bluuebunny/crossref_metadata_2025_split huggingface dataset:
OR22-2 Ghrelin Receptor (GHSR1a) Functional Selectivity As A Novel Pharmacotherapeutic Strategy To Normalize Dysfunctional Metabolic Homeostasis
Authors: Gross Joshua 
Published: November 2022

Abstract
The growth hormone secretagogue receptor-1a (GHSR1a) is the cognate G protein-coupled receptor (GPCR) for the orexigenic agonist ghrelin and the anorexigenic antagonist liver-expressed antimicrobial peptide-2 (LEAP2). The ghrelinergic system is activated under conditions of caloric restriction and/or environmental stress, and it acts pleiotropically to restore physiological homeostasis by modulating both central and peripheral metabolic processes, including food-seeking behavior, glycemia, energy utilization/nutrient partitioning, and cardiovascular function. Consequently, ghrelin/GHSR1a signaling provides an accessible and desirable pharmacological target. GHSR1a-mediated physiological responses rely upon distinct G protein- and β-arrestin (βarr)-dependent signaling pathways, a property referred to as 'functional selectivity' or 'biased signaling.' Thus, when treating disorders of metabolic dysfunction (e.g., obesity, type II diabetes, neurodegenerative disease), a pharmacotherapeutic strategy that modulates 'biased' GHSR1a signaling may uncouple desired therapeutic outcomes from unwanted side effects. For example, animal models bearing G protein- or βarr-biasing GHSR1a mutations may express differences in orexigenic and glucoregulatory effects that are signaling pathway-dependent, and our group has demonstrated that GHSR1a antagonism blunts cocaine-induced neuroadaptive behaviors via a mechanism requiring βarr2 in dopaminergic neurons (Toth et al., 2016, Synapse). Based on these findings and the principle of ligand functional selectivity, we sought to identify new GHSR1a drug candidates that could distinguish between G protein and βarr pathways. We discovered a GHSR1a-selective, G protein-biased agonist — N8279 (NCATS-SM8864) — based on a novel chemotype. Comprehensive pharmacological analysis revealed that N8279 elicits potent and biased Gαq activity at both the apo- and ghrelin-bound GHSR1a. Molecular modeling coupled with mutagenesis and medical chemistry supports that N8279 signals through the GHSR1a via a unique extended binding mode requiring the extracellular loop 2 and thereby, enables preferential signaling through the Gαq pathway over alternative G proteins (Gαi∕o, Gα12∕13) and βarr2. Critically, N8279 is readily brain penetrant in mice, exhibits advantageous pharmacokinetics, and attenuates aberrant dopaminergic behaviors in both genetic and pharmacological mouse models of hyperdopaminergia. Our findings together provide important insights into mechanisms governing GPCR signaling and illustrate how functional selectivity might be leveraged to develop GHSR1a pharmacotherapeutics to normalize pathological disruptions of metabolic homeostasis.
Presentation: Monday, June 13, 2022 11:15 a.m. - 11:30 a.m.
RF17 | PMON23 Argentinian multicentric genetic study of pituitary hormonal deficiencies using a custom panel based on single molecule molecular inversion probes
Authors: Alonso Guillermo , Cau Carolina Arias , Belgorosky Alicia , Benzrihen G , Bergada Ignacio , Braslavsky Debora , Camper Sally , Ciaccio Marta , D'Amato S , Palma Isabel D , Figueroa Veronica , Forclaz Veronica , Keselman Ana , Kitzman Jacob , Gil Susana Mallea , Central Hospital Militar , Argentina Buenos Aires , Marino Roxana , Marti Marcelo , Miras Mirta , Garrido Natalia Perez , Ramirez Pablo , Vishnopolska Sebastian , Camilletti Maria Andrea , Mayer Julian Martinez , Murriello Augusto Chaves , Felker Gonzalo Chirino , Perez-Millan Maria 
Published: November 2022

