bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knowledge of Palestinian women about cervical cancer warning signs: a national cross- sectional study
Authors: Elshami Mohamedraed , Al-Slaibi Ibrahim , Abukmail Hanan , Alser Mohammed , Radaydeh Afnan , Alfuqaha Alaa , Thalji Mariam , Khader Salma , Khatib Lana , Fannoun Nour , Ahmad Bisan , Kassab Lina , Khrishi Hiba , Elhussaini Deniz , Abed Nour , Nammari Aya , Abdallah Tumodir , Alqudwa Zaina , Idais Shahd , Tanbouz Ghaid , Hajajreh Ma’alem , Selmiyh Hala Abu , Abo-Hajouj Zakia , Hebi Haya , Zamel Manar , Skaik Refqa , Hammoud Lama , Rjoub Siba , Ayesh Hadeel , Rjoub Toqa , Zakout Rawan , Alser Amany , Abu-El-Noor Nasser , Bottcher Bettina 
Published: October 2021

Abstract
Background
Timely presentation and diagnosis of cervical cancer (CC) are crucial to decrease its mortality especially in low- and middle-income countries like Palestine. This study aimed to evaluate the knowledge of Palestinian women about CC warning signs and determine the factors associated with good knowledge.

Methods
This was a national cross-sectional study conducted between July 2019 and March 2020 in Palestine. Stratified convenience sampling was used to recruit adult women from hospitals, primary healthcare centers, and public spaces of 11 governorates. A translated-into-Arabic version of the validated CC awareness measure (CeCAM) was used to assess women’s knowledge of 12 CC warning signs.

Results
Of 8086 approached, 7223 participants completed the CeCAM (response rate = 89.3%). A total of 7058 questionnaires were included in the analysis: 2655 from the Gaza Strip and 4403 from the West Bank and Jerusalem (WBJ). The median age [interquartile range] for all participants was 34.0 [24.0, 42.0] years. Participants recruited from the WBJ were older, getting higher monthly income, and having more chronic diseases than those recruited from the Gaza Strip.
The most frequently identified warning sign was ‘vaginal bleeding after menopause’ (n = 5028, 71.2%) followed by ‘extreme generalized fatigue’ (n = 4601, 65.2%) and ‘unexplained weight loss’ (n = 4578, 64.9%). Only 1934 participants (27.4%) demonstrated good knowledge of CC warning signs. Participants from the Gaza Strip were slightly more likely than participants from the WBJ to have a good level of knowledge. Factors associated with having good knowledge included having a bachelor or postgraduate degree, being married, divorced, or widowed as well as knowing someone with cancer.

Conclusion
The overall awareness of CC warning signs was low. Educational interventions are needed to increase Palestinian women’s awareness of CC warning signs.
The cytotoxic effect of Baeckea frustescens extracts in eliminating hypoxic breast cancer cells
Authors: Shahruzaman S. H. , Yusof F. Z. , Maniam S. , Fakurazi S. , Maniam S. 
Published: October 2021

Abstract
Background
Adaptive metabolic response towards a low oxygen environment is essential to maintain rapid tumour proliferation and progression. The vascular network that surrounds the tumour develops an intermittent hypoxic condition and stimulates hypoxia-inducing factors. Baeckea frutescens is used in traditional medicine and known to possess antibacterial and cytoprotective properties. In this study, the cytotoxic effect of B. frutescens leaves and branches extracts against hypoxic human breast cancer (MCF-7) was investigated.

Method
The extracts were prepared using Soxhlet apparatus for ethanol and hexane extracts while the water extracts were freeze-dried. In vitro cytotoxic activities of B. frutescens extracts of various concentrations (20 to 160 μg/mL) at 24, 48, and 72 hours time points were studied using MTT in chemically induced hypoxic condition and in 3-dimensional in vitro cell culture system. An initial characterisation of B. frutescens extracts was carried out using Fourier-transform Infrared- Attenuated Total Reflection (FTIR-ATR) to determine the presence of functional groups.

Results
All leaf extracts except for water showed IC50 values ranging from 23 -158 μg/mL. Hexane extract showed the lowest IC50 value (23 μg/mL), indicating its potent cytotoxic activity. Among the branch extracts, only the 70% ethanolic extract (B70) showed an IC50 value. The hexane leaf extract tested on 3- dimensional cultured cells showed an IC50 value of 17.2 μg/mL. The FTIR-ATR spectroscopy analysis identified various characteristic peak values with different functional groups such as alcohol, alkenes, alkynes, carbonyl, aromatic rings, ethers, ester, and carboxylic acids. Interestingly, the FTIR-ATR spectra report a complex and unique profile of the hexane extract, which warrants further investigation.

