Normal Density Research Articles

Quantitative Eliashberg theory of the superconductivity of thin films.

A quantitative theory of the superconductivity of materials confined at the nanoscale in parameter-free agreement with experimental data has been missing so far.
We present a generalization, in the Eliashberg framework, of a BCS theory of superconductivity in good metals which are confined along one of the three spatial directions, such as thin films. In this formulation of the Eliashberg equations the approximation of taking the normal density of states (DOS) as its value at the Fermi level has been removed. By numerically solving these new Eliashberg-type equations, we find the dependence of the superconducting critical temperature $T_{c}$ on the confinement size $L$, in quantitative agreement with experimental data of Pb and Al thin films with no adjustable parameters. This quantitative agreement provides an indirect confirmation that, upon increasing the confinement, a crossover from a spherical-like Fermi surface, which contains two growing hole pockets caused by the confinement, to a strongly deformed Fermi surface, occurs. This topology of the Fermi sea is implemented in the new Eliashberg-type equations to reproduce the experimentally observed maximum in the critical superconducting temperature vs film thickness of ultra-thin Pb films.

Prednisolone impairs trabecular bone score changes in adolescents with 21-hydroxylase deficiency.

Individuals with 21-hydroxylase deficiency (21OHD) require lifelong glucocorticoid (GC) therapy, which increases their risk of fragility fractures. However, fractures in GC-treated individuals can occur at normal bone mineral density (BMD) levels, suggesting an alteration in the bone microarchitecture. To evaluate trabecular bone microarchitecture and its changes in adolescents with 21OHD. We enrolled 38 adolescents with 21OHD for whom complete clinical data and baseline and follow-up lumbar spine bone mineral density (LSBMD) measurements were available. The mean duration was 1.5 ± 0.6 years. Trabecular bone score (TBS), an indirect measurement of bone microarchitecture, was analyzed using iNsight™ software version 3.0. Impaired BMD and TBS were defined at Z-scores ≤ -1.5. At baseline, participants (55% female; 68% salt-wasting type; mean age, 15.2 ± 3.8 years; bone age, 17.5 ± 2.8 years; mean GC dose, 18.5 ± 6.5 mg/m2/day) had the prevalence of impaired BMD and TBS of 5% and 18%, respectively. During follow-up, adolescents with 21OHD receiving prednisolone showed a lower annual percentage change in TBS than those who received hydrocortisone (p = 0.028). A stepwise regression analysis showed that body mass index percentile (p < 0.001) and testosterone concentration (p = 0.002) were independent positive predictors of the baseline TBS Z-score, whereas prednisolone use was the only negative predictor of the annual percentage change in TBS (p = 0.002). Adolescents with 21OHD have a high prevalence of impaired bone microarchitecture. Furthermore, prednisolone therapy is associated with impaired bone microarchitecture development, suggesting that hydrocortisone may better preserve bone microarchitecture and should be considered the first-line treatment for this population.

Superstatistical functions of modified shifted Morse potential for diatomic molecules

The application of the molecular potential model to the study of different thermodynamic systems has been a focus of interest in recent time due to its importance in molecular and chemical physics. Hence, the asymptotic iteration method and the Laguerre polynomials are employed to obtain the eigensolutions of the Schrödinger equation with the modified shifted Morse potential model. Vibrational energy results for different diatomic molecules have been presented numerically, and these results are compared with experimental data and other results from available literature. The variation of normalised wave function and probability density of modified shifted Morse potential for some selected diatomic molecules at the ground- and first-excited states have been considered. Results obtained show that the equally spaced sinusoidal wave curves and varying nodes depend on the level of electron concentrations in the diatomic molecules considered. Partition function and other superstatistical function expressions of modified shifted Morse potential for some diatomic molecules within the modified Dirac delta distribution are obtained, using the Poisson summation formula. The superstatistical plots show a high level of dependence on the temperature parameter, maximum vibrational quantum number and deformation parameter. The superstatistical functions for a deformation parameter of zero correspond to the conventional thermodynamic functions.

