Postmenopausal Hyperandrogenism Associated With Synchronous Ovarian Brenner Tumor, Bilateral Leydig Cell Tumor, and Adrenal Mass.

Hyperandrogenism in postmenopausal females may arise from either ovarian or adrenal sources and can pose a challenging diagnostic dilemma. We present the case of a 66-year-old female with postmenopausal hyperandrogenism with virilization, adrenal incidentaloma, and concurrent finding of two extremely rare ovarian tumors, including bilateral Leydig cell tumor and Brenner tumor. Laboratory tests showed elevated testosterone and androstenedione and normal dehydroepiandrosterone sulfate (DHEAS). Response to 1 mg overnight dexamethasone suppression test demonstrated persistently elevated testosterone and incomplete suppression of androstenedione. Computed tomography (CT) scan showed a left adrenal nodule and an unremarkable appearance of the ovaries. The pelvic ultrasound did not show an ovarian tumor on the right ovary, and the left ovary was not seen. Adrenal and ovarian vein sampling suggested the ovaries as the source of the testosterone. Given the ovarian vein sampling results, a multidisciplinary discussion between endocrinology and gynecologic oncology concluded that bilateral salpingo-oophorectomy (BSO) was the next best step for diagnosis and management. Laparoscopic BSO was performed. Histopathology showed bilateral Leydig cell tumors and a left ovarian Brenner tumor. At one-year postoperative follow-up, alopecia improved, and testosterone level normalized. This case highlights the importance of diagnostic pathways and interdisciplinary collaboration in managing rare clinical scenarios of hyperandrogenism in postmenopausal females. As in our case, surgeons may be hesitant to remove normal-appearing ovaries. While the three presented tumor types in this case arise from distinct tissues and exhibit different histological characteristics, the presence of such a unique triad prompts consideration of potential unifying pathogenic mechanisms.

A decade of hospitalizations for hyperthyroidism in the US.

The goal of this study was to examine healthcare burden, hospitalizations, mortality, and healthcare cost utilization from hyperthyroidism to further our understanding of the effect of changes in thyroid disease management over the past decade. This was a retrospective longitudinal trends study involving hospitalizations for hyperthyroidism in the US from 2008 to 2018. We trended crude hospitalization rate, estimated incidence of hospitalizations, trends in inpatient mortality rate, mean length of hospital stay, and mean total hospital cost of patients with hyperthyroidism. The number of hyperthyroid hospitalizations decreased from 12,689 in 2008 to 9110 in 2018 (28.2%) (P trend <0.001), with a decrease of crude hospitalization rate from 33 to 25 per 100,000 hospitalizations. The estimated incidence rate of hospitalization in patients with hyperthyroidism decreased from 441 to 288 per 100,000 adults with hyperthyroidism. There was, however, no difference in adjusted mortality in hospitalizations over the study period. Although there has been a significant reduction in hospitalizations due to hyperthyroidism in the US, there has been no significant change in mortality during hospitalizations. This may represent improving outpatient management of hyperthyroidism. However, this improvement has not translated to outcomes in the hospital setting.

Ten-year trends in adrenal insufficiency admissions.

Adrenal insufficiency (AI) is a severe disease that is difficult to manage in both inpatient and outpatient settings. This study describes trends, inpatient outcomes, and the disease burden of hospitalizations for patients with AI. Data are included on hospitalizations with a principal discharge diagnosis of AI using ICD codes from the National Inpatient Sample for the years 2008, 2010, 2012, 2014, 2016, and 2018. Patients <18 years and those with elective hospitalizations were excluded. From 2008 to 2018, the number of AI hospitalizations increased significantly (P-trend < 0.001), with a rising trend in the proportion of patients with Charlson Comorbidity Index scores >3. There was a significant downward trend in the length of stay from 2008 to 2018 (P-trend = 0.005). However, there was no statistically significant trend for mortality or mean total hospital charges during hospitalizations (P-trend = 0.050 and 0.076, respectively). In conclusion, AI hospitalizations significantly increased over the 10 years with an overall decrease in length of stay.

