bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smartphone Psychotherapy Reduces Fear of Cancer Recurrence Among Breast Cancer Survivors: A Fully Decentralized Randomized Controlled Clinical Trial (J-SUPPORT 1703 Study)
Authors: Akechi Tatsuo , Yamaguchi Takuhiro , Uchida Megumi , Imai Fuminobu , Momino Kanae , Katsuki Fujika , Sakurai Naomi , Miyaji Tempei , Mashiko Tomoe , Horikoshi Masaru , Furukawa Toshi A. , Yoshimura Akiyo , Ohno Shinji , Uehiro Natsue , Higaki Kenji , Hasegawa Yoshie , Akahane Kazuhisa , Uchitomi Yosuke , Iwata Hiroji 
Published: November 2022

PURPOSEFear of cancer recurrence (FCR) is a common distressing condition. We investigated the efficacy of smartphone problem-solving therapy and behavioral activation applications in breast cancer survivors.METHODSThis was a decentralized randomized trial. Participants were disease-free breast cancer survivors age 20-49 years who were randomly assigned to the smartphone-based intervention or waitlist control. Both groups received treatment as usual. The control group could access the smartphone apps during weeks 8-24. The intervention comprised smartphone problem-solving therapy and behavioral activation apps. The primary end point was the Concerns About Recurrence Scale at week 8. Secondary outcomes included the Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF), the Hospital Anxiety and Depression Scale (HADS), the Short-form Supportive Care Needs Survey (SCNS-SF34), and the Posttraumatic Growth Inventory at weeks 8 and 24 (trial registration: UMIN-CTR: UMIN000031140).RESULTSThe intervention group included 223 participants, and the control group included 224 participants. Primary outcome data were obtained for 444 participants, and 213 participants in the intervention arm completed the week 24 assessment. The intervention group had statistically greater improvements than controls at week 8 on the Concerns About Recurrence Scale (difference –1.39; 95% CI, –1.93 to –0.85; P < .001), FCRI-SF (difference –1.65; 95% CI, –2.41 to –0.89; P < .001), HADS depression (difference –0.49; 95% CI, –0.98 to 0; P < .05), and SCNS-SF34 psychological domain (difference –1.49; 95% CI, –2.67 to –0.32; P < .05). These scores at week 24 were not statistically significant compared with week 8 although the HADS depression score at week 24 was significantly reduced ( P = .03).CONCLUSIONNovel smartphone psychotherapy offers a promising way to reduce FCR given the large number of survivors and a limited number of therapists to competently conduct psychotherapy.
Determination of Anti-drug Antibody Affinity in Clinical Study Samples Provides a Tool for Evaluation of Immune Response Maturation
Authors: Joyce Alison , Shea Christopher , You Zhiping , Gorovits Boris , Lepsy Christopher 
Published: November 2022

AbstractCharacterization of clinical anti-drug antibody (ADA) responses to biotherapeutics can be important to understanding the consequences of immunogenicity. ADA are expected to be polyclonal, with composition and affinities that evolve over time. Measuring ADA binding affinity can be complicated by the polyclonal nature of response, residual drug in sample, and low ADA levels. We developed a novel workflow to determine the apparent ADA affinity (KD) against a monoclonal antibody biotherapeutic, PF-06480605. An affinity capture elution pre-treatment step was used to isolate ADA and remove residual drug interference from samples. Solution-phase equilibrium incubation was performed using drug and sample ADA as variable and fixed binding interactants, respectively. Unbound ADA concentration was measured using a Singulex Erenna ligand-binding assay (LBA) method. Apparent ADA KD values were calculated using a custom R Shiny algorithm. KD values determined for ADA positive samples showed good correlation with other immunogenicity parameters, including titers and neutralizing antibody (NAb) activity with a general increase in affinity over time, indicative of a maturing immune response. Time of onset of high affinity responses (KD < 100 pM) varied between patients, ranging from 16 to 24 weeks. Antibody responses appeared monophasic at earlier time points, trending towards a biphasic response with a variable transition time and general increase in proportion of high affinity ADA over time. Herein, we provide a novel, sensitive bioanalytical method to determine the KD of ADA in clinical samples. The observed decrease in ADA KD is consistent with evidence of a maturing immune response.
Graphical Abstract
LBSUN85 Acipimox Normalizes The Cardiac Phenotype Induced By Electronic Cigarettes
Authors: Espinoza-Derout Jorge , Shao Xuesi M , Hasan Kamrul M , Rivera Juan-Carlos , Lao Candice , Wilson Julian , Jordan Maria , Roos Kenneth P , Sinha-Hikim Amiya P , Friedman Theodore C 
Published: November 2022

