bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of first-line pharmacological treatments for reproductive outcomes in infertile women with PCOS: a systematic review and network meta-analysis
Authors: Peng Ge , Yan Zhe , Liu Yuqi , Li Juan , Ma Jinfang , Tong Nanwei , Wang Yan 
Published: March 2023

AbstractBackgroundPolycystic ovarian syndrome (PCOS) is one of the most common causes of infertility in reproductive-age women. However, the efficacy and optimal therapeutic strategy for reproductive outcomes are still under debate. We conducted a systematic review and network meta-analysis to compare the efficacy of different first-line pharmacological therapies in terms of reproductive outcomes for women with PCOS and infertility.MethodsA systematic retrieval of databases was conducted, and randomized clinical trials (RCTs) of pharmacological interventions for infertile PCOS women were included. The primary outcomes were clinical pregnancy and live birth, and the secondary outcomes were miscarriage, ectopic pregnancy and multiple pregnancy. A network meta-analysis based on a Bayesian model was performed to compare the effects of the pharmacological strategies.ResultsA total of 27 RCTs with 12 interventions were included, and all therapies tended to increase clinical pregnancy, especially pioglitazone (PIO) (log OR 3.14, 95% CI 1.56 ~ 4.70, moderate confidence), clomiphene citrate (CC) + exenatide (EXE) (2.96, 1.07 ~ 4.82, moderate confidence) and CC + metformin (MET) + PIO (2.82, 0.99 ~ 4.60, moderate confidence). Moreover, CC + MET + PIO (2.8, -0.25 ~ 6.06, very low confidence) could increase live birth most when compared to placebo, even without a significant difference. For secondary outcomes, PIO showed a tendency to increase miscarriage (1.44, -1.69 ~ 5.28, very low confidence). MET (-11.25, -33.7 ~ 0.57, low confidence) and LZ + MET (-10.44, -59.56 ~ 42.11, very low confidence) were beneficial for decreasing ectopic pregnancy. MET (0.07, -4.26 ~ 4.34, low confidence) showed a neutral effect in multiple pregnancy. Subgroup analysis demonstrated no significant difference between these medications and placebo in obese participants.ConclusionsMost first-line pharmacological treatments were effective in improving clinical pregnancy. CC + MET + PIO should be recommended as the optimal therapeutic strategy to improve pregnancy outcomes. However, none of the above treatments had a beneficial effect on clinical pregnancy in obese PCOS.Trial registrationCRD42020183541; 05 July 2020
Induction of DNMT1-dependent demethylation of SHP-1 by the natural flavonoid compound Baicalein overcame Imatinib-resistance in CML CD34+ cells
Authors: Xu Xuefen , Ji Shufan , Chen Yuan , Xia Siwei , Li Yang , Chen Li , Li Yujia , Zhang Feng , Zhang Zili , Zheng Shizhong 
Published: March 2023

Abstract
Background
The most significant cause of treatment failure in chronic myeloid leukemia (CML) is a persistent population of minimal residual cells. Emerging evidences showed that methylation of SHP-1 contributed to Imatinib (IM) resistance. Baicalein was reported to have an effect on reversal of chemotherapeutic agents resistance. However, the molecular mechanism of Baicalein on JAK2/STAT5 signaling inhibition against drug resistance in bone marrow (BM) microenvironment that had not been clearly revealed.

Methods
We co-cultured hBMSCs and CML CD34+ cells as a model of SFM-DR. Further researches were performed to clarify the reverse mechanisms of Baicalein on SFM-DR model and engraftment model. The apoptosis, cytotoxicity, proliferation, GM-CSF secretion, JAK2/STAT5 activity, the expression of SHP-1 and DNMT1 were analyzed. To validate the role of SHP-1 on the reversal effect of Baicalein, the SHP-1 gene was over-expressed by pCMV6-entry shp-1 and silenced by SHP-1 shRNA, respectively. Meanwhile, the DNMT1 inhibitor decitabine was used. The methylation extent of SHP-1 was evaluated using MSP and BSP. The molecular docking was replenished to further explore the binding possibility of Baicalein and DNMT1.

