bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ferritin modifies the relationship between inflammation and arterial stiffness in hypertensive patients with different glucose tolerance
Authors: Sciacqua Angela , Ventura Ettore , Tripepi Giovanni , Cassano Velia , D’Arrigo Graziella , Roumeliotis Stefanos , Maio Raffale , Miceli Sofia , Perticone Maria , Andreozzi Francesco , Sesti Giorgio , Perticone Francesco 
Published: August 2020

Abstract
Background
Ferritin, a crucial element for iron homeostasis, is associated with chronic diseases characterized by subclinical inflammation such as essential arterial hypertension and type 2 diabetes mellitus (T2DM), showing a prognostic value in different clinical settings. We investigated whether ferritin is associated with arterial stiffness (AS), an early indicator of atherosclerosis, and if it could act as effect modifier on the relationship between inflammation and AS in hypertensive patients with different glucose tolerance.

Methods
We enrolled 462 newly diagnosed untreated hypertensive (HT) patients. All subjects underwent an oral glucose tolerance test. Insulin sensitivity was assessed by MATSUDA index and ferritin levels were estimated by immunoradiometric assay. AS was defined by carotid-femoral pulse wave velocity (PWV).

Results
Out of 462 patients, 271 showed normal glucose tolerance (HT/NGT), 146 impaired glucose tolerance (HT/IGT) and 45 were diabetic (HT/T2DM). Iron levels significantly decreased and transferrin and ferritin significantly increased from the first to the third group. PWV values were significantly higher in HT/IGT and HT/T2DM patients. PWV was related directly with ferritin, high sensitivity C reactive protein (hs-CRP), transferrin, and inversely with MATSUDA index. Ferritin resulted the strongest determinant of PWV explaining a 14.9% of its variation; moreover it was a strong modifier of the relationship between hs-CRP and PWV. The estimated augmentation in PWV portended by a fixed increase in hs-CRP, was higher across increasing values of ferritin.

Conclusion
Ferritin represents an independent risk factor of arterial stiffness in our study population and a strong effect modifier on the relationship between inflammation and PWV. However, further studies are needed to fully elucidate the potential role of this biomarker in human atherosclerosis.
The dual functions of α-tubulin acetylation in cellular apoptosis and autophage induced by tanespimycin in lung cancer cells
Authors: Wang Qilin , Liu Xiangguo 
Published: August 2020

Abstract
Background
Reversible acetylation of α-tubulin has been implicated in modulating microtuble structures and functions, which may subsequently involve in cellular apoptosis and autophage. But how to trigger apoptosis or autophage at what level of acetylated α-tubulin (Ac-α-tubulin) are not known. This study aims to demonstrate the dual functions and molecular mechanisms of α-tubulin acetylation in cellular apoptosis and autophage induced by tanespimycin in Calu-1 cells simultaneously.

Methods
Calu-1 cells were treated with tanespimycin alone or combined administrations of different agents (including TSA, Docetaxel, Rapamycin, 3-MA and Z-vad) respectively and cell lysates were prepared to detect the given proteins by Western Blot. The cell survival was observed by inverted phase contrast microscope and estimated by SRB assay. HDAC6, TAT1 and Hsp90α/β proteins were knocked down by siRNA technique.

Results
By combination administration of tanespimycin with TSA or Docetaxel, the expression of Ac-α-tubulin and cellular apoptosis were enhanced markedly. While combination of tanespimycin and Rapamycin, α-tubulin acetylation and apoptosis were inhibited, but LC3B-II expression was facilitated substantially. When tanespimycin was combined with autophage inhibitor 3-MA, α-tubulin acetylation elevation was apparently, but LC3B-II was attenuated. Apoptosis inhibitor Z-vad blocked partially Caspases activation induced by tanespimycin, but failed to hinder α-tubulin acetylation elevation. According to results of RNA interference, acetyltransferase TAT1, deacetylase HDAC6 and Hsp90 modulated the expression level of α-tubulin acetylation.

Conclusion
We have elucidated that acetylation of α-tubulin induced by tanespimycin has dual functions in cellular apoptosis and autophage and the level of α-tubulin acetylation reaches a degree Calu-1 cells undergo cell apoptosis rather than autophage, implying that the level of acetylated α-tubulin may determine cell fate for survival or apoptosis.
Molecular surveillance for drug resistance markers in Plasmodium vivax isolates from symptomatic and asymptomatic infections at the China–Myanmar border
Authors: Zhao Yan , Wang Lin , Soe Myat Thu , Aung Pyae Linn , Wei Haichao , Liu Ziling , Ma Tongyu , Huang Yuanyuan , Menezes Lynette J. , Wang Qinghui , Kyaw Myat Phone , Nyunt Myat Htut , Cui Liwang , Cao Yaming 
Published: August 2020

Abstract
Background
In the Greater Mekong sub-region, Plasmodium vivax has become the predominant species and imposes a major challenge for regional malaria elimination. This study aimed to investigate the variations in genes potentially related to drug resistance in P. vivax populations from the China–Myanmar border area. In addition, this study also wanted to determine whether divergence existed between parasite populations associated with asymptomatic and acute infections.