Conclusion
Adaptation of tumour cells to hypoxia significantly contributes to the aggressiveness and chemoresistance of different tumours. The identification of B. frutescens and its possible role in eliminating breast cancer cells in hypoxic conditions defines a new role of natural product that can be utilised as an effective agent that regulates metabolic reprogramming in breast cancer.
Protocol refinement for a diabetes pragmatic trial using the PRECIS-2 framework
Authors: Glasgow Russell E. , Gurfinkel Dennis , Waxmonsky Jeanette , Rementer Jenny , Ritchie Natalie D. , Dailey-Vail Jennifer , Hosokawa Patrick , Dickinson L. Miriam , Kwan Bethany M. 
Published: October 2021

Abstract
Background
This report describes how we refined a protocol for a pragmatic comparative effectiveness study of two models of an evidence-based diabetes shared medical appointment intervention and used the PRECIS-2 rating system to evaluate these adaptations.

Methods
We report primary data collected between June and August 2019, and protocol refinements completed between 2018 and 2020. Twenty-two members of the study team collaborated in protocol refinement and completed the PRECIS-2 ratings of study pragmatism. We discuss study design refinements made to achieve the desired level of pragmatism vs. experimental control for each of the nine PRECIS-2 dimensions. Study team members received training on PRECIS-2 scoring and were asked to rate the study protocol on the nine PRECIS-2 dimensions. Ratings were compared using descriptive statistics.

Results
In general, the PRECIS-2 ratings revealed high levels of pragmatism, but somewhat less pragmatic ratings on the categories of Delivery and Organization (costs and resources). This variation was purposeful, and we provide the rationale for and steps taken to obtain the targeted level of pragmatism on each PRECIS-2 dimension, as well as detail design changes made to a) make the design more pragmatic and b) address COVID-19 issues. There was general agreement among team members and across different types of stakeholders on PRECIS-2 ratings.

Conclusions
We discuss lessons learned from use of PRECIS-2 and experiences in refining the study to be maximally pragmatic on some dimensions and less so on other dimensions. This paper expands on prior research by describing actions to achieve higher levels of pragmatism and revise our protocol fit to the changed context. We make recommendations for future use of PRECIS-2 to help address changing context and other strategies for the planning of and transparent reporting on pragmatic research and comparative effectiveness research.

Trial registration
Clinicaltrials.gov Registration ID: NCT03590041.
A human iPSC-derived inducible neuronal model of Niemann-Pick disease, type C1
Authors: Prabhu Anika V. , Kang Insung , De Pace Raffaella , Wassif Christopher A. , Fujiwara Hideji , Kell Pamela , Jiang Xuntian , Ory Daniel S. , Bonifacino Juan S. , Ward Michael E. , Porter Forbes D. 
Published: October 2021

Abstract
Background
Niemann-Pick disease, type C (NPC) is a childhood-onset, lethal, neurodegenerative disorder caused by autosomal recessive mutations in the genes NPC1 or NPC2 and characterized by impaired cholesterol homeostasis, a lipid essential for cellular function. Cellular cholesterol levels are tightly regulated, and mutations in either NPC1 or NPC2 lead to deficient transport and accumulation of unesterified cholesterol in the late endosome/lysosome compartment, and progressive neurodegeneration in affected individuals. Previous cell-based studies to understand the NPC cellular pathophysiology and screen for therapeutic agents have mainly used patient fibroblasts. However, these do not allow modeling the neurodegenerative aspect of NPC disease, highlighting the need for an in vitro system that permits understanding the cellular mechanisms underlying neuronal loss and identifying appropriate therapies. This study reports the development of a novel human iPSC-derived, inducible neuronal model of Niemann-Pick disease, type C1 (NPC1).

Results
We generated a null i3Neuron (inducible × integrated × isogenic) (NPC1−/− i3Neuron) iPSC-derived neuron model of NPC1. The NPC1−/− and the corresponding isogenic NPC1+/+ i3Neuron cell lines were used to efficiently generate homogenous, synchronized neurons that can be used in high-throughput screens. NPC1−/− i3Neurons recapitulate cardinal cellular NPC1 pathological features including perinuclear endolysosomal storage of unesterified cholesterol, accumulation of GM2 and GM3 gangliosides, mitochondrial dysfunction, and impaired axonal lysosomal transport. Cholesterol storage, mitochondrial dysfunction, and axonal trafficking defects can be ameliorated by treatment with 2-hydroxypropyl-β-cyclodextrin, a drug that has shown efficacy in NPC1 preclinical models and in a phase 1/2a trial.

