bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of nanobodies targeting hepatocellular carcinoma and application of nanobody-based CAR-T technology
Authors: Lin Keming , Xia Baijin , Wang Xuemei , He Xin , Zhou Mo , Lin Yingtong , Qiao Yidan , Li Rong , Chen Qier , Li Yuzhuang , Feng Jinzhu , Chen Tao , Chen Cancan , Li Xinyu , Zhang Hui , Lu Lijuan , Liu Bingfeng , Zhang Xu 
Published: April 2024

Abstract
Background
Chimeric antigen receptor T (CAR-T) cell therapy, as an emerging anti-tumor treatment, has garnered extensive attention in the study of targeted therapy of multiple tumor-associated antigens in hepatocellular carcinoma (HCC). However, the suppressive microenvironment and individual heterogeneity results in downregulation of these antigens in certain patients’ cancer cells. Therefore, optimizing CAR-T cell therapy for HCC is imperative.

Methods
In this study, we administered FGFR4-ferritin (FGFR4-HPF) nanoparticles to the alpaca and constructed a phage library of nanobodies (Nbs) derived from alpaca, following which we screened for Nbs targeting FGFR4. Then, we conducted the functional validation of Nbs. Furthermore, we developed Nb-derived CAR-T cells and evaluated their anti-tumor ability against HCC through in vitro and in vivo validation.

Results
Our findings demonstrated that we successfully obtained high specificity and high affinity Nbs targeting FGFR4 after screening. And the specificity of Nbs targeting FGFR4 was markedly superior to their binding to other members of the FGFR family proteins. Furthermore, the Nb-derived CAR-T cells, targeting FGFR4, exhibited significantly enhanced anti-tumor efficacy in both experiments when in vitro and in vivo.

Conclusions
In summary, the results of this study suggest that the CAR-T cells derived from high specificity and high affinity Nbs, targeting FGFR4, exhibited significantly enhanced anti-tumor efficacy in vitro and in vivo. This is an exploration of FGFR4 in the field of Nb-derived CAR-T cell therapy for HCC, holding promise for enhancing safety and effectiveness in the clinical treatment of HCC in the future.
Acute exposure to polystyrene nanoparticles promotes liver injury by inducing mitochondrial ROS-dependent necroptosis and augmenting macrophage-hepatocyte crosstalk
Authors: Fan Junjie , Liu Li , Lu Yongling , Chen Qian , Fan Shijun , Yang Yongjun , Long Yupeng , Liu Xin 
Published: April 2024

Abstract
Background
The global use of plastic materials has undergone rapid expansion, resulting in the substantial generation of degraded and synthetic microplastics and nanoplastics (MNPs), which have the potential to impose significant environmental burdens and cause harmful effects on living organisms. Despite this, the detrimental impacts of MNPs exposure towards host cells and tissues have not been thoroughly characterized.

Results
In the present study, we have elucidated a previously unidentified hepatotoxic effect of 20 nm synthetic polystyrene nanoparticles (PSNPs), rather than larger PS beads, by selectively inducing necroptosis in macrophages. Mechanistically, 20 nm PSNPs were rapidly internalized by macrophages and accumulated in the mitochondria, where they disrupted mitochondrial integrity, leading to heightened production of mitochondrial reactive oxygen species (mtROS). This elevated mtROS generation essentially triggered necroptosis in macrophages, resulting in enhanced crosstalk with hepatocytes, ultimately leading to hepatocyte damage. Additionally, it was demonstrated that PSNPs induced necroptosis and promoted acute liver injury in mice. This harmful effect was significantly mitigated by the administration of a necroptosis inhibitor or systemic depletion of macrophages prior to PSNPs injection.

