bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leveraging automated time-lapse microscopy coupled with deep learning to automate colony forming assay
Authors: Klett Anusha , Raith Dennis , Silvestrini Paula , Stingl Matías , Bermeitinger Jonas , Sapre Avani , Condor Martin , Melachrinos Roman , Kusterer Mira , Brand Alexandra , Pisani Guido , Ullrich Evelyn , Follo Marie , Duque-Afonso Jesús , Mertelsmann Roland 
Published: February 2025

IntroductionThe colony forming assay (CFA) stands as a cornerstone technique for evaluating the clonal expansion ability of single cancer cells and is crucial for assessing drug efficacy. However, traditional CFAs rely on labor-intensive, endpoint manual counting, offering limited insights into the dynamic effects of treatment. To overcome these limitations, we developed an Artificial Intelligence (AI)-assisted automated CFA combining time-lapse microscopy for real-time tracking of colony formation.MethodsUsing B-acute lymphoblastic leukemia (B-ALL) cells from an E2A-PBX1 mouse model, we cultured them in a collagen-based 3D matrix with cytokines under static conditions in a low volume (60 µl) culture vessel and validated its comparability to methylcellulose-based media. No significant differences in final colony count or plating efficiency were observed. Our automated platform utilizes a deep learning and multi-object tracking approach for colony counting. Brightfield images were used to train a YOLOv8 object detection network, achieving a mAP50 score of 86% for identifying single cells, clusters, and colonies, and 97% accuracy for Z-stack colony identification with a multi-object tracking algorithm. The detection model accurately identified the majority of objects in the dataset.ResultsThis AI-assisted CFA was successfully applied for density optimization, enabling the determination of seeding densities that maximize plating efficiency (PE), and for IC50 determination, offering an efficient, less labor-intensive method for testing drug concentrations. In conclusion, our novel AI-assisted automated colony counting platform enables automated, high-throughput analysis of colony dynamics, significantly reducing labor and increasing accuracy. Furthermore, it allows detailed, long-term studies of cell-cell interactions and treatment responses using live-cell imaging and AI-assisted cell tracking. DiscussionFuture integration with a perfusion-based drug screening system promises to enhance personalized cancer therapy by optimizing broad drug screening approaches and enabling real-time evaluation of therapeutic efficacy.
Multimodal ultrasound: a non-invasive method for identifying dedifferentiation of papillary thyroid carcinoma during active surveillance
Authors: Dou Qian-Yi , Guo Huan-Ling , Qiu Wan-Bing , Xu Ming , Chen Shu-Ling , Zhang Xiao-Er , Xie Xiao-Yan , Liang Jin-Yu 
Published: February 2025

ObjectivesTo assess the diagnostic accuracy of multimodal ultrasound in differentiating anaplastic thyroid carcinoma (ATC) from papillary thyroid carcinoma (PTC) and to evaluate its capability in detecting thyroid carcinoma (TC) aggressiveness.MethodsSixty nude mice were randomly assigned to ATC and PTC groups and injected subcutaneously with KHM-5M and TPC-1 cell lines, respectively. Tumors were analyzed using B-mode ultrasound (B-US), Color Doppler flow imaging (CDFI), elastography, and contrast-enhanced ultrasound (CEUS). A logistic model integrating multimodal ultrasound data was constructed, and Ki-67 and CD31 expressions in tumor tissues were analyzed immunohistochemically. Correlations between ultrasound features and aggressiveness markers were investigated.ResultsThe ATC group exhibited significantly higher strain-elastography scores (p=0.009) and Adler grades in CDFI (p=0.045). CEUS revealed a higher frequency of heterogeneous enhancement (95.2% vs. 48.1%, p&lt;0.001) and perfusion defects (90.5% vs. 63.0%, p&lt;0.001) in ATC. Model area under the curve (AUC) values for distinguishing ATC from PTC were 0.963 for (B-US + CEUS), 0.926 for CEUS, 0.729 for elastography, 0.663 for CDFI, and 0.675 for B-US. The multimodal ultrasound model demonstrated significant correlations with Ki-67 (p&lt;0.001) and microvessel density (MVD) (p&lt;0.001).ConclusionsMultimodal ultrasound showing high efficacy with an AUC of 0.963 for B-US and CEUS combined in distinguishing ATC from PTC and exhibited strong associations with Ki-67 and MVD. Incorporating multimodal ultrasound, with an emphasis on CEUS, into active surveillance strategies for PTC is recommended. By providing detailed insights into tumor vascularity and aggressiveness, multimodal ultrasound could play a crucial role in early detection and treatment decision-making, improving patient outcomes.
Correlation analysis between the severity of respiratory syncytial virus pneumonia and the expression levels of inflammatory cytokines in bronchoalveolar lavage fluid among infants and young children
Authors: Tan Lin , He Zhaohui , Liang Yongqi , Wang Kuncheng , Chen Xiaoqian 
Published: February 2025

