bluuebunny/crossref_metadata_2025 huggingface dataset:
Label‐Free Leukemia Monitoring by Computer Vision
Authors: Doan Minh , Case Marian , Masic Dino , Hennig Holger , McQuin Claire , Caicedo Juan , Singh Shantanu , Goodman Allen , Wolkenhauer Olaf , Summers Huw D. , Jamieson David , van Delft Frederik W , Filby Andrew , Carpenter Anne E. , Rees Paul , Irving Julie
Published: February 2020

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. While there are a number of well‐recognized prognostic biomarkers at diagnosis, the most powerful independent prognostic factor is the response of the leukemia to induction chemotherapy (Campana and Pui: Blood 129 (2017) 1913–1918). Given the potential for machine learning to improve precision medicine, we tested its capacity to monitor disease in children undergoing ALL treatment. Diagnostic and on‐treatment bone marrow samples were labeled with an ALL‐discriminating antibody combination and analyzed by imaging flow cytometry. Ignoring the fluorescent markers and using only features extracted from bright‐field and dark‐field cell images, a deep learning model was able to identify ALL cells at an accuracy of >88%. This antibody‐free, single cell method is cheap, quick, and could be adapted to a simple, laser‐free cytometer to allow automated, point‐of‐care testing to detect slow early responders. Adaptation to other types of leukemia is feasible, which would revolutionize residual disease monitoring. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.
Development of a sexual dimorphism in a central pattern generator driving a rhythmic behavior: The role of glia‐mediated potassium buffering in the pacemaker nucleus of the weakly electric fishApteronotus leptorhynchus
Authors: Zupanc Günther K. H.
Published: February 2020

Central pattern generators play a critical role in the neural control of rhythmic behaviors. One of their characteristic features is the ability to modulate the oscillatory output. An important yet little‐studied type of modulation involves the generation of oscillations that are sexually dimorphic in frequency. In the weakly electric fishApteronotus leptorhynchus, the pacemaker nucleus serves as a central pattern generator that drives the electric organ discharge of the fish in a one‐to‐one fashion. Males discharge at higher frequencies than females—a sexual dimorphism that develops under the influence of steroid hormones. The two principal neurons that constitute the oscillatory network of the pacemaker nucleus are the pacemaker and relay cells. Whereas the number and size of the pacemaker and relay cells are sexually monomorphic, pronounced sex‐dependent differences exist in the morphology, and subcellular properties of astrocytes, which form a syncytium closely associated with these neurons. In females, compared to males, the astrocytic syncytium covers a larger area surrounding the pacemaker and relay cells and exhibits higher levels of expression of connexin‐43 expression. The latter indicates a strong gap‐junction coupling of the individual cells within the syncytium. It is hypothesized that these sex‐specific differences result in an increased capacity for buffering of extracellular potassium ions, thereby lowering the potassium equilibrium potential, which, in turn, leads to a decrease in the oscillation frequency. This hypothesis has received strong support from simulations based on computational models of individual neurons and the whole neural network of the pacemaker nucleus.
Quantifying the impacts of future sea level rise on nesting sea turtles in the southeastern United States
Authors: Lyons Marta P. , von Holle Betsy , Caffrey Maria A. , Weishampel John F.
Published: February 2020

Sandy beaches, a necessary habitat for nesting sea turtles, are increasingly under threat as they become squeezed between human infrastructure and shorelines that are changing as a result of rising sea levels. Forecasting where shifting sandy beaches will be obstructed and how that directly impacts coastal nesting species is necessary for successful conservation and management. Predicting changes to coastal nesting areas is difficult because of a lack of consensus on the physical attributes used by females in nesting site choice. In this study, we leveraged long‐term data sets of nesting localities for two sea turtle species, loggerhead sea turtle, Caretta caretta, and green sea turtle, Chelonia mydas, within four barrier island National Seashores in the southeastern United States to predict future nesting beach area based on where these species currently nest in relation to mean high water. We predicted the future location of nesting areas based on a sea level rise scenario for 2100 and quantified how impervious surfaces will inhibit future beach movement, which will impact both the total available nesting area and the percentage of nesting area predicted to flood following a hurricane‐related storm surge. Contrary to our expectations, those barrier islands with the greatest levels of human infrastructure were not projected to experience the greatest percentage of sea turtle nesting area loss due to sea level rise or storm surge events. Notably, loss of nesting beach areas will not have equal impacts across the four Seashores; the Seashore projected to have the least amount of total nesting area lost and percentage nesting area lost currently has the highest nesting densities of our two study species, suggesting that even low levels of beach loss could have substantial impacts on future nesting densities and disproportionate impacts on the population growth of these species. Our novel method of estimating current and future nesting beach area can be broadly applied to studies requiring a bounded area that encompasses the part of a beach used by nesting coastal species and will be useful in comparing future global nesting densities and population trajectories under projected future sea level rise and storm surge activity.
Individual variation creates diverse migratory portfolios in native populations of a mountain ungulate
Authors: Lowrey B. , McWhirter D. E. , Proffitt K. M. , Monteith K. L. , Courtemanch A. B. , White P. J. , Paterson J. T. , Dewey S. R. , Garrott R. A.
Published: February 2020

