bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT564 Metastatic Malignant Pleural Effusion In A Patient With Remote History Of FTC
Authors: Lee David M , Gong Michael , Czerlanis Cheryl , Arif Ayesha , Arceo-Mendoza Rod Marianne
Published: October 2023

Disclosure: D.M. Lee: None. M. Gong: None. C. Czerlanis: None. A. Arif: None. R. Arceo-Mendoza: None.

Introduction: Differentiated thyroid follicular epithelial-derived cancers include Papillary (PTC) and Follicular Thyroid Cancer (FTC). FTC is less common, accounting for only 5-15% of all thyroid cancers. It is more common in older patients and spreads via hematogenous route, with distant metastases in 10-15% of patients, commonly in the lungs and bone. We describe an unusual case of a patient with a remote history of FTC who presents with recurrence more than 50 years later in the form of a malignant pleural effusion. Clinical Case: A 79/M with a remote history of FTC that was diagnosed in the 1960s presents with one week of L sided pleuritic chest pain and dyspnea. CXR on admission showed opacification of the L hemidiaphragm. A chest CT confirmed the L sided pleural effusion. Thyroid US showed surgically absent thyroid and a 1.1cm solid nodule in the L surgical bed. PET/CT demonstrated hypermetabolic rim of L pleural effusion with no uptake in the neck. Thoracentesis was done which showed exudative pleural fluid concerning for malignancy. Immunohistochemical stains were positive for TTF-1 and thyroglobulin, consistent with metastatic thyroid cancer. He also underwent L supraclavicular lymph node FNA with findings suspicious for metastatic thyroid cancer with follicular features, with NO nuclear features of PTC. On further history, the patient reports having radiation therapy for acne around age 17 and was then diagnosed with FTC in his 20s. He underwent total thyroidectomy and RAI treatment. He recalls being told that he had a few weeks to live, and an “experimental treatment” was offered at the time, which we suspect was cobalt radiation. The patient unfortunately was eventually lost to endocrine follow up but denies any known recurrence prior to this admission. Upon discharge, an I-123 WBS was performed showing multiple foci in the R neck. Uptake is also noted in bilateral lung base, greater on the left. He was treated with 250 mCi I-131. He is currently doing well overall, asymptomatic, and with stable surveillance imaging. He is on levothyroxine suppression therapy with Tg level on a downward trend. Clinical Lesson/Conclusion: Involvement of pleural fluid by metastatic thyroid cancer though reported, is relatively rare, accounting for only less than 1% in all the patients with malignant pleural effusion. To our knowledge, there are no reported cases of malignant pleural effusions from metastatic FTC presenting remotely so many years after the initial diagnosis. The diagnosis of metastatic thyroid cancer in pleural fluid can be challenging and knowledge of the clinical context, even with remote history dating back 50 years ago just like in our case, and supporting immunohistochemical stains is essential for making the right diagnosis.

Presentation Date: Saturday, June 17, 2023
SAT569 Papillary Thyroid Carcinoma With Renal Metastasis Treated With Radioactive Iodine: A Case Report
Authors: Apa-Ap Archimedes Almasol , Sedurante Myrna Buenaluz , Lacuata Jan Alexeis , Gacula John Kenneth V , Lee Vannah Marjolaine , Hernandez Melfred L
Published: October 2023

Disclosure: A.A. Apa-ap: None. M.B. Sedurante: None. J. Lacuata: None. J. Gacula: None. V. Lee: None. M.L. Hernandez: None.

INTRODUCTION. Papillary thyroid cancer (PTC) is one of the most treatable cancers in comparison to undifferentiated thyroid malignancies. It advances slowly, and there is only 1-4 percent of cases of distant metastases. Renal involvement from PTC is very rare with an incidence of 0.47 percent.

CASE DESCRIPTION. This paper describes a 34-year-old Filipino female presenting with an 8-year history of hoarseness and a gradually enlarging anterior neck mass. Metastatic workup revealed innumerable bilateral pulmonary nodules bilateral cervical lymphadenopathy, and bilateral renal mass on CT scan. The right pole of the kidney shows a solid heterogeneously enhancing partially-exophytic focus measuring 4.9 x 4.2 x 4.3cm likely a primary renal cell carcinoma versus metastasis. The left renal mass shows a hypodense non-enhancing partially-exophytic focus measuring 3.9 x 3.6 x 3.6cm probably a renal cyst. Clinically, the patient did not show any urinary symptoms and creatine clearance was normal. The patient underwent total thyroidectomy and neck dissection and histopathology revealed PTC. The patient underwent simultaneous ultrasound right renal mass biopsy which revealed few fragments of thyroid tissues with atypia most likely representative of metastasis of PTC. Since the radiographic finding was suggestive of a renal cyst, the left renal mass was not biopsied. Patient refused nephrectomy and underwent 1 cycle of Radioactive Iodine (RAI) Therapy. Post therapy whole body scan showed mildly increased and diffuse tracer uptake activity in bilateral lungs and large avid focus, approximately 5.0 x 4.4 cm, seen in the inferior pole of the right kidney. Surveillance showed increased thyroglobulin. To date, the patient still refused surgery and is contemplating undergoing another cycle of RAI therapy.

DISCUSSION. Due to the rarity of the metastatic site, the ideal course of treatment for this illness is unknown. To our knowledge, there are only approximate of 30 case reports on WDTC with renal metastasis in the literature.

Presentation: Saturday, June 17, 2023
SAT311 A Time And Place For Metyrosine: Successful Treatment Of A Pheochromocytoma Presenting With Hypotension And Multisystem Organ Failure
Authors: Shafiq Ramsha , Giordano Jennifer
Published: October 2023

Disclosure: R. Shafiq: None. J. Giordano: None.

