bluuebunny/crossref_metadata_2025 huggingface dataset:
The regulation of plasma gelsolin by DNA methylation in ovarian cancer chemo-resistance
Authors: Manzoor Hafiza Bushra , Asare-Werehene Meshach , Pereira Satyajit Dey , Satyamoorthy Kapaettu , Tsang Benjamin K.
Published: January 2024

Background

Ovarian cancer (OVCA) is the most lethal gynecologic cancer and chemoresistance remains a major hurdle to successful therapy and survival of OVCA patients. Plasma gelsolin (pGSN) is highly expressed in chemoresistant OVCA compared with their chemosensitive counterparts, although the mechanism underlying the differential expression is not known. Also, its overexpression significantly correlates with shortened survival of OVCA patients. In this study, we investigated the methylation role of Ten eleven translocation isoform-1 (TET1) in the regulation of differential pGSN expression and chemosensitivity in OVCA cells.

Methods

Chemosensitive and resistant OVCA cell lines of different histological subtypes were used in this study to measure pGSN and TET1 mRNA abundance (qPCR) as well as protein contents (Western blotting). To investigate the role of DNA methylation specifically in pGSN regulation and pGSN-induced chemoresistance, DNMTs and TETs were pharmacologically inhibited in sensitive and resistant OVCA cells using specific inhibitors. DNA methylation was quantified using EpiTYPER MassARRAY system. Gain-and-loss-of-function assays were used to investigate the relationship between TET1 and pGSN in OVCA chemoresponsiveness.

Results

We observed differential protein and mRNA expressions of pGSN and TET1 between sensitive and resistant OVCA cells and cisplatin reduced their expression in sensitive but not in resistant cells. We observed hypomethylation at pGSN promoter upstream region in resistant cells compared to sensitive cells. Pharmacological inhibition of DNMTs increased pGSN protein levels in sensitive OVCA cells and decreased their responsiveness to cisplatin, however we did not observe any difference in methylation level at pGSN promoter region. TETs inhibition resulted in hypermethylation at multiple CpG sites and decreased pGSN protein level in resistant OVCA cells which was also associated with enhanced response to cisplatin, findings that suggested the methylation role of TETs in the regulation of pGSN expression in OVCA cells. Further, we found that TET1 is inversely related to pGSN but positively related to chemoresponsiveness of OVCA cells.

Conclusion

Our findings broaden our knowledge about the epigenetic regulation of pGSN in OVCA chemoresistance and reveal a novel potential target to re-sensitize resistant OVCA cells. This may provide a future therapeutic strategy to improve the overall OVCA patient survival.
The high impact of zinc chromium oxide nanocombs on development of larvicidal and antimicrobial performance
Authors: Mostafa Wageha A. , Elshanawany Soad A. , Otaif Khadejah D. , khalifa Mona , Elgazzar Elsayed
Published: January 2024

Zinc chromium oxide (Cr/ZnO, 5wt.%) was prepared by a facile chemical co-precipitation route. The structure, composition, and chemical bonding were analyzed using X-ray diffraction (XRD), Energy dispersive X-ray spectroscopy (EDX), and Fourier-transform infrared spectroscopy (FTIR) indicating that chromium ions were integrated the host framework to form Cr/ZnO nanocomposite. Scanning electron microscopy (SEM) and Transmission electron microscopy (TEM) micrographs showed comb-shaped nanoparticles with an average size 20 nm and large surface area. The energy gap of the thin films was estimated from T% and R% measurements which exhibit a strong optical absorption edge close to the visible spectrum. The insecticidal activity of the synthesized nanocombs againstC. pipienslarvae was evaluated with LC50(30.15 ppm) and LC90(100.22 ppm). Besides, the nanocomposite showed high antibacterial performance against gram-positive bacteria (Bacillus subtilis) and gram-negative bacteria (Proteus vulgaris) with inhibition zones 21.9 and 19 mm, respectively.
Sex-dependent circadian alterations of both central and peripheral clock genes expression and gut–microbiota composition during activity-based anorexia in mice
Authors: Salaün Colin , Courvalet Marine , Rousseau Léna , Cailleux Kévin , Breton Jonathan , Bôle-Feysot Christine , Guérin Charlène , Huré Marion , Goichon Alexis , do Rego Jean-Claude , Déchelotte Pierre , Ribet David , Achamrah Najate , Coëffier Moïse
Published: January 2024

Rationale

Patients with anorexia nervosa (AN) often present sleep disorders and circadian hormonal dysregulation. The role of the microbiota–gut–brain axis in the regulation of feeding behavior has emerged during the last decades but its relationships with the circadian rhythm remains poorly documented. Thus, we aimed to characterize the circadian clock genes expression in peripheral and central tissues in the activity-based anorexia mouse model (ABA), as well as the dynamics of the gut–microbiota composition.

Methods

From day 1 to day 17, male and female C57Bl/6 mice were submitted or not to the ABA protocol (ABA and control (CT) groups), which combines a progressive limited access to food and a free access to a running wheel. At day 17, fasted CT and ABA mice were euthanized after either resting (EoR) or activity (EoA) phase (n = 10–12 per group). Circadian clock genes expression was assessed by RT-qPCR on peripheral (liver, colon and ileum) and central (hypothalamic suprachiasmatic nucleus or SCN) tissues. Cecal bacterial taxa abundances were evaluated by qPCR. Data were compared by two-way ANOVA followed by post-tests.

