bluuebunny/crossref_metadata_2025 huggingface dataset:
Make campus safe for students with disabilities
Authors: Rahn Josh
Published: January 2020

Students with disabilities face unique challenges on college campuses. One of those challenges is how to recognize and react appropriately to an emergency or violent incident, such as an active shooter. In New Jersey, the Bergen Community College Office of Specialized Services partnered with campus safety personnel and the Bergen County Sheriff's Office to develop a training program to address this need.
Support student medication adherence
Authors: Bedrossian Louise
Published: January 2020

Disability services providers are positioned to observe changes and difficulties among our students that might indicate medication misuse or abandonment. Encouraging them to adhere to medication use can help them achieve academic success.
Novel word learning deficits in infants at family risk for dyslexia
Authors: Kalashnikova Marina , Goswami Usha , Burnham Denis
Published: January 2020

Children of reading age diagnosed with dyslexia show deficits in reading and spelling skills, but early markers of later dyslexia are already present in infancy in auditory processing and phonological domains. Deficits in lexical development are not typically associated with dyslexia. Nevertheless, it is possible that early auditory/phonological deficits would have detrimental effects on the encoding and storage of novel lexical items. Word‐learning difficulties have been demonstrated in school‐aged dyslexic children using paired associate learning tasks, but earlier manifestations in infants who are at family risk for dyslexia have not been investigated. This study assessed novel word learning in 19‐month‐old infants at risk for dyslexia (by virtue of having one dyslexic parent) and infants not at risk for any developmental disorder. Infants completed a word‐learning task that required them to map two novel words to their corresponding novel referents. Not at‐risk infants showed increased looking time to the novel referents at test compared with at‐risk infants. These findings demonstrate, for the first time, that at‐risk infants show differences in novel word‐learning (fast‐mapping) tasks compared with not at‐risk infants. Our findings have implications for the development and consolidation of early lexical and phonological skills in infants at family risk of later dyslexia.
Early and late diagnosed dyslexia in secondary school: Performance on literacy skills and cognitive correlates
Authors: Bazen Loes , van den Boer Madelon , de Jong Peter F. , de Bree Elise H.
Published: January 2020

Although a diagnosis of dyslexia is often made during elementary school, severe and persistent literacy difficulties of a considerable group of students are only noticed during secondary school. The question arises whether the literacy(‐related) deficits of these late identified students with dyslexia differ from those of early diagnosed students. To address this question, 10th Grade Dutch secondary school students with early (n= 35) and late (n= 19) identified dyslexia and their peers with average to good literacy abilities (n= 24) were compared on literacy skills and underlying cognitive skills. At the group level, both students with an early and late diagnosis performed more poorly than their typical peers, but they did not differ from each other on (pseudo‐)word reading, spelling and underlying cognitive correlates (phonemic awareness, rapid automatized naming and visual attention span). The early and late group contained comparable percentages of students performing poorly on most measures. There were, however, more students in the early group who showed deficits in phonemic awareness. Our results indicate that students with early and late diagnosed dyslexia are highly comparable. Suggestions for fitting interventions are discussed.
Minimizing moving distance in deposition behavior of the subterranean termite
Authors: Lee Sang‐Bin , Su Nan‐Yao , Song Hark‐Soo , Lee Sang‐Hee
Published: January 2020

Subterranean termite nests are located underground and termites forage out by constructing tunnels to reach food resources, and tunneling behavior is critical in order to maximize the foraging efficiency. Excavation, transportation, and deposition behavior are involved in the tunneling, and termites have to move back and forth to do this. Although there are three sequential behaviors, excavation has been the focus of most previous studies. In this study, we investigated the deposition behavior of the Formosan subterranean termite, Coptotermes formosanus Shiraki, in experimental arenas having different widths (2, 3, and 4 mm), and characterized the function of deposited particles. We also simulated moving distance of the termites in different functions. Our results showed that total amounts of deposited particles were significantly higher in broad (4 mm width) than narrow (2 mm) tunnels and most deposited particles were observed near the tip of the tunnel regardless of tunnel widths. In addition, we found that deposited particles followed a quadratic decrease function, and simulation results showed that moving distance of termites in this function was the shortest. The quadratic decrease function of deposited particles in both experiment and simulation suggested that short moving distance in the decrease quadratic function is a strategy to minimize moving distance during the deposition behavior.
Relationship between B‐type natriuretic peptide and invasive haemodynamics in patients with severe aortic valve stenosis
Authors: Maeder Micha T. , Weber Lukas , Ammann Peter , Buser Marc , Ehl Niklas F. , Gerhard Marc , Brenner Roman , Haager Philipp K. , Maisano Francesco , Rickli Hans
Published: January 2020

Aims

In patients with aortic stenosis (AS), B‐type natriuretic peptide (BNP) is a prognostic marker. However, there is little information on the association between BNP and invasive haemodynamics in AS. The aim of the present study was to assess the hitherto not well‐defined relationship between BNP and invasive haemodynamics in patients with severe AS undergoing aortic valve replacement (AVR) with a view to understand the link between high BNP and poor prognosis in these patients. In particular, we were interested in the association between BNP and combined pre‐capillary and post‐capillary pulmonary hypertension (CpcPH).

