bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surrogate endpoints for overall survival in randomized clinical trials testing immune checkpoint inhibitors: a systematic review and meta-analysis
Authors: Sala Isabella , Pagan Eleonora , Pala Laura , Oriecuia Chiara , Musca Marco , Specchia Claudia , De Pas Tommaso , Cortes Javier , Giaccone Giuseppe , Postow Michael , Gelber Richard D. , Bagnardi Vincenzo , Conforti Fabio 
Published: January 2024

IntroductionThere is debate on which are the best surrogate endpoint and metric to capture treatment effect on overall survival (OS) in RCTs testing immune-checkpoint inhibitors (ICIs).MethodsWe systematically searched for RCTs testing ICIs in patients with advanced solid tumors. Inclusion criteria were: RCTs i) assessing PD-(L)1 and CTLA-4 inhibitors either as monotherapy or in combination with another ICI, and/or targeted therapy, and/or chemotherapy, in patients with advanced solid tumors; ii) randomizing at least 100 patients. We performed a meta-analysis of RCTs to compare the surrogacy value of PFS and modified-PFS (mPFS) for OS in RCTs testing ICIs, when the treatment effect is measured by the hazard ratio (HR) for OS, and by the HR and the ratio of restricted mean survival time (rRMST) for PFS and mPFS.Results61 RCTs (67 treatment comparisons and 36,034 patients) were included in the analysis. In comparisons testing ICI plus chemotherapy, HRPFS and HRmPFS both had a strong surrogacy value (R2 = 0.74 and R2 = 0.81, respectively). In comparisons testing ICI as monotherapy, HRPFS was the best surrogate, although having a moderate correlation (R2 = 0.58). In comparisons testing ICI plus other treatment(s), the associations were very weak for all the surrogate endpoints and treatment effect measures, with R2 ranging from 0.01 to 0.22.ConclusionIn RCTs testing ICIs, the value of potential surrogates for HROS was strongly affected by the type of treatment(s) tested. The evidence available supports HRPFS as the best surrogate, and disproves the use of alternative endpoints, such as the mPFS, or treatment effect measures, such as the RMST.
A comparison of machine learning methods for quantifying self-grooming behavior in mice
Authors: Correia Kassi , Walker Raegan , Pittenger Christopher , Fields Christopher 
Published: January 2024

BackgroundAs machine learning technology continues to advance and the need for standardized behavioral quantification grows, commercial and open-source automated behavioral analysis tools are gaining prominence in behavioral neuroscience. We present a comparative analysis of three behavioral analysis pipelines—DeepLabCut (DLC) and Simple Behavioral Analysis (SimBA), HomeCageScan (HCS), and manual scoring—in measuring repetitive self-grooming among mice.MethodsGrooming behavior of mice was recorded at baseline and after water spray or restraint treatments. Videos were processed and analyzed in parallel using 3 methods (DLC/SimBA, HCS, and manual scoring), quantifying both total number of grooming bouts and total grooming duration.ResultsBoth treatment conditions (water spray and restraint) resulted in significant elevation in both total grooming duration and number of grooming bouts. HCS measures of grooming duration were significantly elevated relative to those derived from manual scoring: specifically, HCS tended to overestimate duration at low levels of grooming. DLC/SimBA duration measurements were not significantly different than those derived from manual scoring. However, both SimBA and HCS measures of the number of grooming bouts were significantly different than those derived from manual scoring; the magnitude and direction of the difference depended on treatment condition.ConclusionDLC/SimBA provides a high-throughput pipeline for quantifying grooming duration that correlates well with manual scoring. However, grooming bout data derived from both DLC/SimBA and HCS did not reliably estimate measures obtained via manual scoring.
A systematic review and coordinate-based meta-analysis of fMRI studies on acupuncture at LR 3
Authors: Rao Yawen , Ge Limin , Wu Jiaxin 
Published: January 2024