Results

ABA mice exhibited a lower food intake, a body weight loss and an increase of diurnal physical activity that differ according with the sex. Interestingly, in the SCN, only ABA female mice exhibited altered circadian clock genes expression (Bmal1, Per1, Per2, Cry1, Cry2). In the intestinal tract, modification of clock genes expression was also more marked in females compared to males. For instance, in the ileum, female mice showed alteration of Bmal1, Clock, Per1, Per2, Cry1, Cry2 and Rev-erbα mRNA levels, while only Per2 and Cry1 mRNAs were affected by ABA model in males. By contrast, in the liver, clock genes expression was more markedly affected in males compared to females in response to ABA. Finally, circadian variations of gut–bacteria abundances were observed in both male and female mice and sex-dependent alteration were observed in response to the ABA model.

Conclusions

This study shows that alteration of circadian clock genes expression at both peripheral and central levels occurs in response to the ABA model. In addition, our data underline that circadian variations of the gut–microbiota composition are sex-dependent.
Respiratory particles: from analytical estimates to disease transmission
Authors: Ferreira J. A. , de Oliveira Paula , da Silva P. M.
Published: January 2024

Respiratory particles containing infectious pathogens are responsible for a large number of diseases. To define health politics and save lives, it is important to study their transmission mechanisms, namely the path of particles once expelled. This path depends on several driving factors as intrinsic properties of particles, environmental aspects and morphology of the scenario. Following physical arguments and taking into account the results of experimental works, we consider a mathematical drift model for the mixture composed by two phases: air and particles. The relative motion between the two phases is described by a kinematic constitutive relation. We prove the stability of the model for fixed times and establish an a priori estimate for the total number of infectious particles. The upper bound of this estimate exhibits sound physical dependencies on the driving factors, in agreement with the experimental literature and mounting epidemiological evidences. Namely, we establish that the amount of particles expelled and their emission rate can explain why some people are superspreaders. Several numerical simulations illustrate the theoretical results.
Innovative approaches for mycotoxin detection in various food categories
Authors: Boshra Marina H. , El-Housseiny Ghadir S. , Farag Mohammed M. S. , Aboshanab Khaled M.
Published: January 2024

Mycotoxins (MTs), produced by filamentous fungi, represent a severe hazard to the health of humans and food safety, affecting the quality of various agricultural products. They can contaminate a wide range of foods, during any processing phase before or after harvest. Animals and humans who consume MTs-contaminated food or feed may experience acute or chronic poisoning, which may result in serious pathological consequences. Accordingly, developing rapid, easy, and accurate methods of MTs detection in food becomes highly urgent and critical as a quality control and to guarantee food safety and lower health hazards. In this review, we highlighted and discussed innovative approaches like biosensors, fluorescent polarization, capillary electrophoresis, infrared spectroscopy, and electronic noses for MT identification pointing out current challenges and future directions. The limitations, current challenges, and future directions of conventional detection methods versus innovative methods have also been highlighted and discussed.
Some variants of the hybrid extragradient algorithm in Hilbert spaces
Authors: Arfat Yasir , Kumam Poom , Khan Muhammad Aqeel Ahmad , Seangwattana Thidaporn , Iqbal Zaffar
Published: January 2024

This paper provides convergence analysis of some variants of the hybrid extragradient algorithm (HEA) in Hilbert spaces. We employ the HEA to compute the common solution of the equilibrium problem and split fixed-point problem associated with the finite families of $\Bbbk $
k
-demicontractive mappings. We also incorporate appropriate numerical results concerning the viability of the proposed variants with respect to various real-world applications.
Comparative analysis of COVID-19 and influenza prevalence among Egyptian pilgrims returning from Hajj and Umrah in 2022: epidemiology, clinical characteristics, and genomic sequencing
Authors: Kandeel Amr , Fahim Manal , Deghedy Ola , BahaaEldin Hala , Roshdy Wael H. , Khalifa Mohamed Kamal , Kandeil Ahmed , El Shesheny Rabeh , Naguib Amel , AbdelFatah Mohamad , Afifi Salma , Abdel Ghaffar Khaled
Published: January 2024

Purpose

To describe the changes that occurred in the SARS-CoV-2 and influenza Prevalence, epidemiology, clinical picture, and prevalent genotypes among the Egyptian pilgrims returning from Hajj and Umrah 2022 seasons.

Methods

Pilgrims were contacted at the airport and invited to participate in the survey. Pilgrims who consented were interviewed using a standardized line list that included participant demographics, respiratory symptoms if any, previous COVID-19 infection, influenza vaccination whereas COVID-19 vaccination information were collected from vaccination cards. Participants were asked to provide throat and nasopharyngeal swabs for SARS-CoV-2 and influenza testing using RT-PCR and a subset of isolates were sequenced. Descriptive data analysis was performed to describe the epidemiology and clinical symptoms of SARS-CoV-2 and influenza. Prevalence rates of SARS-CoV-2 and influenza during Hajj were calculated and compared to Umrah surveys using chi2 and t-test with a significance level < 0.05.

Results

Overall, 3,862 Egyptian pilgrims enrolled, their mean age was 50.5 ± 47 years, half of them were > 50 years of age and 58.2% were males. Of them, 384 (9.9%) tested positive for SARS-CoV-2 and 51 (1.3%) for influenza viruses. Prevalence of SARS-CoV-2 infections (vaccine breakthrough) increased significantly between the Umrah and Hajj surveys (6.7% vs. 9.9%, p < 0.001), and variants of the virus varied considerably. Whereas no significant difference was found in influenza prevalence, vaccine coverage and vaccine breakthrough infection rates (11.7 vs. 9.2%, 26.9 vs. 26.8%, and 1.4 vs. 1.1% respectively).

