Rare Group Research Articles

Chromosome-level genome assembly of the cave leech Sinospelaeobdella cavatuses (Hirudinea: Haemadipsidae).

Leeches are famous for their high medical value and wide environmental adaptability. Among them, cave leeches are a very fascinating and rare group, which is an important component in the study of adaptive evolution of leeches. However, no study has yet reported a reference genome for this group. In this study, we assembled a high-quality chromosome-level genome of the cave terrestrial leech Sinospelaeobdella cavatuses, through Illumina and PacBio sequencing, alongside chromosome conformation capture techniques. The resulting genome spans 153.67 Mb across 9 pseudochromosomes(range: 11.33 to 23.53 Mb), with a mounting rate of up to 95.37% and features an N50 length of 17.15 Mb. This genome is composed of 35.16% repetitive elements and contains 21180 predicted protein-coding genes. Decoding the S. cavatuses genome not only promotes future studies on study of its phylogeny, evolution, and behavior, but also provides valuable resources for in-depth investigation on adaptive evolution of leech.

Electrical burns in train climbers treated in the Helsinki Burn Centre during the last 30years.

Patients who climb onto the roof of a stationary train carriage and sustain a high voltage electrical injury from the overhead cables represent a rare type of electrical injury. The aim of this study was to review all the electrical burns and their outcomes in train climbers treated in the Helsinki Burn Centre during the last three decades. 18 patients who had climbed onto the roof of a stationary electric train between November 1993 and December 2022 were included. Trauma- and outcome-related variables were collected. The primary outcome endpoints were in-hospital mortality and major amputations. 16 (88.9%) patients were male. The median age was 15.5years (range: 13-29years). All the burns were high-voltage electrical burns. The mean burn size was 45% of the total body surface area. Three (16.7%) patients died in hospital. The mean length of the Burn Centre stay was 50days. On average, the patients underwent 5 operations (range: 0-32) during their inpatient stay. Three patients required major amputation. Eight of the patients underwent late operations. Seven (38.9%) patients exhibited late neurological dysfunction or neuropsychological symptoms at long term follow-up. In conclusion, train climbers represent a rare group of young patients with electrical burns. Precautionary strategies should be implemented to prevent these injuries that are associated with high morbidity and mortality.

Surgical management of a large cystic trochlear nerve schwannoma mimicking a brainstem glioma: a case report

IntroductionIntracranial schwannomas represent a rare group of intracranial tumors, with purely motor nerve schwannomas being the rarest of them. The anatomical proximity of these tumors to the brainstem may present a radiological challenge in differentiating them from intra–axial brainstem tumors, which can influence further decision–making and treatment options.MethodsWe report on a 47–year–old male patient who was diagnosed with a large cystic intracranial tumor with radiological features suggestive of an intrinsic brainstem glioma.ResultsAfter discussing treatment options and risks based on a presumed radiological diagnosis, microsurgical treatment via lateral–suboccipital craniotomy in semi–sitting position, under continuous intraoperative neuromonitoring was performed. Intraoperative findings proved that the tumor was an extra–axial schwannoma originating from the left trochlear nerve. Gross total removal of the lesion was achieved.ConclusionDue to their rarity, non–specific symptoms and the possibility to mimicking intra–axial brainstem tumors on imaging, these tumors may present a diagnostic challenge and should be taken into account during treatment decision-making.

Biallelic variants in CCN2 underlie an autosomal recessive kyphomelic dysplasia.

Kyphomelic dysplasia is a rare heterogenous group of skeletal dysplasia, characterized by bowing of the limbs, severely affecting femora with distinct facial features. Despite its first description nearly four decades ago, the precise molecular basis of this condition remained elusive until the recent discovery of de novo variants in the KIF5B-related kyphomelic dysplasia. We ascertained two unrelated consanguineous families with kyphomelic dysplasia. They had six affected offsprings and we performed a detailed clinical evaluation, skeletal survey, and exome sequencing in three probands. All the probands had short stature, cleft palate, and micro-retrognathia. Radiographs revealed kyphomelic femora, bowing of long bones, radial head dislocations and mild platyspondyly. We noted two novel homozygous variants in CCN2 as possible candidates that segregated with the phenotype in the families: a missense variant c.443G>A; p.(Cys148Tyr) in exon 3 and a frameshift variant, c.779_786del; p.(Pro260LeufsTer7) in exon 5. CCN2 is crucial for proliferation and differentiation of chondrocytes. Earlier studies have shown that Ccn2-deficient mice exhibit twisted limbs, short and kinked sterna, broad vertebrae, domed cranial vault, shorter mandibles, and cleft palate. We studied the impact of CCN2 knockout in zebrafish models via CRISPR-Cas9 gene editing. F0 knockouts of ccn2a in zebrafish showed altered body curvature, impaired cartilage formation in craniofacial region and either bent or missing tails. Our observations in humans and zebrafish combined with previously described skeletal phenotype of Ccn2 knock out mice, confirm that biallelic loss of function variants in CCN2 result in an autosomal recessive kyphomelic dysplasia.

