bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing survival time of outpatients with cervical cancer: at the university of Gondar referral hospital using the Bayesian approach
Authors: Gashu Chalachew , Tasfa Buzuneh , Alemu Chekol , Kassa Yoseph 
Published: February 2023

AbstractBackgroundCervical cancer is the 4th most common cancer in women worldwide. as well as the 4th most common cause of cancer-related death. The main objective of this study was to identify factors that affect the survival time of outpatients with cervical cancer.MethodsA retrolective study including outpatients with cervical cancer was carried out in a hospital. To achieve the aim, 322 outpatients with cervical cancer were included in the study based on the data taken from the medical records of patients enrolled from May 15, 2018, to May 15, 2022, at the University of Gondar referral hospital, Gondar, Ethiopia. The Kaplan–Meier plots and log-rank test were used for the comparison of survival functions; the Cox-PH model and Bayesian parametric survival models were used to analyze the survival times of outpatients with cervical cancer. Integrated nested Laplace approximation methods have been applied.ResultsOut of a total of 322 patients, 118 (36.6%) died as outpatients. The estimated median survival time for patients was 42 months. Using model selection criteria, the Bayesian log-normal accelerated failure time model was found to be appropriate. According to the results of this model, oral contraceptive use, HIV, stage, grade, co-morbid disease, history of abortion, weight, histology type, FIGO stage, radiation, chemotherapy, LVSI, metastatic number, regional nodes examined, and tumor size all have a significant impact on the survival time of outpatients with cervical cancer. The Bayesian log-normal accelerated failure time model accurately predicted the survival time of cervical cancer outpatients.ConclusionsThe findings of this study suggested that reductions in weight, treatment, the presence of comorbid disease, the presence of HIV, squamous cell histology type, having a history of abortion, oral contraceptive use, a large tumor size, an increase in the International Federation of Gynecologists and Obstetricians stage, an increase in metastasis number, an increase in grade, positive regional nodes, lymphatic vascular space invasion, and late stages of cancer all shortened the survival time of cervical cancer outpatients.
‘Guidance should have been there 15 years ago’ research stakeholders’ perspectives on ancillary care in the global south: a case study of Malawi
Authors: Kapumba Blessings M. , Nyirenda Deborah , Desmond Nicola , Seeley Janet 
Published: February 2023

AbstractBackgroundMedical researchers in resource-constrained settings must make difficult moral decisions about the provision of ancillary care to participants where additional healthcare needs fall outside the scope of the research and are not provided for by the local healthcare system. We examined research stakeholder perceptions and experiences of ancillary care in biomedical research projects in Malawi.MethodsWe conducted 45 qualitative in-depth interviews with key research stakeholders: researchers, health officials, research ethics committee members, research participants and grants officers from international research funding organisations. Thematic analysis was used to analyse and interpret the findings.FindingsAll stakeholders perceived the provision of ancillary care to have potential health benefits to study participants in biomedical research. However, they also had concerns, particularly related to the absence of guidance to support it. Some suggested that consideration for ancillary care provision could be possible on a case-by-case basis but that most of the support from research projects should be directed towards strengthening the public health system, emphasising public good above individual or personal benefits. Some researchers and ethics committee members raised concerns about potential tensions in terms of funding, for example balancing study demands with addressing participants’ additional health needs.ConclusionOur findings highlight the complexities and gaps in the guidance around the provision of ancillary care in Malawi and other resource-constrained settings more generally. To promote the provision of ancillary care, we recommend that national and international guidelines for research ethics include specific recommendations for resource-constrained settings and specific types of research.
Experiences of using surveillance cameras as a monitoring solution at nursing homes: The eldercare personnel’s perspectives
Authors: Emilsson Maria , Karlsson Christina , Svensson Ann 
Published: February 2023

Abstract
Background
As the number of older people increases, so does the need for care. However, the workforce in eldercare cannot increase at the rate required to match the needs. Welfare technologies, such as surveillance cameras, can replace physical visits and be used at night to monitor older people in order to keep them safe, while not disturbing their sleep. The aim of the paper is to analyze obstacles and opportunities associated with implementation and use of surveillance cameras at nursing homes from the perspectives of the practitioners who use the technology, their working environment and the conditions of the older people with cognitive impairment who live in nursing homes.

