bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pseudomonas syringae evades phagocytosis by animal cells via type III effector‐mediated regulation of actin filament plasticity
Authors: Yoon Sung‐Jin , Park Young‐Jun , Kim Jun‐Seob , Lee Soohyun , Lee Sang‐Hyun , Choi Song , Min Jeong‐Ki , Choi Inpyo , Ryu Choong‐Min 
Published: September 2018

SummaryCertain animal and plant pathogenic bacteria have developed virulence factors including effector proteins that enable them to overcome host immunity. A plant pathogen, Pseudomonas syringae pv. tomato (Pto) secretes a large repertoire of effectors via a type III secretory apparatus, thereby suppressing plant immunity. Here, we show that Pto causes sepsis in mice. Surprisingly, the effector HopQ1 disrupted animal phagocytosis by inhibiting actin rearrangement via direct interaction with the LIM domain of the animal target protein LIM kinase, a key regulator of actin polymerization. The results provide novel insight into animal host–plant pathogen interactions. In addition, the current study firstly demonstrates that certain plant pathogenic bacteria such as Pto evade phagocytosis by animal cells due to cross‐kingdom suppression of host immunity.
Bacterial ornithine lipid, a surrogate membrane lipid under phosphate‐limiting conditions, plays important roles in bacterial persistence and interaction with host
Authors: Kim Soo‐Kyoung , Park Soo‐Jin , Li Xi‐Hui , Choi Yu‐Sang , Im Dong‐Soon , Lee Joon‐Hee 
Published: September 2018

SummaryOrnithine lipids (OLs) are bacteria‐specific lipids that are found in the outer membrane of Gram (−) bacteria and increase as surrogates of phospholipids under phosphate‐limited environmental conditions. We investigated the effects of OL increase in bacterial membranes on pathogen virulence and the host immune response. In Pseudomonas aeruginosa, we increased OL levels in membranes by overexpressing the OL‐synthesizing operon (olsBA). These increases changed the bacterial surface charge and hydrophobicity, which reduced bacterial susceptibility to antibiotics and antimicrobial peptides (AMPs), interfered with the binding of macrophages to bacterial cells and enhanced bacterial biofilm formation. When grown under low phosphate conditions, P. aeruginosa became more persistent in the treatment of antibiotics and AMPs in an olsBA‐dependent manner. While OLs increased persistence, they attenuated P. aeruginosa virulence; in host cells, they reduced the production of inflammatory factors (iNOS, COX‐2, PGE2 and nitric oxide) and increased intracellular Ca2+ release. Exogenously added OL had similar effects on P. aeruginosa and host cells. Our results suggest that bacterial OL plays important roles in bacteria‐host interaction in a way that enhances bacterial persistence and develops chronic adaptation to infection.
Diatom populations in an upwelling environment decrease silica content to avoid growth limitation
Authors: McNair Heather M. , Brzezinski Mark A. , Krause Jeffrey W. 
Published: September 2018

SummaryA mix of adaptive strategies enable diatoms to sustain rapid growth in dynamic ocean regions, making diatoms one of the most productive primary producers in the world. We illustrate one such strategy off coastal California that facilitates continued, high, cell division rates despite silicic acid stress. Using a fluorescent dye to measure single‐cell diatom silica production rates, silicification (silica per unit area) and growth rates we show diatoms decrease silicification and maintain growth rate when silicon concentration limits silica production rates. While this physiological response to silicon stress was similar across taxa, in situ silicic acid concentration limited silica production rates by varying degrees for taxa within the same community. Despite this variability among taxa, silicon stress did not alter the contribution of specific taxa to total community silica production or to community composition. Maintenance of division rate at the expense of frustule thickness decreases cell density which could affect regional biogeochemical cycles. The reduction in frustule silicification also creates an ecological tradeoff: thinner frustules increase susceptibility to predation but reducing Si quotas maximizes cell abundance for a given pulse of silicic acid, thereby favouring a larger eventual population size which facilitates diatom persistence in habitats with pulsed resource supplies.
State of emergency medicine in Indonesia
Authors: Yusvirazi Liga , Ramlan Andi Ade Wijaya , Hou Peter C 
Published: September 2018

