bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of upregulated exosomal miRNAs between A2780 and A2780/DDP human ovarian cancer cells by high-throughput sequencing
Authors: Wang Huihui , Liu Li , Liu Qinying , Zheng Jianfeng , Zheng Qiuhong , Chen Yuwei , Xia Hongmei , Wu Qiaoling , Sun Yang 
Published: May 2023

AbstractExosomal miRNAs are known to play important roles in ovarian cancer and chemotherapeutic resistance. However, a systematic evaluation of characteristics of exosomal miRNAs involved in cisplatin resistance in ovarian cancer remains totally unclear. Exosomes (Exo-A2780, Exo-A2780/DDP) were extracted from cisplatin-sensitive cells (A2780) and cisplatin-resistant cells (A2780/DDP). Differential exosomal miRNA expression profiles were found by high-throughput sequencing (HTS). Target genes of the exo-miRNAs were predicted by using two online databases to increase the prediction accuracy. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were utilized to find biological relationships with chemoresistance. RT‒qPCR of three exosomal miRNAs was performed, and a protein‒protein interaction (PPI) network was established to identify the hub genes. The GDSC database was used to prove the association between hsa-miR-675-3p expression and the IC50 value. An integrated miRNA–mRNA network was constructed to predict miRNA–mRNA associations. The connection between hsa-miR-675-3p and ovarian cancer was discovered by immune microenvironment analyses. The upregulated exosomal miRNAs could regulate gene targets through signalling pathways such as the Ras, PI3K/Akt, Wnt, and ErbB pathways. GO and KEGG analyses indicated that the target genes were involved in protein binding, transcription regulator activity and DNA binding. The RT‒qPCR results were consistent with the HTS data, and the results of PPI network analysis suggested that FMR1 and CD86 were the hub genes. GDSC database analysis and construction of the integrated miRNA–mRNA network suggested that hsa-miR-675-3p was associated with drug resistance. Immune microenvironment analyses showed that hsa-miR-675-3p was crucial in ovarian cancer. The study suggested that exosomal hsa-miR-675-3p is a potential target for treating ovarian cancer and overcoming cisplatin resistance.
Lymphocyte-activation gene 3 protein expression in tumor-infiltrating lymphocytes is associated with a poor prognosis of ovarian clear cell carcinoma
Authors: Zaitsu Sumika , Yano Mitsutake , Adachi Sawako , Miwa Maiko , Katoh Tomomi , Kawano Yasushi , Yasuda Masanori 
Published: May 2023

Abstract
Background
Histological analysis has revealed the need for new treatment techniques for epithelial ovarian cancer. Immune checkpoint inhibitors may be a new therapeutic strategy for ovarian clear cell carcinoma (OCCC). Lymphocyte-activation gene 3 (LAG-3), an immune checkpoint, is a poor prognostic factor and a new therapeutic target for several malignancies. In this study, we demonstrated the correlation between LAG-3 expression and the clinicopathological features of OCCC. We evaluated LAG-3 expression in tumor-infiltrating lymphocytes (TILs) via immunohistochemical analysis using tissue microarrays containing surgically resected specimens from 171 patients with OCCC.

Results
The number of LAG-3-positive cases was 48 (28.1%), whereas the number of LAG-3-negative cases was 123 (71.9%). LAG-3 expression significantly increased in patients with advanced stages (P = 0.036) and recurrence (P = 0.012); however, its expression did not correlate with age (P = 0.613), residual tumor (P = 0.156), or death (P = 0.086). Using the Kaplan − Meier method, LAG-3 expression was found to be correlated with poor overall survival (P = 0.020) and progression-free survival (P = 0.019). Multivariate analysis revealed LAG-3 expression (hazard ratio [HR] = 1.86; 95% confidence interval [CI], 1.00 − 3.44, P = 0.049) and residual tumor (HR = 9.71; 95% CI, 5.13 − 18.52, P < 0.001) as independent prognostic factors.

