bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring pathological signatures for predicting the recurrence of early-stage hepatocellular carcinoma based on deep learning
Authors: Qu Wei-Feng , Tian Meng-Xin , Qiu Jing-Tao , Guo Yu-Cheng , Tao Chen-Yang , Liu Wei-Ren , Tang Zheng , Qian Kun , Wang Zhi-Xun , Li Xiao-Yu , Hu Wei-An , Zhou Jian , Fan Jia , Zou Hao , Hou Ying-Yong , Shi Ying-Hong 
Published: August 2022

BackgroundPostoperative recurrence impedes the curability of early-stage hepatocellular carcinoma (E-HCC). We aimed to establish a novel recurrence-related pathological prognosticator with artificial intelligence, and investigate the relationship between pathological features and the local immunological microenvironment.MethodsA total of 576 whole-slide images (WSIs) were collected from 547 patients with E-HCC in the Zhongshan cohort, which was randomly divided into a training cohort and a validation cohort. The external validation cohort comprised 147 Tumor Node Metastasis (TNM) stage I patients from The Cancer Genome Atlas (TCGA) database. Six types of HCC tissues were identified by a weakly supervised convolutional neural network. A recurrence-related histological score (HS) was constructed and validated. The correlation between immune microenvironment and HS was evaluated through extensive immunohistochemical data.ResultsThe overall classification accuracy of HCC tissues was 94.17%. The C-indexes of HS in the training, validation and TCGA cohorts were 0.804, 0.739 and 0.708, respectively. Multivariate analysis showed that the HS (HR= 4.05, 95% CI: 3.40-4.84) was an independent predictor for recurrence-free survival. Patients in HS high-risk group had elevated preoperative alpha-fetoprotein levels, poorer tumor differentiation and a higher proportion of microvascular invasion. The immunohistochemistry data linked the HS to local immune cell infiltration. HS was positively correlated with the expression level of peritumoral CD14+ cells (p= 0.013), and negatively with the intratumoral CD8+ cells (p&lt; 0.001).ConclusionsThe study established a novel histological score that predicted short-term and long-term recurrence for E-HCCs using deep learning, which could facilitate clinical decision making in recurrence prediction and management.
Predicting recurrence and metastasis risk of endometrial carcinoma via prognostic signatures identified from multi-omics data
Authors: Li Ling , Qiu Wenjing , Lin Liang , Liu Jinyang , Shi Xiaoli , Shi Yi 
Published: August 2022

ObjectivesEndometrial carcinoma (EC) is one of the three major gynecological malignancies, in which 15% - 20% patients will have recurrence and metastasis. Though there are many studies on the prognosis on this cancer, the performances of existing models evaluating the risk of its recurrence and metastasis are yet to be improved. In addition, a comprehensive multi-omics analyses on the prognostic signatures of EC are on demand. In this study, we aimed to construct a relatively stable and reliable model for predicting recurrence and metastasis of EC. This will help determine the risk level of patients and choose appropriate adjuvant therapy, thereby avoiding improper treatment, and improving the prognosis of patients.MethodsThe mRNA, microRNA (miRNA), long non-coding RNA (lncRNA), copy number variation (CNV) data and clinical information of patients with EC were downloaded from The Cancer Genome Atlas (TCGA). Differential expression analyses were performed between the recurrence or metastasis group and the non-recurrence/metastasis group. Then, we screened potential prognostic markers from the four kinds of omics data respectively and established prediction models using three classifiers.ResultsWe achieved differential expressed mRNAs, lncRNAs, miRNAs and CNVs between the two groups. According to feature selection scores by the random forest algorithm, 275 CNV features, 50 lncRNA features, 150 miRNA features and 150 mRNA features were selected, respectively. And the prediction model constructed by the features of lncRNA data using random forest method showed the best performance, with an area under the curve of 0.763, and an accuracy of 0.819 under 10-fold cross-validation.ConclusionWe developed a computational model using omics information, which is able to predicting recurrence and metastasis risk of EC accurately.
Monocytes acquire prostate cancer specific chromatin conformations upon indirect co-culture with prostate cancer cells
Authors: Alshaker Heba , Hunter Ewan , Salter Matthew , Ramadass Aroul , Westra Willem , Winkler Mathias , Green Jayne , Akoulitchev Alexandre , Pchejetski Dmitri 
Published: August 2022