Methods and results

BNP was measured in 252 patients (age 74 ± 10 years, 58% male patients) with severe AS [indexed aortic valve area 0.4 ± 0.1 cm2/m2 and left ventricular ejection fraction (LVEF) 57 ± 12%] the day before cardiac catheterization. Patients were followed for a median (interquartile range) period of 3.1 (2.3–4.3) years after surgical (n = 157) or transcatheter (n = 95) AVR. The prevalence of CpcPH (mean pulmonary artery pressure ≥ 25 mmHg, mean pulmonary artery wedge pressure > 15 mmHg, and pulmonary vascular resistance > 3 Wood units) was 13%. The median BNP plasma concentration was 188 (78–452) ng/L. The indexed aortic valve area was similar across BNP quartiles (P = 0.21). Independent predictors of higher BNP (ln transformed) included lower haemoglobin (beta = −0.18; P < 0.001), lower LVEF (beta = −0.20; P < 0.001), more severe mitral regurgitation (beta = 0.20; P < 0.001), higher mean pulmonary artery wedge pressure (beta = −0.37; P < 0.001), and higher pulmonary vascular resistance (beta = 0.21; P < 0.001). In a multivariate model with CpcPH rather than its haemodynamic components, CpcPH was independently associated with higher BNP (0.21; P < 0.001). Higher ln BNP was associated with higher mortality [hazard ratio 1.90 (95% confidence interval 1.33–2.71); P < 0.001] in the univariate analysis. Patients in the third and fourth BNP quartiles had a more than six‐fold risk of death compared with patients in the first and second quartiles [hazard ratio 6.29 (95% confidence interval 1.86–21.27); P = 0.003]. In the multivariate analysis, lower LVEF [hazard ratio 0.96 (95% confidence interval 0.94–0.99) per 1% increase; P = 0.01] and CpcPH [hazard ratio 4.58 (95% confidence interval 1.89–11.09); P = 0.001] but not BNP were independently associated with mortality. The areas under the receiver operator characteristics curve for BNP for the prediction of CpcPH and mortality were 0.88 and 0.74, respectively.

Conclusions

In patients with severe AS, higher BNP is a marker of the presence of CpcPH and its contributors. The association between BNP and such an adverse haemodynamic profile at least in part explains the ability of BNP to predict long‐term post‐AVR mortality.
Prescription patterns of diabetes medications influencing clinical outcomes of heart failure patients with reduced ejection fraction
Authors: Chang Hung‐Yu , Su Yu‐Wen , Feng An‐Ning , Fong Man‐Cai , Huang Kuan‐Chih , Chong Eric , Chen Kuan‐Chun , Yin Wei‐Hsian
Published: January 2020

Aims

We collected the different prescription patterns of diabetes medications in a cohort of patients with heart failure with reduced ejection fraction (HFrEF) and analysed the impact of different prescription patterns on clinical outcomes.

Methods and results

Consecutive diabetic patients with HFrEF from a heart failure referral centre were retrospectively analysed between 2015 and 2016. Exclusion criteria include being lost to follow‐up, not receiving diabetes medications, and having severe renal impairment with a glomerular filtration rate < 30 mL/min/1.73 m2. Prescription of diabetes medications and the respective clinical outcomes were collected between 2016 and 2018. Among 381 patients (mean age, 64.8 ± 12.8 years; 71.9% male; mean left ventricular ejection fraction, 27.6 ± 7.0%; mean body mass index, 26.1 ± 4.7 kg/m2), the prescription rates of sodium‐glucose co‐transporter 2 inhibitor (SGLT2i) increased from 10.3% in 2016 to 17.6% in 2017 and 26.5% in 2018 (P < 0.001); the prescription rates of metformin, sulfonylurea, insulin, and dipeptidyl peptidase‐4 inhibitors did not change significantly over time. The prescription rates of metformin and SGLT2i were significantly higher in patients managed by cardiologists than non‐cardiologists (in 2018, 71.1% vs. 44.2% for metformin, 45.4% vs. 9.9% for SGLT2i, both P < 0.001). During the study period, annualized event rates of cardiovascular death or first unplanned HF hospitalization were 19.0 per 100 patient‐years. After a multivariate analysis, prescriptions of metformin {odds ratio (OR): 0.49 [95% confidence interval (CI) 0.27–0.51], P < 0.001} and SGLT2i [OR: 0.52 (95% CI 0.28–0.98), P = 0.042] were independently associated with lower annualized event rates of cardiovascular death or unplanned HF hospitalization.

Conclusions

Prescription patterns of diabetes medications in diabetics with HFrEF were diverse among different specialists. Prescriptions of metformin and SGLT2i were associated with favourable clinical outcomes. Our finding indicates the importance of awareness of beneficial effect of different classes of diabetes medications and collaboration between specialists in the management of diabetic HFrEF patients.
Copper/Nickel‐Catalyzed Selective C–S/S–S Bond Formation Starting from O‐Alkyl Phenylcarbamothioates
Authors: Peng Kang , Gao Ming‐Yuan , Yi Yu‐Yan , Guo Jia , Dong Zhi‐Bing
Published: January 2020

A convenient and effective method is described to construct C–S/S–S bond starting from O‐alkyl phenylcarbamothioates, giving diverse O‐alkyl S‐phenyl phenylcarbonimidothioates and isothiourea disulfides, respectively. The C–S bond formation products (O‐alkyl S‐phenyl phenylcarbonimidothioates) were synthesized by using Cu2O as catalyst in water (without phase‐transfer catalyst), and the S–S bond formation product (isothiourea disulfides) could be furnished catalyzed by NiBr2 at room temperature. These transformations feature easy control, environmental friendliness, and good to excellent yields, which could be attractive in the selective C–S/S–S bond formation.
Anomalous diffusion in an electrolyte saturated paper matrix
Authors: Das Sankha Shuvra , Kumar Sumeet , Ghosal Sambuddha , Ghosal Sandip , Chakraborty Suman
Published: January 2020