Conclusion
Our study demonstrated that LAG-3 expression in patients with OCCC may be a useful biomarker for the prognosis of OCCC and could serve as a new therapeutic target.
Multidrug resistant 1 (MDR1) C3435T and G2677T gene polymorphism: impact on the risk of acute rejection in pediatric kidney transplant recipients
Authors: Korkor Mai S , el-desoky Tarek , Mosaad Youssef M , Salah Doaa M. , Hammad Ayman 
Published: May 2023

Abstract
Background
Tacrolimus is the backbone drug in kidney transplantation. Single nucleotide polymorphism of Multidrug resistant 1 gene can affect tacrolimus metabolism consequently it can affect tacrolimus trough level and incidence of acute rejection. The aim of this study is to investigate the impact of Multidrug resistant 1 gene, C3435T and G2677T Single nucleotide polymorphisms on tacrolimus pharmacokinetics and on the risk of acute rejection in pediatric kidney transplant recipients.

Methods
Typing of Multidrug resistant 1 gene, C3435T and G2677T gene polymorphism was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for 83 pediatric kidney transplant recipients and 80 matched healthy controls.

Results
In Multidrug resistant 1 gene (C3435T), CC, CT genotypes and C allele were significantly associated with risk of acute rejection when compared to none acute rejection group (P = 0.008, 0.001 and 0.01 respectively). The required tacrolimus doses to achieve trough level were significantly higher among CC than CT than TT genotypes through the 1st 6 months after kidney transplantation. While, in Multidrug resistant 1 gene (G2677T), GT, TT genotypes and T allele were associated with acute rejection when compared to none acute rejection (P = 0.023, 0.033 and 0.028 respectively). The required tacrolimus doses to achieve trough level were significantly higher among TT than GT than GG genotypes through the 1st 6 months after kidney transplantation.

Conclusion
The C allele, CC and CT genotypes of Multidrug resistant 1 gene (C3435T) and the T allele, GT and TT genotypes of Multidrug resistant 1 gene (G2677T) gene polymorphism may be risk factors for acute rejection and this can be attributed to their effect on tacrolimus pharmacokinetics. Tacrolimus therapy may be tailored according to the recipient genotype for better outcome.
The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase
Authors: Monte-Serrano Eva , Morejón-García Patricia , Campillo-Marcos Ignacio , Campos-Díaz Aurora , Navarro-Carrasco Elena , Lazo Pedro A. 
Published: May 2023

Abstract
Background
Dynamic chromatin remodeling is associated with changes in the epigenetic pattern of histone acetylations and methylations required for processes based on dynamic chromatin remodeling and implicated in different nuclear functions. These histone epigenetic modifications need to be coordinated, a role that may be mediated by chromatin kinases such as VRK1, which phosphorylates histones H3 and H2A.

Methods
The effect of VRK1 depletion and VRK1 inhibitor, VRK-IN-1, on the acetylation and methylation of histone H3 in K4, K9 and K27 was determined under different conditions, arrested or proliferating cells, in A549 lung adenocarcinoma and U2OS osteosarcoma cells.

Results
Chromatin organization is determined by the phosphorylation pattern of histones mediated by different types of enzymes. We have studied how the VRK1 chromatin kinase can alter the epigenetic posttranslational modifications of histones by using siRNA, a specific inhibitor of this kinase (VRK-IN-1), and of histone acetyl and methyl transferases, as well as histone deacetylase and demethylase. Loss of VRK1 implicated a switch in the state of H3K9 posttranslational modifications. VRK1 depletion/inhibition causes a loss of H3K9 acetylation and facilitates its methylation. This effect is similar to that of the KAT inhibitor C646, and to KDM inhibitors as iadademstat (ORY-1001) or JMJD2 inhibitor. Alternatively, HDAC inhibitors (selisistat, panobinostat, vorinostat) and KMT inhibitors (tazemetostat, chaetocin) have the opposite effect of VRK1 depletion or inhibition, and cause increase of H3K9ac and a decrease of H3K9me3. VRK1 stably interacts with members of these four enzyme families. However, VRK1 can only play a role on these epigenetic modifications by indirect mechanisms in which these epigenetic enzymes are likely targets to be regulated and coordinated by VRK1.