ObjectivesThe acupoint LR3 (Taichong) is frequently utilized in clinical acupuncture. However, its underlying neural mechanisms remain not fully elucidated, with speculations suggesting its close association with specific brain activity patterns.MethodsA comprehensive literature search was undertaken across several online databases, such as PubMed, Web of Science, Embase, Cochrane Library, CNKI (China National Knowledge Infrastructure), Wanfang Database, VIP Database, and the Chinese Biomedical Database. Two independent researchers handled the study selection, quality assessment, and data extraction processes. Using the seed-based d-mapping meta-analysis approach, we evaluated the brain regions activated by LR3 acupuncture in healthy subjects. Subsequent subgroup analysis was stratified by fMRI types, and regression analyses were performed considering the duration of acupuncture, depth of needle insertion, and needle diameter. The identified active brain regions were then intricately projected onto large-scale functional networks.ResultsA total of 10 studies met the criteria for inclusion, encompassing 319 healthy right-handed participants. The meta-analysis indicates that acupuncture at the LR3 activates regions such as the right postcentral gyrus, left thalamus, left middle frontal gyrus, and right superior frontal gyrus. Additionally, meta-regression analysis highlights that increased acupuncture duration correlates with progressively intensified activation of the right superior frontal gyrus. Subgroup analysis posits that variations in the type of fMRI employed might account for heterogeneity in the pooled results. Concurrently, functional network analysis identifies the primary activated regions as aligning with the Basal ganglia network, Auditory network, Left executive control network, Posterior salience network, Right executive control network, and Sensorimotor networks.ConclusionAcupuncture at the LR3 in healthy subjects selectively activates brain regions linked to pain perception, emotional processing, and linguistic functions. Extending the needle retention duration intensifies the activation of the right superior frontal gyrus. These findings enrich our comprehension of the neurobiological underpinnings of acupuncture’s role in pain mitigation and emotional regulation.
An integrated in vitro approach on the enzymatic and antioxidant mechanisms of four commercially available essential oils (Copaifera officinalis, Gaultheria fragrantissima, Helichrysum italicum, and Syzygium aromaticum) traditionally used topically for their anti-inflammatory effects
Authors: Cebollada Pilar , Gomes Nelson G. M. , Andrade Paula B. , López Víctor 
Published: January 2024

Introduction: Despite the increasing number of essential oils being reported on their potential therapeutic effects, some remain relatively unknown on their biological properties. That is the case of the essential oils obtained from copaiba (Copaifera officinalis L.), wintergreen (Gaultheria fragrantissima Wall.), everlasting (Helichrysum italicum (Roth) G.Don) and clove (Syzygium aromaticum (L.) Merr. &amp; L.M.Perry), commonly labelled as being useful on the amelioration of conditions with an inflammatory background.Methods: To further broaden the current knowledge on the four essential oils, commercially available samples were approached on their effects upon a series of mediators that are involved on the inflammatory and oxidative response, both through in vitro cell-free and cell-based assays (5-lipoxygenase activity, lipid peroxidation, free radical and nitric oxide radical scavenging properties or tyrosinase inhibition).Results: The four oils proved to be active at some of the concentrations tested in most of the performed assays. Significant differences were found between the essential oils, S. aromaticum proving to tbe the most active, followed by G. fragrantissima against 5-lipoxygenase (5-LOX) and linoleic acid peroxidation, proving their potential use as antioxidants and anti-inflammatory agents. In fact, the IC50 value of S. aromaticum in the 5-LOX assay was 62.30 μg mL−1. Besides S. aromaticum efficiently scavenged superoxide radicals generated by xanthine/xanthine oxidase, displaying an IC50 value of 135.26 μg mL−1. The essential oil obtained from H. italicum exhibited a significant decrease in the nitric oxide levels on BV-2 cells, showing its potential as a cytoprotective agent against toxic damage. Copaiba oil ranked first as the most potent tyrosinase inhibitor, exhibiting an IC50 98.22 μg mL−1.Conclusion: More studies are needed to describe the essential oils properties, but these results confirm the potential of these essential oils as anti-inflammatory and antioxidant agents.
Traditional Chinese medicine Zhusha Anshen Wan: protective effects on liver, kidney, and intestine of the individual drugs using 1H NMR metabolomics
Authors: Wang Dalu , Yu Chong , Liu Beixing , Wang Haifeng 
Published: January 2024

