bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liquid biopsy: a step closer to transform diagnosis, prognosis and future of cancer treatments
Authors: Lone Saife N. , Nisar Sabah , Masoodi Tariq , Singh Mayank , Rizwan Arshi , Hashem Sheema , El-Rifai Wael , Bedognetti Davide , Batra Surinder K. , Haris Mohammad , Bhat Ajaz A. , Macha Muzafar A. 
Published: March 2022

AbstractOver the past decade, invasive techniques for diagnosing and monitoring cancers are slowly being replaced by non-invasive methods such as liquid biopsy. Liquid biopsies have drastically revolutionized the field of clinical oncology, offering ease in tumor sampling, continuous monitoring by repeated sampling, devising personalized therapeutic regimens, and screening for therapeutic resistance. Liquid biopsies consist of isolating tumor-derived entities like circulating tumor cells, circulating tumor DNA, tumor extracellular vesicles, etc., present in the body fluids of patients with cancer, followed by an analysis of genomic and proteomic data contained within them. Methods for isolation and analysis of liquid biopsies have rapidly evolved over the past few years as described in the review, thus providing greater details about tumor characteristics such as tumor progression, tumor staging, heterogeneity, gene mutations, and clonal evolution, etc. Liquid biopsies from cancer patients have opened up newer avenues in detection and continuous monitoring, treatment based on precision medicine, and screening of markers for therapeutic resistance. Though the technology of liquid biopsies is still evolving, its non-invasive nature promises to open new eras in clinical oncology. The purpose of this review is to provide an overview of the current methodologies involved in liquid biopsies and their application in isolating tumor markers for detection, prognosis, and monitoring cancer treatment outcomes.
Cholesterol promotes EGFR-TKIs resistance in NSCLC by inducing EGFR/Src/Erk/SP1 signaling-mediated ERRα re-expression
Authors: Pan Zhenzhen , Wang Kai , Wang Xiniao , Jia Zhirong , Yang Yuqi , Duan Yalei , Huang Lianzhan , Wu Zhuo-Xun , Zhang Jian-ye , Ding Xuansheng 
Published: March 2022

AbstractBackgroundThe use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) brings remarkable benefits for the survival of patients with advanced NSCLC harboring EGFR mutations. Unfortunately, acquired resistance seems to be inevitable and limits the application of EGFR-TKIs in clinical practice. This study reported a common molecular mechanism sustaining resistance and potential treatment options to overcome EGFR-TKIs resistance.MethodsEGFR-TKIs resistant NSCLC cells were established and confirmed by MTT assay. Cholesterol content was detected and the promotional function of cholesterol on NSCLC growth was determined in vivo. Then, we identified ERRα expression as the downstream factor of cholesterol-mediated drug resistance. To dissect the regulatory mechanism, we conducted experiments, including immunofluorescence, co-immunoprecipitation, luciferase reporter assay and chromatin immunoprecipitation assay.ResultsLong-term exposure to EGFR-TKIs generate drug resistance with the characteristic of cholesterol accumulation in lipid rafts, which promotes EGFR and Src to interact and lead EGFR/Src/Erk signaling reactivation-mediated SP1 nuclear translocation and ERRα re-expression. Further investigation identifies ERRα as a target gene of SP1. Functionally, re-expression of ERRα sustains cell proliferation by regulating ROS detoxification process. Lovastatin, a drug used to decrease cholesterol level, and XCT790, an inverse agonist of ERRα, overcome gefitinib and osimertinib resistance both in vitro and in vivo.ConclusionsOur study indicates that cholesterol/EGFR/Src/Erk/SP1 axis-induced ERRα re-expression promotes survival of gefitinib and osimertinib-resistant cancer cells. Besides, we demonstrate the potential of lowing cholesterol and downregulation of ERRα as effective adjuvant treatment of NSCLC.
Positive regulation of ataxia-telangiectasia-mutated protein (ATM) by E2F transcription Factor 1 (E2F-1) in cisplatin-resistant nasopharyngeal carcinoma cells
Authors: Zhou Zun-Yan , Yang Ji-Yuan , Shao Cheng-Ze , Luo Fei , Du Wei 
Published: March 2022

Abstract
Objective
To explore the mechanism of E2F transcription Factor 1 (E2F-1)-mediated ataxia-telangiectasia-mutated protein (ATM) in cisplatin (DDP)-resistant nasopharyngeal carcinoma (NPC).