Pheochromocytomas are rare neuroendocrine catecholamine-secreting tumors. The surgical excision of pheochromocytoma is definitive management which requires presurgical preparation with an alpha blocker, beta blocker, and sometimes metyrosine to reduce perioperative hemodynamic instability. We present a case of pheochromocytoma complicated with acute on chronic renal failure and acute on chronic heart failure with hypotension requiring metyrosine in presurgical preparation due to hypotension and intolerance to alpha-blocker with successful surgical excision of the tumor. Case: 67 yo M admitted for acute on chronic heart failure and acute on chronic renal failure. He was noted to have an incidental right adrenal mass of 4.3 x 4.5 cm on the CT chest. He denied any prior history of hypertension, episodes of flushing, sweating, palpitations, headaches, or any family history of adrenal malignancies. His labs were consistent with significantly elevated plasma metanephrines to 4.5 nmol/L (normal range < 0.5 nmol/L) and normetanephrine 36 nmol/L (normal range < 0.9 nmol/L). Levels were repeated with slight worsening of metanephrines to 5.6 and normetanephrine to 42. He was hypotensive on presentation initially on milrinone drip that was slowly tapered off. His echo on admission showed left ventricle global hypokinesis with EF 25-30%. He had a worsening renal function on admission and required a few dialysis sessions before being referred to our hospital. He had an MRI adrenal done w/o contrast in the setting of renal failure with a heterogenous mass concerning for pheochromocytoma. PET CT was done which was negative for metastatic disease. Due to strong suspicion of uncontrolled pheochromocytoma as a cause of his heart failure and acute on chronic renal failure, the team and patient opted for unilateral adrenalectomy. He was started on metyrosine pre-surgically as he could not tolerate alpha blockade due to hypotension. His metanephrine levels improved from 5.6 to 1.8 and normetanephrine from 43 to 15 with metyrosine prior to surgery. He had a successful right adrenalectomy and pathology confirmed pheochromocytoma. Of note, he had a history of diabetes with uncontrolled hyperglycemia during admission. Hyperglycemia resolved after adrenalectomy. His plasma metanephrine levels normalized post-adrenalectomy and remained normal on the follow-up visit. Conclusion: Preoperative medical stabilization is a crucial step before surgical resection of pheochromocytoma that traditionally includes an alpha blocker followed by a beta-blocking agent to reduce intra-operative hypertensive crisis. Metyrosine is an often-overlooked agent due to cost, however, should remain in our armamentarium for pheochromocytoma crisis complicated with hypotension when the patient is unable to tolerate an alpha-blocking agent.

Presentation: Saturday, June 17, 2023
SAT331 A Case Of Iatrogenic Cushing’s Syndrome Due To The Concomitant Use Of Cobicistat With An Inhaled Glucocorticoid Followed By Adrenal Insufficiency Upon Discontinuation Of Cobicistat
Authors: Noor Laila , Mullally Jamie , Glassman Rebecca
Published: October 2023

Disclosure: L. Noor: None. J. Mullally: None. R. Glassman: None.

Cobicistat is an inhibitor of cytochrome P4503A (CYP3A) used to increase the systemic exposure of antiretroviral drugs for treatment of HIV, and because of it’s mechanism of action, can have significant drug interactions. A similar “pharmacologic booster” ritonavir has now been widely reported to cause cases of iatrogenic Cushing’s syndrome when used in combination with glucocorticoids, but the data on this risk with cobicistat is much more limited. This case describes a patient who developed florid Cushing’s syndrome while on cobicistat and inhaled glucocorticoids followed by secondary adrenal insufficiency upon discontinuation of cobicistat.

A 60 year old male with past medical history of well-controlled HIV on elvitegravir, cobicistat, emtricitabine and tenofovir, asthma on chronic inhaled fluticasone/salmeterol, presented with several months of progressive abdominal distention, back pain, irritability, easy bruising, proximal muscle weakness and weight gain. On physical exam, he appeared Cushingoid with central obesity, supraclavicular fullness, dorsocervical fat pad, wide violaceous striae on his abdomen and multiple ecchymoses. Iatrogenic Cushing's syndrome was suspected and labs showed undetectable morning serum cortisol and 24 hour urine free cortisol as well as newly elevated A1C of 5.7%. DEXA scan showed osteopenia. CT abdomen pelvis showed small adrenal glands. His HIV medication was switched to a combination of bictegravir, emtricitabine and tenofovir and he subsequently developed significant fatigue, nausea, abdominal discomfort and headaches. He was started on replacement doses of prednisone and his symptoms improved significantly. The prednisone dose is being gradually tapered, with ongoing recovery of the hypothalamic-pituitary-adrenal(HPA) axis, with now low, but detectable cortisol and ACTH levels.

We present a unique case of iatrogenic Cushing’s syndrome due to concomitant use of cobicistat with inhaled fluticasone and the subsequent development of secondary adrenal insufficiency upon discontinuation of cobicistat. Cobicistat is an inhibitor of CYP3A which can cause decreased metabolism of exogenous glucocorticoids resulting in HPA axis suppression and exogenous Cushing’s syndrome. Fluticasone causes more cortisol suppression than other inhaled steroids because of it’s long half-life, higher binding affinity for glucocorticoid receptors and high lipophilicity. Concomitant use of cobicistat and glucocorticoids, including inhaled fluticasone, should be avoided and clinicians should be aware of the potential for iatrogenic Cushing’s syndrome and consequent adrenal insufficiency upon discontinuation of cobicistat after use with concomitant glucocorticoids.

