bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advancements in surgical education: exploring animal and simulation models in fetal and neonatal surgery training
Authors: Davidson Emily L. , Penniston Kristina L. , Farhat Walid A. 
Published: June 2024

IntroductionSurgical education is undergoing a transformation, moving away from traditional models towards more modern approaches that integrate experiential and didactic methods. This shift is particularly pertinent in the realm of fetal and neonatal surgery, where specialized training is crucial. Historical training methods, such as cadaveric dissection, have been prevalent for centuries, but newer innovations, including animal and non-animal simulation models, are gaining prominence. This manuscript aims to explore the use of both animal and non-animal models in surgical education, with a specific focus on fetal and neonatal surgery.Animal modelsThe use of animal models in surgical training has a long history, dating back to Halsted's introduction in 1889. These models, often utilizing large animals like swine and dogs, offer valuable insights into fetal and neonatal surgeries. They allow for the study of long-term outcomes and the simulation of various diseases and anomalies, providing essential training experiences not readily available in human surgeries. However, there are notable limitations, including anatomical and physiological differences from humans, ethical considerations, and substantial infrastructure and maintenance costs.Simulation modelsSimulation-based training offers several benefits, including standardized and safe learning environments without risks to real patients. Bench models, using synthetic materials or non-living animal tissue, provide cost-effective options for skills development. Virtual reality and 3-D printing technologies further enhance simulation experiences, allowing for the replication of complex clinical scenarios and patient-specific anatomies. While these models offer significant advantages, they lack the complexity of biological systems found in animal models.ConclusionIn conclusion, both animal and non-animal simulation models play crucial roles in enhancing surgical education, particularly in fetal and neonatal surgery. While advancements in non-animal technologies are important for ethical reasons, the continued necessity of animal models in certain areas should be acknowledged. By responsibly integrating these models into training programs, surgical education can be further enriched while upholding ethical standards and ensuring optimal patient outcomes.
Untargeted metabonomics and TLR4/ NF-κB signaling pathway analysis reveals potential mechanism of action of Dendrobium huoshanense polysaccharide in nonalcoholic fatty liver disease
Authors: Deng Guang-hui , Zhao Chen-chen , Cai Xiao , Zhang Xiao-qian , Ma Meng-zhen , Lv Jia-hui , Jiang Wen-li , Peng Dai-yin , Wang Yan-yan , Xing Li-hua , Yu Nian-jun 
Published: June 2024

Nonalcoholic fatty liver disease (NAFLD) is marked by hepatic steatosis accompanied by an inflammatory response. At present, there are no approved therapeutic agents for NAFLD. Dendrobium Huoshanense polysaccharide (DHP), an active ingredient extracted from the stems of Dendrobium Huoshanense, and exerts a protective effect against liver injury. However, the therapeutic effects and mechanisms of action DHP against NAFLD remain unclear. DHP was extracted, characterized, and administered to mice in which NAFLD had been induced with a high-fat and high-fructose drinking (HFHF) diet. Our results showed that DHP used in this research exhibits the characteristic polysaccharide peak with a molecular weight of 179.935 kDa and is composed primarily of Man and Glc in a molar ratio of 68.97:31.03. DHP treatment greatly ameliorated NAFLD by significantly reducing lipid accumulation and the levels of liver function markers in HFHF-induced NAFLD mice, as evidenced by decreased serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC) and total triglyceride (TG). Furthermore, DHP administration reduced hepatic steatosis, as shown by H&amp;E and Oil red O staining. DHP also inhibited the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway expression, thereby reducing levels of hepatic proinflammatory cytokines. Besides, untargeted metabolomics further indicated that 49 metabolites were affected by DHP. These metabolites are strongly associated the metabolism of glycine, serine, threonine, nicotinate and nicotinamide, and arachidonic acid. In conclusion, DHP has a therapeutic effect against NAFLD, whose underlying mechanism may involve the modulation of TLR4/NF-κB, reduction of inflammation, and regulation of the metabolism of glycine, serine, threonine, nicotinate and nicotinamide metabolism, and arachidonic acid metabolism.
Translational PK/PD and the first-in-human dose selection of a PD1/IL15: an engineered recombinant targeted cytokine for cancer immunotherapy
Authors: Yadav Rajbharan , Schubbert Suzanne , Holder Patrick G. , Chiang Eugene Y. , Kiabi Nargess , Bogaert Liz , Leung Irene , Rashid Rumana , Avery Kendra N. , Bonzon Christine , Desjarlais John R. , Sanjabi Shomyseh , Sharma Amy , Lepherd Michelle , Shelton Amy , Chan Pam , Liu Yanqiu , Joslyn Louis , Hosseini Iraj , Stefanich Eric G. , Kamath Amrita V. , Bernett Matthew J. , Shivva Vittal 
Published: June 2024

