bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting cancer cell plasticity by HDAC inhibition to reverse EBV-induced dedifferentiation in nasopharyngeal carcinoma
Authors: Xie Jiajun , Wang Zifeng , Fan Wenjun , Liu Youping , Liu Fang , Wan Xiangbo , Liu Meiling , Wang Xuan , Zeng Deshun , Wang Yan , He Bin , Yan Min , Zhang Zijian , Zhang Mengjuan , Hou Zhijie , Wang Chunli , Kang Zhijie , Fang Wenfeng , Zhang Li , Lam Eric W-F , Guo Xiang , Yan Jinsong , Zeng Yixin , Chen Mingyuan , Liu Quentin 
Published: September 2021

AbstractApplication of differentiation therapy targeting cellular plasticity for the treatment of solid malignancies has been lagging. Nasopharyngeal carcinoma (NPC) is a distinctive cancer with poor differentiation and high prevalence of Epstein-Barr virus (EBV) infection. Here, we show that the expression of EBV latent protein LMP1 induces dedifferentiated and stem-like status with high plasticity through the transcriptional inhibition of CEBPA. Mechanistically, LMP1 upregulates STAT5A and recruits HDAC1/2 to the CEBPA locus to reduce its histone acetylation. HDAC inhibition restored CEBPA expression, reversing cellular dedifferentiation and stem-like status in mouse xenograft models. These findings provide a novel mechanistic epigenetic-based insight into virus-induced cellular plasticity and propose a promising concept of differentiation therapy in solid tumor by using HDAC inhibitors to target cellular plasticity.
Prognostic correlations with the microbiome of breast cancer subtypes
Authors: Banerjee Sagarika , Wei Zhi , Tian Tian , Bose Dipayan , Shih Natalie N. C. , Feldman Michael D. , Khoury Thaer , De Michele Angela , Robertson Erle S. 
Published: September 2021

AbstractAlterations to the natural microbiome are linked to different diseases, and the presence or absence of specific microbes is directly related to disease outcomes. We performed a comprehensive analysis with unique cohorts of the four subtypes of breast cancer (BC) characterized by their microbial signatures, using a pan-pathogen microarray strategy. The signature (includes viruses, bacteria, fungi, and parasites) of each tumor subtype was correlated with clinical data to identify microbes with prognostic potential. The subtypes of BC had specific viromes and microbiomes, with ER+ and TN tumors showing the most and least diverse microbiome, respectively. The specific microbial signatures allowed discrimination between different BC subtypes. Furthermore, we demonstrated correlations between the presence and absence of specific microbes in BC subtypes with the clinical outcomes. This study provides a comprehensive map of the oncobiome of BC subtypes, with insights into disease prognosis that can be critical for precision therapeutic intervention strategies.
Immunomodulatory effect of NEDD8-activating enzyme inhibition in Multiple Myeloma: upregulation of NKG2D ligands and sensitization to Natural Killer cell recognition
Authors: Petillo Sara , Capuano Cristina , Molfetta Rosa , Fionda Cinzia , Mekhloufi Abdelilah , Pighi Chiara , Antonangeli Fabrizio , Zingoni Alessandra , Soriani Alessandra , Petrucci Maria Teresa , Galandrini Ricciarda , Paolini Rossella , Santoni Angela , Cippitelli Marco 
Published: September 2021