Preoperative Prediction of Lymph Node Metastases in Nonfunctional Pancreatic Neuroendocrine Tumors Using a Combined CT Radiomics-Clinical Model.

PanNETs are a rare group of pancreatic tumors that display heterogeneous histopathological and clinical behavior. Nodal disease has been established as one of the strongest predictors of patient outcomes in PanNETs. Lack of accurate preoperative assessment of nodal disease is a major limitation in the management of these patients, in particular those with small (< 2cm) low-grade tumors. The aim of the study was to evaluate the ability of radiomic features (RF) to preoperatively predict the presence of nodal disease in pancreatic neuroendocrine tumors (PanNETs). An institutional database was used to identify patients with nonfunctional PanNETs undergoing resection. Pancreas protocol computed tomography was obtained, manually segmented, and RF were extracted. These were analyzed using the minimum redundancy maximum relevance analysis for hierarchical feature selection. Youden index was used to identify the optimal cutoff for predicting nodal disease. A random forest prediction model was trained using RF and clinicopathological characteristics and validated internally. Of the 320 patients included in the study, 92 (28.8%) had nodal disease based on histopathological assessment of the surgical specimen. A radiomic signature based on ten selected RF was developed. Clinicopathological characteristics predictive of nodal disease included tumor grade and size. Upon internal validation the combined radiomics and clinical feature model demonstrated adequate performance (AUC 0.80) in identifying nodal disease. The model accurately identified nodal disease in 85% of patients with small tumors (< 2cm). Non-invasive preoperative assessment of nodal disease using RF and clinicopathological characteristics is feasible.

Giant benign mesenteric cysts (mesothelioma and lymphangioma): A report of two cases

Introduction and importanceMesenteric cysts are a rare group of intra-abdominal tumors located in the mesentery or omentum, most of this lesion are asymptomatically but occasionally presents with non-specific symptoms, which makes diagnosis difficult. Case presentationWe present two cases of giant mesenteric cyst in our Institution, the first case is a women of 23 years with previous gynecologic surgery with chronic abdominal pain and large abdominal mass CT showed a giant intraabdominal 30 × 25 × 15 cm, the patient went to laparotomy and a large mesenteric tumor found. The Histopathology reported a Benign cyst mesothelioma (BCM). The second case is a 47 year male with intermittent abdominal pain and abdominal CT shows a 20x21x15 cm tumor. Laparotomy was performed. Histopathology reported a large lymphangioma. Clinical discussionBCM tumors are rare intrabdominal lesions often diagnosed in premenopausal women. Its etiopathogenesis is still unclear, associated risk factors are endometriosis, pelvic inflammatory disease and previous pelvic surgery. Lymphangiomas are an infrequent cyst tumors. It results from a failure in the evolutionary development of the lymphatic system, often localized in the head and neck and its localization in the abdomen is even rare. The definitive diagnosis is made by histopathology. ConclusionMesenteric cysts diagnosis if often challenge due to nonspecific symptoms and significant overlap in imaging appearance between the different entities, its diagnosis should be in mind when encounter a cystic abdominal tumor, surgical complete removal of this tumors is the optimal treatment to prevent recurrence and complications.

