bluuebunny/crossref_metadata_2025 huggingface dataset:
Academic pharmacist competencies in ordinary and emergency situations: content validation and pilot description in Lebanese academia
Authors: Safwan Jihan , Akel Marwan , Sacre Hala , Haddad Chadia , Sakr Fouad , Hajj Aline , Zeenny Rony M. , Iskandar Katia , Salameh Pascale
Published: October 2023

Background

In the absence of a similar study in the Lebanese context, this study aimed to validate the content of the specialized competencies frameworks of academic pharmacists (educators, researchers, and clinical preceptors) and pilot their use for practice assessment in the context of multiple severe crises.

Methods

A web-based cross-sectional study was conducted between March and September 2022 among academic pharmacists enrolled by snowball sampling using a questionnaire created on Google Forms.

Results

The suggested frameworks had appropriate content to assess the competencies of academic pharmacists. Educators and clinical preceptors were confident in all their competencies except for emergency preparedness. Researchers had varying levels of confidence, ranging from moderate to high confidence for many competencies, but gaps were reported in fundamental research, conducting clinical trials, and pharmacy practice research (mean < 80). Educators and researchers relied primarily on experience and postgraduate studies, while clinical preceptors emphasized undergraduate studies to acquire their respective competencies. Continuing education sessions/programs were the least cited as a competency-acquiring venue across all roles.

Conclusion

This study could develop and validate the content of frameworks for specialized competencies of academic pharmacists, including educators, researchers, and clinical preceptors, in a challenging setting. The frameworks were also piloted for practice assessment, which could contribute to supporting effective performance and sustained development of practitioners and help link the skills and competencies pharmacists learn during their studies with those required for a career in academia.
Pain science and practice as a ‘threshold concept’ within undergraduate and pre-registration physiotherapy education: a jewel of the curriculum?
Authors: Smart Keith M.
Published: October 2023

Background

Threshold concepts describe learning experiences that transform our understanding of a concept. Threshold concepts are variously: troublesome, transformative, irreversible, integrative and bounded.

Purpose

The aim of this narrative review is to consider the case for characterising pain science and practice as a threshold concept within undergraduate and pre-registration physiotherapy education.

This article considers the underlying tenets of threshold concepts as they relate to teaching and learning and the relative merits and limitations of characterising pain science and practice as a threshold concept within undergraduate and pre-registration physiotherapy education from both pedagogical and epidemiological perspectives. By evaluating pain, as it relates to physiotherapy education and practice, according to the five defining characteristics of a threshold concept then presenting data related to the epidemiology and impact of pain, the worthiness of characterising pain science and practice as a threshold concept will be discussed and further debate invited.
Nursing-sensitive quality indicators for quality improvement in Norwegian nursing homes – a modified Delphi study
Authors: Tevik Kjerstin , Helvik Anne-Sofie , Stensvik Geir-Tore , Nordberg Marion S. , Nakrem Sigrid
Published: October 2023

Background

Use of nursing-sensitive quality indicators (QIs) is one way to monitor the quality of care in nursing homes (NHs). The aim of this study was to develop a consensus list of nursing-sensitive QIs for Norwegian NHs.

Methods

A narrative literature review followed by a non-in-person, two-round, six-step modified Delphi survey was conducted. A five-member project group was established to draw up a list of nursing-sensitive QIs from a preliminary list of 24 QIs selected from Minimum Data Set (2.0) (MDS) and the international Resident Assessment Instrument for Long-Term Care Facilities (interRAI LTCF). We included scientific experts (researchers), clinical experts (healthcare professionals in NHs), and experts of experience (next-of-kin of NH residents). The experts rated nursing-sensitive QIs in two rounds on a seven-point Likert scale. Consensus was based on median value and level of dispersion. Analyses were conducted for four groups: 1) all experts, 2) scientific experts, 3) clinical experts, and 4) experts of experience.

Results

The project group drew up a list of 20 nursing-sensitive QIs. Nineteen QIs were selected from MDS/interRAI LTCF and one (‘systematic medication review’) from the Norwegian quality assessment system IPLOS (‘Statistics linked to individual needs of care’). In the first and second Delphi round, 44 experts (13 researchers, 17 healthcare professionals, 14 next-of-kin) and 28 experts (8 researchers, 10 healthcare professionals, 10 next-of-kin) participated, respectively. The final consensus list consisted of 16 nursing-sensitive QIs, which were ranked in this order by the ‘all expert group’: 1) systematic medication review, 2) pressure ulcers, 3) behavioral symptoms, 4) pain, 5) dehydration, 6) oral/dental health problems, 7) urinary tract infection, 8) fecal impaction, 9) depression, 10) use of aids that inhibit freedom of movement, 11) participation in activities of interest, 12) participation in social activities, 13) decline in activities of daily living, 14) weight loss, 15) falls, and 16) hearing loss without the use of hearing aids.

Conclusions

Multidisciplinary experts were able to reach consensus on 16 nursing-sensitive QIs. The results from this study can be used to implement QIs in Norwegian NHs, which can improve the quality of care.
Unveiling the biology of defective viral genomes in vitro and in vivo: implications for gene expression and pathogenesis of coronavirus
Authors: Lin Ching-Hung , Chen BoJia , Chao Day-Yu , Hsieh Feng-Cheng , Yang Chun-Chun , Hsu Hsuan-Wei , Tam Hon-Man-Herman , Wu Hung-Yi
Published: October 2023

Background

Defective viral genome (DVG) is a truncated version of the full-length virus genome identified in most RNA viruses during infection. The synthesis of DVGs in coronavirus has been suggested; however, the fundamental characteristics of coronavirus DVGs in gene expression and pathogenesis have not been systematically analyzed.

