bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the efficacy and safety of perioperative immunochemotherapeutic strategies for locally advanced esophageal cancer: a systematic review and network meta-analysis
Authors: Zhang Jiao , Zhao Peixi , Xu Rui , Han Le , Chen Wenjuan , Zhang Yili 
Published: December 2024

BackgroundThe aim of this network meta-analysis was to clarify the efficacy and safety of different immune checkpoint inhibitors (ICIs) in combination with chemotherapy in the neoadjuvant phase for the treatment of locally advanced esophageal cancer.MethodsWe searched PubMed, EMBASE, Web of Science, Cochrane Library, CNKI and WanFang databases from January 2000 until May 2024. The primary endpoints were pathological complete response (pCR), major pathological response (MPR), R0 resection rate, objective response rate (ORR), disease control rate (DCR), treatment-related adverse events(TRAEs) of any grade and TRAEs of grade 3 or higher. The Newcastle-Ottawa Scale (NOS) and the Cochrane Risk of Bias tool were used to evaluate risk of bias. To analyze the data, Review Manager 5.3 and Stata16.0 were applied.ResultsFourteen eligible studies (six randomized controlled trials) and 8 retrospective cohort studies) enrolling 1139 patients were included for this network meta-analysis. All studies originated from China. For patients with locally advanced esophageal cancer, neoadjuvant immunochemotherapeutic strategies showed significant advantages over traditional neoadjuvant therapy in terms of pCR, MPR, ORR and DCR. Among the analyzed regimens, camrelizumab plus chemotherapy demonstrated the most pronounced improvements in pCR and MPR, while pembrolizumab plus chemotherapy achieved the best outcomes in terms of ORR and DCR. There were no significant differences observed among the various neoadjuvant treatment strategies regarding R0 resection rate, any grade TRAEs, or grade≥3 TRAEs. The most common TRAEs in the neoadjuvant chemotherapy plus immunotherapy group were myelosuppression and gastrointestinal damage, with most grade 3 or higher TRAEs being hematologic adverse events. The most frequent immune-related adverse events(irAEs) included rash (4.2-21.7%), thyroid dysfunction (hypothyroidism or hyperthyroidism, 6.3-17.4%), and pneumonia (4.2-6.3%), with the majority being mild to moderate (grade 1 or 2).ConclusionsNeoadjuvant immunotherapy combined with chemotherapy regimens demonstrate relatively high efficacy and tolerable safety profiles. Among the evaluated regimens, the combination chemotherapy with camrelizumab had relatively high pCR and MPR, whereas the combination chemotherapy with pembrolizumab had relatively high ORR and DCR. There were no significant differences in safety among the various regimens. Our study suggests that evaluating the efficacy and safety of different ICIs may be helpful in clinical decision-making.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024583548.
Efficacy and safety of adding immune checkpoint inhibitors to first-line standard therapy for recurrent or advanced cervical cancer: a meta-analysis of phase 3 clinical trials
Authors: Zhang Xinmiao , Shen Jinhai , Huang Mengfan , Li Rongxia 
Published: December 2024

BackgroundImmune checkpoint inhibitors (ICIs) combined with standard therapy (ST) have emerged as a novel treatment strategy for recurrent or advanced cervical cancer (r/a CC). However, the available data from phase 3 clinical trials have yielded mixed results. This study aims to evaluate the therapeutic efficacy and safety of adding ICIs to ST in the treatment of r/a CC.MethodsData from four phase 3 clinical trials (KEYNOTE-826, CALLA, BEATcc, and ENGOT-cx11/GOG-3047/KEYNOTE-A18), involving 2,857 patients, were analyzed. Meta-analyses were conducted to combine hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), odds ratios (ORs) for the objective response rate (ORR), and relative risks (RRs) for adverse events (AEs).ResultsThe addition of ICIs to ST significantly improved PFS (HR, 0.67; 95% CI, 0.60-0.75), OS (HR, 0.66; 95% CI, 0.58-0.75), and ORR (OR, 1.48; 95% CI, 1.13-1.94) compared to ST alone. However, there was a modest increase in grade 3-5 AEs (RR, 1.08; 95% CI, 1.03-1.13) with the combined therapy.ConclusionThis meta-analysis indicates that the combination of ICIs with ST in the treatment of r/a CC not only demonstrates superior efficacy over ST alone but also maintains a comparable toxicity profile, offering strong evidence for an effective and relatively safe treatment approach for managing this disease.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024593895.
Unravelling turbot (Scophthalmus maximus) resistance to Aeromonas salmonicida: transcriptomic insights from two full-sibling families with divergent susceptibility
Authors: Pereiro Patricia , Tur Ricardo , García Miguel , Figueras Antonio , Novoa Beatriz 
Published: December 2024