Abstract
Electronic nicotine delivery systems or electronic cigarettes (e-cigarettes) are becoming exceptionally popular in the world as an alternative to conventional nicotine cigarettes, both among smokers and people who have never smoked. Nicotine can induce lipolysis in adipose tissue, leading to increased serum free fatty acids (FFAs). Increased levels of FFAs are one of the key elements in generating a pro-inflammatory response and lead to ectopic lipid accumulation, lipotoxicity, mitochondrial dysfunction, and DNA damage. Our laboratory has shown that e-cigarettes induce cardiac dysfunction associated with oxidative stress and inflammatory phenotype. We investigated the effects of acipimox, an antihyperlipidemic drug that blocks lipolysis, on e-cigarettes-induced cardiac dysfunction and its associated inflammatory signals and oxidative stress. C57BL/6J wild type mice on high fat diet were exposed to saline, e-cigarette with nicotine (2.4%), e-cigarette (2.4%) plus acipimox for 12 weeks. Fractional shortening and ejection fraction was decreased in mice exposed to e-cigarette (2.4%) compared with saline and acipimox. Therefore, acipimox normalized the e-cigarette-induced cardiac dysfunction. Transcriptomic evaluation with Gene Set Enrichment Analysis revealed that e-cigarette treated mice had genes enriched in the G2/M DNA damage checkpoint pathways. These transcriptomic changes were normalized by acipimox. Mice exposed to e-cigarettes had increased circulating levels of M-CSF, IL-6, and FFAs, which were decreased by acipimox. Mice exposed to e-cigarette (2.4%) had increased cardiac Heme oxygenase 1, a marker of oxidative stress. Additionally, treatment with e-cigarette (2.4%) increased the apurinic/apyrimidinic sites. This marker of oxidative DNA damage was normalized by acipimox. Understanding the consequences of e-cigarette use on the cardiovascular system is directly relevant to developing policies related to e-cigarette use.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
LBSUN86 Effects Of Hyperandrogenemia And Western-style Diet On Rhesus Macaque Tissue-resident Memory T-cells And Their Potential Role In Controlling Local Inflammation And Insulin Sensitivity
Authors: Varlamov Oleg , Yusova Sofia , Bishop Cecily V , Robino Jacob J , Takahashi Diana , Roberts Charles , Slayden Ov D , Burwitz Benjamin J , Hennebold Jon D 
Published: November 2022

