bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diel and annual rhythms of tropical stem size changes in the Mayombe forest, Congo Basin
Authors: Luse Belanganayi Basile , Ilondea Bhely Angoboy , Phaka Christophe Mbungu , Laurent Félix , Djiofack Brice Y. , Kafuti Chadrack , Peters Richard L. , Bourland Nils , Beeckman Hans , De Mil Tom 
Published: August 2024

IntroductionThe Congo Basin forests, a crucial global carbon sink, are expected to face increased challenges of climate change by 2027, with an expected temperature rise of 1.5°C above pre-industrial levels, accompanied by increased humidity conditions. However, studies that try to understand their functioning and untangle the species-specific responses about how weather conditions impact secondary growth dynamics are still rare.MethodsHere we present the results of a study on diel and annual stem growth in 17 trees, belonging to 11 most abundant species, both canopy and understory, in the Mayombe forest (Congo Basin) in the Democratic Republic of the Congo (DRC). We measured highly-resolved radial stem size variations and weather conditions, to comprehend the ongoing patterns of secondary growth and examine the potential influence of projected weather conditions on them.ResultsWe found that at the diel scale, trees probably grow mainly from 6pm to 9am, and that at the annual scale, they grow mainly during the rainy season, from October to May. Some trees grow year-round, while others stop growing for a period ranging from 1 to 4 months. This growth cessation typically occurs during the dry season from June to September. A generalized linear mixed-effect model revealed that annual radial stem growth is positively related to rainfall.DiscussionOur results suggest that trees in the study site have a significant potential to cope with the projected 1.5°C increase in global temperature and an additional 50 mm of local rainfall. Trees of the species T. superba exhibited improved growth under the projected scenarios. For the other tree species, no significant difference in growth was observed between the predicted and observed scenarios. We believe that much remains to be done to better understand the tree growth-climate interaction of the large variety of tree species in the Congo Basin.
Good manufacturing practice-grade generation of CD19 and CD123-specific CAR-T cells using piggyBac transposon and allogeneic feeder cells in patients diagnosed with B-cell non-Hodgkin lymphoma and acute myeloid leukemia
Authors: Mucha Martin , Štach Martin , Kaštánková Iva , Rychlá Jana , Vydra Jan , Lesný Petr , Otáhal Pavel 
Published: August 2024

BackgroundThe non-viral production of CAR-T cells through electroporation of transposon DNA plasmids is an alternative approach to lentiviral/retroviral methods. This method is particularly suitable for early-phase clinical trials involving novel types of CAR-T cells. The primary disadvantage of non-viral methods is the lower production efficiency compared to viral-based methods, which becomes a limiting factor for CAR-T production, especially in chemotherapy-pretreated lymphopenic patients.MethodsWe describe a good manufacturing practice (GMP)-compliant protocol for producing CD19 and CD123-specific CAR-T cells based on the electroporation of transposon vectors. The lymphocytes were purified from the blood of patients undergoing chemotherapy for B-NHL or AML and were electroporated with piggyBac transposon encoding CAR19 or CAR123, respectively. Electroporated cells were then polyclonally activated by anti-CD3/CD28 antibodies and a combination of cytokines (IL-4, IL-7, IL-21). The expansion was carried out in the presence of irradiated allogeneic blood-derived mononuclear cells (i.e., the feeder) for up to 21 days.ResultsExpansion in the presence of the feeder enhanced CAR-T production yield (4.5-fold in CAR19 and 9.3-fold in CAR123). Detailed flow-cytometric analysis revealed the persistence of early-memory CAR-T cells and a low vector-copy number after production in the presence of the feeder, with no negative impact on the cytotoxicity of feeder-produced CAR19 and CAR123 T cells. Furthermore, large-scale manufacturing of CAR19 carried out under GMP conditions using PBMCs obtained from B-NHL patients (starting number=200x10e6 cells) enabled the production of &gt;50x10e6 CAR19 in 7 out of 8 cases in the presence of the feeder while only in 2 out of 8 cases without the feeder.ConclusionsThe described approach enables GMP-compatible production of sufficient numbers of CAR19 and CAR123 T cells for clinical application and provides the basis for non-viral manufacturing of novel experimental CAR-T cells that can be tested in early-phase clinical trials. This manufacturing approach can complement and advance novel experimental immunotherapeutic strategies against human hematologic malignancies.
Design of adaptive cruise control strategy for EREV considering driving behavior
Authors: Zhang Jianwei , Wang Tao 
Published: August 2024