Abstract
Hypopituitarism with deficiency of one or more pituitary hormones (combined pituitary hormone deficiency or CPHD) can vary in severity and age at presentation. Additionally, the hormone abnormalities may evolve with time necessitating frequent evaluation. These hormonal deficits can also be present as part of a syndrome, with patients showing extrapituitary abnormalities such as eye or forebrain malformations. Over the past decade, there has been an explosion in the knowledge of the genetic cascade that orchestrates hypothalamic and pituitary development. Several transcription factors and signaling molecules are critical for cell differentiation and proliferation at a very early stage of gestation. However, more genes remain to be identified in order to provide patients with a definitive aetiology. We studied 95 children with congenital hypopituitarism from seven pediatric hospitals from Argentina. Children with non-endocrine, non-familial idiopathic short stature served as a control group (n=100). A custom exon capture panel based on single-molecule molecular inversion probes sequencing (MIPS) was performed in probands and parents. This panel tests 104 genes: including a selection of reported and candidate genes chosen from our knowledge of pituitary development in mice and PROP1 interacting proteins. We found at least 1 variant in 50 probands. The prevalence of known variants in the pituitary transcription factor genes PROP1 and PIT1 (frequently mutated in CPHD) was low in our cohort. A significant number of disease-causing variants were found in LHX3, LHX4, GLI2 and OTX2. An important advance of our study is the identification of pathogenic variants in recently discovered and novel genes. We found an heterozygous variant in the Roundabout (ROBO) receptor homolog 1 gene: ROBO1;p.Arg1504* in a patient with CPHD and septo-optic dysplasia (SOD); two variants in Steroid Receptor SRA1: p. Ile179Thr and p.Val110delinsArgLeu in a patient with CPHD and hypogonadism hypogonadotropic and a missense variant in Semaphorin 3A SEMA3A: p.Val588Leu in a case of CPHD and aortic coarctation. Our findings support evidence that the etiology of congenital hypopituitarism is highly heterogeneous and may be infrequently monogenic with full penetrance, underlying a more complex pathogenesis.
Presentation: Sunday, June 12, 2022 12:36 p.m. - 12:41 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF17 | PMON27 Genetic Subtype Differences in Relation to Health Problems Among Adults With Prader-Willi Syndrome
Authors: Pellikaan Karlijn , Rosenberg Anna , Wellink Charlotte , Garcia Juan Tellez , van Abswoude Denise , van Zutven Laura , Brüggenwirth Hennie , Resnick James , van der Lely Aart Jan , de Graaff Laura 
Published: November 2022

Abstract

Background
Prader-Willi syndrome (PWS) is a complex rare genetic disorder associated with hypothalamic dysfunction, pituitary hormone deficiencies, hyperphagia and (morbid) obesity. PWS is caused by loss of expression of paternally expressed genes on chromosome 15q11.2-q13. The most common genetic mechanisms leading to PWS are paternal deletion (DEL) and maternal uniparental disomy (mUPD). DELs can be subdivided in type 1 and (smaller) type 2 deletions (DEL-1, DEL-2). Most research has focused on behavioral, cognitive and psychological differences between patients with a DEL-1, DEL-2 or mUPD. However, little is known about the genetic subtype differences in relation to physical health problems.

Methods
We reviewed the medical files of all adults with genetically confirmed PWS who visited the outpatient clinic of the Center for Adults with Complex Rare Genetic Syndromes at the Erasmus University Medical Center, Rotterdam, the Netherlands, between January 2015 and June 2021. All patients underwent a systematic health screening, including a structured interview, a medical questionnaire, a complete physical examination, biochemical measurements, and a review of the medical records. Health problems, physical complaints, symptoms of disease and behavioral challenges were compared between adults with an mUPD and DEL and between adults with a DEL-1 and DEL-2.

Results
Twenty-eight adults had an mUPD and 65 a DEL (13 DEL-1, 27 DEL-2, 25 unspecified). Gender, age and BMI did not differ between the genetic subgroups. Although psychiatric problems (psychotic episodes) were significantly more often present in adults with an mUPD (P &lt; 0.001) and scoliosis was more prevalent among patients with DEL (P = 0.04), there was only a slight difference in prevalence of other medical problems like hypertension, cold intolerance, edema, hyperphagia, skin picking, abdominal pain and fatigue. There were no significant differences between DEL-1 and DEL-2. However, fatigue, cold intolerance, edema and hyperphagia were slightly more prevalent among adults with a DEL-1, whereas osteopenia, constipation and skin picking were more prevalent among adults with a DEL-2.

Conclusion
The differences in health problems between PWS adults with DEL-1, DEL-2 and mUPD are mostly present in the psychological domain. Especially psychotic episodes were more frequent in adults with an mUPD. Apart from scoliosis, there were no significant differences in physical health outcomes between the genetic subtypes.
Presentation: Sunday, June 12, 2022 1:00 p.m. - 1:05 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
LBODP076 Hypophysitis Misdiagnosed As Pituitary Macroadenoma During Pregnancy
Authors: Meftali Sabrina , Bilbatua Martha , Bhatt Bankim A 
Published: November 2022

Abstract

Introduction
Surgical treatment of nonfunctioning symptomatic pituitary macroadenoma may be associated with significant morbidity and the need for long-term medications. In late pregnancy and the postpartum periods, lymphocytic hypophysitis can present as a pituitary macroadenoma. We present a rare case of a pregnant patient who underwent pituitary surgery for lymphocytic hypophysitis.