IntroductionInterleukin 15 (IL-15) is a potential anticancer agent and numerous engineered IL-15 agonists are currently under clinical investigation. Selective targeting of IL-15 to specific lymphocytes may enhance therapeutic effects while helping to minimize toxicities.MethodsWe designed and built a heterodimeric targeted cytokine (TaCk) that consists of an anti-programmed cell death 1 receptor antibody (anti-PD-1) and an engineered IL-15. This “PD1/IL15” selectively delivers IL-15 signaling to lymphocytes expressing PD-1. We then investigated the pharmacokinetic (PK) and pharmacodynamic (PD) effects of PD1/IL15 TaCk on immune cell subsets in cynomolgus monkeys after single and repeat intravenous dose administrations. We used these results to determine the first-in-human (FIH) dose and dosing frequency for early clinical trials.ResultsThe PD1/IL15 TaCk exhibited a nonlinear multiphasic PK profile, while the untargeted isotype control TaCk, containing an anti-respiratory syncytial virus antibody (RSV/IL15), showed linear and dose proportional PK. The PD1/IL15 TaCk also displayed a considerably prolonged PK (half-life range ∼1.0–4.1 days) compared to wild-type IL-15 (half-life ∼1.1 h), which led to an enhanced cell expansion PD response. The PD was dose-dependent, durable, and selective for PD-1+ lymphocytes. Notably, the dose- and time-dependent PK was attributed to dynamic TMDD resulting from test article-induced lymphocyte expansion upon repeat administration. The recommended first-in-human (FIH) dose of PD1/IL15 TaCk is 0.003 mg/kg, determined based on a minimum anticipated biological effect level (MABEL) approach utilizing a combination of in vitro and preclinical in vivo data.ConclusionThis work provides insight into the complex PK/PD relationship of PD1/IL15 TaCk in monkeys and informs the recommended starting dose and dosing frequency selection to support clinical evaluation of this novel targeted cytokine.
Helicobacter pylori antibiotic resistance profile in Chinese children with upper gastrointestinal symptoms and a literature review for developing personalized eradicating strategies
Authors: Zhou Danli , Wang Wuyu , Gu Lan , Han Meiling , Hao Wujuan , Huang Junfeng , Lin Qiong , Wang Yan 
Published: June 2024

Background:H. pylori (Helicobacter pylori) infections typically occur in early childhood. Although the prevalence of H. pylori in children is lower than that in adults, the eradication rate of this infection in children is relatively low because of resistance. In this study, we analyzed personalized treatment strategies to achieve treatment goals based on H. pylori resistance characteristics. This retrospective single-center study was conducted between January 2019 and December 2022 and enrolled 1,587 children who presented with upper gastrointestinal symptoms and underwent endoscopy. H. pylori culturing and antimicrobial susceptibility testing were performed.Results: Culture-positive results for H. pylori were obtained in 535 children. The resistance rates to clarithromycin (CLA), metronidazole (MET), and levofloxacin (LEV) were 39.8%, 78.1%, and 20.2%, respectively. None of the isolates were resistant to tetracycline (TET), amoxicillin (AMO), or furazolidone (FZD). Double resistance rates to CLA + MET, CLA + LEV, and MET + LEV were 19.1%, 3.0%, and 5.8%, respectively. Notably, triple-resistant to CLA + MET + LEV was 9.7%. Based on susceptibility tests, individualized triple therapy [proton pump inhibitor (PPI) +AMO + CLA/MET] was selected for 380 children with H. pylori sensitive to MET and/or CLA. In 155 children resistant to CLA and MET, bismuth-based quadruple therapy was recommended; for unable to receive bismuth, concomitant therapy was recommended for 14 children (&lt;8 years of age); triple therapy with TET was recommended for 141 children (&gt;8 years of age), with 43 children (&gt;14 years of age) requiring FZD rather than TET.Conclusion: Resistance to H. pylori in Chinese children was relatively poor. Personalized therapy regimens should be based on susceptibility tests and avoided factors associated with treatment failure.
Effects of exercise dose based on the ACSM recommendations on patients with post-stroke cognitive impairment: a systematic review and meta-analyses
Authors: Zhao Xuejiao , Li Juan , Xue Chao , Li Yujie , Lu Ting 
Published: June 2024