Ecological theory and empirical studies have demonstrated population‐level demographic benefits resulting from a diversity of migratory behaviors with important implications for ecology, conservation, and evolution of migratory organisms. Nevertheless, evaluation of migratory portfolios (i.e., the variation in migratory behaviors across space and time among individuals within populations) has received relatively little attention in migratory ungulates, where research has focused largely on the dichotomous behaviors (e.g., resident and migrant) of partially migratory populations. Using GPS data from 361 female bighorn sheep (Ovis canadensis) across 17 (4 restored, 6 augmented, 7 native) populations in Montana and Wyoming, USA, we (1) characterized migratory portfolios based on behavioral and spatial migratory characteristics and (2) evaluated the relative influence of landscape attributes and management histories on migratory diversity. Native populations, which had been extant on the landscape for many generations, had more diverse migratory portfolios, higher behavioral switching rates, reduced seasonal range fidelity, and broad dispersion of individuals across summer and winter ranges. In contrast, restored populations with an abbreviated history on the landscape were largely non‐migratory with a narrow portfolio of migratory behaviors, less behavioral switching, higher fidelity to seasonal ranges, and less dispersion on summer and winter ranges. Augmented populations were more variable and contained characteristics of both native and restored populations. Differences in migratory diversity among populations were associated with management histories (e.g., restored, augmented, or native). Landscape characteristics such as the duration and regularity of green‐up, human landscape alterations, topography, and snow gradients were not strongly associated with migratory diversity. We suggest a two‐pronged approach to restoring migratory portfolios in ungulates that first develops behavior‐specific habitat models and then places individuals with known migratory behaviors into unoccupied areas in an effort to bolster migratory portfolios in restored populations, potentially with synergistic benefits associated with variation among individuals and resulting portfolio effects. Management efforts to restore diverse migratory portfolios may increase the abundance, resilience, and long‐term viability of ungulate populations.
Early weight gain predicts treatment response in adolescents with anorexia nervosa enrolled in a family‐based partial hospitalization program
Authors: Van Huysse Jessica L. , Smith Kellsey , Mammel Kathleen A. , Prohaska Natalie , Rienecke Renee D.
Published: February 2020

Objective

Improved treatment outcome in family‐based treatment (FBT) for anorexia nervosa (AN) is predicted by weight gain occurring early in the course of treatment (i.e., about 4 lbs by week 4). Although prior work suggests that early weight gain in higher levels of care (e.g., partial hospitalization programs [PHP]) predicts weight restoration at discharge, no study has examined the specific rate of gain within FBT‐informed PHP programs that best predicts treatment response.

Method

This study examined rate of weight gain in pounds and percent expected body weight (EBW) that predicts positive outcome in 70 patients (M age = 15.49 years, SD = 2.56) with AN who were enrolled in a family‐based PHP.

Results

Receiver operator characteristic analyses demonstrated that changes in %EBW during weeks 2–5 were more useful than changes in weight in predicting positive outcome. Gaining at least 8.9 pounds or over 8% of EBW in the first 4 weeks of treatment significantly predicted positive outcome.