Diffusion of colored dye on water saturated paper substrates has been traditionally exploited with great skill by renowned water color artists. The same physics finds more recent practical applications in paper‐based diagnostic devices deploying chemicals that react with a bodily fluid yielding colorimetric signals for disease detection. During spontaneous imbibition through the tortuous pathways of a porous electrolyte saturated paper matrix, a dye molecule undergoes diffusion in a complex network of pores. The advancing front forms a strongly correlated interface that propagates diffusively but with an enhanced effective diffusivity. We measure this effective diffusivity and show that it is several orders of magnitude greater than the free solution diffusivity and has a significant dependence on the solution pH and salt concentration in the background electrolyte. We attribute this to electrically mediated interfacial interactions between the ionic species in the liquid dye and spontaneous surface charges developed at porous interfaces, and introduce a simple theory to explain this phenomenon.
Bottom‐up proteomics of envelope proteins extracted from spinach chloroplast via high organic content CE‐MS
Authors: Cheng Jianhui , Morin Gregg B. , Chen David D. Y.
Published: January 2020

A high organic content CE‐MS/MS (HOCE‐MS/MS) method was developed for the proteomic analysis of envelope proteins extracted from spinach leaves. Separation was performed in a 1‐m long hydroxypropyl cellulose coated capillary, using 8% (v/v) formic acid in 70% (v/v) methanol and 22% water as the BGE. A flow‐through microvial interface was used to couple the CE system with an Orbitrap Fusion Lumos mass spectrometer, and field‐amplified sample stacking was used to improve the concentration sensitivity. Using this optimized method, 3579 peptides and 1141 proteins were identified using the Proteome Discoverer software with a 1% false discovery rate at the protein level. Relative to conventional aqueous CE, HOCE‐MS did a better job of discovering hydrophobic peptides and provided more peptide and protein identifications. Relative to nano‐LC‐MS, it achieved comparable peptide and protein identification performance and detected peptides not identified by LC‐MS: of the full set of peptides identified using the two techniques, 19% were identified only using HOCE‐MS. It also outperformed nano‐LC‐MS with respect to the detection of low molecular weight peptides.
Pushover‐based seismic risk assessment and loss estimation of masonry buildings
Authors: Snoj Jure , Dolšek Matjaž
Published: January 2020

A pushover‐based seismic risk assessment and loss estimation methodology for masonry buildings is introduced. It enables estimation of loss by various performance measures such as the probability of exceeding a designated economic loss, the expected annual loss, and the expected loss given a seismic intensity. The methodology enables the estimation of the economic loss directly from the results of structural analysis, which combines pushover analysis and incremental dynamic analysis of an equivalent SDOF model. The use of the methodology is demonstrated by means of two variants of a three‐storey masonry building both of which have the same geometry, but they are built, respectively, from hollow clay masonry (model H) and solid brick masonry (model S). The probability of collapse given the selected design earthquake corresponding to a return period of 475 years was found to be negligible for model H, which indicates the proper behaviour of such a structure when designed according to the current building codes. However, the corresponding probability of collapse of model S was very high (46%). The expected total loss given the design earthquake was estimated to amount to 28 000 € and 290 000 €, respectively, for models H and S. The expected annual loss per 100 m2 of gross floor area was estimated to amount to 75 € and 191 €, respectively, for models H and S. For the presented examples, it was also observed that nonstructural elements contributed more than 50% of the total loss.
A morphologic and molecular reappraisal of myoepithelial tumors of soft tissue, bone, and viscera with EWSR1 and FUS gene rearrangements
Authors: Suurmeijer Albert J. H. , Dickson Brendan C. , Swanson David , Zhang Lei , Sung Yun‐Shao , Fletcher Christopher D. , Antonescu Cristina R.
Published: January 2020

Myoepithelial tumors (MET) represent a clinicopathologically heterogeneous group of tumors, ranging from benign to highly aggressive lesions. Although MET arising in soft tissue, bone, or viscera share morphologic and immunophenotypic overlap with their salivary gland and cutaneous counterparts, there is still controversy regarding their genetic relationship. Half of MET of soft tissue and bone harbor EWSR1 or FUS related fusions, while MET arising in the salivary gland and skin often show PLAG1 and HMGA2 gene rearrangements. Regardless of the site of origin, the gold standard in diagnosing a MET relies on demonstrating its “myoepithelial immunophenotype” of positivity for EMA/CK and S100 protein or GFAP. However, the morphologic spectrum of MET in soft tissue and bone is quite broad and the above immunoprofile is nonspecific, being shared by other pathogenetically unrelated neoplasms. Moreover, rare MET lack a diagnostic immunoprofile but shows instead the characteristic gene fusions. In this study, we analyzed a large cohort of 66 MET with EWSR1 and FUS gene rearrangements spanning various clinical presentations, to better define their morphologic spectrum and establish relevant pathologic‐molecular correlations. Genetic analysis was carried out by FISH for EWSR1/FUS rearrangements and potential partners, and/or by targeted RNA sequencing. Then, 82% showed EWSR1 rearrangement, while 18% had FUS abnormalities. EWSR1‐POU5F1 occurred with predilection in malignant MET in children and young adults and these tumors had nested epithelioid morphology and clear cytoplasm. In contrast, EWSR1/FUS‐PBX1/3 fusions were associated with benign and sclerotic spindle cell morphology. Tumors with EWSR1‐KLF17 showed chordoma‐like morphology. Our results demonstrate striking morphologic‐molecular correlations in MET of bone, soft tissue and viscera, which might have implications in their clinical behavior.
Hemoglobin, anemia, and poststroke cognitive impairment: A cohort study
Authors: He Weilei , Ruan Yiting , Yuan Chengxiang , Luan Xiaoqian , He Jincai
Published: January 2020

Objectives

Several studies have demonstrated that anemia was associated with cognitive impairment. The aim of this study was to explore the relationship between hemoglobin and cognitive impairment in patient with acute ischemic stroke.