Methods

Nanopore direct RNA sequencing was used to investigate the characteristics of coronavirus DVGs in gene expression including reproducibility, abundance, species and genome structures for bovine coronavirus in cells, and for mouse hepatitis virus (MHV)-A59 (a mouse coronavirus) in cells and in mice. The MHV-A59 full-length genomic cDNAs (~ 31 kilobases) were in vitro constructed to experimentally validate the origin of coronavirus DVG. The synthesis of DVGs was also experimentally identified by RT-PCR followed by sequencing. In addition, the alterations of DVGs in amounts and species under different infection environments and selection pressures including the treatment of antiviral remdesivir and interferon were evaluated based on the banding patterns by RT-PCR.

Results

The results are as follows: (i) the structures of DVGs are with diversity, (ii) DVGs are overall synthesized with moderate (MHV-A59 in cells) to high (BCoV in cells and MHV-A59 in mice) reproducibility under regular infection with the same virus inoculum, (iii) DVGs can be synthesized from the full-length coronavirus genome, (iv) the sequences flanking the recombination point of DVGs are AU-rich and thus may contribute to the recombination events during gene expression, (v) the species and amounts of DVG are altered under different infection environments, and (vi) the biological nature of DVGs between in vitro and in vivo is similar.

Conclusions

The identified biological characteristics of coronavirus DVGs in terms of abundance, reproducibility, and variety extend the current model for coronavirus gene expression. In addition, the biological features of alterations in amounts and species of coronavirus DVGs under different infection environments may assist the coronavirus to adapt to the altered environments for virus fitness and may contribute to the coronavirus pathogenesis. Consequently, the unveiled biological features may assist the community to study the gene expression mechanisms of DVGs and their roles in pathogenesis, contributing to the development of antiviral strategy and public health.
MiR-4649-5p acts as a tumor-suppressive microRNA in triple negative breast cancer by direct interaction with PIP5K1C, thereby potentiating growth-inhibitory effects of the AKT inhibitor capivasertib
Authors: Jonas Katharina , Prinz Felix , Ferracin Manuela , Krajina Katarina , Pasculli Barbara , Deutsch Alexander , Madl Tobias , Rinner Beate , Slaby Ondrej , Klec Christiane , Pichler Martin
Published: October 2023

Background

Triple negative breast cancer (TNBC) is a particularly aggressive and difficult-to-treat subtype of breast cancer that requires the development of novel therapeutic strategies. To pave the way for such developments it is essential to characterize new molecular players in TNBC. MicroRNAs (miRNAs) constitute interesting candidates in this regard as they are frequently deregulated in cancer and contribute to numerous aspects of carcinogenesis.

Methods and results

Here, we discovered that miR-4649-5p, a miRNA yet uncharacterized in breast cancer, is associated with better overall survival of TNBC patients. Ectopic upregulation of the otherwise very low endogenous expression levels of miR-4646-5p significantly decreased the growth, proliferation, and migration of TNBC cells. By performing whole transcriptome analysis and physical interaction assays, we were able to identify the phosphatidylinositol phosphate kinase PIP5K1C as a direct target of miR-4649-5p. Downregulation or pharmacologic inhibition of PIP5K1C phenocopied the growth-reducing effects of miR-4649-5p. PIP5K1C is known to play an important role in migration and cell adhesion, and we could furthermore confirm its impact on downstream PI3K/AKT signaling. Combinations of miR-4649-5p upregulation and PIP5K1C or AKT inhibition, using the pharmacologic inhibitors UNC3230 and capivasertib, respectively, showed additive growth-reducing effects in TNBC cells.

Conclusion

In summary, miR-4649-5p exerts broad tumor-suppressive effects in TNBC and shows potential for combined therapeutic approaches targeting the PIP5K1C/PI3K/AKT signaling axis.
Postgraduates’ time management disposition and mental health: mediating role of life satisfaction and moderating role of core self-evaluations
Authors: Liu Shen , Song Minghua , Teng Han
Published: October 2023

Background

The current study aimed to investigate the relationship between postgraduates’ time management disposition and mental health. As such, it constructed a moderated mediation model to examine the mediating role of life satisfaction on the relationship between graduate students’ time management disposition and mental health and examine whether this role was moderated by core self-evaluations.

Methods

455 postgraduates were surveyed by the Adolescence Time Management Disposition Inventory, the Adolescent Students’ Life Satisfaction Scale, the revised version of the Chinese Core Self-Evaluation Scale, and the revised version of the Chinese General Health Questionnaire.

Results

Time management disposition, life satisfaction, core self-evaluation, and mental health were significantly correlated. Time management disposition indirectly affected mental health through the mediating effect of life satisfaction. Core self-evaluation moderated the second half of the mediating effect of time management disposition on mental health via life satisfaction.