Conclusions
The chromatin kinase VRK1 regulates the epigenetic patterns of histone H3 acetylation and methylation in lysines 4, 9 and 27. VRK1 is a master regulator of chromatin organization associated with its specific functions, such as transcription or DNA repair.
Stress granules: functions and mechanisms in cancer
Authors: Zhou Huan , Luo Jing , Mou Kelin , Peng Lin , Li Xiaoyue , Lei Yulin , Wang Jianmei , Lin Sheng , Luo Yuhao , Xiang Li 
Published: May 2023

AbstractStress granules (SGs) are non-enveloped structures formed primarily via protein and RNA aggregation under various stress conditions, including hypoxia and viral infection, as well as oxidative, osmotic, and heat-shock stress. SGs assembly is a highly conserved cellular strategy to reduce stress-related damage and promote cell survival. At present, the composition and dynamics of SGs are well understood; however, data on the functions and related mechanisms of SGs are limited. In recent years, SGs have continued to attract attention as emerging players in cancer research. Intriguingly, SGs regulate the biological behavior of tumors by participating in various tumor-associated signaling pathways, including cell proliferation, apoptosis, invasion and metastasis, chemotherapy resistance, radiotherapy resistance, and immune escape. This review discusses the roles and mechanisms of SGs in tumors and suggests novel directions for cancer treatment.
Membrane tension-mediated stiff and soft tumor subtypes closely associated with prognosis for prostate cancer patients
Authors: Feng Dechao , Wang Jie , Shi Xu , Li Dengxiong , Wei Wuran , Han Ping 
Published: May 2023

Abstract
Background
Prostate cancer (PCa) is usually considered as cold tumor. Malignancy is associated with cell mechanic changes that contribute to extensive cell deformation required for metastatic dissemination. Thus, we established stiff and soft tumor subtypes for PCa patients from perspective of membrane tension.

Methods
Nonnegative matrix factorization algorithm was used to identify molecular subtypes. We completed analyses using software R 3.6.3 and its suitable packages.

Results
We constructed stiff and soft tumor subtypes using eight membrane tension-related genes through lasso regression and nonnegative matrix factorization analyses. We found that patients in stiff subtype were more prone to biochemical recurrence than those in soft subtype (HR 16.18; p < 0.001), which was externally validated in other three cohorts. The top ten mutation genes between stiff and soft subtypes were DNAH, NYNRIN, PTCHD4, WNK1, ARFGEF1, HRAS, ARHGEF2, MYOM1, ITGB6 and CPS1. E2F targets, base excision repair and notch signaling pathway were highly enriched in stiff subtype. Stiff subtype had significantly higher TMB and T cells follicular helper levels than soft subtype, as well as CTLA4, CD276, CD47 and TNFRSF25.

Conclusions
From the perspective of cell membrane tension, we found that stiff and soft tumor subtypes were closely associated with BCR-free survival for PCa patients, which might be important for the future research in the field of PCa.
Breast cancer prediction using gated attentive multimodal deep learning
Authors: Kayikci Safak , Khoshgoftaar Taghi M. 
Published: May 2023

AbstractWomen are prone to breast cancer, which is a major cause of death. One out of every eight women has a lifetime risk of developing this cancer. Early diagnosis of this disease is critical and enhances the success rate of cure. It is extremely important to determine which genes are associated with the disease. However, too many features make studies on gene data challenging. In this study, an attention-based multimodal deep learning model was created by combining data from clinical, copy number alteration and gene expression sources. Attention-based deep learning models can analyze mammography images and identify subtle patterns or abnormalities that may indicate the presence of cancer. These models can also integrate patient data, such as age and family history, to improve the accuracy of predictions. The objective of this study is to help breast cancer prediction tasks and improve efficiency by incorporating attention mechanisms. Our suggested methodology employs multimodal data and generates insightful characteristics to improve the prediction of the prognosis for breast cancer. It is a two-phase model; the first phase generates the stacked features using a sigmoid gated attention convolutional neural network, and the second phase uses flatten, dense and dropout processes for bi-modal attention. Based on our findings, the proposed model produced successful results and has the potential to significantly improve breast cancer detection and diagnosis, ultimately leading to better patient outcomes.
The incidence of hypotension during general anesthesia: a single-center study at a university hospital
Authors: Katori Nobuyuki , Yamakawa Kentaro , Kida Kotaro , Kimura Yoshihiro , Fujioka Shoko , Tsubokawa Tsunehisa 
Published: May 2023

Abstract
Background
Although intraoperative hypotension (IOH) has been emerging as a serious concern during general anesthesia, the incidence of IOH has not been demonstrated clearly in the Japanese population.

Methods
This single-center retrospective study investigated the incidence and the characteristics of IOH in non-cardiac surgery at a university hospital. IOH was defined as at least one fall of MAP during general anesthesia, which was categorized into the following groups: mild (65 to < 75 mmHg), moderate (55 to < 65 mmHg), severe (45 to < 55 mmHg), and very severe (< 45 mmHg). The incidence of IOH was calculated as a percentage of the number of events to the total anesthesia cases. Logistic regression analysis was performed to examine factors affecting IOH.