Methods

In total, 326 patients with acute ischemic stroke were followed up for 1 month. The main outcome was the incidence and severity of poststroke cognitive impairment (PSCI) assessed by Mini‐Mental State Examination (MMSE). The impact of hemoglobin levels and anemia on PSCI was assessed by multiple regression models controlling for potential confounders.

Results

During the 1‐month follow‐up, 193 (59.2%) patients developed PSCI. Anemia was independently associated with PSCI (OR = 3.637; 95% CI, 1.216‐10.881; P = .021) after adjusting for demographics, vascular risk factors, stroke severity, and functional outcome. When the hemoglobin levels stratified into tertiles, higher hemoglobin levels were associated with better cognitive function. This result was however not significant after adjusting for the same confounders above.

Conclusions

Low hemoglobin levels are associated with an increased risk of PSCI. Targeted interventions in this population may reduce the incidence of PSCI and require further evaluation.
In‐vivo hemodynamic imaging of acute prenatal ethanol exposure in fetal brain by photoacoustic tomography
Authors: Shan Tianqi , Zhao Yuan , Jiang Shixie , Jiang Huabei
Published: January 2020

Prenatal ethanol exposure (PEE) can lead to structural and functional abnormalities in fetal brain. Although neural developmental deficits due to PEE have been recognized, the immediate effects of PEE on fetal brain vasculature and hemodynamics remain poorly understood. One of the major obstacles that preclude the rapid advancement of studies on fetal vascular dynamics is the limitation of the imaging techniques. Thus, a technique for noninvasive in‐vivo imaging of fetal vasculature and hemodynamics is desirable. In this study, we explored the dynamic changes of the vessel dimeter, density and oxygen saturation in fetal brain after acute maternal ethanol exposure in the second‐trimester equivalent murine model using a real‐time photoacoustic tomography system we developed for imaging embryo of small animals. The results indicate a significant decrease in fetal brain vessel diameter, perfusion and oxygen saturation. This work demonstrated that PAT can provide high‐resolution noninvasive imaging ability to monitor fetal vascular dynamics.
Covalent attachment of resveratrol to stainless steel toward the development of a resveratrol‐releasing bare‐metal stent
Authors: Creasey Hannah N. , Brandel Elizabeth Z. , Nguyen Ryan , Bashore Morgan J. , Jones Casey M.
Published: January 2020

Herein, we describe the covalent attachment of resveratrol, a naturally occurring antioxidant, to the surface of stainless‐steel as a model for designing a novel bare‐metal stent to treat coronary artery disease. Resveratrol has been shown to reduce oxidative stress in dysfunctional endothelial cells, and stimulate arterial healing. Resveratrol treatments, however, are limited by low water solubility, such that a localized delivery to the site of arterial narrowing via a coated stent presents a promising strategy for improving stent outcomes. Our attachment strategy utilizes zirconium vapor deposition to lay down a thin layer of zirconium oxide with labile hydrocarbon groups at the surface. Resveratrol can displace these hydrocarbons in aprotic solvent to afford a covalently attached layer of resveratrol. We evaluated the release of resveratrol under a range of pH levels, including physiological conditions (pH = 7.4 and 37 °C). Furthermore, we established that endothelial cells grown on a resveratrol‐bound surface release elevated nitric oxide levels compared to controls, a key endothelial signaling molecule responsible for arterial health. These results are promising toward the development of a resveratrol‐coated bare‐metal stent to improve patient outcomes.
Assessment of Similarity in Antipsychotic Exposure‐Response Relationships in Clinical Trials Between Adults and Adolescents With Acute Exacerbation of Schizophrenia
Authors: Kalaria Shamir N. , Farchione Tiffany R. , Mathis Mitchell V. , Gopalakrishnan Mathangi , Younis Islam , Uppoor Ramana , Mehta Mehul , Wang Yaning , Zhu Hao
Published: January 2020

Despite agreement that early‐onset schizophrenia is continuous with the adult‐onset form, quantitative relationships between antipsychotic exposure and clinical response are relatively unexplored in adolescents, compared to adults. Clinical efficacy data from second‐generation antipsychotic development programs (N = 5951 adults and N = 1035 adolescents ranging from 12 to 17 years old) were collected from available new drug applications submitted to the US Food and Drug Administration from 1993 to 2017. The developed disease–drug trial models adequately predicted the longitudinal trend in total positive and negative syndrome scale scores in both adults and adolescents using a Weibull placebo response, time‐delayed drug effect, and a Weibull structural dropout model. Maximum drug effect was similar between the two populations and was estimated to be between a range of 5% to 11% in adults and 5% to 7% in adolescents. Half maximal effective concentration parameter estimates also indicated similar exposure‐response relationships in adults and adolescents across all 4 antipsychotics. Simulated adolescent data using final model parameter estimates from the adult model were in agreement with adolescent observations. This analysis confirms similarity in exposure‐response for efficacy and could expedite the development of second‐generation antipsychotics for adolescents.
The impacts of Cu(II) complexation on gatifloxacin adsorption onto goethite and hematite
Authors: Li Xiangzhi , Bi Erping
Published: January 2020

