bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circular RNAs in the tumour microenvironment
Authors: Ma Zhonghua , Shuai You , Gao Xiangyu , Wen Xianzi , Ji Jiafu 
Published: January 2020

AbstractBackgroundCircular RNAs (circRNAs) are a new class of endogenous non-coding RNAs (ncRNAs) widely expressed in eukaryotic cells. Mounting evidence has highlighted circRNAs as critical regulators of various tumours. More importantly, circRNAs have been revealed to recruit and reprogram key components involved in the tumour microenvironment (TME), and mediate various signaling pathways, thus affecting tumourigenesis, angiogenesis, immune response, and metastatic progression.Main body of the abstractIn this review, we briefly introduce the biogenesis, characteristics and classification of circRNAs, and describe various mechanistic models of circRNAs. Further, we provide the first systematic overview of the interplay between circRNAs and cellular/non-cellular counterparts of the TME and highlight the potential of circRNAs as prospective biomarkers or targets in cancer clinics. Finally, we discuss the biological mechanisms through which the circRNAs drive development of resistance, revealing the mystery of circRNAs in drug resistance of tumours.Short conclusionDeep understanding the emerging role of circRNAs and their involvements in the TME may provide potential biomarkers and therapeutic targets for cancer patients. The combined targeting of circRNAs and co-activated components in the TME may achieve higher therapeutic efficiency and become a new mode of tumour therapy in the future.
Triglyceride glucose index is a useful marker for predicting subclinical coronary artery disease in the absence of traditional risk factors
Authors: Park Gyung-Min , Cho Young-Rak , Won Ki-Bum , Yang Yu Jin , Park Sangwoo , Ann Soe Hee , Kim Yong-Giun , Park Eun Ji , Kim Shin-Jae , Lee Sang-Gon , Yang Dong Hyun , Kang Joon-Won , Lim Tae-Hwan , Kim Hong-Kyu , Choe Jaewon , Lee Seung-Whan , Kim Young-Hak 
Published: January 2020

Abstract
Background
Atherosclerotic cardiovascular (CV) events commonly occur in individuals with a low CV risk burden. This study evaluated the ability of the triglyceride glucose (TyG) index to predict subclinical coronary artery disease (CAD) in asymptomatic subjects without traditional CV risk factors (CVRFs).

Methods
This retrospective, cross-sectional, and observational study evaluated the association of TyG index with CAD in 1250 (52.8 ± 6.5 years, 46.9% male) asymptomatic individuals without traditional CVRFs (defined as systolic/diastolic blood pressure ≥ 140/90 mmHg; fasting glucose ≥126 mg/dL; total cholesterol ≥240 mg/dL; low-density lipoprotein cholesterol ≥160 mg/dL; high-density lipoprotein cholesterol < 40 mg/dL; body mass index ≥25.0 kg/m2; current smoking; and previous medical history of hypertension, diabetes, or dyslipidemia). CAD was defined as the presence of any coronary plaque on coronary computed tomographic angiography. The participants were divided into three groups based on TyG index tertiles.

Results
The prevalence of CAD increased with elevating TyG index tertiles (group I: 14.8% vs. group II: 19.3% vs. group III: 27.6%; P < 0.001). Multivariate logistic regression models showed that TyG index was associated with an increased risk of CAD (odds ratio [OR] 1.473, 95% confidence interval [CI] 1.026–2.166); especially non-calcified (OR 1.581, 95% CI 1.002–2.493) and mixed plaques (OR 2.419, 95% CI 1.051–5.569) (all P < 0.05). The optimal TyG index cut-off for predicting CAD was 8.44 (sensitivity 47.9%; specificity 68.5%; area under the curve 0.600; P < 0.001). The predictive value of this cut-off improved after considering the non-modifiable factors of old age and male sex.

Conclusions
TyG index is an independent marker for predicting subclinical CAD in individuals conventionally considered healthy.
Assessment of outcomes and novel immune biomarkers in metaplastic breast cancer: a single institution retrospective study
Authors: Morgan Evan , Suresh Anupama , Ganju Akaansha , Stover Daniel G. , Wesolowski Robert , Sardesai Sagar , Noonan Anne , Reinbolt Raquel , VanDeusen Jeffrey , Williams Nicole , Cherian Mathew A. , Li Zaibo , Young Gregory , Palettas Marilly , Stephens Julie , Liu Joseph , Luff Amanda , Ramaswamy Bhuvaneswari , Lustberg Maryam 
Published: January 2020

Abstract
Background
Metaplastic breast cancer remains poorly characterized given its rarity and heterogeneity. The majority of metaplastic breast cancers demonstrate a phenotype of triple-negative breast cancer; however, differences in clinical outcomes between metaplastic breast cancer and triple-negative breast cancer in the era of third-generation chemotherapy remain unclear.