AbstractObjectivesAs an emerging country with the fourth largest population in the world, Indonesia's purchasing power has strengthened, leading to socioeconomic changes that affect its healthcare system. Additionally, there is a surge of healthcare utilisation after the implementation of a new national insurance scheme, particularly within emergency departments. Similar to other low‐ to middle‐income countries, Indonesia has not prioritised the progress of emergency medicine despite existing evidence that suggests that the early intervention of many acute conditions lowers the rates of morbidity and mortality. This article will review the past and current state of emergency medicine in Indonesia.MethodsThe information gathered through PubMed, Ovid, and private and government institution databases, using the search term ‘Indonesia’, ‘Emergency Medicine’, ‘Emergency Medical Services’, and ‘Disaster Medicine’. Additionally, we interviewed physicians who are involved in the development of emergency medicine in Indonesia.ResultsIndonesia's emergency medicine can be broken down into three sections: pre‐hospital, hospital and the development of emergency medicine as a specialty. At the pre‐hospital setting, disaster medicine and emergency medical service have not been established well enough to meet the demands of the population. For hospitals, there are two types of emergency departments – academic versus non‐academic. Currently, there is no accredited emergency medicine residency programme despite the recognition of the specialty.ConclusionThe development of emergency medicine in Indonesia is in its infancy and will require rapid improvement to meet its country's demand. Academic, private and government sectors need to collaborate to promote and invest in emergency medicine.
The face of animal cognition
Authors: HEALY Susan D. 
Published: September 2018

AbstractAs an increasing number of researchers investigate the cognitive abilities of an ever‐wider range of animals, animal cognition is currently among the most exciting fields within animal behavior. Tinbergen would be proud: all four of his approaches are being pursued and we are learning much about how animals collect information and how they use that information to make decisions for their current and future states as well as what animals do not perceive or choose to ignore. Here I provide an overview of this productivity, alighting only briefly on any single example, to showcase the diversity of species, of approaches and the sheer mass of research effort currently under way. We are getting closer to understanding the minds of other animals and the evolution of cognition at an increasingly rapid rate.
Prognostic significance of AKR1B10 in patients with resected lung adenocarcinoma
Authors: Hung Jung‐Jyh , Yeh Yi‐Chen , Hsu Wen‐Hu 
Published: September 2018

BackgroundAldo‐keto reductases (AKRs) modify carbonyl groups on aldehyde or ketones to form primary or secondary alcohols, which are then conjugated with sulfates or glucuronide for excretion. The AKR1B10 gene encodes a member of the AKR superfamily. Overexpression of AKR1B10 plays an important role in the tumorigenesis of lung cancer cells; however, the prognostic value of AKR1B10 expression in patients with lung adenocarcinoma has not been well demonstrated.MethodsA total of 96 patients with resected lung adenocarcinoma were included in the study. AKR1B10 expression was determined by immunohistochemistry in tumor specimens. The prognostic value of AKR1B10 overexpression and its relationship with clinicopathological variables were investigated.ResultsAKR1B10 overexpression was identified in 22 (22.9%) of the 96 patients and tended to be significantly associated with N1 or N2 status (P = 0.055). AKR1B10 overexpression was not a significant prognostic factor for overall survival (P = 0.301) but was a significant prognostic factor for poor recurrence‐free survival (P = 0.015). T status (T3 or T4 vs. T1 or T2; P = 0.020), N1 or N2 (vs. N0; P = 0.019), predominant pattern group (lepidic/acinar/papillary vs. micropapillary/solid; P = 0.023), and AKR1B10 overexpression (P = 0.013) were significant prognostic factors for poor recurrence‐free survival in multivariate analysis.ConclusionsAKR1B10 overexpression was a significant prognostic factor for poor recurrence‐free survival in patients with resected lung adenocarcinoma. This information is useful to stratify patients at high‐risk of recurrence after lung adenocarcinoma resection.
Pleural or pericardial metastasis: A significant factor affecting efficacy and adverse events in lung cancer patients treated with PD‐1/PD‐L1 inhibitors
Authors: Kang Da Hyun , Chung Chaeuk , Kim Ju‐Ock , Jung Sung Soo , Park Hee Sun , Park Dong Il , Jung Sun Young , Park Myoungrin , Lee Jeong Eun 
Published: September 2018