Gatifloxacin (GAT) is a new generation fluoroquinolone antibiotic and its adsorption onto iron minerals influenced by coexisting trace elements [e.g., Cu(II)] has not been well investigated. To evaluate the adsorption behavior of GAT and Cu(II) onto goethite and hematite, the complexation constants of GAT with Cu(II) were determined using potentiometric titration, and the effects of Cu(II) concentration and solution pH on GAT adsorption were investigated using batch experiments. It was observed that GAT adsorption was negatively correlated with molar concentration ratio of Cu(II) to GAT. In our experimental pH range (i.e., 3.0–10.8), the calculated main species involved in GAT adsorption were Cu(GAT±)2+ and Cu(GAT±)22+ under acidic to neutral conditions, and formation of Cu(GAT−)2(s) facilitated the removal of GAT from solution under alkaline condition. The adsorption data were well fitted by the Freundlich model and showed high nonlinearity. In adsorption onto goethite, the primary interactions shifted from electrostatic repulsion to formation of goethite–Cu(II)–GAT ternary surface complexes with increase of GAT concentration. For hematite, electrostatic repulsion was the main inhibiting mechanism and became stronger with increase of Cu(II) concentration. Our findings suggest that it is necessary to consider the complexation between GAT and coexisting metal cations in evaluating its transport in soils rich in different iron minerals.
Suppressed LPS‐mediated TLR4 signaling in the plateau zokor (Eospalax baileyi) compared to the bamboo rat (Rhizomys pruinosus) and rat (Rattus norvegicus)
Authors: Cao Wangjie , Pu Peng , Wang Jinzhou , Niu Zhiyi , Zhang Tao , He Jie , Tang Xiaolong , Chen Qiang
Published: January 2020

Ecological immunology involves the study of the immune function of wildlife, which is seldom compared with that of model animals. Here, we evaluated and compared the level of the innate immune response in the plateau zokor (Eospalax baileyi), an indigenous underground rodent from the Tibetan Plateau, with that in the bamboo rat (Rhizomys pruinosus) and Sprague‐Dawley (SD) rat (Rattus norvegicus). The spleen was observed by ordinary light and transmission electron microscopy, and the spleen index was calculated. After liposaccharide (LPS) challenge, the expression of Toll‐like receptor 2 (TLR2), TLR4, and hypoxia‐inducible factor 1α (HIF‐1α) in the spleen was detected by Western blot analysis and immunofluorescence. The expression of nuclear factor‐κB1 (NF‐κB1) and mitogen‐activated protein kinase 14 (MAPK14) in the spleen was detected by real‐time quantitative polymerase chain reaction, and the levels of interleukin 6 (IL‐6), tumor necrosis factor‐α (TNF‐α), and interferon‐β (IFN‐β) in the spleen were detected by enzyme‐linked immunoassay. The spleen index of the plateau zokor was lower than that of the bamboo rat and SD rat. The expression of TLR4, NF‐κB1, and MAPK14 and the levels of IL‐6 and TNF‐α in the spleen of the plateau zokor were lower than those of the bamboo rat and SD rat, while the expression of TLR2 and HIF‐1α and the level of IFN‐β were higher than those of the bamboo rat and SD rat. We speculate that suppression of the TLR4 signaling pathway in the plateau zokor is an adaptation to hypoxic tunnels that decreases antigenic risk and maintains immune homeostasis. Moreover, the spleen of the plateau zokor is reduced in size, reducing the innate immunity investment in the spleen. We also noted that high levels of HIF‐1α in the spleen of the plateau zokor suppressed crosstalk between HIF‐1α and TLR4, promoting the innate immune response.
Antibacterial, antibiofilm, and antiquorum sensing activities of phytosynthesized silver nanoparticles fabricated fromMespilus germanicaextract against multidrug resistance ofKlebsiella pneumoniaeclinical strains
Authors: Foroohimanjili Fatemeh , Mirzaie Amir , Hamdi Seyed Mohammad Mehdi , Noorbazargan Hassan , Hedayati Ch Mojtaba , Dolatabadi Aghigh , Rezaie Hossein , Bishak Faezeh M.
Published: January 2020

The aim of the present work was to investigate the antibacterial, antibiofilm, and antiquorum sensing activities of phytosynthesized silver nanoparticles (AgNPs) fabricated from Mespilus germanica extract against multidrug‐resistant (MDR) Klebsiella pneumoniae strains. Fifty strains of K. pneumoniae were isolated from various clinical specimens. Biofilm‐forming strains were identified using Congo red agar and polymerase chain reaction (PCR) techniques. Subsequently, the antibacterial activity of phytosynthesized AgNPs on MDR K. pneumoniae strains was investigated by broth microdilution assay and agar well‐diffusion method. Finally (in the last step), the antibiofilm activity of phytosynthesized AgNPs was determined using microtiter plate assay and real‐time PCR (RT‐PCR) methods for the analysis of type 3 fimbriae (mrkA) and quorum‐sensing system (luxS) gene expression. The results of this study showed that the phytosynthesized AgNPs had a spherical nanostructure with the mean size of 17.60 nm. The AgNPs exhibited dose‐dependent antibacterial activity. The results of the microtiter plate and RT‐PCR methods show that AgNPs inhibited the biofilm formation in MDR K. pneumoniae strains, and the expressions of mrkA and luxS genes were downregulated significantly in MDR strains after treatment with a subminimum inhibitory concentration of AgNPs. In conclusion, AgNPs effectively prevent the formation of biofilms and kill bacteria in established biofilms, which suggests that AgNPs might be a promising candidate for the prevention and treatment of biofilm‐related infections caused by MDR K. pneumoniae strains.
Does neoadjuvant therapy for pancreatic head adenocarcinoma increase postoperative morbidity? A systematic review of the literature with meta‐analysis
Authors: Araujo Raphael L. C. , Silva Raphael O. , de Pádua Souza Cristiano , Milani Jean M. , Huguet Florence , Rezende Ana C. , Gaujoux Sebastien
Published: January 2020

