bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tricuspid three-dimensional ring versus fashioned flexible band annuloplasty in management of functional tricuspid valve regurge: comparative long term study
Authors: Nosair Abdallah , Elkahely Mohamed , Nasr Sherif , Alkady Hesham 
Published: May 2020

Abstract
Background
Functional tricuspid valve regurgitation due to left sided valve lesions remains a common finding. Nowadays, different types of three-dimensional rings and flexible bands are considered to be the gold standard techniques for repair of such functional regurgitation. Our study aimed for long-term comparison of the durability and effectiveness of those techniques.

Results
The data of 170 adult patients with moderate or more functional tricuspid regurgitation secondary to mitral stenosis or regurgitation receiving tricuspid valve repair using either rigid 3D rings (contour 3D or MC3 ring) or prosthetic fashioned bands (Dacron or PTFE) and mitral valve surgery between March 2013 and September 2018 were collected and analysed. Patients were classified in two matched groups: ring group (group A) consisting of 90 cases and band group (group B) consisting of 80 cases. follow-up period ranged from 55.2 to 78 months (mean 67.2 ± 10.8), during this period New York heart association for dyspnea functional class evaluation and full echocardiographic assessment were done and was scheduled as following: before hospital discharge, after 6 months of surgery and finally, every 2 years. In-hospital mortality was 1(1.1%) and 2 (2.5%) with p value 0.49 after ring or band annuloplasty, respectively. No significant differences in both groups regarding hospital mortality and morbidities. There was statistically significant decrease in NYHA class, degree of TR, and PASP within the 2 groups postoperatively with p value of 0.03, 0.04, and 0.033, respectively, with no statistically significant difference between both groups (p value > 0.05). There was statistically significant difference in the freedom from recurrent TR and need for reoperation during the follow-up period between both groups with lower recurrence and reoperation rates in group A, (p value 0.03 and 0.001, respectively).

Conclusion
Tricuspid valve repair with different annuloplasty rigid three dimensional rings or fashioned flexible bands for functional tricuspid regurgitation offers good long-term outcome. Yet, the rigid rings maintain their benefits on the rate of recurrent TR and the need for reoperation.
In vitro antioxidant, anti-inflammatory, and anticancer activities of methanolic extract and its metabolites of whole plant Cardiospermum canescens Wall
Authors: Ketha Alekhya , Vedula Girija Sastry , Sastry A. V. S. 
Published: May 2020

AbstractBackgroundTraditionally, the whole plant ofCardiospermum canescenshas wide applications in the management of oxidative stress and inflammation in Africa and Asia. The present study investigated the antioxidant, anti-inflammatory, xanthine oxidase (XO) inhibitory, and anticancer activities of metabolites present in the crude methanolic extract of whole plantC.canescens(CCE).ResultsChemical examination ofCCErevealed the presence of six known compounds (1–6). From the results of in vitro studies, it can confirm thatCCEexhibited notably inhibition of DPPH and superoxide free radicals, along with COX-1, COX-2, 5-LOX, and XO enzymes. Compounds2and3showed significant inhibition of DPPH and superoxide free radicals. Also, compound2exhibited good inhibition of COX-1 and COX-2 enzyme with IC50of 87.0 and 88.0 μg/mL. Furthermore,CCEexhibited significant inhibition of 5-LOX and XO enzymes with IC50of 42.5 and 56.0 μg/mL, respectively, while standard with IC50of 42.5 and 56.0 μg/mL, respectively. Among the test series of cancer cell lines, compounds2,3, andCCEshowed a significant percentage of cell growth lysis of DLD-1 with IC50values of 52.5, 72.5, and 32.5 μg/mL, respectively. Besides, all the metabolites andCCEshowed a very weak degree of specificity against NHME, indicates less toxicity to normal cells.ConclusionTo conclude, the results of the present study indicated that the methanolic extract from the whole plant ofC.canescensdisplayed antioxidant activity by inhibiting DPPH and superoxide free radicals; anti-inflammatory effects by regulating enzymes COX-1, COX-2, 5-LOX, and XO; and anticancer activity by inhibiting the growth of MCF-7, DLD-1, HeLa, and A549. These activities can link to natural active compounds2and3. This study supports the traditional uses of the root ofC.canescens. These data findings suggest thatC.canescenscan be a promising natural source of biological medicines for oxidative stress, inflammation, gout, and cancer.
Embedding neuroscience in psychiatry training
Authors: O'Loughlin Christopher 
Published: May 2020