Case presentation
A 37-year-old woman was evaluated for headaches and double vision during the third trimester of her pregnancy. A visual field exam showed bitemporal hemianopsia. Brain magnetic resonance imaging (MRI) showed a 2 cm intrasellar tumor with suprasellar extension, interpreted as a pituitary macroadenoma. The patient underwent a cesarean section. Labs after delivery showed IGF-1: 153 ng/ml (79-259), LH: &lt; 0.2 mIU/ml (1.9-12.8), FSH: 6.4 mIU/ ml (2.3-12.6), Prolactin: 4.3 ng/ml (2.2-30.3), and a low morning cortisol: 2.4 ug/dl (4.2- 22.4). Pituitary MRI with intravenous contrast found a stable pituitary macroadenoma with suprasellar extension compressing the optic chiasm and prechiasmatic optic nerves without evidence of apoplexy. She underwent image-guided endoscopic transsphenoidal resection of the pituitary mass. Postoperatively, she developed diabetes insipidus that was treated with desmopressin. She was treated with steroids for secondary adrenal insufficiency and levothyroxine for central hypothyroidism. The pathology report showed hypophysitis; a lymphoplasmacytic infiltrate identified within the specimen with increased IgG4 expression. Differential diagnoses included IgG4-related hypophysitis and lymphocytic hypophysitis with an IgG4-expressing plasma cell component. Serum IGG 4 was 62 mg/dl (normal: 2 - 96 mg/dl); however, patient was already on steroids. She has been requiring hydrocortisone, levothyroxine, and desmopressin.

Discussion
Lymphocytic hypophysitis often occurs in late pregnancy or the postpartum period. MRI usually shows a pituitary mass, mimicking an adenoma. However, differences between lymphocytic hypophysitis and pituitary adenoma, using different imaging techniques, have been described. Lymphocytic hypophysitis should be considered in the differential diagnosis of women presenting with pituitary enlargement in the peripartum period. These patients may benefit from conservative treatment with glucocorticoids based on clinical suspicion.
Presentation: No date and time listed
ODP286 A Case of Synchronous Growth Hormone and Adrenocorticotrophic Hormone Secretion in a Patient with an Incidental Pituitary Adenoma.
Authors: Maraqa Sima , Bushnaq Lina , Silverstein Julie M 
Published: November 2022

Abstract
The most common type of co-secreting functional pituitary adenoma is a tumor-producing growth hormone and prolactin. Other types of co-existing functioning adenomas are extremely rare. We present a 68-year-old male patient with a pituitary adenoma presenting with acromegaly and Cushing's disease (CD). A 68-year-old male was referred for an incidental pituitary macroadenoma found on magnetic resonance imaging (MRI) for his chronic nasal congestion. He denied headaches or blurry vision. He reported an increase in shoe size, worsening hypertension and diabetes, and a 40-pounds weight gain over several years. Past medical history included arthritis, type two diabetes mellitus, hypertension, sleep apnea, hypogonadism, chronic kidney disease, and coronary artery disease. Physical exam was notable for BMI of 51 kg/m2 and enlarged hands and feet. No stigmata of Cushing's syndrome were present. MRI showed a 2. 0×2.5 cm sellar mass involving the right cavernous sinus without a mass effect on the optic chiasm. Laboratory workup showed an elevated IGF-1 level of 703 ng/mL and 678 on repeat, growth hormone (GH) 1.1 ng/mL, adrenocorticotropic hormone (ACTH) 41 pg/mL, and am cortisol 15 mcg/dL. Am cortisol after 1 mg of dexamethasone was 6.2 mcg/dL with an appropriate dexamethasone level. His and 24-hour urine-free cortisol was elevated at 87.1 mcg/24h, HgbA1C was 8.3%, testosterone level was low, and PRL and thyroid levels were normal. He underwent transsphenoidal surgery (TSS). Postoperative morning cortisol day 1 was 18.9 mcg/dL. Pathology showed a sparsely granulated somatotroph adenoma. Seven days post-surgery, he presented with diplopia, ophthalmoplegia, and ptosis. MRI showed enlargement of the right cavernous sinus with possible residual tumor and blood products. He underwent a second TSS with evacuation of a hematoma. The patient's nadir postoperative serum cortisol was 14.4 mcg/dL and IGF-1 level 513 ng/mL one month after his initial surgery. Pathology showed organizing hemorrhage and necrotic pituitary adenoma. His ophthalmoplegia resolved, and diplopia partially improved. The synchronous occurrence of CD and acromegaly is an extremely rare condition. It can be secondary to either a plurihormonal adenoma or two functional adenomas. In our case, the pathology findings suggest double adenomas. Surgical resection is first-line therapy for acromegaly and CD. Stereotactic radiosurgery and medical therapy are second-line options in persistent disease. The 5-year remission rates with Gamma Knife radiosurgery are higher in CD (81%) as compared to acromegaly. 1 Pasireotide, a somatostatin receptor ligand approved for both CD and acromegaly. Worsening glycemic control is a significant challenging aspect of its use.
Presentation: No date and time listed
Ciberbullying, ideação suicida e comunicação parento-filial em adolescentes e jovens adultos
Authors: Pereira Mónica , Fernandes Otília Monteiro , Relva Inês Carvalho 
Published: November 2022