Methods
E2F-1 and ATM expression was assessed in DDP-resistant NPC cell lines (CNE2/DDP and HNE1/DDP) and parental cells. Then, DDP-resistant NPC cells were transfected with control shRNA (short hairpin RNA) or E2F-1 shRNAs with or without ATM lentiviral activation particles. The half maximal inhibitory concentration (IC50) was evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, and the cell cycle and cell proliferation were measured by flow cytometry and EdU staining, respectively. In addition, the expression of genes and proteins was quantified by quantitative reverse-transcription polymerase chain reaction (qRT–PCR) and western blotting, respectively.

Results
Both E2F-1 and ATM expression in DDP-resistant NPC cells was much higher than that in parental cells. E2F-1 shRNA reduced ATM expression in DDP-resistant NPC cells, but ATM overexpression had no significant effect on E2F-1. ATM overexpression enhanced DDP resistance in DDP-resistant NPC cells with increased IC50 values, which was reversed by E2F-1 inhibition. Meanwhile, ATM overexpression resulted in upregulation of ABCA2 and ABCA5 in DDP-resistant NPC cells, induced elevations in the transition of the cells into S-phase, and increased cell proliferation with enhanced expression of cyclin E1, CDK2, and Ki67, which was reversed by E2F-1 shRNAs.

Conclusion
Downregulation of E2F-1, possibly by regulating ATM, could block the cell cycle in the G1 phase and reduce the proliferation of CNE2/DDP cells, thereby reversing the resistance of human NPC cells to DDP.
Effects of NAD+ precursor supplementation on glucose and lipid metabolism in humans: a meta-analysis
Authors: Zhong Ou , Wang Jinyuan , Tan Yongpeng , Lei Xiaocan , Tang Zhihan 
Published: March 2022

Abstract
Background
This meta-analysis was performed to investigate the effects of nicotinamide adenine dinucleotide (NAD+) precursor supplementation on glucose and lipid metabolism in human body.

Methods
PubMed, Embase, CENTRAL, Web of Science, Scopus databases were searched to collect clinical studies related to the supplement of NAD+ precursor from inception to February 2021. Then the retrieved documents were screened, the content of the documents that met the requirements was extracted. Meta-analysis and quality evaluation was performed detection were performed using RevMan5.4 software. Stata16 software was used to detect publication bias, Egger and Begg methods were mainly used. The main research terms of NAD+ precursors were Nicotinamide Riboside (NR), Nicotinamide Mononucleotide (NMN), Nicotinic Acid (NA), Nicotinamide (NAM). The changes in the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and fasting blood glucose were mainly concerned.

Results
A total of 40 articles were included in the meta-analysis, with a sample of 14,750 cases, including 7406 cases in the drug group and 7344 cases in the control group. The results of meta-analysis showed that: NAD+ precursor can significantly reduce TG level (SMD = − 0.35, 95% CI (− 0.52, − 0.18), P < 0.0001), and TC (SMD = − 0.33, 95% CI (− 0.51, − 0.14), P = 0.0005), and LDL (SMD = − 0.38, 95% CI (− 0.50, − 0.27), P < 0.00001), increase HDL level (SMD = 0.66, 95% CI (0.56, 0.76), P < 0.00001), and plasma glucose level in the patients (SMD = 0.27, 95% CI (0.12, 0.42), P = 0.0004). Subgroup analysis showed that supplementation of NA had the most significant effect on the levels of TG, TC, LDL, HDL and plasma glucose.

Conclusions
In this study, a meta-analysis based on currently published clinical trials with NAD+ precursors showed that supplementation with NAD+ precursors improved TG, TC, LDL, and HDL levels in humans, but resulted in hyperglycemia, compared with placebo or no treatment. Among them, NA has the most significant effect on improving lipid metabolism. In addition, although NR and NAM supplementation had no significant effect on improving human lipid metabolism, the role of NR and NAM could not be directly denied due to the few relevant studies at present. Based on subgroup analysis, we found that the supplement of NAD+ precursors seems to have little effect on healthy people, but it has a significant beneficial effect on patients with cardiovascular disease and dyslipidemia. Due to the limitation of the number and quality of included studies, the above conclusions need to be verified by more high-quality studies.
Variability of α/β ratios for prostate cancer with the fractionation schedule: caution against using the linear-quadratic model for hypofractionated radiotherapy
Authors: Cui Ming , Gao Xian-Shu , Li Xiaoying , Ma Mingwei , Qi Xin , Shibamoto Yuta 
Published: March 2022