Investigating Calcareous and Silica Sand Behavior at Material Interfaces: A Comprehensive Study

Abstract This study centers on the crucial determination of the mobilized friction angle between soil and various materials, including steel and concrete, to enhance the modeling of soil-structure interaction. The primary objective of the current investigation was to assess the interfacial friction between calcareous and silica sands when interacting with concrete or steel surfaces. To achieve this, direct shear tests were conducted to examine the impacts of relative density (Dr), surface roughness (Rn), and shearing direction. The test results reveal that the shear strength of calcareous sand surpasses that of silica sand when considering a specific Rn. Furthermore, the interface friction of both sand types escalates with an increase in normal stress and Rn, with higher values observed in interactions with steel plates. Notably, the friction angle ratio (the interaction friction angle over the pure sand friction angle) demonstrates minimal dependence on the sand type. The most pronounced divergence in the friction angle ratio is evident at the maximum Rn value, which increases alongside Rn values for both calcareous and siliceous sands. With increasing Rn values, the maximum shear strength, contingent on normal stress and relative density, also rises. The influence of relative density on the interaction friction angle diminishes with escalating surface roughness.

A Comprehensive Approach to Fault Classification of Helicopter Engines with Adaboost Ensemble Model

This work is based on the PHM North America 2024 Conference Data Challenge’s datasets of Helicopter turbine engine performance measurements. These datasets were large and moderately imbalanced. For dealing with these challenges, we demonstrate significant tools covering feature engineering, augmentation and selection, model exploration, visualizations, model explainability and confidence margin estimation. This work was performed in its entirety using MATLAB. All these tools will be generally applicable to data-driven modeling and prediction of health to real life applications. Initially, we explored the 742k observations in the training set, noting a 60-40 split between healthy and faulty labels, and identified two major operational clusters within the data. We enhanced the dataset by removing duplicates and engineered new features based on domain knowledge, expanding the feature set to 242 dimensions. However for the torque margin estimation, we trained a regression model on a limited subset (18 features), which includes engineered features using domain knowledge, quadratic terms and linear interaction between all the terms. For the final submission, we utilized a stepwise linear regression model to optimize feature selection. This approach achieved a perfect regression score on test data, validated by a consistent torque margin residual range of +/- 0.5%. The model's RMSE and MAE metrics were optimal for employing a normal distribution probability density function. For , we reduced the feature set to 58 using dimensionality reduction techniques and balanced the data with upsampling and down-weighing the minority class. We employed ASHA (Asynchronous Successive Halving Algorithm) in conjunction with AutoML to efficiently determine the most suitable model family, significantly saving compute time. Subsequently, we trained ensemble models, including bagged tree and AdaBoost (Adaptive Boosting), which minimized false negatives and positives, achieving robust classification performance. This was particularly critical given the high penalty for false negatives in the data challenge. The MathWorks team score on Testing Data was 0.9686 at the close of competition. This was further improved to 0.9867. Our approach demonstrates the effectiveness of combining strategic data processing, feature engineering, and model selection to enhance predictive accuracy in complex operational datasets.

Forecasting vital rates by a trimodal extension of the flexible generalized skew normal probability density function

Forecasting vital rates by a trimodal extension of the flexible generalized skew normal probability density function

Anisotropy and lateral compressive strength of large-size cement-stabilized macadam for bulging deformation resistance: A numerical analysis

Large-size cement-stabilized macadam (LCSM) base effectively hinders bulging deformation in asphalt pavements. Under vibratory compaction, the embedded skeleton structure and anisotropy of large-size aggregates (LSA) impact the mechanical properties of LCSM mixes. To reveal the mesostructure and anisotropy of LSA and determine the optimal volume percentage of LSA in LCSM mixes against bulging deformation, this study first characterized the bulging deformation resistance of LCSM mixes using lateral compressive strength (LCS). Next, the evolution of coordination number (CN) and distributions of contact force and contact normal for LSAs at different volume percentages under dynamic cyclic loading were investigated using the discrete element method (DEM). In particular, the induced anisotropic behavior was explored. Then, indoor tests and numerical simulations were conducted to assess the mixes’ LCS and vertical compressive strength (VCS); additionally, the compressive damage characteristics were analyzed. The results indicate that increasing the volume percentage of LSA and dynamic cyclic loading enhanced the CN, strong contact force, and contact normal density. LSAs at varying volume percentages exhibited pronounced anisotropic characteristics before and after loading, and the anisotropy factor of the LSA dropped after loading at a volume percentage of 65 %. Furthermore, the mixes’ VCS values exceeded LCS ones at the same LSA volume percentage, and there was a consistent relationship between the LSA anisotropy and the VCS/LCS ratio, suggesting that the optimal LSA volume percentage in LCSM mixes ranged from 60 % to 65 %. Finally, as the LSA volume increased, the skeleton effect became more pronounced than the interface attenuation effect, leading to higher VCS and LCS values in the mixes, thus improving their resistance to bulging deformation.

