bluuebunny/crossref_metadata_2025 huggingface dataset:
Neurocognitive functioning in adults with neurofibromatosis type 1- a nationwide population-based study
Authors: Doser Karoline , Jepsen Jens Richardt Møllegaard , Kenborg Line , Miskowiak Kamilla Woznica , Albieri Vanna , Dalton Susanne Oksbjerg , Krøyer Anja , Hove Hanne , Østergaard John R. , Johansen Christoffer , Sørensen Sven Asger , Mulvihill John , Falck Winther Jeanette , Bidstrup Pernille Envold
Published: November 2024

Background

Neurofibromatosis type 1 (NF1) is a genetic condition characterized by various somatic manifestations and cognitive impairments, but the latter are sparsely described in adults. This study aimed at characterizing potential impairments of neurocognitive functions using neuropsychological tests as well as a self-report questionnaire.

Methods

In a nationwide, population-based study including 103 adults with NF1 and 38 age- and gender-matched NF1-free comparisons, we used a comprehensive neurocognitive test battery to assess intelligence and visual short-term memory, immediate visuospatial recall, reaction time, sustained attention, motor speed, planning, planning time, working memory as well as multitasking and a questionnaire to assess executive functions. Descriptive statistics, multivariate analysis of variance (MANOVA), and general linear models with repeated measure analysis of variance (ANOVA) were used.

Results

We observed a statistically significant difference in overall performance-based cognitive functioning. Adults with NF1 showed significant, moderate-to-severe impairments in intelligence, visual short-term memory, immediate visuospatial recall, sustained attention (p < 0.0001–0.002), and some executive functions (p = 0.008 − 0.001), whereas other cognitive functions (multitasking, reaction time, motor speed, spatial working memory, planning time, and planning efficacy as well as some self-reported executive functions) were unimpaired.

Conclusions

This is the first study with a population-based sample of persons with NF1 and the results show impairments of intelligence and other cognitive functions. The pattern of both significant cognitive impairments and non-significantly different cognitive functions suggests a cognitive profile of selective rather than generalized cognitive deficits in NF1.
Synthetic data-driven overlapped neural spikes sorting: decomposing hidden spikes from overlapping spikes
Authors: Kim Min-Ki , Kim Sung-Phil , Sohn Jeong-Woo
Published: November 2024

Sorting spikes from extracellular recordings, obtained by sensing neuronal activity around an electrode tip, is essential for unravelling the complexities of neural coding and its implications across diverse neuroscientific disciplines. However, the presence of overlapping spikes, originating from neurons firing simultaneously or within a short delay, has been overlooked because of the difficulty in identifying individual neurons due to the lack of ground truth. In this study, we propose a method to identify overlapping spikes in extracellular recordings and to recover hidden spikes by decomposing them. We initially estimate spike waveform templates through a series of steps, including discriminative subspace learning and the isolation forest algorithm. By leveraging these estimated templates, we generate synthetic spikes and train a classifier using their feature components to identify overlapping spikes from observed spike data. The identified overlapping spikes are then decomposed into individual hidden spikes using a particle swarm optimization. Results from the testing of the proposed approach, using the simulation dataset we generated, demonstrated that employing synthetic spikes in the overlapping spike classifier accurately identifies overlapping spikes among the detected ones (the maximum F1 score of 0.88). Additionally, the approach can infer the synchronization between hidden spikes by decomposing the overlapped spikes and reallocating them into distinct clusters. This study advances spike sorting by accurately identifying overlapping spikes, providing a more precise tool for neural activity analysis.
Tailoring glioblastoma treatment based on longitudinal analysis of post-surgical tumor microenvironment
Authors: Bastiancich Chiara , Snacel-Fazy Emmanuel , Fernandez Samantha , Robert Stéphane , Stacchini Roberta , Plantureux Léa , Boissonneau Sébastien , Testud Benoit , Guillet Benjamin , Debarbieux Franck , Luche Hervé , Figarella-Branger Dominique , Estève Marie-Anne , Tabouret Emeline , Tchoghandjian Aurélie
Published: November 2024

Glioblastoma (GBM), an incurable primary brain tumor, typically requires surgical intervention followed by chemoradiation; however, recurrences remain fatal. Our previous work demonstrated that a nanomedicine hydrogel (GemC12-LNC) delays recurrence when administered post-surgery. However, tumor debulking also triggers time-dependent immune reactions that promote recurrence at the resection cavity borders. We hypothesized that combining the hydrogel with an immunomodulatory drug could enhance therapeutic outcomes. A thorough characterization of the post-surgical microenvironment (SMe) is crucial to guide combinatorial approaches.

In this study, we performed cellular resolution imaging, flow cytometry and spatial hyperplexed immunofluorescence imaging to characterize the SMe in a syngeneic mouse model of tumor resection. Owing to our dynamic approach, we observed transient opening of the blood–brain barrier (BBB) during the first week after surgery. BBB permeability post-surgery was also confirmed in GBM patients. In our murine model, we also observed changes in immune cell morphology and spatial location post-surgery over time in resected animals as well as the accumulation of reactive microglia and anti-inflammatory macrophages in recurrences compared to unresected tumors since the first steps of recurrence growth. Therefore we investigated whether starting a systemic treatment with the SMAC mimetic small molecule (GDC-0152) directly after surgery would be beneficial for enhancing microglial anti-tumoral activity and decreasing the number of anti-inflammatory macrophages around the GemC12-LNC hydrogel-loaded tumor cavity. The immunomodulatory effects of this drug combination was firstly shown in patient-derived tumoroids. Its efficacy was confirmed in vivo by survival analysis and correlated with reversal of the immune profile as well as delayed tumor recurrence.