Conclusion

The findings reveal the mechanism between time management disposition and mental health, which will help school educators to guide postgraduates in developing good time management disposition and improving life satisfaction and core self-evaluation, and thus improve their mental health.
Male spiny frogs enter the underwater battlefield with loose skin exhibiting enhanced penetration of capillaries into the epidermis
Authors: Xu Shuang , Dai Qiang , Zheng Yuchi
Published: October 2023

The skin has multiple functions, and capillaries can penetrate the epidermis to shorten the diffusion path while allowing maintenance of overall epidermal thickness for nonrespiratory roles. However, a method for quantifying the capillary penetration extent is lacking. Such a method may facilitate making comparisons and detecting associations, potentially making the extent a useful variable in biological studies. We quantified the extent as the ratio of the average minimum thickness of epidermis overlying each capillary to the average epidermal thickness along a skin section and then explored its performance in the Emei mustache toad, Leptobrachium boringii, a species in which breeding males with loose skin call and fight each other with maxillary spines underwater. The ratio showed informative associations with other variables, such as perfused capillary density. It displayed small intragroup variation and could be more sensitive than other variables in revealing structural differences in the skin. The ratio estimates were lowest and were correlated with epidermal and stratum compactum thicknesses in breeding males, i.e., a covariation but not reinforcement against stabbing, constituting early evidence consistent with the increased extensibility of loose skin conferring a defensive advantage during combat in amphibians. In addition, our results lead to the hypothesis that high hemoglobin density along subepidermal capillaries favors the maintenance of low blood partial oxygen pressure and hence increases cutaneous oxygen uptake. We also provide evidence supporting the new idea that the cooccurrence of loose skin and underwater calling found in some frogs can be explained by the latter benefiting from a large functional respiratory surface area. Awareness of the usefulness of the ratio may promote its application and the quantification of the penetration. Regarding exchange surface design, these findings for L. boringii imply a case in which looseness increases surface area as well as prevents damage.
Recommendations for embedding simulation in health services
Authors: Davies Ellen , Montagu Adam , Brazil Victoria
Published: October 2023

Aspirations to achieve quality and safety goals in health services through simulation have led to significant investments in simulation equipment, space and faculty. However, the optimal governance and operational models through which these resources are expertly applied in health services are not known. There is growing evidence supporting ‘service’ models for simulation. In these models, simulation activities are co-designed and delivered by a team of simulation experts in partnership with health service units, specifically targeting quality and safety goals. Embedded simulation specialist teams working within these programs offer benefits not fully captured by traditional models of health education or by traditional systems for quality and safety.

In this article, we explore broad and specific recommendations for establishing a simulation consultancy service within an Australian metropolitan health service. We base these recommendations on a review of current Australian practice and healthcare simulation literature, and on a specific example within a large outer metropolitan health service. The broad domains discussed include (1) governance and leadership; (2) human resources; (3) principles and planning; (4) operationalise and evaluate and (5) look to the future.

The recommendations recognise that healthcare simulation is moving beyond solely addressing individual learning outcomes. The value of simulation addressing organisation and system objectives through various simulation modalities is increasingly being explored and demonstrating value. There is a growing demand for translational simulation in these contexts, and a consequent requirement for organisations to consider how simulation services can be successfully operationalised. Recommendations included in this paper are discussed and described with the intent of facilitating a deeper appreciation of the complexities associated with, and opportunities afforded by, a well-integrated simulation service.
Knowledge of child sexual abuse and attitudes towards reporting it among teachers and parents of children studying in selected primary schools of Udupi Taluk, India
Authors: Prabhu Shwetha , Prabhu Savitha , Noronha Flavia
Published: October 2023

Background

Child sexual abuse is one of the major issues of concern globally. Teachers and parents being the child’s primary caregivers should be knowledgeable regarding child sexual abuse.

Aim of the study

This study aimed to assess knowledge about child sexual abuse, determine attitudes toward reporting child sexual abuse, and find the relationship between knowledge and the attitude among the teachers and parents of the children studying in selected primary schools of Udupi taluk.

Methods

A descriptive survey design was adopted; the study participants were 90 teachers and 50 parents of the children studying in selected primary schools of Udupi Taluk. The instruments used were demographic proforma, a structured knowledge questionnaire about child sexual abuse, and an attitude scale toward reporting it.

Results

Results depicted that 50% of the teachers had average knowledge and 50% had good knowledge about child sexual abuse. All the teachers reported a favorable attitude towards reporting child sexual abuse. Similarly, 80% of the parents had average knowledge about child sexual abuse, and a majority of 76% had a favorable attitude towards reporting child sexual abuse. Unfavorable attitude towards reporting child sexual abuse was reported by 24% of the parents. No statistically significant correlation was found between knowledge and attitude toward reporting child sexual abuse among parents ((χ2 = 1.891, p = 0.388). A significant association was found between teachers’ knowledge scores, their previous knowledge about child sexual abuse (χ2 = 7.56, p = 0.006), and the existence of a school counselor (χ2 = 5.40, p = 0.020). Likewise, the association was found between parents’ knowledge score, educational level of parents (χ2 = 18.3, p = 0.019), and marital status (χ2 = 18.5, p = 0.005).