Methods
A total of 66 P. vivax isolates were obtained from patients with acute malaria who attended clinics at the Laiza area, Kachin State, Myanmar in 2015. In addition, 102 P. vivax isolates associated with asymptomatic infections were identified by screening of volunteers without signs or symptoms from surrounding villages. Slide-positive samples were verified with nested PCR detecting the 18S rRNA gene. Multiclonal infections were further excluded by genotyping at msp-3α and msp-3β genes. Parasite DNA from 60 symptomatic cases and 81 asymptomatic infections was used to amplify and sequence genes potentially associated with drug resistance, including pvmdr1, pvcrt-o, pvdhfr, pvdhps, and pvk12.

Results
The pvmdr1 Y976F and F1076L mutations were present in 3/113 (2.7%) and 97/113 (85.5%) P. vivax isolates, respectively. The K10 insertion in pvcrt-o gene was found in 28.2% of the parasites. Four mutations in the two antifolate resistance genes reached relatively high levels of prevalence: pvdhfr S58R (53.4%), S117N/T (50.8%), pvdhps A383G (75.0%), and A553G (36.3%). Haplotypes with wild-type pvmdr1 (976Y/997K/1076F) and quadruple mutations in pvdhfr (13I/57L/58R/61M/99H/117T/173I) were significantly more prevalent in symptomatic than asymptomatic infections, whereas the pvmdr1 mutant haplotype 976Y/997K/1076L was significantly more prevalent in asymptomatic than symptomatic infections. In addition, quadruple mutations at codons 57, 58, 61 and 117 of pvdhfr and double mutations at codons 383 and 553 of pvdhps were found both in asymptomatic and symptomatic infections with similar frequencies. No mutations were found in the pvk12 gene.

Conclusions
Mutations in pvdhfr and pvdhps were prevalent in both symptomatic and asymptomatic P. vivax infections, suggestive of resistance to antifolate drugs. Asymptomatic carriers may act as a silent reservoir sustaining drug-resistant parasite transmission necessitating a rational strategy for malaria elimination in this region.
CircRNAs: biogenesis, functions, and role in drug-resistant Tumours
Authors: Ma Shuo , Kong Shan , Wang Feng , Ju Shaoqing 
Published: August 2020

AbstractTargeted treatment, which can specifically kill tumour cells without affecting normal cells, is a new approach for tumour therapy. However, tumour cells tend to acquire resistance to targeted drugs during treatment. Circular RNAs (circRNAs) are single-stranded RNA molecules with unique structures and important functions. With the development of RNA sequencing technology, circRNAs have been found to be widespread in tumour-resistant cells and to play important regulatory roles. In this review, we present the latest advances in circRNA research and summarize the various mechanisms underlying their regulation. Moreover, we review the role of circRNAs in the chemotherapeutic resistance of tumours and explore the clinical value of circRNA regulation in treating tumour resistance.
Offspring sex affects the susceptibility to maternal smoking-induced lung inflammation and the effect of maternal antioxidant supplementation in mice
Authors: Wang Baoming , Chan Yik Lung , Zhou Shengyu , Saad Sonia , Chen Hui , Oliver Brian G 
Published: August 2020

Abstract
Background
Cigarette smoke exposure (SE) during pregnancy is the largest modifiable risk factor for the development of lung disorders in offspring. We have previously shown that maternal L-Carnitine treatment can reduce the adverse impacts of maternal SE on renal and brain disorders in offspring. Here, we investigated the effect of maternal L-Carnitine supplementation on lung inflammatory pathways, autophagy, and mitophagy markers in the offspring in response to maternal SE.

Methods
Female BALB/c mice (8 weeks) were exposed to cigarette smoke for 6 weeks prior to mating, during gestation and lactation. Some of the SE dams were given L-Carnitine supplementation (1.5 mM in drinking water, SE + LC) during gestation and lactation. Lungs from the offspring were studied at birth and adulthood (13 weeks).