Methods
We compared the clinical outcomes between women with metaplastic breast cancer and women with triple-negative breast cancer diagnosed between 1994 and 2014. Metaplastic breast cancer patients were matched 1:3 to triple-negative breast cancer patients by stage and age at diagnosis. Distant disease-free survival (DDFS) and overall survival (OS) were estimated using Kaplan Meier methods and Cox proportional hazard regression models. Immune checkpoint markers were characterized by immunohistochemistry in a subset of samples.

Results
Forty-four metaplastic breast cancer patients (stage I 14%; stage II 73%; stage III 11%; stage IV 2%) with an average age of 55.4 (± 13.9) years at diagnosis. Median follow-up for the included metaplastic breast cancer and triple-negative breast cancer patients (n = 174) was 2.8 (0.1–19.0) years. The DDFS and OS between matched metaplastic breast cancer and triple-negative breast cancer patients were similar, even when adjusting for clinical covariates (DDFS: HR = 1.64, p = 0.22; OS: HR = 1.64, p = 0.26). Metaplastic breast cancer samples (n = 27) demonstrated greater amount of CD163 in the stroma (p = 0.05) and PD-L1 in the tumor (p = 0.01) than triple-negative breast cancer samples (n = 119), although more triple-negative breast cancer samples were positive for CD8 in the tumor than metaplastic breast cancer samples (p = 0.02).

Conclusions
Patients with metaplastic breast cancer had similar outcomes to those with triple-negative breast cancer based on DDFS and OS. The immune checkpoint marker profile of metaplastic breast cancers in this study may prove useful in future studies attempting to demonstrate an association between immune profile and survival.
Targeting the orphan nuclear receptor NR2F6 in T cells primes tumors for immune checkpoint therapy
Authors: Klepsch Victoria , Pommermayr Maria , Humer Dominik , Brigo Natascha , Hermann-Kleiter Natascha , Baier Gottfried 
Published: January 2020

Abstract
Background
NR2F6 has been proposed as an alternative cancer immune checkpoint in the effector T cell compartment. However, a realistic assessment of the in vivo therapeutic potential of NR2F6 requires acute depletion.

Methods
Employing primary T cells isolated from Cas9-transgenic mice for electroporation of chemically synthesized sgRNA, we established a CRISPR/Cas9-mediated acute knockout protocol of Nr2f6 in primary mouse T cells.

Results
Analyzing these Nr2f6CRISPR/Cas9 knockout T cells, we reproducibly observed a hyper-reactive effector phenotype upon CD3/CD28 stimulation in vitro, highly reminiscent to Nr2f6−/− T cells. Importantly, CRISPR/Cas9-mediated Nr2f6 ablation prior to adoptive cell therapy (ACT) of autologous polyclonal T cells into wild-type tumor-bearing recipient mice in combination with PD-L1 or CTLA-4 tumor immune checkpoint blockade significantly delayed MC38 tumor progression and induced superior survival, thus further validating a T cell-inhibitory function of NR2F6 during tumor progression.

Conclusions
These findings indicate that Nr2f6CRISPR/Cas9 knockout T cells are comparable to germline Nr2f6−/− T cells, a result providing an independent confirmation of the immune checkpoint function of lymphatic NR2F6. Taken together, CRISPR/Cas9-mediated acute Nr2f6 gene ablation in primary mouse T cells prior to ACT appeared feasible for potentiating established PD-L1 and CTLA-4 blockade therapies, thereby pioneering NR2F6 inhibition as a sensitizing target for augmented tumor regression.