O ciberbullying constitui uma realidade cada vez mais presente na vida dos mais jovens e desprotegidos, o que pode perturbar o seu desenvolvimento e bem-estar. O presente estudo tem como objetivo explorar a associação entre o ciberbullying, a ideação suicida e a comunicação parento-filial nos adolescentes e jovens adultos. O estudo foi feito com uma amostra de 401 adolescentes e jovens adultos, com idades compreendidas entre os 15 e os 24 anos. Recorreu-se ao Questionário de Cibervitimização (cyvic), ao Questionário de Ideação Suicida (qis) e à Escala de Avaliação da Comunicação na Parentalidade (compa) para coleta dos dados. No que se refere à idade foram encontradas diferenças significativas relativamente à cibervitimização. Quanto ao número de horas de utilização da Internet foram encontradas diferenças em relação à cibervitimização, à ideação suicida e à comunicação parental da figura materna nomeadamente nas subescalas confiança/partilha e metacomunicação. Foram encontradas associações entre a cibervitimização, ideação suicida e a comunicação parental do pai e da mãe. Por fim, observou-se que a ideação suicida prediz a cibervitimização, enquanto a isponibilidade da mãe prediz a cibervitimização. É urgente que este problema de saúde seja multidisciplinarmente identificado e combatido ao mesmo ritmo com que a tecnologia se entrosa e é preponderante na vida das gerações mais novas.
Frailty does not cause all frail symptoms: United States Health and Retirement Study
Authors: Chao Yi-Sheng , Wu Chao-Jung , Po June Y. T. , Huang Shih-Yu , Wu Hsing-Chien , Hsu Hui-Ting , Cheng Yen-Po , Lai Yi-Chun , Chen Wei-Chih 
Published: November 2022

BackgroundFrailty is associated with major health outcomes. However, the relationships between frailty and frailty symptoms haven’t been well studied. This study aims to show the associations between frailty and frailty symptoms.MethodsThe Health and Retirement Study (HRS) is an ongoing longitudinal biannual survey in the United States. Three of the most used frailty diagnoses, defined by the Functional Domains Model, the Burden Model, and the Biologic Syndrome Model, were reproduced according to previous studies. The associations between frailty statuses and input symptoms were assessed using odds ratios and correlation coefficients.ResultsThe sample sizes, mean ages, and frailty prevalence matched those reported in previous studies. Frailty statuses were weakly correlated with each other (coefficients = 0.19 to 0.38, p < 0.001 for all). There were 49 input symptoms identified by these three models. Frailty statuses defined by the three models were not significantly correlated with one or two symptoms defined by the same models (p > 0.05 for all). One to six symptoms defined by the other two models were not significantly correlated with each of the three frailty statuses (p > 0.05 for all). Frailty statuses were significantly correlated with their own bias variables (p < 0.05 for all).ConclusionFrailty diagnoses lack significant correlations with some of their own frailty symptoms and some of the frailty symptoms defined by the other two models. This finding raises questions like whether the frailty symptoms lacking significant correlations with frailty statuses could be included to diagnose frailty and whether frailty exists and causes frailty symptoms.
Applying a deep convolutional neural network to monitor the lateral spread response during microvascular surgery for hemifacial spasm
Authors: Kim Minsoo , Park Sang-Ku , Kubota Yasuhiro , Lee Seunghoon , Park Kwan , Kong Doo-Sik 
Published: November 2022

Background
Intraoperative neurophysiological monitoring is essential in neurosurgical procedures. In this study, we built and evaluated the performance of a deep neural network in differentiating between the presence and absence of a lateral spread response, which provides critical information during microvascular decompression surgery for the treatment of hemifacial spasm using intraoperatively acquired electromyography images.