Conclusions

SARS-CoV-2 prevalence among Egyptian pilgrims returning from Hajj in July increased with reduced vaccine effectiveness compared to Umrah in March 2022 suggesting a possible wave of SARS-CoV-2 in the upcoming winter.
Perspectives of healthcare workers on the integration of overdose detection technologies in acute care settings
Authors: Rioux William , Kilby Kyle , Jones Stephanie , Joshi Pamela , Vandenberg Stephanie , Ghosh S. Monty
Published: January 2024

Background

People who use drugs (PWUD) face disproportionately high rates of hospitalizations and patient-initiated discharge (leaving against medical advice), explained by a combination of stigma, withdrawal, judgment, blame, and improper pain management. In addition, evidence has shown that despite abstinence-based policies within healthcare settings, PWUD continue to use their substances in healthcare environments often hidden away from hospital staff, resulting in fatalities. Various novel overdose detection technologies (ODTs) have been developed with early adoption in a few settings to reduce the morbidity and mortality from risky substance use patterns within healthcare environments. Our study aimed to gain the perspectives of healthcare workers across Canada on implementing ODTs within these settings.

Method

We used purposive and snowball sampling to recruit 16 healthcare professionals to participate in semi-structured interviews completed by two evaluators. Interview transcripts were analyzed using thematic analysis to identify key themes and subthemes.

Results

Participants recognized ODTs as a potentially feasible solution for increasing the safety of PWUD in healthcare settings. Our results suggest the mixed ability of these services to decrease stigma and build rapport with PWUD. Participants further highlighted barriers to implementing these services, including pre-established policies, legal recourse, and coordination of emergency responses to suspected overdoses. Lastly, participants highlight that ODTs should only be one part of a multifaceted approach to reducing harm in healthcare settings and could currently be integrated into discharge planning.

Conclusion

Healthcare professionals from across Canada found ODTs to be an acceptable intervention, but only as part of a larger suite of harm reduction interventions to reduce the harms associated with illicit drug use in healthcare settings. In contrast, participants noted institutional policies, stigma on behalf of healthcare workers and leadership would present significant challenges to their uptake and dissemination.
Antioxidants and the risk of stroke: results from NHANES and two-sample Mendelian randomization study
Authors: Chen Rundong , Liu Hanchen , Zhang Guanghao , Zhang Qian , Hua Weilong , Zhang Lei , Lv Nan , Zhang Yilei , Dai Dongwei , Zhao Rui , Li Qiang , Huang Qinghai , Xu Yi , Yang Pengfei , Liu Jianmin , Zuo Qiao
Published: January 2024

Background

Stroke is the second leading cause of death worldwide, and observational studies have suggested a correlation between antioxidants and reduced stroke risk. However, it remains unclear whether causal relationships exist.

Methods

This study first performed a cross-sectional study of the association between the Composite Dietary Antioxidant Index (CDAI) and stroke using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2018. Second, a two-sample univariable Mendelian Randomization (MR) was performed to analyze the causal effect of circulating levels of antioxidants on different subtypes of stroke.

Results

The cross-sectional study included a total of 24,892 participants representing more than 200 million US non-institutionalized residents, a multivariable logistic regression model revealed that the risk of stroke decreased by 3.4% for each unit increase in CDAI (P = 0.017), with a non-linear association found, indicating a reduction in stroke risk before an inflection point of 3.078. MR analysis revealed that genetically determined levels of retinol had a suggestive protective effect on subarachnoid hemorrhage (SAH) (OR = 0.348, P = 0.025), and genetically determined levels of selenium had a suggestive protective effect against SAH (OR = 0.826, P = 0.007). However, no causal relationship was found between antioxidants and ischemic stroke or intracranial hemorrhage risk.

Conclusions

Evidence suggests that diet-derived antioxidants may reduce the risk of stroke, as indicated by the protective effects of retinol and selenium against SAH. However, more research is needed to fully understand how antioxidants prevent stroke.
Effect of Fiber Orientation on the Fatigue Behavior of Steel Fiber-Reinforced Concrete Specimens by Performing Wedge Splitting Tests and Computed Tomography Scanning
Authors: González Dorys C. , Mena-Alonso Álvaro , Mínguez Jesús , Martínez José A. , Vicente Miguel A.
Published: January 2024

This paper shows the relationship, in steel fiber-reinforced concrete, between fiber orientation and fatigue response through the combined use of computed tomography (CT), digital image processing (DIP) software and wedge splitting test (WST). The WST cubes were extracted from conventional 150 × 150× 600 concrete prisms and a groove and notch were carved on different faces in such a way that in half of the test specimens the fibers are oriented mostly perpendicular to the breaking surface and, in the other half, the fibers are mostly oriented parallel to the breaking surface. Fiber orientation was obtained using a CT device and DIP software from a miniprism extracted from the previously mentioned concrete prisms. The results show that there is a strong correlation between the crack-sewing fiber orientation on the one hand and fatigue life and crack opening rate per cycle on the other hand. Cubes with a higher percentage of fibers perpendicular to the crack surface (i.e., with a higher efficiency index) show a longer fatigue life and a lower crack opening rate per cycle, while cubes with a lower efficiency index show a shorter fatigue life and a higher crack opening rate per cycle.
Knowledge and practice of family planning among pregnant tribal women in Southern India: an observational study
Authors: Muralidhar Kiranmayee , Nishimura Holly , Coursey Kate , Krupp Karl , Jaykrishna Poornima , Srinivas Vijaya , Madhivanan Purnima
Published: January 2024

Background

There are over 700 Scheduled Tribes (ST) living in 30 Indian states. As with other indigenous groups across the world, Indian ST have some of the poorest infant and child health outcomes of any communities in India. A child born to an ST family is 19% more likely to die in the first month of life and has a 45 percent risk of dying in their first year compared with other Indian populations. Research suggests that early conception, high fertility, and low use of family planning methods are large contributors to these disparities.