Results
BCR/ABL-independent activation of JAK2/STAT5 signaling was involved in IM resistance in CML CD34+ subpopulation. Baicalein significantly reversed BM microenvironment-induced IM resistance not through reducing GM-CSF secretion, but interfering DNMT1 expression and activity. Baicalein induced DNMT1-mediated demethylation of the SHP-1 promoter region, and subsequently activated SHP-1 re-expression, which resulted in an inhibition of JAK2/STAT5 signaling in resistant CML CD34+ cells. Molecular docking model indicated that DNMT1 and Baicalein had binding pockets in 3D structures, which further supported Baicalein might be a small-molecule inhibitor targeting DNMT1.

Conclusions
The mechanism of Baicalein on improving the sensitivity of CD34+ cells to IM might be correlated with SHP-1 demethylation by inhibition of DNMT1 expression. These findings suggested that Baicalein could be a promising candidate by targeting DNMT1 to eradicate minimal residual disease in CML patients.
CD206+ tumor-associated macrophages interact with CD4+ tumor-infiltrating lymphocytes and predict adverse patient outcome in human laryngeal squamous cell carcinoma
Authors: Heng Yu , Zhu Xiaoke , Lin Hanqing , jingyu Ma , Ding Xuping , Tao Lei , Lu Liming 
Published: March 2023

Abstract
Background
Tumor-associated macrophages (TAMs) are major component in the tumor microenvironment (TME) and play regulatory role in tumor progression. We aimed to investigate the infiltration and prognostic value of TAMs in laryngeal squamous cell carcinoma (LSCC) and to reveal the underlying mechanism of TAM subgroups in tumorigenesis.

Methods
Hematoxylin and eosin (HE) staining were performed to define the tumor nest and stroma of LSCC tissue microarrays. CD206 + /CD163 + and iNOS + TAM infiltrating profiles were obtained and analyzed through double-labeling immunofluorescence and immunohistochemical staining. The recurrence-free (RFS) and overall survival (OS) curves based on the infiltration of TAMs were plotted using the Kaplan-Meier method. Infiltration of macrophages, T lymphocytes and their corresponding subgroups were analyzed in fresh LSCC tissue samples by flow cytometry.

Results
We found that CD206+ rather than CD163+ M2-like TAMs were the most enriched population in the TME of human LSCC. CD206+ macrophages localized mostly in the tumor stroma (TS) rather than the tumor nest (TN) region. In contrast, relatively low infiltration of iNOS+ M1-like TAMs were found in the TS and almost none in the TN region. High level of TS CD206+ TAM infiltration correlated with poor prognosis. Interestingly, we identified a HLA-DRhigh CD206+ macrophage subgroup that was significantly associated with the tumor-infiltrating CD4+ T lymphocytes and showed different surface costimulatory molecule expression than that of the HLA-DRlow/-CD206+ subgroup. Taken together, our results indicate that HLA-DRhigh-CD206+ is a highly activated subgroup of CD206 + TAMs that may interact with CD4 + T cells through MHC-II axis and promote tumorigenesis.
Speed and quality of interbody fusion in porous bioceramic Al2O3 and polyetheretherketone cages for anterior cervical discectomy and fusion: a comparative study
Authors: Kostysyn Roman , Ryska Pavel , Jandura Jiri , Selke-Krulichova Iva , Poczos Pavel , Hosszu Tomas , Cesak Tomas 
Published: March 2023

Abstract
Background
The objective of this prospective randomized monocentric study is to compare the speed and quality of interbody fusion of implanted porous Al2O3 (aluminium oxide) cages with PEEK (polyetheretherketone) cages in ACDF (anterior cervical discectomy and fusion).

Materials and methods
A total of 111 patients were enrolled in the study, which was carried out between 2015 and 2021. The 18-month follow-up (FU) was completed in 68 patients with an Al2O3 cage and 35 patients with a PEEK cage in one-level ACDF. Initially, the first evidence (initialization) of fusion was evaluated on computed tomography. Subsequently, interbody fusion was evaluated according to the fusion quality scale, fusion rate and incidence of subsidence.

Results
Signs of incipient fusion at 3 months were detected in 22% of cases with the Al2O3 cage and 37.1% with the PEEK cage. At 12-month FU, the fusion rate was 88.2% for Al2O3 and 97.1% for PEEK cages, and at the final FU at 18 months, 92.6% and 100%, respectively. The incidence of subsidence was observed to be 11.8% and 22.9% of cases with Al2O3 and PEEK cages, respectively.