Graphical abstract
‘Social screens’ and ‘the mainstream’: longitudinal competitors of non-organized physical activity in the transition from childhood to adolescence
Authors: Kemp Byron J. , Parrish Anne-Maree , Cliff Dylan P. 
Published: January 2020

Abstract
Background
Physical activity (PA) tends to decline during late childhood and adolescence. In Australia, this decline has been shown to occur particularly in non-organized PA (e.g. active play and informal sport). Using a social marketing approach, segments of youth may be identified and targeted based on their profile of alternative activities that compete with non-organized PA during the transition to adolescence. The objectives of this study were to identify and describe segments of youth whose participation in non-organized PA declined between 11 and 13 years, based on changes in other potential competing activities during this period.

Methods
Data were sourced from Waves 4 and 5 of the Longitudinal Study of Australian Children. Participation in non-organized PA and thirteen alternative activities (e.g. video games, homework, sleep) were measured using 24-h time-use diaries. Analyses were limited to participants whose non-organized PA had declined between 11 and 13 years (n = 1043). Two-stage cluster analysis was conducted and segments were described using chi-square and t-tests.

Results
Among the analytic sample, average non-organized PA participation declined by 87 min/day between 11y and 13y (p < 0.001). Two segments were identified (κ = 0.66). The ‘Social Screens’ segment (n = 143) had large increases in texting, emailing and social media use (+ 56 min/day, p < 0.001) and other internet use (+ 32 min/day, p < 0.001). Conversely, ‘the Mainstream’ segment (n = 900) had smaller increases in a wider range of activities, including other PA (organized PA, active transport, active chores/work) (+ 16.0 min/day, p < 0.001), homework/study (+ 9.5 min/day, p < 0.001) and electronic gaming (+ 6.7 min/day, p < 0.05). ‘Social Screens’ were more likely to attend public school, live in urban areas and have more advanced pubertal development (girls only). ‘The Mainstream’ were more likely to participate in PA and out-of-school activities.

Conclusions
The ‘Social Screens’ segment had a much larger increase in texting, emailing, social media and other internet use, and lower participation in overall PA and out-of-school activities, compared with ‘the Mainstream’. Future research may trial PA promotion strategies to replace benefits that this segment may seek in competing activities (e.g. social PA apps).
Phase I and registry study of autologous bone marrow concentrate evaluated in PDE5 inhibitor refractory erectile dysfunction
Authors: Bieri Mark , Said Elias , Antonini Gabrielle , Dickerson Donald , Tuma Jorge , Bartlett Courtney E. , Patel Amit N. , Gershman Alexander 
Published: January 2020

Abstract
Background
Bone marrow mononuclear cells have been successfully utilized for numerous regenerative purposes. In the current study, patients suffering from erectile dysfunction (ED) unresponsive to phosphodiesterase 5 inhibitors were administered autologous bone marrow concentrate delivered intracavernously utilizing a point of care FDA cleared medical device.

Methods
A total of 40 patients were treated in the primary trial and 100 in the clinical registry, with the longest follow up of 12 months.

Results
Minimal treatment associated adverse effects where observed related to short term bruising at the site of harvest or injection. No long-term adverse events were noted related to the intervention. Mean improvements in IIEF-5 score were 2 in the Caverstem 1.0 low dose group, 3 in the high dose Caverstem 1.0 group and 9 in the Caverstem 2.0 group. Furthermore, improvements peaked by 3 months and maintained at 6 months follow-up.

Conclusion
These data support the safety and efficacy of point of care, minimally to non-manipulated, non-expanded bone marrow concentrate for the treatment of ED.
Trial registration Funded by Creative Medical Health, Inc.; Clinicaltrials.gov number: NCT03699943; https://clinicaltrials.gov/ct2/show/NCT03699943?term=caverstem&rank=1; initially registered December 12, 2015.
Body image perception and body composition: assessment of perception inconsistency by a new index
Authors: Zaccagni Luciana , Rinaldo Natascia , Bramanti Barbara , Mongillo Jessica , Gualdi-Russo Emanuela 
Published: January 2020

Abstract
Background
A correct perception of the body image, as defined by comparison with actual anthropometric analyses, is crucial to ensure the best possible nutritional status of each individual. Bioimpedance analysis (BIA) represents a leading technique to assess body composition parameters and, in particular, the fat mass. This study examined the self-perception of body image at various levels of adiposity proposing a new index.