Introduction: Zhusha Anshen Wan (ZSASW) is a traditional Chinese medicine compound mainly composed of mineral drugs. In clinical practice, ZSASW did not show the toxicity of administering equal doses of cinnabar alone, suggesting that the four combination herbs in ZSASW can alleviate the damage of cinnabar. The effect of each herb on reducing the toxicity of cinnabar has not been fully explained.Methods: In our study, we utilized a metabonomics approach based on high-resolution 1H nuclear magnetic resonance spectroscopy to investigate the reduction of toxicity by each herb in ZSASW. Liver, kidney and intestinal histopathology examinations and biochemical analysis of the serum were also performed.Results: Partial least squares-discriminant analysis (PLS-DA) was conducted to distinct different metabolic profiles in the urine and serum from the rats. Liver and kidney histopathology examinations, as well as analysis of serum clinical chemistry analysis, were also carried out. The metabolic profiles of the urine and serum of the rats in the CGU (treated with cinnabar and Glycyrrhiza uralensis Fisch) and CCC (treated with cinnabar and Coptis chinensis French) groups were remarkably similar to those of the control group, while those of the CRG (treated with cinnabar and Rehmannia glutinosa Libosch) and CAS (treated with cinnabar and Angelica sinensis) groups were close to those of the cinnabar group. The metabolic profiles of the urine and serum of the rats in the CGU and CCC groups were remarkably similar to those of the control group, while those of the CRG and CAS groups were close to those of the cinnabar group. Changes in endogenous metabolites associated with toxicity were identified. Rehmannia glutinosa, Rhizoma Coptidis and Glycyrrhiza uralensis Fisch could maintain the dynamic balance of the intestinal flora. These results were also verified by liver, kidney and intestinal histopathology examinations and biochemical analysis of the serum. The results suggested thatDiscussion: The metabolic mechanism of single drug detoxification in compound prescriptions has been elucidated. Coptis chinensis and Glycyrrhiza uralensis serve as the primary detoxification agents within ZSASW for mitigating liver, kidney, and intestinal damage caused by cinnabar. Detoxification can be observed through changes in the levels of various endogenous metabolites and related metabolic pathways.
Enhancing dendrobine production in Dendrobium nobile through mono-culturing of endophytic fungi, Trichoderma longibrachiatum (MD33) in a temporary immersion bioreactor system
Authors: Sarsaiya Surendra , Jain Archana , Shu Fuxing , Yang Mingfa , Pu Mengxuan , Jia Qi , Gong Qihai , Wu Qin , Qian Xu , Shi Jingshan , Chen Jishuang 
Published: January 2024

IntroductionDendrobine, a valuable alkaloid found in Dendrobium nobile, possesses significant pharmaceutical potential.MethodsIn this study, we explored innovative approaches to enhance dendrobine production by utilizing endophytic fungi in a Temporary Immersion Bioreactor System (TIBS, Nanjing BioFunction Co. Ltd., China) and traditional test bottles. Dendrobine was unequivocally identified and characterised in D. nobile co-culture seedlings through UHPLC analysis and LC-MS qTOF analysis, supported by reference standards.ResultsThe CGTB (control group) and EGTB (experimental group) 12-month-old D. nobile seedlings exhibited similar peak retention times at 7.6±0.1 minutes, with dendrobine identified as C16H25NO2 (molecular weight 264.195). The EGTB, co-cultured with Trichoderma longibrachiatum (MD33), displayed a 2.6-fold dendrobine increase (1804.23 ng/ml) compared to the CGTB (685.95 ng/ml). Furthermore, a bioanalytical approach was applied to investigate the mono-culture of T. longibrachiatum MD33 with or without D. nobile seedlings in test bottles. The newly developed UHPLC-MS method allowed for dendrobine identification at a retention time of 7.6±0.1 minutes for control and 7.6±0.1 minutes for co-culture. Additionally, we explored TIBS to enhance dendrobine production. Co-culturing D. nobile seedlings with Trichoderma longibrachiatum (MD33) in the TIBS system led to a substantial 9.7-fold dendrobine increase (4415.77 ng/ml) compared to the control (454.01 ng/ml) after just 7 days. The comparative analysis of dendrobine concentration between EGTB and EGTIBS highlighted the remarkable potential of TIBS for optimizing dendrobine production. Future research may focus on scaling up the TIBS approach for commercial dendrobine production and investigating the underlying mechanisms for enhanced dendrobine biosynthesis in D. nobile. The structural elucidation of dendrobine was achieved through 1H and 13C NMR spectroscopy, revealing a complex array of proton environments and distinct carbon environments, providing essential insights for the comprehensive characterization of the compound.DiscussionThese findings hold promise for pharmaceutical and industrial applications of dendrobine and underline the role of endophytic fungi in enhancing secondary metabolite production in medicinal plants.
How harassment is depriving universities of talent: a national survey of STEM academics in the UK
Authors: Litzellachner Lukas F. , Barnett Julie , Yeomans Lucy , Blackwood Leda 
Published: January 2024