BackgroundImmunotherapy is a new paradigm for the treatment of non‐small‐cell lung cancer (NSCLC), and targeting the PD‐1 or PD‐L1 pathway is a promising therapeutic option. Although PD‐1/PD‐L1 inhibitors are more effective than standard chemotherapy in lung cancer, clinicians are afraid to actively use them because of hyperprogression and pseudoprogression. The aim of this study was to investigate the factors associated with tumor response and serious outcomes.MethodsWe retrospectively collected the medical records of 51 patients with advanced NSCLC who received PD‐1/PD‐L1 inhibitors between January 2016 and February 2018.ResultsThe mean patient age was 63.9 years, and 72.5% (37/51) were male. Most (92.2%, 47/51) had received previous systemic treatment. The overall response rate was 21.6% (11/51). The response rate was significantly lower in patients with pleural or pericardial metastasis than in patients without pleural or pericardial metastasis (4.3% vs. 35.7%; P = 0.007). Patients with pleural or pericardial metastasis had a significantly higher rate of adverse events of any grade (91.3% vs. 50.0%; P = 0.002) and grade 3–5 adverse events (52.2% vs. 25.0%; P = 0.046).ConclusionPleural or pericardial metastasis is a significant factor affecting the efficacy and rate of adverse events in advanced NSCLC patients treated with PD‐1/PD‐L1 inhibitors. Clinicians should pay attention to the use of immune checkpoint inhibitors in lung cancer patients with pleural or pericardial metastasis.
All Male Panels? Representation and Democratic Legitimacy
Authors: Clayton Amanda , O'Brien Diana Z. , Piscopo Jennifer M. 
Published: September 2018

AbstractWhat does women's presence in political decision‐making bodies signal to citizens? Do these signals differ based on the body's policy decisions? And do women and men respond to women's presence similarly? Though scholars have demonstrated the substantive and symbolic benefits of women's representation, little work has examined how women's presence affects citizens' perceptions of democratic legitimacy. We test the relationship between representation and legitimacy beliefs through survey experiments on a nationally representative sample of U.S. citizens. First, we find that women's equal presence legitimizes decisions that go against women's interests. We show suggestive evidence that this effect is particularly pronounced among men, who tend to hold less certain views on women's rights. Second, across decision outcomes and issue areas, women's equal presence legitimizes decision‐making processes and confers institutional trust and acquiescence. These findings add new theoretical insights into how, when, and for whom inclusive representation increases perceptions of democratic legitimacy.
An update on semen quality among young Finnish men and comparison with Danish data
Authors: Rodprasert W. , Virtanen H. E. , Sadov S. , Perheentupa A. , Skakkebæk N. E. , Jørgensen N. , Toppari J. 
Published: September 2018

AbstractBackgroundFinnish men used to have higher semen quality than Danish men. However, recent studies showed that semen quality in Finland has declined, but it has been relatively stable in Denmark.ObjectiveThis study aimed to compare new data on semen quality of the young Finnish men to that of Danish men.Materials and methodsIn this cross‐sectional study, 18‐ to 19‐year‐old men residing in Turku, Finland and Copenhagen, Denmark, were invited to participate in 2008–2011. Each man filled in a questionnaire, provided one semen sample and underwent andrological examination. Semen samples were analyzed according to WHO. Multiway ANOVA was used to adjust semen variables for duration of sexual abstinence and age (and time from ejaculation to the start of semen analysis for sperm motility).ResultsAltogether 287 Finnish men and 873 Danish men participated in the study. The adjusted median sperm concentrations were 49 and 47 million/mL for Finnish and Danish men, respectively (p = 0.48). The adjusted median total sperm counts were 148 million in Finland and 146 million in Denmark (p = 0.87). The adjusted median percentages of morphologically normal spermatozoa were 6.9% in Finland and 6.5% in Denmark, p = 0.27. Finnish men had higher adjusted median percentages of motile spermatozoa (A+B+C) than Danish men (80% vs. 69%, p < 0.001). The proportion of men who had low semen quality (sperm concentration, percentage of morphologically normal spermatozoa or percentage of progressively motile spermatozoa below WHO reference limits) was lower in Finland (25.4%) than in Denmark (34.6%), p = 0.004.DiscussionConsiderable percentage of men in both countries had low semen quality. The deteriorating semen quality in Finland may result in decreasing fecundity, which is a cause of concern.ConclusionThe formerly high semen quality in Finland has converged to the lower Danish levels. Our findings demonstrate the importance of continuing surveillance of semen quality.
Klotho protein supplementation reduces blood pressure and renal hypertrophy in db/db mice, a model of type 2 diabetes
Authors: Takenaka Tsuneo , Kobori Hiroyuki , Miyazaki Takashi , Suzuki Hiromichi , Nishiyama Akira , Ishii Naohito , Yamashita Maho , Hayashi Matsuhiko 
Published: September 2018