Methods
We investigated 487 young Italian adults (mean age of males: 21.9 ± 2.4 years; mean age of females: 21.0 ± 2.2 years). Each subject could choose, on the Contour Drawing Rating Scale, the silhouette that he/she considered most resembling his/her perceived body image as well as his/her ideal body image. On each subject, we performed anthropometric measurements and determined the values of Fat mass and %Fat with BIA. A new index, FAIFAT (Feel fat status minus Actual fat status Inconsistency), was developed to evaluate possible fat status perception inconsistencies by BIA.

Results
Based on ideal and feel body image comparison, women showed higher dissatisfaction than men and preferred slimmer silhouettes. FAIFAT values indicated that the fat status perception was correct in the majority of the examined individuals and only three subjects showed a serious misperception.

Conclusions
Our findings suggest that FAIFAT is an appropriate index for assessing the perceived fat status from the body image when compared with data obtained by BIA. In a population, the use of this index will allow the correct identification of groups at risk for eating disorders.
IL-23 and PSMA-targeted duo-CAR T cells in Prostate Cancer Eradication in a preclinical model
Authors: Wang Dawei , Shao Yuan , Zhang Xiang , Lu Guoliang , Liu Boke 
Published: January 2020

AbstractBackgroundProstate cancer is one of the most common adult malignancies in men, and nearly all patients with metastatic prostate cancer can develop and receive resistance to primary androgen deprivation therapy (ADT), a state known as metastatic castration-resistant prostate cancer (mCRPC). Recent reports demonstrated the great breakthroughs made by the chimeric antigen receptor T (CAR-T) cell therapy, which is significantly different from traditional T cells therapies. In spite of the progress of CAR-T technology in the treatment of lymphoma, leukemia, and other blood system tumor, there are still many difficulties in the treatment of solid tumors by CAR-T technology.MethodsIn this report, we designed a panel of IL23mAb-PSMA-CARs, including PSMA-CAR, IL23mAb-T2A-PSMA-CAR, IL23mAb-PSMA-CAR, and PSMA-CAR (soluble IL23mAb). And we studied the function of these CARs in mice model.ResultsCo-culture experiments with different CAR T cells have normal lysis function in vitro. The duo-CAR T cells co-expressing the IL-23mAb and PSMA-mAb had a significant higher population than the rest three different CAR T cells in co-culturing experiments at day 28, 35 and 42. A panel of cytokines were differentially secreted at higher amounts in IL23mAb-T2A-PSMA-CAR T cells than CAR T cells in other groups. In NOD/SCID IL-2 gamma (NSG) mice model, IL23mAb-T2A-PSMA-CAR T cells functioned significantly better than CAR T cells from the other groups and eradicated the tumor from these mice starting at day 14 post T cells injection and regained the body weight immediately. In IL23mAb-T2A-PSMA-CAR mice, CD45RO+ CD8+ T cells and CD127+ CD4+ CAR T cells were significantly increased. RNA sequencing revealed a difference expression pattern of genes in IL23mAb-T2A-PSMA-CAR mice. A reverse infusion experiment under the same model further proved the tumor eradication function of IL23mAb-T2A-PSMA-CAR T cells.ConclusionsWe found that IL-23mAb combined PSMA CARs worked better than PSMA CAR only in Prostate Cancer Eradication, and we further discussed the mechanisms among different IL-23mAb combined PSMA CARs in Prostate Cancer Eradication.
Aberrant DNA methylation profile exacerbates inflammation and neurodegeneration in multiple sclerosis patients
Authors: Celarain Naiara , Tomas-Roig Jordi 
Published: January 2020

AbstractMultiple sclerosis (MS) is an autoimmune and demyelinating disease of the central nervous system characterised by incoordination, sensory loss, weakness, changes in bladder capacity and bowel function, fatigue and cognitive impairment, creating a significant socioeconomic burden. The pathogenesis of MS involves both genetic susceptibility and exposure to distinct environmental risk factors. The gene x environment interaction is regulated by epigenetic mechanisms. Epigenetics refers to a complex system that modifies gene expression without altering the DNA sequence. The most studied epigenetic mechanism is DNA methylation. This epigenetic mark participates in distinct MS pathophysiological processes, including blood–brain barrier breakdown, inflammatory response, demyelination, remyelination failure and neurodegeneration. In this study, we also accurately summarised a list of environmental factors involved in the MS pathogenesis and its clinical course. A literature search was conducted using MEDLINE through PubMED and Scopus. In conclusion, an exhaustive study of DNA methylation might contribute towards new pharmacological interventions in MS by use of epigenetic drugs.
Endothelial-specific deficiency of megalin in the brain protects mice against high-fat diet challenge
Authors: Bartolome Fernando , Antequera Desiree , de la Cueva Macarena , Rubio-Fernandez Marcos , Castro Nerea , Pascual Consuelo , Camins Antoni , Carro Eva 
Published: January 2020