PurposeRSV is the primary cause of lower respiratory tract infections in infants and young children. Current study aims to investigate the correlation between the severity of respiratory syncytial virus pneumonia (RSVP) in infants and young children and the number of RSV infection sequences as well as the levels of cytokines in bronchoalveolar lavage fluid (BALF).MethodsMetagenomics next-generation sequencing (mNGS) and enzyme-linked immunosorbent assay (ELISA) were used to detect the number of RSV infection sequences and the levels of related inflammatory cytokines in BALF samples. Comparisons between groups and Logistic regression analysis were performed to examine the differences in RSV infection sequences and inflammatory cytokine levels between the sRSVP and nsRSVP groups. Spearman's correlation coefficient was used to analyze the correlations among PCIS, RSV infection sequences, and inflammatory cytokines. Finally, ROC curve analysis was conducted to assess the diagnostic performance of inflammatory cytokines as biomarkers in determining the severity of RSVP.ResultsA total of 49 infants and young children diagnosed with RSV infection were enrolled and divided into severe RSVP (sRSVP) and non-severe RSVP (nsRSVP) groups based on the pediatric critical illness score (PCIS) scale. The levels of Interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor α (TNF-α), IL-17A, and monocyte chemotactic protein 1 (MCP-1) as well as the number of RSV sequences in BALF were significantly higher in the sRSVP group than in the nsRSVP group. Additionally, elevated levels of IL-6, IL-10, TNF-α, IL-17A, and the number of RSV sequences were identified as risk factors for the severity of RSVP. Spearman's correlation analysis revealed significant negative correlations between the levels of IL-6, IL-10, TNF-α, IL-17A, and MCP-1 in BALF with PCIS, and significant positive correlations with the number of RSV sequences. Furthermore, a significant negative correlation was observed between RSV sequence count and PCIS. ROC curve analysis showed that the levels of IL-6, IL-10, TNF-α, IL-17A, and MCP-1, as well as their combined diagnostic approach, exhibited high diagnostic performance in determining the severity of RSVP.ConclusionThe levels of inflammatory cytokines and RSV sequences in BALF are significantly correlated with the severity of RSVP in infants and young children. The levels of IL-6, IL-10, TNF-α, IL-17A, and MCP-1 can serve as potential biomarkers for diagnosing the severity of RSVP.
Curative effect of laparoscopic ureteral end-to-side anastomosis at the pelvic level for a duplex kidney in children
Authors: Bian Zedong , Xiong Geng , Liu Tong , Zhi Yong , Liu Ming 
Published: February 2025

BackgroundTo analyze the clinical efficacy and experience with laparoscopic ureteral end-to-side anastomosis at the pelvic level for a duplex kidney (DK) in children.MethodsThis was a retrospective analysis of 20 children diagnosed with a complete DK in the pediatric surgery department of the Affiliated Hospital of Southwest Medical University between January 2018 and July 2024. The cohort comprised 15 girls and five boys aged 5–100 months (mean ± SD, 38.5 ± 29.9). There were 16 cases on the left side and four cases on the right side. There were five cases of simple upper ureterovesical junction stenosis, seven cases of upper ureteroceles, seven cases of upper ureteral ectopic opening, and one case of postoperative vesicoureteral reflux with fenestration for upper ureteroceles. The major clinical symptoms were intermittent perineal urinary leakage and repeated infection of the urinary tract. Laparoscopic duplex ureteral end-to-side anastomosis (between the end section of the upper ureter and the lateral section of the lower ureter) at the pelvic level was performed in all patients with an intraoperative indwelling ureteral stent.ResultsLaparoscopy with no conversion to open was undertaken in the 20 cases. The duration of the procedure was 85–140 (112.9 ± 14.3) min. Intraoperative blood loss was 5–15 (8.2 ± 4.4) ml. Postoperative duration of hospital stay was 5–9 (6.5 ± 0.9) days. No anastomosis fistula, anastomotic stenosis, ureteral stump infection or other complications occurred. The ureteral stent was removed 8 weeks after surgery. All children were followed up for 4–68 (median, 32) months. Clinical symptoms disappeared, and the degree of upper renal hydronephrosis decreased.ConclusionsLaparoscopic ureteral end-to-side anastomosis at the pelvic level for a DK in children is safe and efficacious. It is a minimally invasive procedure that is simple with few complications, and merits wider popularization.
Potential efficacy and mechanisms of icariin for the animal model of osteonecrosis of the femoral head
Authors: Xu Jie , Deng Wei , Zhu Xun , Han Deyu , Zheng Yu , Zheng Qun 
Published: February 2025