Methods

A cross sectional survey in Kannada was conducted among 303 pregnant tribal women in Mysore, India after obtaining informed consent. Univariate and multivariable analyses were carried out to determine the demographic and psychosocial factors associated with knowledge of contraceptive methods using Stata 14.0.

Results

There was widespread knowledge about female sterilization, while only 39.3% of women reported hearing about one or more forms of temporary contraception, and 36.3% knew where to get them. The largest proportion of women had heard about copper-T (33.0%), followed by oral contraceptive pills (23.8%), condoms (11.9%), and injectables (4.6%). Only 2.7% of women reported ever using any form of temporary contraception. Results from the multivariable logistic regression indicated that knowledge of at least one form of temporary contraception was linked to higher age (adjusted odds ratio[AOR]: 1.09; 95% CI: 1.02, 1.17), greater number of years of marriage (AOR: 0.90; 95% CI: 0.85, 0.96), and last birth in a government facility (AOR: 3.67; 95% CI: 1.99, 6.82).

Conclusions

The study revealed poor knowledge and utilization of temporary contraceptive methods among a tribal population in rural Mysore, India. Interventions aiming to increase knowledge of contraceptive options are important for birth spacing in this population and should target younger women and those without contact with government health facilities.
Impact of financial literacy, perceived access to finance, ICT use, and digitization on credit constraints: evidence from Qatari MSME importers
Authors: Charfeddine Lanouar , Umlai Mohamed Ismail , El-Masri Mazen
Published: January 2024

This study investigates the role of financial literacy (FL), perceived access to finance (PAF), information communication technology (ICT) usage, and digitization in alleviating the level of credit constraint that micro, small, and medium enterprises (MSMEs) face in an emerging market. We draw on the economic research theories of human capital, knowledge-based view, and lifecycle hypothesis to explain the relationship between the variables. Using survey data collected from 333 MSME importers in Qatar—a country with heavy reliance on foreign goods—we find strong evidence that FL, PAF, ICT usage, and digitization are key determinants of Qatari MSME access to credit. In particular, PAF and FL are significant and have their expected signs in almost all the Probit regressions. For ICT usage and digitization, although they are key determinants of credit constraints, the findings are more sensitive and dependent on the type of financing and the resulting type of credit constraint.
Radiofrequency guidewire-facilitated recanalization of chronic thoracic central venous occlusions in hemodialysis patients
Authors: Moawad Sherif , Vance Ansar Z. , Cobb Ryan M. , Mantell Mark P. , Cohen Raphael , Clark Timothy W. I.
Published: January 2024

Purpose

To assess the outcome and safety of radiofrequency (RF) wire recanalization in patients with end-stage renal disease (ESRD) and chronic central venous occlusions (CVO).

Materials and Methods

A retrospective review of ESRD patients who underwent RF-wire recanalization of symptomatic chronic thoracic CVO from January 2017 to August 2022 yielded 20 patients who underwent 21 procedures. All patients had undergone at least one prior unsuccessful attempt at central venous recanalization using conventional catheter-based techniques. Technical success was defined by the ability to cross the CVO using RF-wire recanalization enabling endovascular treatment. Access circuit patency was evaluated based on follow-up imaging and symptomatic improvement.

Results

Radiofrequency wire recanalization was successful in 17/21 procedures (81%) with all patients (100%) reporting resolution of arm ± facial swelling. Three major complications occurred (14%): two hemothoraces and one hemopericardium. Medial stent diameter was 13 mm (range, 9–14 mm). Mean duration of hospital stay was 2 days ± 3 days. Mean procedure time was 158 ± 46 min with a mean fluoroscopy time of 31.7 ± 16.3 min. Primary unassisted patency at 6 and 12 months was 94 ± 6% and 85 ± 10%, respectively. Additional interventions resulted in significantly increased stent graft patency (P = 0.006).

Conclusion

Radiofrequency wire-enabled recanalization of CVO in symptomatic dialysis patients has a high rate of technical success with resolution of arm and facial swelling and resumed use of the ipsilateral dialysis access. Although a superior safety profile was seen than with needle-based techniques such as sharp recanalization, major complications were not infrequent indicating that this RF-wire procedure should be performed in centers equipped to manage central venous perforations.
Enhanced deep learning model enables accurate alignment measurement across diverse institutional imaging protocols
Authors: Kim Sung Eun , Nam Jun Woo , Kim Joong Il , Kim Jong-Keun , Ro Du Hyun
Published: January 2024

Background

Achieving consistent accuracy in radiographic measurements across different equipment and protocols is challenging. This study evaluates an advanced deep learning (DL) model, building upon a precursor, for its proficiency in generating uniform and precise alignment measurements in full-leg radiographs irrespective of institutional imaging differences.

