Preservation of epidermal melanocyte integrity in an ex vivo co-culture skin model with sebocytes.

A direct contact co-culture of skin explants to SZ95 sebocytes (3D-SeboSkin) has been shown to preserve the integrity of epidermal keratinocytes and dermis. In this study, the properties of epidermal melanocytes were evaluated in the same 3D SeboSkin ex vivo model. Skin explants (n = 6) were maintained in the 3D-SeboSkin model, in direct contact to fibroblasts and alone in serum-free medium (SFM). Histopathological, immunohistochemical, apoptosis and oil red staining evaluations were performed at Days 0 and 6 of incubation. Results revealed preservation and prominent proliferation of basal keratinocytes of the skin explants in addition to preservation of dermal collagen and vasculature at Day 6 in the 3D-SeboSkin culture model and to a lesser extent in co-culture with fibroblasts but not in SFM alone. Melan-A+/Ki67- epidermal melanocytes remained attached to the dermis even at sites of epidermal detachment in the three skin explant models tested. However, the number of epidermal melanocytes was significantly conserved in 3D-SeboSkin cultures in comparison with skin explants in SFM (p < 0.05), whereas no difference was found in comparison with the co-culture with fibroblasts. Few DAPI/TUNEL+ apoptotic melanocytes could mostly be observed in SFM-incubated skin explants. Furthermore, only SZ95 sebocytes in contact to skin explants in 3D-SeboSkin exhibited increased lipogenesis with accumulation of abundant lipid droplets. These results denote that the 3D-SeboSkin model yielded significant preservation of epidermal melanocytes and hence it is optimal for ex vivo studies of abnormalities of skin pigmentation, melanocyte neoplasms and effects of different hormones, cytokines, carcinogens and various therapeutics in a pattern that recapitulates the in vivo environment.

Effect of dietary supplementation of alpha-galactosidase on the growth performance, ileal digestibility, intestinal morphology, and biochemical parameters in broiler chickens.

BACKGROUND: This study was performed to investigate the effect of Alpha-galactosidase (AlphaGal) supplementation with two energy levels on the growth performance, amino acid ileal digestibility coefficient "AID%," economic value, intestinal histology, and blood biochemical parameters of broiler chickens. Two-hundred 3-day-old broiler chicks (average body weight 74.34 g ±0.52 Ross 308) were randomly assigned to a 2 × 2 factorial arrangement consisting of two energy diets groups: in the first group, the birds were fed on a recommended energy diet (RED) while the second group was reduced 120 kcal/kg diet as a low energy diet (LED) and two levels of AlphaGal (0 or 50 mg/kg diet) for RED and LED for the 35-day feeding period. RESULTS: The interaction effects between the energy level and the AlphaGal supplementations resulted in significant decrease (P ≤ 0.05) in the body weight, body weight gain, and the relative growth rate. The feed conversion ratio was signficantly increased in LED without supplementation of AlphaGal group during the entire experimental period, this negative effect on the growth performance was corrected by AlphaGal supplementation. The AID% value was increased significantly by AlphaGal supplementation. Blood triglyceride concentrations were significantly decreased (P = 0.02) in the LED group with or without AlphaGal supplementation, while the level of high-density lipoprotein (HDL) was significantly decreased (P = 0.01) in the LED or RED groups supplemented with 50 mg RED AlphaGal. Histologically, the number of intestinal glands and goblet cells increased in both RED and LED groups supplemented with AlphaGal and their secretions were mainly neutral mucopolysaccharides and less acidic mucopolysaccharides. CONCLUSION: AlphaGal supplementation improved the growth performance of broiler chickens fed LED and the growth performance is similar to those fed RED, thereby consequently improving the economic value of these diets. AlphaGal supplementation improves intestinal histology and morphology as well.

Breast Tumor Diagnosis Using Finite-Element Modeling Based on Clinical in vivo Elastographic Data.