Discussion

Findings suggest that positive outcome in an FBT‐informed PHP is predicted by rapid weight gain in the initial weeks of treatment. Research is needed to identify specific family and patient characteristics that facilitate weight gain and to develop corresponding interventions to improve outcome.
Spatial and temporal variation in prey color patterns for background matching across a continuous heterogeneous environment
Authors: Baling Marleen , Stuart‐Fox Devi , Brunton Dianne H. , Dale James
Published: February 2020

In heterogeneous habitats, camouflage via background matching can be challenging because visual characteristics can vary dramatically across small spatial scales. Additionally, temporal variation in signaling functions of coloration can affect crypsis, especially when animals use coloration seasonally for intraspecific signaling (e.g., mate selection). We currently have a poor understanding of how wild prey optimize background matching within continuously heterogeneous habitats, and whether this is affected by requirements of intraspecific signaling across biological seasons. Here, we quantified color patterns of a wild population of shore skink (Oligosoma smithi), a variably colored lizard endemic to New Zealand, to (a) investigate whether background matching varies across a vegetation gradient; (b) assess potential signaling functions of color; and (c) to determine whether there is a trade‐off between requirements for crypsis and intraspecific signaling in coloration across seasons. Although all pattern types occurred throughout the vegetation gradient, we found evidence for background matching in skinks across the vegetation gradient, where dorsal brightness and pattern complexity corresponded with the proportion of vegetation cover. There was also a significant disparity between ventral color (saturation) of juveniles and adults, and also between sexes, suggestive of sex recognition. However, there was little indication that color was condition‐dependent in adults. Despite some evidence for a potential role in signaling, crypsis did not greatly differ across seasons. Our study suggests that selection favors a mix of generalist and specialist background matching strategies across continuously heterogeneous habitats.
The metabolic basis of nonalcoholic steatohepatitis
Authors: Chakravarthy Manu V. , Neuschwander‐Tetri Brent A.
Published: February 2020

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and is associated with significant morbidity and mortality worldwide, with a high incidence in Western countries and non‐Western countries that have adopted a Western diet. NAFLD is commonly associated with components of the metabolic syndrome, type 2 diabetes mellitus and cardiovascular disease, suggesting a common mechanistic basis. An inability to metabolically handle free fatty acid overload–metabolic inflexibility–constitutes a core node for NAFLD pathogenesis, with resulting lipotoxicity, mitochondrial dysfunction and cellular stress leading to inflammation, apoptosis and fibrogenesis. These responses can lead to the histological phenotype of nonalcoholic steatohepatitis (NASH) with varying degrees of fibrosis, which can progress to cirrhosis. This perspective review describes the key cellular and molecular mechanisms of NAFLD and NASH, namely an excessive burden of carbohydrates and fatty acids that contribute to lipotoxicity resulting in hepatocellular injury and fibrogenesis. Understanding the extrahepatic dysmetabolic contributors to NASH is crucial for the development of safe, effective and durable treatment approaches for this increasingly common disease.
Clinical importance of urinary sodium excretion in acute heart failure
Authors: Damman Kevin , Ter Maaten Jozine M. , Coster Jenifer E. , Krikken Jan A. , van Deursen Vincent M. , Krijnen Hidde K. , Hofman Mischa , Nieuwland Wybe , van Veldhuisen Dirk J. , Voors Adriaan A. , van der Meer Peter
Published: February 2020

Aims

Urinary sodium assessment has recently been proposed as a target for loop diuretic therapy in acute heart failure (AHF). We aimed to investigate the time course, clinical correlates and prognostic importance of urinary sodium excretion in AHF.

Methods and results

In a prospective cohort of 175 consecutive patients with an admission for AHF we evaluated urinary sodium excretion 6 h after initiation of loop diuretic therapy. Clinical outcome was all‐cause mortality or heart failure rehospitalization. Mean age was 71 ± 14 years, and 44% were female. Median urinary sodium excretion was 130 (67–229) mmol at 6 h, 347 (211–526) mmol at 24 h, and decreased from day 2 to day 4. Lower urinary sodium excretion was independently associated with male gender, younger age, renal dysfunction and pre‐admission loop diuretic use. There was a strong association between urinary sodium excretion at 6 h and 24 h urine volume (beta = 0.702, P < 0.001). Urinary sodium excretion after 6 h was a strong predictor of all‐cause mortality after a median follow‐up of 257 days (hazard ratio 3.81, 95% confidence interval 1.92–7.57; P < 0.001 for the lowest vs. the highest tertile of urinary sodium excretion) independent of established risk factors and urinary volume. Urinary sodium excretion was not associated with heart failure rehospitalization.