Conclusions
Porous Al2O3 cages demonstrated a lower speed and quality of fusion in comparison with PEEK cages. However, the fusion rate of Al2O3 cages was within the range of published results for various cages. The incidence of subsidence of Al2O3 cages was lower compared to published results. We consider the porous Al2O3 cage as safe for a stand-alone disc replacement in ACDF.
How high is the quality of the videos about children's elbow fractures on Youtube?
Authors: Kıvrak Aybars , Ulusoy İbrahim 
Published: March 2023

Abstract
Objective
Pediatric elbow fractures are children's most common fractures. People use the internet to get information about their illnesses and also to search for treatment options. Videos uploaded to Youtube do not go through the review process. The aim of our study is to determine the quality of videos related to child elbow fractures on Youtube.

Material method
The study was carried out with the data obtained from the video-sharing site www.youtube.com on 01.12.2022. Pediatric elbow fractures are written in the search engine section. Information about the number of views of the videos, upload date, view rate (number of views per day), number of comments, number of likes and dislikes, duration, whether they contain animation and the publishing source were evaluated. The videos are divided into 5 groups according to their sources: medical society/non-profit organization, physician, healthrelated website, university/academic, and patient/independent user/other. The quality of the videos was evaluated using the Global Quality Scale (GQS). All videos have been evaluated by 2 researchers.

Results
In the study, 50 videos were included. In the statistical evaluation, no significant correlation was found between the modified discern score and GQS found by both researchers, and the number of views, the rate of views, comments, likes and dislikes, video duration and VPI. In addition, when the GQS and modified discern scores were compared according to the source of the video, it was found that the patient/independent user/other group scores were lower numerically, but there was no statistically significant difference in comparison.

Conclusion
Most of the videos about child elbow fractures have been uploaded by healthcare professionals. Therefore, we concluded that the videos are quite informative in terms of accurate information and quality content.
Novel agents and regimens in acute myeloid leukemia: latest updates from 2022 ASH Annual Meeting
Authors: DiNardo Katherine W. , LeBlanc Thomas W. , Chen Hui 
Published: March 2023

AbstractDevelopments in investigational agents and novel regimens in acute myeloid leukemia (AML) were reported in the 2022 American Society of Hematology (ASH) annual meeting. Encouraging efficacy data were presented from first-in-human studies of two investigational menin inhibitors, SNDX-5613 and KO-539, in relapsed and refractory (R/R) acute myeloid leukemia (AML) with KMT2A rearrangement or mutant NPM1, with overall response rates (ORR) of 53% (32/60) and 40% (8/20), respectively. The addition of the novel drug pivekimab sunirine, a first-in-class antibody–drug conjugate targeting CD123, to azacitidine and venetoclax in R/R AML resulted in an ORR of 45% (41/91), which rose to 53% in those who were venetoclax naïve. Additional novel triplet treatment combinations included the addition of magrolimab, an anti-CD47 antibody, to azacitidine and venetoclax, with an ORR of 81% (35/43) in newly diagnosed AML, including an ORR of 74% (20/27) in TP53 mutated AML. The addition of the FLT3 inhibitor gilteritinib to azacitidine/venetoclax was also featured, with an ORR of 100% (27/27) in newly diagnosed AML and an ORR of 70% (14/20) in R/R AML.
NAD pool as an antitumor target against cancer stem cells in head and neck cancer
Authors: Navas Lola E. , Blanco-Alcaina Elena , Suarez-Martinez Elisa , Verdugo-Sivianes Eva M. , Espinosa-Sanchez Asuncion , Sanchez-Diaz Laura , Dominguez-Medina Eduardo , Fernandez-Rozadilla Ceres , Carracedo Angel , Wu Lindsay E. , Carnero Amancio 
Published: March 2023