The Survival and Medical Dilemma of Rare Disease Patients in the Greater Bay Area

The population of rare disease patients in China faces many difficulties in disease diagnosis and treatment, medical security, economic burden, quality of life, social assistance, employment opportunities, mental health, and other aspects. It is of great significance to identify the common problems faced by this group and try to propose possible solutions, calling on all sectors of society to pay attention to the rare disease minority group, help them solve their survival and security difficulties, and enable more patients to return to society. This paper investigates and addresses the survival and security challenges faced by rare disease minority patients in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) of China. Through a survey of 223 rare disease patients in the Greater Bay Area, the study reveals that these patients face many challenges in diagnosis, treatment, drug access, and economic support. The conclusion emphasizes the necessity of improving diagnostic efficiency, accelerating drug development, and improving the medical insurance system. Thus, it further puts forward practical suggestions.

Xanthine Oxidase Inhibition by Monoterpene-Chalcone Conjugates from Kaempferia subglobosa and Molecular Docking Insights.

Kaempferia subglobosa is a perennial medicinal plant in the Zingiberaceae family, identified as a new species in January 2024. To uncover the biological benefits of K. subglobosa and its compounds, investigation of the metabolites of the roots and rhizomes, yielded three new monoterpene-chalcone conjugates, the globosones A-C, representing a rare metabolite group within the Zingiberaceae, along with six known compounds. The biogenetic pathway for the globosones involves an oxidative [3+2] cycloaddition between α-phellandrene and 4'-methoxy-4,2',6'-trihydroxychalcone. Biological testing revealed potent xanthine oxidase (XO) inhibition by globosones A and B, with IC50 values of 7.0±1.0 and 3.0±0.2 μM, respectively, surpassing the positive control drug allopurinol (IC50 7.2±0.1 μM). Globosones A-C also showed good aromatase inhibition (IC50 3.0-3.5 μM). Molecular docking studies indicated that globosones A and B may inhibit xanthine oxidase through binding at the FAD domain site. The physicochemical properties of these isolates suggest that they possess characteristics suitable for additional biological assessment in more advanced test systems. This study enhances an understanding of monoterpene-chalcone conjugate inhibitors of XO, and offers preliminary insights into the metabolites and bioactivities of K. subglobosa, uncovering potent biological activities associated with this newly discovered plant species.

Target Discovery of Dhilirane-Type Meroterpenoids by Biosynthesis Guidance and Tailoring Enzyme Catalysis.

Dhilirane-type meroterpenoids (DMs) featuring a 6/6/6/5/5 ring system represent a rare group of fungal meroterpenoids. To date, merely 11 DMs have been isolated or derived, leaving their chemical diversity predominantly unexplored. Herein, we leverage an understanding of biosynthesis to develop a workflow for discovery of DMs by genome mining, metabolite analysis, and tailoring enzyme catalysis. Twenty-three new DMs, including seven unprecedented scaffolds, were consequently identified. An α-ketoglutarate (α-KG)-dependent oxygenase DhiD was found to catalyze the stereodivergent ring contraction of dhilirolide D to form the dhilirane skeleton; while the cytochrome P450 DhiH reshaped the structural diversity by establishing diverse C-C bonds and oxidation. Crystallographic and mutagenesis experiments provide a molecular basis for the DhiD reaction and its stereodivergent products. Notably, DhiD exhibits substrate-controlled catalytic versatility in the chemical expansion of DMs through ring contraction, hydroxylation, dehydrogenation, epoxidation, isomerization, epimerization, and α-ketol cleavage. Bioassay results demonstrated that the obtained meroterpenoids exhibited anti-inflammatory and insecticidal activities. Our work provides insight into nature's arsenal for DM biosynthesis and the functional versatility of α-KG-dependent oxygenase and P450, which can be applied for target discovery and diversification of DM-type natural products.

Perceptions of patients and caregivers toward the management of rare disease in Malaysia: a qualitative research study.

The management of rare diseases is rarely addressed among policymakers and public communities. It is hindered by the lack of information on its epidemiology and burden, especially from the perspective of patients and families with rare diseases. This study aims to understand the perceptions of rare disease patients and their families in the management of rare diseases in Malaysia. A qualitative interview was used to explore the perceptions of patients and families regarding the management of rare diseases in Malaysia. In-depth interviews were conducted with the rare disease patients or their parents/guardians provided by three major rare disease advocacy groups, between 1 July and 15 September 2016. The interviews focused on two key areas: the challenges associated with rare disease and the issues related to accessing medication. Out of the nineteen recruited participants, seventeen (89.5 percent) completed the interview sessions. The significance of awareness, knowledge, and support from others emerged as crucial for families and patients living with rare diseases. Despite facing delayed diagnosis and treatment, a majority of patients and parents expressed satisfaction with the advancements in rare disease management. Nevertheless, a prominent challenge revolves around access to enzyme replacement therapy for eligible patients. This study emphasizes the importance of healthcare professionals understanding patient with rare diseases perceptions to tailor communication strategies, provide accurate information, and address concerns effectively. The message underscores the significance of collaboration between healthcare providers and patient support groups to deliver adequate health information, potentially enhancing patients' understanding and their illness perceptions.