Methods
Individual semi-structured interviews were conducted with the eldercare personnel at nursing homes to understand their experiences of implementation and use of surveillance cameras. The transcribed interviews were analyzed using qualitative content analysis. The consolidated criteria for reporting qualitative research (COREQ) was used as a guidance tool.

Results
The results show that the eldercare personnel experienced lack of adequate information, education and support related to using surveillance cameras. Several benefits are highlighted, such as better working environment and that the residents were not unnecessarily disturbed at night. However, the results also show that it is important to clarify that surveillance cameras cannot replace the human presence.

Conclusions
The conclusions from this study are the importance of prerequisites for implementation, and that using surveillance cameras contributed to improvements in the working environment at night and created possibilities to maintain security and integrity for older people living in nursing homes.
Systemic proinflammatory−profibrotic response in aortic stenosis patients with diabetes and its relationship with myocardial remodeling and clinical outcome
Authors: Lee Hyun-Jung , Park Chan Soon , Lee Sahmin , Park Jun-Bean , Kim Hyung-Kwan , Park Sung-Ji , Kim Yong-Jin , Lee Seung-Pyo 
Published: February 2023

Abstract
Background
Previous studies have mainly focused more on how diabetes affects the valve than the myocardium in aortic stenosis (AS). In the pressure-overloaded heart, myocardial fibrosis is an important driver of the progression from compensated hypertrophy to heart failure. Using comprehensive noninvasive imaging and plasma proteomics, we investigated whether and how diabetes aggravates the remodeling of the myocardium and its relation with prognosis in AS patients.

Methods
Severe AS patients were enrolled in two prospective cohorts for imaging and biomarker analysis. The imaging cohort (n = 253) underwent echocardiography and cardiac magnetic resonance, and the biomarker cohort (n = 100) blood sampling with multiplex proximity extension assay for 92 proteomic biomarkers. The composite outcome of hospitalization for heart failure admissions and death was assessed in the imaging cohort.

Results
Diabetic patients were older (70.4 ± 6.8 versus 66.7 ± 10.1 years) with more advanced ventricular diastolic dysfunction and increased replacement and diffuse interstitial fibrosis (late gadolinium enhancement % 0.3 [0.0–1.6] versus 0.0 [0.0–0.5], p = 0.009; extracellular volume fraction % 27.9 [25.7–30.1] versus 26.7 [24.9–28.5], p = 0.025) in the imaging cohort. Plasma proteomics analysis of the biomarker cohort revealed that 9 proteins (E-selectin, interleukin-1 receptor type 1, interleukin-1 receptor type 2, galectin-4, intercellular adhesion molecule 2, integrin beta-2, galectin-3, growth differentiation factor 15, and cathepsin D) were significantly elevated and that pathways related to inflammatory response and extracellular matrix components were enriched in diabetic AS patients. During follow-up (median 6.3 years), there were 53 unexpected heart failure admissions or death in the imaging cohort. Diabetes was a significant predictor of heart failure and death, independent of clinical covariates and aortic valve replacement (HR 1.88, 95% CI 1.06−3.31, p = 0.030).

Conclusions
Plasma proteomic analyses indicate that diabetes potentiates the systemic proinflammatory−profibrotic milieu in AS patients. These systemic biological changes underlie the increase of myocardial fibrosis, diastolic dysfunction, and worse clinical outcomes in severe AS patients with concomitant diabetes.
The various role of microRNAs in breast cancer angiogenesis, with a special focus on novel miRNA-based delivery strategies
Authors: Yang Min , Zhang Ying , Li Min , Liu Xinglong , Darvishi Mohammad 
Published: February 2023