Therapeutic Potential of Stearoyl-CoA Desaturase1 (SCD1) in Modulating the Effects of Fatty Acids on Osteoporosis.

Osteoporosis is a common skeletal disease, primarily associated with aging, that results from decreased bone density and bone volume. This reduction significantly increases the risk of fractures in osteoporosis patients compared to individuals with normal bone density. Additionally, the bone regeneration process in these patients is slow, making complete healing difficult. Along with the decline in bone volume and density, osteoporosis is characterized by an increase in marrow adipose tissue (MAT), which is fat within the bone. In this altered bone microenvironment, osteoblasts are influenced by various factors secreted by adipocytes. Notably, saturated fatty acids promote osteoclast activity, inhibit osteoblast differentiation, and induce apoptosis, further reducing osteoblast formation. In contrast, monounsaturated fatty acids inhibit osteoclast formation and mitigate the apoptosis caused by saturated fatty acids. Leveraging these properties, we aimed to investigate the effects of overexpressing stearoyl-CoA desaturase 1 (SCD1), an enzyme that converts saturated fatty acids into monounsaturated fatty acids, on osteogenic differentiation and bone regeneration in both in vivo and in vitro models. Through this novel approach, we seek to develop a stem cell-based therapeutic strategy that harnesses SCD1 to improve bone regeneration in the adipocyte-rich osteoporotic environment.

A Calculating Method for the Height of Multi-Type Buildings Based on 3D Point Cloud

Building height is a critical variable in urban studies, and the automated acquisition of the precise building height is essential for intelligent construction, safety, and the sustainable development of cities. The building height is often approximated by the building’s highest point. However, the calculation method of the building height of the various roof types differs according to building codes, making it challenging to accurately calculate the height of buildings with complex roof structures or multiple upper appendages. Consequently, this paper utilizes point clouds to propose an automated method for calculating building heights conforming to design codes. The model considers roof types and allows for fast, automated, and highly accurate building height estimation. First, roofs are extracted from the point cloud by combining normal vector density clustering with a region-growing algorithm. Second, combined with variational Bayes, a Gaussian mixture model is employed to segment the roof surfaces. Finally, roofs are classified based on slope characteristics, achieving the automatic acquisition of building heights for various roof types over large areas. Experiments were conducted on Vaihingen and STPLS3D datasets. In the Vaihingen area, the maximum error, root-mean-square-error (RMSE), and mean absolute error (MAE) of the measured heights are 1.92 cm, 1.18 cm, and 1.13 cm, respectively. In the STPLS3D area, these values are 1.79 cm, 0.82 cm, and 0.68 cm, respectively. The results demonstrate that the proposed method is reliable and effective, which offers valuable data for the development, construction, and planning of three-dimensional (3D) cities.

Deformability of filament-wound GFRP tubes filled with lightweight aggregate concrete: Experimental and improved analytical studies

Previous research indicates that lightweight aggregate (LWA) concrete exhibits more brittle failure under compression than conventional normal density (ND) concrete. In contrast, angle-ply fiber-reinforced polymer (FRP) filament-wound tubes filled with ND concrete show significant improvements in strength and deformability compared to hollow tubes. This study evaluates the impact of these tubes on LWA concrete to mitigate its brittle behavior. Sixteen concrete-filled FRP filament-wound tubes (CFFTs) made of ±55° filament-wound glass FRP (GFRP) were tested under axial compression. The GFRP tube’s mechanical properties and fiber winding angle of ±55° allowed for a compressive strength enhancement factor ranging from two to five for the CFFTs compared to unconfined specimens. Results also revealed substantial nonlinearity and deformability in the LWA-CFFTs due to the angle-ply tube orientation. An iterative analytical model predicted the CFFT’s nonlinear response, validated by experimental data. The findings demonstrate that angle-ply FRP tubes effectively enhance the bearing capacity and deformability of inherently brittle unconfined LWA concrete.