This comprehensive study identified critical time frames and immune cellular targets within the SMe, aiding in the rational design of combination therapies to delay recurrence onset. Our findings suggest that post-surgical systemic injection of GDC-0152 in combination with GemC12-LNC local treatment is a promising and innovative approach for managing GBM recurrence, with potential for future translation to human patient.

Graphical Abstract
Intracranial hemorrhage in an infant leads to the diagnosis and treatment of severe hemophilia B: a case report
Authors: Lassandro Giuseppe , Palladino Valentina , Giordano Paola
Published: November 2024

Background

Hemophilia B is a rare bleeding disorder in males, characterized by a deficiency in coagulation factor IX (FIX). Replacement of FIX with a recombinant FIX (rFIX) fusion protein, to sustain therapeutic plasma levels, is recommended as both treatment and prophylaxis to prevent bleeding episodes, particularly intracranial hemorrhage (ICH).

Case presentation

This case report outlines the management of ICH in a 7-month-old infant with severe hemophilia B, following an accidental trauma-related event, resulting in a thin compound fracture of the left occiput. FIX levels were extremely low (˂1.0%) and large deletions of the coagulation F9 gene (including exons 1–6) were identified. Intensive treatment with a rFIX fusion protein conjugated to the immunoglobulin Fc fragment (rFIXFc) continued for 18 days before hospital discharge. A continuous regimen of weekly rFIXFc infusions was implemented. Thirty days after initiating rFIXFc therapy, neutralizing antibodies or FIX inhibitors (common in patients with large F9 gene deletions) were observed, causing a diffuse skin rash. Such allergic reactions typically indicate progression to potentially serious nephrotic syndrome. A unique immunotolerance regimen of oral oxatomide and intravenous hydrocortisone was started to proactively prevent allergic reactions in this patient during rFIXFc prophylaxis. Even though low titers of the inhibitor (0.6–1.0 Bethesda units) were observed occasionally during subsequent follow-up, there were no signs of further allergies or development of nephrotic syndrome.

Conclusion

This is an uncommon case in which rFIXFc was continued despite the appearance of an allergic reaction and the development of FIX inhibitors. Subsequent allergic reactions were prevented with a combination of oral oxatomide and intravenous hydrocortisone given prior to prophylactic rFIXFc. Further studies are recommended to determine the usefulness of this combination with rFIX therapy.
Impact of mesenchymal stem cell size and adhesion modulation on in vivo distribution: insights from quantitative PET imaging
Authors: Ji Xin , Wang Lizhen , Zhong Yudan , Xu Qian , Yan Junjie , Pan Donghui , Xu Yuping , Chen Chongyang , Wang Jing , Wang Guangji , Yang Min , Li Tiannv , Tang Lijun , Wang Xinyu
Published: November 2024

Background

Successful engraftment and localization of mesenchymal stem cells (MSCs) within target tissues are critical factors influencing their therapeutic efficacy for tissue repair and regeneration. However, the relative contributions of biophysical factors like cell size and adhesion capacity in regulating MSC distribution in vivo remain incompletely understood.

Methods

Cell adhesion peptides and hanging drop method were used to modify the adhesive capacity and size of MSCs. To quantitatively track the real-time biodistribution of transplanted MSCs with defined size and adhesion profiles in living mice and rats, the non-invasive positron emission tomography (PET) imaging was applied.

Results

Surface modification with integrin binding peptides like RGD, GFOGER, and HAVDI reduced MSC adhesion capacity in vitro by up to 43.5% without altering cell size, but did not significantly decrease lung entrapment in vivo. In contrast, culturing MSCs as 3D spheroids for 48 h reduced their cell diameter by 34.6% and markedly enhanced their ability to pass through the lungs and migrate to other organs like the liver after intravenous administration. This size-dependent effect on MSC distribution was more pronounced in rats compared to mice, likely due to differences in pulmonary microvessel diameters between species.

Conclusion

Our findings reveal that cell size is a predominant biophysical regulator of MSC localization in vivo compared to adhesion capacity, providing crucial insights to guide optimization of MSC delivery strategies for enhanced therapeutic efficacy.

Graphical abstract
cidalsDB: an AI-empowered platform for anti-pathogen therapeutics research
Authors: Harigua-Souiai Emna , Masmoudi Ons , Makni Samer , Oualha Rafeh , Abdelkrim Yosser Z. , Hamdi Sara , Souiai Oussama , Guizani Ikram
Published: November 2024

Computer-aided drug discovery (CADD) is nurtured by late advances in big data analytics and Artificial Intelligence (AI) towards enhanced drug discovery (DD) outcomes. In this context, reliable datasets are of utmost importance. We herein present CidalsDB a novel web server for AI-assisted DD against infectious pathogens, namely Leishmania parasites and Coronaviruses. We performed a literature search on molecules with validated anti-pathogen effects. Then, we consolidated these data with bioassays from PubChem. Finally, we constructed a database to store these datasets and make them accessible and ready-to-use for the scientific community through CidalsDB, a web-based interface. In a second step, we implemented and optimized four machine learning (ML) and three deep learning (DL) algorithms that optimally predicted the biological activity of molecules. Random Forests (RF), Multi-Layer Perceptron (MLP) and ChemBERTa were the best classifiers of anti-Leishmania molecules, while Gradient Boosting (GB), Graph-Convolutional Network (GCN) and ChemBERTa achieved the best performances on the Coronaviruses dataset. All six models were optimized and deployed through CidalsDB as anti-pathogen activity prediction models.