Results
Eleven thousand two hundred ten cases out of 13,226 adult patients were included in the analysis. We found moderate to very severe hypotension occurred in 86.3% of the patients for at least 1 to 5 min, and 48.5% experienced severe or very severe hypotension. The results of the logistic regression analysis indicated female gender, vascular surgery, American Society of Anesthesiologists physical status classification (ASA-PS) 4 or 5 in emergency surgery, and the combination with the epidural block (EDB) were significant factors of IOH.

Conclusions
IOH during general anesthesia was very frequent in the Japanese population. Female gender, vascular surgery, ASA-PA 4 or 5 in emergency surgery, and the combination with EDB were independent risk factors associated with IOH. However, the association with patient outcomes were not elucidated.
Low Circulating Valine Associate With High Risk of Hip Fractures
Authors: Grahnemo Louise , Eriksson Anna L , Nethander Maria , Johansson Robert , Lorentzon Mattias , Mellström Dan , Pettersson-Kymmer Ulrika , Ohlsson Claes 
Published: May 2023

Abstract

Context
Hip fractures constitute a major health concern. An adequate supply of amino acids is crucial to ensure optimal acquisition and remodeling of bone. Circulating amino acid levels have been proposed as markers of bone mineral density, but data on their ability to predict incident fractures are scarce.

Objectives
To investigate the associations between circulating amino acids and incident fractures.

Methods
We used UK Biobank (n = 111 257; 901 hip fracture cases) as a discovery cohort and the Umeå Fracture and Osteoporosis (UFO) hip fracture study (hip fracture cases n = 2225; controls n = 2225) for replication. Associations with bone microstructure parameters were tested in a subsample of Osteoporotic Fractures in Men Sweden (n = 449).

Results
Circulating valine was robustly associated with hip fractures in the UK Biobank (HR per SD increase 0.79, 95% CI 0.73-0.84), and this finding was replicated in the UFO study (combined meta-analysis including 3126 incident hip fracture cases, odds ratio per SD increase 0.84, 95% CI 0.80-0.88). Detailed bone microstructure analyses showed that high circulating valine was associated with high cortical bone area and trabecular thickness.

Conclusion
Low circulating valine is a robust predictor of incident hip fractures. We propose that circulating valine may add information for hip fracture prediction. Future studies are warranted to determine whether low valine is causally associated with hip fractures.
Sports Participation and Sports-Related Neurologic Injuries in Pediatric Patients With Arachnoid Cysts
Authors: Lee Johan H. , Holste Katherine G. , Selzer Bela J. , Garton Hugh J. L. , Muraszko Karin M. , Maher Cormac O. 
Published: May 2023

BACKGROUND:
Currently, there is no consensus recommendation regarding the safety of sports participation for pediatric patients with arachnoid cysts (ACs).

OBJECTIVE:
To prospectively survey patients with ACs to define the risk of sports-associated neurologic injury in untreated and treated patients.

METHODS:
A prospectively administered survey was given to all patients diagnosed with an AC who presented to a single pediatric neurosurgery clinic between December 2010 and December 2021. Data were recorded on demographic information, imaging characteristics, treatment, sports participation, and presence of sports-related neurologic injury. The type and date of surgery for the AC were noted if surgery was performed.

RESULTS:
Of the 303 patients with completed surveys, 189 patients participated in sports, and 94 patients had prospective data available. There was no significant difference in cyst location or Galassi score between patients who did and did not participate in contact vs noncontact sports and those who did and did not experience a concussion. A cumulative total of 2700.5 seasons of sports were played (2499.7 in untreated and 200.8 in treated patients). There were 44 sports-related concussions among 34 patients: 43 in untreated patients and 1 in a treated patient. For all participants, the concussion rate was 16.3 per 1000 seasons of all sports and 14.8 per 1000 seasons of contact sports. The concussion rate after AC treatment was 4.9 per 1000 seasons of all sports. Three patients experienced sports-related AC rupture or hemorrhage, none of which required surgery or resulted in lasting neurologic symptoms or deficits.