OBJECTIVES: This study exploited finite-element modeling (FEM) to simulate breast tissue multicompression during ultrasound elastography to classify breast tumors based on their nonlinear biomechanical properties. METHODS: Numeric simulations were first calculated by using 3-dimensional (3D) virtual models with an assumed tumor's geometric dimensions but with actual material properties to test and validate the FEM. Further numeric simulations were used to construct 3D models based on in vivo experimental data to verify our models. The models were designed for each individual in vivo case, emphasizing the geometry, position, and biomechanical properties of the breast tissue. At different compression levels, tissue strains were analyzed between the tumors and the background normal tissues to explore their nonlinearity and classify the tumor type. Tumor classification parameters were deduced by using a power-law relationship between the applied compressive forces and strain differences. RESULTS: Classification parameters were compared between benign and malignant tumors, for which they were found to be statistically significant in classifying the tumor types (P < .05) by both the validation and verification of FEM. We compared the classification parameters between the in vivo and FEM classifications, for which they were found to be strongly correlated (R = 0.875; P < .001), with no statistical differences between their outcomes (P = .909). CONCLUSIONS: Good agreement between the model outcomes and the in vivo diagnostics was reported. The implemented models were validated and verified. The introduced 3D modeling method may augment elastographic methods to preliminary classify breast tumors at an early stage.

Healthcare providers' perspectives on family presence during resuscitation in the emergency departments of the Kingdom of Bahrain.

BACKGROUND: Worldwide, policies exist on family presence during resuscitation (FPDR), however, this is still lacking in the Gulf Corporation Countries (GCC) in general and in the Kingdom of Bahrain in particular. The aim of this study is to assess the perspectives of healthcare providers (HP) on FPDR among those working in the emergency departments (EDs) in the Kingdom. METHODS: A self-administered anonymous electronic survey was collected from 146 HPs (emergency physicians and nurses) working in the three major EDs in the Kingdom of Bahrain. Besides demographic data, 18 items measuring HPs' perceptions of FPDR were generated using the 5-point Likert scale. RESULTS: Surveys (n = 146) from physicians and nurses were analysed (45.9% vs. 54.1%, respectively). There were significant differences between physicians and nurses in terms of personal beliefs, FPDR enhancing professional satisfaction and behaviour, and the importance of a support person and saying goodbye (p < 0.001). However, general responses demonstrated that the majority of HPs encouraged and supported FPDR, but with greater support from physicians than nurses. CONCLUSION: The study reflects that many HPs in EDs participated in and are familiar with FPDR, with the majority of ED physicians supporting it. Further studies should investigate the reasons for the lack of support from nurses. Results may contribute to the development of hospital ED policies that allow FPDR in the region.

Adipose tissue, fillers, and skin tightening.

The role of adipose tissue has long been underestimated in esthetic dermatology. With the development of liposculpture and lipolysis, subcutaneous adipose tissue has gained an increasing interest. Harvested tissue has been used for lipofilling. In recent years, a better understanding of adipocyte physiology and its role in aging opened a new road for targeted treatments. Subcutaneous adipose tissue is no longer an innocent bystander in the combat of aging and the correction in esthetics. Adipose tissue is of importance for metabolic function and thermoregulation. Adipose tissue is involved in inflammation. Adipose tissue is heterogeneous in sense of function, color and size of adipocytes. The tissue is an important source of somatic stem cells.

Schistosomiasis (bilharziasis) and male infertility.

Schistosomiasis (bilharziasis) is an endemic parasitic disease of a major source of morbidity and mortality for developing countries. It is caused by different species of blood flukes (trematode worms) of the genus Schistosoma, the most important of which are S. haematobium which infests the genitourinary tract and S. mansoni and S. japonicum which infest the gastrointestinal tract. The incidence of schistosome-induced male infertility is not known and probably underestimated being overshadowed by the more severe and often fatal urinary and gastrointestinal complications. Several causes may contribute to schistosomiasis-induced male infertility, such as hormonal imbalance, testicular tissue damage and genital ductal system obstruction, in addition to decreased libido and erectile dysfunction due to associated hormonal imbalance and prostatic infestation. Demonstration of the schistosome ova in seminal plasma or testicular tissue confirms the diagnosis. Treatment of schistosomiasis-induced male infertility depends on clinical evaluation and includes, besides anthelmintic treatment, hormonal replacement and assisted reproduction (IVF/ICSI) in cases of severe oligozoospermia and or obstructive and nonobstructive azoospermia.