Presentation: Saturday, June 17, 2023
THU421 Utility Of Forearm DXA As A Tool For Identification Of Osteoporosis: A Cleveland Clinic Experience
Authors: Ishola Adeola F , Alsibai Khaled , Iqbal Anira , Elsherif Ayat , Rao Pratibha , Khan Leila Zeinab
Published: October 2023

Disclosure: A.F. Ishola: None. K. Alsibai: None. A. Iqbal: None. A. Elsherif: None. P. Rao: None. L.Z. Khan: None.

Background: Osteoporosis is a preventable and treatable condition with a significant impact on the quality of life. According to the National Osteoporosis Foundation, 10.2 million Americans have osteoporosis. In addition, more than 2 million osteoporosis-related fractures occur annually in the US and >70% of these occur in women. Unfortunately, most individuals at risk do not undergo appropriate assessment or treatment. Clinically osteoporosis may be diagnosed if there is a fragility fracture, independent of bone mineral density (BMD) T-score value. Diagnosis based on BMD can also be made with a T-score of − 2.5 or below in the lumbar spine, femoral neck, total proximal femur, or distal 1/3 radius. Due to the limitations in interpreting BMD values in patients with degenerative joint disease (DJD), using the forearm (distal 33% radius) as an alternative skeletal site could serve as a more sensitive screening test. Our study primary aims were to assess the frequency at which females age ≥ 65 undergoing BMD testing had DJD of the spine, to determine the frequency at which BMD testing of the forearm was performed in patients with DJD of the spine, and to assess skeletal site-specific rates of osteoporosis. Methods: This is a large, single-center, retrospective, IRB- approved study conducted at Cleveland Clinic Foundation. Postmenopausal female patients above the age of 65 who underwent DXA scans between January 2018 and December 2019 were identified. Manual chart reviews were performed. Patients receiving osteoporosis treatment and those with hyperparathyroidism were excluded. Results: 195 patients were eligible for the study. The mean age was 73.4 ± 8.2 years. DJD of spine and osteoarthritis were present in 74.5% and 58.2% of patients respectively. Forearm BMD testing was only performed in 18.9% of patients with DJD of the spine. Osteoporosis was diagnosed in 39.1 % at the femoral neck, 35.4% of patients at the lumbar spine, 9.3 % at the distal 1/3 radius, and 6.8% at the total hip. Conclusion: DJD of the spine and hip osteoarthritis often lead to falsely elevated T-scores resulting in under-diagnosis and under-treatment of osteoporosis. Although there is a higher sensitivity of using forearm BMD values to diagnose osteoporosis in patients with DJD of spine and/or osteoporosis, our preliminary data show that the forearm DXA scan is an under-utilized clinical tool in cases of DJD of spine, osteoarthritis, and hip replacement.

Presentation: Thursday, June 15, 2023
THU425 Brief, Low-impact, High-intensity Osteogenic Loading Training Utilizing Proprietary Osteostrong Devices With Once-A-Week, 10 Minute Treatments Improves Bone Mineral Density In Women With Osteoporosis Of The Lumbar Spine
Authors: Papadopoulou-Marketou Nektaria , Papageorgiou Anna , Vavetsis George , Panagiotis Tsiamyrtzis , Chrousos George P
Published: October 2023

Disclosure: N. Papadopoulou-Marketou: None. A. Papageorgiou: None. G. Vavetsis: None. T. Panagiotis: None. G.P. Chrousos: None.

Introduction: Osteoporosis is a chronic condition characterized by a decrease in bone density and deterioration of microarchitecture. It has been associated with a high bone-fracture risk, an increased mortality, and vast health-care costs. Pharmaceutical treatment along with resistance exercise are usually prescribed. “Osteostrong” is a type of bone strengthening that uses brief (12 min), weekly, low-impact, high-intensity osteogenic loading. Aim: to investigate the therapeutic impact of Osteostrong in people with osteoporosis. Methods: In total, 140 postmenopausal women with osteoporosis of the lumbar spine, followed at the Unit on Clinical and Translational Research in Endocrinology, University of Athens, Athens, Greece, were enrolled. They were divided into 2 groups. Group A (GA) included 70 women who were treated with Osteostrong (mean age: 57,7 y, 95% CI 54, 9-60,6 y); Group B (GB) included 70 women who had no exercise intervention (mean age 59,2 y, 95% CI 55,6-61,9 y). All the participants had a complete physical examination, an assessment for exclusion of secondary osteoporosis, bone markers CTX1 and PINP, and a DXA examination [Horizon W (S/N 300472M], twice, at the time of inclusion in the trial, at 9 and 12 months after onset of intervention. Preliminary data at 9 months are shown. Statistical analysis, Medcalc version 20.2. Results: Paired Student t-test (chi-squared) of Bone Mass Density (BMD) and T-score before (1) and after intervention (2) in GA and GB showed: BMD lumbar spine (L1-L4) and T-score L1-L4: GA1 (mean:0.815), GA2 (mean:0.833) (p<0.0007) and GA1 (mean: −2.27), GA2 (mean: −1.93) (p<0.0001)/ GB1 (mean: 0.852), GB2 (mean: 0.851) (p=0.93) and GB1 (mean: −1.98), GB2 (mean: −1.80) (p=0.054), respectively. Trabecular bone score (TBS) and T-score TBS: GA1 (mean: 1.217), GA2 (mean: 1.238), (p=0.036) and GA1 (mean: −2.76), GA2 (mean: −2.52), (p=0.045)/ GB1 (mean:1.22), GB2 (mean: 1.204) (p=0.14) and GB1 (mean: −2.75), GB2 (mean: −2.85), (p= 0.560), respectively. The CTX1 and PINP values were within normal reference range at 9 months. Discussion: The study showed a statistically significant improvement of BMD in the lumbar spine and TBS in people with osteoporosis treated with Osteostrong. The Osteostrong method may have a synergistic effect with anti-osteoporotic medication, significantly reducing bone fracture risk. Conservative therapeutic interventions are important challenges to minimize the osteoporosis-related poor quality of life and mortality.