AbstractMultiple Myeloma (MM) is an incurable hematologic malignancy of terminally differentiated plasma cells (PCs), where immune interactions play a key role in the control of cancer cell growth and survival. In particular, MM is characterized by a highly immunosuppressive bone marrow microenvironment where the anticancer/cytotoxic activity of Natural Killer (NK) cells is impaired. This study is focused on understanding whether modulation of neddylation can regulate NK cell-activating ligands expression and sensitize MM to NK cell killing. Neddylation is a post-translational modification that adds a ubiquitin-like protein, NEDD8, to selected substrate proteins, affecting their stability, conformation, subcellular localization, and function. We found that pharmacologic inhibition of neddylation using a small-molecule inhibitor, MLN4924/Pevonedistat, increases the expression of the NK cell-activating receptor NKG2D ligands MICA and MICB on the plasma membrane of different MM cell lines and patient-derived PCs, leading to enhanced NK cell degranulation. Mechanistically, MICA expression is upregulated at mRNA level, and this is the result of an increased promoter activity after the inhibition of IRF4 and IKZF3, two transcriptional repressors of this gene. Differently, MLN4924/Pevonedistat induced accumulation of MICB on the plasma membrane with no change of its mRNA levels, indicating a post-translational regulatory mechanism. Moreover, inhibition of neddylation can cooperate with immunomodulatory drugs (IMiDs) in upregulating MICA surface levels in MM cells due to increased expression of CRBN, the cellular target of these drugs. In summary, MLN4924/Pevonedistat sensitizes MM to NK cell recognition, adding novel information on the anticancer activity of neddylation inhibition.
Tail-vein injection of MSC-derived small extracellular vesicles facilitates the restoration of hippocampal neuronal morphology and function in APP / PS1 mice
Authors: Wang Han , Liu Yuqi , Li Junchen , Wang Tian , Hei Yue , Li Huiming , Wang Xue , Wang Lina , Zhao Ruijing , Liu Weiping , Long Qianfa 
Published: September 2021

AbstractMesenchymal stem-cell-derived small extracellular vesicles (MSC-EVs), as a therapeutic agent, have shown great promise in the treatment of neurological diseases. To date, the neurorestorative effects and underlying mechanism of MSC-EVs in Alzheimer’s disease (AD) are not well known. Herein, we aimed to investigate the action of MSC-EVs on the neuronal deficits in β-amyloid protein (Aβ)-stimulated hippocampal neurons, or AD cell (SHSY5Y cell lines) and animal (APPswe / PS1dE9 mice) models. In the present study, the cell and AD models received a single-dose of MSC-EVs, and were then assessed for behavioral deficits, pathological changes, intracellular calcium transients, neuronal morphology alterations, or electrophysiological variations. Additionally, the nuclear factor E2-related factor 2 (Nrf2, a key mediator of neuronal injury in AD) signaling pathway was probed by western blotting in vitro and in vivo models of AD. Our results showed that MSC-EVs therapy improved the cognitive impairments and reduced the hippocampal Aβ aggregation and neuronal loss in AD mice. Markedly, EV treatment restored the calcium oscillations, dendritic spine alterations, action potential abnormalities, or mitochondrial changes in the hippocampus of AD models. Also, we found that the Nrf2 signaling pathway participated in the actions of MSC-EVs in the cell and animal models. Together, these data indicate that MS-EVs as promising nanotherapeutics for restoration of hippocampal neuronal morphology and function in APP / PS1 mice, further highlighting the clinical values of MSC-EVs in the treatment of AD.
Wind farms in AGC: Modelling, simulation and validation
Authors: Doenges Kai , Sigrist Lukas , Egido Ignacio , Lobato Enrique , Rouco Luis 
Published: September 2021

AbstractWind farms are increasingly interested in participating in the secondary frequency control, especially in power systems where AGC is organized by regulation zones comprising generation units of different technologies. In order to estimate the wind farms behaviour and overall impact on automatic generation control (AGC), a reasonably simple wind farm model is needed. First‐order and second‐order linear models of wind farms are proposed in the literature in AGC‐related studies. However, these simple models neglect key dynamic features for AGC integration of wind farms, such as artificial ramp limitations, dead bands, communication delays and start‐up delays caused by turbine orientation. This paper presents a still simple wind farm model, however representing all relevant dynamics and availability constraints at power system control level. Applying an illustrative case study, model parameters are tuned and validated by means of field measurements, recorded during a response trail run of a real wind farm of 30 MW installed power operating within the Spanish power system.
Physical activity on mental wellbeing in senior English Premier League soccer players during the COVID‐19 pandemic and the lockdown
Authors: Grimson Sophie , Brickley Gary , Smeeton Nicholas J. , Abbott Will , Brett Adam 
Published: September 2021