BackgroundThree-dimensional chromosome loop conformations are powerful regulators of gene expression. These chromosome conformations can be detected both in tumour and in circulating cells and have significant disease biomarker potential. We have recently detected specific chromosome conformations in circulating cells of patients with prostate cancer (PCa) which were similar to ones found in their primary tumours, however, the possibility of horizontal transfer of chromosome conformations was not studied previously.MethodsHuman monocytes (U937) were co-cultured in Boyden chambers through 0.4 uM membrane with or without PC-3 human PCa cells or their conditioned media and a custom DNA microarray for 900,000 chromosomal loops covering all coding loci and non-coding RNA genes was performed on each part of the co-culture system.ResultsWe have detected 684 PC-3 cell-specific chromosome conformations across the whole genome that were absent in naïve monocytes but appeared in monocytes co-cultured with PC-3 cells or with PC-3-conditioned media. Comparing PC3-specific conformations to the ones we have previously detected in systemic circulation of high-risk PCa patients revealed 9 positive loops present in both settings.ConclusionsOur results demonstrate for the first time a proof of concept for horizontal transfer of chromosome conformations without direct cell-cell contact. This carries high clinical relevance as we have previously observed chromatin conformations in circulating cells of patients with melanoma and PCa similar to ones in their primary tumours. These changes can be used as highly specific biomarkers for diagnosis and prognosis. Further studies are required to elucidate the specific mechanism of chromosome conformations transfer and its clinical significance in particular diseases.
A correlation between Magnetic Resonance Spectroscopy (1-H MRS) and the neurodevelopment of two-year-olds born preterm in an EPIRMEX cohort study
Authors: Gire Catherine , Berbis Julie , Dequin Marion , Marret Stéphane , Muller Jean-Baptiste , Saliba Elie , Tosello Barthélémy 
Published: August 2022

BackgroundPreterm infants are at risk of neurodevelopmental impairments. At present, proton magnetic resonance spectroscopy (1H-MRS) is currently used to evaluate brain metabolites in asphyxiated term infants. The purpose of this study was to identify in the preterm EPIRMEX cohort any correlations between (1H-MRS) metabolites ratio at term equivalent age (TEA) and neurodevelopmental outcomes at 2 years.MethodsOur study included EPIRMEX eligible patients who were very preterm infants (gestational age at birth ≤32 weeks) and who underwent a brain MRI at TEA and 1H-MRS using a monovoxel technique. The volumes of interest (VOI) were periventricular white matter posterior area and basal ganglia. The ratio of N Acetyl Aspartate (NAA) to Cho (Choline), NAA to Cr (creatine), Cho to Cr, and Lac (Lactate) to Cr were measured. Neurodevelopment was assessed at 24 months TEA with ASQ (Ages and Stages Questionnaire).ResultsA total of 69 very preterm infants had a 1H-MRS at TEA. In white matter there was a significant correlation between a reduction in the NAA/Cho ratio and a total ASQ and/or abnormal communication score, and an increase in the Lac/Cr ratio and an abnormality of fine motor skills. In the gray nuclei there was a trend correlation between the reduction in the NAA/Cho ratio and sociability disorders; and the increase in the Lac/Cr ratio and an anomaly in problem-solving.ConclusionsUsing NAA as a biomarker, the vulnerability of immature oligodendrocytes in preterm children at TEA was correlated to neurodevelopment at 2 years. Similarly, the presence of lactate at TEA was associated with abnormal neurodevelopment at 2 years in the preterm brain.
Bioactive natural products in COVID-19 therapy
Authors: Wang Zhonglei , Wang Ning , Yang Liyan , Song Xian-qing 
Published: August 2022