Conclusion
Collectively, our study suggests a profound toxicity of environmental PSNP exposure by triggering macrophage necroptosis, which in turn induces hepatotoxicity via intercellular crosstalk between macrophages and hepatocytes in the hepatic microenvironment.
Cryopreservation of sessile oak (Quercus petraea (Matt.) Liebl.) plumules using aluminium cryo-plates: influence of cryoprotection and drying
Authors: Wasileńczyk Urszula , Wawrzyniak Mikołaj Krzysztof , Martins João Paulo Rodrigues , Kosek Paulina , Chmielarz Paweł 
Published: April 2024

Abstract
Background Quercus
seeds that are recalcitrant to desiccation and freezing temperatures cannot be stored in gene banks under conventional conditions. However, the germplasm of some recalcitrant seeded species can be stored in liquid nitrogen (–196 °C). Unfortunately, for many species, among them for almost the whole genus Quercus, an effective cryostorage method is still unknown. In this study, we propose a successful cryostorage protocol for Quercus petraea (Matt.) Liebl. germplasm using plumules (a shoot apical meristem of an embryo) frozen on aluminium cryo-plates.

Results
The plumules isolated from the acorns of ten provenances were prestored in 0.5 M sucrose solution (for 18 h). To form alginate beads (one plumule per bead), the plumules were placed in the wells of a cryo-plate and embedded in calcium alginate gel. For cryoprotection, the encapsulated plumules were immersed in cryoprotectant solution containing 2.0 M glycerol and different concentrations of sucrose (0.8–1.2 M) for 40 min at 25 °C and desiccated under a laminar flow cabinet for 1.0–4.0 h. Cryo-plates with plumules were directly immersed in liquid nitrogen and then cryostored for 30 min. For rewarming, cryo-plates with plumules were immersed in 1.0 M sucrose solution and rehydrated for 15 min at 25 °C. Survival rates varied from 25.8 to 83.4 were achieved after cryoprotection in 1.0 M sucrose solution and the drying of plumules for 2 h. The in vitro regrowth rate of cryopreserved plumules varied among provenances and was 26–77%.

Conclusions
This study presents, for the first time, a successful, simple and effective protocol for the cryopreservation of Q. petraea germplasm that could be used in gene banks. The experiment was successfully repeated on seeds from various provenances, each yielding similar, good results. However, seed quality and storage time after harvesting are important factors in plumule regrowth after cryopreservation.
Left ventricular free wall rupture caused by myocardial ischemia without treatable atherosclerotic coronary disease: a case series
Authors: Andrási Terézia B. , Abudureheman Nunijiati , Glück Alannah C. , Dielmann Kai , Dinges Gerhard 
Published: April 2024

Abstract
Background
The clinical presentation of left ventricular free wall rupture (LVFWR) varies ranging from uneventful condition to congestive heart failure.

Case summary
Here we report two cases of LVFWR with different clinical presentation and notable outcome. A 53-year-old male presenting emergently with signs of myocardial infarction received immediate coronary angiography and thoracic CT-scan showing occlusion of the first marginal coronary branch without possibility of revascularization and minimal pericardial extravasation. Under ICU surveillance, LVFWR occurred 24 h later and was treated by pericardiocentesis and ECMO support followed by immediate uncomplicated surgical repair. Postoperative therapy-refractory vasoplegia and electromechanical dissociation caused fulminant deterioration and the early death of the patient. The second case is a 76-year old male brought to the emergency room after sudden syncope, clinical sings of pericardial tamponade and suspicion of a type A acute aortic dissection. Immediate CT-angiography excluded aortic dissection and revealed massive pericardial effusion and a hypoperfused myocardial area on the territory of the first marginal branch. Immediate sternotomy under mechanical resuscitation enabled removal of the massive intrapericardial clot and revealed LVFWR. After an uncomplicated surgical repair, an uneventful postoperative course, the patient was discharged with sinus rhythm and good biventricular function. One year after the operation, he is living at home, symptom free.

Discussion
Whereas the younger patient, who was clinically stable at hospital admission received delayed surgery and did not survive treatment, the older patient, clinically unstable at presentation, went into immediate surgery and had a flawless postoperative course. Thus, early surgical repair of LVFWR leads to best outcome and treating LVFWR as a high emergency regardless of the symptoms improve survival.
Clinical investigator perspectives on patient outcomes in children with neuronopathic mucopolysaccharidosis II during intrathecal idursulfase-IT treatment
Authors: Yee Karen S. , Alexanderian David , Martin Susan , Olayinka-Amao Bimpe , Whiteman David A. H. 
Published: April 2024