Salivary Gland Tumours in Children and Adolescents-A Study in Shaheed Monsur Ali Medical College &amp; Hospital, Uttara, Dhaka, Bangladesh

Introduction: Salivary gland carcinomas (SGCs) are rare neoplasms in adults, but are exceedingly infrequent in children, with a reported annual incidence of 0.8–1.4 per million populations under 20 years old. Like other pediatric very rare tumors, SGCs in children and adolescents often present diagnostic and therapeutic challenges for pathologists, surgeons, and pediatric oncologists. Objective: To assess the salivary gland tumours in children and adolescents. Methods: A cross-sectional observational study was carried out at Dept. of ENT, Shaheed Monsur Ali Medical College &amp; Hospital, Uttara, Dhaka, Bangladesh from January to June 2023. Total 60 patients included in our study. Our pre-operative clinical diagnoses were based on size, shape, mobility, fixity of the tumour to the underlying structures, ulceration of overlying skin, involvement of facial nerve by its malignant transformation and fine needle aspiration cytology. All patients, or their guardians, gave their informed consent for data collection within the national rare tumour group and analysis. Results: Total sixty (60) cases of salivary gland tumours were available for our study. Out of 55% were male and 45% were female patients. Incidence of tumours is highest in the age group of 41-50 with 13 cases (21.6% of the total). The least affected age group was the 0-10 group with only one patient (3.3%). Women accounted for 16 cases of the total 33 benign neoplasias (55% of the total). Of the 33 benign tumour, 18 were in males (54.5% of all benign tumours) and 15 were in females (45.5%). Total 60 operated cases). Of these, 32 were pleomorphic adenomas (53.3%) and 1 was an adenolymphoma (1.6%). the total number of malignant tumours confirmed by HPE were 27 (45%). Of these, most numerous was adenoid cystic carcinoma in 8 cases (13.3%). squamous cell carcinoma and muco epidermoid carcinoma were found in 6 cases each (10%). There were 4 and 3 cases of adenocarcinoma (6.6%) and acinic cell carcinoma (5%) respectively. The parotid glands were also the sole location for the 3 acinic cell carcinomas. No tumours were found in the sublingual gland. The majority of the tumours found in the parotid gland were benign tumours, mainly pleomorphic adenomas with 24 cases (75% of the total parotid tumours). Conclusions: The tumours were equally distributed between males and females. The tumours were most commonly found in the third to fifth decades of life. The most common benign tumour and the most common tumour overall was pleomorphic adenoma making up 54.5% of all tumours. Surgical excision was the most commonly done treatment. The most commonly done surgical procedure was superficial parotidectomy.

Heterologous Expression of Type II PKS Gene Cluster Leads to Diversified Angucyclines in Streptomyces albus J1074

Heterologous expression has emerged as an effective strategy in activating Streptomyces cryptic gene clusters or improving yield. Eight compounds were successfully obtained by heterologous expression of the type II PKS gene cluster spi derived from marine Streptomyces sp. HDN155000 in the chassis host Streptomyces albus J1074. The structures with absolute configurations were elucidated using extensive MS and NMR spectroscopic methods, as well as theoretical NMR calculations and electronic circular dichroism (ECD) calculations. Interestingly, compound WS009 Z (2) contains a rare thiomethyl group, angumycinone T (4) has a novel oxo-bridge formed between C12a and C4, and angumycinone X (3) showed cytotoxicity toward K562 and NCI-H446/EP cell lines.