The devastating COVID-19 pandemic has caused more than six million deaths worldwide during the last 2 years. Effective therapeutic agents are greatly needed, yet promising magic bullets still do not exist. Numerous natural products (cordycepin, gallinamide A, plitidepsin, telocinobufagin, and tylophorine) have been widely studied and play a potential function in treating COVID-19. In this paper, we reviewed published studies (from May 2021 to April 2022) relating closely to bioactive natural products (isolated from medicinal plants, animals products, and marine organisms) in COVID-19 therapyin vitroto provide some essential guidance for anti-SARS-CoV-2 drug research and development.
The evaluation of ADME and pharmacokinetic properties of decoquinate derivatives for the treatment of malaria
Authors: Watson Daniel J. , Laing Lizahn , Beteck Richard M. , Gibhard Liezl , Haynes Richard K. , Wiesner Lubbe 
Published: August 2022

The emergence of Plasmodium falciparum (Pf) parasite strains tolerant of the artemisinin component and resistant to the other drug component in artemisinin combination therapies (ACTs) used for treatment now markedly complicates malaria control. Thus, development of new combination therapies are urgently required. For the non-artemisinin component, the quinolone ester decoquinate (DQ) that possesses potent activities against blood stage Pf and acts on a distinct target, namely the Pf cytochrome bc1 complex, was first considered. However, DQ has poor drug properties including high lipophilicity and exceedingly poor aqueous solubility (0.06 μg/ml), rendering it difficult to administer. Thus, DQ was chemically modified to provide the secondary amide derivative RMB005 and the quinoline O-carbamate derivatives RMB059 and RMB060. The last possesses sub-nanomolar activities against multidrug resistant blood stages of Pf, and P. berghei sporozoite liver stages. Here we present the results of ADME analyses in vitro and pharmacokinetic analyses using C57BL/6 mice. The amide RMB005 had a maximum mean whole blood concentration of 0.49 ± 0.02 µM following oral administration; however, the area under the curve (AUC), elimination half-life (t1/2) and bioavailability (BA) were not significantly better than those of DQ. Surprisingly, the quinoline O-carbamates which can be recrystallized without decomposition were rapidly converted into DQ in human plasma and blood samples. The maximum concentrations of DQ reached after oral administration of RMB059 and RMB060 were 0.23 ± 0.05 and 0.11 ± 0.01 µM, the DQ elimination half-lives were 4.79 ± 1.66 and 4.66 ± 1.16 h, and the DQ clearance were 19.40 ± 3.14 and 21.50 ± 3.38 respectively. Under these assay conditions, the BA of DQ could not be calculated Overall although RMB059 and -060 are labile in physiological medium with respect to the DQ parent, the potential to apply these as prodrugs is apparent from the current data coupled with their ease of preparation.
Potential therapeutic applications of infusions and hydroalcoholic extracts of Romanian glutinous sage (Salvia glutinosa L.)
Authors: Nicolescu Alexandru , Babotă Mihai , Ilea Maria , Dias Maria Inês , Calhelha Ricardo C. , Gavrilaș Laura , Rocchetti Gabriele , Crișan Gianina , Mocan Andrei , Barros Lillian , Pârvu Alina Elena 
Published: August 2022