Methods

The enhanced DL model was trained on over 10,000 radiographs. Utilizing a segmented approach, it separately identified and evaluated regions of interest (ROIs) for the hip, knee, and ankle, subsequently integrating these regions. For external validation, 300 datasets from three distinct institutes with varied imaging protocols and equipment were employed. The study measured seven radiologic parameters: hip-knee-ankle angle, lateral distal femoral angle, medial proximal tibial angle, joint line convergence angle, weight-bearing line ratio, joint line obliquity angle, and lateral distal tibial angle. Measurements by the model were compared with an orthopedic specialist's evaluations using inter-observer and intra-observer intraclass correlation coefficients (ICCs). Additionally, the absolute error percentage in alignment measurements was assessed, and the processing duration for radiograph evaluation was recorded.

Results

The DL model exhibited excellent performance, achieving an inter-observer ICC between 0.936 and 0.997, on par with an orthopedic specialist, and an intra-observer ICC of 1.000. The model's consistency was robust across different institutional imaging protocols. Its accuracy was particularly notable in measuring the hip-knee-ankle angle, with no instances of absolute error exceeding 1.5 degrees. The enhanced model significantly improved processing speed, reducing the time by 30-fold from an initial 10–11 s to 300 ms.

Conclusions

The enhanced DL model demonstrated its ability for accurate, rapid alignment measurements in full-leg radiographs, regardless of protocol variations, signifying its potential for broad clinical and research applicability.
Metacognitive Exam Preparation Assignments in an Introductory Biology Course Improve Exam Scores for Lower ACT Students Compared with Assignments that Focus on Terms
Authors: Angell Diane K. , Lane-Getaz Sharon , Okonek Taylor , Smith Stephanie
Published: January 2024

Completing open-ended metacognitive assignments ahead of exams resulted in higher exam scores for lower ACT students compared to those assigned to define terms. However, asking students such open-ended questions about their understanding of the material and their overconfidence did not result in their adjusting their grade predictions.
Mediated semi-quantum key distribution protocol mixing single-state and entangled-state
Authors: Du Zhenye , Yang Youlong , Ning Tong
Published: January 2024

Mediated semi-quantum key distribution (MSQKD) is a popular topic in quantum cryptography, which requires less quantum abilities from legitimate users, Alice and Bob, and has the advantage of high noise tolerance. In this paper, we propose a new MSQKD protocol where the third-party quantum server M can randomly send single-state and entangled-state without informing Alice and Bob of the type of qubit. In addition, in the case where M has an infinite quantum source, we derive the key rate and noise tolerance of the protocol, which proves the unconditional security of the protocol. Furthermore, as M changes the ratio of single-state and entangled-state, the noise tolerance also changes. In particular, when M sends only single-state or entangled-state, our protocol degenerates into the previous MSQKD protocols, and we derive a higher noise tolerance by analysing the mismatch terms.
P-07 Unraveling the Mystery-Conn's Syndrome
Authors: Shree Yv , Rao Mohan K
Published: January 2024

Background

Conn's syndrome, also known as primary aldosteronism, is a rare disease that can manifest at a young age. Resolving the underlying cause of hypertension is crucial, as seen in this case report.

Clinical Case

A 17-year-old female patient was admitted with a history of recurrent fever over the past 6 months, bifrontal headaches, palpitations, and myalgia for the past 4 months. Examination revealed resistant hypertension, and laboratory results showed persistent hypokalemia and an elevated aldosterone/renin ratio. CT imaging revealed a left adrenal adenoma. A laparoscopic intervention successfully addressed the uncontrolled hypertension. Histological examination confirmed a diagnosis of a benign adrenal cortical adenoma.

Conclusion

Post-surgery, the patient's overall condition significantly improved, and blood pressure was effectively controlled. This case report underscores the rare presentation of Conn's syndrome in young individuals and emphasizes the importance of investigating specific underlying causes of hypertension to prevent associated morbidity and mortality.Figure 1.Conns syndrome, CT scan, histology section gross.CECT scan of abdomen and pelvis - left adrenal adenoma gross section - cut section adrenal gland -showing 2 cysts one on medial side 1*1cm and inferiolateral side 1*0.5cm histology of the removed adrenal confirmed diagnosis of benign adrenal cortical adenoma  Table 1.Conns syndrome investigations  Table 2.Conns syndrome investigations
P-10 A rare case of Triple A Syndrome with familial involvement
Authors: Ozturk Sadettin , Imre Eren , Özenmis Tahsin
Published: January 2024

Introduction

Alacrimia, achalasia cardia, and adrenocorticotrophic hormone (ACTH)-resistant adrenal insufficiency make up the triple-A syndrome. It is an uncommon disease with an autosomal recessive inheritance pattern. The AAAS gene, which codes for the ALADIN protein and is located on chromosome 12q13, is the cause of Allgrove syndrome. The initial and typical symptoms are achalasia cardia and adrenal insufficiency. The majority of neurological disorders have autonomic signs, and they typically show in later life. The other typical neurological conditions are polyneuropathy, amyotrophy, and optic atrophy.

Clinical Case

A 25-year-old female patient presented to our clinic with complaints of weakness, dizziness, and hyperpigmentation of the skin. Her medical history revealed a recent intensive care unit (ICU) stay due to hypotension, during which her condition was managed with steroid therapy. However, she did not continue the steroid treatment after discharge. Notably, the patient had a family history of achalasia with operative intervention in all three siblings. The patient and her family members were also under the care of a gastroenterology specialist. Additionally, the patient reported experiencing dry eyes, for which she was using artificial tears. Physical examination revealed hyperpigmentation of tongue, gums and buccal mucosa.

