials.gov ID): NCT06235723; 01/02/2024; retrospectively registered. This study adheres to the standard checklist of CONSORT guidelines.

Abstract Rational/Aims and Objectives Ward rounds are a core routine for interprofessional communication and clinical care planning: Health care professionals and patients meet regularly and it encourages patients to actively participate. In paediatric oncology, the long treatment process, the serious diagnosis, and involvement of both patients and their parents in shared-decision-making require specific ward round skills. Despite its high value for patient-centred care, a universal definition of ward round is lacking. Little is known about attitudes and expectations of different participants towards a ‘good’ ward round. This study aims to capture experiences and expectations of different stakeholders to better understand ward round needs in paediatric oncology and serve as a basis to improve future ward rounds. Method Semi-structured interviews were conducted with patients, parents, nurses and medical doctors of a paediatric oncology ward until theoretical saturation (13 interviews). A standardised qualitative analysis using the phenomenological framework defined by Colaizzi was used to identify important aspects in the interviews. Results Three major themes were identified in the interviews: [1] Structure and Organisation; [2] Communication; [3] Education. Further analysis revealed 23 categories and elucidated several opportunities and unmet needs recognized by stakeholders: Ward round functions in comforting families in stressful situations, and relationship building. Interviewees expressed their concerns about missing structures. Families pleaded for smaller ward round teams and layperson language. Health care professionals underscored the lack of ward round training. Paediatric patients stated that ward round scared them without proper explanation. All interviewees emphasized the need for professionalization of the ward round in the setting of paediatric oncology. Conclusion This study gives important insights into ward round functions and organisational requirements. It addresses special challenges for ward round participants in paediatric oncology, such as consideration of the emotional aspect of cancer treatment or the limits of shared decision making. Furthermore, this study underscores the great significance of ward rounds in paediatric oncology, with an emphasis on communication and relationship-building. Although performed universally, ward rounds are poorly explored or evaluated. This structured analysis synthesizes important expectations of different WR stakeholders, revealing opportunities of improvement and stressing the need for guidelines, training, and preparation.

Abstract Transcriptional regulators encoded by the Myocyte Enhancer Factor 2 (MEF2) gene family play a fundamental role in cardiac development, homeostasis and pathology. Previous studies indicate that MEF2A protein-protein interactions serve as a network hub in several cardiomyocyte cellular processes. Based on the idea that interactions with regulatory protein partners underly the diverse roles of MEF2A in cardiomyocyte gene expression, we undertook a systematic unbiased screen of the MEF2A protein interactome in primary cardiomyocytes using an affinity purification-based quantitative mass spectrometry approach. Bioinformatic processing of the MEF2A interactome revealed protein networks involved in the regulation of programmed cell death, inflammatory responses, actin dynamics and stress signaling in primary cardiomyocytes. Further biochemical and functional confirmation of specific protein-protein interactions documented a dynamic interaction between MEF2A and STAT3 proteins. Integration of transcriptome level data from MEF2A and STAT3-depleted cardiomyocytes reveals that the balance between MEF2A and STAT3 activity exerts a level of executive control over the inflammatory response and cardiomyocyte cell survival and experimentally ameliorates Phenylephrine induced cardiomyocyte hypertrophy. Lastly, we identified several MEF2A/STAT3 co-regulated genes, including the MMP9 gene. Herein, we document the cardiomyocyte MEF2A interactome, which furthers our understanding of protein networks involved in the hierarchical control of normal and pathophysiological cardiomyocyte gene expression in the mammalian heart.