Time-resolved diffuse optical tomography system using an accelerated inverse problem solver.

A computationally efficient time-resolved diffuse optical tomography (TR-DOT) prototype was demonstrated using an accelerated inverse problem solver to reconstruct high quality 3D images of highly scattering media such as tissues. The inverse problem solver utilizes seven well-defined points on each experimentally recorded histogram of the distribution time-of-flight (DToF). In this work, the accuracy of the recovered optical properties, and the computational load and time of TR-DOT prototype were investigated using cylindrical turbid phantoms. These phantoms were measured using transmittance geometry under different conditions in multiple experiments to evaluate the performance of this prototype. Overall, the results of evaluation are important in the realization of a real-time and highly accurate TR-DOT system for diffuse optical imaging applications.

Surgical Treatment for Extramammary Paget's Disease.

OPINION STATEMENT: Extramammary Paget's disease (EMPD) is a rare, slow growing non-melanoma skin cancer.Diagnosis is often significantly delayed, since clinical presentation may resemble common benign dermatoses. Treatment is characterized by high recurrence rates. This is in part due to ill-defined margins and by frequent development of satellites. Improvement of outcome needs a better preoperative planning with fluorescence diagnostics or scouting biopsies. Mohs micrographic surgery has some advantages for patients, such as reduced relapse rates and prolonged relapse-free survival. Improved identification of Paget cells in cryosections by immunostainings or alternatively the use of delayed Mohs with formalin-fixed material reduces the rate of false-negative results. Surgery remains the cornerstone of treatment.

Schistosomiasis (Bilharziasis) ova: An incidental finding in testicular tissue of an obstructive azoospermic man.

Congenital bilateral absence of vas deferens (CBAVD) results in obstructive azoospermia in which testicular function, such as spermatogenesis, is preserved. Bilateral testicular biopsy is not only diagnostic but also therapeutic as retrieved spermatozoa are usually cryopreserved for assisted reproduction. In this case report, CBAVD was confirmed in a 24-year-old azoospermic man on the basis of persistent azoospermia associated with low semen volume, absent fructose and normal hormonal levels, ultrasonographically (absent seminal vesicles) and histologically (intact spermatogenesis). Interestingly and incidentally, only the right testicular biopsy showed ova of two parasitic species of Schistosoma, namely Schistosoma haematobium which infests the genitourinary tract and Schistosoma mansoni which infests the gastrointestinal tract. Both species are rare causes of azoospermia, and the case should be further managed as CBAVD in which the left testicle is considered the preferred site of sperm retrieval for assisted reproduction.

Skin manifestations of growth hormone-induced diseases.

The human skin is a well-organized organ bearing different types of cells in a well-structured interference to each other including epidermal and follicular keratinocytes, sebocytes, melanocytes, dermal papilla cells and fibroblasts, endothelial cells, sweat gland cells as well as nerves. Several hormones act on different cell types of the skin, while it is also considered an endocrine organ secreting hormones that act at several sites of the organism. GH receptors are found in almost all cell types forming the skin, while IGF-1 receptors' expression is restricted to the epidermal keratinocytes. Both Growth Hormone (GH) excess, as in the case of Acromegaly in adults, or Gigantism in growing children, and GH deficiency states lead to skin manifestations. In case of GH excess the main dermatological findings are skin thickening, coarsening of facial features, acrochordons, puffy hands and feet, oily skin and hyperhidrosis, while GH deficiency, on the contrary, is characterized by thin, dry skin and disorder of normal sweating. Moreover, special disorders associated with GH excess may have specific characteristics, as is the case of café-au-lait spots in Neurofibromatosis, or big café-au-lait skin hyperpigmented regions with irregular margins, as is the case in McCune-Albright syndrome. Meticulous examination of the skin may therefore contribute to the final diagnosis in cases of GH-induced disorders.

Increased Activity and Number of Epidermal Melanocytes in Lesional Psoriatic Skin.