Effect of Water Content and Degree of Compaction of Clay Subgrade Soil on the Interface Shear Strength Using Geogrid

Pavement performance in clay soil roads can be enhanced with the help of the geogrid concept by increasing lateral confinement, bearing capacity, and overall rigidity of the pavement. Also, geogrid is useful in minimizing vertical and lateral pavement deformations. In this study, 65 tests are performed without and with two types of geogrid, and the aim behind it is to investigate the effect of the moisture content and degree of compaction of clay soil on the interface shear strength. The number of materials used to conduct this study, included subbase granular (type B), clay subgrade soil, the Biaxial and SS2 geogrid which is used as a reinforcing material. Testing the direct shear is conducted by a large-scale direct shear manufactured device contains an upper box with side lengths of (20×20×10) cm, and a lower box with side lengths of (20×25×10) cm. Results show that for all tests the normal applied stresses are 25, 50, 75 and 100 kPa, the shear stress displacement curves for all cases follow similar trends and they are affected by normal stress, density and water content of subgrade soil and type of geogrid. Also, it is obvious that the shear stress increases by increasing the normal applied stress and degree of compaction of clay subgrade soil reaching its maximum value at 95% degree of compaction while it decreases by increasing the water content of subgrade soil. The maximum value of shear strength is observed when water content is equal to 8% (dry side) and finally, the Biaxial geogrid BX1100 (G1) is more efficient in reinforcing clay-subbase interface as compared with SS2 geogrid (G2).

Comparison of Shear-Wave Elastography USG and CT: Composition Analysis of Rectus Femoris Muscle in Healthy Adults and Chronic Kidney Disease Patients.

This study aimed to compare shear-wave elastography (SWE) USG and composition analysis of CT on the right mid-rectus femoris muscle (RF) in both healthy adults and chronic kidney disease (CKD) patients. Sixty-three healthy adults and 22 CKD patients were included. One musculoskeletal radiologist performed right RF SWE USG, while two radiologists measured shear-wave velocity (SWV) from the same SWE images. CT scan was performed, and muscle composition was measured using imageJ, categorized into four HU-based compositions. Interobserver agreement for SWV between two readers was evaluated. Correlations between SWV and CT compositions were analyzed using Pearson's or Spearman's correlation. SWV of healthy group was significantly higher than CKD group by each reader (p = 0.030 and 0.038). The percentage of low-density muscle was higher in CKD group than healthy group (p < 0.001), and the percentage of normal density muscle was higher in healthy group than CKD (p < 0.001) by each reader. Interobserver agreement of SWV by the two readers was almost perfect in both groups (k = 0.957-0.984, 0.959-0.993). There was a statistically significant correlation between SWV and the percentage of normal density muscle on CT in both healthy adults and CKD patient groups (Reader 1, r = 0.318-0.480, p = 0.001 and 0.024; Reader 2, r = 0.511-0.518, p < 0.001 and p = 0.013). SWV demonstrated a significant correlation with the percentage of normal density muscle on CT in both healthy adults and CKD patients by each reader. SWE provides a radiation-free approach that may offer an objective method for evaluating muscle quality, potentially making it an option for muscle monitoring.

Therapeutic Effects of Ginseng and Doxorubicin on DMBA-Induced Ovarian Cancer in Wistar Rats

ABSTRACT Background Ovarian cancer can be attributed to various external factors, such as tobacco use, exposure to chemicals and radiation, and infections. Internal factors, including inherited mutations, hormonal factors, immune conditions, and random mutations, also play a role in its development. Exposure to carcinogen such as 7,12 Dimethyl Benz Anthracene can induce ovarian cancer. The aim of the study is to investigate the effect of Ginseng and Doxorubicin on Ovotoxicity induced by DMBA in Wistar rat. s Methods A total number of twenty-five females (25) wistar rats which average weight was 135g were used and the animals were randomly split into five groups (A, B, C, D, E) with each group comprising of five rats. Group A (served as the control) given physiological saline only, Group B were induced with 7,12 Dimethyl Benz Anthracene and post treated with Ginseng (50 mg/kg) (GIN). Group C were induced with 7,12 DMBA and post treated with Doxorubicin (25mg/kg). Group D were induced with 7,12 DMBA and post treated with Doxorubicin (25 mg/kg) and Ginseng (50 mg/kg). Group E were induced with 7,12 Dimethyl Benz (a) Anthracene (DMBA) (50mg/kg). Drug administration was done orally using oral cannula and intramuscularly using syringe and needle. Results Ovary histoarchitecture for control group A, B (GIN group), and D (DOX+GIN group) revealed intact organization and structure of the ovary. In these groups, no observable pathological changes were seen as the ovaries were characterized with the presence of numerous follicular cells with a normal and well-defined cellular density. For C (DOX group), the histoarchitecture showed a localized collection of blood outside the blood vessels, typically resulting from a ruptured blood vessel (hematoma of blood vessels) and slight degenerative changes in the ovary. For E (DMBA group), showed atrophied and atretic ovarian cells, necrotic oocyte, severe degenerative changes were also observed. For Hormonal analysis, there was a significant decrease in Serum FSH &amp; LH concentration in DMBA treated group compared to the Ginseng and control groups. Conclusions DMBA evidently induced ovarian toxicity, and its effects were efficiently attenuated by the use of Ginseng and Doxorubicin.