ABSTRACTThe COVID‐19 pandemic and the subsequent lockdown created new stressors that could potentially attenuate mental wellbeing (MW) in athletes, who are already susceptible to poor MW. This study aims to describe fluctuations to MW during “lockdown” and subsequent “return to sport” protocols, in comparison to the normal “in‐season” in professional soccer. Twenty‐five English Premier League (EPL) soccer players completed the Warwick‐Edinburgh Mental Wellbeing Scale (WEMWBS) every two weeks, during the 2019/2020 season, and every week during “lockdown” and “return to training” for 28 weeks. The duration of each physical activity (PA) session completed was recorded. No significant differences were found for MW between time points (In‐season, lockdown, return to training and the restart) (51.5 ± 5.6 vs. 50.7 ± 4.8 vs. 50.8 ± 5.7 vs. 50.7 ± 5.6 (p > 0.05)) respectively. Individually, differences were identified; in‐season weekly session duration (243 ± 38 min) was higher than during lockdown (180 ± 62 min) (p < 0.05). During lockdown, weekly MW scores were related to the previous 7‐day number of sessions (r = 0.151) and active min (r = 0.142) (p < 0.05). Furthermore, participants that exercised >250 min in lockdown, had higher MW scores (52.46 ± 4.65) than <250 min (50.35 ± 6.55) (p < 0.05). MW responses to lockdown were best understood on an individual basis. Additionally, PA only had a measurable effect on MW when >250 min. Further, stressors imposed upon players during an EPL season, are potentially greater than those inflicted by the lockdown. Implications for monitoring MW in EPL soccer players and the potential inclusion of an in‐season break are discussed.Highlights
Mental Wellbeing Responses, as measured by the Warwick‐Edinburgh Mental Wellbeing scale did not change significantly at a group level across the four phases of the season. However, on an individual level changes were evident.
There was a decline in the trend of wellbeing scores during in‐season, return to training and the restart, but an increase in wellbeing scores during lockdown.
Physical Activity had a measurable effect on wellbeing, when physical activity was >250 min during lockdown.
These findings highlight the need for individual monitoring of wellbeing and longitudinal monitoring in sport to identify decline in wellbeing and implement intervention. In addition, the prescription of physical activity >250 min per week during lockdown in trained athletes may promote positive mental health.
The assessment of hypertension in kidney transplant patients: time to change our approach?
Authors: Demiray Atalay , Kanbay Mehmet 
Published: September 2021

ABSTRACT
Kidney transplantation (KT) is an increasingly utilized treatment for end-stage kidney disease. Hypertension either as a cause of kidney disease or as a complication of chronic kidney disease is the most frequently encountered comorbidity of KT patients. Hence, the management of hypertension in KT patients is crucial to prolong patient and graft survival. Ambulatory blood pressure monitoring (ABPM) appeared as a promising technique that has superiority over office and home blood pressure (BP) monitoring to correctly diagnose and manage hypertension. A recent meta-analysis by Pisano et al. including 42 studies with 4115 participants provided strong data for the comparison of ABPM with office BP monitoring in KT patients. In addition to the current literature knowledge, the findings of Pisano et al. filled the long-awaited evidence gap to suggest ABPM as a first-line BP monitoring technique for KT patients. Despite its disadvantages, such as patient discomfort, cost–effectiveness and limited availability, ABPM has crucial advantages in the management of hypertension including the detection of abnormal circadian BP patterns, the assessment of effects of physical activity and short-term variability of BP, and the exclusion of masked and white-coat hypertension.
Patterns of chronic and transient hyperkalaemia and clinically important outcomes in patients with chronic kidney disease
Authors: Trevisan Marco , Clase Catherine M , Evans Marie , Popov Tamara , Ludvigsson Jonas F , Sjölander Arvid , Carrero Juan Jesus 
Published: September 2021

ABSTRACT

Background
Whether hyperkalaemia in CKD is chronic or transient, and whether this has different outcome implications, is not known.