Abstract Background and objective The diagnosis of rare diseases (RDs) is often challenging due to their rarity, variability and the high number of individual RDs, resulting in a delay in diagnosis with adverse effects for patients and healthcare systems. The development of computer assisted diagnostic decision support systems could help to improve these problems by supporting differential diagnosis and by prompting physicians to initiate the right diagnostic tests. Towards this end, we developed, trained and tested a machine learning model implemented as part of the software called Pain2D to classify four rare diseases (EDS, GBS, FSHD and PROMM), as well as a control group of unspecific chronic pain, from pen-and-paper pain drawings filled in by patients. Methods Pain drawings (PDs) were collected from patients suffering from one of the four RDs, or from unspecific chronic pain. The latter PDs were used as an outgroup in order to test how Pain2D handles more common pain causes. A total of 262 (59 EDS, 29 GBS, 35 FSHD, 89 PROMM, 50 unspecific chronic pain) PDs were collected and used to generate disease specific pain profiles. PDs were then classified by Pain2D in a leave-one-out-cross-validation approach. Results Pain2D was able to classify the four rare diseases with an accuracy of 61–77% with its binary classifier. EDS, GBS and FSHD were classified correctly by the Pain2D k-disease classifier with sensitivities between 63 and 86% and specificities between 81 and 89%. For PROMM, the k-disease classifier achieved a sensitivity of 51% and specificity of 90%. Conclusions Pain2D is a scalable, open-source tool that could potentially be trained for all diseases presenting with pain.

Summary: Messenger RNAs (mRNAs) in higher eukaryotes that encode proteins important for the assembly of the translational apparatus (e.g., ribosomal proteins) often harbor a pyrimidine-rich motif at the extreme 5′ end known as a 5′ terminal oligopyrimidine (5′TOP) sequence. Members of the La-related protein 1 (LARP1) family control 5′TOP expression through a conserved DM15 motif, but the mechanism is not well understood. 5′TOP motifs have not been described in many lower organisms, and fission yeast harbors a LARP1 homolog that also lacks a DM15 motif. In this work, we show that the fission yeast LARP1 homolog, Slr1p, controls the translation and stability of mRNAs encoding proteins analogous to 5′TOP mRNAs in higher eukaryotes, which we thus refer to as proto-5′TOPs. Our data suggest that the LARP1 DM15 motif and the mRNA 5′TOP motif may be features that were scaffolded over a more fundamental mechanism of LARP1-associated control of gene expression.

Abstract Mucopolysaccharidosis type I (MPS I) is an autosomal‐recessive metabolic disorder caused by an enzyme deficiency of lysosomal alpha‐l‐iduronidase (IDUA). Haematopoietic stem cell transplantation (HSCT) is the therapeutic option of choice in MPS I patients younger than 2.5 years, which has a positive impact on neurocognitive development. However, impaired growth remains a problem. In this monocentric study, 14 patients with MPS I (mean age 1.72 years, range 0.81–3.08) were monitored according to a standardised follow‐up program after successful allogeneic HSCT. A detailed anthropometric program was carried out to identify growth patterns and to determine predictors of growth in these children. All patients are alive and in outpatient care (mean follow‐up 8.1 years, range 0.1–16.0). Progressively lower standard deviation scores (SDS) were observed for body length (mean SDS −1.61; −4.58 – 3.29), weight (−0.56; −3.19 – 2.95), sitting height (−3.28; −7.37 – 0.26), leg length (−1.64; −3.88 – 1.49) and head circumference (0.91; −2.52 – 6.09). Already at the age of 24 months, significant disproportions were detected being associated with increasing deterioration in growth for age. Younger age at HSCT, lower counts for haemoglobin and platelets, lower potassium, higher donor‐derived chimerism, higher counts for leukocytes and recruitment of a matched unrelated donor (MUD) positively correlated with body length (p ≤ 0.05). In conclusion, this study characterised predictors and aspects of growth patterns in children with MPS I after HSCT, underlining that early HSCT of MUD is essential for slowing body disproportion.

There exists a remarkable evolutionary breadth of telomerase holoenzyme components among eukaryotes. Here the authors report that the fission yeast methyl phosphate capping enzyme Bin3/Bmc1 regulates telomerase activity by promoting holoenzyme formation.