IntroductionFurunculosis, caused by the gram-negative bacterium Aeromonas salmonicida subsp. salmonicida, remains a significant threat to turbot (Scophthalmus maximus) aquaculture. Identifying genetic backgrounds with enhanced disease resistance is critical for improving aquaculture health management, reducing antibiotic dependency, and mitigating economic losses. MethodsIn this study, five full-sibling turbot families were challenged with A. salmonicida, which revealed one family with significantly greater resistance. Transcriptomic analyses (RNA-Seq) were performed on resistant and susceptible families, examining both naïve and 24-h postinfection (hpi) samples from head kidney and liver tissues. ResultsIn the absence of infection, differentially expressed genes (DEGs) were identified predominantly in the liver. Following infection, a marked increase in DEGs was observed in the head kidney, with many genes linked to immune functions. Interestingly, the resistant family displayed a more controlled inflammatory response and upregulation of genes related to antigen presentation and T-cell activity in the head kidney at early infection stages, which may have contributed to its increased survival rate. In the liver, transcriptomic differences between the families were associated mainly with cytoskeletal organization, cell cycle regulation, and metabolic processes, including insulin signalling and lipid metabolism, regardless of infection status. Additionally, many DEGs overlapped with previously identified quantitative trait loci (QTLs) associated with resistance to A. salmonicida, providing further insights into the genetic basis of disease resistance. DiscussionThis study represents the first RNA-Seq analysis comparing resistant and susceptible turbot families and contributes valuable knowledge for the development of selective breeding programs targeting disease resistance in turbot and other aquaculture species susceptible to A. salmonicida.
Second-order sliding mode optimization control of an inverted pendulum system based on fuzzy adaptive technology
Authors: Leng Xuefeng 
Published: December 2024

IntroductionThis paper aims at the control problem of nonlinear systems with uncertainty in general, and avoids the deviation of sliding mode controller from the preset constraint region during the convergence process.MethodsA sliding mode control method based on fuzzy adaptive technique was proposed by constructing obstacle Lyapunov function (BLF). Design problem of fuzzy adaptive second-order sliding mode controller considering output constraints. The Lyapunov function of the cutting barrier is designed, and the fuzzy adaptive second-order sliding mode controller is constructed by combining the Lyapunov function with the regression method. A second-order finite output sliding mode controller is designed for the inverted pendulum system. In the case of unknown external disturbance, the mathematical modeling and force analysis of the first order inverted pendulum system are carried out, and the design problem of the fuzzy adaptive second-order sliding mode controller with output restriction is studied.Results and DiscussionThe proposed fuzzy adaptive second-order sliding mode controller has a good control effect in the inverted pendulum system. The fuzzy adaptive second-order controller stabilizes the sliding mode at 0.1 in 1.25 s, while the fuzzy adaptive second-order controller makes the system state reach equilibrium in 15 s. The accuracy of fuzzy adaptive second-order sliding mode controller reaches 99.2%, which is superior to other methods in terms of balance accuracy and recall rate. The controller not only has a fast response speed, but also can effectively suppress system flutter and ensure the rapid stability of the system after constraints. This research method lays a foundation for the design of fuzzy adaptive sliding mode control algorithm.
Challenging perceptions about rural practice using narratives: a living library approach in medical education
Authors: Perez Grace , Malhi Rebecca , Bressler Kamiko , Monaghan Melissa , Johnston Aaron 
Published: December 2024