Presentation: Thursday, June 15, 2023
FRI661 Assessing The Current State Of Screening And Managementof Non-alcoholic Fatty Liver Disease In An Academic Endocrinology Clinic
Authors: Matthew Myers Kyle , Dean Hendrickson Chase
Published: October 2023

Disclosure: K.M. Myers: None. C.D. Hendrickson: None.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease and the second most common cause of liver failure leading to transplantation. NAFLD is strongly associated with factors of metabolic syndrome including diabetes mellitus (DM), with which it shares a strong bi-directional relationship. Up to 70% of patients with DM also have NAFLD, and DM is a risk factor for higher rates of NAFLD progression leading to steatohepatitis, fibrosis and cirrhosis. In September 2021, the American Gastroenterological Association published recommendations including endocrinology in the screening and management of NAFLD patients. Screening for NAFLD involves computing a FIB-4 score to risk-stratify patients into low, intermediate or high risk of having liver fibrosis. The FIB-4 score is calculated using patient age, AST, ALT and platelet count. Further management is determined by the level of risk identified, with some indeterminate-risk and all high-risk patients needing referral to hepatology clinic. Methods: Deidentified patient data was abstracted from an electronic health record registry associated with a large academic medical center. Patient qualifiers included: age over 18 years, diagnosis of type 2 DM, a prior visit within 5 years at one of two endocrinology clinic locations and having a primary care physician associated with the system. Of these patients, lab data was obtained for AST, ALT and platelet count. Additionally, the presence or absence of a prior hepatology clinic encounter was assessed. Two endocrinology clinics were analyzed, including one clinic at the main hospital campus and a second, smaller clinic located in an adjacent county. Results: Within the larger clinic, 16,398 patients met the above criteria; however, only 1797 (11.0%) had all lab components evaluated within 5 years to calculate a FIB-4 score, largely due to only 11.3% of total patients having platelet count data available. Of patients with a FIB-4 score, 342 had a score over 2.67, indicating high-risk for liver fibrosis. Of these 342 patients, 181 (53.0%) had an associated hepatology visit. Within the smaller clinic, 3844 patients met the above criteria; however, only 1055 (274%) had all lab components evaluated within 5 years to calculate a FIB-4 score, again largely due to only 30.0% of total patients having platelet count data available. Of the patients with a FIB-4 score, 148 had a score ≥ 2.67, indicating high-risk for liver fibrosis. Of these 148 patients, 47 (31.8%) had an associated encounter with hepatology. Conclusion: This study highlights a need for improved screening and risk-stratification of diabetic patients for NAFLD, including the increased awareness of screening with appropriate lab evaluation and subsequent referral to hepatology when appropriate.

Presentation: Friday, June 16, 2023
OR12-02 NRF2 Is Essential For Expanding Pancreatic Beta-Cell Mass During Pregnancy
Authors: Baumel-Alterzon Sharon , Garcia-Ocana Adolfo , Scott Donald K
Published: October 2023

Disclosure: S. Baumel-Alterzon: None. A. Garcia-Ocana: None. D.K. Scott: None.

The late stages of the mammalian pregnancy are accompanied with increased insulin resistance due to the increased glucose demand of the growing fetus. Therefore, as a compensatory response, in order to maintain the maternal normal blood glucose levels, maternal beta-cell mass expands leading to increased insulin release. Beta-cell proliferation, beta-cell neogenesis, and decreased beta-cell apoptosis, are major contributors for the beta-cell adaptive response during pregnancy. Defects in these cellular processes can lead to gestational diabetes mellitus (GDM). GDM, which occurs in ∼7-8% of the total pregnancy cases within the U.S, results in adverse outcomes for both the mother and newborn. This highlights the urgent need for exploring the yet undefined intracellular mechanisms that regulate functional beta-cell mass expansion during pregnancy. GWAS analysis revealed several mutations in the Nrf2 antioxidant pathway that are associated with diabetes. Additionally, we previously found that Nrf2 is required for adaptive beta-cell expansion after high fat feeding via stimulation of beta-cell proliferation, increased beta-cell survival, and maintenance of beta-cell identity. Interestingly, Nrf2 expression levels are increased by 4.3-fold (+/- 6.60, p<0.05, n=3-4) in maternal beta-cells during pregnancy, peaking at gestational day (GD)19, while returning to normal levels postpartum. Based on these observations, we hypothesize that Nrf2 might play an important role in expanding beta-cell mass during pregnancy and that disruption of Nrf2 expression or function might lead to GDM. In order to test our hypothesis, we generated tamoxifen (Tam)-induced beta cell-specific deletion of Nrf2 in female mice by crossing MIP-CreERTTAM with Nrf2lox/lox mice (βNrf2KO). In order to exclude any effect of Tam on pregnancy outcomes, females mice were injected with Tam (or vehicle control) a month before gestation. Pancreata were harvested at GD15 or GD19 and immunolabeled with Ki67 and insulin (proliferation assay), TUNEL and insulin (apoptotic assay) or insulin alone (beta-cell mass analysis). Our results show that βNrf2KO mice exhibit 70% reduction (+/- 0.25, p<0.01, n=4-6) in beta-cell proliferation and a 0.13% increase in beta-cell death (+/- 0.03, p<0.05, n=4-6) at GD15 compared to littermate controls. Importantly, βNrf2KO pregnant mice display a remarkable decrease in beta-cell mass at GD19 (50%) (+/- 0.68, p<0.05, n=4) compared with control mice, accompanied by a trending decrease in plasma insulin and increase in blood glucose. No changes were observed in the average number of embryos between βNrf2KO and control pregnant mice. We conclude that Nrf2 is required for beta-cell mass expansion during pregnancy by controlling beta-cell proliferation and survival and alterations in Nrf2 action could potentially lead to development of GDM.