CONCLUSION:
The rates of sports-related concussion and cyst rupture in patients with AC in both treated and untreated populations were low. We advocate for a generally permissive posture toward sports participation in this population.
Efficacy and safety of intensity Modulated Radiation therapy combined with Concurrent Chemoradiotherapy in the treatment of Recurrent Cervical Cancer
Authors: Jin Ge , Li Kuixiu , Niu Shuhuai , Fan Xiaomei , Guo Yunfeng 
Published: May 2023

Objective: To evaluate the clinical value of intensity modulated radiation therapy (IMRT) combined with concurrent chemoradiotherapy in the treatment of recurrent cervical cancer.
Methods: This was a retrospective study. Eighty patients with recurrent cervical cancer were recruited and randomly divided into two groups: the experimental group and the control group, with 40 cases in each group at The Fourth Hospital of Hebei Medical University from April, 2017 to April, 2022. Patients in the control group were only given IMRT, while those in the experimental group were given concurrent chemoradiotherapy with paclitaxel and cisplatin based on IMRT. All patients were evaluated for clinical efficacy, adverse drug reactions, and differences in the levels of SCC-Ag, CEA and CA724 and other tumor markers before and after treatment.
Results: The total effective rate in the experimental group was significantly better than in the control group (p=0.02). The incidence of adverse reactions was 40% in the experimental group and 32.5% in the control group, with no statistically significant difference (p=0.48). After treatment, the levels of tumor markers in the experimental group were significantly lower than those in the control group, with a statistically significant difference (p=0.00). The three years survival rate was 80% in the experimental group and 55% in the control group (p=0.03). The five years survival rate was 65% in the experimental group and 42.5% in the control group, with a statistically significant difference (p=0.04).
Conclusion: Intensity modulated radiation therapy (IMRT) combined with concurrent chemoradiotherapy is a safe and effective regimen for recurrent cervical cancer, boasting significant clinical efficacy, reduced tumor markers, no significant increase in adverse reactions, and significantly improved three-years and five years survival rate.
doi: https://doi.org/10.12669/pjms.39.4.6784
How to cite this: Jin G, Li K, Niu S, Fan X, Guo Y. Efficacy and safety of intensity Modulated Radiation therapy combined with Concurrent Chemoradiotherapy in the treatment of Recurrent Cervical Cancer. Pak J Med Sci. 2023;39(4):---------. doi: https://doi.org/10.12669/pjms.39.4.6784
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Clinical changes of serum melatonin and ICAM-1 levels in patients with basal ganglia hypertensive intracerebral hemorrhage
Authors: Hou Hongbo , Li Xin 
Published: May 2023

Objective: To investigate the clinical changes of serum melatonin and intercellular adhesion molecule-1 (ICAM-1) levels in patients with basal ganglia hypertensive intracerebral hemorrhage (HICH).
Methods: In this retrospective observational study, patients with HICH in Suzhou Hospital of Traditional Chinese and Western Medicine from January 2020 to January 2021 were included as the observation group (n=120), and 120 healthy volunteers who underwent physical examination were included as the control group. According to the Glasgow Coma Scale (GCS), the observation group was divided into four subgroups: normal group (n=27), mild group (n=51), moderate group (n=24), and severe group (n=18). Differences in serum melatonin and ICAM-1 were compared between the observation group and the control group, and between the subgroups. Logistic regression was used to analyze the risk factors of poor prognosis, and the ROC curve was used to analyze the influence of melatonin and ICAM-1 levels on patient prognosis.
Results: Serum melatonin levels were lower in the observation group compared to the control group, while ICAM-1 levels were higher (P<0.05). With the aggravation of brain injury, serum melatonin decreased and ICAM increased (P<0.05). Decreased serum melatonin and increased ICAM-1 were independent risk factors for poor prognosis in patients with HICH. The combined AUC of serum melatonin and ICAM-1 for the detection of poor prognosis in patients with HICH was 0.860, which was higher than that of the two alone (P<0.05).
Conclusions: Low serum melatonin levels and high ICAM-1 levels are associated with poor prognosis in patients with HICH and can be used as predictors of patients’ prognosis.
doi: https://doi.org/10.12669/pjms.39.4.7252
How to cite this: Hou H, Li X. Clinical changes of serum melatonin and ICAM-1 levels in patients with basal ganglia hypertensive intracerebral hemorrhage. Pak J Med Sci. 2023;39(4):---------. doi: https://doi.org/10.12669/pjms.39.4.7252
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.