Conclusion

In a modern, unselected, contemporary AHF population, low urinary sodium excretion during the first 6 h after initiation of loop diuretic therapy is associated with lower urine output in the first day and independently associated with all‐cause mortality.
Hhex regulates murine lymphoid progenitor survival independently of Stat5 and Cdkn2a
Authors: Jackson Jacob T. , O'Donnell Kristy , Light Amanda , Goh Wilford , Huntington Nicholas D. , Tarlinton David M. , McCormack Matthew P.
Published: February 2020

The transcription factor Hhex (hematopoietically expressed homeobox gene) is critical for development of multiple lymphoid lineages beyond the common lymphoid progenitor. In addition, Hhex regulates hematopoietic stem cell (HSC) self‐renewal, emergency hematopoiesis, and acute myeloid leukemia initiation and maintenance. Hhex mediates its effects on HSCs and acute myeloid leukemia stem cells via repression of the Cdkn2a tumor suppressor locus. However, we report here that loss of Cdkn2a does not rescue the failure of lymphoid development caused by loss of Hhex. As loss of Hhex causes apoptosis of lymphoid progenitors associated with impaired Bcl2 expression and defective Stat5b signaling, we tested the effects of rescuing these pathways using transgenic mice. Expression of the anti‐apoptotic factor Bcl2, but not activated Stat5, rescued the development of T‐, B‐, and NK‐cell lineages in the absence of Hhex. These results indicate that Bcl2 expression, but not Stat5b signaling or loss of Cdkn2a, can overcome the lymphoid deficiencies caused by the absence of Hhex, suggesting that the primary role of this transcription factor is to promote survival of lymphoid progenitors during early lymphoid development.
Synthesis, Crystal Structure, and Characterization of a Noncentrosymmetric Sulfate Cs2Ca2(SO4)3
Authors: Shen Yaoguo , Xue Xiaoling , Tu Wenyuan , Liu Zhiqun , Yan Renwen , Zhang Hong , Jia Junrong
Published: February 2020

The noncentrosymmetric structure is one prerequisite of a nonlinear optical (NLO) material. Here, a sulfate Cs2Ca2(SO4)3 with a noncentrosymmetric structure was synthesized by high‐temperature solid‐state reaction, and its crystals were grown by spontaneous crystallization. Single‐crystal X‐ray diffraction indicates that Cs2Ca2(SO4)3 features a three‐dimensional framework constituted by corner‐sharing CaO6 octahedra and SO4 tetrahedra. Optical characterizations suggest that Cs2Ca2(SO4)3 is transparent down to 200 nm and exhibits a moderate second‐order NLO response of about 0.6 × KH2PO4. Electronic band structure calculations were performed to elucidate the optical origin. Furthermore, the title compound has good thermal stability of up to about 1000 K, which is greatly higher than those of NLO sulfates reported recently. This work may shed useful light on the development of new NLO sulfates with high thermal stability.
Genetic generalized epilepsies with frontal lesions mimicking migratory disorders on the epilepsy monitoring unit
Authors: Fauser Susanne , Cloppenborg Thomas , Polster Tilman , Specht Ulrich , Woermann Friedrich G. , Bien Christian G.
Published: February 2020

Objective

Some patients with genetic generalized epilepsy (GGE) may present with ambiguous and atypical findings and even focal brain abnormalities. Correct diagnosis may therefore be difficult.

Methods

We retrospectively collected six patients investigated on the epilepsy monitoring unit with MRI abnormalities mimicking focal cortical dysplasia (FCD‐like) or heterotopias, but with semiology and EEG features of GGE. We compared them to four additional patients with GGE and nonmigratory abnormalities.

Results

All six patients presented with frontal MRI lesions: radial (“transmantle,” n = 4), cortical‐subcortical (n = 1), and periventricular heterotopia (n = 1). Five had positive family histories. Semiologic lateralizing signs compatible with the lesion were seen in four. Five patients had 3/s spike‐wave complexes, with an asymmetric appearance in three. Regional EEG changes matched with the side of the abnormality in three patients. Invasive EEG (n = 2) or postoperative outcomes (n = 3) argued against an ictogenic role of the MRI abnormalities. Histology showed mild malformation of cortical development, but no focal cortical dysplasia. The six patients were finally diagnosed with juvenile myoclonic epilepsy (n = 2), juvenile absence epilepsy (n = 2), or GGE not further specified (nfs, n = 2). Compared to these patients, the other four (final diagnoses: childhood absence epilepsy, n = 1; perioral myoclonia with absences, n = 1; and GGE nfs, n = 2) had no lateralizing EEG findings.