IntroductionIcariin (ICA), one of the main active components of Epimediumis, is reported to revere osteonecrosis of the femoral head (ONFH). The aim of this study is to further explore the mechanisms and efficacy of ICA in animal models of ONFH and simultaneously analyze methodological issues in the field of researches.MethodsAccording to the established search strategy, we searched 14 studies from eight databases from their inception dates to November 2024. The CAMARADES 10-item checklist was utilized to evaluate the methodological quality of the stuies and Rev-Man 5.3 software to analyze differences in outcome indicators.ResultsThe quality score for the included articles ranges from 1/10 to 6/10 with an average of 4.5 and the defects in aspects of blinding assessment of outcome, randomization and sample size calculation are the main losing points. Compared with the control group, 10 stuies reported ICA could partially improve bone pathology including reducing the empty of bone lacunae, maturing osteoblasts of ONFH and decreasing chondroid bone matrix and fibrous connective tissue. Eight stuies indicates that ICA could improve bone-related parameters under imageology including F-BMD, Tb.N, Tb.Th, BV/TV and Tb. Sp.DiscussionThe preclinical systematic review provided preliminary evidence that ICA partially reversing ONFH in animal models probably via promoting angiogenesis, anti-apoptosis, and regulating the activities of osteoblasts and osteoclasts. Randomization, blinding and sample size calculation should be focused on in future studies of ONFH. These findings suggest that ICA is a potential candidate for further clinical trials of ONFH.
The clinically applied PARP inhibitor talazoparib ameliorates imiquimod-induced psoriasis in mice without reducing skin inflammation
Authors: Molnár Petra , Demény Máté Ágoston , Várkonyi Beáta , Polgár Zsuzsanna , Pór Ágnes , Kovács Ilona , Szegedi Andrea , Szöllősi Attila Gábor , Szántó Magdolna 
Published: February 2025

BackgroundConsidering the role PARPs play in inflammation, we assessed the effect of PARP inhibition in an inflammatory skin condition, psoriasis, to explore novel avenues for the potential repurposing of PARP inhibitors that are currently used in tumour therapy.MethodsThe imiquimod (IMQ)-induced model of psoriasis was applied in BALB/c mice. Mice received daily intraperitoneal injection of either one of four PARP inhibitors or their vehicle prior to treatment of the shaved back skin of mice with IMQ-containing cream or control cream for four days. The appearance of the skin of mice was scored daily according to the extent of erythema, induration and scaling. The most effective PARP inhibitor was selected for detailed studies on mouse skin and in a human keratinocyte cell line.ResultsOf the PARP inhibitors, talazoparib and rucaparib improved the imiquimod-induced symptoms on mouse skin. Application of talazoparib in the psoriasis model resulted in maintained terminal differentiation and reduced proliferation of epidermal keratinocytes. Conversely, talazoparib also enhanced the production of pro-inflammatory chemokines in the skin of mice. These effects of talazoparib was associated with increased mitochondrial production of reactive oxygen species and a consequent activation of pro-apoptotic and pro-inflammatory pathways in keratinocytes.ConclusionPARP inhibition by talazoparib promotes terminal differentiation of epidermal keratinocytes that may be beneficial in psoriasis. Despite the fact that talazoparib exerted a pro-inflammatory effect in the skin, which is not unprecedented in anti-psoriatic therapy, these findings may advance the conduction of pre-clinical and clinical trials with PARP inhibitors in psoriasis management.
Ergothioneine attenuates psoriasis symptoms through modulation of M1/M2 macrophage polarisation via the NF-κB/JAK-STAT3 pathway
Authors: Li Ang , Liu Yanjie , Yu Peiling , Zhang Zhiyuan , Huang Tengxiao , Li Hang , Wu Songzhi , Rong Xiaoyu , Liao Wensheng , Wang Hongqiang , Gao Yanzheng 
Published: February 2025