Scientific contribution

CidalsDB is an open access web-based tool that allows browsing and access to ready-to-use datasets of anti-pathogen molecules, alongside best performing AI models for biological activity prediction. It offers a democratized no-code platform for AI-based CADD, which shall foster innovation and collaboration within the DD community. CidalsDB is accessible through https://cidalsdb.streamlit.app/.
Efficacy of restrictive versus liberal transfusion strategies in patients with traumatic brain injury: a systematic review and meta-analysis of randomized controlled trials
Authors: Yuan Xiang , Zhang Sen , Wan Jun , Chen Cheng , Wang Peng , Fan Shijie , Liu Yuyang , Yang Jingxian , Hou Jiayi , You Qiaoyu , Li Xiao , Li Kuilin , Xiang Ziyan , Rao Yang , Zhang Yu
Published: November 2024

Background

The effects of restrictive versus liberal transfusion strategies in critically ill patients with traumatic brain injury (TBI) and anemia, particularly in adult patients with moderate to severe TBI, remain inconclusive. Therefore, this systematic review and meta-analysis aim to evaluate the comparative impact of restrictive and liberal red blood cell transfusion strategies among critically ill adult patients with moderate to severe TBI.

Methods

We conducted a search of PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from their inception through October 20, 2024, to identify randomized controlled trials that compared restrictive (transfusions at a hemoglobin level of ≤ 7 g/dL) and liberal (transfusions at a hemoglobin level of ≤ 9–10 g/dL) transfusion strategies in adult patients with TBI. The primary outcome was mortality, with secondary outcomes including an unfavorable neurological outcome at six months, as determined by the Glasgow Outcome Scale (GOS < 4; or Glasgow Outcome Scale-Extended [GOSE] < 6), and the number of units of packed red blood cells (pRBCs) transfused.

Results

Five randomized controlled trials involving 1,528 patients were included in the analysis. The results showed that restrictive transfusion, compared to liberal transfusion, had no impact on mortality (RR 1.00, 95% CI 0.80 to 1.24, I2 = 0%) or unfavorable neurological outcome at 6 months (RR 1.06, 95% CI 0.94 to 1.20, I2 = 47%). Restrictive transfusion was associated with a reduction in the number of units of pRBCs transfused (MD -2.62, 95% CI -3.33 to -1.90, I2 = 63%).

Conclusion

In patients with TBI, a restrictive transfusion strategy did not reduce the risk of mortality or unfavorable neurological outcome compared with a liberal transfusion strategy.
Sociocultural attitudes towards appearance questionnaire-4-revised (SATAQ-4R): validation in a community sample of Norwegian adolescents
Authors: Lie Selma Øverland , Bastos Rafael Valdece Sousa , Sundgot-Borgen Christine , Wisting Line , Dahlgren Camilla Lindvall
Published: November 2024

Background

Negative body image and disordered eating are common among adolescents and young adults. The Sociocultural Attitudes Towards Appearance Questionnaire-4-Revised (SATAQ-4R) captures the internalization of societal appearance ideals and perceived pressures from others but has not been validated in a Norwegian adolescent population.

Methods

The current study explored the factor structure of SATAQ-4R in a sample of adolescent Norwegian males and females (n = 1558, mean age 17.04 ± 0.95) using confirmatory factor analysis (CFA) for a 6- and 7-factor structure in females, and a 7-factor structure in males. Correlations between subscales, internal consistency and reliability, and comparisons with convergent measures (disordered eating, body mass index, negative influence of social media) were explored.

Results

The CFA supported a 7-factor structure of the SATAQ-4R for both males and females. Internal consistency and reliability were acceptable. SATAQ-4R subscales largely correlated with disordered eating and additional convergent measures.

Conclusions

Results confirm the structure and reliability of the SATAQ-4R in a Norwegian adolescent population. The subscales showed good convergent validity, and high scores on internalization and societal pressures were related to higher levels of disordered eating and negative social media influence. The Norwegian version of the SATAQ-4R thus demonstrates good psychometric properties in adolescent males and females, and is well suited to capture internalization and sociocultural pressures that particularly affect adolescents. Results highlight the need to continue working towards reducing adverse internalization and improving body image among adolescents.
CardioAtlas: deciphering the single-cell transcriptome landscape in cardiovascular tissues and diseases
Authors: Jiang Tiantongfei , Jin Xiaoyan , Gao Yueying , Zhou Weiwei , Yu Jinyang , Li Yongsheng , Xu Juan , Cai Benzhi
Published: November 2024