AbstractBackgroundProstate cancer (PCa) is known to be suitable for hypofractionated radiotherapy due to the very low α/β ratio (about 1.5–3 Gy). However, several randomized controlled trials have not shown the superiority of hypofractionated radiotherapy over conventionally fractionated radiotherapy. Besides, in vivo and in vitro experimental results show that the linear-quadratic (LQ) model may not be appropriate for hypofractionated radiotherapy, and we guess it may be due to the influence of fractionation schedules on the α/β ratio. Therefore, this study attempted to estimate the α/β ratio in different fractionation schedules and evaluate the applicability of the LQ model in hypofractionated radiotherapy.MethodsThe maximum likelihood principle in mathematical statistics was used to fit the parameters: α and β values in the tumor control probability (TCP) formula derived from the LQ model. In addition, the fitting results were substituted into the original TCP formula to calculate 5-year biochemical relapse-free survival for further verification.ResultsInformation necessary for fitting could be extracted from a total of 23,281 PCa patients. A total of 16,442 PCa patients were grouped according to fractionation schedules. We found that, for patients who received conventionally fractionated radiotherapy, moderately hypofractionated radiotherapy, and stereotactic body radiotherapy, the average α/β ratios were 1.78 Gy (95% CI 1.59–1.98), 3.46 Gy (95% CI 3.27–3.65), and 4.24 Gy (95% CI 4.10–4.39), respectively. Hence, the calculated α/β ratios for PCa tended to become higher when the dose per fraction increased. Among all PCa patients, 14,641 could be grouped according to the risks of PCa in patients receiving radiotherapy with different fractionation schedules. The results showed that as the risk increased, the k (natural logarithm of an effective target cell number) and α values decreased, indicating that the number of effective target cells decreased and the radioresistance increased.ConclusionsThe LQ model appeared to be inappropriate for high doses per fraction owing to α/β ratios tending to become higher when the dose per fraction increased. Therefore, to convert the conventionally fractionated radiation doses to equivalent high doses per fraction using the standard LQ model, a higher α/β ratio should be used for calculation.
Minimally invasive surgery in emergency surgery: a WSES survey
Authors: Ceresoli Marco , Pisano Michele , Abu-Zidan Fikri , Allievi Niccolò , Gurusamy Kurinchi , Biffl Walt L. , Tebala Giovanni D. , Catena Fausto , Ansaloni Luca , Sartelli Massimo , Kluger Yoram , Baiocchi Gianluca ,   WSES MIS working group, Fette Andreas , Hecker Andreas , Litvin Andrey , Forgione Antonello , Leppaniemi Ari , De Simone Belinda , Sakakushev Boris , Palmatier Casey R. , Bendinelli Cino , Damaskos Dimitris , Picetti Edoardo , Tan Edward , Poiasina Elia , Pikoulis Emmanouil , Cicuttin Enrico , Moore Ernest E. , Velmahos George , Fraga Gustavo , Van Goor Harry , Civil Ian , Wani Imtiz , Di Carlo Isidoro , Galante Joseph , Søreide Kjetil , Degrate Luca , Zorcolo Luigi , De Moya Marc , Braga Marco , Cereda Marco , Sugrue Micheal , Chirica Mircea , De Angelis Nicola , Stahel Philip F. , Ivatury Rao , Ten Broek Richard , Di Saverio Salomone , Beka Solomon Gurmu , Magnone Stefano , Cui Yunfeng , Balogh Zsolt J. , Kelly Micheal Dennis , Inaba Kenji ,   WSES MIS consortia, Coccolini Federico 
Published: March 2022

Abstract
Background
The diffusion of minimally invasive surgery in emergency surgery still represents a developing challenge. Evidence about the use of minimally invasive surgery shows its feasibility and safety; however, the diffusion of these techniques is still poor. The aims of the present survey were to explore the diffusion and variations in the use of minimally invasive surgery among surgeons in the emergency setting.

Methods
This is a web-based survey administered to all the WSES members investigating the diffusion of minimally invasive surgery in emergency. The survey investigated personal characteristics of participants, hospital characteristics, personal confidence in the use of minimally invasive surgery in emergency, limitations in the use of it and limitations to prosecute minimally invasive surgery in emergency surgery. Characteristics related to the use of minimally invasive surgery were studied with a multivariate ordinal regression.