IntroductionThe shortage of physicians in rural Canada is a continuing challenge. Canadian medical schools have adapted strategies to increase the supply of rural physicians. This study appraises the effectiveness of the living library (also called Human Library©) in medical education, as an avenue for medical and pre-medical students to engage in dialogue with rural health professionals. Similar to a conventional library, readers check out books, except that “books” are human volunteers willing to share relevant personal experiences, and “readers” are the learners. The reading is the personal interaction between human books and students through narratives of experiences. The program “The Library of Life—Stories of Rural Medicine” (TLoL), was developed to provide students with better understanding of rural life and practice through narratives.MethodsThis is a mixed methods study, using pre- and post-event surveys. Statistical comparisons were done using Wilcoxon and McNemar’s tests. Thematic analysis was used to explore students’ expectations of TLoL and to describe their experience and key takeaways.ResultsMost of the participants were from an urban background, had low familiarity with rural medicine and only 44% would consider a rural career prior to TLoL. After TLoL, improvements were observed in: (i) envisioning rural medicine as career option (p = 0.009), (ii) appreciation of rural living (p = 0.013), (iii) need for rural physicians (p &lt; 0.001). and (iv) rural practice consideration (p = 0.001). Themes from students’ motivations for participation were: (i) students’ curiosity, interest, and (ii) their willingness to engage in dialogue with the human books. Themes from the key takeaways were that TLoL allowed students: (i) to walk in a rural professional’s shoes, enabling them to see “rural” in a new light, and (ii) to self-reflect and gain a sense of personal growth.ConclusionStudents made gains in attitudes and perceptions toward rural practice. Narratives have the power to challenge held beliefs around rural practice and life, and can encourage students to consider things that traditional medical teaching may not. TLoL can be an effective learning modality in medical education to provide information about rural medicine, in combination with learning opportunities such as rural block rotations and longitudinal clinical clerkship immersions.
Effects of computer-generated patterns with different temporal and spatial frequencies on choroidal thickness, retinal dopamine and candidate genes in chickens wearing lenses
Authors: Liu Hong , Schaeffel Frank , Feldkaemper Marita Pauline 
Published: December 2024

PurposeChanges in choroidal thickness (ChT) are proposed to predict myopia development but evidence is mixed. We investigated time courses of choroidal responses, following different types of dynamic artificial stimulation in chicks with and without spectacle lenses, as well as changes in retinal dopamine metabolism and expression of candidate genes.MethodsChicks were kept in an arena surrounded by computer monitors presenting dynamic checkerboard fields of small, medium and large size. Fields were displayed with different cycle frequencies, as ON (rapid rise, slow decay) or OFF (slow rise, rapid decay) temporal luminance profile. Refractive errors, ocular biometry and ChT were assessed. Dopamine metabolism and candidate gene expression levels were also measured. Stimuli were applied for (1) 3 h with no lens, (2) 3 h and monocular treatment with −7D or +7D lenses, (3) 3 or 7 days.Results(1) The smallest fields caused the largest decrease in ChT. (2) Negative lens treatment induced on average 11.7 μm thinner choroids. ChT thinning was enhanced by 10 Hz-ON medium field size flicker which also reduced choroidal thickening with positive lenses. (3) With prolonged treatment, the choroid recovered from initial thinning in all groups although to varying degrees which were dependent on stimulus parameters. Relative ChT changes were positively correlated with the vitreal level of dopamine metabolites. Retinal EGR-1 mRNA level was positively correlated with choroidal thickness. Retinal melanopsin mRNA was increased by 10 Hz-ON stimulation and choroidal BMPR1A mRNA increased with 10 Hz-OFF stimulation. On average, early choroidal thinning did not predict the amount of negative lens-induced eye growth changes after 7 days, whereas later ChT changes showed a weak association.ConclusionNegative lenses caused long-lasting choroidal thinning, with some recovery during lens wear, especially after stimulation with 10 Hz. The dynamic stimuli modulated choroidal thinning but effects were small. There was little difference between ON and OFF stimulation, perhaps because the checkerboard patterns were too coarse. 10 Hz cycle frequency increased dopamine release. Less dopamine was correlated with thinner choroids. Result do not exclude a predictive value of choroidal thickening for future refractive development since we almost exclusively tested choroidal thinning effects.
Insight into the microbial diversity and community in the sacrificial pits of Sanxingdui site (Sichuan, China)
Authors: Chen Ruru , Xie Zhenbin , Xiao Qing , Wang Chong , Wen Rui 
Published: December 2024