Presentation: Friday, June 16, 2023
SAT045 Sexually Dimorphic Effects Of CCN5/WISP2 Overexpression On HFD-STZ Induced Diabetes And Glucose Intolerance
Authors: Alami Tara , Zakikhani Mahvash , Xega Viktoria , Liu Jun-Li
Published: October 2023

Disclosure: T. Alami: None. M. Zakikhani: None. V. Xega: None. J. Liu: None.

Matricellular protein CCN5/WISP2 is a novel target of IGF-1 and WNT signaling within the pancreatic islets (1). Our previous works suggest that CCN5 promotes β-cell proliferation and survival via Akt/PKB and focal adhesion kinase. Last year, we reported sexually dimorphic effects of CCN5 knockout in glucose tolerance and insulin sensitivity in high-fat diet (HFD)-induced obesity, supporting a trophic role of endogenous CCN5 expression on pancreatic islets, albeit mostly in male mice (PSUN136, ENDO 2022). In order to further establish the in vivo effect of CCN5 in a gain-of-function approach, we assessed aP2-CCN5 transgenic mice which overexpress CCN5 in adipose tissues (2). These mice have increased serum level of CCN5, lean body mass and whole-body energy expenditure and hyperplastic adipose and cardiac tissues. Obese aP2-CCN5 mice remained insulin sensitive, glucose tolerant with a reduced insulin level. We first fed wild-type and transgenic mice, both male and female, a 60% HFD (Research Diets, D12492) for two weeks before administering 50 mg/kg streptozotocin (STZ) injections for 5 days, every other day. (i) In male mice, the HFD-STZ induced a steady elevation in glycemia from ∼9 to 25 mM in 7 weeks; CCN5 overexpression slowed down and curtailed the elevation to only 16 mM, and improved glucose tolerance at 48 days, suggesting a partial but significant protection from diabetes. (ii) Using the same dose of STZ, female wild-type mice exhibited only a slight elevation in glycemia from 8 to 12 mM. However, female aP2-CCN5 mice displayed a steady increase in glycemia to 18 mM and significantly impaired glucose tolerance at 16 and 48 days, suggesting rather worsening diabetes due to CCN5. In both male and female mice, there was no obvious difference in insulin sensitivity at 21 days nor in the overall weight loss caused by STZ injections. We are still analyzing the corresponding changes in serum insulin level and β-cell morphometry. Our results further support the notion that increased CCN5 level protects the β-cells, although only in male mice. The female environment, however, would abolish CCN5-induced protection.

(1) Chowdhury S, Wang X, Srikant CB, Li Q, Fu M, Gong YJ, Ning G, Liu JL. IGF-I stimulates CCN5/WISP2 gene expression in pancreatic beta-cells, which promotes cell proliferation and survival against streptozotocin. Endocrinology. 2014; 155: 1629-1642.

(2) Grunberg JR, Hoffmann JM, Hedjazifar S, Nerstedt A, Jenndahl L, Elvin J, Castellot J, Wei L, Moverare-Skrtic S, Ohlsson C, Holm LM, Backhed F, Syed I, Bosch F, Saghatelian A, Kahn BB, Hammarstedt A, Smith U. Overexpressing the novel autocrine/endocrine adipokine WISP2 induces hyperplasia of the heart, white and brown adipose tissues and prevents insulin resistance. Sci Rep. 2017; 7:43515

Presentation: Saturday, June 17, 2023
Great Britain and the War of the Triple Alliance: The Lincolnshire Farmers Colonization Scheme to Paraguay and the Fourth Ally Thesis
Authors: Nickson Andrew
Published: October 2023

This article challenges the fourth ally thesis, which argues that Great Britain was a crucial actor underpinning the combined forces of Argentina, Brazil, and Uruguay that defeated Paraguay in the 1864–70 War of the Triple Alliance. To date, the debate has focused on British involvement in the genesis and financing of the allied war effort. This article instead focuses on the postwar behavior of the British government, exploring its attitude to the 892 mainly English colonists of the failed 1872–73 Lincolnshire farmers emigration scheme to Paraguay. The British government's open hostility to the scheme and its lack of concern for the plight of the colonists offer new evidence suggesting that the War of the Triple Alliance was of little interest to British imperialism in general and to settler colonialism in particular.
Medicaid Home and Community-Based Services in the Wake of the COVID-19 Pandemic
Authors: Miller Edward Alan , Beauregard Lisa Kalimon
Published: October 2023