Significance

Patients with GGE may have coincidental MRI abnormalities. These cases are challenging as frontal epilepsy and GGE can present with similar semiologies. GGE with coincidental FCD‐like lesions/heterotopias is in particular difficult to diagnose as patients have more lateralizing features (in semiology and EEG) than those with tumors. A detailed noninvasive presurgical evaluation may be justified. We point out red flags that may help to distinguish GGE from frontal epilepsy, even in the presence of brain abnormalities: 3/s spike waves (even if asymmetric), changing lateralizing signs at different times, and a positive family history hinting at GGE.
Bidirectional shaking table tests of a low‐cost friction sliding system with flat‐inclined surfaces
Authors: Brito Miguel B. , Akiyama Mitsuyoshi , Ichikawa Yoshitaka , Yamaguchi Hiroki , Honda Riki , Ishigaki Naomitsu
Published: February 2020

A novel low‐cost friction sliding system for bidirectional excitation is developed to improve the seismic performance of reinforced concrete (RC) bridge piers. The sliding system is a spherical prototype developed by combining a central flat surface with an inclined spherical segment, characterized by stable oscillation and a large reduction in response accelerations on the flat surface. The inclined part provides a restoring force that limits the residual displacements of the system. Conventional steel and concrete are employed to construct a flat‐inclined spherical surface atop an RC pier. The seismic forces are dissipated through the frictions generated during the sliding movements; hence, the seismic resilience of bridges can be ensured with a low‐cost design solution. The proposed system is fabricated utilizing a mold created by a three‐dimensional printer, which facilitates the use of conventional concrete to construct spherical shapes. The concrete surface is lubricated with a resin material to prevent abrasion from multiple input ground motions. To demonstrate the effectiveness of the system, bidirectional shaking table tests are conducted in the longitudinal and transverse directions of a scaled bridge model. The effect of the inclination angle and the flat surface size is investigated. The results demonstrate a large decrease in response acceleration when the system exhibits circular sliding displacement. Furthermore, the inclination angle that generates the smallest residual displacement is identified experimentally.
Fuel economy and exhaust emissions of a diesel vehicle under real traffic conditions
Authors: Gao Jianbing , Chen Haibo , Dave Kaushali , Chen Junyan , Jia Dongyao
Published: February 2020

Traffic and vehicle simulations are often developed individually. However, vehicle performance is heavily affected by traffic conditions. Cosimulations of traffic and vehicle under real‐road situations can reflect the semi‐real‐world performance of vehicles, with traffic conditions being taken into considerations. This paper proposed an approach to combine the traffic and vehicle simulations that are realized by simulation of urban mobility (SUMO) and GT‐Suite software, respectively. In this paper, the sensitivities of the road grade and vehicle speed to the fuel economy and exhaust emissions were investigated; vehicle fuel consumption and regular exhaust emissions on a real‐road were analyzed; the effect of the traffic accident and congestions on fuel consumption and exhaust emissions were quantified. The results indicated that nitrogen oxides (NOx) and soot emission were consistent with fuel consumption rate, which was dominated by vehicle acceleration whose effect was aggravated by road grade. The fuel penalties caused by accident were in the range of 0.015‐0.023 kg depending on the severity of the accidents. The fuel consumption increased from 1.199 to 1.312 kg and 1.559 kg for 900 and 1800 vehicles/h traffic flow cases compared with 180 vehicles/h traffic flow.
Growth and influence of a porous iron oxide nanolayer on LiMn2O4 in an aqueous rechargeable lithium‐ion battery
Authors: Schuppert Nicholas D. , Mukherjee Santanu , Bates Alex , Jasinski Jacek B. , Lee Sang C. , Park Sam
Published: February 2020

A porous iron oxide nanolayer coating is grown on LiMn2O4 by a facile in‐situ method. Evolution of this coating and its influence on the structural retention and electrochemical activity of LiMn2O4 is examined and compared to a control in the environment of an aqueous rechargeable lithium‐ion battery. Two coinciding mechanisms of porous iron oxide nanolayer deposition and their depency on electrolyte pH are identified and discussed. The coating is found to significantly reduce Li2MnO3 surface formation, a major source of capacity fade in LiMn2O4 electrodes, thereby improving the structural retention. The nanolayer was also found to improve the electrochemical stability of the underlying LiMn2O4 in the potential window of lithium intercalation, reduce the growth rate of mass transfer and solid electrolyte interface resistances over the control, while also providing reduced charge transfer resistances over the pristine LiMn2O4 material. The totality of these improvements provided by the porous iron oxide nanolayer preserved the electrochemical and structural integrity of LiMn2O4 over the course of 500 deep discharge cycles in aqueous media.
The medical care costs of obesity and severe obesity in youth: An instrumental variables approach
Authors: Biener Adam I. , Cawley John , Meyerhoefer Chad
Published: February 2020