Intelligent resolution: Integrating Cryo-EM with AI-driven multi-resolution simulations to observe the severe acute respiratory syndrome coronavirus-2 replication-transcription machinery in action.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) replication transcription complex (RTC) is a multi-domain protein responsible for replicating and transcribing the viral mRNA inside a human cell. Attacking RTC function with pharmaceutical compounds is a pathway to treating COVID-19. Conventional tools, e.g., cryo-electron microscopy and all-atom molecular dynamics (AAMD), do not provide sufficiently high resolution or timescale to capture important dynamics of this molecular machine. Consequently, we develop an innovative workflow that bridges the gap between these resolutions, using mesoscale fluctuating finite element analysis (FFEA) continuum simulations and a hierarchy of AI-methods that continually learn and infer features for maintaining consistency between AAMD and FFEA simulations. We leverage a multi-site distributed workflow manager to orchestrate AI, FFEA, and AAMD jobs, providing optimal resource utilization across HPC centers. Our study provides unprecedented access to study the SARS-CoV-2 RTC machinery, while providing general capability for AI-enabled multi-resolution simulations at scale.

Outcomes and Predictors of 30-Day Readmissions for Hyperthyroidism: A Nationwide Study.

Hyperthyroidism is associated with an elevated risk of cardiovascular events and worse hospital outcomes. The Nationwide Readmissions Database (NRD) 2018 was used to determine the characteristics of 30-day readmission in patients with hyperthyroidism. The 30-day all-cause readmission rate for hyperthyroidism was 10.3%. About 21.7% had hyperthyroidism as the principal diagnosis on readmission. Readmissions were associated with an increased odds of inpatient mortality (odds ratio, 7.04; 95% confidence interval [CI], 3.97 to 12.49), length of stay (5.2 days vs. 4.0 days; 95% CI, 0.7 to 1.8), total hospital charges, and cost of hospitalizations. Independent predictors of 30-day all-cause readmissions included Charlson Comorbidity Index ≥3 (adjusted hazard ratio [aHR], 1.76; 95% CI, 1.15 to 2.71), discharge against medical advice (aHR, 2.30; 95% CI, 1.50 to 3.53), protein-energy malnutrition (aHR, 1.54; 95% CI, 1.15 to 2.07), and atrial fibrillation (aHR, 1.41; 95% CI, 1.11 to 1.79). Aggressive but appropriate monitoring is warranted in patients with hyperthyroidism to prevent readmissions.

TIO Associated with Hyperparathyroidism: A Rarity, a Rule, or a Novel HPT-PMT Syndrome-A Case Study with Literature Review.

OBJECTIVE: Association of primary hyperparathyroidism (pHPT) with phosphaturic mesenchymal tumors (PMT) is rarely reported. This report entertains the hypothesis of the causal association of HPT with tumor-induced osteomalacia (TIO) and of the existence of HPT-PMT syndrome. Case Presentation. A 49-year-old man presented with fragility rib fractures, generalized bone pain, and muscle weakness worsening over the past 3 years. Initial tests demonstrated hypophosphatemia and high PTH. The diagnosis of pHPT was entertained, but parathyroid scan was negative. During a 2-year follow-up, the patient reported minimal improvement of symptoms after intermittent treatment with calcitriol and phosphate. Biochemical evaluation showed persistent hypophosphatemia with renal phosphate wasting, elevated FGF23, and osteopenia on DXA scan. TIO was suspected. Multiple MRIs and whole-body FDG-PET scans were inconclusive. The patient subsequently underwent 68Ga-DOTATATE PET-CT, which revealed a somatostatin receptor-positive lesion in the lung. The resected mass was confirmed as PMT. The patient had dramatically improved symptoms, normal phosphate, calcium, and FGF23. During follow-up over 3 years postsurgery, the patient had slowly rising calcium and persistently elevated PTH. CONCLUSION: The debate whether the patient had pHPT or tertiary HPT prompted literature review showing that aberrant genes including FGFR1, FGF1, fibronectin 1, and Klotho were mechanistically involved in the HPT-PMT association. This case highlights the pitfalls contributing to delayed diagnosis and treatment of TIO and hypothesizes the association between pHPT and PMT.