IntroductionThe underlying cause of psoriasis, a chronic inflammatory skin condition driven by an immune response, remains a topic of active investigation and is not yet fully elucidated. Recent studies have revealed that ergothioneine, a small molecule sulfur-containing histidine derivative that can be ingested from the daily diet and accumulated in the body, exhibits antioxidant capacity that is comparable to that of glutathione. Nevertheless, there is a paucity of empirical data concerning the precise impact of ergothioneine in the context of anti-inflammatory processes, particularly in the context of psoriasis. In the light of the aforementioned considerations, the present study was undertaken with the objective of conducting a comprehensive evaluation of the anti-inflammatory potential of ergothioneine (EGT) and to investigate its potential impact on the pathogenesis of psoriasis.Methods:The efficacy of EGT in reducing the extent of dorsal skin lesions in psoriasis model mice was confirmed through in vivo experimental observation. Furthermore, the inhibitory effect of EGT on inflammatory responses at the cellular level was investigated, specifically in LPS-induced mouse macrophage (RAW264.7) and human keratinocyte-forming cell (HaCaT) models.ResultsThe results demonstrated that the introduction of different concentrations of EGT into the LPS-induced inflammatory cell model resulted in notable anti-inflammatory effects, as evidenced by a reduction in inflammatory responses and a dose dependent decline in the concentrations of key inflammatory cytokines, including interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2) and tumour necrosis factor-α (TNF-α). Furthermore, EGT was observed to reverse the LPS induced increase in the ratio of M1 to M2 macrophages. EGT was also observed to markedly suppress the LPS-induced phosphorylation of JAK/STAT3 and NF-κB, offering a novel insight into the anti-inflammatory mechanism of EGT.DiscussionIn conclusion, the findings of the present study consistently demonstrated that ergothioneine had a significant ameliorative effect on the imiquimod-induced psoriasis model by modulating the NF-κB/JAK-STAT3 signalling pathway. This provides a strong experimental rationale for its potential application in psoriasis treatment.
Male mouse skeletal muscle lacking HuR shows enhanced glucose disposal at a young age
Authors: Noland Robert C. , Ghosh Sujoy , Crisanto Carlos J. , Aleman Antonio , Chaney McKenna K. , Chauhan Maitri K. , Loftis Layla G. , Goad Ally C. , Rickman Christin F. , Velasquez Samuel E. , Warfel Jaycob D. 
Published: February 2025

IntroductionMetabolic flexibility is the ability of a system to switch between metabolic substrates. Human and murine skeletal muscle tissues and cells with decreased activity of the regulatory RNA-binding protein, human antigen R (HuR), have decreased capacity for fat oxidation, and thus decreased metabolic flexibility. In this study, we aimed to assess the preference for carbohydrates in mice lacking HuR in skeletal muscle.MethodsExperiments were performed on weight-matched control and HuR knockout mice of both sexes. Palmitate and pyruvate oxidation were performed in mouse muscle following the release of 14CO2. In vivo glucose and lipid uptake were assayed in mouse tissue following nonmetabolizable 3H-2-deoxyglucose or 14C-bromopalmitate injection. Transcriptomic analyses were performed in the skeletal muscle of all mice, followed by qPCR validation of select genes. Serum lactate and glucose levels were measured in mice via tail nick, and the muscle glycogen level was measured through colorimetric assay. Indirect calorimetry was used to measure respiratory exchange ratios.ResultsMale muscle-specific HuR knockout mice showed increased glucose uptake relative to controls, specifically in skeletal muscle, and have increased muscle glycogen content. These mice also displayed greater respiratory exchange ratios than controls. None of these differences were noted in females. Transcriptomics showed far more differences between male and female mice than between control and HuR knockout mice. However, differential gene expression between male and female mice was diminished by 50% following the removal of HuR. Male HuR knockout mouse skeletal muscle had increased glycolytic gene expression relative to controls but showed no difference relative to females of the same genotype. Both palmitate and pyruvate oxidation were decreased in the skeletal muscle of male HuR knockout mice relative to controls, and serum lactate levels were increased. No notable differences were seen in females between genotypes.DiscussionThe increase in the markers of glucose utilization with decreased HuR activity in male mice may indicate a switch toward glycolysis as compensation for decreased fat oxidation. These results continue to highlight a sex dependence on HuR as a driver of fat oxidation in mouse skeletal muscle while also indicating that muscle itself shows greater ambiguity between males and females following the removal of HuR.
Loss rate of net primary productivity under drought stress on the Yinshanbeilu of Inner Mongolia, China
Authors: Sinan Wang , Wu Yingjie , Wang Wenjun , Guo Jianyin , Li Mingyang 
Published: February 2025