Increasing scRNA-seq data in cardiovascular research have substantially improved our knowledge on the development of the cardiovascular system and the mechanisms underlying cardiovascular diseases. However, the single-cell transcriptome datasets were dispersed in literature and no resource for cardiovascular systems and diseases. Here, we constructed an organized resource CardioAtlas, which provides comprehensive analysis results for > 1,929,000 cells in 27 human data sets and > 1,088,000 cells in 39 mouse data sets. Through large-scale literature retrieval and manual annotation, we constructed 12 and 15 scRNA-seq reference atlas for common human and mouse cardiovascular systems and diseases, covering 43 and 39 cell types. In particular, CardioAtlas provides five analytic modules, including cell-type prediction, identification of marker genes, functional enrichment analysis, identification of cell-type-specific transcription regulons, and cell-cell communication analysis. In addition, users can upload scRNA-seq data for personalized analysis. CardioAtlas is available at http://bio-bigdata.hrbmu.edu.cn/CardioAtlas. CardioAtlas provides the first comprehensive and well-crafted reference atlas of cardiovascular systems and diseases and describes in detail previously unrecognized cell populations across a large number of humans and mice.
CT radiomics and human-machine hybrid system for differentiating mediastinal lymphomas from thymic epithelial tumors
Authors: Xia Han , Yu Jiahui , Nie Kehui , Yang Jun , Zhu Li , Zhang Shengjian
Published: November 2024

Background

It is difficult for radiologists, especially junior radiologists with limited experience to make differential diagnoses between mediastinal lymphomas and thymic epithelial tumors (TETs) due to the overlapping imaging features. The purpose of this study was to develop and validate a CT-based clinico-radiomics model for differentiating lymphomas from TETs and to investigate whether a human-machine hybrid system can assist junior radiologists in improving their diagnostic performance.

Methods

The patients who underwent contrast-enhanced chest CT and pathologically confirmed with lymphoma or TET at two centers from January 2011 to December 2019 and from January 2017 to December 2021 were retrospectively included and split as training/validation set and external test set, respectively. Clinical and radiomic signatures were pre-selected by elastic-net, and the models were established with the selected signatures using ensemble learning. Three radiologists independently reviewed CT images and assessed each case of the external test set with knowledge of the relevant clinical information. The diagnoses of reader 1, reader 2, and reader 3 were compared with those of the models in the external test set and further separately input to the model’s ensemble process as a human-machine system to make final decisions in the external test set. The improvement of diagnostic performance of radiologists by human-machine system was evaluated by the area under the receiver operating characteristic curve and increase rate.

Results

A total of 95 patients (51 with lymphomas and 44 with TETs) at Center 1 and 94 (52 with lymphomas and 42 with TETs) at Center 2 were enrolled and divided into training/validation sets and external test set, respectively. The diagnostic performance of the clinico-radiomics model has outperformed the junior radiologists and senior radiologist in AUC (clinico-radiomics model: 0.85 (0.76,0.92); reader 2: 0.70 (0.60,0.80); reader 3: 0.60 (0.49,0.71), reader 1: 0.76 (0.66,0.86), respectively) in the external test set. The human-machine hybrid system demonstrated significant increases in AUC (reader 1 + model: 0.87 (0.79,0.94), an increase of 14%; reader 2 + model: 0.86 (0.77,0.93), an increase of 23%; reader 3 + model: 0.84 (0.76,0.91), an increase of 40%), compared to the human performance alone.

Conclusions

The clinico-radiomics model outperformed three radiologists in differentiating lymphomas from TETs on CT. The use of the human-machine hybrid system significantly improved the performance of radiologists, especially junior radiologists. It provides a real-time decision tool to reduce bias and mistakes in radiologist diagnosis and enhances the diagnostic confidence of junior radiologists. This attempt may lead to more human-machine hybrid systems being explored in the diagnosis of different diseases to drive future clinical applications.
Analysis of factors related to anesthetic management affecting acute kidney injury occurring within 72 h after esophagectomy for esophageal cancer: a historical cohort study
Authors: Ishikawa Seiji , Hirashima Junko , Hiroyama Makiko , Ozato Shojiro , Watanabe Masayuki , Terajima Katsuyuki
Published: November 2024

Background

The effects of factors related to anesthetic management, including anesthesia methods and infusion volume, on acute kidney injury (AKI) after esophagectomy have not been thoroughly investigated.

Methods

A historical cohort study of patients who underwent esophagectomy between January 2008 and December 2022 was conducted. AKI was defined according to the Kidney Disease Improving Global Outcomes creatinine criteria within 72 h after esophagectomy. Logistic regression was used to model the association between perioperative factors, including factors related to anesthetic management, and postoperative AKI.

Results

Of 1005 patients, 48 patients (4.8%) had AKI (40 stage 1 and 8 stage 2). AKI patients were older (67.8 vs. 65.0 years, P = 0.046) and more likely to have hypertension (72.9 vs. 37.9%, P < 0.001), chronic kidney disease (39.6 vs. 14.3%, P < 0.0001), red blood cell (RBC) transfusions (12.5 vs. 3.4%, P = 0.0085), and longer duration of anesthesia (518 vs. 490 min, P = 0.0058) than non-AKI patients. AKI patients were less likely to have epidural anesthesia (72.9 vs. 91.5%, P < 0.001). The distribution of inhaled anesthetics chosen was not significantly different between AKI and non-AKI patients. On multivariable logistic regression analysis, AKI was associated with the Brinkman index (per 100 units, odds ratio (OR) = 1.06), hypertension (OR = 3.39), chronic kidney disease (OR = 2.58), duration of anesthesia (per 10 min, OR = 1.03), epidural anesthesia (OR = 0.35) and RBC transfusion (OR = 3.27).