PurposeThis review aimed to assess the impact of different exercise dosages on cognitive function in individuals with post-stroke cognitive impairment (PSCI).MethodsFour electronic databases—Embase, PubMed, Web of Science, and Cochrane Library—were systematically searched from inception to 01 January 2024, focusing on the impact of exercise therapy on cognitive function in individuals with PSCI. Only randomized controlled trials meeting the criteria were included. The exercise therapy dose and adherence were evaluated following the American College of Sports Medicine (ACSM) guidelines, categorized into a high compliance group with ACSM recommendations and a low or uncertain compliance group. A random-effects model compared the effect of ACSM compliance on cognitive function in individuals with PSCI, with the effect size represented by the standardized mean difference (SMD) and a 95% confidence interval (CI).ResultsIn total, 18 studies meeting the criteria were included, with data from 1,742 participants. The findings suggested a beneficial effect of exercise on cognitive function in individuals with PSCI [SMD = 0.42, 95% CI (0.20, 0.65)]. Ten studies were categorized as the “high adherence group” and eight in the “low or uncertain adherence group” based on the ACSM recommendations. The subgroup analysis revealed that the SMD of the high compliance group was 0.46 (95% CI: 0.10, 0.82) (p = 0.01), while the SMD of the low or uncertain compliance group was 0.38 (95% CI: 0.07, 0.70) (p = 0.02).ConclusionOur study indicates the beneficial impact of exercise for patients with PSCI over no exercise. Furthermore, high adherence to the exercise dose recommended by ACSM guidelines demonstrated a more substantial improvement in cognitive function than low or uncertain adherence in patients with PSCI.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/#myprospero, identifier CRD42023487915.
High-density linkage to physical mapping in a unique Tall × Dwarf coconut (Cocos nucifera L.) outbred F2 uncovers a major QTL for flowering time colocalized with the FLOWERING LOCUS T (FT)
Authors: Grattapaglia Dario , Alves Wellington Bruno dos Santos , Pacheco Cleso Antônio Patto 
Published: June 2024

IntroductionThe coconut tree crop (Cocos nucifera L.) provides vital resources for millions of people worldwide. Coconut germplasm is largely classified into ‘Tall’ (Typica) and ‘Dwarf’ (Nana) types. While Tall coconuts are outcrossing, stress tolerant, and late flowering, Dwarf coconuts are inbred and flower early with a high rate of bunch emission. Precocity determines the earlier production of a plantation and facilitates management and harvest.MethodsA unique outbred F2 population was used, generated by intercrossing F1 hybrids between Brazilian Green Dwarf from Jiqui (BGDJ) and West African Tall (WAT) cultivars. Single-nucleotide polymorphism (SNP) markers fixed for alternative alleles in the two varieties, segregating in an F2 configuration, were used to build a high-density linkage map with ~3,000 SNPs, anchored to the existing chromosome-level genome assemblies, and a quantitative trait locus (QTL) mapping analysis was carried out.ResultsThe linkage map established the chromosome numbering correspondence between the two reference genome versions and the relationship between recombination rate, physical distance, and gene density in the coconut genomes. Leveraging the strong segregation for precocity inherited from the Dwarf cultivar in the F2, a major effect QTL with incomplete dominance was mapped for flowering time. FLOWERING LOCUS T (FT) gene homologs of coconut previously described as putatively involved in flowering time by alternative splice variant analysis were colocalized within a ~200-kb window of the major effect QTL [logarithm of the odds (LOD) = 11.86].DiscussionOur work provides strong phenotype-based evidence for the role of the FT locus as the putative underlying functional variant for the flowering time difference between Dwarf and Tall coconuts. Major effect QTLs were also detected for developmental traits of the palm, plausibly suggesting pleiotropism of the FT locus for other precocity traits. Haplotypes of the two SNPs flanking the flowering time QTL inherited from the Dwarf parent BGDJ caused a reduction in the time to flower of approximately 400 days. These SNPs could be used for high-throughput marker-assisted selection of early-flowering and higher-productivity recombinant lines, providing innovative genetic material to the coconut industry.
Genome-wide profiling of WRKY genes involved in flavonoid biosynthesis in Erigeron breviscapus
Authors: Song Wanling , Zhang Shuangyan , Li Qi , Xiang Guisheng , Zhao Yan , Wei Fan , Zhang Guanghui , Yang Shengchao , Hao Bing 
Published: June 2024