Neoadjuvant treatment (NT) for pancreatic head cancer may allow some patients to undergo curative resection, but its impact on postoperative complications remains unclear. A systematic review and meta‐analysis were performed to compare overall postoperative morbidity, pancreatic fistula, and mortality between patients who underwent upfront surgery and those who underwent neoadjuvant therapy first. Forty‐five studies with 3359 patients were included. No significant differences in morbidity and mortality rates associated with NT for pancreatic head cancer were detected in this study.
Prognostic role of tumor mutation burden in hepatocellular carcinoma after radical hepatectomy
Authors: Cai Huayong , Zhang Yu , Zhang Haoyun , Cui Chao , Li Chonghui , Lu Shichun
Published: January 2020

Background and Aim

This study aimed to assess the potential relationship between tumor mutation burden (TMB) and the recurrence risk of hepatocellular cancer (HCC) after curative resection and tried to develop a reliable TMB based nomogram.

Methods

This retrospective study was conducted in 128 patients (40 patients suffered from a recurrence of HCC) who had received radical hepatectomy by the same surgical team. A nomogram model was constructed using the R and EmpowerStats software.

Results

TMB was not associated with maximum tumor size and the presence of microvascular invasion (MVI). In the whole population or subgroups, the recurrence‐free survival (RFS) rate was significantly lower in the TMB high group. In multivariate analysis, TMB (hazard ratio [HR], 10.12; 95% confidence interval [CI], 5.03‐20.31; P < .001), large tumor diameter (HR, 2.91; 95% CI, 1.51‐5.63; P = .001), presence of MVI (HR, 1.93; 95% CI, 1.03‐3.65; P = .042) were independent predictors of RFS. The predictive power of the nomogram integrating TMB, tumor size and MVI was higher than model only incorporating tumor size and MVI.

Conclusion

This study demonstrated for the first time that higher TMB was associated with poor prognosis in patients with HCC who had received curative resection, and a TMB based nomogram model had a well predictive performance for RFS in this population.
A Color Flow Tract in Ultrasound‐Guided Random Renal Core Biopsy Predicts Complications
Authors: Gagnon Marie‐Helene , Lin Michael F. , Lancia Samantha , Salter Amber , Yano Motoyo
Published: January 2020

Objectives

To determine patient and procedural risk factors for major complications in ultrasound (US)‐guided random renal core biopsy.

Methods

Random renal biopsies performed by radiologists in the US department at a single institution between 2014 and 2018 were retrospectively reviewed. The patient's age, sex, race, and estimated glomerular filtration rate (eGFR) were recorded. The biopsy approach, needle gauge, length of cores, number of throws, and presence of a color flow tract were recorded. Outcome data included minor and major complications. Associations between variables were tested with χ2 analyses and univariable/multivariable logistic regression models.

Results

A total of 231 biopsies (167 native and 64 allografts) were reviewed. There was no significant difference in the sex, age, race, or eGFR between native and allograft groups. The overall rate for any complication was 18.2%, with a 4.3% rate of major complications, which was significantly greater in native compared to allograft biopsies (6% versus 0%; P = .045). A risk analysis in native biopsies only showed that major complications were significantly associated with a low eGFR such that patients with stage 4 or 5 kidney disease had higher odds of complications (odds ratio [95% confidence interval]: stage 4, 9.405 [1.995–44.338]; P = .0393; stage 5, 10.749 [2.218–52.080]; P = .0203) than patients with normal function (eGFR >60 mL/min). The presence of a color flow tract portended a 10.7 times greater risk of having any complication (95% confidence interval, 4.595–24.994; P < .001). Other procedural factors were not significantly associated with complications.

Conclusions

There is an increased risk of major complications in US‐guided random native kidney biopsy in patients with a low eGFR (<30 mL/min) and a patent color flow tract in the immediate postbiopsy setting.
HOW LONGEVITY IS SHAPING THE WORKFORCE OF THE FUTURE
Authors: Jenkins Jo Ann
Published: January 2020

This article asserts that global aging is about more than demographics. People are living longer and in better health, and we have extended middle age. This has created a new life stage opening up new possibilities for how people live and age. Various concepts are noted from the author's book Disrupt Aging: A Bold New Path to Living Your Best Life at Every Age, including that there is a conversation to be had around the potential historic benefits of living longer. Statistics are provided on this phenomenon, such as that in the United States, 10,000 people a day are turning 65—a trend that will continue for the next 10 years; and that the fastest growing age group is people 85+. The influence of longevity on the workplace is discussed, including the following four factors: more people living longer and in generally better health; more nonphysically demanding jobs; the need to continue earning—not just to survive, but to thrive; and the desire to keep contributing to society, be engaged and make a difference. The conclusion notes that by embracing the five‐generation workforce disruptive demographics can be turned into productive possibilities for employers and employees.
Supramolecularly Designed Thermoresponsive Polymers in Different Polymer Backbones
Authors: Naya Masami , Kokado Kenta , Landenberger Kira Beth , Kanaoka Shokyoku , Aoshima Sadahito , Sada Kazuki
Published: January 2020