IntroductionTraditional adaptive cruise control systems ignore the impact of the driver’s intentions and driving behavior on system performance.MethodsIn response to this issue, this study designs a new adaptive cruise control system by combining personalized driving style recognition, dynamic distance control, prospective energy management, and a model predictive control framework that integrates long short-term memory neural networks and ensemble learning.ResultsIt was verified that the accuracy of the algorithm was 96.2%. In addition, experts had average ratings of 95, 96, and 98 for the economy, safety, and comfort of the system, respectively.DiscussionThis model is expected to achieve comprehensive performance optimization and improvement of EREV in complex driving environments, injecting new vitality and power into the intelligent development of electric vehicles.
Influence of a simple cyst on kidney function
Authors: Malkhasyan Vigen , Makhmudov Tukhtasin , Gilfanov Yunus , Semenyakin Igor , Sukhikh Sergey , Grigoryan Bagrat , Pushkar Dmitry 
Published: August 2024

IntroductionThe aim of the study was to estimate the influence of a simple kidney cyst on kidney function and to determine indications for surgical treatment.Materials and methodsIn this prospective cohort study, we analyze data on 109 patients who sought counseling with a simple kidney cyst. Patients with solitary cyst of the right or left kidney, grade I-IIF according to the Bosniak classification, were included. Split glomerular filtration rate (sGFR) was calculated. The maximum size of the cyst, single kidney volumes (SKV) and the volume of the lost (atrophied) parenchyma were estimated with computed tomography (CT) scan of the urinary tract with contrast.ResultsThe average difference between the sGFR of a healthy and affected kidney cyst was 11 [8.70; 13.44] ml/min, which is a statistically significant value (p = 0.001). Correlation analysis revealed a statistically significant relationship between the proportion of lost parenchyma and the maximum cyst size: p = 0.37 with 95% CI [0.20; 0.52] (p = 0). A multivariate logistic regression model showed that a statistically significant factor influencing the likelihood of a significant decrease in sGFR is the percentage of lost kidney parenchyma (OR = 1.13; p = 0).ConclusionThe growth of kidney cyst causes atrophy of the renal parenchyma and a decrease in the sGFR of the affected kidney. An increase in the volume of the atrophied parenchyma leads to a decrease in the sGFR of the affected kidney.
Development and applications of graduate outcome-based curriculum for basic medical education
Authors: Chen Guang , Wang Hongmei , Zhou Lingling , Yang Jingjin , Xu Linglong , Liang Yong 
Published: August 2024

IntroductionOutcome-based education (OBE) leads to revolutionary change in medical education, but each medical school is acknowledged to develop suited framework based on specific positioning, educational philosophy and expected outcomes.MethodsBased on the graduate outcomes of basic medical education in China released by Working Committee for the Accreditation of Medical Education (WCAME) which officially recognized by World Federation for Medical Education (WFME), Taizhou University re-documented the overall organization of the curriculum and classified the courses as “Crucial, Supporting and Associated (CSA)” categories to connect the graduate outcomes and course objectives.ResultsWe redefined the standard for graduates in Taizhou University Medical School including 34 items in four domains and redesigned the curriculum with 76 courses classified as CSA. Empirical data reveals a substantial improvement in students’ performance on Standardized Competence Test for Clinical Medicine Undergraduates in China (SCTCMU) by implementing the CSA system between 2022 and 2023. Notably, in 2023, Taizhou University’s students achieved pass rates more than 20 percentage points higher than the national average, demonstrating a profound and unprecedented impact.ConclusionThe CSA classification system provides a notably clear and structured framework for categorizing courses based on their direct or indirect relevance to educational objectives, which provides clarity to educators and empowers students with a more purposeful approach to their studies.
Metabolomics combined with intestinal microbiota reveals the mechanism of compound Qilian tablets against diabetic retinopathy
Authors: Jia Jiangwei , Liu Bo , Wang Xin , Ji Fenglan , Wen Fuchun , Xu Huibo , Ding Tao 
Published: August 2024