Conclusions

Except for epidural anesthesia, no significant association was found between AKI and factors related to anesthetic management. Epidural anesthesia may protect against early postoperative AKI in patients undergoing esophagectomy.
Anti-oxidative, anti-AChE and neuroprotective effect of hydro-alcoholic extract of Sansevieria cylindrica leaves and Plumeria obtusa seed pods in Wistar rats
Authors: Shewale Sunil , Undale Vaishali , Bhalchim Vrushali , Kuchekar Mohini , Warude Bhagyashri , Mali Mayur
Published: November 2024

The rising incidence of neurodegenerative diseases represents a significant global health concern. The prognosis for such diseases is often unfavorable, and patients require supportive treatment to manage their condition effectively. The present study investigated the anti-oxidative, anti-acetylcholinesterase (anti-AChE) effect of hydro-alcoholic extract of Sansevieria cylindrica leaves and Plumeria obtusa seed pods in Wistar rats. Plants were authenticated followed by pharmacognostic evaluation. The antioxidant and anti-AChE activities were evaluated by scopolamine-induced oxidative stress and acetylcholine level alterations in Wistar rats. On the 0th, 7th, and 14th days during study period behavioral parameters were evaluated, including open field test, new object recognition test, and Morris water maze task. Different antioxidant enzymes were also evaluated in brain homogenate post 7 days treatment. AChE levels in rats’ brains were assessed post 14 days of treatment. Finally, histopathology of brains samples was performed. Correspondingly, in-vitro and in-silico studies were done to support the study findings.

Results

Sansevieria cylindrica and Plumeria obtusa exhibited strong antioxidant and anti-AChE activities due to secondary metabolites content. Rearing and, line crossing by rats showed substantial alteration (p < 0.05) by combination of both plants at high dose. The escape latency found to be reduced significantly (p < 0.05) by Sansevieria cylindrica individually and in combination with Plumeria obtusa at all doses. The lipid peroxidation level in brain was decreased significantly than standard at 1:1 combination of plants extracts. The levels of GSH, CAT and SOD were attenuated significantly by different concentration of extracts (p < 0.05 and p < 0.001, respectively). The reduction in AChE levels was around 34.62% and 31.10% in male and female rats, respectively in combination of both plants at high dose compared to disease control group. It was further evident in brain histopathology. All in-vivo results were supported by in-vitro free radicals scavenging effect and in-silico study.

Conclusion

The hydro-alcoholic extracts from Plumeria obtusa seed pods and Sansevieria cylindrica leaves showed a strong natural antioxidant, and acetylcholinesterase inhibitions which can aid in the treatment of neurodegerative diseases including Alzheimer.
Different approaches in management of neonatal unconjugated hyperbilirubinemia: a review article
Authors: Fouly Amira A. , Bendas Ehab R. , Farid Yasmin A. , Sabry Sarah , Abou El Fadl Dina K.
Published: November 2024

Background

Neonatal hyperbilirubinemia is a prevalent condition that affects newborns, characterized by elevated serum bilirubin levels. The accumulation of bilirubin can cause neurotoxicity, resulting in various complications, and in severe cases, even mortality. The underlying pathophysiology of this condition primarily involves an inconsistency between the synthesis and excretion of bilirubin. Despite the short- and long-term side effects of phototherapy, it is considered a core treatment of neonatal hyperbilirubinemia. Exchange transfusion is considered a last resort in cases where phototherapy fails. Several studies have investigated the use of various agents either to replace phototherapy or to be added as adjuvants to reduce the time required for phototherapy and hence minimize the adverse effects. Some of these studies have demonstrated positive outcomes, indicating their effectiveness, while others have failed to yield any significant differences in treatment duration.

Main text

The present review summarized the etiology of neonatal hyperbilirubinemia. It was demonstrated that neonatal hyperbilirubinemia has mainly two types: Conjugated and unconjugated hyperbilirubinemia. Treatment options for neonatal hyperbilirubinemia were discussed with phototherapy as the most prevalent and successful option followed by exchange transfusion. Side effects of phototherapy were also discussed together with the different approaches introduced to clinical practice to minimize these side effects.

Conclusion

Phototherapy is the most successful treatment of neonatal hyperbilirubinemia, although its side effects are of great concern. Studies introducing adjuvants such as zinc sulfate and ursodeoxycholic acid have demonstrated promising results in reducing the duration of phototherapy and minimizing the side effects. However, these results are inconclusive, and further research is required to validate the safety and efficacy of these adjuvants.
A Novel Y-Shaped Pegylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency
Authors: Liang Yan , Wei Haiyan , Yang Fan , Zhang Hua , Chen Linqi , Yao Hui , Luo Xiaoming , Cheng Xinran , Yang Yu , Lian Qun , Du Hongwei , Li Tang , Li Pin , Zhang Gaixiu , Song Fuying , Liang Liyang , Liu Deyun , Zhu Shunye , Gong Haihong , Gong Chunxiu , Cheng Xiangao , Xu Zhuangjian , Ma Yaping , Su Zhe , Zhou Weidong , He Ruoyi , Yin Yalin , Sun Li , Luo Xiaoping
Published: November 2024

Context

Pegpesen is a novel Y-shape pegylated recombinant human growth hormone (rhGH) for once-weekly treatment of children with growth hormone deficiency (GHD).

Objective

This work aimed to evaluate the efficacy and safety of Pegpesen in children with GHD vs daily rhGH.