AbstractAfter skin malignancy, breast cancer is the most widely recognized cancer detected in women in the United States. Breast cancer (BCa) can happen in all kinds of people, but it's much more common in women. One in four cases of cancer and one in six deaths due to cancer are related to breast cancer. Angiogenesis is an essential factor in the growth of tumors and metastases in various malignancies. An expanded level of angiogenesis is related to diminished endurance in BCa patients. This function assumes a fundamental part inside the human body, from the beginning phases of life to dangerous malignancy. Various factors, referred to as angiogenic factors, work to make a new capillary. Expanding proof demonstrates that angiogenesis is managed by microRNAs (miRNAs), which are small non-coding RNA with 19–25 nucleotides. MiRNA is a post-transcriptional regulator of gene expression that controls many critical biological processes. Endothelial miRNAs, referred to as angiomiRs, are probably concerned with tumor improvement and angiogenesis via regulation of pro-and anti-angiogenic factors. In this article, we reviewed therapeutic functions of miRNAs in BCa angiogenesis, several novel delivery carriers for miRNA-based therapeutics, as well as CRISPR/Cas9 as a targeted therapy in breast cancer.
Anti-obesity effect of the bacterial product nisin in an NIH Swiss mouse model
Authors: Al-Emarah M. K. , Kazerani H. R. , Taghizad F. , Dehghani H. , Elahi M. 
Published: February 2023

AbstractObesity is a life-threatening metabolic disorder that predisposes individuals to other diseases. In this study, the effect of nisin, a bacteriocin produced by some bacteria, on an animal model of obesity based on selected parameters was investigated. Forty Swiss NIH mice were randomly divided into four groups and received either a placebo (saline) or nisin (25, 50, or 100 μg/kg, ip) daily for 8 weeks. The mice in all groups were fed a high-sugar diet throughout the experiment. Bodyweight and food intake were measured weekly, and at the end of the experiment, the levels of FBS, serum triglyceride, cholesterol, high-density lipoprotein, low-density lipoprotein, and hepatic enzymes were tested, and red and white blood cell counts, hemoglobin concentration, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were determined. Finally, the expression levels of some obesity-related genes, including stearoyl-CoA desaturase-1 (SCD-1), glucose transporter-4 (GLUT4), zinc finger protein 423 (zfp423), 422 (ap2), and tumor necrosis factor-alpha (TNF-α), were assessed using reverse transcriptase-quantitative polymerase chain reaction (RT–qPCR). After the experiment, the body weights, abdominal fat, and body mass index were significantly lower in the nisin-treated groups than in the control group. The highest effect was observed with 50 μg/kg nisin. The expression of SCD-1, GLUT4, 422(ap2), and TNF-α decreased significantly following treatment with nisin. No significant differences were observed in the other studied parameters, and no toxic effects were observed for nisin under these experimental conditions. The results suggested that nisin could have antiobesity effects.
Long-lasting postoperative analgesia with local anesthetic-loaded hydrogels prevent tumor recurrence via enhancing CD8+T cell infiltration
Authors: Zhao Mingxu , Zhu Shasha , Zhang Ding , Zhou Chang , Yang Zhilai , Wang Chunhui , Liu Xuesheng , Zhang Jiqian 
Published: February 2023

AbstractPostoperative pain (POP) can promote tumor recurrence and reduce the cancer patient's quality of life. However, POP management has always been separated from tumor treatment in clinical practice, and traditional postoperative analgesia using opioids is still unsatisfactory for patients, which is not conducive to tumor treatment. Here, ropivacaine, a popular amide-type LA, was introduced into a Pluronic F127 hydrogel. Postoperative analgesia with ropivacaine-loaded hydrogels reduced the incidence of high-dose ropivacaine-induced convulsions and prolonged pain relief for more than 16 h. More interestingly, ropivacaine-loaded hydrogel was found to upregulate major histocompatibility complex class I (MHC-I) in tumor cells by impairing autophagy. Therefore, a hydrogel co-dopped with ropivacaine and TLR7 agonist imiquimod (PFRM) was rationally synthesized. After postoperative analgesia with PFRM, imiquimod primes tumor-specific CD8+T cells through promoting DCs maturation, and ropivacaine facilitates tumor cells recognition by primed CD8+T cells through upregulating MHC-I. Consequently, postoperative analgesia with PFRM maximumly increases CD8+T cells infiltration into residual tumor tissue and prevents tumor recurrence. Overall, this study for the first time provides an LA-based approach for simultaneous long-lasting postoperative analgesia and prevention of tumor recurrence.
The members of the miR-148/152 family inhibit cancer stem cell-like properties in gastric cancer via negative regulation of ITGA5
Authors: Li Xiaoying , Li Lin , Wu Jiangying 
Published: February 2023

Abstract
Background
The role of microRNA (miRNA) in modulating the function of cancer stem cells through diverse signaling pathway has been evidenced. We here identified a role of microRNA (miRNA) family, specifically miR-148/152, in gastric cancer and delineated its functional effects on gastric cancer stem cells.