The transcription factors of WRKY genes play essential roles in plant growth, stress responses, and metabolite biosynthesis. Erigeron breviscapus, a traditional Chinese herb, is abundant in flavonoids and has been used for centuries to treat cardiovascular and cerebrovascular diseases. However, the WRKY transcription factors that regulate flavonoid biosynthesis in E. breviscapus remain unknown. In this study, a total of 75 EbWRKY transcription factors were predicted through comprehensive genome-wide characterization of E. breviscapus and the chromosomal localization of each EbWRKY gene was investigated. RNA sequencing revealed transient responses of 74 predicted EbWRKY genes to exogenous abscisic acid (ABA), salicylic acid (SA), and gibberellin 3 (GA3) after 4 h of treatment. In contrast, the expression of key structural genes involved in flavonoid biosynthesis increased after 4 h in GA3 treatment. However, the content of flavonoid metabolites in leaves significantly increased at 12 h. The qRT-PCR results showed that the expression patterns of EbWRKY11, EbWRKY30, EbWRKY31, EbWRKY36, and EbWRKY44 transcription factors exhibited a high degree of similarity to the 11 structural genes involved in flavonoid biosynthesis. Protein-DNA interactions were performed between the key genes involved in scutellarin biosynthesis and candidate WRKYs. The result showed that F7GAT interacts with EbWRKY11, EbWRKY36, and EbWRKY44, while EbF6H has a self-activation function. This study provides comprehensive information on the regulatory control network of flavonoid accumulation mechanisms, offering valuable insights for breeding E. breviscapus varieties with enhanced scutellarin content.
Impaired episodic verbal memory recall after 1 week and elevated forgetting in children after mild traumatic brain injury – results from a short-term longitudinal study
Authors: Lidzba Karen , Afridi Zainab , Romano Fabrizio , Wingeier Kevin , Bigi Sandra , Studer Martina 
Published: June 2024

ObjectiveThere is preliminary evidence that children after traumatic brain injury (TBI) have accelerated long-term forgetting (ALF), i.e., an adequate learning and memory performance in standardized memory tests, but an excessive rate of forgetting over delays of days or weeks. The main aim of this study was to investigate episodic memory performance, including delayed retrieval 1 week after learning, in children after mild TBI (mTBI).MethodsThis prospective study with two time-points (T1: 1 week after injury and T2: 3–6 months after injury), included data of 64 children after mTBI and 57 healthy control children aged between 8 and 16 years. We assessed episodic learning and memory using an auditory word learning test and compared executive functions (interference control, working memory, semantic fluency and flexibility) and divided attention between groups. We explored correlations between memory performance and executive functions. Furthermore, we examined predictive factors for delayed memory retrieval 1 week after learning as well as for forgetting over time.ResultsCompared to healthy controls, patients showed an impaired delayed recall and recognition performance 3–6 months after injury. Executive functions, but not divided attention, were reduced in children after mTBI. Furthermore, parents rated episodic memory as impaired 3–6 months after injury. Additionally, verbal learning and group, but not executive functions, were predictive for delayed recall performance at both time-points, whereas forgetting was predicted by group.DiscussionDelayed recall and forgetting over time were significantly different between groups, both post-acutely and in the chronic phase after pediatric mTBI, even in a very mildly injured patient sample. Delayed memory performance should be included in clinical evaluations of episodic memory and further research is needed to understand the mechanisms of ALF.
Perceptions of parental involvement in youth handball players, the effects of sport participation stage and sports injury
Authors: Kovács Krisztina , Takács Johanna , Juhász István , Kovács Katalin 
Published: June 2024