BackgroundDiabetic retinopathy (DR) is one of the common chronic complications of diabetes mellitus, which has developed into the leading cause of irreversible visual impairment in adults worldwide. Compound Qilian tablets (CQLT) is a traditional Chinese medicine (TCM) developed for treating DR, but its mechanism is still unclear. This study explored the mechanism of action of CQLT in treating DR through metabolomics and intestinal microbiota.MethodsHistopathologic examination of the pancreas and retina of Zucker diabetic fatty (ZDF) rats and immunohistochemistry were used to determine the expression levels of retinal nerve damage indicators ionized calcium binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP). Rat fecal samples were tested by LC-MS metabolomics to search for potential biomarkers and metabolic pathways for CQLT treatment of DR. Characteristic nucleic acid sequences of rat intestinal microbiota from each group were revealed using 16S rDNA technology to explore key microbes and related pathways for CQLT treatment of DR. At the same time, we investigated the effect of CQLT on the gluconeogenic pathway.ResultsAfter CQLT intervention, islet cell status was improved, Iba-1 and GFAP expression were significantly decreased, and abnormal retinal microvascular proliferation and exudation were ameliorated. Metabolomics results showed that CQLT reversed 20 differential metabolites that were abnormally altered in DR rats. Intestinal microbiota analysis showed that treatment with CQLT improved the abundance and diversity of intestinal flora. Functional annotation of metabolites and intestinal flora revealed that glycolysis/gluconeogenesis, alanine, aspartate and glutamate metabolism, starch and sucrose metabolism were the main pathways for CQLT in treating DR. According to the results of correlation analysis, there were significant correlations between Iba-1, GFAP, and intestinal microbiota and metabolites affected by CQLT. In addition, we found that CQLT effectively inhibited the gluconeogenesis process in diabetic mice.ConclusionIn conclusion, CQLT could potentially reshape intestinal microbiota composition and regulate metabolite profiles to protect retinal morphology and function, thereby ameliorating the progression of DR.
New evidence supports RYR3 as a candidate gene for developmental and epileptic encephalopathy
Authors: Li Jieling , Ou Yuexu , Duan Yuanhui , Gan Xiaoming , Liu Hu , Cao Jie 
Published: August 2024

BackgroundThe ryanodine receptor 3 (RYR3) is involved in skeletal muscle contraction by releasing calcium from the sarcoplasmic reticulum and subsequent T-tubule depolarization. It is also expressed in the brain, and variants in the RYR3 gene can lead to congenital myopathy type 20 (MIM: #620310).MethodsWe retrospectively analyzed the clinical characteristics and prognosis of a case of West syndrome, developmental and epileptic encephalopathy (DEE) caused by a missense variant in the RYR3 gene. We also reviewed and summarized the literature on epilepsy cases caused by RYR3 gene variants.ResultsA 10-month-old female child with delayed psychomotor development and recurrent spasm-like seizures was diagnosed with infantile spasm syndrome and DEE. Treatment with various antiepileptic drugs resulted in initial improvement but ultimately failed to control the seizures. Whole-exome sequencing revealed a novel heterozygous variant c.10943C &gt; T/p.T3648M in the RYR3 gene, and genome-wide sequencing ruled out other potentially pathogenic variants. Three previous reports have described RYR3 variants causing DEE, two of which were attributed to de novo heterozygous variants, and one was a compound heterozygote.ConclusionThe present case of DEE caused by a RYR3 heterozygous variant is consistent with previous rare cases of epilepsy caused by RYR3 gene variants in terms of pathogenesis and clinical features, but significantly different from congenital myopathy type 20. Our findings provide important evidence for the diagnosis of RYR3-related DEE, and we hypothesize that RYR3 gain-of-function variants resulting in “leaky” Ca2+ release channels may be a molecular genetic feature leading to DEE rather than myopathy.
Identification and Mendelian randomization validation of pathogenic gene biomarkers in obstructive sleep apnea
Authors: Gong Nianjin , Tuo Yu , Liu Peijun 
Published: August 2024