Clinical outcomes among patients with chronic kidney disease hospitalized with diabetic foot disorders: A nationwide retrospective study.

INTRODUCTION: Diabetic foot ulcerations or infections (DFUs/DFIs) are common complications of patients with diabetes. This study aimed to explore the impact of non-dialysis and dialysis CKD on hospitalized patients with DFUs/DFIs. METHODS: A retrospective cohort study was conducted using the National Inpatient Sample database for the years 2017 and 2018. Patients hospitalized for DFUs/DFIs were included in the study. The primary outcome was lower limb amputations. The secondary outcomes were inpatient mortality, sepsis, length of stay (LOS), total hospitalization charges (THC) and disposition. RESULTS: A total of 121,815 hospitalizations were included (26.1% non-dialysis CKD; 8.4% dialysis CKD). There was no significant difference in amputation rates between those on non-dialysis CKD (adjusted odds ratio [aOR]: 0.96; 95% confidence interval [CI]: 0.87-1.06) and dialysis CKD (aOR: 1.04, [95% CI: 0.91-1.12]) when compared to non-CKD group. Dialysis CKD group had increased odds of undergoing major amputation (aOR: 1.74, [95% CI: 1.32-2.29]), in-hospital mortality (aOR: 3.77 [95% CI: 1.94-7.31]), sepsis (aOR: 1.83 [95% CI: 1.27-2.62]), longer LOS (adjusted mean difference [aMD]: 1.46 [95 CI: 1.12-1.80) and higher THC (adjusted mean difference [aMD]: $20,148 [95% CI: $15,968-$24,327]). Non-dialysis CKD group had increased odds of sepsis (aOR: 1.36 [95% CI: 1.02-1.82]), less likely to be discharged home (aOR: 0.87 [95% CI: 0.80-0.95]), longer LOS (aMD: 0.91 [95% CI 0.69-1.13]) and higher THC (aMD: $20,148 [95% CI: $15,968-$24,327]). CONCLUSION: Patients with CKD on dialysis had higher odds of undergoing major amputation. CKD increased the odds of in-hospital morbidity and resource utilization, with the most significant is for those on dialysis.

Predictors of HbA1c among Adipocytokine Biomarkers in African-American Men with Varied Glucose Tolerance.

This study explored adipocytokine associations with acute and chronic hyperglycemia in African-American men (AAM). Fourteen adipocytokines were measured from men with normal glucose tolerance (NGT) or type 2 diabetes (T2D, drug-naïve MF(-) or using metformin MF(+)). Acute and chronic hyperglycemia were evaluated by 120 min oral glucose tolerance test (OGTT) and glycohemoglobin A1c (HbA1c). AAM with T2D (n = 21) compared to NGT (n = 20) were older, had higher BMI and slightly higher glucose and insulin. In the fasted state, TNF-α, IL-6, PAI-1, IL-13, adiponectin, adipsin, and lipocalin were lower in T2D vs. NGT. At 120 min post-glucose load, TNF-α, IL-6, IL-13, IL-8, PAI-1, adiponectin, adipsin, lipocalin, and resistin were lower in T2D vs. NGT. There were no statistical differences for GM-CSF, IL-7, IL-10, IP-10, and MCP-1. Regression analysis showed that fasting IL-8, TNF-α, adiponectin, lipocalin, resistin, adipsin, and PAI-1 were associated with HbA1c. After adjusting for age, BMI, glucose tolerance, and metformin use, only adipsin remained significantly associated with HbA1c (p = 0.021). The model including adipsin, TNF-α, age, BMI, and group designation (i.e., NGT, MF(-), MF(+)) explained 86% of HbA1c variability. The data suggested that adipsin could be associated with HbA1c in AAM with varied glucose tolerance.

Fast Phenomics in Vineyards: Development of GRover, the Grapevine Rover, and LiDAR for Assessing Grapevine Traits in the Field.