Methods

A multicenter, randomized, controlled phase 3 clinical trial was conducted at 23 centers in China with a duration of 52 weeks’ treatment. There were 391 pediatric participants diagnosed with GHD. Participants were randomly assigned 2:1 to a weekly Pegpesen group (140 μg/kg/week) or a daily rhGH group (245 μg/kg/week) for 52 weeks. The primary end point was the growth velocity (GV) at 52 weeks, and the secondary end points mainly involved changes from baseline in height SD scores for chronological age and bone age (ΔHt SDS CA and ΔHt SDS BA).

Results

At 52 weeks, the least squares mean (LS means) of GV was 9.910 cm/year in the Pegpesen group and 10.037 cm/year in the daily rhGH group. The LS means difference between groups was −0.127 (95% CI, −0.4868 to 0.2332), confirming that weekly Pegpesen is noninferior to daily rhGH. The LS means of ΔHt SDS CA, ΔHt SDS BA, were similar across both groups (all P > .05). Safety profiles and adherence were comparable.

Conclusion

Pegpesen was noninferior to daily rhGH, with similar safety, lower dosage requirements, thus presenting a new therapeutic option for children with GHD.
Characterization of a Novel Variant in the NR3C1 Gene: Differentiating Glucocorticoid Resistance From Cushing Syndrome
Authors: Laulhé Margaux , Yacobi Bach Michal , Perrot Julie , Gershinsky Michal , Fagart Jérôme , Shefer Gabi , Amazit Larbi , Kamenický Peter , Viengchareun Say , Martinerie Laetitia , Greenman Yona
Published: November 2024

Context

Primary generalized glucocorticoid resistance syndrome (GGRS) is a rare endocrine disease caused by loss-of-function variants of the NR3C1 gene encoding the glucocorticoid receptor (GR).

Objective

We describe a novel heterozygous missense variant (NM_000176.3, c.1330T>G, p.Phe444Val) within the DNA-binding domain.

Clinical Case

Elevated urinary free cortisol levels were detected in a 59-year-old male patient before bariatric surgery (body mass index 39.9 kg/m2). Early-onset hypertension was well controlled. The low-dose dexamethasone suppression test was pathologic, but ACTH and midnight salivary cortisol levels were normal. The patient was initially referred to transsphenoidal surgery for a presumed diagnosis of Cushing disease. He presented to our department at the age of 68, when the clinical diagnosis of GGRS was established.

Methods

Functional characterization of the variant was performed ex vivo through transient transfection assays in HEK 293T cells to assess transcriptional activity and nuclear translocation.

Results

The variant showed a lack of transcriptional activity (GRWT: 91.5 [80.5; 101.2] vs GRF444V: 1.0 [1.0; 1.0]) despite efficient nuclear translocation in response to dexamethasone, suggesting a DNA binding defect of the variant. These results are discussed in the light of previously reported GGRS cases.

Conclusion

We have described a novel heterozygous mutation of the NR3C1 gene associated with primary GGRS. This case highlights the importance of raising awareness of clinical and laboratory features of this rare disorder, to enable early diagnosis and avoid unnecessary and potentially dangerous diagnostic and therapeutic procedures.
Role of the GH-IGF Axis in Statural Growth and Harmonious Body Proportionality: In Search of Vitruvian Man?
Authors: Guevara-Aguirre Jaime , Bright George M , Guevara Alexandra , Tite Maria , Saavedra Jannette , Teran Enrique , Rosenfeld Ron G
Published: November 2024

Context

Body proportions are the objective parameters of harmonious growth and reflect the interplay of genetic, environmental, metabolic, and hormonal actions. Mutations in the growth hormone receptor gene (GHR) result in severe growth failure. The study of individuals affected with these mutations can inform us about the role of growth peptides in harmonious, proportional growth.

Objective

The aim of this study was to critically assess the role of the growth hormone–insulin-like growth factor (GH-IGF) axis in statural growth and in particular body proportionality.

Methods

In this epidemiological, noninterventional study, we compared the anthropometric measurements and body proportions of an Ecuadorian cohort of adults with GH insensitivity (GHI) due to a homozygous mutation at codon 180/exon 6 of GHR, to their carrier and noncarrier relatives, and to noncarrier unrelated controls. We also investigated the relations between serum IGF-I concentrations and auxological determinations.

Results

In this cohort of 201 adults, sex-specific distributions of height (Ht), lower segment, upper segment, arm span, head circumference (HC), and hand and foot length were lower in the GHI individuals than in the other groups. The GHI individuals had the lowest lower segment/Ht, the highest upper segment/Ht, the lowest arm span/Ht and the highest HC/Ht ratio. Hand and foot length/Ht ratios were not uniformly affected. Serum IGF-I concentrations displayed a positive logarithmic correlation with all body measurements but were negatively correlated with the HC/Ht ratio.

Conclusion

These findings indicate that individuals homozygous for the GHR mutation have disharmonious body proportions due to abnormal GH/IGF-I action on the growth of the long bones. Contrary to common assumptions, disruption of the GH-IGF axis results in disproportionality and disharmonious growth.
Evaluation of Sleep Health in Children With Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency
Authors: Golob Laura , Mercado-Munoz Yesica , Liu Wenxi , Singh Anvita , Hodges James S , Siegel Lianne , Morero Helena , Gao Zan , Tipp Angela , Simon Stacey L , Sarafoglou Kyriakie
Published: November 2024

Context

Literature on sleep health in children with congenital adrenal hyperplasia (CAH) is sparse despite the important role the hypothalamic-pituitary-adrenal axis plays in sleep onset, duration, and awakenings after sleep onset.

