bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: Whole exome sequencing identifies compound heterozygous variants in the TRAPPC9 gene in a child with developmental delay
Authors: Yu Bingxuan , Chen Jing , Yang Shuo , Wang He , Xiao Yuanyuan , Liu Shanling 
Published: August 2024

BackgroundDevelopmental delay in children under 5 years old, which occurs globally with an incidence of 10%–15%, is caused by multiple factors including genetics, prenatal conditions, perinatal complications, postnatal influences, social factors, and nutritional deficiencies. Gene variants such as EFNB1, MECP2 and TRAPPC9 play a significant role in protein deformation and downregulation of nuclear factor κB (NF-κB) activity.MethodsA 3-year-old girl, who exhibits poor gross motor skills, personal-social development, auditory language, hand-eye coordination, and visual performance, was diagnosed with global developmental delay. Trio whole exome sequencing was conducted to identify the genetic etiology of her condition. The identified genetic etiology was then validated through Sanger sequencing and quantitative polymerase chain reaction (qPCR).ResultsGenetic analysis revealed that the patient had compound heterozygous variants in the TRAPPC9 gene. These include a c.1928del frameshift variant inherited from the unaffected father and a deletion in exon 12 inherited from the unaffected mother. According to the American College of Medical Genetics (ACMG) guidelines, these variants were classified as “likely pathogenic”.ConclusionThe study revealed that compound heterozygous TRAPPC9 gene variants cause developmental delay in a Chinese girl. These variants have been classified as having significant pathogenic effect according to the ACMG criteria, suggesting a recessive genetic pattern and highlighting the importance of prenatal testing for future offspring. Furthermore, our findings expand the genotype spectrum of the TRAPPC9 gene, and provide more comprehensive information regarding genetic counseling for children experiencing developmental delay.
Microplastics and gut microbiomes impact on Yunnan snub-nosed monkeys in the Three Parallel Rivers region in China
Authors: Xia Wancai , Zhou Jiajie , Lu Zhongwei , Li Liang , Zhang Yuan , Fan Shiyuan , Krzton Ali , Li Dayong 
Published: August 2024

BackgroundMicroplastics (MPs) has been rapidly increasing and interacting with wildlife. As the highest altitudes inhabited non-human primate, Yunnan snub-nosed monkey (Rhinopithecus bieti) have been proven to be an umbrella and flagship species to indicate ecosystem changes and help develop environmental management strategies. In this study, we aimed to investigate the behavioral and ecological reasons for the types, content and differences of MPs in the feces of R. bieti, and explored the effects of MPs on gut microbiome of R. bieti.MethodsWe used the Agilent 8700 LDIR to identify the abundance and size distribution of MPs in fecal samples, and then analyzed the causes of differences in MPs content by combining data from different populations (wild group, provisioned wild group) and dominance hierarchy. At the same times, the relationships were investigated between gut microbiome diversity and MPs content.ResultsWe first demonstrate MPs ingestion by R. bieti, which highlights the potential impacts of MPs pollution in such high-altitude, inaccessible protected areas. A total of 36 types of MPs were detected, with an average of 75.263 ± 58.141MPs/g. Food provisioning and tourism significantly increased the content of MPs in the feces of R. bieti, but tourism alone did not significantly increase the content of MPs as food provisioning. At the same time, the study found that there was no significant difference in the content of MPs between different sex groups, however, the feces MPs content of adult R. bieti was significantly lower than that of juvenile, and the social dominance hierarchies among OMUs was positively correlated with the exposure of MPs. The current level of MPs pollution did not cause gut microbiome dysbiosis of R. bieti.ConclusionOur study proved from behavioral and ecological perspectives that the R. bieti exposure to MPs was related to provisioned food, and was closely related to dominance hierarchy and age. From the perspective of intestinal microbiology, it was proved that the current intake of MPs did not cause gut microbiome dysbiosis of R. bieti. Our study provided scientific basis for formulating effective protection measures and promoting the effective protection of rare and endangered animals.
Clinical characteristics and predisposing factors of lung metastasis in sacral chordoma: a cross-sectional cohort study of 221 cases
Authors: Shi Qianyu , Guo Wei , Yu Siyue , Xu Jiuhui , Ji Tao , Tang Xiaodong 
Published: August 2024