SummaryHead and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumors that affect different anatomical locations. Despite this heterogeneity, HNSCC treatment depends on the anatomical location, TNM stage and resectability of the tumor. Classical chemotherapy is based on platinum-derived drugs (cisplatin, carboplatin and oxaliplatin), taxanes (docetaxel, paclitaxel) and 5-fluorouracil1. Despite advances in HNSCC treatment, the rate of tumor recurrence and patient mortality remain high. Therefore, the search for new prognostic identifiers and treatments targeting therapy-resistant tumor cells is vital. Our work demonstrates that there are different subgroups with high phenotypic plasticity within the CSC population in HNSCC. CD10, CD184, and CD166 may identify some of these CSC subpopulations with NAMPT as a common metabolic gene for the resilient cells of these subpopulations. We observed that NAMPT reduction causes a decrease in tumorigenic and stemness properties, migration capacity and CSC phenotype through NAD pool depletion. However, NAMPT-inhibited cells can acquire resistance by activating the NAPRT enzyme of the Preiss-Handler pathway. We observed that coadministration of the NAMPT inhibitor with the NAPRT inhibitor cooperated inhibiting tumor growth. The use of an NAPRT inhibitor as an adjuvant improved NAMPT inhibitor efficacy and reduced the dose and toxicity of these inhibitors. Therefore, it seems that the reduction in the NAD pool could have efficacy in tumor therapy. This was confirmed by in vitro assays supplying the cells with products of inhibited enzymes (NA, NMN or NAD) and restoring their tumorigenic and stemness properties. In conclusion, the coinhibition of NAMPT and NAPRT improved the efficacy of antitumor treatment, indicating that the reduction in the NAD pool is important to prevent tumor growth.
Identification of specific susceptibility loci for the early-onset colorectal cancer
Authors: Wang Haoxue , Cai Yimin , Jin Meng , Huang Chao Qun , Ning Caibo , Niu Siyuan , Fan Linyun , Li Bin , Zhang Ming , Lu Zequn , Dong Xuesi , Luo Zilin , Zhong Rong , Li Heng , Zhu Ying , Miao Xiaoping , Yang Xiaojun , Chang Jiang , Li Ni , Tian Jianbo 
Published: March 2023

Abstract
Background
The incidence of early-onset colorectal cancer (EOCRC; patients < 50 years old) has been rising rapidly, whereas the EOCRC genetic susceptibility remains incompletely investigated. Here, we aimed to systematically identify specific susceptible genetic variants for EOCRC.

Methods
Two parallel GWASs were conducted in 17,789 CRC cases (including 1490 EOCRC cases) and 19,951 healthy controls. A polygenic risk score (PRS) model was built based on identified EOCRC-specific susceptibility variants by using the UK Biobank cohort. We also interpreted the potential biological mechanisms of the prioritized risk variant.

Results
We identified 49 independent susceptibility loci that were significantly associated with the susceptibility to EOCRC and the diagnosed age of CRC (both P < 5.0×10−4), replicating 3 previous CRC GWAS loci. There are 88 assigned susceptibility genes involved in chromatin assembly and DNA replication pathways, mainly associating with precancerous polyps. Additionally, we assessed the genetic effect of the identified variants by developing a PRS model. Compared to the individuals in the low genetic risk group, the individuals in the high genetic risk group have increased EOCRC risk, and these results were replicated in the UKB cohort with a 1.63-fold risk (95% CI: 1.32–2.02, P = 7.67×10−6). The addition of the identified EOCRC risk loci significantly increased the prediction accuracy of the PRS model, compared to the PRS model derived from the previous GWAS-identified loci. Mechanistically, we also elucidated that rs12794623 may contribute to the early stage of CRC carcinogenesis via allele-specific regulating the expression of POLA2.

Conclusions
These findings will broaden the understanding of the etiology of EOCRC and may facilitate the early screening and individualized prevention.

Graphical Abstract
DNA methylation landscape reveals LIN7A as a decitabine-responsive marker in patients with t(8;21) acute myeloid leukemia
Authors: He Shujiao , Li Yan , Shi Xuanren , Wang Lei , Cai Diya , Zhou Jingfeng , Yu Li 
Published: March 2023

Abstract
Background
Despite its inconsistent response rate, decitabine, a demethylating agent, is often used as a non-intensive alternative therapeutic agent for acute myeloid leukemia (AML). It has been reported that relapsed/refractory AML patients with t(8;21) translocation achieved better clinical outcomes with a decitabine-based combination regimen than other AML subtypes; however, the mechanisms underlying this phenomenon remain unknown. Herein, the DNA methylation landscape of de novo patients with the t(8;21) translocation was compared with that of patients without the translocation. Moreover, the methylation changes induced by decitabine-based combination regimens in de novo/complete remission paired samples were investigated to elucidate the mechanisms underlying the better responses observed in t(8;21) AML patients treated with decitabine.

Methods
Thirty-three bone marrow samples from 28 non-M3 AML patients were subjected to DNA methylation sequencing to identify the differentially methylated regions and genes of interest. TCGA-AML Genome Atlas-AML transcriptome dataset was used to identify decitabine-sensitive genes that were downregulated following exposure to a decitabine-based regimen. In addition, the effect of decitabine-sensitive gene on cell apoptosis was examined in vitro using Kasumi-1 and SKNO-1 cells.