SUMMARYTraining in neuroscience is vital to the future of psychiatry as a medical specialty. Trainees and trainers alike demonstrate a desire to keep up to date with developments in the associated scientific fields. Neuroscience increasingly underpins clinical assessments, treatment options and patients’ expectations. Psychiatry training in the UK can embrace neuroscience at many levels, from discussing patient presentations with supervisors, to teaching programmes supported by the Royal College of Psychiatrists’ activities. Although challenges remain, neuroscience literacy enhances the specialty and will improve patient care.
Children and young people who die by suicide: childhood-related antecedents, gender differences and service contact
Authors: Rodway Cathryn , Tham Su-Gwan , Ibrahim Saied , Turnbull Pauline , Kapur Nav , Appleby Louis 
Published: May 2020

Background
Worldwide suicide is commonest in young people and in many countries, including the UK, suicide rates in young people are rising.

Aims
To investigate the stresses young people face before they take their lives, their contact with services that could be preventative and whether these differ in girls and boys.

Method
We identified a 3-year UK national consecutive case series of deaths by suicide in people aged 10–19, based on national mortality data. We extracted information on the antecedents of suicide from official investigations, primarily inquests.

Results
Between 2014 and 2016, there were 595 suicides by young people, almost 200 per year; 71% were male (n = 425). Suicide rates increased from the mid-teens, most deaths occurred in those aged 17–19 (443, 74%). We obtained data about the antecedents of suicide for 544 (91%). A number of previous and recent stresses were reported including witnessing domestic violence, bullying, self-harm, bereavement (including by suicide) and academic pressures. These experiences were generally more common in girls than boys, whereas drug misuse (odds ratio (OR) = 0.54, 95% CI 0.35–0.83, P = 0.006) and workplace problems (OR 0.52, 95% CI 0.28–0.96, P = 0.04) were less common in girls. A total of 329 (60%) had been in contact with specialist children's services, and this was more common in girls (OR 1.86, 95% CI 1.19–2.94, P = 0.007).

Conclusions
There are several antecedents to suicide in young people, particularly girls, which are important in a multiagency approach to prevention incorporating education, social care, health services and the third sector. Some of these may also have contributed to the recent rise.
Quality by Design–Based Assessment for Analytical Similarity of Adalimumab Biosimilar HLX03 to Humira®
Authors: Zhang Erhui , Xie Liqi , Qin Peilan , Lu Lihong , Xu Yanpeng , Gao Wenyuan , Wang Linlin , Xie Michael Hongwei , Jiang Weidong , Liu Scott 
Published: May 2020

AbstractQuality by design (QbD) is an efficient but challenging approach for the development of biosimilar due to the complex relationship among process, quality, and efficacy. Here, the analytical similarity of adalimumab biosimilar HLX03 to Humira® was successfully established following a QbD quality study. Quality target product profile (QTPP) of HLX03 was first generated according to the public available information and initial characterization of 3 batches of Humira®. The critical quality attributes (CQAs) were then identified through risk assessment according to impact of each quality attribute on efficacy and safety. The anticipated range for each CQA was derived from similarity acceptance range and/or the corresponding regulatory guidelines. Finally, a panel of advanced and orthogonal physicochemical and functional tests and comparison of 6 batches of HLX03 and 10 batches of the reference standard demonstrated high similarity of HLX03 to Humira®, except for slightly lower percentage of high mannosylated glycans (%HM) in HLX03 which had no effect on FcγRIII binding and antibody-dependent cell-mediated cytotoxicity (ADCC) activity in human peripheral blood mononuclear cell (PBMC). All above demonstrated the feasibility and efficiency of QbD-based similarity assessment of a biosimilar monoclonal antibody (mAb).
SUN-092 Effect of Pubertal Induction with Gonadotropins and GnRH Therapy in Male Hypogonadotropic Hypogonadism: Meta-Analysis
Authors: Agarwal Swashti , Austin Paul , Wood Alexis C , Karaviti Lefkothea P 
Published: May 2020