IntroductionLimited studies are available on the topic of lung metastasis in sacral chordoma. The primary objective of this study was to investigate the prevalence, characteristics, associated factors, and prognosis of lung metastasis in sacral chordoma.MethodsA total of 221 cases with primary sacral chordoma, all of whom underwent surgical resection at our center, were included in this study. Comprehensive demographic information, imaging findings, and oncological evaluations were collected and thoroughly analyzed. The diagnosis of lung metastasis in the majority of cases was established through radiographic examinations.ResultsThe prevalence of lung metastasis in the cohort was 19.5%, with the lung emerging as the predominant site of distant metastasis. Recurrent chordoma cases exhibited a significantly higher lung metastasis rate in comparison to newly diagnosed chordoma cases (33.33% and 12.76%, p=0.0005). Patients with lung metastasis had a larger tumor size, a higher proportion of previous sacral chordoma surgeries and a greater likelihood of postoperative recurrence. Associated factors of lung metastasis were tumor size, postoperative recurrence and radiotherapy. Patients with lung metastasis exhibited decreased median overall survival (91 vs. 144 months for those without lung metastasis, p&lt;0.05) and recurrence-free survival (27 vs. 68 months, p&lt;0.001) times.DiscussionLung is the most common site of distant metastasis in sacral chordoma with an incidence rate nearly 20%. Larger tumor size and postoperative recurrence are risk factors for lung metastasis while radiotherapy is a protective factor. Occurrence of lung metastasis in sacral chordoma is a negative prognostic factor.
Clinical experience with adaptive MRI-guided pancreatic SBRT and the use of abdominal compression to reduce treatment volume
Authors: Ferris William S. , George Benjamin , Plichta Kristin A. , Caster Joseph M. , Hyer Daniel E. , Smith Blake R. , St-Aubin Joel J. 
Published: August 2024

IntroductionThis work presents a method to treat stereotactic body radiation therapy (SBRT) for pancreatic cancer on a magnetic resonance-guided linear accelerator (MR-linac) using daily adaptation, real-time motion monitoring, and abdominal compression.MethodsThe motion management and treatment planning process involves a magnetic resonance imaging (MRI) simulation with cine and 3D images, a computed tomography (CT) simulation with a breath-hold CT and a 4DCT, pre-treatment verification and planning MRI, and intrafraction MRI cine images.ResultsThe results from 26 patients were included in this work. Our motion management process results in consistent motion analysis on the CT simulation, MRI simulation, and each treatment fraction. The liver dome was found to be an overestimate of tumor superior/inferior (SI) motion for most patients. Adding compression reduced SI liver dome motion by 6.2 mm on average. Clinical outcomes are similar to those observed in the literature.ConclusionsIn this work, we demonstrate how pancreatic SBRT can be successfully treated on an MR-linac using abdominal compression. This allows for an increased duty cycle compared to gating and/or breath-hold techniques.
Adverse event reporting of the IGF-1R monoclonal antibody teprotumumab: a real-world study based on the US food and drug administration adverse event reporting system
Authors: Zhao Jiawei , Tao Yong 
Published: August 2024

BackgroundTeprotumumab, an IGF-1R monoclonal antibody, has shown significant efficacy in treating thyroid eye disease (TED). However, since teprotumumab was launched in 2020 and first approved in the United States, there were limited reports of post-marketing adverse events (AEs). In this study, we aimed to mine and analyze the AEs signals with teprotumumab on the basis of the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to provide instructions in clinical practice concerning adverse reactions and assistance in drug development and import/export into other countries.MethodsAll AE reports were obtained from the FAERS database from the first quarter of 2020 to the fourth quarter of 2023. To comprehensively analyze the AEs, we applied four disproportionality analysis algorithms, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms.ResultsA total of 687 reports from 200 patients related to administration of teprotumumab were obtained, and 78% of the cases was female. Signal detection of teprotumumab at the system organ class (SOC) level included gastrointestinal disorders, ear and labyrinth disorders, general disorders and administration site conditions, nervous system disorders, and musculoskeletal and connective tissue disorders. AEs that ranked top five at the preferred terms (PTs) level were muscle spasms, fatigue, tinnitus, headache, and deafness. The median time to those AEs onsets was 48 days (interquartile range 19.0–92.0 days) after administering drugs. Additionally, our results indicated the AEs in reproductive system and breast disorders because the prevalence of TED was more common in women.ConclusionThis study identified many AEs associated with teprotumumab and unveiled potential new AE signals. These results can provide valuable evidence for further clinical application of teprotumumab and are important in enhancing clinical medication safety.
11-Hydroxyeicosatetraenoics induces cellular hypertrophy in an enantioselective manner
Authors: Helal Sara A. , El-Sherbeni Ahmed A. , El-Kadi Ayman O. S. 
Published: August 2024