Methods and findings
A total of 3,674 image screenshots of monitoring devices from 50 patients were prepared, preprocessed, and then adopted into training and validation sets. A deep neural network was constructed using current-standard, off-the-shelf tools. The neural network correctly differentiated 50 test images (accuracy, 100%; area under the curve, 0.96) collected from 25 patients whose data were never exposed to the neural network during training or validation. The accuracy of the network was equivalent to that of the neuromonitoring technologists (p = 0.3013) and higher than that of neurosurgeons experienced in hemifacial spasm (p < 0.0001). Heatmaps obtained to highlight the key region of interest achieved a level similar to that of trained human professionals. Provisional clinical application showed that the neural network was preferable as an auxiliary tool.

Conclusions
A deep neural network trained on a dataset of intraoperatively collected electromyography data could classify the presence and absence of the lateral spread response with equivalent performance to human professionals. Well-designated applications based upon the neural network may provide useful auxiliary tools for surgical teams during operations.
Traditional Medicine Beliefs and Practices among Caregivers of Children under Five Years—The Child Health and Mortality Prevention Surveillance (CHAMPS), Western Kenya: A qualitative study
Authors: Ngere Sarah Hawi , Akelo Victor , Ondeng’e Ken , Ridzon Renee , Otieno Peter , Nyanjom Maryanne , Omore Richard , Barr Beth A. Tippett 
Published: November 2022

Background
Approximately 80% of the population residing in sub-Saharan Africa relies on Traditional Medicine (TM). However, literature on factors motivating the use of TM for children under the age of five in these settings is limited. Such information can guide policy formulation for integration of TM into mainstream health care services. This study aimed to describe the motivation on use of TM among caregivers of children residing in rural and urban communities in western Kenya.

Methods
The socio-behavioral sciences (SBS) arm of the Child Health and Mortality Prevention Surveillance (CHAMPS) program in western Kenya, conducted a cross-sectional qualitative study in Manyatta—an urban informal settlement located in Kisumu town and Karemo—a rural setting in Siaya County. We performed 29 in-depth interviews, 5 focus group discussions and 11 semi-structured interviews with community representatives (n = 53), health workers (n = 17), and community leaders (n = 18). All the participants were purposively sampled. We performed thematic analysis using both inductive and deductive approaches. Data management was completed on Nvivo 11.0 software (QSR International, Melbourne, Australia).

Results
Our findings reveal that some caregivers prefer TM to treat some childhood diseases. Use of TM was informed by illness beliefs about etiology of disease. We observed an appreciation from the study participants that malaria can effectively be treated by Conventional Medicine (CM) while TM was preferred to treat measles and diseases believed to be associated with supernatural etiology such as witchcraft, evil spirit or breaching cultural taboos. TM was also used in instances where CM failed to provide a diagnosis or when CM was ‘slow’. TM in such cases was used as a last resort.

Conclusion
We observed varied beliefs that motivate caregivers’ choice of TM use among children in western Kenya. It is therefore crucial to consider perceptions and socio-cultural beliefs about illnesses when formulating interventions that are geared towards child health.
A national study of burnout and spiritual health in UK general practitioners during the COVID-19 pandemic
Authors: Whitehead Ishbel Orla , Moffatt Suzanne , Jagger Carol , Hanratty Barbara 
Published: November 2022

Objectives
To quantify the burnout and spiritual health of general practitioners (GPs) in the United Kingdom (UK) who worked during the Covid-19 Pandemic.

Design
Online survey, April/May 2021, distributed via emails to general practices, Clinical Commissioning Groups (CCGs), Health boards, Clinical Research Networks, professional groups, social media GP groups and networks.

Setting
United Kingdom.

Participants
1318 GPs who had worked in the National Health Service (NHS) during the COVID-19 pandemic (March 2020 –May 2021).

Main outcome measures
Burnout scores, measured by the Maslach Burnout Inventory (MBI) for Medical Personnel; spiritual health, measured using the Functional Assessment of Chronic Illness Therapy—Spiritual Well-Being, Non-Illness (FACIT-SP-NI).

Results
19% of surveyed GPs were at the highest risk for burnout, using accepted MBI ‘cut off’ levels. There was no evidence of a difference in burnout by gender, ethnicity, or length of service. GP burnout was associated with GP spiritual health, regardless of identification with a religion. GPs with low spiritual health were five times more likely to be in the highest risk group for burnout.

Conclusions
Burnout is at crisis levels amongst GPs in the UK NHS. A comprehensive response is required, identifying protective and precipitating factors for burnout. The potentially protective impact of spiritual health merits further investigation.