BACKGROUND: Psoriatic lesions may resolve with hypo- or hyperpigmentation. The involvement of melanocytes in this dichotomous clinical outcome is not fully investigated. OBJECTIVES: Qualitative and quantitative assessment of melanocytes in untreated lesional and non-lesional psoriatic skin (n = 15) and healthy controls (n = 10). METHODS: Skin biopsies were labelled immunohistochemically (APAAP technique) with the antimelanocyte monoclonal antibodies (MoAbs) HMB45, Melan A, tyrosinase and microphthalmia-associated transcription factor (MITF). The labelled melanocytes were evaluated by an independent investigator with a digital image analyser. RESULTS: Lesional melanocytes, in contrast to those in non-lesional and healthy skin, exhibited features of activation in the form of dilatation, prominent and long dendrites and intense labelling. The number of melanocytes was significantly increased in psoriatic lesions in comparison with non-lesional psoriatic and healthy skin as shown by counts of cells labelled with the MoAbs HMB45 (3-fold; p < 0.001), Melan A (1.6-fold; p < 0.01) and tyrosinase (1.5-fold; p < 0.01). In contrast, labelling with MITF revealed no significant difference (1.2-fold increase; p > 0.05). Likewise, no significant difference between non-lesional psoriatic and healthy skin control was found (p > 0.05). Furthermore, no positively labelled dermal cells were detected, apart from few only detected with Melan A. CONCLUSIONS: Epidermal melanocyte activity and numbers are increased in the epidermal compartment of psoriatic lesions providing an explanation for postinflammatory hyperpigmentation.

Biodegradable suture development-based albumin composites for tissue engineering applications.

Recent advancements in the field of biomedical engineering have underscored the pivotal role of biodegradable materials in addressing the challenges associated with tissue regeneration therapies. The spectrum of biodegradable materials presently encompasses ceramics, polymers, metals, and composites, each offering distinct advantages for the replacement or repair of compromised human tissues. Despite their utility, these biomaterials are not devoid of limitations, with issues such as suboptimal tissue integration, potential cytotoxicity, and mechanical mismatch (stress shielding) emerging as significant concerns. To mitigate these drawbacks, our research collective has embarked on the development of protein-based composite materials, showcasing enhanced biodegradability and biocompatibility. This study is dedicated to the elaboration and characterization of an innovative suture fabricated from human serum albumin through an extrusion methodology. Employing a suite of analytical techniques-namely tensile testing, scanning electron microscopy (SEM), and thermal gravimetric analysis (TGA)-we endeavored to elucidate the physicochemical attributes of the engineered suture. Additionally, the investigation extends to assessing the influence of integrating biodegradable organic modifiers on the suture's mechanical performance. Preliminary tensile testing has delineated the mechanical profile of the Filament Suture (FS), delineating tensile strengths spanning 1.3 to 9.616 MPa and elongation at break percentages ranging from 11.5 to 146.64%. These findings illuminate the mechanical versatility of the suture, hinting at its applicability across a broad spectrum of medical interventions. Subsequent analyses via SEM and TGA are anticipated to further delineate the suture's morphological features and thermal resilience, thereby enriching our comprehension of its overall performance characteristics. Moreover, the investigation delves into the ramifications of incorporating biodegradable organic constituents on the suture's mechanical integrity. Collectively, the study not only sheds light on the mechanical and thermal dynamics of a novel suture material derived from human serum albumin but also explores the prospective enhancements afforded by the amalgamation of biodegradable organic compounds, thereby broadening the horizon for future biomedical applications.

A Novel PTRH2 Gene Mutation Causing Infantile-onset Multisystem Neurologic, Endocrine, and Pancreatic Disease in a Bahraini Patient.

Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) is a rare autosomal recessive multisystemic disease with a prevalence of < 1/1 000 000. The wide spectrum of symptoms and associated diseases makes the diagnosis of this disease particularly challenging. Here, we report a 12-year-old Bahraini male who presented with the core clinical features of IMNEPD including intellectual disability, global developmental delay, sensorineural hearing loss, endocrine dysfunction, and exocrine pancreatic insufficiency. The diagnosis was confirmed by genetic testing using whole exome sequencing. This is the first reported case of IMNEPD from Bahrain and was found to have a novel homozygous peptidyl-tRNA hydrolase 2 (PTRH2) gene mutation (NM_001015509.2: c.370del p.(Glu124Lysfs*4)). Moreover, we conducted an extensive literature review with an emphasis on the variable clinical spectrum and genotypes of previously reported patients in comparison to our case.

Does Speckle Tracking Transthoracic Echocardiography Indicate Subtle Changes in Left Ventricular Function in Heart Failure Patients with Reduced Ejection Fraction Treated by Sacubitril-valsartan?

Background: In heart failure patients and reduced ejection fraction (HFrEF), assessing subtle changes in left ventricle (LV) function is crucial for monitoring treatment efficacy. This study aims to determine the effect of valsartan/sacubitril on LV ejection fraction (EF) assessed by two-dimensional (2D) transthoracic echocardiography (TTE) in comparison to that assessed by 2D TTE speckle tracking in patients with HFrEF ≤35% after 6 months of treatment. Patients and Methods: A prospective study will be conducted on 200 heart failure patients with reduced EF (HFrEF) undergoing sacubitril-valsartan treatment. Each participant underwent a comprehensive evaluation, including physical examination, history taking, serial 12-lead electrocardiogram, and 2D echo to evaluate cardiac parameters. In addition, 2D speckle tracking echocardiography (STE) assessments were conducted before and after 6 months of valsartan/sacubitril treatment. Results: The enrolled patients had an average age of 48 years with 63% females. At the beginning of the study, 9 (4.5%) patients were classified as New York Heart Association (NYHA) FC I, 120 (60%) as NYHA FC II, 64 (32%) as NYHA FC III, and 7 (3.5%) as FC IV. Following treatment, 82 (41%) patients improved to NYHA FC I, and 118 (59%) were in NYHA FC II. Notably, 82 (41%) patients showed improved left ventricular EF (LVEF), detected either by traditional TTE or STE, whereas 118 (59%) showed no improvement in EF through traditional TTE. In addition, 74 (37%) patients demonstrated improvement detected by STE. In contrast, 44 (22%) patients demonstrated no improvement in EF detected by either TTE or STE. Conclusion: STE was a more reliable diagnostic method for seeing early LVEF improvement in patients with HFrEF receiving valsartan/sacubitril treatment not seen by conventional TTE.

Artificial intelligence uncertainty quantification in radiotherapy applications - A scoping review.

BACKGROUND/PURPOSE: The use of artificial intelligence (AI) in radiotherapy (RT) is expanding rapidly. However, there exists a notable lack of clinician trust in AI models, underscoring the need for effective uncertainty quantification (UQ) methods. The purpose of this study was to scope existing literature related to UQ in RT, identify areas of improvement, and determine future directions. METHODS: We followed the PRISMA-ScR scoping review reporting guidelines. We utilized the population (human cancer patients), concept (utilization of AI UQ), context (radiotherapy applications) framework to structure our search and screening process. We conducted a systematic search spanning seven databases, supplemented by manual curation, up to January 2024. Our search yielded a total of 8980 articles for initial review. Manuscript screening and data extraction was performed in Covidence. Data extraction categories included general study characteristics, RT characteristics, AI characteristics, and UQ characteristics. RESULTS: We identified 56 articles published from 2015 to 2024. 10 domains of RT applications were represented; most studies evaluated auto-contouring (50 %), followed by image-synthesis (13 %), and multiple applications simultaneously (11 %). 12 disease sites were represented, with head and neck cancer being the most common disease site independent of application space (32 %). Imaging data was used in 91 % of studies, while only 13 % incorporated RT dose information. Most studies focused on failure detection as the main application of UQ (60 %), with Monte Carlo dropout being the most commonly implemented UQ method (32 %) followed by ensembling (16 %). 55 % of studies did not share code or datasets. CONCLUSION: Our review revealed a lack of diversity in UQ for RT applications beyond auto-contouring. Moreover, we identified a clear need to study additional UQ methods, such as conformal prediction. Our results may incentivize the development of guidelines for reporting and implementation of UQ in RT.