Results
At birth, in male offspring, there were increased levels of inflammatory markers (phosphorylated(p)-ERK1,2, p-P38 MAPK, p- NF-κB), and inflammasome marker (NLRP3), as well as mitophagy fission marker Drp-1 and autophagosome marker (LC3A/B-II) in the lung. Maternal L-Carnitine supplementation significantly reduced NLRP3 level. In contrast, maternal SE only increased IL1-β in female offspring, which was reversed by maternal L-Carnitine supplementation. At 13 weeks, there was an increase in LC3A/B-II and p- NF-κB in the male SE offspring with reduced p-JNK1,2, which were partially normalised by maternal L-Carnitine treatment. Female offspring were not affected by maternal SE at this age.

Conclusion
Maternal SE had adverse impacts on the male offspring’s lung, which were partially alleviated by maternal L-Carnitine supplementation. Females seem to be less affected by the adverse effects of maternal SE.
Potential interaction between lysophosphatidic acid and tumor-associated macrophages in ovarian carcinoma
Authors: Feng Ying , Xiao Meizhu , Zhang Zihan , Cui Ran , Jiang Xuan , Wang Shuzhen , Bai Huimin , Liu Chongdong , Zhang Zhenyu 
Published: August 2020

AbstractOvarian carcinoma is the deadliest type of gynecological cancer. The unique tumor microenvironment enables specific and efficient metastasis, weakens immunological monitoring, and mediates drug resistance. Tumor associated macrophages (TAMs) are a crucial part of the TME and are involved in various aspects of tumor behavior. Lysophosphatidic acid (LPA) is elevated in the blood of ovarian carcinoma patients, as well as in the tumor tissues and ascites, which make it a useful biomarker and a potential therapeutic target. Recent studies have shown that LPA transforms monocytes into macrophages and regulates the formation of macrophages through the AKT/mTOR pathway, and PPAR γ is a major regulator of LPA-derived macrophages. In addition, TAMs synthesize and secrete LPA and express LPA receptor (LPAR) on the surface. With these data in mind, we hypothesize that LPA can convert monocytes directly into TAMs in the microenvironment of ovarian cancer. LPA may mediate TAM formation by activating the PI3K/AKT/mTOR signaling pathway through LPAR on the cell surface, which may also affect the function of PPAR γ, leading to increased LPA production by TAMs. Thus, LPA and TAMs form a vicious circle that affects the malignant behavior of ovarian cancer.
N-acetylcysteine alleviates post-resuscitation myocardial dysfunction and improves survival outcomes via partly inhibiting NLRP3 inflammasome induced-pyroptosis
Authors: He Fenglian , Zheng Guanghui , Hou Jingying , Hu Qiaohua , Ling Qin , Wu Gongfa , Zhao Hui , Yang Jin , Wang Yue , Jiang Longyuan , Tang Wanchun , Yang Zhengfei 
Published: August 2020

AbstractBackgroundNOD-like receptor 3 (NLRP3) inflammasome is necessary to initiate acute sterile inflammation. Increasing evidence indicates the activation of NLRP3 inflammasome induced pyroptosis is closely related to reactive oxygen species (ROS) in the sterile inflammatory response triggered by ischemia/reperfusion (I/R) injury. N-acetylcysteine (NAC) is an antioxidant and plays a protective role in local myocardial I/R injury, while its effect on post-resuscitation myocardial dysfunction, as well as its mechanisms, remain elusive. In this study, we aimed to investigate the effect of NAC on post-resuscitation myocardial dysfunction in a cardiac arrest rat model, and whether its underlying mechanism may be linked to ROS and NLRP3 inflammasome-induced pyroptosis.MethodsThe rats were randomized into three groups: (1) sham group, (2) cardiopulmonary resuscitation (CPR) group, and (3) CPR + NAC group. CPR group and CPR + NAC group went through the induction of ventricular fibrillation (VF) and resuscitation. After return of spontaneous circulation (ROSC), rats in the CPR and CPR + NAC groups were again randomly divided into two subgroups, ROSC 6 h and ROSC 72 h, for further analysis. Hemodynamic measurements and myocardial function were measured by echocardiography, and western blot was used to detect the expression of proteins.ResultsResults showed that after treatment with NAC, there was significantly better myocardial function and survival duration; protein expression levels of NLRP3, adaptor apoptosis-associated speck-like protein (ASC), Cleaved-Caspase-1 and gasdermin D (GSDMD) in myocardial tissues were significantly decreased; and inflammatory cytokines levels were reduced. The marker of oxidative stress malondialdehyde (MDA) decreased and superoxide dismutase (SOD) increased with NAC treatment.ConclusionsNAC improved myocardial dysfunction and prolonged animal survival duration in a rat model of cardiac arrest. Moreover, possibly by partly inhibiting ROS-mediated NLRP3 inflammasome-induced pryoptosis.
Clinical outcomes of Preimplantation genetic testing (PGT) application in couples with chromosomal inversion, a study in the Chinese Han population
Authors: Shao Yuhan , Li Jing , Lu Juanjuan , Li Hongchang , Zhu Yueting , Jiang Wenjie , Yan Junhao 
Published: August 2020