Results
A total of 1377 differentially methylated regions that specifically responsive to decitabine in t(8;21) AML were identified, of which 210 showed hypomethylation patterns following decitabine treatment aligned with the promoter regions of 72 genes. And the methylation-silencing genes, LIN7A, CEBPA, BASP1, and EMB were identified as critical decitabine-sensitive genes in t(8;21) AML. Moreover, AML patients with hypermethylated LIN7A and reduced LIN7A expression had poor clinical outcomes. Meanwhile, the downregulation of LIN7A inhibited decitabine/cytarabine combination treatment-induced apoptosis in t(8;21) AML cells in vitro.

Conclusion
The findings of this study suggest that LIN7A is a decitabine-sensitive gene in t(8;21) AML patients that may serve as a prognostic biomarker for decitabine-based therapy.
Multiple maxillary periodontal abscesses as a manifestation of post-coronavirus disease 2019 mucormycosis: a case report
Authors: Khoshkhou Hossein , Hasheminasab Mahboube , Goudarzi Pour Daryoush , Jamali Raika , Morshedzadeh Tehrani Ghazal , Moslemi Neda 
Published: March 2023

Abstract
Background
Coronavirus disease 2019 makes patients more susceptible to superinfection of fungal disease as a consequence of immunological system impairment. Mucormycosis is a fungal infection that is rare but has a high mortality rate and mostly affects patients with poorly controlled diabetes mellitus or those receiving corticosteroids.

Case presentation
Here, we present a case of post-coronavirus disease 2019 mucormycosis in a 37-year-old Persian male presenting with multiple periodontal abscess with purulent discharge and necrosis of maxillary bone (without oroantral communication). Surgical debridement following antifungal therapy was the treatment of choice.

Conclusion
Early diagnosis and immediate referral are the cornerstone of comprehensive treatment.
Modeling drug-induced liver injury and screening for anti-hepatofibrotic compounds using human PSC-derived organoids
Authors: Wu Xiaoshan , Jiang Dacheng , Yang Yi , Li Shuang , Ding Qiurong 
Published: March 2023

AbstractPreclinical models that can accurately predict the toxicity and efficacy of candidate drugs to human liver tissue are in urgent need. Human liver organoid (HLO) derived from human pluripotent stem cells offers a possible solution. Herein, we generated HLOs, and demonstrated the utility of these HLOs in modeling a diversity of phenotypes associated with drug-induced liver injury (DILI), including steatosis, fibrosis, and immune responses. Phenotypic changes in HLOs after treatment with tool compounds such as acetaminophen, fialuridine, methotrexate, or TAK-875 showed high concordance with human clinical data in drug safety testings. Moreover, HLOs were able to model liver fibrogenesis induced by TGFβ or LPS treatment. We further devised a high-content analysis system, and established a high-throughput anti-fibrosis drug screening system using HLOs. SD208 and Imatinib were identified that can significantly suppress fibrogenesis induced by TGFβ, LPS, or methotrexate. Taken together, our studies demonstrated the potential applications of HLOs in drug safety testing and anti-fibrotic drug screening.
VMD and self-attention mechanism-based Bi-LSTM model for fault detection of optical fiber composite submarine cables
Authors: Lu Jie , Feng Wenjiang , Li Yuan , Zhang Juntao , Zou Yongqi , Li Jingfu 
Published: March 2023

AbstractAs the main electrical equipment of offshore power grids, optical fiber composite submarine cables undertake the task of power transmission and data communication. In order to ensure the proper functioning of the submarine cable, it is necessary to analyze the working state of it and identify the fault event. This paper proposes a fault detection method for submarine cables, that is, the VMD and self-attention-based Bi-LSTM model. First, we use ANSYS software to generate the vibration waveforms of three main fault events of optical fiber composite submarine cables. Then, by generating the detection matrix of background noise and the vibration waveforms, it can realize the orientation and detection of fault events in single submarine cable. In addition, the vibration signal can be decomposed into IMF components using variational mode decomposition (VMD) for feature extraction. Moreover, the IMF components are input to the self-attention layer for feature fusion and Bi-LSTM module for further feature extraction. Finally, the result of the fault detection is output through the classification layer. According to the comparative experiment and the ablation experiment, the proposed model has proved to outperform the other benchmark models and is robust and stable under the condition of different signal-to-noise ratios.