Conclusion

Child sexual abuse is one of the major issues of concern globally. Teachers and parents being the child’s primary caregivers should be knowledgeable regarding child sexual abuse. As parents are not exposed to any training regarding identifying and reporting child sexual abuse, they may have unfavorable attitudes toward reporting it.
Smart phone-macro lens setup (SPMLS): a low-cost and portable photography device for amateur taxonomists, biodiversity researchers, and citizen enthusiasts
Authors: Riyaz Muzafar , Ignacimuthu Savarimuthu
Published: October 2023

Background

In the present era of scientific and technological advancements, the use of smartphones among people has witnessed a large-scale progression. The camera serves as an important tool on smartphones, and the quality of the built-in camera varies with megapixels. The quality of photography and videography can be enhanced by employing macro lenses that can provide precise and high-quality photographs for the documentation and monitoring of macroorganisms, particularly insects. We used a smartphone-macro lens setup (SPMLS), comprising a Redmi Note 8 Pro and Skyvik Signi-20 mm lens, along with Snapseed for image processing. The SPMLS, costing USD 217, was employed in the Hirpora Wildlife Sanctuary, Kashmir, during May to October 2021 for insect diversity documentation. The aim of this study is to introduce and demonstrate the utility of SPMLS as an affordable and portable photography solution for enhancing image quality in biodiversity documentation, making it accessible to a wide range of users.

Results

In this study, we report a device that uses a smartphone and macro lens (SPMLS), which is a portable and low-cost photography gear for researchers, photographers, citizen enthusiasts, and the general public who are not able to buy high-end and costly photography equipment for field-based biodiversity studies. The utilization of SPMLS has significantly augmented the image resolution and pixel density, thereby substantially enhancing the overall photographic quality, demonstrating its substantial scientific utility.

Conclusions

The SPMLS device presented in this study can be useful for researchers, scientists, students, citizen enthusiasts, and common people that are engaged in the biodiversity monitoring and conservation of animal and plant species across the globe. In addition, the post-photography part of this paper provides users with an outlook on image editing, processing, uploading, and marketing of photographs on different platforms.
Application of UVC-LED/H2O2 in wastewater treatments: treatment efficacy on disinfection byproduct precursors and micropollutants
Authors: Leong Dexter , Chen Hao-Bin , Wang Gen-Shuh
Published: October 2023

The applications of advanced oxidation processes (AOPs) for controlling microcontaminants are essential to meet the water quality criteria for potable or nonpotable water reuses. The objective of this study is to demonstrate the application of light emitting diode (LED) as a possible light source to substitute traditional low-pressure mercury lamp (LPUV) in UV/H2O2 processes in treating precursors of disinfection byproducts (DBPs) and pharmaceutical and personals care products (PPCPs) in wastewater. The results of this study revealed that UV fluence plays the most crucial role in the efficiency of UV/H2O2. At the same time, the initial concentration of H2O2, dissolved organic carbon (DOC), and turbidity had minimal effects, except that poor efficiency result of UV/H2O2 was observed at a solution with low DOC concentration (2.4 mg L−1). Although the concentrations of organic matter decreased after UV/H2O2 treatment, the concentration of precursors of DBPs increased in the early stage of the photolysis process and decreased after that; moreover, the profiles of precursors for trihalomethanes and haloacetic acids were different. A comparison between LPUV and UVC-LED as light sources revealed that, at a fixed UV fluence input into the UV/H2O2 process, the trends and efficiencies in the degradation of organic matter and DBP precursors were similar. Meanwhile, the photoelectric conversion efficiency of UVC-LED should be improved for future applications in water treatment. Based on the UV/H2O2 treatment results on synthetic PPCPs wastewater solution, this study showed the effectiveness of UV/H2O2 to degrade micro organic contaminants.
Partial arch replacement of type A aortic dissection after thoracic endovascular aortic repair for type B dissection
Authors: Nakajima Tomohiro , Iba Yutaka , Ogura Keishi , Kawaharada Nobuyoshi
Published: October 2023

Background

Stent graft-induced new entry (SINE), defined as the stent graft-induced formation of a new entry point for blood to enter an area, is increasingly being observed after thoracic endovascular aortic repair (TEVAR) for Stanford type B aortic dissection worldwide. We herein describe a case of Stanford type A aortic dissection due to proximal SINE after TEVAR for Stanford type B dissection.

Case presentation

This case involved a 58-year-old man with type A aortic dissection due to SINE. Six years previously, he had developed severe back pain and was diagnosed with type B aortic dissection after computed tomography examination. Because the primary entry was positioned at the descending aorta, we conducted TEVAR for exclusion of the entry with a GORE TAG conformable thoracic aortic graft. He was thereafter followed by our hospital. Six years later, he developed jaw pain and was examined at another hospital. He was transferred to our hospital because of the possibility of type A dissection. Computed tomography revealed type A aortic dissection with proximal site SINE. Emergency partial arch replacement was conducted, and he was discharged on postoperative day 27. Because the entry was at the lesser curve of the arch, we excluded the entry and conducted partial arch replacement.

Conclusions

In this case, proximal SINE occurred 6 years after TEVAR. Because SINE may occur even in the long term after TEVAR, careful follow-up is necessary.
Influence of different Wastewater Treatment Processes on the rate and characteristics of MPs released from WWTPs in Fiji, South Pacific
Authors: Rokomatu Malelili Naulivou , Bhagwat-Russell Geetika , Panneerselvan Logeshwaran , Raju Subash , Savou Viliame , Waqainabete Timaima , Palanisami Thavamani
Published: October 2023