IntroductionDespite efforts to increase girls’ interest in subjects related to science, technology, engineering, and mathematics (STEM) careers, there remains a large gender gap in STEM academic faculty.MethodsWe conducted a national survey comprising 732 early career and senior academics from 40 universities in the UK to investigate the role of pull (receiving career advancement opportunities) and push (experiencing harassment) factors in shaping people’s intentions to stay in STEM academia, and the mediating role of perceived workplace climate, academic identification, and beliefs about the ability to succeed (job-related self-efficacy).ResultsOur findings show the differential effect of harassment experiences for women, relative to men. Women experienced more harassment than men, which contributes to their higher intentions to leave academia through enhancing perceptions of a negative workplace climate (i.e., a less collaborative, fair, and inclusive climate) and lower job-related identification (i.e., believing in their ability to succeed as researchers). While receiving opportunities also related to intentions of leaving academia, we did not observe a gender difference in this factor.DiscussionThe result of our analysis underlines the critical importance of preventing and addressing harassment in academic institutions for the retention of female academic talent.
Psychological burden and quality of life in newly diagnosed inflammatory bowel disease patients
Authors: Bernabeu Purificación , Belén-Galipienso Olivia , van-der Hofstadt Carlos , Gutiérrez Ana , Madero-Velázquez Lucía , García del Castillo Gloria , García-Sepulcre Mariana-Fe , Aguas Mariam , Zapater Pedro , Rodríguez-Marín Jesús , Ruiz-Cantero María-Teresa , Cameo José I. , Jover Rodrigo , Sempere Laura 
Published: January 2024

ObjectivePsychological factors, such as stress, anxiety, and depression, are frequently related to inflammatory bowel disease (IBD). However, few studies have examined these factors in patients newly diagnosed with IBD. The aim of the present study was to test the psychological burden in patients with a recent diagnosis of IBD and the factors related to this psychological burden.MethodsWe performed a prospective, multi-center, observational study in patients with a new diagnosis of IBD (≤6 months). The patients were recruited from four different Spanish hospitals. Clinical and demographic characteristics were collected. Patients were evaluated using the Hospital Anxiety and Depression Scale and quality of life questionnaire for patients with inflammatory bowel disease (IBDQ-32). The Scale of Stress Perceived by the Disease was used to assess stressful life events.ResultsWe included 156 patients newly diagnosed with IBD [69 women; 80 Crohn’s disease (CD) and 76 ulcerative colitis (UC)], with a mean age of 42.3 (SD 16.21) years. A total of 37.2% of patients had symptoms of anxiety and 17.3% had symptoms of depression. Quality of life was affected in 30.1% of patients. Factors related to anxiety in early IBD were being a woman and having CD. The only factor related to depression was the presence of comorbidity. Being a woman and having suffered previous stressful life events were factors related to impaired quality of life.ConclusionAnxiety, depression, and impaired quality of life are frequent in patients with a recent diagnosis of IBD. This psychological burden is greater in women.
Managing patient safety and staff safety in nursing homes: exploring how leaders of nursing homes negotiate their dual responsibilities—a case study
Authors: Magerøy Malin Rosell , Macrae Carl , Braut Geir Sverre , Wiig Siri 
Published: January 2024

