bluuebunny/crossref_metadata_2025_split huggingface dataset:
A nano-cocktail of the PARP inhibitor talazoparib and CDK inhibitor dinaciclib for the treatment of triple negative breast cancer
Authors: Baldwin Paige , Yang Shicheng , Orriols Adrienne , Wang Sherrie , Brown Needa , Sridhar Srinivas 
Published: March 2024

Abstract
Background
The addition of the cyclin dependent kinase inhibitor (CDKi) dinaciclib to Poly-(ADP-ribose) polymerase inhibitor (PARPi) therapy is a strategy to overcome resistance to PARPi in tumors that exhibit homologous recombination (HR) deficiencies as well as to expand PARPi therapy to tumors that do not exhibit HR deficiencies. However, combination therapy using pathway inhibitors has been plagued by an inability to administer doses sufficient to achieve clinical benefit due to synergistic toxicities. Here we sought to combine nanoformulations of the PARPi talazoparib, nTLZ, and the CDKi dinaciclib, nDCB, in a nano-cocktail to enhance therapeutic efficacy while maintaining lower doses.

Methods
Pharmacokinetics of nDCB were assessed to ensure it is compatible with nTLZ. nDCB was combined with nTLZ to generate a nano-cocktail nDCB:nTLZ, which elicits greater cell death in vitro compared to the combination of the free drugs. MDA-MB-231-LUC-D3H2LN xenografts were utilized to assess therapeutic efficacy of the nano-cocktail in terms of tumor progression.

Results
Administration of the nano-cocktail significantly slowed tumor progression in the HR proficient animal model compared to administration of free talazoparib and free dinaciclib at the same doses. Histology of the liver, spleen, and kidneys revealed long-term treatment did not induce nanoparticle associated morphological changes. Complete blood count did not reveal any significant hematologic changes after treatment with either the free combination or nano-cocktail.

Conclusions
The efficacy and toxicity data suggest that further dose escalation can be pursued in order to achieve a stronger response. These data suggest the administration of combination therapy through the nano-cocktail leads to a better response than the use of free compounds and is a promising strategy for implementing combination therapy in the clinic.
Human-derived bacterial strains mitigate colitis via modulating gut microbiota and repairing intestinal barrier function in mice
Authors: Dai Juanjuan , Jiang Mingjie , Wang Xiaoxin , Lang Tao , Wan Leilei , Wang Jingjing 
Published: March 2024

Abstract
Background
Unbalanced gut microbiota is considered as a pivotal etiological factor in colitis. Nevertheless, the precise influence of the endogenous gut microbiota composition on the therapeutic efficacy of probiotics in colitis remains largely unexplored.

Results
In this study, we isolated bacteria from fecal samples of a healthy donor and a patient with ulcerative colitis in remission. Subsequently, we identified three bacterial strains that exhibited a notable ability to ameliorate dextran sulfate sodium (DSS)-induced colitis, as evidenced by increased colon length, reduced disease activity index, and improved histological score. Further analysis revealed that each of Pediococcus acidilactici CGMCC NO.17,943, Enterococcus faecium CGMCC NO.17,944 and Escherichia coli CGMCC NO.17,945 significantly attenuated inflammatory responses and restored gut barrier dysfunction in mice. Mechanistically, bacterial 16S rRNA gene sequencing indicated that these three strains partially restored the overall structure of the gut microbiota disrupted by DSS. Specially, they promoted the growth of Faecalibaculum and Lactobacillus murinus, which were positively correlated with gut barrier function, while suppressing Odoribacter, Rikenella, Oscillibacter and Parasutterella, which were related to inflammation. Additionally, these strains modulated the composition of short chain fatty acids (SCFAs) in the cecal content, leading to an increase in acetate and a decrease in butyrate. Furthermore, the expression of metabolites related receptors, such as receptor G Protein-coupled receptor (GPR) 43, were also affected. Notably, the depletion of endogenous gut microbiota using broad-spectrum antibiotics completely abrogated these protective effects.