Ethnopharmacological relevance:Salvia glutinosa, also known as the glutinous sage, has been used in Romanian folk medicine in the treatment of inflammation, injuries, and mild infections. However, there is no direct scientific evidence to demonstrate these activities.Aim of the Study: The present research was based on evaluating antioxidant, antiproliferative, and α-glucosidase inhibitory activity of S. glutinosa extracts, as well as the in vivo anti-inflammatory activity.Materials and Methods: Infusions and 70% (v:v) ethanol solution extracts of S. glutinosa stems and leaves, collected from two different locations in Romania, were prepared. Ten phenolic compounds were identified and quantified using the LC-DAD-ESI/MSn method, and total phenolic and flavonoid content, as well as in vitro antioxidant (DPPH, ABTS, and FRAP assays), antiproliferative, anti-inflammatory and alpha-glucosidase inhibitory activities were determined. A rat model of induced inflammation with turpentine oil was used for the examination of in vivo effects of the extracts, using diclofenac as an anti-inflammatory control.Results: The highest inhibitory α-glucosidase activity was determined to be IC50 = 0.546 mg/ml for the hydroalcoholic extract made with plant material collected on the road to Sighișoara. The highest cytotoxic activity against HepG2 cell line was determined to be GI50 = 131.68 ± 5.03 μg/ml, for the hydroalcoholic extract made with plant material from Sighișoara. In vivo administration of extract (200 mg lyophilized powder/ml) showed a significant reduction of NO production.Conclusion: Our findings indicate that S. glutinosa extracts exhibit antioxidant, α-glucosidase inhibitory activity, as well as a modest cytotoxic effect on HepG2 cell line. By in vivo administration, the extracts show anti-inflammatory and antioxidant activity, which correlates with the traditional use of the species. The environmental conditions seemed to induce important changes in the chemical composition and the bioactivity of the herbal preparations derived from S. glutinosa.
The expression and significance of efferocytosis and immune checkpoint related molecules in pancancer samples and the correlation of their expression with anticancer drug sensitivity
Authors: Cheng Lin , Weng Bangbi , Jia Changsheng , Zhang Lin , Hu Bin , Deng Li , Mou Nan , Sun Fengjun , Hu Jing 
Published: August 2022

Background: The efferocytosis-related molecules have been considered to be correlated with the resistance to cancer chemotherapy. The aim of this study was to investigate the expression and significance of efferocytosis-related molecules in cancers and the correlation of their expression with anticancer drug sensitivity, and provide new potential targets and treatment options for cancers.Methods: We investigated the differential expression of 15 efferocytosis-related molecules (Axl, Tyro3, MerTK, CX3CL1, Tim-4, BAI1, Stab2, Gas6, IDO1, Rac1, MFGE8, ICAM-1, CD47, CD31, and PD-L1) and other 12 common immune checkpoint-related molecules in tumor and normal tissues, the correlation between their expression and various clinicopathological features in 16 types of cancers using publicly available pancancer datasets in The Cancer Genome Atlas. We also analyzed the correlation of the expression of efferocytosis and immune checkpoint related molecules with 126 types of anticancer drugs sensitivity using drug-RNA-seq data.Results: There is a panel of circulating molecules among the 27 molecules. Based on the results of differential expression and correlation with various clinicopathological features of efferocytosis-related molecules in cancers, we identified new potential therapeutic targets for anticancer therapy, such as Axl for kidney renal clear cell carcinoma, Tyro3 for liver hepatocellular carcinoma, and IDO1 for renal papillary cell carcinoma. Except for BAI1, CD31, and MerTK, the enhanced expressions of Axl, Tyro3, Gas6, MFGE8, Stab2, Tim-4, CX3CL1, IDO1, Rac1, and PD-L1 were associated with decreased sensitivity of the cancer cells to many anti-cancer drugs; however, for other common immune checkpoint-related molecules, only enhanced expressions of PD-1, CD28, CTLA4, and HVEM were associated with decreased sensitivity of the cancer cells to a few drugs.Conclusion: The efferocytosis-related molecules were significantly associated with clinical outcomes in many types of cancers and played important roles in resistance to chemotherapy. Combination therapy targeting efferocytosis-related molecules and other immune checkpoint-related molecules is necessary to reduce resistance to chemotherapy.
Time Course of Recovery Following CrossFit® Karen Benchmark Workout in Trained Men
Authors: Sousa Neto Ivo Vieira de , Sousa Nuno Manuel Frade de , Neto Frederico Ribeiro , Falk Neto Joao Henrique , Tibana Ramires Alsamir 
Published: August 2022