Conclusion
Our data demonstrate the utility of this new cell line in high-throughput drug/chemical screens to identify potential therapeutic agents. The NPC1−/− i3Neuron line will also be a valuable tool for the NPC1 research community to explore the pathological mechanisms contributing to neuronal degeneration.

Graphical abstract
Prognostic significance of preoperative serum triglycerides and high-density lipoproteins cholesterol in patients with non-small cell lung cancer: a retrospective study
Authors: Ma Cong , Wang Xiaoyan , Guo Jingjing , Liu Ping 
Published: October 2021

Abstract
Background
Abnormalities in serum lipids and lipoproteins have been documented to link to the risk of cancers in recent years, but its prognostic value for cancer is not known. This study retrospectively evaluated the significance of preoperative serum lipids and lipoproteins for NSCLC’s prognosis.

Methods
A retrospective review was implemented of 551 patients succumbed to NSCLC. A ROC curve was utilized to determine the best cut-off value and area under the ROC curve. Kaplan-Meier and a Cox proportional hazards model were utilized to perform survival analysis.

Results
With a median follow-up of 42 months, the NSCLC patients in the high TG (> 1.21 mmol/L) and low HDL-C (≤ 1.26 mmol/L) two groups exhibited shorter OS and DFS. In multivariable analysis, preoperative HDL-C and TG can work as independent prognosis factors for OS (P<0.001 for both) and DFS (P<0.05 for both) in patients succumbed to NSCLC.

Conclusion
Abnormalities of serum lipids and lipoproteins metabolism linked to the survival outcomes of NSCLC. Preoperative serum HDL-C and TG may be promising biomarkers to predict the NSCLC patients’ prognosis.
Combination of transcatheter arterial chemoembolization and portal vein embolization for patients with hepatocellular carcinoma: a review
Authors: Shao Zhiying , Liu Xin , Peng Chanjuan , Wang Liping , Xu Dong 
Published: October 2021

Abstract
Background
Transcatheter arterial chemoembolization has been widely used in patients with hepatocellular carcinoma. However, double blood supply and the existence of portal vein tumor thrombus influence the efficacy of transcatheter arterial chemoembolization.

Main body
Theoretically, portal vein embolization combined with transcatheter arterial chemoembolization may bring a breakthrough in the therapeutic effect of hepatocellular carcinoma. The feasibility, efficacy, long-term survival benefits, and side effects of the combined treatment have been explored in previous studies. Chemotherapeutic agents may also be added in the portal vein embolization procedure to further improve the treatment response.

Conclusion
In this study, we review the existing data and studies on the combined treatment in patients with hepatocellular carcinoma and provide an overall view of the strategy.
Mapping a mammalian adult adrenal gland hierarchy across species by microwell-seq
Authors: Lai Shujing , Ma Lifeng , E Weigao , Ye Fang , Chen Haide , Han Xiaoping , Guo Guoji 
Published: October 2021

AbstractRecently, single-cell RNA-seq technologies have been rapidly updated, leading to a revolution in biology. We previously developed Microwell-seq, a cost-effective and high-throughput single cell RNA sequencing(scRNA-seq) method with a very simple device. Most cDNA libraries are sequenced using an expensive Illumina platform. Here, we present the first report showing combined Microwell-seq and BGI MGISEQ2000, a less expensive sequencing platform, to profile the whole transcriptome of 11,883 individual mouse adult adrenal gland cells and identify 18 transcriptionally distinct clusters. Moreover, we performed a single-cell comparative analysis of human and mouse adult adrenal glands to reveal the conserved genetic networks in these mammalian systems. These results provide new insights into the sophisticated adrenal gland hierarchy and provide a benchmark, low-cost strategy for high-throughput single-cell RNA study.
CRISPR/Cas: a potential gene-editing tool in the nervous system
Authors: Gao Yanxia , Gao Kexin , Yang Hui 
Published: October 2021