7686 A Case Of A 66-Year-Old Male With Systemic Macrocytosis Complicated By Osteoporosis

Abstract Disclosure: J.M. Gri: None. M. Hillhouse: None. P. madhavan: None. Background: Osteoporosis in men is underestimated and warrants investigation for secondary causes of osteoporosis. Systemic mastocytosis is a rare secondary cause of osteoporosis. Clinical Case: This is a 66-year-old male with a past medical history of severe persistent asthma, eczema, hypertension, GERD with esophagitis, basal cell carcinoma, and systemic mastocytosis (diagnosed in 2010). Family history was significant for lung cancer in both of his parents. Patient was first noted to have hyperpigmented skin lesions on his legs, trunk and upper extremities in the early 1990s. The spots were biopsied and he was diagnosed with urticaria pigmentosa in 1998. Due to persistent symptoms of facial flushing and soft stool, he was referred to Hematology and was started on antihistamines. He later underwent a bone marrow biopsy in 2010 which showed multifocal mast cell aggregates but normal trilineage hematopoiesis. He endorsed back pain shortly after his diagnosis and a DXA scan was completed. The DXA scan showed osteopenia of the spine T score of -1.8, BMD 0.999 mg/mm3 and normal bone density in bilateral hips. He had no history of fractures. He was started on alendronate and remained on the medication from 2012 to 2015. It was stopped due to intolerable symptoms of acid reflux and he required proton pump inhibitors. DXA scan in 2017 showed normal bone density of the hips and osteopenia of the lumbar spine (T score -1.2). DXA scan in 2022 showed a decrease in spine BMD by 6% (T score -1.8) from 2017 to 2022 but unchanged from 2010. Hip bone mineral density was normal but decreased by 10% since 2010 and by 6% since 2017. Labs obtained in May 2022 showed normal serum electrophoresis, normal urine calcium and creatinine ratio, calcium and vitamin D level and urine NTX of 41 nM BCE/mM (21-83) and bone specific alkaline phosphatase level of 31.5 U/L (15-41.3). After discussion with the patient, conservative management with calcium, vitamin D and exercise has been implemented along with close follow up. Should the patient’s bone turnover markers increase or fracture risk increase, additional antiresorptive therapy will be initiated. Conclusion: This case study highlights the importance of screening for osteoporosis in patients with systemic macrocytosis. As this patient was diagnosed with osteopenia at age 53, this case also emphasizes the importance of early screening in both women and men with this rare condition. Presentation: 6/3/2024