Objective

To evaluate sleep health in children and adolescents with CAH as measured by wrist actigraphy and validated sleep questionnaires.

Methods

Cross-sectional study at our multidisciplinary CAH clinic. Participants aged 3 to 18 years with classic CAH wore an ActiGraph GT3X+ accelerometer for 1 week. Children and parents completed sleep questionnaires, and the results were compared to published samples from the community and children with sleep disorders (clinical). Actigraphy sleep health measures were compared to consensus sleep duration recommendations and normative data in healthy children.

Results

Forty-four participants (23 male) with CAH completed the study. Actigraphy found sleep duration in children with CAH was less than recommended guidelines with significantly worse sleep efficiency and increased wake after sleep onset (P < .05) compared to healthy children. After sleep onset, the average number of awakenings increased from 1.67 per hour during the first 2 hours after the evening hydrocortisone dose to 3.12 per hour 4 to 7 hours after the dose, corresponding with washout of the evening hydrocortisone dose. Parents of 3- to 10-year-olds reported significantly worse sleep onset delay and decreased sleep duration than both the community and clinical samples, and significantly more night awakenings than the community sample.

Conclusion

Our findings suggest that sleep health is impaired in children with CAH and is an important consideration for both clinical practice and future research.
Severe, Symptomatic Hypercalcemia Secondary to PTH-secreting Pancreatoblastoma
Authors: Gandhi Anand D , McCallum James D , Fisher Jonathan S
Published: November 2024

Hypercalcemia may be induced by a variety of etiologies, most commonly primary hyperparathyroidism. Although primary hyperparathyroidism represents a relatively common endocrinological disorder, ectopic PTH secretion is a rare entity that is less well described in literature. We describe the first case to our knowledge of severe, symptomatic hypercalcemia found to be secondary to a PTH-secreting pancreatoblastoma. The patient initially presented with fatigue and progressive upper extremity intermittent muscular twitching. He was found to have biochemical evidence of primary hyperparathyroidism. A computed tomography scan of the neck and a sestamibi nuclear scan failed to definitively demonstrate a parathyroid adenoma or hyperplasia and bilateral surgical parathyroid exploration was unrevealing for any pathology. Abdominal imaging via computed tomography was obtained for evaluation of progressive postoperative epigastric pain, and the patient was found to have a retroperitoneal mass that, after biopsy, was diagnostic for a pancreatoblastoma. This mass was resected resulting in a fall in intraoperative PTH values and subsequent postoperative hypocalcemia secondary to hungry bone syndrome. Upon follow-up, the patient's parathyroid function recovered and doses of supplemental calcium and vitamin D could be tapered. Ectopic PTH-secreting masses represent a rare entity but should be considered in individuals with unclear etiology of recalcitrant primary hyperparathyroidism.
Disparities in Diabetes Technology Uptake in Youth and Young Adults With Type 1 Diabetes: A Global Perspective
Authors: Conway Rebecca Baqiyyah , Snell-Bergeon Janet , Honda-Kohmo Kyoko , Peddi Anil Kumar , Isa Salbiah Binti , Sulong Shakira , Sibomana Laurien , Gerard Gonzalez Andrea , Song Jooyoun , Lomax Kate Elizabeth , Lo Ching-Nien , Kim Wondong , Haynes Aveni , de Bock Martin , Burckhardt Marie-Anne , Schwab Savannah , Hong Kwanho
Published: November 2024

Globally, nearly 9 million people are living with type 1 diabetes (T1D). Although the incidence of T1D is not affected by socioeconomic status, the development of complications and limited access to modern therapy is overrepresented in vulnerable populations. Diabetes technology, specifically continuous glucose monitoring and automated insulin delivery systems, are considered the gold standard for management of T1D, yet access to these technologies varies widely across countries and regions, and varies widely even within high-income countries. This review focuses on disparities in diabetes technology use among adolescents and young adults with T1D, barriers to access and use, and summarizes common themes emerging across countries and regions. We conducted a survey among medical technology manufacturers and physicians in various countries across diverse geographical regions and performed extensive literature searches. Across all countries and regions, economic barriers stand out as the largest and most common barriers, either preventing market penetrance of technology into a country or limiting its access to the individual with diabetes due to high out of pocket costs. Other common barriers include structural or accessibility barriers, such as stringent eligibility requirements by insurance providers, regardless of whether the insurance was private or government-based, and provider/individual level barriers. Based on the evidence presented, we suggest the need for a joint effort involving governments, private health insurers, technology manufacturers, and healthcare providers to address the global disparities of diabetic technology utilization and ensure equitable access for all individuals living with T1D worldwide.
Early-life challenge enhances cortisol regulation in zebrafish larvae
Authors: Castillo-Ramírez Luis A. , Herget Ulrich , Ryu Soojin , De Marco Rodrigo J.
Published: November 2024