Abstract
We have previously demonstrated that the combination of chronic hyperandrogenemia (elevated circulating testosterone; T) and an obesogenic Western-style diet (WSD) exerts synergistic effects on the metabolic and reproductive axis, leading to the development of insulin resistance, visceral obesity, and ovarian dysfunction in female rhesus macaques. The underlying cellular connection between T+WSD treatment and abnormal metabolic and reproductive function is not well understood. Tissue resident-memory T-cells (Trm) have emerged as potent regulators of local inflammation. Thus, we hypothesized that T+WSD treatment drives proinflammatory phenotypic changes in Trm cells. To address this hypothesis, we studied a cohort of adult female rhesus macaque exposed to a low-fat diet and no exogenous T (controls) versus those treated with T+WSD for one year. T+WSD animals became insulin resistant and had higher visceral adiposity than control animals. During the mid-luteal phase, all animals were necropsied and immune cells residing in visceral omental white adipose tissue (OM-WAT), the corpus luteum (CL), the contralateral ovary not containing the CL (OV), endometrium (ENDO), lymph nodes (LN), bone marrow (BM), and peripheral blood mononuclear cells (PBMC) were characterized by flow cytometry. Non-activated CD4+ and CD8+ naïve/central memory cells expressing CD28 were detected in all tissue examined. However, the tissue retention receptor CD69 was expressed only on CD4+ and CD8+ cells residing in OM-WAT, CL, OV, and ENDO. These Trm subsets expressed high levels of the C-C Motif Chemokine Receptor 5 (CCR5), whose role in inflammation has been previously reported. Combined T+WSD treatment resulted in a significant increase in CD8+ Trm cell populations in OM-WAT. Notably, the frequencies of Trm in OM-WAT were positively correlated with HOMA-IR, the indicator of insulin resistance. Collectively, our data indicate that combined hyperandrogenemia and WSD can lead to selective recruitment or local differentiation of Trm cells in visceral fat. Trm activation in fat may drive the development of a proinflammatory environment that negatively affects adipose metabolic function, leading to altered systemic metabolic parameters (i. e., hyperinsulinemia) that influence ovarian and uterine processes. Future studies are warranted to define how Trm cell-adipocyte interactions affect adipose metabolic processes.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
ODP002 ASSOCIATION BETWEEN OBESITY AND DIABETES POTENTIATES RENAL FUNCTION IMPAIRMENT IN BARIATRIC PATIENTS
Authors: Naliato Erika 
Published: November 2022

Abstract

Obesity may impair renal function directly or through comorbidities and complications, such as Diabetes Mellitus (DM), hypertension, and dyslipidemia.

Aim
To evaluate renal function in obese patients before treatment with bariatric surgery.

Material & Methods
Serum creatinine was evaluated pre-operatively in 68 obese patients referred to treatment with sleeve gastroplasty. Glomerular filtration rate (eGFR) was estimated through the CKD-EPI Creatinine 2009 Equation. Data on prevalence and occasionally treatment of DM and hypertension were obtained and an additional biochemical work-up (hbA1c, lipid profile, vitamin D) was performed.

Results
Fifty-one subjects had class III obesity (75%) and 17 were classified as class II with metabolic or locomotor complications (25%). Most patients were women (70.6%), had hypertension (66.2%) and low vitamin D (85.9%) and HDL (52.9%) levels. Mean age was 37.8± 8.6 years and mean BMI 43.43± 5.72 kg/m2. The prevalence of DM was 47.6%. While 47.1% of the patients were using renin–angiotensin–aldosterone system inhibitors, only a few were using reno-protective antidiabetic drugs (4.4% on SGLT2 inhibitors and 1.5% on GLP1 agonists). Mean serum creatinine was 0.8± 0.2 mg/dL and eGFR, 100.9± 18. 0 mL/min/1.73m2 (26.5% of patients had eGFR below 90 and 1.5%, values above 130 mL/min/1.73m2). Mean HbA1c was 5.9±0.8% (DM: 6.4±0.9%, non-diabetics: 5.4±0.2%, p &lt; 0. 0001) and HbA1c was above 6.5% in 16.9% of the patients. Mean LDL, HDL, and triglycerides were, respectively, 121.2± 29.9, 47.1± 10.2, and 148.4± 64.6 mg/mL and mean 25OH vitamin D was 22.6± 8. 0 ng/mL. Creatinine levels of patients with class II and III obesity were similar (0.8± 0.1 vs. 0.8± 0.2 mg/dL, respectively, p = 0.3273) and there was no significant difference when eGFR of these two groups was compared (100.9± 15.5 vs. 100.9± 18.8 mL/min/1.73m2, respectively, p = 1. 0000). Patients with DM had higher creatinine levels (0.9± 0.2 vs. 0.8± 0.1 mg/dL, p = 0. 0154) and lower eGFR (96.3 ± 18.3 vs. 105. 0 ± 16.9mL/min/1.73m2, p = 0. 0439) than non-diabetics. Linear regression models indicated statistically significant associations between creatinine and eGFR and the presence of DM (p = 0. 0154 and 0. 0439, respectively). No association involving creatinine or eGFR and presence of hypertension, or levels of BMI, LDL, HDL, triglycerides, vitamin D or HbA1c was detected.