The global effects of MP (MP) pollution on the environment are concerning, and they are exacerbated by the multiple sources of pollution in aquatic environments such as urban runoff, waste mismanagement, industrial pollution, and so on. South pacific islands host a large diversity of aquatic flora and fauna and given its ecological significance it is necessary to identify the sources of MP pollution in the region. To date, very little attention has been given to identify whether effluents from wastewater treatment plants (WWTP) are acting as a significant source of MP in the South Pacific region and its countries. Therefore, the present study analyzed and compared the treatment methods and fate of MPs in the country’s two main WWTPs: 1) the Kinoya WWTP (simple secondary clarifier and trickling filter) and 2) Natabua WWTP (secondary pond treatment system). Sampling locations were based on the different treatment stages, and samples were collected from each stage of treatment before effluents were released into the ocean. Kinoya WWTP had an average of 3.45 ± 0.3 particles/L in the inlet stage and released an average of 0.3 ± 0.26 particles/L of MP through the outlet with 91% removal efficiency (RE) with an output equivalent of 4500 particles per day. The initial stage of treatment from the anaerobic pond outlet at Natabua had an average of 2.9 ± 1.05 particles/L, and the maturation outlet had an average of 0.53 ± 0.42 particles/L, a removal efficiency of 81% and thus an output equivalent of 4558 particles/L of MP. Polymer analysis under FTIR confirmed that cellophane or semi-synthetic cellulose and polypropylene were common polymers in the final effluent in Kinoya WWTP, and Natabua plant has cellophane or semi-synthetic cellulose, polypropylene and polyethylene were observed as common polymers. Although there are numerous study that have compared wastewater treatment processes, this is the first study in Fiji that investigates the efficiency of the two methods of water treatment process in the context of microplastic pollution and emphasizes the effectiveness of the treatment stages in determining the concentration of MP released into the ocean.
Burnout in mental health services in Ireland during the COVID-19 pandemic
Authors: Adamis Dimitrios , Minihan Elisha , Hannan Noel , Doherty Anne M. , McNicholas Fiona
Published: October 2023

Background

Burnout is a consequence of chronic occupational stress. Specific work-related factors may contribute to burnout experienced by those working in mental health services (MHS), many of which have increased since the COVID-19 pandemic.

Aims

To examine personal, work- and patient-related burnout among MHS staff in Ireland during the COVID-19 pandemic, and explore the impact of work-related conditions on burnout.

Method

We conducted a cross-sectional survey of three MHS across Ireland utilising a study-specific questionnaire, the Copenhagen Burnout Inventory and the Effort–Reward Imbalance scale.

Results

Of 396 participants, 270 (70.6%) were female. Moderate and high personal burnout was experienced by 244 (64.1%) participants; work-related burnout by 231 (58.5%) participants and patient-related burnout by 83 (21.5%) participants. Risk factors for both personal and work-related burnout were female gender, urban service, time spent outside main responsibilities, overcommitment, high score on the Effort–Reward Imbalance scale and intention to change job. Being younger, with high workload and deterioration of personal mental health during the pandemic was associated with higher personal burnout, whereas a lack of opportunity to talk about work-related stress contributed to work-related burnout. Fewer factors were associated with patient-related burnout, namely overcommitment, working in urban services and poorer physical and mental health during the COVID-19 pandemic.

Conclusions

High levels of personal and work-related burnout were found among mental health workers. The weak association with COVID-19-related factors suggest levels of burnout predated the pandemic. This has implications for MHS given the recognised additional work burden created by COVID-19.
Effect of Radioactive Iodine Therapy on Cancer-Specific Survival of Papillary Thyroid Cancer Tall Cell Variant
Authors: Dai Ping , Zhao Wanjun , Zheng Xun , Luo Han , Wang Xiaofei
Published: October 2023

Context

Radioactive iodine (RAI) therapy is often used as an adjuvant treatment to reduce the risk of recurrence in patients with papillary thyroid cancer (PTC). However, the effect of RAI therapy on cancer-specific survival (CSS) in patients with tall cell variant (TCV) remains controversial.

Objective

This study aimed to investigate the impact of RAI therapy on CSS in patients with TCV-PTC by analyzing data from the Surveillance, Epidemiology, and End Results database.

Methods

We identified 1281 patients with TCV-PTC in the SEER database who underwent total thyroidectomy between 2004 and 2019. Of these, 866 (67.6%) patients received RAI therapy and 415 (32.4%) did not. Propensity score matching was conducted to balance the baseline characteristics between the 2 groups. Cox proportional hazards regression models were used to estimate the hazard ratio (HR) and 95% CI for the effect of RAI therapy on CSS.

Results

After propensity score matching, 373 pairs of patients were included in the analysis. The results showed no significant difference in CSS between the RAI therapy group and the non-RAI therapy group (HR 0.54, 95% CI 0.25-1.17, P = .120). Subgroup analyses indicated similar results.

Conclusion

RAI therapy may not improve CSS in patients with TCV-PTC after total thyroidectomy. Future studies with larger sample sizes, longer follow-up periods, and better study designs are needed to confirm or refine our research findings.
FRI074 Rise In Fasting Ghrelin Level In Response To Weight Loss Predicts Future Weight Regain In The POUNDS LOST Trial
Authors: Tong Jenny , Heianza Yoriko , Schur Ellen Anne , Sacks Frank , Qi Lu , Boyko Edward J
Published: October 2023

Disclosure: J. Tong: None. Y. Heianza: None. E.A. Schur: None. F. Sacks: None. L. Qi: None. E.J. Boyko: None.