Methods
This was an observational study of adults with CKD G3–5 from Stockholm, Sweden 2006–11. We examined individual trajectories of potassium from all measurements obtained through routine outpatient care. For each month of follow-up, we created a rolling assessment of the proportion of time in which potassium was abnormal during the previous 12 months. We defined patterns of hyperkalaemia as transient (≤50% of time during the previous year with potassium &gt;5.0 mmol/L) and chronic (&gt;50% of time with potassium &gt;5.0 mmol/L), and examined whether previous hyperkalaemia pattern offers additional predictive value beyond that provided by the most recent (current) potassium value.

Results
We included 36 511 participants (56% women) with CKD G3–5 and median estimated glomerular filtration rate 46 mL/min/1.73 m2. Transient and chronic hyperkalaemia, respectively, were observed in 15% and 4% of patients with CKD G3a, and in 50% and 17% of patients with CKD G5. In fully adjusted models, transient (hazard ratio 1.36, 95% confidence interval 1.29–1.46) or chronic (1.16, 1.04–1.32) hyperkalaemia patterns, but not current hyperkalaemia, were associated with major adverse cardiovascular events (MACE), compared with normokalaemia. Transient hyperkalaemia (1.43, 1.35–1.52) and current potassium values, but not chronic hyperkalaemia, were associated with the risk of death.

Conclusions
Between 4% and 17% of patients with CKD G3–5 develop chronic hyperkalaemia. In general, hyperkalaemia predicted MACE and death; however, the lack of effect of current potassium on MACE when adjusted for the previous pattern, and the stronger effects on death than on MACE, lead us to question whether hyperkalaemia is causal in these relationships.
Pre-emptive BioGlue priming of the branched Evita Open NEO hybrid prosthesis: tackling excessive oozing
Authors: Ho Jacky Y K , Lim Kevin , Fujikawa Takuya , Wong Randolph H L 
Published: September 2021

Abstract
Excessive oozing after total arch replacement with the frozen elephant trunk technique through the fabric of the E-vita Open NEO raised concern about its early adaptation. The mechanism is speculated to be multifactorial. Our goal was to report our approach using pre-emptive BioGlue priming on the fabric against the oozing phenomenon.
A review: antimicrobial properties of several medicinal plants widely used in Traditional Chinese Medicine
Authors: Chen Kun , Wu Wei , Hou Xiudan , Yang Qingli , Li Zhaojie 
Published: September 2021

AbstractDue to the dramatic increase in the use of antibiotics and growing health threat of bacterial resistance to many commonly used antibiotics, many studies have been directed at developing new and effective antibacterial compounds, among which many new, natural, and effective antibacterial compounds discovered from medicinal plants have drawn great interest and raised new hope for treating the challenges of antibiotic resistance. This review aimed to summarize the most important and widely used medicinal plants that were reported to have antibacterial activities. A general literature search from 2010 to 2020 was conducted using different databases, including Science Direct, Web of Science, and PubMed. According to the literature, three medicinal plants with outstanding antibacterial activities, Taraxacum officinale, Coptis Rhizome, and Scutellaria baicalensis, were screened and reviewed by prioritization. The extraction methods, antibacterial activities of different parts of plants or the plant-derived compounds, spectra of antibacterial activities, and toxicity were described, respectively. However, the antibacterial activities of the extracts or pure compounds as reported in the reviewed literature were mostly based on in vitro assays, and moreover, the deeper antibacterial mechanisms have not been elucidated clearly. Therefore, further studies are required in the fields of purification and identification of the antibacterial compounds, its mechanisms of action, and synergistic effects in combination with other antibacterial drugs, which may be helpful in the development of new antibacterial drugs.
Projecting Ancient Ancestry in Modern-Day Arabians and Iranians: A Key Role of the Past Exposed Arabo-Persian Gulf on Human Migrations
Authors: Ferreira Joana C , Alshamali Farida , Montinaro Francesco , Cavadas Bruno , Torroni Antonio , Pereira Luisa , Raveane Alessandro , Fernandes Veronica 
Published: September 2021