Longitudinal changes in the carotid arteries of head and neck cancer patients following radiation therapy: Results from a prospective serial imaging biomarker characterization study.

INTRODUCTION: We prospectively evaluated morphologic and functional changes in the carotid arteries of patients treated with unilateral neck radiation therapy (RT) for head and neck cancer. METHODS: Bilateral carotid artery duplex studies were performed at 0, 3, 6, 12, 18 months and 2, 3, 4, and 5 years following RT. Intima media thickness (IMT); global and regional circumferential, as well as radial strain, arterial elasticity, stiffness, and distensibility were calculated. RESULTS: Thirty-eight patients were included. A significant difference in the IMT from baseline between irradiated and unirradiated carotid arteries was detected at 18 months (median, 0.073 mm vs -0.003 mm; P = 0.014), which increased at 3 and 4 years (0.128 mm vs 0.013 mm, P = 0.016, and 0.177 mm vs 0.023 mm, P = 0.0002, respectively). A significant transient change was noted in global circumferential strain between the irradiated and unirradiated arteries at 6 months (median difference, -0.89, P = 0.023), which did not persist. No significant differences were detected in the other measures of elasticity, stiffness, and distensibility. CONCLUSIONS: Functional and morphologic changes of the carotid arteries detected by carotid ultrasound, such as changes in global circumferential strain at 6 months and carotid IMT at 18 months, may be useful for the early detection of radiation-induced carotid artery injury, can guide future research aiming to mitigate carotid artery stenosis, and should be considered for clinical surveillance survivorship recommendations after head and neck RT.

Artificial Intelligence Uncertainty Quantification in Radiotherapy Applications - A Scoping Review.

Background/purpose: The use of artificial intelligence (AI) in radiotherapy (RT) is expanding rapidly. However, there exists a notable lack of clinician trust in AI models, underscoring the need for effective uncertainty quantification (UQ) methods. The purpose of this study was to scope existing literature related to UQ in RT, identify areas of improvement, and determine future directions. Methods: We followed the PRISMA-ScR scoping review reporting guidelines. We utilized the population (human cancer patients), concept (utilization of AI UQ), context (radiotherapy applications) framework to structure our search and screening process. We conducted a systematic search spanning seven databases, supplemented by manual curation, up to January 2024. Our search yielded a total of 8980 articles for initial review. Manuscript screening and data extraction was performed in Covidence. Data extraction categories included general study characteristics, RT characteristics, AI characteristics, and UQ characteristics. Results: We identified 56 articles published from 2015-2024. 10 domains of RT applications were represented; most studies evaluated auto-contouring (50%), followed by image-synthesis (13%), and multiple applications simultaneously (11%). 12 disease sites were represented, with head and neck cancer being the most common disease site independent of application space (32%). Imaging data was used in 91% of studies, while only 13% incorporated RT dose information. Most studies focused on failure detection as the main application of UQ (60%), with Monte Carlo dropout being the most commonly implemented UQ method (32%) followed by ensembling (16%). 55% of studies did not share code or datasets. Conclusion: Our review revealed a lack of diversity in UQ for RT applications beyond auto-contouring. Moreover, there was a clear need to study additional UQ methods, such as conformal prediction. Our results may incentivize the development of guidelines for reporting and implementation of UQ in RT.

Application of simultaneous uncertainty quantification and segmentation for oropharyngeal cancer use-case with Bayesian deep learning.

BACKGROUND: Radiotherapy is a core treatment modality for oropharyngeal cancer (OPC), where the primary gross tumor volume (GTVp) is manually segmented with high interobserver variability. This calls for reliable and trustworthy automated tools in clinician workflow. Therefore, accurate uncertainty quantification and its downstream utilization is critical. METHODS: Here we propose uncertainty-aware deep learning for OPC GTVp segmentation, and illustrate the utility of uncertainty in multiple applications. We examine two Bayesian deep learning (BDL) models and eight uncertainty measures, and utilize a large multi-institute dataset of 292 PET/CT scans to systematically analyze our approach. RESULTS: We show that our uncertainty-based approach accurately predicts the quality of the deep learning segmentation in 86.6% of cases, identifies low performance cases for semi-automated correction, and visualizes regions of the scans where the segmentations likely fail. CONCLUSIONS: Our BDL-based analysis provides a first-step towards more widespread implementation of uncertainty quantification in OPC GTVp segmentation.