Introduction: Mucopolysaccharidosis is a rare and congenital autosomal recessive lysosomal storage disorder of glycosaminoglycans. An enzyme defect leads to cell, tissue and organ dysfunction. Carpal tunnel syndrome and trigger finger are the results of mucopolysaccharid deposition.Material and methods: We are treating 6 patients with mucopolysaccharide associated trigger fingers in an interdisciplinary setting with the department of pediatric hematology and oncology at Hannover Medical School, where each patient is examined inter alia for symptoms of trigger finger annually.Besides an interview of the parents about abnormalities with regard to hand function, pain and/or neurologic symptoms the children are examined by palpation and by assessment of the active and passive range of finger motion.In the case of finger locking due to an impaired excursion of the flexor tendons in the A2 and A3 pulley region, we performed a trap-door incision technique for A2 pulley widening and a simple release of the A3 pulley.Results: In 6 patients 43 fingers were affected. The average age was 10 years. Pulley thickening was palpated in 19 fingers of to the left hand and 24 fingers of the right hand. In 7 fingers the A1 pulley was affected, in 28 fingers the A2 pulley and in 25 fingers the A3 pulley. The A4 and A5 pulley were not affected in any case. Trigger symptoms were seen in 13 fingers. Five of the 6 children were given an operation indication. In these cases we performed carpal tunnel release, release of Loge de Guyon, and trigger finger release, either in combination or alone. In all cases the procedure led to pain relief and functional improvement.Conclusion: The treatment of trigger fingers in children with mucopolysaccharidosis as a rare disease is challenging with regard to diagnostics and indication.The main treatment goal is pain relief and improvement of hand function.

Objective: During the early Covid 19 pandemic, undergraduate medical teaching of pediatric medicine had to be switched to online teaching at the Hanover Medical School (MHH). The aim was to develop an online module together with students.Methodology: In a multi-stage process, a working group consisting of lecturers and students developed the concept and implemented it. Afterwards the online module was evaluated.Results: The conceptualization process and the implementation of the module together with students can be represented as a modified PDCA cycle (Plan-Do-Check-Act). We showed that including students in the development of an online module is helpful in times of limited resources e.g. such as personnel and time.Conclusion: The cooperation between students and lecturers is suitable for developing and implementing an online module in a short time. In the future, in addition to joint conceptualization phases, digital elements (e.g. preparatory webinars) for the module itself in attendance phases should be retained.

BackgroundDiagnostic delay in rare disease (RD) is common, occasionally lasting up to more than 20 years. In attempting to reduce it, diagnostic support tools have been studied extensively. However, social platforms have not yet been used for systematic diagnostic support. This paper illustrates the development and prototypic application of a social network using scientifically developed questions to match individuals without a diagnosis. ObjectiveThe study aimed to outline, create, and evaluate a prototype tool (a social network platform named RarePairs), helping patients with undiagnosed RDs to find individuals with similar symptoms. The prototype includes a matching algorithm, bringing together individuals with similar disease burden in the lead-up to diagnosis. MethodsWe divided our project into 4 phases. In phase 1, we used known data and findings in the literature to understand and specify the context of use. In phase 2, we specified the user requirements. In phase 3, we designed a prototype based on the results of phases 1 and 2, as well as incorporating a state-of-the-art questionnaire with 53 items for recognizing an RD. Lastly, we evaluated this prototype with a data set of 973 questionnaires from individuals suffering from different RDs using 24 distance calculating methods. ResultsBased on a step-by-step construction process, the digital patient platform prototype, RarePairs, was developed. In order to match individuals with similar experiences, it uses answer patterns generated by a specifically designed questionnaire (Q53). A total of 973 questionnaires answered by patients with RDs were used to construct and test an artificial intelligence (AI) algorithm like the k-nearest neighbor search. With this, we found matches for every single one of the 973 records. The cross-validation of those matches showed that the algorithm outperforms random matching significantly. Statistically, for every data set the algorithm found at least one other record (match) with the same diagnosis. ConclusionsDiagnostic delay is torturous for patients without a diagnosis. Shortening the delay is important for both doctors and patients. Diagnostic support using AI can be promoted differently. The prototype of the social media platform RarePairs might be a low-threshold patient platform, and proved suitable to match and connect different individuals with comparable symptoms. This exchange promoted through RarePairs might be used to speed up the diagnostic process. Further studies include its evaluation in a prospective setting and implementation of RarePairs as a mobile phone app.