Thermoresponsive polymers in water, for example, poly(N‐isopropylacrylamide) (PNIPAM) are investigated extensively, due to a wide range of biomedical applications. However, the attempts to control thermoresponsiveness are still rare in less or nonpolar media. Herein, the three thermoresponsive homopolymers tethering an N‐butylurea group in the side chain with a different polymer backbone are reported. They exhibit lower critical solution temperature (LCST)‐type and upper critical solution temperature (UCST)‐type thermoresponsiveness depending on association of the urea group in the polymer chain and hydrogen bonding small molecules (effectors) in ternary systems (polymer/effector/organic solvent). The difference of polymer backbone appears as their change of solvophobicity in organic solvents. Poly(methacrylate) backbone needs more amount of the effector in nonpolar organic solvents, and poly(vinyl ether) backbone needs more amount in polar organic solvents. However, the influence of polymer backbone is too little to change the phase transition behavior, and the thermoresponsiveness is dominated by association and dissociation of hydrogen bondings between polymers and effectors. The supramolecular design of the thermoresponsive polymers is strong and extensible for the design of their phase transitions.
Relationship of Movement Disorders Society–Unified Parkinson's Disease Rating Scale Nonmotor Symptoms to Cognitive Functioning in Patients with Parkinson's Disease
Authors: Bernard Bryan A. , Carns Danielle , Stebbins Glenn T. , Goldman Jennifer G. , Goetz Christopher G.
Published: January 2020

Background

Few studies assess the relationships between nonmotor aspects of experiences of daily living and cognitive functioning in Parkinson's disease (PD).

Objective

To evaluate the relationships among the Movement Disorders Society–Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) part I items and neuropsychological tests in PD.Methods: We assessed 151 PD patients with the MDS‐UPDRS part I and a battery of cognitive tests focused on the following 5 cognitive domains: attention/working memory, executive functioning, recent memory, language, visuoperception. Raw scores for individual cognitive tests were transformed to z scores, and cognitive domain scores were calculated by averaging z scores within each domain. Individual items from the MDS‐UPDRS part I were entered in a stepwise linear regression analysis assessing item contribution to cognitive domain scores.

Results

The MDS‐UPDRS part I item scores for hallucinations and psychosis and light headedness on standing predicted attention/working memory domain scores (P = 0.004). These same item scores, along with apathy, depressed mood, and dopamine dysregulation syndrome, predicted executive functioning (P = 0.044). The apathy and dopamine dysregulation syndrome items predicted language (P = 0.006). In addition, the cognitive impairment and sleep items were predictors of recent memory (P = 0.031). None of the items were predictors of visuoperception (P = 0.006). Other part I items were not significantly related to cognitive domain scores.

Conclusions

Specific nonmotor MDS‐UPDRS part I items, particularly mood, behavior, and autonomic‐related items, exhibited significant relationships with cognitive domains. The highest number of items were predictive of the executive functioning domain, which is the hallmark cognitive dysfunction in PD.
An unresolved issue in rhabdomyosarcoma treatment: The duration of chemotherapy
Authors: Bisogno Gianni , Hawkins Douglas S.
Published: January 2020

Clinical trials have tested different chemotherapy regimens to improve outcome for patients with rhabdomyosarcoma (RMS), but therapy duration has never been explicitly evaluated. North American trials evolved from longer (104 weeks) to shorter duration (24‐42 weeks). In Europe, treatment duration similarly evolved from 35 to 48 to 22 weeks for lower risk patients and from 56 to 72 to 27 weeks for higher risk patients. There was no evidence that chemotherapy duration influenced outcome over time. The recent RMS2005 trial showed an improved survival with the addition of 24 weeks of low‐dose chemotherapy. Treatment duration remains a question to be addressed in future trials.
Adsorber Particles with Magnetically‐Supported Improved Electrochemical Conversion Behavior for Waste Water Treatment Processes
Authors: Schneider Michael , Tschöpe André , Hanselmann Doris , Ballweg Thomas , Gellermann Carsten , Franzreb Matthias , Mandel Karl
Published: January 2020

Micron‐sized supraparticles, consisting of a plurality of discrete nano‐ and microscale functional units, are assembled and fused by means of a droplet extrusion process. By combining nano magnetite, activated carbon, and conductive carbon with a polymeric binder matrix, particles are obtained which unite good magnetic properties, electrical conductivity, and adsorber activity through the high accessible surface area of the incorporated activated carbon of about 570 m2 g−1, thereby enabling a new approach toward sustainable water treatment processes. Due to the interplay of the components, it is possible to adsorb target substances, dissolved in the water which is demonstrated by the adsorption of the model dye methylene blue. A very fast adsorption kinetic and an adsorption capacity of about 400 mg g−1 is determined. By using the developed composite particles, it is also possible to electrochemically alter substances flowing through a magnetically‐stabilized fluidized‐bed reactor by electrochemically charging/discharging, significantly supported by the magnetic field enabling alternatingly optimum mobility/adsorption phases with contact/charging intervals. The electrochemical conversion can be increased up to 151% depending on the applied flow‐rate and electrical voltage. By applying an external magnetic field, a further increase of electrochemical conversion of up to 70% can be observed.
Establishing Trypanosoma cruzi farnesyl pyrophosphate synthase as a viable target for biosensor driven fragment‐based lead discovery
Authors: Opassi Giulia , Nordström Helena , Lundin Arne , Napolitano Valeria , Magari Francesca , Dzus Tom , Klebe Gerhard , Danielson U. Helena
Published: January 2020