Abstract
The Arabian Peninsula is strategic for investigations centered on the early structuring of modern humans in the wake of the out-of-Africa migration. Despite its poor climatic conditions for the recovery of ancient human DNA evidence, the availability of both genomic data from neighboring ancient specimens and informative statistical tools allow modeling the ancestry of local modern populations. We applied this approach to a data set of 741,000 variants screened in 291 Arabians and 78 Iranians, and obtained insightful evidence. The west-east axis was a strong forcer of population structure in the Peninsula, and, more importantly, there were clear continuums throughout time linking western Arabia with the Levant, and eastern Arabia with Iran and the Caucasus. Eastern Arabians also displayed the highest levels of the basal Eurasian lineage of all tested modern-day populations, a signal that was maintained even after correcting for a possible bias due to a recent sub-Saharan African input in their genomes. Not surprisingly, eastern Arabians were also the ones with highest similarity with Iberomaurusians, who were, so far, the best proxy for the basal Eurasians amongst the known ancient specimens. The basal Eurasian lineage is the signature of ancient non-Africans who diverged from the common European-eastern Asian pool before 50,000 years ago, prior to the later interbred with Neanderthals. Our results appear to indicate that the exposed basin of the Arabo-Persian Gulf was the possible home of basal Eurasians, a scenario to be further investigated by searching ancient Arabian human specimens.
Pension Policy Literacy and Retirement Expectations: A Cross-Country Survey Experiment
Authors: Radl Jonas , Fernández Juan J 
Published: September 2021

Abstract

Objectives
This study reports the findings of the first cross-national survey experiment on the effects of information on the expected retirement age. Given the drawbacks of unrealistic retirement expectations, the study examines the impacts of nonpartisan information about future demographic aging and forecasted pension benefit levels.

Methods
An online survey experiment was conducted in the United States, Germany, and Spain in 2018 using an internet access panel. We assigned respondents to 2 random treatments: one citing the change in the projected share of the population older than 65 years (demographic treatment) and another citing the projected change in pension replacement rates (benefits treatment), both for 2015–2040. Treatment effects on the expected retirement age are reported.

Results
The benefits treatment has a strong influence on retirement expectations. In the United States, respondents informed of the expected decline in pension replacement rates expect to retire 2 years later than respondents not informed of the decline. In Spain, this treatment leads to an approximately 9-month postponement of expected retirement, while no significant effect is found in Germany. In addition, the demographic treatment does not affect retirement expectations in the countries studied. Respondents in all countries informed of future population aging do not show different expected retirement ages than respondents not given this information.

Discussion
People’s retirement expectations are sensitive to information on future changes in pension generosity but not to information on population aging. The results suggest information campaigns focused on declining pension replacement rates may help extend working lives.
Early Diagnosis, Early Stratification, and Early Intervention to Deliver Precision Medicine in IBD
Authors: Noor Nurulamin M , Sousa Paula , Paul Stéphane , Roblin Xavier 
Published: September 2021

Abstract
Despite huge advances in understanding the molecular basis of IBD, clinical management has continued to rely on a “trial and error” approach. In addition, a therapeutic ceiling has emerged whereby even the most effective interventions are only beneficial for approximately 30% of patients. Consequently, several tools have been developed to aid stratification and guide treatment-decisions.
We review the potential application for many of these precision medicine approaches, which are now almost within reach. We highlight the importance of early action (and avoiding inaction) to ensure the best outcomes for patients and how combining early action with precision tools will likely ensure the right treatment is delivered at the right time and place for each individual person living with IBD.
The lack of clinical impact to date from precision medicine, despite much hype and investment, should be tempered with the knowledge that clinical translation can take a long time, and many promising breakthroughs might be ready for clinical implementation in the near future. We discuss some of the remaining challenges and barriers to overcome for clinical adoption. We also highlight that early recognition, early diagnosis, early stratification, and early intervention go hand in hand with precision medicine tools. It is the combination of these approaches that offer the greatest opportunity to finally deliver on the promise of precision medicine in IBD.