ObjectiveWithin healthcare, the role of leader is becoming more complex, and healthcare leaders carry an increasing responsibility for the performance of employees, the experience and safety of patients and the quality of care provision. This study aimed to explore how leaders of nursing homes manage the dual responsibility of both Health, Safety and Environment (HSE) and Quality and Patient Safety (QPS), focusing particularly on the approaches leaders take and the dilemmas they face. In addition, we wanted to examine how leaders experience and manage the challenges of HSE and QPS in a holistic way.Design/settingThe study was designed as a case study. Data were collected through semi structured individual interviews with leaders of nursing homes in five Norwegian municipalities.Participants13 leaders of nursing homes in urban and rural municipalities participated in this study.ResultsData analysis resulted in four themes explaining how leaders of nursing homes manage the dual responsibility of HSE and QPS, and the approaches they take and the dilemmas they face:
1.Establishing good systems and building a culture for a work environment that promotes health and patient safety.2.Establish channels for internal and external collaboration and communication.3.Establish room for maneuver to exercise leadership.4.Recognizing and having the mandate to handle possible tensions in the dual responsibility of HSE and QPS.ConclusionsThe study showed that leaders of nursing homes who are responsible for ensuring quality and safety for both patients and staff, experience tensions in handling this dual responsibility. They acknowledged the importance of having time to be present as a leader, to have robust systems to maintain HSE and QPS, and that conflicting aspects of legislation are an everyday challenge.
Whole-Genome Sequencing Analyses Reveal the Whip-like Tail Formation, Innate Immune Evolution, and DNA Repair Mechanisms of Eupleurogrammus muticus
Authors: Han Fang-Yuan , Wu Ren-Xie , Miao Ben-Ben , Niu Su-Fang , Wang Qing-Hua , Liang Zhen-Bang 
Published: January 2024

Smallhead hairtail (Eupleurogrammus muticus) is an important marine economic fish distributed along the northern Indian Ocean and the northwest Pacific coast; however, little is known about the mechanism of its genetic evolution. This study generated the first genome assembly of E. muticus at the chromosomal level using a combination of PacBio SMRT, Illumina Nova-Seq, and Hi-C technologies. The final assembled genome size was 709.27 Mb, with a contig N50 of 25.07 Mb, GC content of 40.81%, heterozygosity rate of 1.18%, and repetitive sequence rate of 35.43%. E. muticus genome contained 21,949 protein-coding genes (97.92% of the genes were functionally annotated) and 24 chromosomes. There were 143 expansion gene families, 708 contraction gene families, and 4888 positively selected genes in the genome. Based on the comparative genomic analyses, we screened several candidate genes and pathways related to whip-like tail formation, innate immunity, and DNA repair in E. muticus. These findings preliminarily reveal some molecular evolutionary mechanisms of E. muticus at the genomic level and provide important reference genomic data for the genetic studies of other trichiurids.
Applicability of Thermal Dissipation Method in Sap Flow Measurement of Karst Shrub Community
Authors: Qin Jiashuang , Ni Longkang , Gu Daxing , Yang Kaijun , Huang Qibo , Tan Yu , Liao Suhui 
Published: January 2024

Although the thermal dissipation probe (TDP) method is prominent in forest transpiration studies, the accurate estimation of sap flow density in particular trees with different wood structures remains highly variable. To verify the applicability of the TDP method in the measurement of the transpirational water consumption of shrub communities in degraded karst areas in southern China, Granier’s original formula was validated and corrected using the isolated stem segment method with Celtis sinensis, Xylosma congesta, Triadica sebifera, Paliurus ramosissimus, Pyracantha fortuneana, Sageretia thea, and Phanera championii. Finally, the correction coefficients were analyzed in relation to wood structural parameters. Our study reveals that the sap flow density estimated using Granier’s original formula exhibited varying degrees of overestimation or underestimation compared to the measured sap flow density. The differences ranged from −78.9% to 114.2%, highlighting the need for formula correction. Consequently, we adjusted the coefficients α and β of the original formula (n = 3–5), resulting in a revised range of 0.0047–0.0509 g cm−2 s−1 and 0.5882–1.9821 (R2 = 0.81–0.97), respectively. The conduit diameter was significantly correlated with the correction coefficient α. It is currently unknown whether the results obtained for a particular species can be applied to different growth environments and more prominent individuals of the same species. In conclusion, it is necessary to verify the applicability of Granier’s original formula when estimating water consumption through transpiration in trees.