Weight loss maintenance is a challenging problem commonly encountered in obesity management. The biological mechanism for weight regain following diet-induced weight loss is not well understood. The orexigenic gut hormone ghrelin increases appetite and food intake and promote positive energy balance. We aim to investigate whether weight-loss induced fasting ghrelin changes predict subsequent weight regain in the POUNDS LOST trial. Methods: This study included 244 overweight or obese adults (age: 52.9±8.8 yr; 66% female; BMI 32.4±3.9 kg/m2 [mean ± SD]) randomly assigned to 1 of 4 weight-loss diets varying in macronutrient intake who had fasting plasma total ghrelin levels measured at baseline, 6 and 24 months after the intervention. We examined associations between fasting ghrelin levels changes between baseline and 6-months (weight change: -7.1±5.3 kg) and body weight change between 12 and 24 months (3.2±3.9 kg). Results: Fasting plasma ghrelin level increased significantly at 6 months (from 487.3±251.1 to 574.0±274.5 pg/mL) and remained elevated at 24 months despite weight regain (684.0±411.0 pg/mL). Increases in ghrelin level from baseline to 6 months (86.7±167.4 pg/mL) were correlated with weight regain from 12 to 24 months (p=0.018). The association was unchanged after adjustment for age, sex, race, and diet assignment at baseline; fat and carbohydrate craving scores, hunger and fullness ratings, dietary restraint and disinhibition scores measured at 6 months, prior to onset of weight regain. Conclusions: Fasting ghrelin levels rose in response to diet-induced weight loss and persisted for 2 years despite weight regain. Ghrelin change during the weight loss phase predicts subsequent weight regain independent of appetite and craving measures. Understanding the mechanistic connection between ghrelin action and weight regain may shed light on novel approaches to weight loss maintenance.

Presentation: Friday, June 16, 2023
THU030 Evaluation Of Combined CRH And HDDST Test Performance
Authors: Elenius Henrik , McGlotten Raven , Nieman Lynnette K
Published: October 2023

Disclosure: H. Elenius: None. R. McGlotten: None. L.K. Nieman: None.

Introduction: Determining the etiology of ACTH-dependent Cushing’s Syndrome (CS) is frequently a diagnostic challenge. Non-invasive tests to distinguish Cushing’s Disease (CD) from Ectopic ACTH Syndrome (EAS) are the CRH stimulation test and the 8 mg overnight high dose dexamethasone suppression test (HDDST). The CRH test is more accurate (sensitivity (Se) 83-93%, specificity (Sp) 85-100%) than the HDDST (Se 56-95%, Sp 67-100%), depending on the type of CRH and criteria used. We retrospectively reviewed the results of each test at our institution between 2005-2019 to evaluate the tests' performance at established cut offs, identify optimal response criteria and to see whether combining the two tests provided additional diagnostic accuracy. Methods: CD or EAS was confirmed by either surgical pathology or biochemical cure after tumor resection or imputed from IPSS results (n=7). We identified 100 patients with CD and 34 with EAS. Two EAS patients with cyclic CS each underwent tests with or without active hypercortisolism. Test criteria to identify CD were ≥50% suppression of cortisol for the HDDST and a ≥35% increase in mean ACTH at 15-30 minutes or a ≥20% increase in mean cortisol at 30-45 minutes for the ovine CRH test. Results: The HDDST had a Se of 81%, Sp of 81% and diagnostic accuracy (DA) of 81%, while the CRH test had Se 95%, Sp 75% and DA 90%. Each test improved with modified response criteria. Using a HDDST suppression criterion of ≥63% gave Se 78%, Sp 89% and DA 81%. Using CRH test response criteria of ≥39% increase in ACTH or ≥30% increase in cortisol gave Se 94%, Sp 92% and DA 93%. Performance improved further by combining the two tests, using the optimized criteria (≥63% for HDDST and ≥39% or ≥30% for the CRH test). Test results were concordant in 80%, giving a Se of 96%, Sp 97% and DA 96%. Among EAS patients, this approach only misidentified one subject with cyclic CS who was tested while hypocortisolemic. Removing this test improved combined test performance to Se 96%, Sp 100% and DA 97%. Among the 26 patients with discordant results (CD = 22, EAS = 4), the HDDST result was likelier to be correct in EAS vs CD (50% vs 14%, PPV 60%), while the CRH test was more often correct in CD vs EAS (86% vs 50%, PPV 90%). Conclusions: Based on this series that included a large proportion of EAS patients, the CRH test performed better than the HDDST, in line with earlier data. In cyclic CS, tests performed better in hypercortisolemic patients. The optimal response criteria were ≥63% cortisol suppression for HDDST and ≥39% ACTH or ≥30% cortisol increase for the CRH test. In the 81% of hypercortisolemic cases with concordant test results, these combined optimized cut offs provided the best diagnostic performance, improving it to Se 96%, Sp 100%, DA 97%. When results were discordant, the CRH test worked better to identify patients with CD.

Presentation: Thursday, June 15, 2023
THU078 The Definition And Epidemiology Of Giant Pituitary GH-Secreting Adenomas Based On Clinical, Imaging, And Hormonal Parameters: A Pilot Study
Authors: Del Corso Leticia Marinho , Marcela Cunha da Silva , Kusma Fidalski Solena Ziemer , Boguszewski Cesar Luiz
Published: October 2023

Disclosure: L.M. Del Corso: None. M.C. Silva: None. S.Z. Fidalski: None. C.L. Boguszewski: None.