AbstractThe rapidly developmental RNA-guided CRISPR/Cas system is a powerful tool for RNA and DNA editing in a variety of cells from different species and makes a great contribution to gene function research, disease model generation and gene therapy development in the past few years. The ease of use, low cost and high efficiency of CRISPR/Cas make it commonly used in various conditions. In this review, we introduce the CRISPR/Cas system and its diverse applications in nervous system briefly, which provides a better understanding for its potential application values.
Capn3 depletion causes Chk1 and Wee1 accumulation and disrupts synchronization of cell cycle reentry during liver regeneration after partial hepatectomy
Authors: Chen Feng , Huang Delai , Shi Hui , Gao Ce , Wang Yingchun , Peng Jinrong 
Published: October 2021

AbstractRecovery of liver mass to a healthy liver donor by compensatory regeneration after partial hepatectomy (PH) is a prerequisite for liver transplantation. Synchronized cell cycle reentry of the existing hepatocytes after PH is seemingly a hallmark of liver compensatory regeneration. Although the molecular control of the PH-triggered cell cycle reentry has been extensively studied, little is known about how the synchronization is achieved after PH. The nucleolus-localized protein cleavage complex formed by the nucleolar protein Digestive-organ expansion factor (Def) and cysteine proteinase Calpain 3 (Capn3) has been implicated to control wounding healing during liver regeneration through selectively cleaving the tumor suppressor p53 in the nucleolus. However, whether the Def-Capn3 complex participates in regulating the synchronization of cell cycle reentry after PH is unknown. In this report, we generated a zebrafish capn3b null mutant (capn3b∆19∆14). The homozygous mutant was viable and fertile, but suffered from a delayed liver regeneration after PH. Delayed liver regeneration in capn3b∆19∆14 was due to disruption of synchronized cell proliferation after PH. Mass spectrometry (MS) analysis of nuclear proteins revealed that a number of negative regulators of cell cycle are accumulated in the capn3b∆19∆14 liver after PH. Moreover, we demonstrated that Check-point kinase 1 (Chk1) and Wee1, two key negative regulators of G2 to M transition, are substrates of Capn3. We also demonstrated that Chk1 and Wee1 were abnormally accumulated in the nucleoli of amputated capn3b∆19∆14 liver. In conclusion, our findings suggest that the nucleolar-localized Def-Capn3 complex acts as a novel regulatory pathway for the synchronization of cell cycle reentry, at least partially, through inactivating Chk1 and Wee1 during liver regeneration after PH.
Consistent apparent Young’s modulus of human embryonic stem cells and derived cell types stabilized by substrate stiffness regulation promotes lineage specificity maintenance
Authors: Guo Anqi , Wang Bingjie , Lyu Cheng , Li Wenjing , Wu Yaozu , Zhu Lu , Bi Ran , Huang Chenyu , Li Jiao Jiao , Du Yanan 
Published: October 2021

Abstract
Background
Apparent Young’s modulus (AYM), which reflects the fundamental mechanical property of live cells measured by atomic force microscopy and is determined by substrate stiffness regulated cytoskeletal organization, has been investigated as potential indicators of cell fate in specific cell types. However, applying biophysical cues, such as modulating the substrate stiffness, to regulate AYM and thereby reflect and/or control stem cell lineage specificity for downstream applications, remains a primary challenge during in vitro stem cell expansion. Moreover, substrate stiffness could modulate cell heterogeneity in the single-cell stage and contribute to cell fate regulation, yet the indicative link between AYM and cell fate determination during in vitro dynamic cell expansion (from single-cell stage to multi-cell stage) has not been established.

Results
Here, we show that the AYM of cells changed dynamically during passaging and proliferation on substrates with different stiffness. Moreover, the same change in substrate stiffness caused different patterns of AYM change in epithelial and mesenchymal cell types. Embryonic stem cells and their derived progenitor cells exhibited distinguishing AYM changes in response to different substrate stiffness that had significant effects on their maintenance of pluripotency and/or lineage-specific characteristics. On substrates that were too rigid or too soft, fluctuations in AYM occurred during cell passaging and proliferation that led to a loss in lineage specificity. On a substrate with ‘optimal’ stiffness (i.e., 3.5 kPa), the AYM was maintained at a constant level that was consistent with the parental cells during passaging and proliferation and led to preservation of lineage specificity. The effects of substrate stiffness on AYM and downstream cell fate were correlated with intracellular cytoskeletal organization and nuclear/cytoplasmic localization of YAP.