Conclusions
Our findings suggest that selected human-derived bacterial strains alleviate experimental colitis and intestinal barrier dysfunction through mediating resident gut microbiota and their metabolites in mice. This study provides valuable insights into the potential therapeutic application of probiotics in the treatment of colitis.
Clostridium butyricum inhibits the inflammation in children with primary nephrotic syndrome by regulating Th17/Tregs balance via gut-kidney axis
Authors: Li Ting , Ma Xiaolong , Wang Ting , Tian Wenyan , Liu Jian , Shen Wenke , Liu Yuanyuan , Li Yiwei , Zhang Xiaoxu , Ma Junbai , Zhang Xiaoxia , Ma Jinhai , Wang Hao 
Published: March 2024

Abstract
Background
Primary nephrotic syndrome (PNS) is a common glomerular disease in children. Clostridium butyricum (C. butyricum), a probiotic producing butyric acid, exerts effective in regulating inflammation. This study was designed to elucidate the effect of C. butyricum on PNS inflammation through the gut-kidney axis.

Method
BALB/c mice were randomly divided into 4 groups: normal control group (CON), C. butyricum control group (CON+C. butyricum), PNS model group (PNS), and PNS with C. butyricum group (PNS+C. butyricum). The PNS model was established by a single injection of doxorubicin hydrochloride (DOX) through the tail vein. After 1 week of modeling, the mice were treated with C. butyricum for 6 weeks. At the end of the experiment, the mice were euthanized and associated indications were investigated.

Results
Since the successful modeling of the PNS, the 24 h urine protein, blood urea nitrogen (BUN), serum creatinine (SCr), urine urea nitrogen (UUN), urine creatinine (UCr), lipopolysaccharides (LPS), pro-inflammatory interleukin (IL)-6, IL-17A were increased, the kidney pathological damage was aggravated, while a reduction of body weights of the mice and the anti-inflammatory IL-10 significantly reduced. However, these abnormalities could be dramatically reversed by C. butyricum treatment. The crucial Th17/Tregs axis in PNS inflammation also was proved to be effectively regulated by C. butyricum treatment. This probiotic intervention notably affected the expression levels of signal transducer and activator of transcription 3 (STAT3), Heme oxygenase-1 (HO-1) protein, and retinoic acid-related orphan receptor gamma t (RORγt). 16S rRNA sequencing showed that C. butyricum could regulate the composition of the intestinal microbial community and found Proteobacteria was more abundant in urine microorganisms in mice with PNS. Short-chain fatty acids (SCFAs) were measured and showed that C. butyricum treatment increased the contents of acetic acid, propionic acid, butyric acid in feces, acetic acid, and valeric acid in urine. Correlation analysis showed that there was a closely complicated correlation among inflammatory indicators, metabolic indicators, microbiota, and associated metabolic SCFAs in the gut-kidney axis.

Conclusion
C. butyricum regulates Th17/Tregs balance via the gut-kidney axis to suppress the immune inflammatory response in mice with PNS, which may potentially contribute to a safe and inexpensive therapeutic agent for PNS.
Integrating genes and metabolites: unraveling mango's drought resilience mechanisms
Authors: Hou Xianbin , Kong Yu , Teng Zheng , Yang Cuifeng , Li Yufeng , Zhu Zhengjie 
Published: March 2024

Abstract
Background
Mango (Mangifera indica L.) faces escalating challenges from increasing drought stress due to erratic climate patterns, threatening yields, and quality. Understanding mango's drought response mechanisms is pivotal for resilience and food security.

Results
Our RNA-seq analyses unveil 12,752 differentially expressed genes linked to stress signaling, hormone regulation, and osmotic adjustment. Weighted Gene Co-expression Network Analysis identified three essential genes—WRKY transcription factor 3, polyamine oxidase 4, and protein MEI2-like 1—as drought defense components. WRKY3 having a role in stress signaling and defense validates its importance. Polyamine oxidase 4, vital in stress adaptation, enhances drought defense. Protein MEI2-like 1's significance emerges, hinting at novel roles in stress responses. Metabolite profiling illuminated Mango’s metabolic responses to drought stress by presenting 990 differentially abundant metabolites, mainly related to amino acids, phenolic acids, and flavonoids, contributing to a deeper understanding of adaptation strategies. The integration between genes and metabolites provided valuable insights by revealing the correlation of WRKY3, polyamine oxidase 4 and MEI2-like 1 with amino acids, D-sphingnosine and 2,5-Dimethyl pyrazine.