Background: Mucopolysaccharidosis type IIIA (MPS IIIA, Sanfilippo A syndrome) is a chronic progressive neurodegenerative storage disorder caused by a deficiency of lysosomal sulfamidase. The clinical hallmarks are sleep disturbances, behavioral abnormalities and loss of cognitive, speech and motor abilities. Affected children show developmental slowing from the second year of life, dementia occurs by the age of 5 years followed by death in the second decade of life. Only a few studies concerning HSCT in MPS IIIA have been published and do not document a clear benefit of treatment. Methods: The present study summarizes the clinical outcome of a girl with MPS IIIA who received HSCT at the age of 2.5 years. Her clinical course was compared with the natural history of six untreated MPS IIIA patients carrying the same mutations (p.R74C and p. R245H) in the SGSH-gene. Results: Eight years after successful HSCT, the patient showed a global developmental delay. However, cognitive abilities continued to develop, albeit very slowly. There was no sign of regression. She could talk in short sentences, had good motor abilities and performed basic daily living activities by herself. She did not present with sleeping problems, but behavioral abnormalities were profound. In contrast, the six untreated patients with identical mutations in the SGSH-gene showed the typical progressive course of disease with early and continuous loss of abilities. Conclusions: The present data suggest a beneficial effect of HSCT performed at an early stage of MPS IIIA on cognitive skills, motor function and quality of life.

Background Studies of the effects of electromagnetic fields (EMFs) on cartilaginous cells show a broad range of outcomes. However EMFs are not yet clinically applied as standard treatment of osteoarthritis, as EMF effects are showing varying outcomes in the literature. The aim of this study was to examine effects of EMFs (5 mT or 8 mT) on osteoarthritic (OA) and non-OA chondrocytes in order to investigate whether EMF effects are related to chondrocyte and EMF quality. Methods Pellets of human OA and non-OA chondrocytes were exposed to a sinusoidal 15 Hz EMF produced by a solenoid. Control groups were cultivated without EMF under standard conditions for 7 days. Cultures were examined by staining, immunohistochemistry and quantitative real-time PCR for RNA corresponding to cartilage specific proteins (COL2A1, ACAN, SOX9). Results OA chondrocytes increased the expression of COL2A1 and ACAN under 5 mT EMF compared to control. In contrast no changes in gene expression were observed in non-OA chondrocytes. OA and non-OA chondrocytes showed no significant changes in gene expression under 8 mT EMF. Conclusion A 5 mT EMF increased the expression of cartilage specific genes in OA chondrocytes whereas in non-OA chondrocytes no changes in gene expression were observed. An 8 mT EMF however showed no effect altogether. This suggests that EMF effects are related to EMF but also to chondrocyte quality. Further studies about the clinical relevance of this effect are necessary.

Abstract Myocyte Enhancer Factor 2 (MEF2) mediates cardiac remodelling in heart failure (HF) and is also a target of β-adrenergic signalling, a front-line treatment for HF. We identified global gene transcription networks involved in HF with and without β-blocker treatment. Experimental HF by transverse aortic constriction (TAC) in a MEF2 “sensor” mouse model (6 weeks) was followed by four weeks of β-blockade with Atenolol (AT) or Solvent (Sol) treatment. Transcriptome analysis (RNA-seq) from left ventricular RNA samples and MEF2A depleted cardiomyocytes was performed. AT treatment resulted in an overall improvement in cardiac function of TAC mice and repression of MEF2 activity. RNA-seq identified 65 differentially expressed genes (DEGs) due to TAC treatment with enriched GO clusters including the inflammatory system, cell migration and apoptosis. These genes were mapped against DEGs in cardiomyocytes in which MEF2A expression was suppressed. Of the 65 TAC mediated DEGs, AT reversed the expression of 28 mRNAs. Rarres2 was identified as a novel MEF2 target gene that is upregulated with TAC in vivo and isoproterenol treatment in vitro which may have implications in cardiomyocyte apoptosis and hypertrophy. These studies identify a cohort of genes with vast potential for disease diagnosis and therapeutic intervention in heart failure.