Methods
Bioinformatics analysis was conducted to analyze expression of integrin α5 (ITGA5) which was verified through expression determination in clinical tissue samples. Next, the upstream regulatory factors of ITGA5 were determined. CD44+EpCAM (high) cells sorted from AGS cells subjected to gain-of-function experiments, followed by evaluation of their capacity of colony formation, generation of tumorosphere, cell migration and viability in vitro and xenograft tumor formation in vivo.

Results
ITGA5 was elevated in gastric cancer tissues and confirmed as a target gene of the miR-148/152 family members. The miR-148/152 family members were downregulated in gastric cancer tissues and cells. Decreased expression of miR-148/152 family members was also detected in gastric cancer stem cells. However, the raised expression led to reduced colony formation, tumorosphere, cell migration, cell viability, and drug resistance of CD44+EpCAM (high) AGS cells in vitro, and tumorigenesis in vitro. ITGA5 overexpression reversed the effect of the miR-148/152 family members.

Conclusions
This study demonstrates that the miR-148/152 family members may prevent gastric cancer stem cell-like properties by targeting ITGA5, which can serve as an appealing target for gastric cancer treatment.
The genetic basis of multiple system atrophy
Authors: Tseng Fan Shuen , Foo Joel Qi Xuan , Mai Aaron Shengting , Tan Eng-King 
Published: February 2023

AbstractMultiple system atrophy (MSA) is a heterogenous, uniformly fatal neurodegenerative ɑ-synucleinopathy. Patients present with varying degrees of dysautonomia, parkinsonism, cerebellar dysfunction, and corticospinal degeneration. The underlying pathophysiology is postulated to arise from aberrant ɑ-synuclein deposition, mitochondrial dysfunction, oxidative stress and neuroinflammation. Although MSA is regarded as a primarily sporadic disease, there is a possible genetic component that is poorly understood. This review summarizes current literature on genetic risk factors and potential pathogenic genes and loci linked to both sporadic and familial MSA, and underlines the biological mechanisms that support the role of genetics in MSA. We discuss a broad range of genes that have been associated with MSA including genes related to Parkinson’s disease (PD), oxidative stress, inflammation, and tandem gene repeat expansions, among several others. Furthermore, we highlight various genetic polymorphisms that modulate MSA risk, including complex gene–gene and gene-environment interactions, which influence the disease phenotype and have clinical significance in both presentation and prognosis. Deciphering the exact mechanism of how MSA can result from genetic aberrations in both experimental and clinical models will facilitate the identification of novel pathophysiologic clues, and pave the way for translational research into the development of disease-modifying therapeutic targets.
Association between oxidative stress, mitochondrial function of peripheral blood mononuclear cells and gastrointestinal cancers
Authors: Liu Weili , Gao Yuan , Li Hua , Wang Xinxing , Jin Min , Shen Zhiqiang , Yang Dong , Zhang Xuelian , Wei Zilin , Chen Zhaoli , Li Junwen 
Published: February 2023

Abstract
Background
The incidence and mortality rate of gastrointestinal cancers are high worldwide. Increasing studies have illustrated that the occurrence, progression, metastasis and prognosis of cancers are intimately linked to the immune system. Mitochondria, as the main source of cellular energy, play an important role in maintaining the physiological function of immune cells. However, the relationship between mitochondrial function of immune cells and tumorigenesis has not yet been systematically investigated.

Methods
A total of 150 cases, including 60 healthy donors and 90 primary gastrointestinal cancer patients without anti-tumor treatments (30 with gastric cancer, 30 with liver cancer and 30 with colorectal cancer) were involved in our study. The oxidant/antioxidant and cytokine levels in plasma, the ROS level, mitochondrial function and apoptosis ratio of peripheral blood mononuclear cells (PBMCs) were evaluated.