Acromegaly is a chronic disease, caused by a GH-secreting pituitary adenoma in most cases. At diagnosis, around 75% of patients have a macroadenoma, which constitute a heterogeneous group with variable biological behavior, therapeutic response, and prognosis. Giant adenomas (GA) have been defined as those which are more than 40 mm at their largest in diameter, but this is an arbitrary definition lacking comparative studies to investigate tumor size at diagnosis with clinical presentation, response to treatment and the evolution of acromegaly patients. Thus, the aim of our study was to compare the aforementioned variables according to the tumor size at diagnosis and review the diagnostic criteria for giant GH-secreting adenomas. In this observational, retrospective, single-centre pilot study, we have retrieved data from 161 medical records and evaluated age, sex, duration of symptoms, GH levels, presence of type 2 diabetes mellitus (T2DM), hypertension and hypopituitarism, imaging characteristics, and the need for adjuvant therapy with somatostatin receptor ligands (SRL) or other drugs. Study population was classified into four groups according to tumor size at diagnosis: (I) <10 mm (microadenomas; n=14); (II) 10-29 mm (n=84); (III) 30-39 mm (n=10); (IV) 40 mm or more (n=9). The final study group consisted of 117 individuals (49% men; mean age 43 ± 13 yrs). Hypopituitarism was significantly more frequent in groups III and IV compared to groups I and II (p=0.004), with no difference between groups III and IV (p=0,3). There was a higher proportion of invasive adenomas when the lesions ≥ 30 mm were compared to groups I and II (p=0.008), but with no difference between groups III and IV (p=0.62). Sixty percent of patients in group III (n=6) and 44% of patients in group IV (n=4) needed other drug therapy than SRL (cabergoline and/or pegvisomant), a higher proportion compared to those of groups I (n=1; 7%) and II (n=25; 30%) (p=0.04), again without difference between groups III and IV (p=0,7). Regarding the initial levels of GH, a significant difference was observed between groups I and IV (p=0.04), but this difference was not observed in the other groups. There were no statistical differences in relation to sex, duration of symptoms, need for SRL therapy, prevalence of hypertension and T2DM between study groups. Our study raises the hypothesis that giant adenomas should be defined as tumors larger than 30 mm, as the clinical behavior of tumors above this cutoff point seems to be similar in comparison with tumors larger than 40 mm but different from those of smaller sizes.

Presentation: Thursday, June 15, 2023
SAT673 Novel Mutation Of TBX3 Associated With Morbid Obesity In Human
Authors: Alkaissi Hussam R , Ji Beisi , McFarlane Samy
Published: October 2023

Disclosure: H.R. Alkaissi: None. B. Ji: None. S. McFarlane: None.

Background: TBX3 is a transcription involved in the development of the heart conduction system, apocrine and mammary glands, limbs, and lung development and maturation, with variable oncogenic roles. Recently, the role of TBX3 and body weight control has been demonstrated in animal models, showing an essential role for TBX3 in hypothalamic arcuate neuronal maturation, function, and identity [1]. Case: 26-year-old woman referred for the management of morbid obesity and menstrual irregularities. The patient weighed 330 lbs, with a BMI of 55 kg/m2, with hypertension T2DM. The patient had a normal development until age five, after which she experienced regression in milestones and lost the ability to communicate, and was diagnosed with autism. She had a history of food-seeking behavior, leading to progressive weight gain, which was managed by blocking access to food, such as locking the fridge. The patient's weight fluctuated from 290 lbs to 330 lbs. Family history of T2DM in her maternal relatives. She was diagnosed with T2DM at the age of 18, with HbA1c level of 9.4%. Autoantibody testing was negative for glutamic acid decarboxylase (GAD), islet cell antibody (ICA), and zinc transporter 8 (ZnT8). The fasting C-peptide level was detectable at 1.87 ng/mL. T2DM was well controlled with an HbA1C range of 6.0-6.7% with the use of short and long-acting insulin regimen. However, with improved glycemic control, short-acting insulin was stopped and she was started on liraglutide. Syndromic obesity was suspected due to early-onset of the disease and the developmental regression. Testing for Prader-Willi syndrome was negative, based on a normal chromosome 15 methylation study. Leptin levels were elevated at 66 ng/mL, prompting further testing for obesity-related genetic mutations. Next-generation sequencing and targeted Sanger sequencing for 79 genes associated with obesity in human and animal models was performed. A novel mutation was identified in TBX3 activation domain, c. C1513T (p.P505S). UniProt peptide sequence alignment analyzed for sequence conservation. ClinVar, HGMD and GWAS Catalogue databases screened for similar variants. Discussion: We present the first case in human, where novel TBX3 mutation results in hypothalamic dysfunction, leptin resistance manifesting as morbid obesity, hyperphagia, and menstrual irregularities. The reported mutation in the activation domain (A) of TBX3. In silico analysis showed high evolutionary conservation of the mutated domain (across vertebrate species), indicating the mutation is likely pathogenic. References:1. Quarta C, Fisette A, Xu Y, et al. Functional identity of hypothalamic melanocortin neurons depends on Tbx3. Nat Metab. 2019 Feb;1(2):222-235. doi: 10.1038/s42255-018-0028-1. Epub 2019 Jan 28. PMID: 32694784; PMCID: PMC8291379.

Presentation: Saturday, June 17, 2023
FRI275 Glutamate Receptor Agonists Stimulate Kisspeptin Neurons In The Arcuate Nucleus Of The Hypothalamus
Authors: Bearss Robin , Piet Richard
Published: October 2023

Disclosure: R. Bearss: None. R. Piet: None.