Upon examination, her baseline investigations revealed a hemoglobin of 11.4 g/dL, sodium 137 mmol/L and potassium 4.0 mmol/L. The patient's adrenocorticotropic hormone (ACTH) level was measured at 1250 pg/ml, with a basal cortisol level of 0.5 ug/dL, leading to the diagnosis of adrenal insufficiency. Hydrocortisone treatment was initiated at a dosage of 2×10mg, resulting in a decline of the ACTH level to 31. Given the combination of symptoms including achalasia, alacrima, and adrenal insufficiency, genetic testing was conducted. Both alleles revealed a homozygous c.1432C>T (p.Arg478*) mutation, confirming the diagnosis of Triple A Syndrome.

Following the genetic diagnosis, a familial investigation was initiated. This investigation revealed the presence of the homozygous positive mutation in two siblings and two cousins. The constellation of symptoms and the genetic findings confirmed the occurrence of Triple A Syndrome within this family.

Conclusion

This case highlights the significance of recognizing Triple A Syndrome as an underlying cause of adrenal insufficiency in the presence of achalasia, alacrima, and a suggestive clinical history. In order to confirm the diagnosis and identify any affected family members, genetic testing is crucial. To avoid potential complications brought on by adrenal insufficiency and other systemic Triple A Syndrome manifestations, early identification and treatment are crucial.
O-12 A rare cause of parathyroid hormone independent hypercalcemia: 1,25-(OH)2D-24 Hydroxylase (CYP24A1) deficiency
Authors: Ünal Fatma Tuğçe Şah , Büşra Dağviren Cennet , Faik Erdoğan Murat
Published: January 2024

Background

Common causes of parathyroid hormon (PTH)-independent hypercalcemia in adulthood are malignancy, granulomatous diseases, and endocrinopathies. Loss-of-function mutations of CYP24A1 gene, encoding for 1,25-dihydroxyvitamin D3 24-hydroxylase, can also be a rare cause of supressed intact PTH levels, usually associated with, nephrolithiasis and nephrocalcinosis. This disease, defined as idiopathic infantile hypercalcemia, classically presents with hypercalcemia in infants. However, some individuals have also been reported with late-onset clinical manifestation or late diagnosis in adulthood.

Clinical Case

A 59-year-old male patient with a known diagnosis of type 2 diabetes mellitus for 30 years. He had a history of recurrent kidney stones since 2006. His blood and urine tests revealed elevated creatinine level, hypercalcemia with normal phosphorus levels, normal 25-hydroxycholecalciferol levels, suppressed intact PTH level and normal 24-hour urinary calcium level (Table 1). Urinary ultrasonography was consisted with medullary nephrocalcinosis and chronic kidney disease. PTH-independent causes of hypercalcemia were investigated. Malignancies, granulomatous diseases and endocrinopathies were ruled out. The 1,25-dihydroxycholecalciferol level was within the normal range. Parathormone related peptide level was determined as 1.60 pmol/L (normal value <4.2). Genetic workup revealed a homozygous loss-of-function mutation p.E143del in the CYP24A1 gene. Thereupon, genetic screening started on the siblings of the patient which not been finalized yet. However, none of them were found to have hypercalcemia in the laboratory evaluation. Treatment was started with low-dose fluconazole, which inhibits enzymes (including 25-hydroxylases and 1-α-hydroxylase) synthesizing vitamin D. After a month of treatment at a dose of 50 mg/day, no change was observed in the patient's calcium values. Follow-up with calcium-restricted diet and adequate oral hydration therapy was planned.

Conclusion

Idiopathic infantile hypercalcemia may manifest later or diagnosed later in adulthood. Genetic examination should be considered in adult patients in whom other causes of PTH-independent hypercalcemia have been excluded.Table 1.Patient's laboratory parameters
P-31 GLP1 receptor agonist in end-stage kidney disease: Are they safe and effective?
Authors: Rocha José Vicente , Lopes Marta Vaz , Peixe Carolina , De Griné Severino Mariana , Alexandre Maria Inês , Gomes Ana Coelho , Bugalho Maria João
Published: January 2024

Introduction

The novel antidiabetic therapies have been showing promising results in cardiovascular and renal protection besides diabetes treatment. GLP-1 receptor agonists (GLP-1RA) are well tolerated drugs with few side effects, but they are only approved for a glomerular filtration rate (GFR) higher than 15 mL/min. Anecdotal reports have been made of therapy with GLP-1RA in patients undergoing hemodialysis and intermittent hemodialysis with good results.

Clinical Case

A sixty-five-year-old male patient with stage 4 chronic kidney disease in the setting of hypertensive and diabetic nephropathy is accompanied at our Endocrinology Department due to non-insulin treated type 2 diabetes. His past-history was notable for atrial fibrillation, obstructive sleep apnea and chronic obstructive pulmonary disease. In what diabetes is concerned, he was under empagliflozin 10mg daily and dulaglutide 1.5mg weekly with excellent glycemic control.

Despite optimized treatment and Nephrology follow-up, GFR continued to decay, standing currently at 11 mL/min, without any acute insult, acidosis or hyperkalemia. The patient is starting preparation for hemodialysis with construction of an arteriovenous fistula. At last appointment, despite the lower GFR he maintained an excellent glycemic control with HbA1c of 6% without hypoglycemia and remained clinically asymptomatic without nausea, vomiting, or abdominal pain.