Clinical and molecular epidemiology of malignant salivary gland tumors

Salivary gland carcinomas are a rare and heterogeneous group of malignant tumors, accounting for 3-6% of all malignant tumors in the head and neck region. The 1-, 3- and 5-year survival rates are 83%, 69% and 63% respectively. Due to new molecular pathological and genetic findings, new entities are constantly being defined as part of the recurring WHO classification of salivary gland carcinomas, so that the incidence rates of the entities are subject to constant change. The only certain risk factor for the development of salivary gland carcinomas is ionizing radiation. In addition, large tumors, cervical lymph node involvement and perineural sheath involvement significantly worsen the prognosis. Today, molecular pathology is coming to the fore, with which potential targets have been identified that can offer prognosis-improving treatment options, particularly in recurrent or distant metastatic stages. Entity-specific tyrosine kinase inhibitors such as axitinib in adenoid cystic carcinoma or larotrectinib in secretory carcinoma and cross-entity therapies such as HER2 inhibition and androgen deprivation can prolong median and progression-free survival with a favorable side effect profile.

A rare case of Anti-Jk3 Alloimmunization

Abstract Introduction/Objective The Kidd blood group system was discovered in 1951 and consists of two antithetical antigens, Jka and Jkb, in addition to a third high-incidence antigen, Jk3. Jk null, also known as Jk(a-b-), is an extremely rare blood group in which all Kidd antigens are absent. Jk is a urea transporter found in the renal medulla, and Jk-deficient individuals are unable to concentrate urine to its maximum concentration. If these individuals are exposed to the Jk antigen via transfusion or pregnancy, they are able to produce antibodies against the Jk3 antigen with a high incidence. Jk3 is expressed in over 99.9% of the blood donor pool, which has severe clinical implications and complicates transfusion. Methods/Case Report CASE PRESENTATION: A 68-year-old male was admitted to the Stanford Medical Center with chronic right midshaft tibia osteomyelitis and a sinus drainage tract for a right tibial diaphysectomy. His test for antibodies was positive. Plasma from the patient is reactive with all tested cells except auto control, AHG in PEG, and solid phase. Phenotyping yielded negative results for Jka and Jkb, suggesting that the antibody is Jk3. Anti-Jk3 was eliminated by adsorption and rendered nonreactive. Results (if a Case Study enter NA) NA Conclusion Anti-Jk3 should be suspected in a previously pregnant or transfused patient during antibody screening and identification if it demonstrates the pattern of an antibody reacting to all cells in the panel, i.e., reacting to a high- frequency antigen with negative autocontrol. Awareness on the part of blood bank personnel regarding the variability of the blood group phenotype and the capricious nature of Kidd antibodies may aid in the improved management of these patients. It is recommended that patients with rare antibodies carry an antibody ID card indicating the rare antibody they have to prevent further exposure. A patient may be advised to undergo an autologous transfusion. Fortunately, the patient’s procedures were uncomplicated, so a blood transfusion was unnecessary. Awareness on the part of blood bank staff regarding the variability of the blood group phenotype and the unpredictability of Anti-Jk3 may aid in improving patient care. To prevent further exposure, it is recommended that patients with rare antibodies carry an Antibody ID card indicating the rare antibody they possess.Jk3 antigen blood donors are underrepresented in the general donor pool. It is recommended to develop a systematic recruitment for Jk3 antigen donors.

Emc1 is essential for vision and zebrafish photoreceptor outer segment morphogenesis.

Inherited retinal diseases (IRDs) are a rare group of eye disorders characterized by progressive dysfunction and degeneration of retinal cells. In this study, we characterized the raifteirí (raf) zebrafish, a novel model of inherited blindness, identified through an unbiased ENU mutagenesis screen. A mutation in the largest subunit of the endoplasmic reticulum membrane protein complex, emc1 was subsequently identified as the causative raf mutation. We sought to elucidate the cellular and molecular phenotypes in the emc1-/- knockout model and explore the association of emc1 with retinal degeneration. Visual behavior and retinal electrophysiology assays demonstrated that emc1-/- mutants had severe visual impairments. Retinal histology and morphometric analysis revealed extensive abnormalities, including thinning of the photoreceptor layer, in addition to large gaps surrounding the lens. Notably, photoreceptor outer segments were drastically smaller, outer segment protein expression was altered and hyaloid vasculature development was disrupted. Transcriptomic profiling identified cone and rod-specific phototransduction genes significantly downregulated by loss of emc1. These data shed light on why emc1 is a causative gene in inherited retinal disease and how outer segment morphogenesis is regulated.