The need to bolster Medicaid home and community-based services (HCBS) became more evident during the COVID-19 pandemic. This recognition stemmed from the challenges of keeping people safe in nursing homes and the acute workforce shortages in the HCBS sector. This article examines two major federal developments and state responses in HCBS options as a result of the pandemic. The first initiative entails a one-year increase of the federal Medicaid matching rate for HCBS included in the American Rescue Plan Act championed by the Biden administration. The second initiative encompasses administrative flexibilities that permitted states to temporarily expand and modify their existing Medicaid HCBS programs. The article concludes that the effects of the pandemic flexibilities and enhanced federal funding on most state HCBS programs will be limited without continued investment and leadership on the part of the federal government, which is a Biden administration priority. States that make the American Rescue Act and COVID-19 flexibilities initiatives permanent are states that have the fiscal resources and political commitment to expanding HCBS benefits that other states lack. States’ different approaches to bolstering Medicaid HCBS during the pandemic may contribute to widening disparities in access and quality of HCBS across states and populations who depend on Medicaid HCBS.
Actl7b deficiency leads to mislocalization of LC8 type dynein light chains and disruption of murine spermatogenesis
Authors: Merges Gina E. , Arévalo Lena , Kovacevic Andjela , Lohanadan Keerthika , de Rooij Dirk G. , Simon Carla , Jokwitz Melanie , Witke Walter , Schorle Hubert
Published: October 2023

Actin-related proteins (Arps) are classified according to their similarity to actin and are involved in diverse cellular processes. ACTL7B is a testis-specific Arp, and is highly conserved in rodents and primates. ACTL7B is specifically expressed in round and elongating spermatids during spermiogenesis. Here, we have generated an Actl7b-null allele in mice to unravel the role of ACTL7B in sperm formation. Male mice homozygous for the Actl7b-null allele (Actl7b−/−) were infertile, whereas heterozygous males (Actl7b+/−) were fertile. Severe spermatid defects, such as detached acrosomes, disrupted membranes and flagella malformations start to appear after spermiogenesis step 9 in Actl7b−/− mice, finally resulting in spermatogenic arrest. Abnormal spermatids were degraded and levels of autophagy markers were increased. Co-immunoprecipitation with mass spectrometry experiments identified an interaction between ACTL7B and the LC8 dynein light chains DYNLL1 and DYNLL2, which are first detected in step 9 spermatids and mislocalized when ACTL7B is absent. Our data unequivocally establish that mutations in ACTL7B are directly related to male infertility, pressing for additional research in humans.
SciPROP-R: An Effective Bisphosphine Ligand for the Chemo-Selective Iron-Catalyzed Suzuki–Miyaura Coupling of Alkyl Chlorides
Authors: Nakajima Sho , Hashimoto Toru , Lu Siming , Hashizume Daisuke , Matsuda Hiroshi , Hatakeyama Takuji , Isozaki Katsuhiro , Takaya Hikaru , Nakamura Masaharu
Published: October 2023

Novel 2-substituted 1,3-bis[bis(3′,5′-di-tert-butylphenyl)phosphino]propanes (SciPROP-R; 1-R), as well as their iron complexes FeCl2(SciPROP-R) 2-R, are synthesized. Single-crystal X-ray analysis and solution-phase Fe K- and L-edge XAS of 2-R reveals that these complexes maintain tetrahedral geometry and hence paramagnetic high-spin properties both in the solid state and in the solution phase. 31P NMR results demonstrate that the superior coordination ability of SciPROP-TB (1-TB) is due to the bulky tert-butyl group at position 2 of the propane-1,3-diyl linker of the ligand. These novel iron-complexes catalyze Suzuki–Miyaura-type cross coupling under mild conditions. Notably, iron(II) chloride–1-TB complex (2-TB) exhibits excellent catalytic activity owing to the high coordination ability and electron-donating nature of 1-TB, being effective for chemoselective cross coupling between various alkyl chlorides and arylboron compounds.
Rehabilitation of Annular Pulley Injuries of the Fingers in Climbers: A Clinical Commentary
Authors: Ehiogu Uzo Dimma , Schöffl Volker , Jones Gareth
Published: October 2023

The annular pulley ligaments of the fingers are one of the most injured anatomical structures in those who participate in climbing. Despite this, there is a paucity of guidance clearly describing the rehabilitation and physical preparation parameters to return to sport following such injuries. The foundation of effective rehabilitation is the judicious application of progressive loading to increase the morphological and material properties of the damaged tissues. We maintain the optimal management of the climbing athlete after a traumatic annular flexor pulley system rupture should be grounded in the principles of strength and conditioning.
Οι προϋποθέσεις πρόσληψης της φιλοσοφίας στα δογματικά και ασκητικά έργα του Βασιλείου Καισαρείας
Authors: Βαλτογιάννης Ανάργυρος-Μάριος
Published: October 2023

Η παρούσα διδακτορική διατριβή εξετάζει τις κοσμολογικές διαφορές μεταξύ της αρχαιοελληνικής φιλοσοφίας και ορθόδοξης παραδόσεως, όπως αυτή απαντάται στα Δογματικά και Ασκητικά έργα του Βασιλείου Καισαρείας, ως τη βασική προϋπόθεση πρόσληψης των φιλοσοφικών εκφραστικών μέσων από την Εκκλησία.
“Coloured Stones” and Other Sartorial Details on the Eve of the Greek Revolution
Authors: Evangelidou Olga
Published: October 2023

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The altered sputum microbiome profile in patients with moderate and severe COPD compared to the healthy group in the Indian population
Authors: Hazra Druti , SM Fayaz , Chawla Kiran , Sintchenko Vitali , Martinez Elena , Magazine Rahul , Siddalingaiah Nayana
Published: October 2023

Background: Microbial culture-independent sequencing techniques have advanced our understanding of host-microbiome interactions in health and disease. The purpose of this study was to explore the dysbiosis of airway microbiota in patients with moderate or severe chronic obstructive pulmonary disease (COPD) and compare them with healthy controls.