AbstractBackgroundChromosomal inversion was considered to have adverse effects on pregnancy outcomes through abnormal gametogenesis. The purpose of this retrospective study was to investigate whether preimplantation genetic testing (PGT) improves pregnancy outcomes for couples with chromosomal inversion.MethodsA total of 188 cycles from 165 couples with one chromosomal inversion carrier were divided into two groups: PGT (136 cycles, 125 couples) and non-PGT (52 cycles, 50 couples). Biochemical pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage and live birth rates of their first transfer cycles, as well as cumulative live birth rates of each cycle and euploidy rates, were analyzed.ResultsThere were no statistically significant differences in the pregnancy outcomes between the two groups. The euploidy rate of pericentric inversion carriers was not higher than that of paracentric inversion carriers in PGT group (60.71% vs 50.54%,P = 0.073). Similarly, the euploid rate of male carriers was not higher than that of female carriers (61.2% vs 56.1%,P = 0.256).ConclusionsDue to limitation of retrospective study and small sample size, our current data showed that PGT cannot provide prominent benefits for inversion carriers in the Chinese Han population. Further prospective randomized controlled trials are needed to evaluate the effects of PGT.
Ischemia considerations for the development of an organ and tissue donor derived bone marrow bank
Authors: Woods Erik J. , Sherry Aubrey M. , Woods John R. , Hardin James W. , LaFontaine Michael , Brandacher Gerald , Johnstone Brian H. 
Published: August 2020

Abstract
Background
Deceased organ donors represent an untapped source of therapeutic bone marrow (BM) that can be recovered in 3–5 times the volume of that obtained from living donors, tested for quality, cryopreserved, and banked indefinitely for future on-demand use. A challenge for a future BM banking system will be to manage the prolonged ischemia times that are inevitable when bones procured at geographically-dispersed locations are shipped to distant facilities for processing. Our objectives were to: (a) quantify, under realistic field conditions, the relationship between ischemia time and the quality of hematopoietic stem and progenitor cells (HSPCs) derived from deceased-donor BM; (b) identify ischemia-time boundaries beyond which HSPC quality is adversely affected; (c) investigate whole-body cooling as a strategy for preserving cell quality; and (d) investigate processing experience as a variable affecting quality.

Methods
Seventy-five bones from 62 donors were analyzed for CD34+ viability following their exposure to various periods of warm-ischemia time (WIT), cold-ischemia time (CIT), and body-cooling time (BCT). Regression models were developed to quantify the independent associations of WIT, CIT, and BCT, with the viability and function of recovered HSPCs.

Results
Results demonstrate that under “real-world” scenarios: (a) combinations of warm- and cold-ischemia times favorable to the recovery of high-quality HSPCs are achievable (e.g., CD34+ cell viabilities in the range of 80–90% were commonly observed); (b) body cooling prior to bone recovery is detrimental to cell viability (e.g., CD34+ viability < 73% with, vs. > 89% without body cooling); (c) vertebral bodies (VBs) are a superior source of HSPCs compared to ilia (IL) (e.g., %CD34+ viability > 80% when VBs were the source, vs. < 74% when IL were the source); and (d) processing experience is a critical variable affecting quality.

Conclusions
Our models can be used by an emerging BM banking system to formulate ischemia-time tolerance limits and data-driven HSPC quality-acceptance standards.
Practicability of clinical application of bladder cancer molecular classification and additional value of epithelial-to-mesenchymal transition: prognostic value of vimentin expression
Authors: Lobo João , Monteiro-Reis Sara , Guimarães-Teixeira Catarina , Lopes Paula , Carneiro Isa , Jerónimo Carmen , Henrique Rui 
Published: August 2020

Abstract
Background
Bladder cancer (BlCa) taxonomy has proved its impact in patient outcome and selection for targeted therapies, but such transcriptomic-based classification has not yet translated to routine practice. Moreover, epithelial-to-mesenchymal transition (EMT) has shown relevance in acquisition of more aggressive BlCa phenotype. We aimed to test the usefulness of the molecular classification, as defined by immunohistochemistry (a routinely performed and easy-to-implement technique), in a well-defined BlCa cohort of both non-muscle invasive (NMIBC) and muscle invasive (MIBC) disease. Also, we aimed to assess the additional prognostic value of the mesenchymal marker vimentin to the stratification strategy.