BackgroundR/S enantiomers of 11-hydroxyeicosatertraenoic acid (11-HETE) are formed from arachidonic acid by enzymatic and non-enzymatic pathways. 11-HETE is predominately formed by the cytochrome P450 1B1 (CYP1B1). The role of CYP1B1 in the development of cardiovascular diseases is well established.ObjectivesThis study aimed to assess the cellular hypertrophic effect of 11-HETE enantiomers in human RL-14 cardiomyocyte cell line and to examine their association with CYP1B1 levels.MethodsHuman fetal ventricular cardiomyocyte, RL-14 cells, were treated with 20 µM (R) or (S) 11-HETE for 24 h. Thereafter, cellular hypertrophic markers and cell size were then determined using real-time polymerase chain reaction (RT-PCR) and phase-contrast imaging, respectively. The mRNA and protein levels of selected CYPs were determined using RT-PCR and Western blot, respectively. In addition, we examined the effect of (R) and (S) 11-HETE on CYP1B1 catalytic activity using human recombinant CYP1B1 and human liver microsomes.ResultsBoth (R) and (S) 11-HETE induced cellular hypertrophic markers and cell surface area in RL-14 cells. Both enantiomers significantly upregulated CYP1B1, CYP1A1, CYP4F2, and CYP4A11 at the mRNA and protein levels, however, the effect of the S-enantiomer was more pronounced. Furthermore, 11(S)-HETE increased the mRNA and protein levels of CYP2J and CYP4F2, whereas 11(R)-HETE increased only CYP4F2. Only 11(S)-HETE significantly increased the catalytic activity of CYP1B1 in recombinant human CYP1B1, suggesting allosteric activation in an enantioselective manner.ConclusionOur study provides the first evidence that 11-HETE can induce cellular hypertrophy in RL-14 cells via the increase in CYP1B1 mRNA, protein, and activity levels.
eLIFEwithIBD: study protocol for a randomized controlled trial of an online acceptance and commitment therapy and compassion-based intervention in inflammatory bowel disease
Authors: Ferreira Cláudia , Pereira Joana , Matos-Pina Inês , Skvarc David , Galhardo Ana , Ferreira Nuno , Carvalho Sérgio A. , Lucena-Santos Paola , Rocha Bárbara S. , Oliveira Sara , Portela Francisco , Trindade Inês A. 
Published: August 2024

BackgroundInflammatory bowel disease (IBD) entails physical, psychological, and social burden and holds a significant impact on quality of life. Experiential avoidance, cognitive fusion, shame, and self-criticism have been identified as possible therapeutic targets for improving mental health in people with IBD. Traditional face-to-face psychological therapy continues to provide obstacles for patients seeking assistance. Online psychological therapies centered on acceptance, mindfulness, and compassion have been shown to improve psychological distress in other populations.ObjectiveThis paper presents the study protocol of a two-arm Randomized Controlled Trial (RCT) of an ACT and compassion-based, online intervention – eLIFEwithIBD - on the improvement of psychological distress, quality of life, work and social functioning, IBD symptom perception, illness-related shame, psychological flexibility, and self-compassion.MethodsThe eLIFEwithIBD intervention is an adaptation of the LIFEwithIBD programme (delivered through an in-person group format) and entails an ACT, mindfulness, and compassion-based intervention designed to be delivered as an e-health tool for people with IBD. This protocol outlines the structure and contents of the eLIFEwithIBD intervention. Participants were recruited by an advertisement on the social media platforms of Portuguese Associations for IBD in January 2022. A psychologist conducted a brief interview with 80 patients who were interested in participating. Fifty-five participants were selected and randomly assigned to one of two conditions [experimental group (eLIFEwithIBD + medical TAU; n = 37) or control group (medical TAU; n = 18)]. Outcome measurement took place at baseline, post-intervention, and 4-month follow-up. All analyses are planned as intent-to-treat (ITT).ResultsThe eLIFEwithIBD intervention is expected to empower people with IBD by fostering psychological strategies that promote illness adjustment and well-being and prevent subsequent distress. The eLIFEwithIBD aims to gain a novel and better understanding of the role of online contextual behavioral interventions on improving the quality of life and mental health of people with IBD.Clinical Trial Registrationhttps://classic.clinicaltrials.gov/ct2/show/NCT05405855, NCT05405855.
Pilot testing the Engaging Generations (eGen) Program to address social well-being among lower-income older adults
Authors: Tsotsoros Cindy E. , Pascuzzi Emma , Brasher Melanie , Souza Kristin , Leedahl Skye N. 
Published: August 2024