Conclusions
This study provides insights into mango's adaptive tactics, guiding future research for fortified crop resilience and sustainable agriculture. Harnessing key genes and metabolites holds promise for innovative strategies enhancing drought tolerance in mango cultivation, contributing to global food security efforts.
Predictors of improvement in left ventricular systolic function after catheter ablation in patients with persistent atrial fibrillation complicated with heart failure
Authors: Zhao Xinliang , Hu Xiaoqin , Bao Wei , Huang Shuo , Li Fei , Liu Chen , Ge Liqi , Zhang Quan , Zhang Chaoqun , Li Chengzong 
Published: March 2024

Abstract
Aims
The current management of patients with atrial fibrillation (AF) and concomitant heart failure (HF) remains a significant challenge. Catheter ablation (CA) has been shown to improve left ventricular ejection fraction (LVEF) in these patients, but which patients can benefit from CA is still poorly understood. The aim of our study was to determine the predictors of improved ejection fraction in patients with persistent atrial fibrillation (PeAF) complicated with HF undergoing CA.

Methods and results
A total of 435 patients with persistent AF underwent an initial CA between January 2019 and March 2023 in our hospital. We investigated consecutive patients with left ventricular systolic dysfunction (LVEF < 50%) measured by transthoracic echocardiography (TTE) within one month before CA. According to the LVEF changes at 6 months, these patients were divided into an improved group (fulfilling the ‘2021 Universal Definition of HF’ criteria for LVEF recovery) and a nonimproved group. Eighty patients were analyzed, and the improvement group consisted of 60 patients (75.0%). In the univariate analysis, left ventricular end-diastolic diameter (P = 0.005) and low voltage zones in the left atrium (P = 0.043) were associated with improvement of LVEF. A receiver operating characteristic analysis determined that the suitable cutoff value for left ventricular end-diastolic diameter (LVDd) was 59 mm (sensitivity: 85.0%, specificity: 55.0%, area under curve: 0.709). A multivariate analysis showed that LVDd (OR = 0.85; 95% CI: 0.76–0.95, P = 0.005) and low voltage zones (LVZs) (OR = 0.26; 95% CI: 0.07–0.96, P = 0.043) were significantly independently associated with the improvement of LVEF. Additionally, parameters were significantly improved regarding the left atrial diameter, LVDd and ventricular rate after radiofrequency catheter ablation (all p < 0.05).

Conclusions
The improvement of left ventricular ejection fraction (LVEF) occurred in 75.0% of patients. Our study provides additional evidence that LVDd < 59 mm and no low voltage zones in the left atrium can be used to jointly predict the improvement of LVEF after atrial fibrillation ablation.
Pre-lacteal feeding practice and associated factors among mothers having children aged less than six months in Dilla town, Southern Ethiopia
Authors: Gashaw Anteneh , Mitku Haymanot 
Published: March 2024

Abstract
Background
Pre-lacteal feeding, the introduction of liquids or non-breast milk foods before establishing regular breastfeeding, poses significant risks to newborns, depriving them of vital nutrients and the protective benefits of colostrum while exposing them to infection hazards. Despite breast milk being a renewable and comprehensive source of infant nutrition for the first six months of life, prevalent in many low income country are pre-lacteal feeds such as honey, sugar-water, jiggery water, castor oil, and goat’s milk. These practices, widespread in such regions, carry potential risks of infection and aspiration. The objective of this study is to assess the prevalence of pre-lacteal feeding and identify associated factors among mothers with children under six months in Dilla Town, Southern Ethiopia.

Method
A community-based cross-sectional study took place in Dilla town, southern Ethiopia, spanning from June 20 to August 20, 2022. The study included a total of 372 participants, selected through simple random sampling for kebele and systematic random sampling for individual participants. Data was collected using interviewer-administered structured questionnaires and subsequently coded, entered, cleaned, and edited using SPSS version 23.0 software. The presentation of data utilized tables and figures, followed by a logistic regression analysis to identify potential factors associated with pre-lacteal feeding. The significance level was set at a p-value less than 0.05 for the final model.

Result
The prevalence of pre-lacteal feeding practice was 176 (47.3%) in the study area and having no maternal education (AOR = 3.68, 95% CI; [1.01–5.84] colostrum avoidance (AOR = 4.20, 95% CI; [2.03–6.86] and lack of breast feeding counseling (AOR = 2.00, 95% CI; 1.40–2.57), were factors associated with pre-lacteal feeding practices.