AbstractBackgroundMucopolysaccharidosis II (MPS II) is a rare lysosomal storage disease characterized by iduronate-2-sulfatase gene (IDS) deficiency and downstream glycosaminoglycan accumulation. Two-thirds of patients present with neuronopathic disease and evaluating cognitive function in these patients is challenging owing to limitations of currently available tests. During the clinical development of intrathecal idursulfase (idursulfase-IT), regulatory authorities requested qualitative data to further understand the neurocognitive changes observed by the investigators through the clinical trials.ResultsThis qualitative study consisted of semi-structured interviews with all nine of the principal investigators who participated in the idursulfase-IT phase 2/3 (NCT02055118) and extension (NCT02412787) trials. These investigators enrolled the 56 patients with neuronopathic MPS II who qualified for the extension phase of the trial. The investigators were asked to rate the disease status of their patients. Of the 56 patients, 49 (88%) were rated as having disease that was improved/improving, stabilized or slowing progression compared with the expected outcomes with no treatment. Three patients were rated as worsening, while the remaining four patients were considered to have slowing progression or worsening disease. Similar results were demonstrated for patients aged from 3 to under 6 years at baseline, with 33 of 39 patients (85%) rated as having disease that was improved/improving, stabilized or slowing progression. Of the seven patients rated with slowing progression/worsening or worsening disease, five of them had anIDSvariant other than missense, while two had a missense class variant. All the assigned improved/improving ratings were in patients receiving idursulfase-IT from the start of the phase 2/3 trial. Moreover, patients under 3 years of age at baseline were all rated as either improved/improving or stabilized disease. In a blinded review of patient profiles, investigators were requested to assign a disease status rating to 18 patients with largeIDSdeletions; 67% of these patients were rated as improved/improving or stabilized disease.ConclusionsThis qualitative analysis provides a snapshot of clinicians’ considerations when evaluating treatment in patients with neuronopathic MPS II, compared with the expected decline in cognitive function in the absence of treatment. The results highlight the importance of robust assessment tools in treatment evaluation.
Clinical and genetic study of ABCB4 gene-related cholestatic liver disease in China: children and adults
Authors: Cao Lili , Ling Xiuxin , Yan Jianguo , Feng Danni , Dong Yi , Xu Zhiqiang , Wang Fuchuan , Zhu Shishu , Gao Yinjie , Cao Zhenhua , Zhang Min 
Published: April 2024

Abstract
Background
ABCB4 gene-related cholestatic liver diseases have a wide spectrum of clinical and genetic variations. The correlation between genotype and clinical phenotype still unclear. This study retrospectively analyzed the clinical and pathological characteristics of 23 patients with ABCB4 gene-related cholestatic liver diseases. Next-generation sequencing was used to identify the genetic causes.

Results
The 23 included patients (15 children and 8 adults) were diagnosed as progressive familial intrahepatic cholestasis type 3 (PFIC3), drug-induced liver injury (DILI), cirrhosis cholestasis, cirrhosis, and mild liver fibrosis. Nineteen patients underwent liver pathological examination of the liver, exhibiting fibrosis, small bile duct hyperplasia, CK7(+), Cu(+), bile duct deletion, and cirrhosis. Thirty ABCB4 variants were identified, including 18 novel variants.

Conclusion
ABCB4 gene-related cholestatic liver diseases have a wide spectrum of clinical and genetic variations. Biallelic ABCB4 mutation carriers tended to severe PFIC3, which mostly occurs in children; while ABCB4 non-biallelic variants can lead to milder ICP, LACP, DILI or overlapping, mostly in adults. Thus, the ABCB4 genotype has a specific correlation with the phenotype, but there are exceptions. Non-biallelic null mutations can cause severe diseases. The mechanisms underlying this genetic phenotype require further investigation.

Graphical Abstract
Metabolomics assisted by transcriptomics analysis to reveal metabolic characteristics and potential biomarkers associated with treatment response of neoadjuvant therapy with TCbHP regimen in HER2 + breast cancer
Authors: Zhang Ningning , Huang Yuxin , Wang Guanwen , Xiang Yimei , Jing Zhouhong , Zeng Junjie , Yu Feng , Pan Xianjun , Zhou Wenqi , Zeng Xiaohua 
Published: April 2024

Abstract
Background
This study aimed to explore potential indicators associated with the neoadjuvant efficacy of TCbHP regimen (taxane, carboplatin, trastuzumab, and pertuzumab) in HER2 + breast cancer (BrCa) patients.