6722 Increase in Femoral Neck BMD After Parathyroidectomy in Patients with Mild Primary Hyperparathyroidism

Abstract Disclosure: F. Abdul Kather: None. G.A. Clines: None. C. Janney: None. D.T. Hughes: None. N.H. Esfandiari: None. S. Saberi: None. Objective: This study aimed to assess changes in bone mineral density (BMD) following parathyroidectomy in patients with mild primary hyperparathyroidism, defined as serum calcium 10.4 mg/dl to 11.2 mg/dl, by comparing distinct patient variables. Hypothesis: Pre-op demographic factors, laboratory values, and BMD significantly influence post-parathyroidectomy BMD. Methods: This retrospective chart review included 93 subjects with primary hyperparathyroidism who underwent parathyroidectomy between 2000-2022 with BMD measurements performed at the same site pre- and post-parathyroidectomy. Exclusion criteria were age &amp;lt;50 years, GFR &amp;lt;30, recurrent primary hyperparathyroidism, chronic oral glucocorticoid use (&amp;gt;1 month), rheumatoid arthritis, suppressed serum TSH, hormone-deprivation therapy, cinacalcet use, and prescription osteoporosis medication therapy. Statistical analyses were performed using ANOVA and a p-value of &amp;lt;0.05 was considered statistically significant. Results: The mean age of the subjects was 63.65 ± 6.58 years, who were mostly female (84.9%) and white (88.2%). Pre-op laboratory values revealed mean uncorrected calcium 10.52 ±0.26 mg/dL, corrected calcium 10.25 ± 0.32 mg/dL, 25-OH vitamin D 35.82 ±15.31 ng/mL, and parathyroid hormone (PTH) 99.12 ±37.06 pg/mL. Pre-op mean bone densities for the lumbar spine, femoral neck, and total hip were 1.04 ± 0.16, 0.81 ± 0.11, and 0.87 ± 0.11 g/cm2, respectively, with corresponding T-scores of -1.13 ± 1.23, -1.60 ± 0.74, and -1.13 ± 0.89. Changes in BMD post-parathyroidectomy were determined by comparing pre-op and post-op DXA scans. No statistically significant differences in DXA were found between ages of 50-55 vs. &amp;gt;55, post-op timing of DXA 1-2 years post parathyroidectomy vs. &amp;gt;2 years post parathyroidectomy, number of parathyroid glands removed, the total weight of resected parathyroid glands, pre-op vitamin D level &amp;lt;30 ng/mL vs. ≥30 ng/mL, or pre-op urinary calcium levels &amp;lt;200 mg/day vs. ≥200 mg/day. Grouping subjects by pre-operative DXA T-scores revealed a statistically significant improvement in femoral neck bone density between osteoporotic and osteopenic subjects (p=0.018) and between osteoporotic and normal bone density subjects (p=0.019). No significant differences were identified in the spine and total hip bone density changes among these groups. Conclusion: In subjects with osteoporosis undergoing parathyroidectomy, a significant improvement in femoral neck bone density was observed, unaffected by pre-op variables of age, timing of DXA post parathyroidectomy, parathyroid gland characteristics, and pre-op vitamin D and urinary calcium levels. These findings underscore the potential for tailored interventions in managing bone health post-parathyroid surgery, emphasizing the need for personalized approaches to optimize outcomes in individuals with mild hyperparathyroidism. Presentation: 6/2/2024

6983 Pembrolizimab Induced Hypophysitis: Uncommon Side Effect Leading To Late Diagnosis

Abstract Disclosure: T. Chaudhary: None. O. Syed: None. A. Shridar: None. R. Kaur: None. O. Chaudhary: None. M.S. Zubair: None. Background: Pembrolizumab, an immune checkpoint inhibitor, has shown efficacy inducing remission in various malignancies. Associated immune-related adverse effects (irAEs) have been recorded but cases of concomitant hypophysitis and thyroiditis are rare. Clinical case: The patient is a 41-year-old male with a past medical history significant for metastatic melanoma of the left calf, status post sentinel lymph node biopsy and left inguinal lymph node dissection, treated with pembrolizumab for one year. He initially presented with a severe headache that was preceded by two months of fatigue and impaired concentration. CT and MRI head were both unremarkable while lab work was significant for cortisol 0.2 ug/dL and adrenocorticotropic hormone (ACTH) 1.1 pmol/L. A full hormone panel was ordered which showed normal insulin-like growth factor-1 (IGF-1), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Free testosterone was at the lower end of normal. Prolactin was elevated at 27.3 ng/mL. The thyroid function tests showed primary hypothyroidism with elevated thyroid stimulating hormone (TSH) at 109 uIU/mL, low T4 at 1.5 ug/dL, and low free T4 at 0.4 ng/dL. There were no signs or symptoms of posterior pituitary dysfunction. The patient was diagnosed with hypophysitis and started on hydrocortisone 20 mg once daily along with levothyroxine 175 mcg once daily. DEXA scan showed normal bone mineral density. Subsequently, the patient presented to our care and reported symptom improvement after taking the prescribed medication however he continued to develop fatigue by the end of the day. Therefore, hydrocortisone prescription was switched to 15 mg in the morning and 10 mg at noon. A repeat thyroid function panel, sex hormone binding globulin, and LH were ordered, to be followed up at the patient's next visit. The patient was also advised to wear a medical alert bracelet at all times moving forward. Conclusion: Due to non-specific symptoms at onset, hypophysitis can be undiagnosed or misdiagnosed therefore it is important to have a high clinical suspicion with patients on PD-1 inhibitors presenting with such symptoms. It is also imperative to order a full set of hormones as this patient had concomitant primary hypothyroidism. Presentation: 6/1/2024