Results
The survey collected a total of 415 answers; 42.2% of participants declared a working experience > 15 years and 69.4% of responders worked in tertiary level center or academic hospital. In primary emergencies, only 28,7% of participants declared the use of laparoscopy in more than 50% of times. Personal confidence with minimally invasive techniques was the highest for appendectomy and cholecystectomy. At multivariate ordinal regression, a longer professional experience, the use of laparoscopy in major elective surgery and bariatric surgery expertise were related to a higher use of laparoscopy in emergency surgery.

Conclusions
The survey shows that minimally invasive techniques in emergency surgery are still underutilized. Greater focus should be placed on the development of dedicated training in laparoscopy among emergency surgeons.
Large medial meniscus extrusion and varus are poor prognostic factors of arthroscopic partial meniscectomy for degenerative medial meniscus lesions
Authors: Xu Tao , Xu Liuhai , Li Xinzhi , Zhou You 
Published: March 2022

AbstractBackgroundThe indications and efficacy after arthroscopic partial meniscectomy (APM) for degenerative medial meniscus lesions (DMMLs) have been controversial. The purpose of this study was to identify predictors of unfavorable clinical and radiologic outcomes after APM for DMMLs and to choose appropriate indications and improve treatment efficacy.MethodsA total of 86 patients with DMMLs undergoing APM were retrospectively reviewed. The mean follow-up time was 32.1 months. Clinical outcomes (including Lysholm score) and radiographic results (including Kellgren-Lawrence grade (K–L grade: 0/1/2/3/4) were evaluated at preoperative and final follow-up. Preoperative prognostic factors, including gender, age, Body Mass Index (BMI), Hip–Knee–Ankle (HKA), Medial Posterior Tibial Slope (MPTS), Medial Meniscus Extrusion (MME), K–L grade, occupational kneeling, and cartilaginous condition (Outerbridge grade ≤ 2, VS ≥ 3), for relatively unfavorable (fair or poor grade) Lysholm and progression of K–L grade, were investigated by multivariate logistic regression analysis. Receiver operating characteristic curve was used to identify a cutoff point for the extent of medial meniscal extrusion that was associated with the final Lysholm score.ResultsA significantly improved postoperative Lysholm score (84.5 ± 9.7) compared with the preoperative score (63.8 ± 9.3) (P < 0.001), but a progression of K–L grade (20/36/30/0/0–15/27/25/19/0) (P < 0.001). The adverse prognostic factor of Lysholm score was the advancing age (OR 1.109,P = 0.05) and HKA (OR 0.255,P < 0.001). The adverse prognostic factor of K–L grade progression was MME (OR 10.327,P < 0.001). The cutoff point for the relative value of preoperative medial meniscal extrusion associated with relatively unfavorable Lysholm scores was 2.05 mm (Area = 0.8668,Pvalue < 0.0001, Sensitivity = 62.16%, Specificity = 93.88%).ConclusionsClinically, varus alignment, large MME, and older age were found to predict a poor prognosis after APM for DMMLs. The preoperative extent of MME can be used as a predictive factor for osteoarthritis in APM. Patients with varus and MME should avoid APM. High tibial osteotomy may be an effective treatment strategy.
MiR-539-3p inhibited chondrogenic differentiation in human adipose stem cells by targeting Sox9
Authors: Qin Feng , Wang Fang , Wang Xiao-Ping , Chen Jie , Zeng Feng-hua , Sun Cui-Lan , Mao Jia-Cuo Peng , Li Chun-Liang 
Published: March 2022

Abstract
Background
Mesenchymal stem cells (MSCs) have emerged as the attractive candidates for cell therapy for cartilage repair in clinical therapy of osteoarthritis (OA). MiR-539-3p was reported to differentially express during chondrogenic differentiation of adipose stem cells (ASCs) by miRNA microarrays. The aim of the study was to investigate the effects and underlying mechanisms of miR-539-3p on chondrogenic differentiation of ASCs.

Methods
Human ASCs (hASCs) were obtained from liposuction and transfected with miR-539-3p mimic or inhibitor. Then, the cells were cultured in chondrogenic differentiation medium including transforming growth factor-β1 (TGF-β1).