IntroductionThroughout the COVID-19 pandemic, the need to address digital inclusion and social well-being for older adults was particularly apparent for those from disadvantaged communities. This pilot program provided access to technology and intergenerational mentorship to older adult participants interested in receiving and learning how to utilize an iPad. Pre/post-changes were examined for social well-being in the areas of quality of life, social isolation, and loneliness.MethodsThis study conducted pre- and post-surveys with older participants (n = 145) from five disadvantaged communities in the United States utilizing standardized measures. One-on-one interviews were conducted post-program (n = 98) to examine participants’ perceptions of the program and evaluate its impact on social measures.ResultsThe study sample included older adults (Mean age = 72.3) who were mostly lower income (82.3%) and self-reported as Black (13.6%), Hispanic (21.7%), and White (56.5%). Significant differences were identified in participant pre/post-survey scores for social isolation, loneliness, and a global measure of quality of life. Qualitative analyses suggest improvements in various aspects of social well-being. Themes showed that participants believed the program contributed to (1) enhanced mood and mental health, (2) improved quality of life, (3) sense of purpose and feelings of being less alone, (4) ability to use video calling to connect with others; and (5) ability to more freely use email, texting, and messaging to communicate with others.DiscussionThis research demonstrates that this pilot program seemed to contribute to reduced social isolation and loneliness for participants, and participants stated more positive social well-being following program participation. However, future research with larger samples is needed to expand upon these findings. Future studies will examine the pathways between technology improvements and social well-being and examine group differences.
Complement Component C5a and Fungal Pathogen Induce Diverse Responses through Crosstalk between Transient Receptor Potential Channel (TRPs) Subtypes in Human Conjunctival Epithelial Cells
Authors: Rech Loreena , Dietrich-Ntoukas Tina , Reinach Peter S. , Brockmann Tobias , Pleyer Uwe , Mergler Stefan 
Published: August 2024

The conjunctiva has immune-responsive properties to protect the eye from infections. Its innate immune system reacts against external pathogens, such as fungi. The complement factor C5a is an important contributor to the initial immune response. It is known that activation of transient-receptor-potential-vanilloid 1 (TRPV1) and TRP-melastatin 8 (TRPM8) channels is involved in different immune reactions and inflammation in the human body. The aim of this study was to determine if C5a and mucor racemosus e voluminae cellulae (MR) modulate Ca2+-signaling through changes in TRPs activity in human conjunctival epithelial cells (HCjECs). Furthermore, crosstalk was examined between C5a and MR in mediating calcium regulation. Intracellular Ca2+-concentration ([Ca2+]i) was measured by fluorescence calcium imaging, and whole-cell currents were recorded using the planar-patch-clamp technique. MR was used as a purified extract. Application of C5a (0.05–50 ng/mL) increased both [Ca2+]i and whole-cell currents, which were suppressed by either the TRPV1-blocker AMG 9810 or the TRPM8-blocker AMTB (both 20 µM). The N-terminal peptide C5L2p (20–50 ng/mL) blocked rises in [Ca2+]i induced by C5a. Moreover, the MR-induced rise in Ca2+-influx was suppressed by AMG 9810 and AMTB, as well as 0.05 ng/mL C5a. In conclusion, crosstalk between C5a and MR controls human conjunctival cell function through modulating interactions between TRPV1 and TRPM8 channel activity.
The Burden of Deep Vein Thrombosis and Risk Factors in Pregnancy and Postpartum—Mirroring Our Region’s Particularities
Authors: Filip Catalina , Socolov Sofia Alexandra , Matasariu Daniela Roxana , Ursache Alexandra , Pisla Karina Delia , Gisca Tudor Catalin , Mihalceanu Elena , Boiculese Vasile Lucian , Socolov Demetra 
Published: August 2024