Conclusion
The study points to the importance of pre-operative renal function screening in bariatric patients, since more than a quarter of the subjects had a decrease in glomerular filtration before surgery at a relatively young age. Although no association between long-term glucose control, represented by HbA1c, and renal function was detected, obese patients with DM seem to be at higher risk for precocious renal function impairment.
Presentation: No date and time listed
LBODP010 A Case of Glucocorticoid Resistance Syndrome
Authors: Sudhakar Shwetha Mallesara , Story Shannon Ellen 
Published: November 2022

Abstract

Case presentation
A 55 yr old female presented with persistent mild elevation of cortisol for the previous 7 years. Four years prior to presentation, she was incidentally noted to have a small left sided adrenal nodule on CT scan of the abdomen. Biochemical evaluation of the nodule showed 24 hour urine cortisol of 176(0-50), morning cortisol of 36 ug/dl(6.2-19.4), ACTH 18 pg/ml(7.3-66.3), two out of three salivary samples with elevated cortisol. High dose dexamethasone suppressed ACTH to &lt;1.1 from 13.8, cortisol from 30 to 3.3. She did not have signs and symptoms of Cushing's syndrome, mineralocorticoid excess nor androgen excess. Serum testosterone and DHEA were normal. DEXA revealed normal bone density. MRI brain demonstrated normal pituitary . She had no family history of pituitary or adrenal tumors nor endocrine syndromes. She underwent laparoscopic left adrenalectomy with pathology demonstrating benign adrenal adenoma, although the pathologist was unable to exclude nodular hyperplasia due to fragmented specimen. Elevation of 24 hour urine cortisol, serum cortisol and ACTH have persisted after surgery, without any clinical features of Cushing's. Gene sequencing with copy number analysis revealed heterozygous variant in the NR3C1 gene c.2239A&gt;T(p. Ile747Phe), suspicious for autosomal dominant hereditary primary glucocorticoid resistance syndrome also known as Chrousos syndrome.

Discussion
Glucocorticoid resistance syndrome is rare, may be familial or sporadic, and is characterized by end organ insensitivity to glucocorticoids. Glucocorticoids are steroid hormones synthesized and secreted by adrenal cortex. The actions of glucocorticoids are mediated by the glucocorticoid receptor, which belongs to nuclear receptor family of ligand-dependent transcription factors. Affected individuals have elevations in circulating cortisol and ACTH, but no clinical evidence of hypercortisolism. Excess ACTH can result in increased mineralocorticoid and/or androgenic activity resulting in HTN and/or hypokalemic alkalosis and acne/hirsutism/infertility/male pattern hair loss. Asymptomatic, normotensive patients with primary glucocorticoid resistance do not require any treatment. Aim of treatment is to suppress excess ACTH to decrease mineralocorticoid and androgen effects. Treatment involves high doses of dexamethasone(1-3 mg/day), which activate the mutated and/or wild type hGR alpha and suppresses endogenous secretion of ACTH.

Conclusion
Mutations in human GR gene impair one or more molecular mechanisms of glucocorticoid action affecting signal transduction and altering tissue sensitivity to these hormones. Recognition of this condition avoids unnecessary adrenal surgery and informs appropriate treatment and long term follow up of patients and family members.
Presentation: No date and time listed
LBSAT56 Adrenal And Juxta-adrenal Schwannomas: A Single Center Study
Authors: Rolak Stacey , Dogra Prerna , McKenzie Travis , Young William F , Bancos Irina 
Published: November 2022

Abstract

Objectives
Adrenal schwannomas and juxta-adrenal schwannomas are rare tumors with limited data on clinical and radiologic features. We aimed to summarize the clinical, biochemical, and imaging characteristics of adrenal and juxta-adrenal schwannomas.

Methods
We performed a single-center retrospective study of patients with a histopathologic diagnosis of adrenal or juxta-adrenal schwannoma between 1995-2022.