Methods
A total of 120 plasma samples from 40 patients with HER2 + BrCa were prospectively collected at three treatment times of neoadjuvant therapy (NAT) with TCbHP regimen. Serum metabolites were analyzed based on LC-MS and GC-MS data. Random forest was used to establish predictive models based on pre-therapeutic differentially expressed metabolites. Time series analysis was used to obtain potential monitors for treatment response. Transcriptome analysis was performed in nine available pre‑therapeutic specimens of core needle biopsies. Integrated analyses of metabolomics and transcriptomics were also performed in these nine patients. qRT-PCR was used to detect altered genes in trastuzumab-sensitive and trastuzumab-resistant cell lines.

Results
Twenty-one patients achieved pCR, and 19 patients achieved non-pCR. There were significant differences in plasma metabolic profiles before and during treatment. A total of 100 differential metabolites were identified between pCR patients and non-pCR patients at baseline; these metabolites were markedly enriched in 40 metabolic pathways. The area under the curve (AUC) values for discriminating the pCR and non-PCR groups from the NAT of the single potential metabolite [sophorose, N-(2-acetamido) iminodiacetic acid, taurine and 6-hydroxy-2-aminohexanoic acid] or combined panel of these metabolites were greater than 0.910. Eighteen metabolites exhibited potential for monitoring efficacy. Several validated genes might be associated with trastuzumab resistance. Thirty-nine altered pathways were found to be abnormally expressed at both the transcriptional and metabolic levels.

Conclusion
Serum-metabolomics could be used as a powerful tool for exploring informative biomarkers for predicting or monitoring treatment efficacy. Metabolomics integrated with transcriptomics analysis could assist in obtaining new insights into biochemical pathophysiology and might facilitate the development of new treatment targets for insensitive patients.
Parietal abdominal pain with lower leg discrepancy: a case report
Authors: Gritli Agnès , Ramirez David Cadavid , Decavel Pierre 
Published: April 2024

Abstract
Background
This report involves the first publication describing a case of parietal abdominal pain due to lower limb length discrepancy.

Case presentation
A Caucasian male patient in his 50s was referred to our rehabilitation department with chronic abdominal pain that began in childhood. This chronic pain was associated with episodes of acute pain that were partially relieved by grade 3 analgesics. The patient was unable to sit for long periods, had recently lost his job, and was unable to participate in recreational activities with his children. Investigations revealed contracture and hypertrophy of the external oblique muscle and an limb length discrepancy of 3.8 cm (1.5 inches) in the left lower limb. The patient was effectively treated with a heel raise, physiotherapy, intramuscular injection of botulinum toxin, and lidocaine. The patient achieved the therapeutic goals of returning to work, and reducing analgesic use.

Conclusions
Structural misbalances, as may be caused by lower leg discrepancy, may trigger muscular compensations and pain. Complete anamnesis and clinical examination must not be trivialized and may reveal previously ignored information leading to a proper diagnosis.
Does arthroscopic or open washout in native knee septic arthritis result in superior post-operative function? A systematic review and meta-analysis of randomised controlled trials and observational studies
Authors: Kennedy Grace E. M. , Tharmaseelan Abisha , Phillips Jonathan R. A. , Evans Jon T. , Kunutsor Setor K. 
Published: April 2024

Abstract
Aims
Septic arthritis (SA) of the native knee joint is associated with significant morbidity. This review compared post-operative functional outcomes (patient-reported outcome measures (PROMs) and range of movement (ROM)) following arthroscopic washout (AW) and open washout (OW) amongst adult patients with SA of the native knee. The need for further operative intervention was also considered.

Methods
Electronic databases of PubMed, MEDLINE, Embase, Cochrane, Web of Science and Scopus were searched between 16 February 2023 and 18 March 2023. Randomised controlled trials (RCTs) and comparative observational analytic studies comparing function (reflected in PROMs or ROM) at latest follow-up following AW and OW were included. A narrative summary was provided concerning post-operative PROMs. Pooled estimates for mean ROM and re-operation rates were conducted using the random-effects model. The risk of bias was assessed using the Cochrane risk-of-bias assessment tool-2 for RCTs and the Risk of Bias in Non-Randomized Studies of Interventions tool for observational analytic studies.