KNDy neurons co-express kisspeptin, neurokinin B (NKB), dynorphin A (Dyn A), and glutamate. These neurons, located in the arcuate nucleus of the hypothalamus, drive pulsatile gonadotropin releasing hormone (GnRH) secretion. This eventually promotes pulsatile gonadotropin hormone release from the anterior pituitary, important for fertility in both sexes. The current hypothesized mechanism for pulse generation involves KNDy neuron interconnectivity and reciprocal regulation through the combined actions of NKB, DynA and glutamate to coordinate KNDy neuron activity. There is evidence that KNDy neurons express NKB, Dyn A and glutamate receptors and that NKB stimulates KNDy neuron electrical activity while Dyn A suppresses it. There is also evidence that ionotropic glutamate receptor antagonists can inhibit KNDy neuron coordinated activity and pulsatile gonadotropin hormone release, indicating that glutamatergic neurotransmission plays a significant role in activity coordination. The purpose of the following experiments was to investigate the response of KNDy neurons to varied glutamate receptor activation. We used calcium imaging to monitor the activity of KNDy neurons in brain slices. We crossed Kiss1-Cre mice—expressing Cre recombinase (Cre) in kisspeptin neurons—with Cre-dependent GCaMP6f mice to generate Kiss1-Cre x GCaMP6f mice that express GCaMP6f in kisspeptin neurons. GCaMP6f fluorescence increases when binding to intracellular calcium and can, thus, be used as an inferential marker of electrical activity. Coronal brain slices (200 µm thickness) obtained from male Kiss1-cre x GCaMP6f mice and containing the arcuate nucleus were placed in a recording chamber under an epifluorescence microscope. KNDy neurons were exposed for 2 minutes to a bath application of either the ionotropic glutamate receptor agonist α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA, 10µM), the ionotropic glutamate receptor agonist N-methyl-D-aspartate (NMDA, 50µM), or the group 1 metabotropic glutamate receptor (mGluR) agonist (S)-3,5-dihydroxyphenylglycine (DHPG, 50µM). AMPA, NMDA, and DHPG increased KNDy neuron fluorescence by 7.8±0.5% (n=113 in 7 slices from 6 mice), 7.5±0.5% (n=154 in 6 slices from 5 mice), and 6.1±0.7% (n=159 in 7 slices from 5 mice) respectively. All cells that were excited by NMDA or DHPG were also excited by AMPA. These experiments provide evidence that activation of ionotropic AMPA and NMDA receptors as well as group 1 mGluRs stimulate KNDy neuron activity. Further investigation into the precise role of individual glutamate receptor subtypes on KNDy neuron coordinated activity is needed.

Presentation: Friday, June 16, 2023
FRI281 Sexual Dimorphism In The LH Responses To Kisspeptin And Senktide Administration In Prepubertal Mice
Authors: Maione Luigi , Naule Lydie , Li Chloe , Magnuson Melissa , Young Jacques , Carroll Rona Stephanie , Kaiser Ursula B
Published: October 2023

Disclosure: L. Maione: Consulting Fee; Self; Pfizer, Inc., Ipsen. L. Naule: None. C. Li: None. M. Magnuson: None. J. Young: Consulting Fee; Self; Serono Laboratories, Ferring Pharmaceuticals. R.S. Carroll: None. U.B. Kaiser: None.

Introduction: The hypothalamic-pituitary-gonadal (HPG) axis is regulated by pulsatile GnRH secretion and its action on the anterior pituitary, leading to the synthesis and secretion of LH and FSH. KNDy neurons, expressing kisspeptin, neurokinin B and dynorphin A, are the GnRH/LH pulse generator and are key regulators of puberty and fertility. The HPG axis is active during prenatal and early postnatal life in humans and rodents, but then remains quiescent until puberty in both species. The response of gonadotropes to exogenous upstream GnRH signals such as kisspeptin and neurokinin during prepubertal development in mice is unknown. Aim: To conduct a systematic assessment of LH responsiveness to exogenous kisspeptin and to the neurokinin-3 receptor agonist senktide at regular intervals postnatally and across pubertal maturation in mice. Materials and Methods: Male and female J129Sv mice were treated with intraperitoneal injections of kisspeptin-10 (0.0023 nmol/g), senktide (0.023 nmol/g) or vehicle every 3 days from postnatal day (PND) 10 until completion of puberty. Serum LH was measured by an ultra-sensitive ELISA at baseline and 15 minutes after injection. Results: Prepubertal mice responded in an age-dependent and sexually dimorphic manner to kisspeptin and senktide. LH levels increased following kisspeptin stimulation in both sexes, but responses were higher in females than in males from PND10 to PND16. The highest response was observed at PND10, with a pattern of decreasing response with advancing age. Senktide induced a robust increase in serum LH in females from PND10 to PND16, with a decrease in response with age, similar to that observed after kisspeptin treatment. In contrast, in males there was no increase in serum LH in response to senktide at any age. No difference in the onset of puberty or body weight was observed across treatment groups. Conclusions: The assessment of serum LH levels following IP administration of kisspeptin and senktide in prepubertal male and female mice demonstrated distinct age and sexually-dimorphic patterns of LH responses to GnRH upstream signals. LH responses are maximal at early ages with a decreasing pattern overtime, and are higher in females than in males, suggesting a different distribution of kisspeptin/neurokinin receptors or the presence of different and/or additional restraining factors on GnRH/LH in the two sexes. These findings provide new evidence for sexual dimorphism of the HPG axis in mice early in postnatal life, prior to the onset of puberty.

Presentation: Friday, June 16, 2023