BackgroundBy 2020, obstructive sleep apnea (OSA), a prevalent respiratory disorder, had affected 26.6–43.2% of males and 8.7–27.8% of females worldwide. OSA is associated with conditions such as hypertension, diabetes, and tumor progression; however, the precise underlying pathways remain elusive. This study aims to identify genetic markers and molecular mechanisms of OSA to improve understanding and treatment strategies.MethodsThe GSE135917 dataset related to OSA was obtained from the GEO database. Differentially expressed genes (DEGs) were subsequently identified. Weighted gene co-expression network analysis (WGCNA) was conducted to pinpoint disease-associated genes. The intersection of these data enabled the identification of potential diagnostic DEGs. Further analyses included Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment studies, exploration of protein–protein interactions based on these genes, and an examination of immune infiltration. Mendelian randomization was employed to validate core genes against the Genome-Wide Association Study database.ResultsA total of 194 DEGs were identified in this study. WGCNA network analysis highlighted 2,502 DEGs associated with OSA. By intersecting these datasets, 53 diagnostic DEGs primarily involved in metabolic pathways were identified. Significant alterations were observed in immune cell populations, including memory B cells, plasma cells, naive CD4 T cells, M0 macrophages, and activated dendritic cells. CETN3, EEF1E1, PMM2, GTF2A2, and RRM2 emerged as hub genes implicated in the pathogenesis. A line graph model provides diagnostic insights. Mendelian randomization analysis confirmed a causal link between CETN3 and GTF2A2 with OSA.ConclusionThrough WGCNA, this analysis uncovered significant genetic foundations of OSA, identifying 2,502 DEGs and 194 genes associated with the disorder. Among these, CETN3 and GTF2A2 were found to have causal relationships with OSA.
Is there creatine in plants? The true compound behind the 1H NMR signal at 3.05 ppm in plant extracts
Authors: Novais Leice Milla Ribeiro de , Ali Sher , D’Oca Caroline Da Ros Montes , Salome Kahlil Schwanka , Barison Andersson 
Published: August 2024

IntroductionSome papers describe the presence of creatine in plants, based on a singlet signal at 3.02–3.05 ppm in the 1H NMR spectra. Although is there creatine in plants? Therefore, to answer this question, a comprehensive NMR investigation has been performed aiming the unambiguous assignment of the compound responsible for that signal.ObjectiveDetermine whether the compound behind the signal at 3.05 ppm is truly creatine or if it was just a misassignment, instead.MethodsSamples of leaves and cherries from Eugenia uniflora in their natural swollen state were submitted to HR-MAS NMR analysis.ResultsIt was found that the signal at 3.05 ppm was misassigned to creatine. The exhaustive NMR investigation revealed that the signal is related to the amino acid 4-hydroxy-N-methyl proline, instead.ConclusionThe comprehensive NMR investigation revealed that there is no creatine in plants, it was just a misassignment.
Impacts of people at-risk of either cow milk allergies or lactose intolerance on their daily calcium intake and bone mineral density
Authors: Kongpharm Kornkanok , Nakklay Parinda , Kongtong Chunhakan , Tanapumchai Pichaya , Prapkree Lukkamol , Rueangsri Narisa , Singhato Alongkote 
Published: August 2024

BackgroundPeople who are at risk of either cow milk allergies or lactose intolerance may need to avoid consuming milk and milk products, which are well-known abundant sources of calcium (Ca). This limitation in calcium intake could affect bone health. Currently, there is limited knowledge on the impact of avoiding the consumption of milk and milk products on the daily Ca intake and bone mineral density (BMD) of people at risk of cow milk allergies. This study aimed to investigate the differences between the amount of Ca intake and BMD values between people who are at risk of cow milk allergies and those who are not.MethodsA total of 80 participants were recruited, and further divided into two groups, the at-risk cow milk allergies (AR) group (n = 40) and the normal (NOR) group, using the cow milk allergies and lactose intolerance screening questionnaire. The anthropometric assessment, body composition analyses, 3-day dietary record, and bone mass density (wrist and ankle bones) measurement of all participants were collected using the dual x-ray absorptiometry (DEXA) technique to compare the differences of variables between the two groups.ResultsThe participants in the AR group presented a significantly lower amount of Ca intake (317 mg/day) than those in the NOR group (623 mg/day) (p &lt; 0.05). The bone mineral density (BMD) parameters indicated that the NOR group presented significantly higher T-scores and BMD values of the wrist (T-score = −0.27 and BMD = 0.57 g/cm2) and ankle (T-score = −0.01 and BMD = 0.59 g/cm2) bones when compared with the AR group (T-score = −1.96 and BMD = 0.48 g/cm2 for the wrist bone, and T-score = −1.18 and BMD = 0.47 g/cm2 for the ankle bone) (p &lt; 0.05). In addition, the results indicated significantly positive correlations between the amount of Ca intake and the T-scores and BMD values of both the wrist and ankle bones among all participants (p &lt; 0.05).ConclusionIn this responding sample, participants at risk of cow milk allergies experienced a significantly negative impact on the amount of Ca intake and BMD values. Professionals in nutrition and dietetics should provide nutrition education and strategies that can enhance the Ca intake among this population to help them meet the daily Ca intake recommendation, ultimately leading to better bone health.
Association between triglyceride glucose-body mass index and obstructive sleep apnea: a study from NHANES 2015–2018
Authors: Meng Xingru , Wen Haihua , Lian Leshen 
Published: August 2024