Results
Our results found that miR-539-3p was gradually down-regulated during chondrogenic differentiation of hASCs. MiR-539-3p overexpression inhibited TGF-β1-induced chondrogenic differentiation of hASCs, as supported by reducing the gene and protein expression of chondrogenic differentiation markers type II collagen alpha 1 (COL2A1), aggrecan (ACAN), and type II collagen. In contrast, miR-539-3p inhibitor significantly promoted the chondrogenic differentiation of hASCs. Dual luciferase reporter assay demonstrated that Sox9 was a direct target gene of miR-539-3p. The expression of SRY-box transcription factor 9 (Sox9) was up-regulated progressively over time during chondrogenic differentiation of hASCs. Additionally, Sox9 overexpression notably reversed chondrogenic differentiation of hASCs inhibited by miR-539-3p mimic, as demonstrated by the decreased expression of COL2A1, ACAN, and type II collagen.

Conclusions
Altogether, miR-539-3p inhibited chondrogenic differentiation of hASCs by targeting Sox9. MiR-539-3p may have significant clinical applications for use as a targeted therapy of OA.
A novel 3D-printed patient-specific instrument based on “H-point” for medial opening wedge high tibial osteotomy: a cadaver study
Authors: Liu Guo-Bin , Liu Sen , Zhu Chao-Hua , Li Jia , Li Jun , Jia Guo-Xing , Dong Wei , Zhao Feng , Huang Ye 
Published: March 2022

Abstract
Background
Opening wedge high tibial osteotomy (OWHTO) is an effective surgical treatment for knee osteoarthritis. This study aimed to explore the feasibility and accuracy of a novel 3D-printed patient-specific instrument (PSI) based on “H-point” for medial OWHTO in a prospective cadaver study.

Methods
Twenty-six fresh-frozen lower limbs were collected and randomly divided into two groups: PSI group treated with 3D virtual preoperative planning and a novel 3D-printed PSI; control group with the standard technique. 3D models were reversely reconstructed for preoperative surgical planning, guide plate design, and simulated osteotomy. Anatomic features of “H-point,” surgical time, fluoroscopic dose, correction accuracy including tibiofemoral angle (FTA) and posterior tibial slope (TS) angle were measured.

Results
First, H-point was always described as a bony bulge in the posteromedial to the proximal tibia and had a relatively constant relationship with the osteotomy site. Second, the absolute correction error of mFTA and TS were significantly smaller in the PSI group. The effective rate of TS in the PSI group was more concentrated with absolute correction error within 1° and within 2° for 53.3% and 93.3%, compared to 9.1% and 45.5% in the control group. The total operation time, positioning osteotomy time, distraction correction time and fluoroscopy dose in the PSI group were significantly less than those in the control group.

Conclusions
The novel 3D-printed PSI based on H-point is feasibility and accuracy with advantages in terms of TS, surgery time and radiation dose for OWHTO.
Development and validation of derivative UV spectroscopic method for simultaneous estimation of nicotinamide and tretinoin in their binary mixtures and pharmaceutical preparations
Authors: Sarkis Nazira , Sawan Abdulkader 
Published: March 2022

AbstractAn accurate, precise, sensitive, and simple spectroscopic method was developed and validated for simultaneous quantification analysis of tretinoin (TRT) and nicotinamide (NCT) with a ratio of 1:40 (TRT: NCT) in a synthetic mixture from dermal pharmaceutical preparations (solution and cream). Wavelengths were chosen in the first and second-order derivatives which are valid for the determination of NCT with the existence of TRT and excipients of the tested pharmaceutical preparations. Wavelength 253 nm was picked for the first-order derivative. Wavelengths 245 and 269 nm were picked for the second derivative. All previous wavelengths were zero-crossing points for TRT and its pharmaceutical preparations. Zero-order spectroscopy was used to determine TRT at the wavelength 348 nm, where no interference with NCT or any substance in the previous pharmaceutical preparation. The linearity range was studied and found to be 20–120 μg/mL and 0.5–5.0 μg/mL for NCT and TRT respectively. The correlation coefficient was 0.9995–0.9999 for NCT and 0.9998–0.9999 for TRT. The limit of detection (LOD) and the limit of quantification (LOQ) of NCT were 1.510 μg/mL and 4.590 μg/mL respectively at the wavelength 269 nm of the second-order derivative.