7633 Novel CASR Gene Mutation in a patient with Familial Hypocalciuric Hypercalcemia and Papillary Thyroid Cancer

Abstract Disclosure: A. Parihar: None. E.S. Nylen: None. S.M. Gandhi: None. Familial Hypocalciuric Hypercalcemia (FHH) is predominantly caused by loss-of-function mutations in the calcium-sensing receptor (CaSR) characterized by a benign elevation in calcium and PTH which can be mistaken for primary hyperparathyroidism (PHPT). Missense mutations in the CaSR gene causing FHH have been documented but not much is known regarding their clinical significance. We describe a patient with FHH found to have a novel variant mutation. A 37-year-old male with hypogonadism and fatty liver was incidentally found to have hypercalcemia suggestive of PHPT with elevated PTH (102-114 pg/ml), normal vitamin D, and Fractional Excretion of Calcium (FECa) of 0.014. His father also had hypercalcemia and had undergone parathyroid surgery. The patient denied kidney stones and had a normal bone density. Subsequent Sestamibi and 4D CT scan suggested parathyroid adenoma on the left mid-lower pole of the thyroid. Neck ultrasound also showed a left 1.2 x 1 x 1 cm thyroid nodule as well as a left neck mass with calcifications. Fine needle aspiration was positive for metastatic Papillary thyroid cancer(PTC) in the left neck mass and patient underwent total thyroidectomy along with subtotal parathyroidectomy and lateral neck dissection. Thyroid pathology confirmed multifocal PTC with lymph node involvement that were BRAF V600 positive. Parathyroid pathology was benign hyperplasia. The PTH level decreased appropriately intraoperatively (69%), but postoperatively a rise was noted with levels remaining 70-90 pg/ml with normal calcium levels. Repeat FECa was 0.007, supporting the diagnosis of FHH. Given patient’s father also had hypercalcemia, genetic testing was pursued. This revealed CaSR gene missense mutation (c.1382T&amp;gt;C p.Leu461Pro, heterozygous). This variation is not present in population databases and has been classified as a variant of uncertain significance. It can be difficult to distinguish PHPT from FHH based on FECa as in this case. The patient also had PTC which is not known to be associated with FHH. Due to uncertain significance of this novel CaSR missense mutation, long term follow-up and further familial genetic testing will help better understand clinical implications. Presentation: 6/2/2024

8305 Assessing The Relationship Between Oral Health And Bone Disease Among Post-menopausal Women

Abstract Disclosure: N. Tahir: None. S. Ahmad: None. K. Batra: None. A. Gupta: None. K.E. Izuora: Research Investigator; Self; Novo Nordisk. Background: Menopause is associated with significant bone loss and worsening oral health, especially periodontal disease (PD). The purpose of this study was to understand the relationship between oral health and bone loss and the factors that influence this relationship. This will help better understand their pathophysiology and provide guidance for more appropriate care. Methods: ​​This cross-sectional study included post-menopausal women undergoing routine bone density evaluation at a diagnostic radiology center. After participants signed informed consent, histories were collected via an investigator-administered questionnaire, the oral cavity was inspected for teeth loss and PD, and a bone density assessment, interpreted by a radiologist, was obtained. The significance level was set at 5% and data were analyzed using chi-square and logistic regression tests. Results: In a sample of 100 eligible participants, the mean age and body mass index (BMI) were 68.17 ± 8.33 years and 29.59 ± 6.13 kg/m2 respectively. Twenty-three participants (23.0%) had T2DM, 29 (29.0%) had &amp;lt; 20 natural teeth and 17 (17.0%) had normal bone mineral density. In an unadjusted simple logistic regression, age, BMI, race/ethnicity, number of natural teeth, history of PD, and history of osteoporotic fracture were associated with bone loss. However, in the binary logistic regression, the only significant predictors of bone loss included age (aOR 1.171, p&amp;lt;0.001), BMI (aOR 0.763, p&amp;lt;0.001), and the history of osteoporotic fractures (aOR 21.273, p=0.021). Conclusion: Clinical variables associated with bone loss in our study included older age, lower BMI, and history of osteoporotic fracture. These are established risk factors for bone loss. Although unadjusted results suggest a relationship between oral health measures and bone loss, these relationships were not present when other factors were included in a multivariate model. These findings suggest PD by itself may not be a risk factor for bone loss but may reflect the similarity in the risk factors for both conditions. Presentation: 6/3/2024