IntroductionThe Sanxingdui site (Sichuan, China) is the typical representative of the ancient Shu culture, which lasts from the late Neolithic to early Western Zhou. The sacrificial pits are located in the core region of Sanxingdui site, and numerous artifacts are unearthed including ivory, seashells, bronzes, pottery, jade, stone, gold, bone, and horn products. The function of the pits and buried artifacts has always been the focus, but the microbiome around artifacts attracts less attention. Recently, the microbiome in buried ivory soil has just been identified; however, the microbiome around other artifacts has never been studied. In term of the unique perspective for interpretation the archaeological issues, the study was carried out for: (1) the microbial diversity and community of soil in the lower layer of artifacts in sacrificial pits, (2) the potential biodeterioration behavior of organic and inorganic relics, and (3) the impact of sacrificial and burial activities in different sacrificial pits on microbiome.MethodsThere were 45 soil samples around different artifacts in three sacrificial pits and 12 raw soil samples inside or outside the sacrificial pit sampling from Sanxingdui site. The microbial genomes were then identified and analyzed using the next-generation high-throughput sequencing.ResultsThe represented bacterial phyla were Proteobacteria, Actinobacteriota, GAL15, Chloroflexi, Acidobacteriota, Methylomirabilota, Thermoplasmatota, Crenarchaeota, Gemmatimonadota, and Firmicutes, and the represented fungal phyla were Ascomycota, Mortierellomycota, and Basidiomycota. Further microbial functional analysis found that the bacterial genera Sphingopyxis, Limnobacter, and Streptomyces and the fungal genera Cladosporium, Acremonium, and Mortierella were concerned with the degradation of organic matter, while the genera Pseudomonas, Arthrobacter, Variovorax, Aspergillus, and Penicillium might be related to the biocorrosion of bronzes. In addition, the microbial composition and principal co-ordinate analysis (PCoA) demonstrated the significant differences in microbial composition and structure between the raw soil samples and the soil samples around the artifacts and also between the soil samples in different sacrificial pits.DiscussionIt is important to understand the biodeterioration of the buried artifacts and the sacrificial activities in Sanxingdui site according to the results of microbial diversity and community. The combination of microbiology and archaeology will shed light on the archaeological issues related to the ancient human activities and behaviors.
Investigation of functional connectivity differences based on anxiety tendencies
Authors: Oishi Misuzu , Sakurai Noriko , Kawasaki Yuki , Sasaki Kei , Kasai Satoshi , Kodama Naoki 
Published: December 2024