Abstract
Background
The increasing risk of obesity and diabetes among other metabolic disorders are the consequence of shifts in dietary patterns with high caloric-content food intake. We previously reported that megalin regulates energy homeostasis using blood-brain barrier (BBB) endothelial megalin-deficient (EMD) mice, since these animals developed obesity and metabolic syndrome upon normal chow diet administration. Obesity in mid-life appears to be related to greater dementia risk and represents an increasing global health issue. We demonstrated that EMD phenotype induced impaired learning ability and recognition memory, neurodegeneration, neuroinflammation, reduced neurogenesis, and mitochondrial deregulation associated with higher mitochondrial mass in cortical tissues.

Methods
EMD mice were subjected to normal chow and high-fat diet (HFD) for 14 weeks and metabolic changes were evaluated.

Results
Surprisingly, BBB megalin deficiency protected against HFD-induced obesity improving glucose tolerance and preventing hepatic steatosis. Compared to wild type (wt), the brain cortex in EMD mice showed increased levels of the mitochondrial biogenesis regulator, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), and uncoupling protein 2 (UCP2), a thermogenic protein involved in the regulation of energy metabolism. This agreed with the previously found increased mitochondrial mass in the transgenic mice. Upon HFD challenge, we demonstrated these two proteins were found elevated in wt mice but reported no changes over the already increased levels in EMD animals.

Conclusion
We propose a protective role for megalin on diet-induce obesity, suggesting this could be related to metabolic disturbances found in dementia through brain endocrine system communications.
Folic acid and melatonin mitigate diabetic nephropathy in rats via inhibition of oxidative stress
Authors: Ebaid Hossam , Bashandy Samir A. E. , Abdel-Mageed Ahmad M. , Al-Tamimi Jameel , Hassan Iftekhar , Alhazza Ibrahim M. 
Published: January 2020

AbstractBackgroundDiabetes mellitus is a global epidemic leads to multiple serious health complications, including nephropathy. Diabetic nephropathy is a serious kidney-related complication of type 1 or 2 diabetes that is prevalent in almost 40% of the people with diabetes. We examined whether folic acid and melatonin can reduce progression of nephropathy in rats of type 1 diabetes mellitus by controlling the level of oxidative stress, glucose, lipids, and cytokines.MethodsForty-two male albino rats were distributed into six groups, (n = 7 per group). Five of the groups were induced with diabetes by a single intraperitoneal injection of freshly prepared streptozotocin at a dose of 50 mg/kg body weight. After the induction of diabetes, the rats were treated with folic acid (100 mg/kg) and melatonin (10 mg/kg) separately and in combination daily for 6 weeks, whereas, the other diabetic group was treated with glibenclamide (5 mg/kg). One of the diabetic groups served as a positive control. One-way ANOVA was used to compare those five subfields ability followed by LSD multiple comparisons.ResultsThe data indicated that diabetes significantly altered the body weight, lipids and kidney function. Diabetic rats exhibited a significant increase in plasma levels of urea, uric acid, creatinine, sodium, tumor necrosis factor alpha (TNF-α), interleukin-6(IL-6), cholesterol, triglycerides, and low-density lipoprotein (LDL). In contrast, plasma total protein, potassium, high-density lipoprotein (HDL) and interleukin-10 (IL-10) decreased significantly in diabetic rats compared to the control rats. Moreover, levels of renal malondialdehyde (MDA) and nitric oxide (NO) were significantly increased while the levels of renal glutathione(GSH), superoxide dismutase(SOD), and catalase (CAT) were significantly decreased in diabetic rats comparison to those in the control rats. Hence, diabetic rats treated with folic acid and melatonin alone as well as in combination showed improvements with respect to the indices in addition to a significant recovery observed via histopathology when compared to the diabetic group.ConclusionsThese results revealed that treatment with folic acid in combination with melatonin in diabetic rats was more effective than treatment with either of folic acid or melatonin alone to alleviate the symptoms of diabetic nephropathy.