Procedures for producing and exploring Trypanosoma cruzi farnesyl pyrophosphate synthase (tcFPPS) for surface plasmon resonance (SPR) biosensor‐driven fragment‐based discovery have been established. The method requires functional sensor surfaces with high sensitivity for extended times and appropriate controls. Initial problems with protein stability and lack of useful reference compounds motivated optimization of experimental procedures and conditions. The improved methods enabled the production of pure, folded and dimeric protein, and identified procedures for storage and handling. A new coupled enzymatic assay, using luciferase for detection of pyrophosphate, was developed and used to confirm that the purified enzyme was active after purification and storage. It also confirmed that sensor surfaces prepared with structurally intact protein was active. An SPR‐biosensor assay for fragment library screening and hit confirmation was developed. A thermal shift assay was used in parallel. A library of 90 fragments was efficiently screened by both assays at a single concentration in the presence and absence of the catalytic cofactor Mg2+. Hits were selected on the basis of response levels or ΔT
m > 1°C and selectivity for tcFPPS in the presence of Mg2+. Characterization of hits by SPR showed that all had low affinities and the relationships between steady‐state responses and concentrations were not sufficiently hyperbolic for determination of KD‐values. Instead, ranking could be performed from the slope of the linear relationship at low concentrations. This pilot screen confirms that the procedures developed herein enables SPR‐biosensor driven fragment‐based discovery of leads targeting tcFPPS, despite the lack of a reference compound.

Significance Statement

To enable the discovery of drugs, it is essential to have access to relevant forms of the target protein and valid biochemical methods for studying the protein and effects of compounds that may be evolved into drugs. We have established methods for the discovery of drugs for treatment of American Trypanosomiasis (Chagas disease), using farnesyl pyrophosphate synthase from Trypanosoma cruzi as a target.
Differential roles and activation of mammalian target of rapamycin complexes 1 and 2 during cell migration in prostate cancer cells
Authors: Venugopal Smrruthi Vaidegi , Caggia Silvia , Gambrell‐Sanders DaJhnae , Khan Shafiq A.
Published: January 2020

Background

Mammalian target of rapamycin (mTOR) is a downstream substrate activated by PI3K/AKT pathway and it is essential for cell migration. It exists as two complexes: mTORC1 and mTORC2. mTORC1 is known to be regulated by active AKT, but the activation of mTORC2 is poorly understood. In this study, we investigated the roles and differential activation of the two mTOR complexes during cell migration in prostate cancer cells.

Methods

We used small interfering RNA to silence the expression of Rac1 and the main components of mTOR complexes (regulatory associated protein of mTOR [RAPTOR] and rapamycin‐insensitive companion of mTOR [RICTOR]) in LNCaP, DU145, and PC3 prostate cancer cell lines. We performed transwell migration assay to evaluate the migratory capability of the cells, and Western blot analysis to study the activation levels of mTOR complexes.

Results

Specific knockdown of RAPTOR and RICTOR caused a decrease of cell migration, suggesting their essential role in prostate cancer cell movement. Furthermore, epidermal growth factor (EGF) treatments induced the activation of both the mTOR complexes. Lack of Rac1 activity in prostate cancer cells blocked EGF‐induced activation of mTORC2, but had no effect on mTORC1 activation. Furthermore, the overexpression of constitutively active Rac1 resulted in significant increase in cell migration and activation of mTORC2 in PC3 cells, but had no effect on mTORC1 activation. Active Rac1 was localized in the plasma membrane and was found to be in a protein complex, with RICTOR, but not RAPTOR.

Conclusion

We suggest that EGF‐induced activation of Rac1 causes the activation of mTORC2 via RICTOR. This mechanism plays a critical role in prostate cancer cell migration.
Understanding the Dehydration Stress in Lipid Vesicles by a Combined Quartz Crystal Microbalance and Dielectric Spectroscopy Study
Authors: Gennaro Alessia , Deschaume Olivier , Pfeiffer Helge , Bartic Carmen , Wagner Patrick , Wübbenhorst Michael
Published: January 2020

Herein, 1‐palmitoyl‐2‐oleoyl‐glycero‐3‐phosphocholine (POPC) vesicles are studied using a newly designed setup that combines dielectric and gravimetric (quartz crystal microbalance, QCM) measurements. This setup allows to monitor the molecular dynamics and phase transitions of lipid structures under controlled humidity and temperature conditions. The main relaxation process (R2), related to the intrinsic headgroups' dynamics, is found in all phases and reveals a systematic acceleration with increasing hydration level. In contrast, a faster relaxation mode (R1) is found exclusively in the “liquid‐crystalline,” high‐temperature state, favoring water clusters located in the disordered aliphatic phase as origin. A third process (R3), being slower than the R2 mode, is attributed to a decoupled dynamics of hydration water in the hydrophilic part of the lipid bilayers occurring at higher hydration levels. In addition to molecular dynamics, both QCM and dielectric relaxation spectroscopy (DRS) measurements are demonstrated to yield consistent information on the phase behavior of the POPC samples which show a marked sensitivity to the hydration level. Moreover, contact angle measurements and atomic force microscopy confirm irreversible changes from the initial vesicles to a stacked bilayer structure upon repeated hydration‐dehydration, which manifests in the hydrophobization of the surface and water reduced absorption kinetics.