The establishment of fatigue following the acute exercise stimulus is a complex and multi-factorial process, that might arise due to a range of distinct physiological mechanisms. However, a practical method of assessing CrossFit® athletes’ recovery status has been neglected entirely in real-world sporting practice. The study describes the acute and delayed time course of recovery following the CrossFit® Benchmark Workout Karen. Eight trained men (28.4 ± 6.4 years; 1RM back squat 139.1 ± 26.0 kg) undertook the Karen protocol. The protocol consists of 150 Wall Balls (9 kg), aiming to hit a target 3 m high. Countermovement jump height (CMJ), creatine kinase (CK), and perceived recovery status scale (PRS) (general, lower and upper limbs) were assessed pre, post-0h, 24, 48 and 72 h after the session. The creatine kinase concentration 24 h after was higher than pre-exercise (338.4 U/L vs. 143.3 U/L; p = 0.040). At 48h and 72 h following exercise, CK concentration had returned to baseline levels (p &gt; 0.05). The general, lower and upper limbs PRS scores were lower in the 24-h post-exercise compared to pre-exercise (general PRS: 4.7 ± 1.5 and 7.7 ± 1.7; p = 0.013; upper limbs PRS: 6.6 ± 1.3 and 7.5 ± 1.3; p = 0.037; lower limbs PRS: 3.9 ± 2.5 and 7.3 ± 0.1; p = 0.046). Our findings provide insights into the fatigue profile and recovery in acute CrossFit® and can be useful to coaches and practitioners when planning training programs. Moreover, recovery status can be useful to optimize training monitoring and to minimize the potential detrimental effects associated with the performance of repeated high-intensity sessions of CrossFit®.
Effects of high-intensity interval training with hyperbaric oxygen
Authors: Alvarez Villela Miguel , Dunworth Sophia A. , Kraft Bryan D. , Harlan Nicole P. , Natoli Michael J. , Suliman Hagir B. , Moon Richard E. 
Published: August 2022

Hyperbaric Oxygen (HBO2) has been proposed as a pre-conditioning method to enhance exercise performance. Most prior studies testing this effect have been limited by inadequate methodologies. Its potential efficacy and mechanism of action remain unknown. We hypothesized that HBO2 could enhance aerobic capacity by inducing mitochondrial biogenesis via redox signaling in skeletal muscle. HBO2 was administered in combination with high-intensity interval training (HIIT), a potent redox stimulus known to induce mitochondrial biogenesis. Aerobic capacity was tested during acute hypobaric hypoxia seeking to shift the limiting site of whole body V̇O2 from convection to diffusion, more closely isolating any effect of improved oxidative capacity. Healthy volunteers were screened with sea-level (SL) V̇O2peak testing. Seventeen subjects were enrolled (10 men, 7 women, ages 26.5±1.3 years, BMI 24.6±0.6 kg m−2, V̇O2peak SL = 43.4±2.1). Each completed 6 HIIT sessions over 2 weeks randomized to breathing normobaric air, “HIIT+Air” (PiO2 = 0.21 ATM) or HBO2 (PiO2 = 1.4 ATM) during training, “HIIT+HBO2” group. Training workloads were individualized based on V̇O2peak SL test. Vastus Lateralis (VL) muscle biopsies were performed before and after HIIT in both groups. Baseline and post-training V̇O2peak tests were conducted in a hypobaric chamber at PiO2 = 0.12 ATM. HIIT significantly increased V̇O2peak in both groups: HIIT+HBO2 31.4±1.5 to 35.2±1.2 ml kg−1·min−1 and HIIT+Air 29.0±3.1 to 33.2±2.5 ml kg−1·min−1 (p = 0.005) without an additional effect of HBO2 (p = 0.9 for interaction of HIIT x HBO2). Subjects randomized to HIIT+HBO2 displayed higher skeletal muscle mRNA levels of PPARGC1A, a regulator of mitochondrial biogenesis, and HK2 and SLC2A4, regulators of glucose utilization and storage. All other tested markers of mitochondrial biogenesis showed no additional effect of HBO2 to HIIT. When combined with HIIT, short-term modest HBO2 (1.4 ATA) has does not increase whole-body V̇O2peak during acute hypobaric hypoxia. (ClinicalTrials.gov Identifier: NCT02356900; https://clinicaltrials.gov/ct2/show/NCT02356900).
A combination of cherry juice and cold water immersion does not enhance marathon recovery compared to either treatment in isolation: A randomized placebo-controlled trial
Authors: Difranco Isabella , Cockburn Emma , Dimitriou Lygeri , Paice Katherine , Sinclair Scott , Faki Tanwir , Hills Frank A. , Gondek Marcela B. , Wood Alyssa , Wilson Laura J. 
Published: August 2022