(1) Background: The three factors within the Virchow triad play the leading role in the development of deep vein thrombosis (DVT) during pregnancy. (2) Methods: This research approaches the various risk factors associated with DVT and its most representative complications, pulmonary thromboembolism and cerebral venous thrombosis, in pregnant and postpartum women across a 15-year period (2007–2021). (3) Results: A total of 201 out of 287 patients with DVT had associated risk factors, while 86 did not present with any. Out of the 201 patients with risk factors, 47 developed pulmonary thromboembolism, while 12 experienced cerebral thrombosis. The statistical analysis of risk factors involved in DVT revealed high significance for obesity (OR 3.676; CI 2.484–5.439), gestational diabetes (OR 3.394; CI 2.101–5.483), hypertension (OR 2.325; CI 1.591–3.397), preeclampsia (OR 4.753; CI 2.342–9.645), thrombophilia (OR 12.138; CI 8.973–16.417), and varicose veins (OR 9.678; CI 7.321–12.793); for pulmonary thromboembolism, there was high significance for obesity (OR 7.867; CI 4.297–14.401), hypertension (OR 2.605; CI 1.246–5.446), preeclampsia (OR 7.483; CI 2.346–23.872), thrombophilia (OR 11.035; CI 5.910–20.602), and varicose veins (OR 6.837; CI 3.665–12.757); and for cerebral thromboembolism (CTE), the risk factors identified were obesity (OR 6.755; CI 1.954–23.347), hypertension (OR 1.167; CI 0.155–8.770), preeclampsia (OR 9.655; CI 1.283–72.672), and thrombophilia (OR 33.275; CI 12.884–85.939). (4) Conclusions: Obesity was the only significant factor found to influence DVT, pulmonary embolism and CTE risks, and hereditary thrombophilia was the main factor influencing the risk for pulmonary thromboembolism and CTE. Systemic lupus erythematosus and gestational diabetes revealed conflicting results that require further investigation.
Maximizing Computation Rate for Sustainable Wireless-Powered MEC Network: An Efficient Dynamic Task Offloading Algorithm with User Assistance
Authors: He Huaiwen , Huang Feng , Zhou Chenghao , Shen Hong , Yang Yihong 
Published: August 2024

In the Internet of Things (IoT) era, Mobile Edge Computing (MEC) significantly enhances the efficiency of smart devices but is limited by battery life issues. Wireless Power Transfer (WPT) addresses this issue by providing a stable energy supply. However, effectively managing overall energy consumption remains a critical and under-addressed aspect for ensuring the network’s sustainable operation and growth. In this paper, we consider a WPT-MEC network with user cooperation to migrate the double near–far effect for the mobile node (MD) far from the base station. We formulate the problem of maximizing long-term computation rates under a power consumption constraint as a multi-stage stochastic optimization (MSSO) problem. This approach is tailored for a sustainable WPT-MEC network, considering the dynamic and varying MEC network environment, including randomness in task arrivals and fluctuating channels. We introduce a virtual queue to transform the time-average energy constraint into a queue stability problem. Using the Lyapunov optimization technique, we decouple the stochastic optimization problem into a deterministic problem for each time slot, which can be further transformed into a convex problem and solved efficiently. Our proposed algorithm works efficiently online without requiring further system information. Extensive simulation results demonstrate that our proposed algorithm outperforms baseline schemes, achieving approximately 4% enhancement while maintain the queues stability. Rigorous mathematical analysis and experimental results show that our algorithm achieves O(1/V),O(V) trade-off between computation rate and queue stability.