Abstract
Background: The use of gonadotropins is a recent strategy for inducing puberty in adolescent males with hypogonadotropic hypogonadism (HH). Testosterone use has been discouraged in patients who desire to preserve fertility. Human chorionic gonadotropin (hCG) has been recommended for inducing puberty in HH; however, several clinicians administer hCG in combination with other gonadotropins. The benefits of using combination gonadotropin therapies (hCG+) over hCG monotherapy in pre-pubertal adolescent males with HH has not been clearly established. We performed a meta-analysis to assess the outcomes of hCG compared to hCG+ in terms of virilizing effects and testicular growth in peripubertal boys with HH.
Methods: We evaluated for heterogeneity among studies. We calculated pooled means for the post-treatment mean testicular volume (MTV), testosterone (T) level, and penile length for the hCG monotherapy and hCG+ treatment groups. We performed a meta-regression analysis to examine the contribution of various factors to post-treatment outcomes including baseline T level, age, treatment duration, and study quality.
Results: The meta-analysis included seven studies. All participants were prepubertal (age range: 13.3–25.9 years), with weighted mean treatment durations of 10.95 months for hCG monotherapy and 28.2 months for hCG. There was significant heterogeneity in baseline age (Q = 121.71; df = 1; P &lt; 0.001) and T levels (Q = 436.74; df = 1; P &lt; 0.001) between the two treatment groups. The hCG+ group had a larger post-treatment MTV, but it was not significantly different between the two groups (6.60 mL [95% CI, 3.18–10.02] for hCG monotherapy vs. 10.02 mL [95% CI, 8.30–11.75] for hCG+; P = 0.079). Post-treatment T levels differed significantly between the two groups (101.89 ng/dL [95% CI, 50.7–153.08] for hCG monotherapy vs. 424.10 ng/dL [95% CI, 304.59–543.62] for hCG+; P &lt; 0.0001). A meta-regression analysis of post-treatment T levels showed that baseline age, baseline T level, and study grade did not contribute significantly to the difference between treatment groups. Treatment duration explained 3.04% of the difference between the two groups (P &lt; 0.0001). After adjusting for treatment duration, the post-treatment T level remained significantly higher in the hCG+ group compared to the hCG monotherapy group. The hCG+ was also associated with better outcomes for post-treatment penile length, although these findings relied on data from only three studies.
Conclusion: Our study indicates that hCG+ therapies provide potential benefits over hCG monotherapy for pubertal induction in males with HH, regarding T levels and penile growth, with no difference in testicular growth between treatments. Prospective pediatric studies are needed to assess the benefits of these therapies in patients with HH and, ultimately, to establish guidelines for gonadotropin therapy in the adolescent population.
MON-355 Charge Syndrome: Unusual Cause of Hypogonadism Leading to Osteoporosis
Authors: Modi Ankur , Piziak Veronica 
Published: May 2020

Abstract
CHARGE syndrome is an unusual cause of hypogonadism; it is characterized by coloboma, heart defect, ateresia choanae, retarded growth and development, genital hypoplasia and ear anomalies. Two-thirds of affected patients have a mutation within the chromodomain helicase DNA-binding protein-7 gene, which is involved in embryonic development. The involvement of this gene in the pathogenesis of isolated idiopathic hypogonadotropic hypogonadism (HH) has been postulated. The reported incidence of this syndrome ranges from 0.1–0.2/10000 (1).
A 24 year old female presented to our facility for further management of her HH and osteoporosis in the setting of her CHARGE syndrome. She was born full-term and diagnosed with this condition at the age of 6. Formal genetic testing as an adult demonstrated mutation within the CHD7 gene (chr 8:61,757,970). She had delayed puberty secondary to her hypogonadism; she was not treated with HRT as benefits were not considered significantly sufficient. She subsequently developed osteoporosis at the age of 20 which was treated at an outside facility with pamidronate IV Q4 months along with calcium and Vitamin D supplementation. Her initial Dual-energy X-ray absorptiometry (DXA) showed scoliosis in the lumbar spine [bone mass density (BMD): 0.514,osteoporosis by Z-score] with total hip showing BMD: 0.738,osteopenia by Z-score. Follow-up DXA after 3 years showed statistically significant improvement in bone mineralization of her L-spine [BMD: 0.595, +16%] and total hip [BMD: 0.777, +13.5%]. She presented to our facility in 2018 with labs showing normal calcium and 25-OH D; treatment with pamidronate was continued. She had a repeat DXA in 2019 which showed Z-scores of 0 in the left and right femoral necks. She was given the option of continued treatment for her osteoporosis versus monitoring and chose the latter with follow-up DXA.
Hypogonadotropic hypogonadism is associated with delays in puberty or pubertal arrest. Luteinizing Hormone Releasing Hormone and HCG tests should be performed within the four months of life or at puberty in cases of hypogenitalism. GH deficiency should be investigated as a cause for growth retardation with GH stimulation levels. Hormone replacement is often required at puberty for females and is indicated for prevention of osteoporosis. Radiological testing with DXA scan should be included. Early proper endocrinological assessment and management is essential for adequate sexual development in these patients; this leads to improved overall quality of life along with prevention of serious morbidities, including bone demineralization (2).
1. Blake K D, Prasad C. CHARGE syndrome. Orphanet Journal of Rare Diseases 2006, 1:34.
2. Foppiani L, Maffe A. CHARGE syndrome as unusual cause of hypogonadism: endocrine and molecular evaluation. Andrologia (2010). 42: 326–330.
MON-359 Hollow Bones: A Case Report of Immobilization Osteoporosis in a Young Female
Authors: Bhat Salman Zahoor , Goyal Itivrita , Chaudhuri Ajay 
Published: May 2020