AbstractAimsKlotho interacts with various membrane proteins, such as receptors for transforming growth factor (TGF)‐β and insulin‐like growth factor (IGF), to alter their function. Renal expression of klotho is diminished in diabetes. The present study examined whether exogenous klotho protein supplementation ameliorates kidney injury and renin–angiotensin system (RAS) in db/db mice.MethodsWe investigated the effects of klotho supplementation on diabetic kidney injury and RAS. Recombinant human klotho protein (10 μg/kg/d) was administered to db/db mice daily.ResultsKlotho protein supplementation reduced kidney weight, systolic blood pressure (SBP), albuminuria, glomerular filtration rate, and 8‐epi‐prostaglandin F2α excretion without affecting body weight. Although klotho supplementation did not alter glycated albumin, it reduced renal angiotensin II levels associated with reduced renal expression of angiotensinogen. Klotho supplementation improved renal expression of superoxide dismutase (SOD), and endogenous renal expression of klotho. Klotho supplementation reduced the levels of hypoxia‐inducible factor, phosphorylated Akt, and phosphorylated mTOR and decreased the renal expression of TGF‐β, tumour necrosis factor (TNF), and fibronectin.ConclusionsThese data indicate that klotho supplementation reduces blood pressure and albuminuria along with ameliorating renal RAS activation in db/db mice. Furthermore, these results suggest that klotho inhibits IGF signalling, induces SOD expression to reduce oxidative stress, and suppresses Akt‐mTOR signalling to inhibit abnormal kidney growth. Collectively, the results suggest that klotho inhibits TGF‐β and TNF signalling, resulting in a decline in renal fibrosis.
Optimal maternal and neonatal outcomes and associated hospital characteristics
Authors: Campbell Katherine H. , Illuzzi Jessica L. , Lee Henry C. , Lin Haiqun , Lipkind Heather S. , Lundsberg Lisbet S. , Pettker Christian M. , Xu Xiao 
Published: September 2018

AbstractBackgroundThis study aims to examine hospital variation in both maternal and neonatal morbidities and identify institutional characteristics associated with hospital performance in a combined measure of maternal and neonatal outcomes.MethodsUsing the California Linked Birth File containing data from birth certificate and hospital discharge records, we identified 1 322 713 term births delivered at 248 hospitals during 2010‐2012. For each hospital, a risk‐standardized rate of severe maternal morbidities and a risk‐standardized rate of severe newborn morbidities were calculated after adjusting for patient clinical risk factors. Hospitals were ranked based on combined information on their maternal and newborn morbidity rates.ResultsRisk‐standardized severe maternal and severe newborn morbidity rates varied substantially across hospitals (10th to 90th percentile range = 67.5‐148.2 and 141.8‐508.0 per 10 000 term births, respectively), although there was no significant association between the two (P = 0.15). Government hospitals (non‐Federal) were more likely than other hospitals to be in worse rank quartiles (P value for trend = 0.004), whereas larger volume was associated with better rank among hospitals in the first three quartiles (P = 0.004). The most prevalent morbidities that differed progressively across hospital rank quartiles were severe hemorrhage, disseminated intravascular coagulation, and heart failure during procedure/surgery for mothers, and severe infection, respiratory complication, and shock/resuscitation for neonates.ConclusionsHospitals with low maternal morbidity rates may not have low neonatal morbidity rates and vice versa, highlighting the importance of assessing joint maternal‐newborn outcomes in order to fully characterize a hospital's obstetrical performance. Hospitals with smaller volume and government ownership tend to have less desirable outcomes and warrant additional attention in future quality improvement efforts.
Tumour contact surface area as a predictor of postoperative complications and renal function in patients undergoing partial nephrectomy for renal tumours
Authors: Ficarra Vincenzo , Crestani Alessandro , Bertolo Riccardo , Antonelli Alessandro , Longo Nicola , Minervini Andrea , Novara Giacomo , Simeone Claudio , Carini Marco , Mirone Vincenzo , Porpiglia Francesco ,   Collaborators
Published: September 2018