BackgroundThe association between TyG-BMI index and the risk of obstructive sleep apnea (OSA), a recently identified biomarker indicating insulin resistance, has yet to be elucidated. Therefore, this study aimed to investigate the association between TyG-BMI index and the risk of OSA using the NHANES database.MethodsAnalyses were performed on NHANES data conducted between 2015 and 2018. Logistic regression, stratified analyses, curve-fitting analyses, and threshold effects analyses were utilized to assess the association between TyG-BMI index and the risk of OSA.ResultsThe study included 4,588 participants. Multifactorial logistic regression analyses found a significant association between TyG-BMI and increased risk of OSA [OR: 1.54 (CI:1.39–1.70)]. In stratified analyses, age interacted with the association, with TyG-BMI being associated with increased risk of OSA only in a subgroup of subjects younger than 60 years [1.31 (1.14–1.50)], but gender, smoking status, and alcohol use, did not influence the association. The presence of diabetes, hypertension, and cardiovascular diseases also modified the association, but the number of the included subjects with such conditions was significantly lower, therefore the significance of associations was not observed in those subgroups. Additionally, the risk was non-linearly associated, with the inflection point of TyG-BMI at 12.09, after which the lower slope in the risk was observed.ConclusionThis study demonstrates that elevated levels of the TyG-BMI index are correlated with risk for OSA, underscoring the significance of these findings in facilitating early prevention or timely intervention for OSA.
Early phase clinical trials in pediatric oncology: Swedish pediatric oncologists’ experiences of balancing hope and expectations in life-threatening illnesses
Authors: Håkansson Anna Schröder , Andersson Ann-Christine , Abrahamsson Jonas , Stenmarker Margaretha 
Published: August 2024

AimTo study Swedish pediatric oncologists’ practical and emotional experiences of referring, including and/or treating children in early-phase clinical trials.MethodsA nationwide study was conducted using a mixed-method approach. Structured interviews based on a study-specific questionnaire and participants’ personal reflections were utilized. Survey responses were analyzed using descriptive statistics, while participants’ comments were analyzed using thematic analysis. All interviews were recorded and transcribed verbatim.ResultsIn total, 29 physicians with 4 to 32 years of experience in pediatric oncology participated, with 19 (66%) having &gt; 10 years of experience. Three themes appeared: 1) Optimization-based approach focused on finding the most suitable treatment and care for every child with a refractory/relapsed cancer eligible for an early-phase clinical trial; 2) Team-based approach aimed at establishing local and national consensus in decision-making for treatment options, including early-phase clinical trials and palliative care; 3) Family-based approach in which the physicians provided families with actionable information, listened to their desires, and endeavored to maintain hope in challenging circumstances. Several participants (40% with ≤ 10 years of experience and 58% with &gt; 10 years of experience) viewed the early-phase clinical trial as a potential “chance of cure”. A majority (80%) of physicians with ≤ 10 years of experience, reported that they often or always felt personally and emotionally affected by communication regarding early-phase clinical trials. Delivering difficult news in cases of uncertain prognosis was identified as the major challenge. None of the study participants felt adequately prepared in terms of sufficient knowledge and experience regarding early-phase clinical trials. The physicians expressed a need for guidance and training in communication to address these challenges.ConclusionsWorking with early-phase clinical trials highlight a field where physicians cannot solely rely on their expertise or past experiences, and where they are likely to be deeply emotionally involved. Physicians who care for children eligible for such studies require targeted educational initiatives and supervision.