Abstract
Abstract
Introduction:
Osteoporosis is defined as decreased bone strength due to reduced bone mineral density (BMD) and/or abnormal bone architecture leading to bone fragility and increased risk of pathologic fractures. Typically a disease of post-menopausal females, osteoporosis is uncommon in the young. We present a case of a 34-year-old woman, who was diagnosed with severe osteoporosis in the setting of prolonged immobilization.
Clinical Case:
A 34-year-old woman was admitted for treatment of bacteremia in the setting of IV drug use and right hip septic arthritis leading to femoral head osteonecrosis requiring a long course of antibiotic treatment and resulting in prolonged immobilization. She was readmitted 2 months later with septic shock and bilateral septic arthritis needing right hip replacement for source control. She developed multiple contractures of lower extremities due to prolonged immobility and was immobile for a total of 11 months despite significant physical therapy (PT) involvement. A few months into her hospital stay, she developed acute onset right ankle pain with no falls or trauma. Xrays showed right tibial metaphyseal fracture and severe demineralization of bones of lower extremities. History and physical exam showed no signs/symptoms of malabsorption, hyperthyroidism or Cushing’s syndrome. Laboratory evaluation showed calcium (Ca) of 11.8 mg/dL (8.5–10.4), parathyroid hormone (PTH) &lt; 3 ng/dL (12–72), C-telopeptide (Ctx) 1806 pg/ml (60–650) and normal phosphate, TSH, prolactin, 25-hydroxy and 1,25-dihydroxy vitamin D levels. PTHrP (parathyroid hormone related peptide) was &lt; 2 pmol/L. 24-hour urine Ca was 414 mg (50–150). Serum and urine protein electrophoresis showed no monoclonal spike. Gonadal profile showed estrogen 42 pg/dL, FSH 1 mU /mL, LSH 0.1 mU /mL. DEXA scan showed severe osteoporosis with T-score of -3.2 at both the left femoral neck and lumbar spine. Osteoporosis and hypercalcemia were attributed to protracted immobilization. Therapy was initiated with alendronate 70 mg weekly along with vitamin D. Teriparatide was not used due to high serum Ca. Repeat labs at 6 months showed good response to alendronate with Ca 9.6, PTH 58, 24 hr urine Ca 96 and Ctx 1092. Mobilization of patient and regular PT were performed.
Conclusion:
Osteoporosis in a young adult is a rare entity and demands evaluation for secondary causes. An important and overlooked cause of bone loss is immobility and decreased load development on bones. Bone is a piezoelectric material and immobilization causes negative bone turnover. Early physical mobility and weight bearing is the most effective method of reducing bone loss. Teriparatide, due to anabolic effects has an advantage over bisphosphonates. Romosozumab (anti-sclerostin antibody) and whole body vibration are also being studied for disuse osteoporosis. Calcium and vitamin D supplementation are essential.
SUN-347 Glucagon-like Peptide 1 (GLP-1) Acts Directly On Human Osteoclasts To Increase Differentiation And Bone Resorptive Activity
Authors: Hansen Morten Steen , Søe Kent , Gorvin Caroline , Frost Morten 
Published: May 2020