Results
The imbalance between oxidant and antioxidant in plasma was discovered in the primary gastrointestinal cancer patients. The levels of cell reactive oxygen species (ROS) and mitochondrial ROS in PBMCs of primary gastrointestinal cancers were significantly increased compared with that in healthy donors. Meanwhile, the ATP content, the mtDNA copy number and the mitochondrial membrane potential (MMP) in PBMCs of patients with primary gastrointestinal cancers were lower than those in control group. The decreased MMP also occurred in immune cells of gastrointestinal cancers, including T cell, B cell, NK cell and monocyte. Furthermore, the PBMCs apoptosis ratio of primary gastrointestinal cancer patients was significantly higher than that of control group. Importantly, an increase of IL-2 and IL-6 and a decrease of IgG in plasma were found in the patients with primary gastrointestinal cancers. These changes of mitochondrial function in immune cells were consistent among primary gastrointestinal cancers without anti-tumor treatments, such as liver cancer, gastric cancer and colorectal cancer.

Conclusion
Our study demonstrated that the imbalance of oxidation/antioxidation in primary gastrointestinal cancer patients without anti-tumor treatments results in excessive ROS. The oxidative stress was associated to the mitochondrial dysfunction, the apoptosis of immune cells and eventually the abnormal immune function in primary gastrointestinal cancers. The application of immune cell mitochondrial dysfunction into clinical evaluation is anticipated.
Cellular senescence in the response of HR+ breast cancer to radiotherapy and CDK4/6 inhibitors
Authors: Klapp Vanessa , Buqué Aitziber , Bloy Norma , Sato Ai , Yamazaki Takahiro , Zhou Xi Kathy , Formenti Silvia C. , Galluzzi Lorenzo , Petroni Giulia 
Published: February 2023

Abstract
Background
Preclinical evidence from us and others demonstrates that the anticancer effects of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors can be enhanced with focal radiation therapy (RT), but only when RT is delivered prior to (rather than after) CDK4/6 inhibition. Depending on tumor model, cellular senescence (an irreversible proliferative arrest that is associated with the secretion of numerous bioactive factors) has been attributed beneficial or detrimental effects on response to treatment. As both RT and CDK4/6 inhibitors elicit cellular senescence, we hypothesized that a differential accumulation of senescent cells in the tumor microenvironment could explain such an observation, i.e., the inferiority of CDK4/6 inhibition with palbociclib (P) followed by RT (P→RT) as compared to RT followed by palbociclib (RT→P).

Methods
The impact of cellular senescence on the interaction between RT and P was assessed by harnessing female INK-ATTAC mice, which express a dimerizable form of caspase 8 (CASP8) under the promoter of cyclin dependent kinase inhibitor 2A (Cdkn2a, coding for p16Ink4), as host for endogenous mammary tumors induced by the subcutaneous implantation of medroxyprogesterone acetate (MPA, M) pellets combined with the subsequent oral administration of 7,12-dimethylbenz[a]anthracene (DMBA, D). This endogenous mouse model of HR+ mammary carcinogenesis recapitulates key immunobiological aspects of human HR+ breast cancer. Mice bearing M/D-driven tumors were allocated to RT, P or their combination in the optional presence of the CASP8 dimerizer AP20187, and monitored for tumor growth, progression-free survival and overall survival. In parallel, induction of senescence in vitro, in cultured human mammary hormone receptor (HR)+ adenocarcinoma MCF7 cells, triple negative breast carcinoma MDA-MB-231 cells and mouse HR+ mammary carcinoma TS/A cells treated with RT, P or their combination, was determined by colorimetric assessment of senescence-associated β-galactosidase activity after 3 or 7 days of treatment.

Results
In vivo depletion of p16Ink4-expressing (senescent) cells ameliorated the efficacy of P→RT (but not that of RT→P) in the M/D-driven model of HR+ mammary carcinogenesis. Accordingly, P→RT induced higher levels of cellular senescence than R→TP in cultured human and mouse breast cancer cell lines.

Conclusions
Pending validation in other experimental systems, these findings suggest that a program of cellular senescence in malignant cells may explain (at least partially) the inferiority of P→RT versus RT→P in preclinical models of HR+ breast cancer.