ObjectivesTo evaluate the ability of original tumour contact surface area (CSA) to predict postoperative complications and renal function impairment in a series of patients who underwent elective partial nephrectomy (PN) for renal masses.Materials and MethodsWe analysed the clinical records of 531 consecutive patients who underwent elective PN because of a suspicion of kidney cancer at five academic, high‐volume centres between January 2014 and December 2016. Each participating centre evaluated prospectively the radiological images to evaluate the CSA and to assign a PADUA score. Several expert surgeons performed the surgical procedures in each participating centre. Binary logistic regression was used to perform both univariable and multivariable analyses to identify predictors of postoperative complications. Linear regression analysis was used to identify independent predictors of absolute change in estimated glomerular filtration rate (eGFR; ACE).ResultsThe median (interquartile range) CSA value was 14.2 (7.4–25.1) cm2. A total of 349 tumours (65.7%) had a CSA ≤ 20 cm2 and the remaining 182 (34.3%) had a CSA > 20 cm2. PNs were performed using an open approach in 237 (44.6%) cases, a pure laparoscopic approach in 152 cases (28.6%), and a robot‐assisted approach in the remaining 142 cases (26.7%). Multivariable analyses found that only age (odds ratio [OR] 1.037, 95% confidence interval [CI] 1.018–1.057) and PADUA score (OR 1.289, 95%CI 1.132–1.469) were independent predictors of postoperative complications. Tumour CSA (OR 1.020, 95%CI 1.010–1.030) was found to be an independent predictor of postoperative complications only when PADUA score was removed from the model. Age (from −0.639 to −0.306; P < 0.001); body mass index (from 0.267 to 1.076; P = 0.001), age‐adjusted Charlson score (from −3.193 to −0.259; P = 0.02), preoperative eGFR value (from −0.939 to −0.862; P < 0.001) and tumour CSA (from −0.260 to −0.048; P = 0.005) were found to be independent predictors of ACE.ConclusionsTumour CSA is an independent predictor of postoperative renal function. Conversely, at multivariable analysis, PADUA score outperformed tumour CSA to predict postoperative complications after PN. The complexity of The Leslie et al. formula for calculating tumour CSA is a potential limitation with regard to its diffusion and application in clinical practice.
Design, synthesis, and biological evaluation of quinazoline derivatives as dual HDAC1 and HDAC6 inhibitors for the treatment of cancer
Authors: Chen Jinying , Sang Zitai , Jiang Youjun , Yang Chao , He Linhong 
Published: September 2018

AbstractFifty‐eight quinazoline‐based compounds were designed and synthesized based on the structural optimizations from the lead compound 23bb in an attempt to search for more potent dual HDAC1 and HDAC6 inhibitors. Among them, 32c (HDAC1, IC50 = 31.10 ± 0.37 nM; HDAC6, IC50 = 16.15 ± 0.62 nM) and 32d (HDAC1, IC50 = 37.00 ± 0.24 nM; HDAC6, IC50 = 35.00 ± 0.71 nM) were not only identified as potent dual‐acting HDAC1 and HDAC6 inhibitors with over 10‐fold selectivity to the other HDACs, but also displayed activities in tubulin acetylation and histone H3 acetylation induction. Importantly, both of them displayed strong antiproliferative activities against various tumor cell lines in vitro with IC50 values less than 40 nM, especially for hematologic tumors cells (U266 and RPMI8226, IC50 < 1 nM), which were even better than 23bb and SAHA. Furthermore, 32c showed a significant tumor growth inhibition (antitumor rate = 63.98%, p < 0.05) in the resistant MCF‐7/ADR xenograft model without any obvious body weight changes and abnormal behaviors. Our findings validate that 32c is a potent dual inhibitor of HDAC1/6 that can be an efficacious treatment for breast cancer with Adriamycin resistance.