Radiotherapy is used as a treatment for people with oropharyngeal cancer. It is important to distinguish the areas where cancer is present so the radiotherapy treatment can be targeted at the cancer. Computational methods based on artificial intelligence can automate this task but need to be able to distinguish areas where it is unclear whether cancer is present. In this study we compare these computational methods that are able to highlight areas where it is unclear whether or not cancer is present. Our approach accurately predicts how well these areas are distinguished by the models. Our results could be applied to improve the computational methods used during radiotherapy treatment. This could enable more targeted treatment to be used in the future, which could result in better outcomes for people with oropharyngeal cancer.

Multi-modal segmentation with missing image data for automatic delineation of gross tumor volumes in head and neck cancers.

BACKGROUND: Head and neck (HN) gross tumor volume (GTV) auto-segmentation is challenging due to the morphological complexity and low image contrast of targets. Multi-modality images, including computed tomography (CT) and positron emission tomography (PET), are used in the routine clinic to assist radiation oncologists for accurate GTV delineation. However, the availability of PET imaging may not always be guaranteed. PURPOSE: To develop a deep learning segmentation framework for automated GTV delineation of HN cancers using a combination of PET/CT images, while addressing the challenge of missing PET data. METHODS: Two datasets were included for this study: Dataset I: 524 (training) and 359 (testing) oropharyngeal cancer patients from different institutions with their PET/CT pairs provided by the HECKTOR Challenge; Dataset II: 90 HN patients(testing) from a local institution with their planning CT, PET/CT pairs. To handle potentially missing PET images, a model training strategy named the "Blank Channel" method was implemented. To simulate the absence of a PET image, a blank array with the same dimensions as the CT image was generated to meet the dual-channel input requirement of the deep learning model. During the model training process, the model was randomly presented with either a real PET/CT pair or a blank/CT pair. This allowed the model to learn the relationship between the CT image and the corresponding GTV delineation based on available modalities. As a result, our model had the ability to handle flexible inputs during prediction, making it suitable for cases where PET images are missing. To evaluate the performance of our proposed model, we trained it using training patients from Dataset I and tested it with Dataset II. We compared our model (Model 1) with two other models which were trained for specific modality segmentations: Model 2 trained with only CT images, and Model 3 trained with real PET/CT pairs. The performance of the models was evaluated using quantitative metrics, including Dice similarity coefficient (DSC), mean surface distance (MSD), and 95% Hausdorff Distance (HD95). In addition, we evaluated our Model 1 and Model 3 using the 359 test cases in Dataset I. RESULTS: Our proposed model(Model 1) achieved promising results for GTV auto-segmentation using PET/CT images, with the flexibility of missing PET images. Specifically, when assessed with only CT images in Dataset II, Model 1 achieved DSC of 0.56 ± 0.16, MSD of 3.4 ± 2.1 mm, and HD95 of 13.9 ± 7.6 mm. When the PET images were included, the performance of our model was improved to DSC of 0.62 ± 0.14, MSD of 2.8 ± 1.7 mm, and HD95 of 10.5 ± 6.5 mm. These results are comparable to those achieved by Model 2 and Model 3, illustrating Model 1's effectiveness in utilizing flexible input modalities. Further analysis using the test dataset from Dataset I showed that Model 1 achieved an average DSC of 0.77, surpassing the overall average DSC of 0.72 among all participants in the HECKTOR Challenge. CONCLUSIONS: We successfully refined a multi-modal segmentation tool for accurate GTV delineation for HN cancer. Our method addressed the issue of missing PET images by allowing flexible data input, thereby providing a practical solution for clinical settings where access to PET imaging may be limited.