A pharmacokinetics study revealed a similar exposure to semaglutide independent of renal function (including severe renal impairment [10 patients] and end-stage kidney disease [10 patients]) with the drug being well tolerated in both subgroups without the need for dose adjustments. In our case, the patient maintained the weekly treatment, without reported and/or documented hypoglycemia and possible advantageous cardiovascular profile. In the future, GLP1RA may be a treatment option independently of the patient renal function.
P-33 A rare form of diabetes: MELAS
Authors: Akçay Seçkin , Kapan Ece , Yavuz Dilek
Published: January 2024

Introduction

MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) is a fatal multisystemic condition caused by a mitochondrial DNA mutation, the most prevalent is m.3243AAG. Diagnosis is common at a young age,and individuals with late diagnosis due to comorbidities have a shorter life expectancy. It causes dementia, epilepsy, myopathy, hearing loss, diabetes, and growth retardation. We present a patient with MELAS who was diagnosed late since it is a rare manifestation of diabetes with a different treatment than regular diabetes.

Clinical Case

A fifty-year-old female patient requested regulation of her blood sugar. She had type 2 diabetes for 20 years and hypertension, hyperlipidemia; she had a coronary bypass surgery three years ago and had been using a hearing implant for one year. She is under insulin treatment since 2018. Her 13-year-old daughter was just diagnosed with MELAS due to growth and development delays, and the m.3243AG mutation was discovered. She also screened for MELAS and found heteroplasmic m.3243A<G mutation. Her height was 143 cm, weight was 38 kg and BMI was 18.5 kg/m2. The patient was oriented and cooperative, but reluctant to answer questions. Her speech was slow, she was partial numbness, and she was not open to communication due to hearing loss, questions were always answered by her daughter. She exhibited a poor memory and calculation functions. She had muscle weakness in both extremities with a proximal muscles strength level of 3 and also described exercise intolerance. The patient did not have any seizures. She described a loss of hearing in the left ear and very poor hearing in the right ear. She had attacks of a migraine-like headache in left side of head and palpitation. Her medications included insulin glargine 1×22 units, insulin glulisine 3×8 units, coenzyme Q10 2×100 mg, arginine 3×2.5 grams, ranolazine 375 mg, perindopril 5 mg, sprinolactone 25 mg, metoprolol 50 mg, and rosuvastatin 20 mg. While Hba1c was 10.4 µg/dl, there were postprandial hyperglycemias with the highest 372 mg/dl and fasting hypoglycemias with the lowest 55 mg/dl in blood sugar follow-ups. The patient's treatment was arranged as 2×15 units of insulin degludec aspart and 1×8 units of insulin glulisine before lunch. Linagliptin was preferred instead of the weight-loss GLP-1 agonist to reduce mitochondrial stress in the patient with low BMI. Diabetic oral nutrition therapy was recommended to the malnourished patient. For cardiac evaluation, echocardiography and rhythm holter were requested. The patient was referred to the dementia outpatient clinic for memory and poor higher neurological function. Our patient had late diagnosis of MELAS with multiple complications including sensorineural deafness, a short stature and neurologic manifestations. Considering MELAS in diabetic patients with hearing loss, neurodegenerative findings, low body mass index and intolerant of metformin will significantly reduce the morbidity of the disease by enabling early diagnosis and treatment.
P-36 Hidden cause of decreased fertility rate during Grave's disease
Authors: Kutchukhidze Tinatin , Khurodze Tea
Published: January 2024

Introduction

Thyroid autoimmune disorders interfere with the physiology of reproduction, cause premature ovarianfailure, and mimic the early stage of menopause. Recently, no specific research was made to measure Grave's disease and infertility rates in young patients.

Clinical Case

Due to an inability to conceive for two years, a 24-year-old Caucasian female was referred to the clinic with typical symptoms and complaints of Grave's disease. She has a family history of Grave's disease and Diabetes mellitus. Ultrasound confirmed the presence of a highly vascularized non-homogeneous hyperplastic thyroid gland. A thyroid scan with Tc99m revealed generalized increased uptake. Laboratory investigations showed a decrease in TSH-!0.005mIU/ml (n.0.4mIU/ml - 4.0mIU/ml), elevated FT4-31.8 pmol/l (n.8.0pmol/l-22.0pmol/l), FT3- 9.69pmol/l (n3.4 pmol/l-6.76pmol/l) and positive Anti-TG -190.05 AU/ml (n>150), Anti-TPO - 75.7 IU/ml (n>75) Anti-TSHR-27.3 IU/l (n>1,5). Prolactin and gonadal hormones were within normal limits AMH - 1.8 ng/ml(n1.52ng/ml-9.95ng/ml), Fsh- 6mIU/ml(n3.9mIU/ml-12.4mIU/ml). The patient was started on Methimazole and Beta-blocker. While decreasing the Methimazole dosage for further discontinuation, disease recurrence developed, and a total thyroidectomy was performed. Post- operatively, the patient was maintained on Levothyroxine. After 6 months of follow-up due to irregular Levothyroxine intake, the patient reached a hypothyroid status, during which, the patient had 2 consecutive spontaneous pregnancies, from which, one ended with spontaneous miscarriage in the early weeks of pregnancy and another, ectopic pregnancy treated with right salpingectomy. HSG confirmed weak left fallopian tube patency. After several months of keeping TSH below 2.5 mIU/ml, IVF treatment was scheduled. The results of the infertility workup showed a decrease in ovarian reserve AMH - 0.163ng/ml (n1.52ng/ml-9.95ng/ml), Fsh-16.23 mIU/ml(n3.9mIU/ml- 12.4mIU/ml), due to it, modified natural cycle IVF was performed. She received 2 oocytes and 2 embryos. One high-grade blastocyst was transferred in a fresh cycle that ended with pregnancy and delivery. The child was born without a genetic disorder but with natal teeth.