Results
A total of 24 patients (18, 75% women) were diagnosed with either primary adrenal schwannoma (8, 33%) or a juxta-adrenal schwannoma (16, 67%) at a median age of 57 years (range, 27 - 77 years). Most tumors (21, 88%) were discovered incidentally on imaging, while 2 were diagnosed because of symptoms of mass effect, and 1 diagnosed incidentally on pathology during nephrectomy performed for renal cell carcinoma. None of the patients had a known genetic syndrome. The median time from identification of schwannoma on imaging to hormonal evaluation was 62 days (range, 0–2076 days). All tumors were unilateral, with 15 (62%) on the left and 9 (38%) on the right. At diagnosis, the median tumor size was 4 cm (range, 2 - 13 cm). Adrenal schwannomas were smaller when compared to juxta-adrenal schwannomas (median of 3.1 cm [range, 2 - 9 cm] vs 4.6 cm [range, 2.3 - 13.3 cm]) (P=0. 037). On imaging, the tumors were round or oval in shape in 16 (70%), lobulated in 7 (30%), solid in 15 (68%), solid-cystic in 7 (32%), heterogeneous in 14 (61%), and homogeneous in 9 (39%). Scattered or peripheral calcifications were seen in 2 cases. In 9 patients with available contrast-enhanced CT, all of the schwannomas demonstrated enhancement. The median unenhanced CT attenuation was 30 Hounsfield units (HU) (range, 12 - 38 HU). In 6 patients with available follow-up imaging of at least 6 months, median growth per year was 0.27 cm (range, 0 - 0.8 cm). Of the 20 patients who underwent complete hormonal testing, all had non-functioning tumors. Biopsy was performed in 5 (20%) patients and all were diagnostic of schwannoma. Adrenalectomy was performed in in 23 (96%) patients (laparoscopic in 16 [70%] and open in 7 [30%]). Open adrenalectomy was more common in patients with larger tumors (median size 7.5 cm; range, 2–13.3 cm) when compared to patients treated laparoscopically (median size 4 cm; range, 2.3–5.4 cm) (P=0. 041). Postoperatively, patients were followed clinically for a median of 1.7 years (range, 0-19 years) or radiographically (n=11) for a median of 2 years (range, 0. 01-11 years), without recurrence or new tumor development.

Conclusions
Adrenal and juxta-adrenal schwannomas are nonfunctioning benign tumors that present with indeterminate radiographic features, including large tumor size and increased unenhanced CT attenuation. We did not find an imaging phenotype that was diagnostic of schwannoma. The diagnosis of this rare tumor is based on biopsy or resection.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
ODP015 "Malignant" Hypertension in an Older Male
Authors: Naha Sowjanya , Gardner Michael 
Published: November 2022

Abstract

Background
Malignant hypertension connotates extreme elevation of blood pressure with associated acute target organ injury. Secondary causes of hypertension should always be considered in patients presenting with acute organ dysfunction especially when the hypertension is also resistant. Clinical case: A 66-year-old male was transferred to our hospital after two successive admissions to a local hospital with acute confusion. Importantly, he was noted to have acute kidney injury and hypokalemia in the course of those admissions. On review of his records, it was noted that he had been evaluated recently for chest pain with a contrast enhanced chest CT which incidentally detected a left adrenal mass. Biopsy of the mass had been performed and returned positive for adrenocortical carcinoma. Past history was also notable for chronic hypertension, type 2 diabetes and hypothyroidism for which he was on appropriate therapy. On physical examination, the patient was noted to be hypertensive. Other pertinent findings included facial plethora, extensive bruising and supraclavicular fat pad fullness. Abdominal striae were not seen. Laboratory investigations showed hyperglycemia (glucose: 201 mg/dL), hypokalemia (potassium: 3. 0 mmol/L) and metabolic alkalosis (bicarbonate: 30 mmol/L). Endocrine work up showed suppressed aldosterone (&lt;4. 0 ng/dL, n: &lt;21 ng/dL), total testosterone (31 ng/dL, n: 240-950 ng/dL) and ACTH (&lt;5. 0 pg/mL, n: 7.2-63 pg/mL). Dehydroepiandrosterone (474 mcg/dL, n: 12-227 mcg/dL) and androstenedione (219 ng/dL, n: 40-150 ng/dL) levels were elevated. Cortisol levels did not suppress with overnight dexamethasone suppression test (29.8 mcg/dL). A diagnosis of Cushing's syndrome secondary to adrenocortical carcinoma was made. The patient was initiated on chemotherapy with carboplatin and etoposide. He was planned for mitotane therapy but passed away unexpectedly before the drug could be arranged.