Methods: The COPD patients were investigated for disease severity based on airflow limitations and divided into moderate (50%≤FEV1<80% predicted) and severe groups (FEV1<50% predicted). Spontaneous sputum samples were collected and, the V3-V4 regions of the 16S rRNA coding gene were sequenced to examine the microbiome profile of COPD and healthy participants. 

Results: A total of 45 sputum samples were collected from 17 severe COPD, 12 moderate COPD cases, and 16 healthy volunteers. The bacterial alpha diversity (Shannon and Simpson’s index) significantly decreased in the moderate and severe COPD groups, compared to healthy samples. A significantly higher proportion of Firmicutes and Actinobacteria were present in moderate COPD, and Proteobacteria numbers were comparatively increased in severe COPD. In healthy samples, Bacteroidetes and Fusobacteria were more abundant in comparison to both the COPD groups. Among the most commonly detected 20 bacterial genera, Streptococcus was predominant among the COPD sputum samples, whereas Prevotella was the top genus in healthy controls. Linear discriminant analysis (LDA>2) revealed that marker genera like Streptococcus and Rothia were abundant in moderate COPD. For severe COPD, the genera Pseudomonas and Leptotrichia were most prevalent, whereas Fusobacterium and Prevotella were dominant in the healthy group.

Conclusions: Our findings suggest a significant dysbiosis of the respiratory microbiome in COPD patients. The decreased microbial diversity may influence the host immune response and provide microbiological biomarkers for the diagnosis and monitoring of COPD.
Comparative evaluation of apical debris extrusion during root canal preparation using three different rotary file systems
Authors: Rajnekar Rutuja , Mankar Nikhil , Nikhade Pradnya , Chandak Manoj
Published: October 2023

Background: Endodontic success depends on the complete cleaning and shaping of the root canal. In order to achieve this goal, debris removal is essential. Even with improvements in instrument design, apical debris extrusion continues to be a cause of periradicular inflammation. The current study aimed to compare the amount of apically extruded debris throughout the canal instrumentation with TruNatomy, ProTaper Next, 2Shape rotary systems.

Methods: A total of 60 freshly extracted single‑rooted mandibular premolars were used. An access opening was made, and a working length was estimated. The samples were arbitrarily allocated into three groups i.e. Group I: TruNatomy (n = 20), Group II: ProTaper Next (n = 20), Group III: 2Shape (n = 20). During the canal instrumentation, the extruded debris were collected in preweighed Eppendorf tubes. Post-instrumentation, the tubes were placed in a hot air oven at 140°C for five hours. For calculating the dry debris weight, the tube’s pre-instrumentation weight was deducted from the post-instrumentation weight. The data was analysed using one‑way analysis of variance and post hoc Tukey’s test.

Results: Extrusion of debris was noted in all the specimens. TruNatomy rotary system showed least debris extrusion in comparison to ProTaper Next and 2Shape (P < 0.05). However, the results were statistically non-significant between ProTaper Next and 2Shape (P > 0.05). 

Conclusions: It was noted that all instruments apically extruded debris, with TruNatomy system being related to minimum extrusion.
RETRACTED: The effect of obesity on the outcome of total knee replacement (TKR) [version 1; peer review: 1 approved with reservations]
Authors: AlOmran Abdullah
Published: October 2023

RETRACTION NOTICE (6th October 2023): The article by AlOmran A. ‘The effect of obesity on the outcome of total knee replacement (TKR)’ [version 1; peer review: 1 approved with reservations]. F1000Research 2022, 11:1406 (https://doi.org/10.12688/f1000research.126901.1) has been retracted from F1000Research by the F1000 Editorial Team.

After publication, concerns were raised to the F1000 Editorial Team by a potential peer reviewer about the integrity of the data presented in the article. Investigation into the content of the article was performed by the F1000 Editorial Team, which revealed that the article had been published without the raw underlying data.

The Editorial Team requested the raw underlying data for the research from the author, including a request for the ethical approval document, on 22nd March, 24th March, 19th April and 24th April 2023. The author did not respond to the requests to provide the underlying data, however, they did provide an ethical approval document. On review of the ethical approval document, its authenticity could not be validated. The author's institution was contacted on 22nd June, 24th July and 11th August 2023 to request further information about the underlying data and verify the ethical approval document. The author's institution has not responded to these requests.

Therefore, the decision was made by the F1000 Editorial Team to retract this article, due to the inability to verify the ethical approval for this study and concerns over the integrity of the data. As per F1000Research policies, ethical approval for this type of study must be sought prior to the study start and all articles that report original results should provide access to all data underlying the results, unless there is good justification.

The author has seen a copy of this retraction notice and has not responded.
Phylogenetic inference of pneumococcal transmission from cross-sectional data, a pilot study
Authors: Hackman Jada , Sheppard Carmen , Phelan Jody , Jones-Warner William , Sobkowiak Ben , Shah Sonal , Litt David , Fry Norman K. , Toizumi Michiko , Yoshida Lay-Myint , Hibberd Martin , Miller Elizabeth , Flasche Stefan , Hué Stéphane
Published: October 2023

Background: Inference on pneumococcal transmission has mostly relied on longitudinal studies which are costly and resource intensive. Therefore, we conducted a pilot study to test the ability to infer who infected whom from cross-sectional pneumococcal sequences using phylogenetic inference.

Methods: Five suspected transmission pairs, for which there was epidemiological evidence of who infected whom, were selected from a household study. For each pair, Streptococcus pneumoniae full genomes were sequenced from nasopharyngeal swabs collected on the same day. The within-host genetic diversity of the pneumococcal population was used to infer the transmission direction and then cross-validated with the direction suggested by the epidemiological records.