IntroductionAnxiety is an emotion necessary for human survival. However, persistent and excessive anxiety can be clinically challenging. Increased anxiety affects daily life and requires early detection and intervention. Therefore, a better understanding of the neural basis of mild anxiety is needed. However, previous studies have focused primarily on resting-state functional magnetic resonance imaging (rs-fMRI) in patients with psychiatric disorders presenting with anxiety. Notably, only a few studies have been conducted on healthy participants, and the relationship between anxiety and functional brain connectivity in the healthy range remains unclear. Therefore, in this study, we aimed to clarify the differences in functional brain connectivity at different degrees of anxiety among healthy participants.MethodsThis study included 48 healthy participants with no history of psychiatric disorders. Participants were administered The General Health Questionnaire (GHQ) 60, a psychological test for assessing anxiety, and the Manifest Anxiety Scale (MAS). The participants then underwent rs-fMRI. Based on the results of each psychological test, the participants were classified into normal and anxiety groups, and the functional connectivity between the two groups was compared using a seed-to-voxel analysis.ResultsComparison of functional brain connectivity between the normal and anxiety groups classified based on the GHQ60 and MAS revealed differences between brain regions comprising the salience network (SN) in both psychological tests. For the GHQ60, the anxiety group showed reduced connectivity between the right supramarginal gyrus and insular cortex compared with the normal group. However, for the MAS, the anxiety group showed reduced connectivity between the right supramarginal and anterior cingulate cortical gyri compared with the normal group.ConclusionFunctional connectivity within the SN was reduced in the group with higher anxiety when functional brain connectivity at different anxiety levels was examined in healthy participants. This suggests that anxiety is involved in changes in the functional brain connectivity associated with emotional processing and cognitive control.
Association between hypothyroidism and obstructive sleep apnea: a bidirectional Mendelian randomization study combined with the geo database
Authors: Zhao Mingyu , Huang Xu , Zheng Hu , Cai Yuhang , Han Wenjia , Wang Yuanyin , Chen Ran 
Published: December 2024

BackgroundThe causal relationship between hypothyroidism and obstructive sleep apnea (OSA) remains controversial. Therefore, our research used a bidirectional Mendelian randomization (MR) method in an attempt to determine the causal relationship between hypothyroidism and OSA.MethodsFrom the publicly accessible genome-wide association analysis (GWAS) summary database, we obtained single nucleotide polymorphism (SNPs) data pertaining to hypothyroidism and OSA. Inverse variance weighting (IVW) was the principal method of analysis utilized, with validation also conducted via weighted median, MR-Egger, simple model, and weighted model approaches. To further evaluate the robustness of the results, heterogeneity testing, pleiotropy testing, and the “leave-one-out” sensitivity analysis were performed. Differentially expressed genes (DEGs) from the OSA dataset (GSE135917) and hypothyroidism dataset (GSE176153) derived from the Gene Expression Omnibus (GEO) database were screened using the “limma” package. The “clusterProfiler” and “GO plot” packages were used for further enrichment analysis in order to validate the findings of the MR study. The Cytoscape software was utilized to build a protein–protein interaction (PPI) network of DEGs and to screen for hub genes.ResultsThe MR analysis showed that genetically predicted hypothyroidism was associated with an increased risk of OSA [IVW odds ratio (OR) = 1.734; 95% confidence interval (CI) = 1.073–2.801; p = 0.025]. The trend of the outcomes of the other approaches is consistent with the trend of the IVW outcome. However, the reverse MR analysis suggested no evidence for the causal effect of OSA on hypothyroidism (IVW OR = 1.002, 95% CI: 0.996–1.009, p = 0.454). The robustness of the results was confirmed by the sensitivity analysis. Bioinformatics analysis revealed that there were DEGs that hypothyroidism and OSA have in common.ConclusionOur findings suggested that hypothyroidism may increase the risk of OSA, while the effect of OSA on hypothyroidism was not found in this MR study. Thus, patients with hypothyroidism should be enhanced with screening for OSA for early diagnosis and appropriate treatment.
Dual-stent thrombectomy for recanalization of cerebral embolism caused by infective endocarditis: a case report
Authors: Zhang Haiqi , Chen Jianfei , Chang Wansheng , Lin Feng , Yin Jijun 
Published: December 2024

MethodsIn this case report, we present an in-depth narrative of a patient who was subjected to mechanical thrombectomy (MT) for an obstruction in the main trunk and bifurcation of the left middle cerebral artery subsequent to Infective Endocarditis (IE). Initial intervention using a solitary-stent technique proved to be ineffective; thus, we shifted to a dual-stent strategy, which successfully recanalized the compromised blood vessel.ResultsThe dual-stent retriever method can be especially advantageous for treating persistent clots that occur at arterial bifurcations resisting the efforts of a single-stent retriever during the MT process.ConclusionDual-stent thrombectomy increases the likelihood of clot extraction due to its ability to encompass a larger area of the thrombus within the stent’s framework, potentially improving the clinical outcomes.