Conclusion
Adrenocortical carcinoma can present with rapid onset of Cushingoid symptoms as well as sudden decompensation of previously controlled chronic hypertension, both of which were seen in this case. Although relatively uncommon, it remains a treatable and yet deadly cause for secondary hypertension, and should be considered in the appropriate clinical and biochemical settings.
Presentation: No date and time listed
ODP294 An Unusual Case of Endocrine Disruption as an Early Expression of Low Grade Intra Sellar Chordoma
Authors: Babu Vedesh Kumar , Suravajjala Devi , Kolli Swapna , Eranki Madhuri , Eranki Vijay 
Published: November 2022

Abstract
A 53y/o male patient presented to his PCP with fatigue and diagnosed with low testosterone and was started on testosterone. P ituitary labs were not checked then. After 6-8 weeks he was referred to neurology for new onset vision problems, diplopia, and daily headaches. MRI brain then showed a sellar mass of 2.4×2.6×2.7 cm with sphenoid sinus extension and bony thinning alongthe margins of the sella turcica which was nearly imperceptible. On testosterone replacement, biochemical assessment of anterior pituitary function showed total testosterone: 836 (264–916 ng/dl), Free Testosterone: 32.6 (2.5-9.5 ng/ml), LH&lt;0.1 (1.2-8.6 IU/L), FSH 0.2 (1.5-12.4 IU/L), Prolactin 18 (4-26 ng/ml), TSH 0. 03(0.4-4.1 UIU/ml), FT4 0.63 (0.8-1.9ng/dl), IGF 188 (55-186 ng/ml), ACTH&lt;5 (10-65 pg/ml), Cortisol&lt;1 (4.8-19.5 ug/dl). Endoscopic endonasal surgery was performed with complete removal of the tumorand abdominal fat graft harvest. Histopathological findings confirmed well differentiated low grade chordoma. Post operatively he improved, and headaches and visual disturbances resolved. Patient was sent home on Hydrocortisone 10mg am/5mg pm. Then, he presented to our endocrine clinic for initial hormonal evaluation. On steroid replacement, endocrine testing was repeated four weeks post-surgery. Labs showedTSH 2. 070 (0.4-4.1 UIU/ml), FT4 1.16 (0.8-1.9ng/dl), FSH&lt;0.3(1.5-12.4 IU/L), LH&lt;0.3(1.2-8.6 IU/L), Prolactin 26 (4 -26), ACTH 19.6 (10-65 pg/ml), Cortisol 7 (4.8-19.5 ug/dl), IGF-1 129 (55-186 ng/ml). Four months after the surgery, patient passed the cosyntropin stimulation test and was able to wean off the hydrocortisone replacement. Post-op repeat MRI brain showed complete resolution of the clivial mass. Current, he remains stable with regular follow ups. The most common presenting symptoms of a sellar chordoma include visual problems and uncommonly hypopituitarism. Our case shows that non-adenomatous tumors can still challenge us with the original presentation as an endocrine deficit. In a case series, only one of nine cases had presented with pituitary dysfunction. Our patient was noted to have hypogonadism and started on testosterone supplementation without further investigation. It is important to evaluate hormonal status in all pituitary masses and recognize that some cases of sellar chordoma can present with endocrine dysfunction as the initial manifestation. In our case, endocrine function of the patient returned to normal once the pituitary compression from chordoma was eliminated.
Presentation: No date and time listed