The hypothalamic-pituitary-adrenal (HPA) axis in mammals and the hypothalamic-pituitary-interrenal (HPI) axis in fish are open systems that adapt to the environment during development. Little is known about how this adaptation begins and regulates early stress responses. We used larval zebrafish to examine the impact of prolonged forced swimming at 5 days post-fertilization (dpf), termed early-life challenge (ELC), on cortisol responses, neuropeptide expression in the nucleus preopticus (NPO), and gene transcript levels. At 6 dpf, ELC-exposed larvae showed normal baseline cortisol but reduced reactivity to an initial stressor. Conversely, they showed increased reactivity to a second stressor within the 30-min refractory period, when cortisol responses are typically suppressed. ELC larvae had fewer corticotropin-releasing hormone (crh), arginine vasopressin (avp), and oxytocin (oxt)-positive cells in the NPO, with reduced crh and avp co-expression. Gene expression analysis revealed upregulation of genes related to cortisol metabolism (hsd11b2, cyp11c1), steroidogenesis (star), and stress modulation (crh, avp, oxt). These results suggest that early environmental challenge initiates adaptive plasticity in the HPI axis, tuning cortisol regulation to balance responsiveness and protection during repeated stress. Future studies should explore the broader physiological effects of prolonged forced swimming and its long-term impact on cortisol regulation and stress-related circuits.
A experiência do Rock in Rio: navegando no Oceano Azul com estratégia e inovação
Authors: Filardi Fernando , Lavrado Fernando Passeri , Biscaia Gabriel , Coco Vivian Luiz
Published: November 2024

Este estudo de caso explora os desafios enfrentados pelo Rock in Rio (RIR) ao longo de seus quase 40 anos de existência. O objetivo é provocar a reflexão acerca de possíveis soluções e estratégias de inovação empresarial para que o RIR continue a inovar e manter sua relevância no competitivo mercado de entretenimento global. O trabalho se baseia em estudo exploratório, por meio de pesquisa documental, revisão de artigos acadêmicos, e informações sobre o RIR obtidas em sites institucionais. A revisão da literatura mostra que os dilemas do caso seriam mais bem explorados desde a visão reconstrutivista do Business Model Canvas e da estratégia do oceano azul. Este estudo contribui para o aprofundamento e a compreensão de como as empresas do setor de entretenimento podem adotar estratégias inovadoras para prosperar e se diferenciar, mesmo em mercados saturados.
Conhecimento em clínica médica: resultados de Teste de Progresso de uma instituição do Nordeste
Authors: Martins Presta Paola , Pereira de Oliveira Alex , Rarunna Muniz Moreira Mara Lyvia , Otavio Ferreira da Costa Grijalva , PEIXOTO RAQUEL AUTRAN COELHO
Published: November 2024

O Teste de Progresso (TP) permite avaliar o ganho de conhecimento dos estudantes ao longo do curso de graduação. Neste estudo retrospectivo, analisamos as características psicométricas dos itens e o desempenho dos estudantes na área de clínica médica (CM) do TP de 2018 a 2024. Para as análises, usamos os pressupostos da Teoria Clássica dos Testes. Foram coletados dados de absenteísmo, índices psicométricos e médias de desempenho de estudantes do 12º semestre. Os resultados indicaram que os itens de CM apresentaram baixa dificuldade (índice médio de 0,31) e discriminação fraca (índice médio de 0,27), adequados para identificar estudantes com diferentes níveis de desempenho. A prova que envolveu mais instituições na elaboração (2022.2) foi a que obteve melhor discriminação. O ganho de conhecimento foi progressivo, com estudantes do 6º ano alcançando 70 -75% de acertos. Observou-se também uma participação elevada no TP, com média de adesão de 94,3%. A aplicação longitudinal do TP permite a análise do currículo e a identificação de lacunas, incentivando melhorias nas metodologias de ensino e suporte à formação médica. A integração de feedback regular e a utilização de metodologias ativas são recomendadas para o desenvolvimento contínuo dos estudantes e ajustes curriculares, fortalecendo a preparação para a prática médica e a qualidade do atendimento à saúde.
Impact of chlorine dioxide and chlorhexidine mouthwashes on friction and surface roughness of orthodontic stainless steel wires: an in-vitro comparative study
Authors: Apte Shivani , S Divya , Urala Arun S
Published: November 2024

Objectives Good oral hygiene measures are important for successful orthodontic treatment. They involve various types of mouthwashes which have been reported to cause alteration of mechanical properties of archwires. This study aimed to evaluate the effects of a new kind of chlorine-dioxide-containing mouthwash on the mechanical properties and surface morphology of stainless steel orthodontic archwires against the already prevalent chlorhexidine mouthwash in the market. Method Group A – Chlorhexidine mouthwash 0.2% (study), Group B – Chlorine Dioxide mouthwash (study), and Group C – Artificial Saliva (control). 42 specimens of 5 cm long 19x25 inch SS archwires were immersed in each group equally. Post immersion, the frictional force was analyzed in the universal testing machine for each group using custom-made acrylic jigs for 10 specimens. The remaining 4 specimens from each group were sent for surface morphology evaluation using an atomic force microscope. Results Friction resistance evaluation for the archwires revealed a mean friction of 0.011 ± 0.0056 in Group A, 0.015 ± 0.0052 in Group B, and 0.010 ± 0.0067 in Group C. Results suggested that the static friction of Group C (control group) was found to be the least when compared with the experimental groups, although not producing statistically significant values. Surface roughness of archwires compared at a 10μm range revealed a mean roughness of 19.38 ± 0.82 in Group A, 25.39 ± 7.01 in Group B, and 16.65 ± 3.07 in Group C which shows there wasn’t any statistically significant difference in the mean roughness midst the three sets. Conclusion Chlorine dioxide and Chlorhexidine mouthwashes caused an increase in the frictional resistance of the archwires when compared to the control group. This increase was statistically insignificant. When measured at a range of 10μm the mean surface roughness did not statistically differ across the control and the experimental groups.