IntroductionThe increasing intensity and frequency of droughts seriously threaten the structure and function of terrestrial ecosystems. In order to ensure the normal play of ecosystem service function under future stress, the temporal and spatial characteristics of ecosystem productivity response to drought need to be explored.MethodsThe net primary production (NPP) of vegetation in the Yinshanbeilu was calculated using the Carnegie-Ames-Stanford Approach (CASA) model, and subsequent study concentrated on the NPP’s geographical and temporal variable characteristics. By the calculation of the standard precipitation evapotranspiration index (SPEI), the study also sought to examine the relationship between drought and NPP at various time scales. Researchers also built drought loss rate curves based on various fertility stages using the vulnerability curve construction method.Results and discussionFindings revealed that the SPEI had varying degrees of efficacy in capturing drought conditions at various time frames. Nonetheless, the SPEI’s spatial distribution, which shows a wet distribution in the east and an arid distribution in the west, exhibited identical characteristics for all scales and may be used to indicate drought. Significant interannual variation was seen in the NPP of the study area’s vegetation, which fluctuated in an upward direction from 2000 to 2020. 75.89%, 77.23%, 81.35%, and 83.56% of the area were found to have a positive correlation between the SPEI and vegetation NPP at various time scales, with 42.53%, 48.15%, 90.72%, and 92.75% of the area passing the significance test (p &lt; 0.05), in that order. Their results showed that as the SPEI time scale was increased, the link between vegetation NPP and SPEI became stronger. The loss rate of vegetation NPP fluctuated and grew regularly with the expansion of drought degree, varying between 20-50%, according to drought loss rate curves created for each fertility period.
The cultural adaptation of the Friendship Bench Intervention to address perinatal psychological distress in Sierra Leone: an application of the ADAPT-ITT framework and the Ecological Validity Model
Authors: Bah Abdulai Jawo , Wurie Haja Ramatulai , Samai Mohamed , Horn Rebecca , Ager Alastair 
Published: February 2025

BackgroundIn Sierra Leone, women of reproductive age represent a significant portion of the population and face heightened mental health challenges due to the lasting effects of civil war, the Ebola epidemic, and the COVID-19 pandemic. This study aimed to culturally adapt the Friendship Bench Intervention (FBI) for perinatal psychological distress in Sierra Leone.MethodWe utilized the ADAPT-ITT framework and Bernal’s Ecological Validity Model (EVM) for culturally adapting the FBI’s process and content. The adaptation stages included a formative study to assess perinatal women’s mental health needs. We screened the FBI for modifications based on the data from the formative study and EVM. The initial FBI manual was presented to mother-mother support groups (MMSGs, n=5) and primary health workers (n=3) for feedback (version 1.0). A theatre test with perinatal women (n=10) was conducted led by MMSGs, yielding further feedback (version 2.0). The revised manual was then reviewed by topical experts (n=2), whose insights were incorporated (version 3.0).ResultsThe Friendship Bench manual for Sierra Leone has been revised to better meet the cultural needs of perinatal women. The cover now illustrates an elderly woman conversing with a new mother, emphasizing community support. Culturally relevant idioms, such as “poil at” and “mind not steady,” replace previous terms, and new screening tools, the Sierra Leone Perinatal Psychological Distress Scale (SLPPDS) and the Function Scale, have been introduced. The problem-solving therapy was simplified from seven to four steps, and training duration was reduced from nine days to two, using visual aids to enhance comprehension for those with low literacy levels.ConclusionThrough this systematic approach, we successfully culturally adapted the FBI for treating perinatal psychological distress in Sierra Leone. The next step is to evaluate it feasibility, acceptability, and preliminary effectiveness in perinatal care settings.