Conclusion

This is a rare case of infertility with diminished ovarian reserve due to Grave's disease. A pregnancy was reached by proper correction of thyroid hormonal parameters and modified natural cycle IVF. It indicates a possible need for close monitoring of the functional ovarian reserve in patients planning pregnancy even at the young age group.
O-06 Efficacy of Lutetium-Peptide Receptor Radionuclide Therapy and osilodrostat treatment at achiving eucortisolism and tumour stabilization in a patient with metastatic ectopic ACTH-syndrome
Authors: Khandaeva Patimat , Golounina Olga , Feidorov Ilia , Przhiyalkovskaya Elena , Mel’nichenko Galina , Belaya Zhanna
Published: January 2024

Introduction

Ectopic ACTH syndrome (EAS) is a rare cause of endogenous hypercortisolism. We present a case of a patient diagnosed with severe EAS, achieving eucortisolism and a favorable outcome of ACTH-producing metastatic pancreatic neuroendocrine tumor (NET) after 177Lu-DOTATATE and osilodrostat treatment.

Clinical Case

A female patient was admitted to our clinic at the age of 55 complaining of severe fatigue, facial and leg edema. Laboratory tests revealed a significant degree of ACTH-dependent hypercortisolemia (late-night serum cortisol 1856 nmol/L (64–327), late-night salivary cortisol (LNSC) 387.7 nmol/L (0.5–9.65), 24hUFC 8561 nmol/L (100–379), ACTH 332.8 pg/mL (7.2–63.3)), hypokalemia (1.88 mmol/L), increased liver enzymes (alanine aminotransferase (ALT) 303.2 U/L (0–55), aspartate aminotransferase (AST) 94.3 U/L (5–34)). MRI of the brain was negative for pituitary abnormalities. CT and somatostatin receptor scintigraphy with 99mTc-Tektrotyd revealed NET of the pancreas and multiple liver metastases. Subsequent biopsy confirmed NET grade 2, Ki67 – 7%. Treatment with lanreotide 120 mg every four weeks was initiated. In order to control hypercortisolism the patient received osilodrostat at a dose of 10 mg daily, which improved the patient's general condition in the first days of therapy. After 1 month of treatment, her hypercortisolism symptoms improved, LNSC dropped to 0.54 nmol/L and morning cortisol dropped from 1451 nmol/L (101–535) to 60.7 nmol/L, which could suggest adrenal insufficiency. She also had normalization of potassium and liver enzymes (ALT 18.4 U/L, AST 23 U/L). The dose of osilodrostat was firstly reduced and then discontinued. 177Lu-DOTATATE treatment was offered with four doses (7.4 GBq (200 mCi) every 8 weeks). The first dose was administered in January 2023. The SPECT-CT performed after the second dose demonstrated disease stabilization. At the time of writing, the patient remains in eucortisolism (LNSC 5,36 nmol/L, morning cortisol 140 nmol/L, ACTH 36.4 pg/ml) with tumor stabilisation after 4 doses of 177Lu-DOTATATE. However, the most recent routine blood test revealed thrombocytopenia (platelets 44×109/μl (150–400)), decreased white blood cell count (3.24×109/μl (4.5–11)), lymphocytes (0.71×109/μl (1.18–1.34)) and hemoglobin 98 g/L (117–160). Nevertheless, her general condition remains stable and significantly improved versus the initial investigation.

Conclusion

This observation highlights the feasibility and efficacy of a combined approach using osilodrostat and 177Lu-DOTATATE in the management of patients with metastatic ACTH-producing NET. This approach resulted in a substantially improved patient quality of life.

Funding Russian Scientific Foundation 19-15-00398
A Zika virus protein expression screen in Drosophila to investigate targeted host pathways during development
Authors: Link Nichole , Harnish J. Michael , Hull Brooke , Gibson Shelley , Dietze Miranda , Mgbike Uchechukwu E. , Medina-Balcazar Silvia , Shah Priya S. , Yamamoto Shinya
Published: January 2024

In the past decade, Zika virus (ZIKV) emerged as a global public health concern. Although adult infections are typically mild, maternal infection can lead to adverse fetal outcomes. Understanding how ZIKV proteins disrupt development can provide insights into the molecular mechanisms of disease caused by this virus, which includes microcephaly. In this study, we generated a toolkit to ectopically express ZIKV proteins in vivo in Drosophila melanogaster in a tissue-specific manner using the GAL4/UAS system. We used this toolkit to identify phenotypes and potential host pathways targeted by the virus. Our work identified that expression of most ZIKV proteins caused scorable phenotypes, such as overall lethality, gross morphological defects, reduced brain size and neuronal function defects. We further used this system to identify strain-dependent phenotypes that may have contributed to the increased pathogenesis associated with the outbreak of ZIKV in the Americas in 2015. Our work demonstrates the use of Drosophila as an efficient in vivo model to rapidly decipher how pathogens cause disease and lays the groundwork for further molecular study of ZIKV pathogenesis in flies.