IntroductionGlobally, from the age of 14, the dropout rate of young athletes is high in all sports games in Hungary. The reasons for dropping out are complex, however parental support is critical to succeed or continue, especially after failure or injury. The present study explored the main effects of sports injury and sport participation stage on parental involvement in sports.Methods1,174 parents and 690 athletes completed our questionnaire, which contains questions on young players’ sport participation, injury background and Parental Involvement in Sport Questionnaire.ResultsParents’ self-perceived level of involvement differed from the parental involvement perceived by their children. The significant predictors were the person who completed, the parent/athlete, the athlete’s previous sports injury and the child’s current stage of sport participation. In Directive Behavior, the main effect of stages is only seen in parents whose child has been injured. In the sample of injured athletes, the rate of perceived parental Praise and Understanding tends to be lower in the specializing stage.DiscussionOur findings suggest that these two behaviors could be part of the same parenting style, which requires further investigation. The results expand the existing knowledge of the complexity of parents’ involvement in children’s sports careers. These findings have implications beyond parental psychoeducation impacting the work of coaches, sports physicians and rehabilitation experts.
Latent class analysis and longitudinal development trajectory study of psychological distress in patients with stroke: a study protocol
Authors: Guo Yunmei , Zhou Ming , Yan Xin , Liu Ying , Wang Lianhong 
Published: June 2024

BackgroundPsychological distress affects the treatment and rehabilitation of patients with stroke, affects their long-term functional exercise and quality of life, and increases the risk of stroke recurrence and even death. This is a multi-dimensional and multi-level mental health problem and a dynamic process variable that shows a dynamic development trend with time. However, previous studies have been insufficient to deeply study the change mechanism of psychological distress, and there remains a lack of forward-looking longitudinal studies to analyze its change trajectory. This study aimed to investigate potential categories and how psychological distress changes over time and to examine conversion probability in these transformation processes.MethodsThis prospective longitudinal mixed-method study investigated the potential categories and change trajectories of distress in patients with stroke. A total of 492 participants from three hospitals were recruited for quantitative analysis. Latent class analysis and latent transition analysis (LCA/LTA) were used to identify meaningful subgroups, transitions between those classes across time, and baseline demographic features that help predict and design tailored interventions.DiscussionA comprehensive understanding of the potential category and transformation processes of psychological distress over time, including the impact of the sense of demographic data on the role of shame and loneliness, can lead to the development of psychological distress treatment tailored to the unique needs of patients with stroke. Thus, this study can promote more effective and successful treatment outcomes, reduce the stigma surrounding disease issues among patients, and encourage them to use psychological consultation.
Prevalence of smartphone addiction and its relation with psychological distress and internet gaming disorder among medical college students
Authors: Zhang Ming , Chi Chenru , Liu Qingwei , Zhang Yuhao , Tao Xiubin , Liu Huan , Xuan Bin 
Published: June 2024

BackgroundThe incidence of smartphone addiction has been widely studied, but the research on the relationship between smartphone addiction and psychological distress and internet gaming disorder is limited. This study investigated the characteristics and prevalence of smartphone addiction and its relation with psychological distress and internet gaming disorder. Furthermore, it provides the scientific basis for intervention measures in schools, families, and society.MethodsA random cluster sampling method was applied to investigate 656 medical students from grades 1 to 4 at Wannan Medical College in Anhui province, People’s Republic of China. The questionnaire consisted of general information, a smartphone addiction scale, an Internet gaming disorder scale, and a Kessler 6-item psychological distress test. The obtained results were first summarized using descriptive statistics. The Chi-square test was used to compare the status of smartphone addiction. Binary logistic regression was used to analyze the relationship between smartphone addiction and various variables.ResultsOur results showed that the prevalence of smartphone addiction in medical students was 49.5% (325/656). Psychological distress (p &lt; 0.001), internet gaming disorder (p &lt; 0.001), and childhood trauma (p = 0.001) were highly correlated with smartphone addiction in medical students. Psychological distress, and internet gaming disorder were positively associated with smartphone addiction (p &lt; 0.000).ConclusionThe prevalence of smartphone addiction is high among medical students in Chinese. Smartphone addiction is highly related to related to internet gaming disorder and psychological distress.