Conclusion and recommendation
Pre-lacteal feeding practice among mothers of children aged less than 6 months in Dilla town was found to be higher than the national prevalence. No formal education, colostrum avoidance, lack of breastfeeding counseling, were factors associated with pre-lacteal feeding practices. So awareness creation activities on the risks of PLF (pre-lacteal feeding) and improving breastfeeding counseling targeted to all mothers and care givers including their families within the study area is vital.
Spontaneous tumor lysis syndrome (STLS) during biopsy for burkitt lymphoma: a case report
Authors: Pan Sirui , Shen Qiyang , Zhou Jianfeng , Li Tao 
Published: March 2024

Abstract
Background
Tumor lysis syndrome (TLS) is a hematologic oncological emergency characterized by metabolic and electrolyte imbalances. On breakdown of tumor cells, enormous amounts of potassium, phosphate, and nucleic acids are released into systemic circulation. TLS mainly occurs during chemotherapy. However, there are rare incidences of spontaneous tumor lysis syndrome (STLS) prior to commencement of therapy.

Case presentation
In the case being reported, the child had just undergone a biopsy. As the incision was being closed, there was a sudden onset of high fever, arrhythmia, severe hyperkalemia, hypocalcemia, and acidosis. Following timely symptomatic treatment and continuous renal replacement therapy(CRRT), the child’s laboratory results improved, and organ function was restored to normal. The final pathological diagnosis confirmed Burkitt lymphoma. The boy is currently on maintenance chemotherapy.

Conclusions
TLS is a potentially life-threatening complication in hematologic oncology. Several important conclusions can be drawn from this case, reminding clinicians to: (1) be fully aware of the risk factors of TLS and evaluate the level of risk; (2) pay attention to the possibility of STLS during operation, if surgical procedures are necessary and operate with minimal trauma and in the shortest time possibly; (3) take preoperative prophylaxis actively for high-risk TLS patients, including aggressive fluid management and rational use of diuretics and uric-acid-lowering drugs. In addition, this case confirms the effectiveness of CRRT for severe STLS.
The effect of cuff arthropathy stage on sleep disturbance and kinesiophobia in reverse shoulder arthroplasty patients
Authors: Ilyas Gokhan , Egeli Ercument , Ipci Fikri Burak , Gokalp Oguzhan 
Published: March 2024

Abstract
Background
The current study aimed to determine the changes in pre-and post-operative Pittsburg sleep quality index (PSQI) and Tampa scale of kinesiophobia (TSK) values ​​according to the Hamada classification in patients who underwent reverse shoulder arthroplasty (RSA) for rotator cuff tear arthropathy (RCTA).

Methods
One hundred and eight patients who underwent RSA for RCTA were reviewed retrospectively. The patients were divided into two groups with low grade (stages 1-2-3) (n = 49) and high grade (stages 4a-4b-5) (n = 59) according to the Hamada classification, which is the radiographic evaluation of RCTA. PSQI and TSK values ​​were calculated preoperatively, and post-operatively at the 6th week, 6th month, and 1st year. The change in PSQI and TSK values ​​between the evaluations and the effect of staging according to the Hamada classification on this change was examined.

Results
When compared in preoperative evaluations, PSQI and TSK scores were found to be lower in low-grade group 1 (7.39 ± 1.56, 51.88 ± 4.62, respectively) than in high-grade group 2 (10.47 ± 2.39, 57.05 ± 3.25, respectively) according to Hamada classification (both p < 0.001). In the postoperative evaluations, PSQI and TSK results decreased gradually compared to the preoperative evaluations, and there was a severe decrease in both parameters between the 6th-week and 6th-month evaluations (both p < 0.001). Preoperatively, 102 (95%) patients had sleep disturbance (PSQI ≥ 6), and 108 (100%) patients had high kinesiophobia (TSK > 37). In the 1st year follow-ups, sleep disturbance was observed in 5 (5%) patients and kinesiophobia in 1 (1%) patient. When the Hamada stages were compared, it was seen that there was a significant difference before the operation (both p < 0.001), but the statistically significant difference disappeared in the PSQI value in the 1st year (p = 0.092) and in the TSK value in the 6th month (p = 0.164) post-operatively. It was observed that Hamada staging caused significant differences in PSQI and TSK values ​​in the preoperative period but did not affect the clinical results after treatment.