Results: The pneumococcal genomes clustered into the five households from which the samples were taken. The proportion of concordantly inferred transmission direction generally increased with increasing minimum genome fragment size and single nucleotide polymorphisms. We observed a larger proportion of unique polymorphic sites in the source bacterial population compared to that of the recipient in four of the five pairs, as expected in the case of a transmission bottleneck. The only pair that did not exhibit this effect was also the pair that had consistent discordant transmission direction compared to the epidemiological records suggesting potential misdirection as a result of false-negative sampling.

Conclusions: This pilot provided support for further studies to test if the direction of pneumococcal transmission can be reliably inferred from cross-sectional samples if sequenced with sufficient depth and fragment length.
Multidisciplinary approach to community engagement in global public health research
Authors: Adeagbo Oluwafemi , Hlongwa Mbuzeleni , Tleis Malak , Dubey Priyanka , Afifi Rima , Butali Azeez
Published: October 2023

Recently, there has been a renewed interest in the role of community engagement in knowledge production and ethical issues such as ‘helicopter research’, indicating exploitative research activities of some researchers as well as short-term relationships with research communities especially in low- and middle-income countries. This approach is detrimental to both communities and the larger scientific community as this may breed mistrust. Major institutions such as the National Institute of Health and Care Research in the United Kingdom have highlighted the importance of community engagement as a tool to improve the reach, quality, and impact of the research by incorporating the voices and concerns of marginalized communities. Similarly, in its 2022 guidance, the American Society for Human Genetics (ASGH) highlights the need to address underrepresentation in genomics research through community engagement.  Establishing ethical and meaningful long-term relationships can be challenging especially for researchers who are not members of the community or those from other countries. This article describes how ‘community-engaged research’ can address some ethical challenges in global public health in different cultural settings.
The genome sequence of the Scalloped Oak, Crocallis elinguaria (Linneas, 1758)
Authors: Boyes Douglas , Boyes Clare ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life programme,   Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: October 2023

We present a genome assembly from an individual female Crocallis elinguaria (the Scalloped Oak; Arthropoda; Insecta; Lepidoptera; Geometridae). The genome sequence is 430.4 megabases in span. Most of the assembly is scaffolded into 17 chromosomal pseudomolecules, including the Z and W sex chromosomes. The mitochondrial genome has also been assembled and is 16.86 kilobases in length. Gene annotation of this assembly on Ensembl identified 17,741 protein coding genes.
The genome sequence of the Crescent Plume, Marasmarcha lunaedactyla (Haworth, 1811)
Authors: Boyes Douglas , Boyes Clare ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life programme,   Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: October 2023

We present a genome assembly from an individual female Marasmarcha lunaedactyla (the Crescent Plume; Arthropoda; Insecta; Lepidoptera; Pterophoridae). The genome sequence is 771.1 megabases in span. Most of the assembly is scaffolded into 31 chromosomal pseudomolecules, including the W and Z sex chromosomes. The mitochondrial genome has also been assembled and is 16.43 kilobases in length. Gene annotation of this assembly on Ensembl identified 21,571 protein coding genes.
The genome sequence of a druid fly, Clusia tigrina (Fallén, 1820)
Authors: Crowley Liam M. , Akinmusola Ruth Y. ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life programme,   Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective,   Tree of Life Core Informatics collective,   Darwin Tree of Life Consortium
Published: October 2023

We present a genome assembly from an individual male Clusia tigrina (a druid fly; Arthropoda; Insecta; Diptera; Clusiidae). The genome sequence is 1,216.4 megabases in span. Most of the assembly is scaffolded into 5 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 17.68 kilobases in length.
Institutional Design of Financial Audit
Authors: Dymova I. , Dymova Yulia
Published: October 2023

The article presents an overview of the development of the system of institutional regulation of auditing activities in Russia. A comparison was made of previously adopted Russian auditing standards and international auditing standards that are currently in force in the Russian Federation. At the same time, the question was raised about the advisability of introducing international auditing standards in the Russian Federation and abolishing Russian auditing standards, which were already developed taking into account international auditing standards, but in Russian and adapted to Russian accounting and auditing practice. The article presents the dynamics of the number of legal entities and individuals eligible to carry out audit activities in Russia and the dynamics of their income for the period from 2018 to 2022. Based on the eight principles of institutional design formulated by E. Ostrom at the end of the 20th century, the authors propose the basic principles necessary for determining the institutional framework for audit, the observance of which will ensure the development of audit activities and maintaining a high level of audit services quality.
Disclosure of Individual Information When Presenting Items in the Financial Statements of a Commercial Organization
Authors: Krishtaleva Taisiya
Published: October 2023

The article discusses the problems of information disclosure, shows what and to what extent information in reporting should be disclosed in order to meet the requirements of regulations, taking into account the needs of the main users of reporting. When preparing financial statements, companies need to consider whether the primary users of the financial statements will understand that portion of the information that is not disclosed in detail. Similarly, judgments regarding materiality must take into account the quantitative and qualitative characteristics of a piece of information, its relevance and necessity to the primary users of the financial statements. It is important to determine the necessary amount and structure of information to present it in financial statements in a manner that is understandable and sufficient for users.
Changes Are Expected in Financial Markets
Authors: Smirnov E.
Published: October 2023

Last summer, the Russian Parliament adopted Federal Law No. 340-FZ dated July 24, 2023 “On Amendments to Certain Legislative Acts of the Russian Federation,” which provides for the introduction of a digital ruble into the country’s financial sector.