PurposeCherry juice (CJ) and cold water immersion (CWI) are both effective recovery strategies following strenuous endurance exercise. However, athletes routinely combine recovery interventions and less is known about the impact of a combined CJ and CWI protocol. Therefore, this study investigated the effects of combining CWI and CJ (a “cocktail” (CT)) on inflammation and muscle damage following a marathon.MethodsA total 39 endurance trained males were randomly assigned to a placebo (PL), CWI, CJ, or CT group before completing a trail marathon run. Muscle damage (creatine kinase (CK)), muscle function (maximal voluntary isometric contraction (MVIC)), and inflammation (interleukin-6 (IL-6); C-reactive protein (CRP)) were measured at baseline, immediately after marathon (only IL-6), 24 h, and 48 h after marathon.ResultsThere were no statistically significant differences between groups and no group × time interaction effects for any of the dependent variables. Confidence intervals (CI) illustrated that CT had unclear effects on inflammation (IL-6; CRP) and MVIC, but may have increased CK to a greater extent than PL and CJ conditions.ConclusionThere is no evidence of an additive effect of CJ and CWI when the treatments are used in conjunction with each other. On the contrary, combining CJ and CWI may result in slightly increased circulating CK.
An improved bone transport surgical method for treating chronic ischemic ulcers (thromboangiitis obliterans)
Authors: Zhao Liang , Lei Yu , Pang Mengru , Wei Zairong 
Published: August 2022

IntroductionThe chronic ischemic injury of the upper/lower limbs caused by thromboangiitis obliterans (TAO, Buerger's disease) is difficult to heal, leading to high morbidity and amputation risk, seriously lowering the quality of life of patients. So far, the pathogenesis of this disease is still not clear, and there are still no effective therapeutic approaches. Here, we first use an improved bone transport technique to treat TAO-related foot ulcers and achieve good therapeutic effects.Materials and MethodsIn this report, 22 patients met the inclusion criteria, and we provide an improved bone transport technique to repair TAO-related chronic lower limb wounds, which have a minimally surgical incision and a satisfying surgical field.ResultsThe improved bone transport technique resulted in TAO-related chronic lower extremity wound healing in most patients (18, M:F 16:2) within the first treatment cycle. All wounds healed completely after two treatment cycles. After these cycles, the cold sensation in the patients’ feet was significantly relieved, and the rest pain in the lower extremities was significantly relieved (Visual Analog Scale, P &lt; 0.0001). Furthermore, the Laser Doppler flowmeter showed that the blood perfusion and percutaneous oxygen pressure of the affected foot were higher than in preoperation (P &lt; 0.0001). To conclude, bone transport technology is available for the refractory wounds of the extremity, which may promote healing by increasing blood circulation and tissue oxygen supply.ConclusionsIn summary, the improved surgical method of the bone transport technique is worth considering in the treatment of thromboangiitis obliterans–related foot ulcers.