Results
Of 2580 retrieved citations, 7 articles (1 RCT and 6 cohort studies) met the inclusion criteria. Of these, five had some concerns/moderate risk of bias, and two had serious risk. There was a slight tendency for superior mean PROMs following AW compared with OW, but due to small effect sizes, this was unlikely clinically relevant. Additionally, the use of four different PROMs scales made direct comparisons impossible. AW was associated with superior ROM (mean difference 20.18° (95% CI 14.35, 26.02; p < 0.00001)), whilst there was a tendency for lower re-operation requirements following AW (OR 0.64, 95% CI 0.26, 1.57, p = 0.44).

Conclusions
AW was associated with equivalent to superior post-operative function and lower requirement for further intervention compared with OW. Results need to be interpreted cautiously, taking into consideration the methodological and clinical heterogeneity of the included studies.

Systematic review registration
PROSPERO 2022, CRD42022364062.
Performance and harmonic detection algorithm of phase locked Loop for parallel APF
Authors: Wang Dan , Yang Linsen , Ni Lei 
Published: April 2024

AbstractAs the boost of power electronics technology, the harmonic problem in the power system is becoming increasingly prominent. Fourier decomposition is performed on the load current in the power system, and components with a frequency that is an integer multiple of the fundamental wave are referred to as harmonic components. Harmonic control is essential to establish a safe and reliable power grid environment and provide high-quality and clean electricity to power users. The study focused on parallel active power filters, proposed a specific harmonic detection method on the grounds of synchronous harmonic rotating coordinate system, and developed a phase-locked loop design on the grounds of order generalized integrator. Meanwhile, a compensation current control method on the grounds of space vector pulse width modulation was introduced. The results showed that in the full compensation simulation experiment, the compensated A-phase grid side current waveform was significantly improved and presented a sinusoidal shape. After 0.05 s, the actual output compensation current closely followed the command current. Meanwhile, after compensation, the total harmonic distortion rate decreased from 26.58 to 3.06%. In specific harmonic compensation simulation experiments, when the sum of 5th, 7th, and 11th harmonic components was used as the command current for compensation, the distortion of the current waveform was improved after the load undergoes a sudden change. After compensation, the 5th, 7th, and 11th harmonic content significantly decreased, and the total harmonic distortion rate decreased to 4.08%. This indicated that the proposed phase-locked loop design and harmonic detection method for active power filters had high stability and effectiveness. The study’s primary contribution is to enhance the utilization efficiency of DC voltage and improve the dynamic response ability of current. Additionally, it offers a new method for reducing the impact of harmonics on the power grid and improving power quality. It provided an effective method reference for technological progress in related fields such as power electronics and control engineering.
A modified local thermal non-equilibrium model of transient phase-change transpiration cooling for hypersonic thermal protection
Authors: Jin Kaiyan , Zhao Jin , Yao Guice , Wen Dongsheng 
Published: April 2024

AbstractAiming to efficiently simulate the transient process of transpiration cooling with phase change and reveal the convection mechanism between fluid and porous media particles in a continuum scale, a new two-phase mixture model is developed by incorporating the local thermal non-equilibrium effect. Considering the low-pressure and high overload working conditions of hypersonic flying, the heat and mass transfer induced by capillary and inertial body forces are analyzed for sub-cooled, saturated and super-heated states of water coolant under varying saturation pressures. After the validation of the model, transient simulations for different external factors, including spatially-varied heat flux, coolant mass flux, time-dependent external pressure and aircraft acceleration are conducted. The results show that the vapor blockage patterns at the outlet are highly dependent on the injection mass flux value and the external pressure, and the reduced saturation temperature at low external pressure leads to early boiling off and vapor blockage. The motion of flying has a large influence on the cooling effect, as the inertial force could change the flow pattern of the fluid inside significantly. The comparison of the results from 2-D and 3-D simulations suggests that 3-D simulation shall be conducted for practical application of transpiration cooling, as the thermal protection efficiency may be overestimated by the 2-D results due to the assumption of an infinite width length of the porous plate.