Methods
A total of 186 samples were available. Immunohistochemistry/RT-qPCR for luminal markers GATA3/FOXA1, basal markers KRT5/KRT6A and vimentin were performed.

Results
mRNA expression levels of the markers positively correlated with immunoexpression scores. We found substantial overlapping in immunoexpression of luminal and basal markers, evidencing tumor heterogeneity. In MIBC, basal tumors developed recurrence more frequently. NMIBC patients with higher vimentin immunoexpression endured poorer disease-free survival, and increased expression was observed from normal bladder-NMIBC-MIBC-metastases.

Conclusions
The classification has the potential to be implemented in routine, but further adjustments in practical scoring should be defined; focusing on additional markers, including those related to EMT, may further refine BlCa molecular taxonomy.
Molecular identification of severe fever with thrombocytopenia syndrome viruses from tick and bitten patient in Southeast China
Authors: Tong Yongxi , Wang Qiujing , Fu Yongfeng , Li Shibo , Zhang Zhao , Zhang Zheen , Yu Xuewen 
Published: August 2020

Abstract
Background
Severe fever and thrombocytopenia bunyavirus (SFTSV) infection causes severe fever and thrombocytopenia syndrome with high mortality. It is extremely rare that a transmitting tick can be directly captured in bite wounds, and that SFTSV can be isolated from both the captured tick and patient’s serum to establish a solid pathogen diagnosis.

Case presentation
We report a case infected with severe fever and thrombocytopenia bunyavirus. The 69-year-old male patient presented with fever and tenderness on two lymph nodes in the right groin. A visible tick bite mark appeared on right upper quadrant of the patient’s abdomen, and a live tick was captured in the bite wound upon physical examination. The virus was detected in both the blood of the patient and in the tick that stayed in the bite wound for 7 days. The phylogenetic analysis indicated that the SFTSV isolated from the tick and the patient’s serum sample belonged to type B, in which the L/S segment of these two isolates shared 100% homology, while the M segment had 99.9% homology. The bitten patient was given various supportive care, but eventually died of multiple organ failure.

Conclusion
The present case provides strong evidence of SFTSV transmission from H. longicornis to humans, and suggests that direct cross-species transmission can occur without additional intermediate hosts.
Patterns of ecstasy use amongst live music event attendees and their opinions on pill testing: a cross sectional study
Authors: Southey Madeleine , Kathirgamalingam Ashwini , Crawford Benjamin , Kaul Rohan , McNamara Jack , John-Leader Franklin , Heslop Jenny , Pit Sabrina Winona 
Published: August 2020

Abstract
Background
Pill testing services could potentially be used to reduce drug-related harm. This study aims to identify patterns of ecstasy use among live music event attendees; explore the opinions and potential usage of illicit pill testing programs and examine factors associated with the likelihood of still taking a pill containing a potential harmful substance.

Methods
A cross-sectional survey was completed by 760 people attending a major Australian live music event in 2017.

Results
The most commonly used drug in the last 12 months was ecstasy (73.9%). About 5% of people who use drugs had sought medical attention due to consumption of ecstasy. People who use drugs agreed “a lot” that pill testing should be provided for free at live music events (82.2%) and that it should be combined with harm reduction advice (62.9%). Additionally, 32% of all participants agreed ‘a lot’ that they would be more likely to take illicit drugs at a music festival if pill-testing services were present. However, if people perceived that a harmful substance was detected in their drugs after using a pill testing service, 52.3% of people who have used illicit drugs reported that they would ‘not at all’ be likely to still consume the drug. They also reported that they would still take a pill if testing demonstrated the presence of unintended MDMA-type substances (70.3%), amphetamines (31.2%) or ketamine (27.8%). Multivariate analyses demonstrated that only increased frequency of ecstasy use was significantly associated with taking a pill despite pill testing services detecting a harmful substance. Gender, age, alcohol and previously seeking ecstasy-related medical attention were not associated in the multivariate analyses.

Conclusions
A high proportion of live music attendees consume alcohol and ecstasy. Both people who have and who have not used illicit drugs support the implementation of pill testing services. People reported they would change their consumption patterns according to the results given by pill testing services. The findings may be used to stimulate public debate, and assist drug and alcohol policy makers in the implementation of harm minimisation strategies such as combining pill testing services with harm reduction advice.