BackgroundRare diseases (RD) result in a wide variety of clinical presentations, and this creates a significant diagnostic challenge for health care professionals. We hypothesized that there exist a set of consistent and shared phenomena among all individuals affected by (different) RD during the time before diagnosis is established.ObjectiveWe aimed to identify commonalities between different RD and developed a machine learning diagnostic support tool for RD.Methods20 interviews with affected individuals with different RD, focusing on the time period before their diagnosis, were performed and qualitatively analyzed. Out of these pre-diagnostic experiences, we distilled key phenomena and created a questionnaire which was then distributed among individuals with the established diagnosis of i.) RD, ii.) other common non-rare diseases (NRO) iii.) common chronic diseases (CD), iv.), or psychosomatic/somatoform disorders (PSY). Finally, four combined single machine learning methods and a fusion algorithm were used to distinguish the different answer patterns of the questionnaires.ResultsThe questionnaire contained 53 questions. A total sum of 1763 questionnaires (758 RD, 149 CD, 48 PSY, 200 NRO, 34 healthy individuals and 574 not evaluable questionnaires) were collected. Based on 3 independent data sets the 10-fold stratified cross-validation method for the answer-pattern recognition resulted in sensitivity values of 88.9% to detect the answer pattern of a RD, 86.6% for NRO, 87.7% for CD and 84.2% for PSY.ConclusionDespite the great diversity in presentation and pathogenesis of each RD, patients with RD share surprisingly similar pre-diagnosis experiences. Our questionnaire and data-mining based approach successfully detected unique patterns in groups of individuals affected by a broad range of different rare diseases. Therefore, these results indicate distinct patterns that may be used for diagnostic support in RD.

BACKGROUND:Worldwide approximately 7,000 rare diseases have been identified. Accordingly, 4 million individuals live with a rare disease in Germany. The mean time to diagnosis is about 6 years and patients receive several incorrect diagnoses during this time. A multiplicity of factors renders diagnosing a rare disease extremely difficult. Detection of shared phenomena among individuals with different rare diseases could assist the diagnostic process. In order to explore the demand for diagnostic support and to obtain the commonalities among patients, a nationwide Delphi survey of centers for rare diseases and patient groups was conducted. METHODS:A two-step Delphi survey was conducted using web-based technologies in all centers for rare diseases in Germany. Moreover, the leading patient support group, the German foundation for rare diseases (ACHSE), was contacted to involve patients as experts in their disease. In the survey the experts were invited to name rare diseases with special need for diagnostic improvement. Secondly, communal experiences of affected individuals were collected. RESULTS:166 of 474 contacted experts (35%) participated in the first round of the Delphi process and 95 of 166 (57%) participated in the second round. Metabolic (n = 74) and autoimmune diseases (n = 39) were ranked the highest for need for diagnostic support. For three diseases (i.e. scleroderma, Pompe's disease, and pulmonary arterial hypertension), a crucial need for diagnostic support was explicitly stated. A typical experience of individuals with a rare disease was stigmatization of having psychological or psychosomatic problems. In addition, most experts endured an 'odyssey' of seeing many different medical specialists before a correct diagnosis (n = 38) was confirmed. CONCLUSION:There is need for improving the diagnostic process in individuals with rare diseases. Shared experiences in individuals with a rare disease were observed, which could possibly be utilized for diagnostic support in the future.

The aim of this research is to investigate the influence of oleic acid concentration on the cell growth and the physical properties of the polymer formed by cultures of Ralstonia eutropha in mineral medium. Cells were cultivated in Erlenmeyer flasks with 300 mL of mineral medium, containing glucose and fructose as a carbon source (30 g/L) and ammonium sulphate (5.0 g/L) as a nitrogen source. Oleic acid was added as nutritional supplement in different concentrations (0, 0.3, 0.9, 1.5 and 3.0 g/L) and the cells were incubated at 30 °C and 150 rpm. The films prepared by casting were evaluated by X-ray diffraction, thermogravimetry and differential scanning calorimetry. These results indicate that the increase of oleic acid concentrations leads to a higher specific growth rate and cell productivity. The characterization of the films revealed that the increase of the concentration of oleic acid from 0 to 1.5 g/L has no influence on thermal behaviour and crystallinity degree. However, the thermal stability, melting temperature, glass transition temperatures and crystallinity degree decreased when 3.0 g/L of oleic acid were used.