The role of endoscopic endonasal surgery in the management of sinonasal malignant tumors with skull base involvement

Sinonasal malignant tumors (SNMTs) represent a rare and heterogeneous group of tumors. SNMTs often present late which can lead to complex, patient-specific treatment decisions. Over the last two decades, endoscopic endonasal surgery (EES) has become a more frequently utilized surgical approach to removing these tumors. Increasingly, studies have compared the outcomes of this approach to traditional open approaches for different SNMTs. Differences in histology and extent of invasion impact the utility of EES. Negative margins are critical for improving survival; however, skull base involvement can add anatomical challenges for achieving negative margins during EES. This paper reviews the literature on outcomes of EES for SNMTs with skull base involvement and presents evidence supporting the utility of EES for select patients. EES is a safe and effective treatment in patients with less invasive SNMTs or less aggressive histology and can provide patients with fewer complications and morbidity than traditional open approaches. As such, it plays a key role in surgical management, providing either sole access or a critical avenue for SNMT removal. EES plays a key role in the multimodal oncological approach to the treatment of different SNMT histologies.

Identification, structural revision and biological evaluation of the phyllocladane-type diterpenoids from Callicarpa longifolia var. floccosa

Phyllocladane-type diterpenoids represent a rare group of tetracyclic diterpenes. Two diterpenoids (1 and 2) were extracted from Callicarpa longifolia var. floccosa, along with the Chemically synthesized derivatized compound 3. The crystal data for compound 1 were first reported in this study, and compound 2 was identified as a novel phyllocladane-type diterpenoid. In addition, calliterpenone monoacetate was previously erroneously reported as compound 2. We corrected the structure of calliterpenone monoacetate to 2a by X-ray diffraction, NMR calculations, and chemical synthesis, as well as the TDDFT-ECD method. At the same time, the antitumor activity of compounds 1 and 2 was studied.

Comprehensive treatment strategy for improving surgical resection rate of retroperitoneal sarcomas: a histology-specific approach narrative review.

Retroperitoneal sarcoma (RPS) represents a rare and heterogeneous group of malignancies, posing significant challenges in evaluation and management. Surgery, the cornerstone of RPS treatment, critically depends on complete resection for a favorable prognosis. The extent of resection is a crucial determinant of local control and survival. This review delves into the evolution of multidisciplinary management of localized RPS, highlighting the imperative to adapt surgical strategies to tumor histology, location, and patient functional status. We explore the principles of compartmental surgery-an extended first-line approach that involves resecting adjacent viscera for wide negative margins-and its effectiveness across different histological subtypes of RPS and more limited resections for other types. Particular emphasis is placed on the heterogeneity of the disease, as various histological subtypes exhibit distinct biological behaviors. This necessitates a shift away from a one-size-fits-all treatment approach. The review analyzes the role of different surgical strategies, focusing on histological type and location. Additionally, the potential benefits of (neo)adjuvant treatments, such as radiotherapy and chemotherapy, are examined, recognizing their specific histological indications and limitations. This comprehensive review consolidates recent data on surgical strategies and complementary therapies, advocating for a personalized approach tailored to histology. As understanding of the molecular and genetic underpinnings of RPS continues to evolve, so will strategies for its effective management, underscoring the need for global collaboration among specialists in this field to enhance our collective knowledge and treatment methodologies.

Applying Deep Generative Neural Networks to Data Augmentation for Consumer Survey Data with a Small Sample Size