5159 Bone Disease Related To PLS3 Gene Mutation

Abstract Disclosure: S. Saberi: None. N. Esfandiari: None. Background: A variety of genes play a role in the development of osteoporosis. One of these is PLS3, located on the X chromosome. PLS3 gene mutation leads to defective function of the protein Plastin 3. Plastin 3 functions in the binding and bundling of F-actin, a main component of the actin cytoskeleton. In the skeletal system the actin cytoskeleton regulates adaption to gravity and mechanical stress. Dysregulation of this gene is associated with diseases of the bone, including osteoporosis. Clinical Case: A 60-year-old man with a history of hearing loss since age 52, hypothyroidism diagnosed at age 57 presents to the Genetics Clinic after 2 grandsons were diagnosed with osteogenesis imperfecta. The mothers (his two daughters) of the two grandsons were found to be carriers of the PLS3 gene mutation. Because of their carrier status the patient was screened and a pathogenic partial gene deletion of exons 8 to 16 in the PLS3 gene was detected. The patient has a history of a right wrist fracture at age 16 in a fall from 8 feet height from a ladder, right leg fracture at age 45 when his leg got caught and twisted in a ladder rung, 5 rib fractures and shoulder fracture at age 53 in a fall from 3 feet into a utility hole. A DXA scan showed osteopenia in his left femoral neck (T-score -1.3), normal bone density in his total hip (T score -0.1) and lumbar spine (L1-L4 T-score -0.4). FRAX score for major osteoporotic fracture was 9.4% and hip fracture was 1.2%. Labs for secondary causes of osteoporosis were normal. Due to his gene mutation and fracture history a bisphosphonate was recommended.Clinical Lessons:Obtaining a thorough family history in people with fractures can determine the need for screening for gene mutations associated with osteoporosis. This can identify patients who need more aggressive management. Presentation: 6/2/2024

7336 Decades In The Dark: The Long Road To Diagnosing And Treating Hypophosphatasia

Abstract Disclosure: V.A. Mendpara: None. G. Madrigal Loria: None. L.Z. Khan: None. Background: Hypophosphatasia (HPP) is a rare bone disorder that results from deficient activity of the tissue non-specific isoenzyme alkaline phosphatase (ALP).[1] This case highlights a patient whose diagnosis of this treatable genetic condition was significantly delayed for almost two decades, despite receiving care at a prominent academic institution. The patient's persistently low ALP levels in routine lab tests were overlooked by multiple clinicians, leading to a delay in her care and eventual treatment. Case presentation: A 61-year-old Caucasian woman presented at the endocrinology clinic with complaints of severe fatigue, generalized pain, multiple childhood fractures, and ongoing dental issues. The rheumatology clinic to which she was referred for polyarthralgia diagnosed her with Hypophosphatasia (HPP) after noting chronically low alkaline phosphatase (ALP) levels from her previous charts ranging from 15 to 24 U/L (normal range: 34 to 123 U/L) over two decades. Her serum calcium, parathyroid hormone (PTH), and 25-hydroxy vitamin D levels were within normal ranges. A DEXA scan revealed normal bone density, effectively ruling out osteoporosis. Further investigation showed elevated Vitamin B6 levels at 219.6 nmol/L (normal range: 20.0 to 125.0 nmol/L), raising suspicion for HPP. The patient's family history provided additional insight, with her mother having a history of short stature and fractures and her son experiencing premature tooth loss at the age of 2. A genetic evaluation identified a heterozygous pathogenic variant in the ALPL gene (c.881A&amp;gt;C, p.Asp294Ala), confirming the diagnosis of autosomal dominant HPP. Initiating treatment with Asfotase alfa, a medication targeting HPP, resulted in a marked improvement in the patient's symptoms. Discussion: This case shows the diagnostic complexities of HPP, stressing the significance of actively screening for this condition via ALP levels in routine laboratory testing or during osteoporosis evaluations. The diagnostic process is critical to distinguish HPP from primary osteoporosis, as treatment and potential risks differ significantly. Inadvertent use of bisphosphonates can worsen hypomineralization and lead to atypical femoral fractures in HPP patients. Asfotase alfa enzyme replacement therapy, available since 2015, offers a targeted approach by replacing the enzyme defect, thereby mitigating symptoms. Heightened awareness among healthcare providers of HPP in adults holds the potential to enhance diagnosis rates and facilitate improved treatment outcomes for this highly treatable condition.[1] Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, Eighth Edition. ASBMR. Presentation: 6/2/2024