This paper introduces GRover (the grapevine rover), an adaptable mobile platform for the deployment and testing of proximal imaging sensors in vineyards for the non-destructive assessment of trunk and cordon volume and pruning weight. A SICK LMS-400 light detection and ranging (LiDAR) radar mounted on GRover was capable of producing precise (±3 mm) 3D point clouds of vine rows. Vineyard scans of the grapevine variety Shiraz grown under different management systems at two separate locations have demonstrated that GRover is able to successfully reproduce a variety of vine structures. Correlations of pruning weight and vine wood (trunk and cordon) volume with LiDAR scans have resulted in high coefficients of determination (R² = 0.91 for pruning weight; 0.76 for wood volume). This is the first time that a LiDAR of this type has been extensively tested in vineyards. Its high scanning rate, eye safe laser and ability to distinguish tissue types make it an appealing option for further development to offer breeders, and potentially growers, quantified measurements of traits that otherwise would be difficult to determine.

Ice Ih anomalies: Thermal contraction, anomalous volume isotope effect, and pressure-induced amorphization.

Ice Ih displays several anomalous thermodynamic properties such as thermal contraction at low temperatures, an anomalous volume isotope effect (VIE) rendering the volume of D2O ice greater than that of H2O ice, and a pressure-induced transition to the high-density amorphous (HDA) phase. Furthermore, the anomalous VIE increases with temperature, despite its quantum-mechanical origin. Here, embedded-fragment ab initio second-order many-body perturbation (MP2) theory in the quasiharmonic approximation (QHA) is applied to the Gibbs energy of an infinite, proton-disordered crystal of ice Ih at wide ranges of temperatures and pressures. The quantum effect of nuclei moving in anharmonic potentials is taken into account from first principles without any empirical or nonsystematic approximation to either the electronic or vibrational Hamiltonian. MP2 predicts quantitatively correctly the thermal contraction at low temperatures, which is confirmed to originate from the volume-contracting hydrogen-bond bending modes (acoustic phonons). It qualitatively reproduces (but underestimates) the thermal expansion at higher temperatures, caused by the volume-expanding hydrogen-bond stretching (and to a lesser extent librational) modes. The anomalous VIE is found to be the result of subtle cancellations among closely competing isotope effects on volume from all modes. Consequently, even ab initio MP2 with the aug-cc-pVDZ and aug-cc-pVTZ basis sets has difficulty reproducing this anomaly, yielding qualitatively varied predictions of the sign of the VIE depending on such computational details as the choice of the embedding field. However, the temperature growth of the anomalous VIE is reproduced robustly and is ascribed to the librational modes. These solid-state MP2 calculations, as well as MP2 Born-Oppenheimer molecular dynamics, find a volume collapse and a loss of symmetry and long-range order in ice Ih upon pressure loading of 2.35 GPa or higher. Concomitantly, rapid softening of acoustic phonons is observed starting around 2 GPa. They constitute a computational detection of a mechanical instability in ice Ih and the resulting pressure-induced amorphization to HDA.

Ab initio molecular dynamics of liquid water using embedded-fragment second-order many-body perturbation theory towards its accurate property prediction.

A direct, simultaneous calculation of properties of a liquid using an ab initio electron-correlated theory has long been unthinkable. Here we present structural, dynamical, and response properties of liquid water calculated by ab initio molecular dynamics using the embedded-fragment spin-component-scaled second-order many-body perturbation method with the aug-cc-pVDZ basis set. This level of theory is chosen as it accurately and inexpensively reproduces the water dimer potential energy surface from the coupled-cluster singles, doubles, and noniterative triples with the aug-cc-pVQZ basis set, which is nearly exact. The calculated radial distribution function, self-diffusion coefficient, coordinate number, and dipole moment, as well as the infrared and Raman spectra are in excellent agreement with experimental results. The shapes and widths of the OH stretching bands in the infrared and Raman spectra and their isotropic-anisotropic Raman noncoincidence, which reflect the diverse local hydrogen-bond environment, are also reproduced computationally. The simulation also reveals intriguing dynamic features of the environment, which are difficult to probe experimentally, such as a surprisingly large fluctuation in the coordination number and the detailed mechanism by which the hydrogen donating water molecules move across the first and second shells, thereby causing this fluctuation.