Questionnaire consumer survey research is primarily used for marketing research. To obtain credible results, collecting responses from numerous participants is necessary. However, two crucial challenges prevent marketers from conducting large-sample size surveys. The first is cost, as organizations with limited marketing budgets struggle to gather sufficient data. The second involves rare population groups, where it is difficult to obtain representative samples. Furthermore, the increasing awareness of privacy and security concerns has made it challenging to ask sensitive and personal questions, further complicating respondent recruitment. To address these challenges, we augmented small-sized datawith synthesized data generated using deep generative neural networks (DGNNs). The synthesized data from three types of DGNNs (CTGAN, TVAE, and CopulaGAN) were based on seed data. For validation, 11 datasets were prepared: real data (original and seed), synthesized data (CTGAN, TVAE, and CopulaGAN), and augmented data (original + CTGAN, original + TVAE, original + CopulaGAN, seed + CTGAN, seed + TVAE, and seed + CopulaGAN). The large-sample-sized data, termed “original data”, served as the benchmark, whereas the small-sample-sized data acted as the foundation for synthesizing additional data. These datasets were evaluated using machine learning algorithms, particularly focusing on classification tasks. Conclusively, augmenting and synthesizing consumer survey data have shown potential in enhancing predictive performance, irrespective of the dataset’s size. Nonetheless, the challenge remains to minimize discrepancies between the original data and other datasets concerning the values and orders of feature importance. Although the efficacy of all three approaches should be improved in future work, CopulaGAN more accurately grasps the dependencies between the variables in table data compared with the other two DGNNs. The results provide cues for augmenting data with dependencies between variables in various fields.

6400 An Unusual Presentation of Silent Corticotroph Pituitary Macroadenoma

Abstract Disclosure: N. Mon: None. V. Lohano: None. B. Williams: None. N. Lehman: None. R. Kulkarni: None. S.L. Mokshagundam: None. Silent Corticotroph Pituitary Adenomas (SCA) are a rare group of nonfunctioning pituitary adenomas (NFA) comprising 3-6% of all pituitary adenomas and up to 20% of corticotroph adenomas. SCA are biologically and clinically distinct from Cushing disease and NFA. SCA present with headache, visual field impairment, hypopituitarism, and pituitary apoplexy. We present a case of SCA with the initial presentation of syncope with undetectable ACTH and very low AM cortisol level.A 67 year-old-female was incidentally found to have a pituitary macroadenoma in MRI brain for syncope work up in 2017. MRI reported 1.4 x 1.2 x 1.3 cm sellar mass with suprasellar extension, minimal mass effect on the optic chiasm and no cavernous sinus invasion. Initial labs showed ACTH &amp;lt;5 (7.2-63.3 pg/mL), AM cortisol 0.8 (6-28ug/dl), Prolactin 101.1 (3.3-27 ng/mL), TSH 0.08 (0.34-5.60 uIU/mL), Free T4 0.6 (0.58-1.64 ng/dL), FSH 1.7 (2-5 mIU/mL), LH &amp;lt;0.2 (1-13 mIU/mL), IGF-1 33 ( 41-279 ng/mL). ACTH stimulation test: cortisol 0.5 ug/dl at baseline, 5.8 ug/dl at 60min. She was diagnosed with panhypopituitarism and hyperprolactinemia due to stalk effect. Hydrocortisone and Levothyroxine (LT4) were started. She underwent pituitary macroadenoma resection for optic chiasm decompression in 2017. Pathology reported pituitary neuroendocrine tumor (pitNET), but no immunostaining was done at that time. Follow up MRI in 2019 showed residual pituitary tumor. In 2023, she endorsed headaches, mood changes, fatigue and weight gain. Physical exam was unremarkable except BMI 34.75. Prolactin, Free T4, IGF-1 were normal. MRI in 2023 revealed recurrent and enlarging pituitary adenoma (1.9 x 1.4 x 1.6 cm) with suprasellar extension, abutting the optic chiasm, and left cavernous sinus invasion with internal carotid artery encasement. She underwent revision transsphenoidal resection of pituitary tumor to decompress the optic chiasm with plan for subsequent focused radiation to the cavernous sinus portion. Postoperative period was uneventful and hydrocortisone and LT4 were continued on discharge. Final pathology reported silent corticotroph lineage pitNET with low Ki67, immunostaining positive for TPIT, CAM5.2, and negative for ACTH. ACTH-negative SCA are a rare subtype and more likely to have lower ACTH levels, and multiple microcysts on MRI than ACTH-positive SCA. New WHO classification of pitNET highlights the histological typing and subtyping based on immunostaining of pituitary lineage transcription factors as the cornerstone for accurate classification. SCA are more biologically aggressive tumors with a high propensity of recurrence and resistance to conventional treatment. TPIT and ACTH immunostaining significantly improved the diagnosis of SCA and thereby close clinical follow up for early recognition and management of SCA recurrence. Absence of serum markers of recurrence makes this challenging. Presentation: 6/1/2024