Conclusions
RSA performed based on RCTA improves sleep quality and reduces kinesiophobia. RCTA stage negatively affects PSQI and TSK before the operation but does not show any effect after the treatment.
Identification of allograft inflammatory factor-1 suppressing the progression and indicating good prognosis of osteosarcoma
Authors: Liu Wenda , Shi Tao , Zheng Di , Ke Guangshui , Chen Jingteng 
Published: March 2024

Abstract
Background
Osteosarcoma is one of the most common cancers worldwide. Intense efforts have been made to elucidate the pathogeny, but the mechanisms of osteosarcoma are still not well understood. We aimed to investigate the potential biomarker, allograft inflammatory factor-1 (AIF1), affecting the progression and prognosis of osteosarcoma.

Methods
Three microarray datasets were downloaded from GEO datasets and one was obtained from the TCGA dataset. The differentially expressed genes (DEGs) were identified. GO and KEGG functional enrichment analyses of overlapped DEGs were performed. The PPI network of overlapped DEGs was constructed by STRING and visualized with Cytoscape. Overall survival (OS) and Metastasis free survival (MFS) were analyzed from GSE21257. Finally, the effect of the most relevant core gene affecting the progression of osteosarcoma was examined in vitro.

Results
One hundred twenty six DEGs were identified, consisting of 65 upregulated and 61 downregulated genes. Only AIF1 was significantly associated with OS and MFS. It was found that AIF1 could be enriched into the NF-κB signaling pathway. GSEA and ssGSEA analyses showed that AIF1 was associated with the immune invasion of tumors. Cell experiments showed that AIF1 was underexpressed in osteosarcoma cell lines, while the malignant propriety was attenuated after overexpressing the expression of AIF1. Moreover, AIF1 also affects the expression of the NF-κB pathway.

Conclusion
In conclusion, DEGs and hub genes identified in the present study help us understand the molecular mechanisms underlying the carcinogenesis and progression of osteosarcoma, and provide candidate targets for diagnosis and treatment of osteosarcoma.
A review of the clinical efficacy of FDA-approved antibody‒drug conjugates in human cancers
Authors: Liu Kaifeng , Li Meijia , Li Yudong , Li Yutong , Chen Zixin , Tang Yiqi , Yang Meitian , Deng Guoquan , Liu Hongwei 
Published: March 2024

AbstractWhile strategies such as chemotherapy and immunotherapy have become the first-line standard therapies for patients with advanced or metastatic cancer, acquired resistance is still inevitable in most cases. The introduction of antibody‒drug conjugates (ADCs) provides a novel alternative. ADCs are a new class of anticancer drugs comprising the coupling of antitumor mAbs with cytotoxic drugs. Compared with chemotherapeutic drugs, ADCs have the advantages of good tolerance, accurate target recognition, and small effects on noncancerous cells. ADCs occupy an increasingly important position in the therapeutic field. Currently, there are 13 Food and Drug Administration (FDA)‒approved ADCs and more than 100 ADC drugs at different stages of clinical trials. This review briefly describes the efficacy and safety of FDA-approved ADCs, and discusses the related problems and challenges to provide a reference for clinical work.
A novel microglia-targeting strategy based on nanoparticle-mediated delivery of miR-26a-5p for long-lasting analgesia in chronic pain
Authors: Lu Yitian , Liu Shuai , Wang Peng , Guo Xiangna , Qin Zaisheng , Hou Honghao , Tao Tao 
Published: March 2024

AbstractAccumulating evidence supports the notion that microglia play versatile roles in different chronic pain conditions. However, therapeutic strategies of chronic pain by targeting microglia remain largely overlooked. This study seeks to develop a miRNA-loaded nano-delivery system by targeting microglia, which could provide a decent and long-lasting analgesia for chronic pain. Surface aminated mesoporous silica nanoparticles were adopted to load miR-26a-5p, a potent analgesic miRNA, by electrostatic adsorption, which can avoid miR-26a-5p is rapidly released and degraded. Then, targeting peptide MG1 was modified on the surface of aminated mesoporous silica particles for microglia targeting. In peripheral nerve injury induced neuropathic pain model, a satisfactory anti-allodynia effect with about 6 weeks pain-relief duration were achieved through targeting microglia strategy, which decreased microglia activation and inflammation by Wnt5a, a non-canonical Wnt pathway. In inflammatory pain and chemotherapy induced peripheral neuropathic pain, microglia targeting strategy also exhibited more efficient analgesia and longer pain-relief duration than others. Overall, we developed a microglia-targeting nano-delivery system, which facilitates precisely miR-26a-5p delivery to enhance analgesic effect and duration for several chronic pain conditions.
Graphical Abstract