Conclusions
In summary, this study suggests that optimal substrate stiffness regulated consistent AYM during passaging and proliferation reflects and contributes to hESCs and their derived progenitor cells lineage specificity maintenance, through the underlying mechanistic pathways of stiffness-induced cytoskeletal organization and the downstream YAP signaling. These findings highlighted the potential of AYM as an indicator to select suitable substrate stiffness for stem cell specificity maintenance during in vitro expansion for regenerative applications.
Organoid based personalized medicine: from bench to bedside
Authors: Li Yaqi , Tang Peiyuan , Cai Sanjun , Peng Junjie , Hua Guoqiang 
Published: October 2021

AbstractThree-dimensional cultured organoids have become a powerful in vitro research tool that preserves genetic, phenotypic and behavioral trait of in vivo organs, which can be established from both pluripotent stem cells and adult stem cells. Organoids derived from adult stem cells can be established directly from diseased epithelium and matched normal tissues, and organoids can also be genetically manipulated by CRISPR-Cas9 technology. Applications of organoids in basic research involve the modeling of human development and diseases, including genetic, infectious and malignant diseases. Importantly, accumulating evidence suggests that biobanks of patient-derived organoids for many cancers and cystic fibrosis have great value for drug development and personalized medicine. In addition, organoids hold promise for regenerative medicine. In the present review, we discuss the applications of organoids in the basic and translational research.
Protein quality control of cell stemness
Authors: Yan Pengze , Ren Jie , Zhang Weiqi , Qu Jing , Liu Guang-Hui 
Published: October 2021

AbstractProtein quality control (PQC) systems play essential roles in the recognition, refolding and clearance of aberrant proteins, thus ensuring cellular protein homeostasis, or proteostasis. Especially, continued proliferation and differentiation of stem cells require a high rate of translation; therefore, accurate PQC systems are essential to maintain stem cell function. Growing evidence suggested crucial roles of PQC systems in regulating the stemness and differentiation of stem cells. This review focuses on current knowledge regarding the components of the proteostasis network in stem cells, and the importance of proteostasis in maintaining stem cell identity and regenerative functions. A complete understanding of this process might uncover potential applications in aging intervention and aging-related diseases.
Proteins in DNA methylation and their role in neural stem cell proliferation and differentiation
Authors: Sun Jiaqi , Yang Junzheng , Miao Xiaoli , Loh Horace H. , Pei Duanqing , Zheng Hui 
Published: October 2021

Abstract
Background
Epigenetic modifications, namely non-coding RNAs, DNA methylation, and histone modifications such as methylation, phosphorylation, acetylation, ubiquitylation, and sumoylation play a significant role in brain development. DNA methyltransferases, methyl-CpG binding proteins, and ten-eleven translocation proteins facilitate the maintenance, interpretation, and removal of DNA methylation, respectively. Different forms of methylation, including 5-methylcytosine, 5-hydroxymethylcytosine, and other oxidized forms, have been detected by recently developed sequencing technologies. Emerging evidence suggests that the diversity of DNA methylation patterns in the brain plays a key role in fine-tuning and coordinating gene expression in the development, plasticity, and disorders of the mammalian central nervous system. Neural stem cells (NSCs), originating from the neuroepithelium, generate neurons and glial cells in the central nervous system and contribute to brain plasticity in the adult mammalian brain.

Main body
Here, we summarized recent research in proteins responsible for the establishment, maintenance, interpretation, and removal of DNA methylation and those involved in the regulation of the proliferation and differentiation of NSCs. In addition, we discussed the interactions of chemicals with epigenetic pathways to regulate NSCs as well as the connections between proteins involved in DNA methylation and human diseases.

Conclusion
Understanding the interplay between DNA methylation and NSCs in a broad biological context can facilitate the related studies and reduce potential misunderstanding.
The interaction of Notch and Wnt signaling pathways in vertebrate regeneration
Authors: Gao Junying , Fan Lixia , Zhao Long , Su Ying 
Published: October 2021

AbstractRegeneration is an evolutionarily conserved process in animal kingdoms, however, the regenerative capacities differ from species and organ/tissues. Mammals possess very limited regenerative potential to replace damaged organs, whereas non-mammalian species usually have impressive abilities to regenerate organs. The regeneration process requires proper spatiotemporal regulation from key signaling pathways. The canonical Notch and Wnt signaling pathways, two fundamental signals guiding animal development, have been demonstrated to play significant roles in the regeneration of vertebrates. In recent years, increasing evidence has implicated the cross-talking between Notch and Wnt signals during organ regeneration. In this review, we summarize the roles of Notch signaling and Wnt signaling during several representative organ regenerative events, emphasizing the functions and molecular bases of their interplay in these processes, shedding light on utilizing these two signaling pathways to enhance regeneration in mammals and design legitimate therapeutic strategies.