Abstract
Glucagon-like peptide 1 (GLP-1) is an intestinal hormone released in response to nutrient intake that promotes glucose-dependent insulin secretion by acting upon the pancreatic GLP-1 receptor (GLP-1R). GLP-1R agonists (GLP-1RAs) are widely used in treatment of type 2 diabetes. Preclinical data indicate that GLP-1RAs could be repurposed to treat low bone mass as GLP-1R-depleted mice have higher bone resorption and thinner cortical bones, while insulinopenic and insulin resistant rats have improved bone formation and reduced bone mass deterioration when treated with GLP-1 or GLP-1RAs. However, the effect of GLP-1 and GLP-1RAs on human bone cells remains undetermined. We aimed to elucidate the effect of GLP-1 on primary human osteoclast (OC) and osteoblast (OB) cultures. OCs were differentiated over 10 days from human blood-derived CD14+ monocytes and OBs over 4–6 weeks from human bone. Cells were seeded on bovine bone slices and studies performed using fetal bovine serum, MCSF and RANKL (OC monocultures) or MCSF only (OB monocultures and OB+OC co-cultures). We first investigated the effect of GLP-1 on bone resorptive activity of mature OCs on bovine bone slices. GLP-1 increased the eroded bone surface percentage compared to vehicle in both OC monocultures (1nM P=0.002; 10nM P=0.023; n=8 donors) and OC+OB co-cultures (1nM P=0.013; 10nM P=0.012; n=8 donors). We then tested the effects of GLP-1 on osteoblast activity in OC+OB co-cultures by measuring alkaline phosphatase (ALP). We found that GLP-1 increased ALP in OC+OB cultures (1nM, P=0.049; 10nM, P=0.019) and these effects were reversed by the GLP-1R antagonist exendin 9–39 (1nM, P=0.93, 10nM, P=0.64). However, in OB monocultures GLP-1 had no effects on ALP (1nM P=0.93, 10nM P=0.64) indicating a GLP-1-driven increase in osteoblast activity through osteoclast-osteoblast coupling. We then assessed the effect of GLP-1 on OC differentiation by assessing TRAcP activity. Although there was a trend towards increased TRAcP activity upon stimulation with GLP-1 on day 10 of osteoclastogenesis, this was not statistically significant (1nM P=0.12; n=8 donors; 10nM P=0.29, n=4 donors). Our studies indicated GLP-1 may have a direct effect on osteoclasts, and we therefore sought to characterise GLP-1-mediated signalling in these cells. We assessed the effect of GLP-1 on cAMP signalling using LANCE assays and assessed phosphorylation of ERK proteins by Western blot analysis in human OC cultures. OCs treated with 10nM GLP-1 for 30 minutes had increased cAMP signaling (P=0.004, n=12 bone slices from 2 donors) when compared to vehicle. Furthermore, 10nM GLP-1 induced rapid increases in phosphorylated ERK (P=0.03 following 2 minutes exposure, n=4 blots). In conclusion, our studies reveal that GLP-1 increases activity in primary mature human OCs, and OBs, via OCs. Our signaling studies in OCs indicate this is mediated by direct action of GLP-1 on human bone cells.
MON-249 SDHD Mutation: Nonfunctional Paragangliomas Presenting as Bilateral Carotid Body Tumors with Syncope
Authors: LaChance David , Hoang Thanh Duc , Shakir Mohamed K M 
Published: May 2020

Abstract
SDHD Mutation: Nonfunctional paragangliomas presenting as bilateral carotid body tumors with syncope
Background:
A mutation of the SDHD gene is associated with hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndromes which most commonly originate in the head and neck region, and usually form in the carotid body. Paragangliomas (PGL) can be secretory or non-secretory with about 95% of head and neck PGL being non-secretory. They can rarely present with symptoms due to compression, however, as in this case of a 29 year-old female presenting with syncope.
Clinical Case:
A 29 year-old female presented for evaluation after syncope. She had a syncopal event and fell down while walking in her home. Syncope was preceded by about 15 minutes of flushing, nausea and palpitations. She reported similar episodes once weekly in the preceding months, which generally lasted an hour. Initial workup included normal vital signs at presentation, normal ECG and echocardiogram, normal TFT, CBC, complete metabolic panel. Subsequent head/neck CT revealed bilateral masses in the carotid bifurcations consistent with carotid body tumors. Further history revealed a family history of bilateral carotid body tumors in her father which had never been evaluated. Plasma and urine metanephrines were normal. She underwent carotid body tumor excision. The left carotid body tumor was successfully excised and pathology revealed a paraganglioma with positive synaptophysin and chromogranin stains. Genetic testing revealed an SDHD (succinate dehydrogenase complex subunit D) gene mutation. Repeat biochemical assessment 4 months later was again negative and patient remained asymptomatic postoperatively.
Conclusion:
Paragangliomas can be secretory or non-secretory with about 95% of head and neck paragangliomas being non-secretory, as in this case. Symptoms can arise from catecholamine hypersecretion, which generally presents as hypertension, headaches, diaphoresis, flushing, anxiety or palpitations, and can be episodic or sustained, or mass effect. Syncope as a presenting symptom is rare, however, and has not been quantified but only reported in case reports. The exact etiology of syncope in our patient is not clear. Hereditary PGL/PCC syndromes should be suspected in any individual with multiple, recurrent, early-onset (age less than 45 years) or family history of PGL/PCC, as these syndromes are inherited in an autosomal dominant manner.