Clinical symptoms in children with pulmonary diseases are frequently non-specific. Rare diseases such as primary ciliary dyskinesia (PCD), cystic fibrosis (CF) or protracted bacterial bronchitis (PBB) can be easily missed at the general practitioner (GP).To develop and test a questionnaire-based and data mining-supported tool providing diagnostic support for selected pulmonary diseases.First, interviews with parents of affected children were conducted and analysed. These parental observations during the pre-diagnostic time formed the basis for a new questionnaire addressing the parents' view on the disease. Secondly, parents with a sick child (e.g. PCD, PBB) answered the questionnaire and a data base was set up. Finally, a computer program consisting of eight different classifiers (support vector machine (SVM), artificial neural network (ANN), fuzzy rule-based, random forest, logistic regression, linear discriminant analysis, naive Bayes and nearest neighbour) and an ensemble classifier was developed and trained to categorise any given new questionnaire and suggest a diagnosis. For estimating the diagnostic accuracy, we applied ten-fold stratified cross validation.All questionnaires of patients suffering from CF, asthma (AS), PCD, acute bronchitis (AB) and the healthy control group were correctly diagnosed by the fusion algorithm. For the pneumonia (PM) group 19/21 (90.5%) and for the PBB group 17/18 (94.4%) correct diagnoses could be reached. The program detected the correct diagnoses with an overall sensitivity of 98.8%. Receiver operating characteristics (ROC) analyses confirmed the accuracy of this diagnostic tool. Case studies highlighted the applicability of the tool in the daily work of a GP.For children with symptoms of pulmonary diseases a questionnaire-based diagnostic support tool using data mining techniques exhibited good results in arriving at diagnostic suggestions. In the hands of a doctor, this tool could be of value in arousing awareness for rare pulmonary diseases such as PCD or CF.

The genomes of plus-strand RNA viruses contain many regulatory sequences and structures that direct different viral processes. The traditional view of these RNA elements are as local structures present in non-coding regions. However, this view is changing due to the discovery of regulatory elements in coding regions and functional long-range intra-genomic base pairing interactions. The ∼4.8 kb long RNA genome of the tombusvirus tomato bushy stunt virus (TBSV) contains these types of structural features, including six different functional long-distance interactions. We hypothesized that to achieve these multiple interactions this viral genome must utilize a large-scale organizational strategy and, accordingly, we sought to assess the global conformation of the entire TBSV genome. Atomic force micrographs of the genome indicated a mostly condensed structure composed of interconnected protrusions extending from a central hub. This configuration was consistent with the genomic secondary structure model generated using high-throughput selective 2'-hydroxyl acylation analysed by primer extension (i.e. SHAPE), which predicted different sized RNA domains originating from a central region. Known RNA elements were identified in both domain and inter-domain regions, and novel structural features were predicted and functionally confirmed. Interestingly, only two of the six long-range interactions known to form were present in the structural model. However, for those interactions that did not form, complementary partner sequences were positioned relatively close to each other in the structure, suggesting that the secondary structure level of viral genome structure could provide a basic scaffold for the formation of different long-range interactions. The higher-order structural model for the TBSV RNA genome provides a snapshot of the complex framework that allows multiple functional components to operate in concert within a confined context.

In our recent study, tissue proteomic analysis of oral pre-malignant lesions (OPLs) and normal oral mucosa led to the identification of a panel of biomarkers, including prothymosin alpha (PTMA), to distinguish OPLs from histologically normal oral tissues. This study aimed to determine the clinical significance of PTMA overexpression in oral squamous cell hyperplasia, dysplasia and head and neck squamous cell carcinoma (HNSCC).Immunohistochemistry of PTMA protein was performed in HNSCCs (n = 100), squamous cell hyperplasia (n = 116), dysplasia (n = 50) and histologically normal oral tissues (n = 100). Statistical analysis was carried out to determine the association of PTMA overexpression with clinicopathological parameters and disease prognosis over 7 years for HNSCC patients.Our immunohistochemical analysis demonstrated significant overexpression of nuclear PTMA in squamous cell hyperplasia (63.8%), dysplasia (50%) and HNSCC (61%) in comparison with oral normal mucosa (p(trend)