This paper is the first to use the method of instrumental variables to estimate the impact of obesity and severe obesity in youth. on U.S. medical care costs. We examine data from the Medical Expenditure Panel Survey for 2001–2015 and instrument for child BMI using the BMI of the child's biological mother. Instrumental variables estimates indicate that obesity in youth raises annual medical care costs by $907 (in 2015 dollars) or 92%, which is considerably higher than previous estimates of the association of youth obesity with medical costs. We find that obesity in youth significantly raises costs in all major categories of medical care: outpatient doctor visits, inpatient hospital stays, and prescription drugs. The costs of youth obesity are borne almost entirely by third‐party payers, which is consistent with substantial externalities of youth obesity, which in turn represents an economic rationale for government intervention.
Simeprevir, daclatasvir, and sofosbuvir for hepatitis C virus‐infected patients: Long‐term follow‐up results from the open‐label, Phase II IMPACT study
Authors: Lawitz Eric , Poordad Fred , Gutierrez Julio A. , Beumont Maria , Beets Greet , Vandevoorde Ann , Remoortere Pieter Van , Luo Donghan , Vijgen Leen , Eygen Veerle Van , Gamil Mohamed
Published: February 2020

Background and aims

Direct‐acting antiviral agents (DAAs) for hepatitis C virus (HCV) infection have resulted in high rates of sustained virologic response (SVR) following 8 to 24 weeks of treatment. However, difficult‐to‐cure/cirrhotic patients typically require a longer treatment duration and less is known regarding the long‐term durability of SVR or effect on liver disease progression; to assess this, the IMPACT study followed patients for a 3‐year period after end of treatment.

Methods

The Phase II, open‐label, nonrandomized IMPACT study assessed the efficacy, safety, and pharmacokinetics of the combination of three DAAs (simeprevir, sofosbuvir, and daclatasvir) in HCV genotype 1/4‐infected, treatment‐naïve/‐experienced cirrhotic patients with portal hypertension or decompensated liver disease. Patients from a single site in the United States were assigned to one of two groups by Child–Pugh (CP) score: CP A, CP score less than 7 and evidence of portal hypertension; CP B, CP score of 7 to 9. All patients received simeprevir 150 mg, daclatasvir 60 mg, and sofosbuvir 400 mg once‐daily for 12 weeks between September 2014 and August 2015. All 40 patients included in the study (male, 63%; median age, 58.5 years) achieved SVR 12 and 24 weeks after end of treatment, and the combination was well tolerated.

Results

All patients who reached the 3‐year follow‐up timepoint maintained SVR (CP A, 15/15; CP B, 18/18). CP scores and Model for End‐stage Liver Disease scores remained relatively stable, and mean FibroScan and FibroTest scores declined. No new safety signals were identified.

Conclusions

In the IMPACT study, virologic response to simeprevir, sofosbuvir, and daclatasvir was durable over 3 years (ClinicalTrials.gov number: NCT02262728).
Buchwald‐Type Ligands on Gold(I) Catalysis
Authors: Zuccarello Giuseppe , Zanini Margherita , Echavarren Antonio M.
Published: February 2020

Dialkyl biarylphosphine ligands, presented in the context of Pd‐catalyzed cross‐coupling reactions, have been extensively applied in gold(I) catalysis giving rise to numerous transformations and reaction pathways otherwise inaccessible under the action of other gold(I) catalysts. This review emphasizes how this privileged ligand class, as well as recent modifications on the biarylphosphine motive, have triggered the discovery of new reactivities in our research program. Finally, the introduction of chiral information on the ligand scaffold provides new solutions to challenging gold(I)‐catalyzed enantioselective transformations.
In vitro and in vivo effects of concentrated growth factor on cells and tissues
Authors: Tabatabaei Fahimeh , Aghamohammadi Zahra , Tayebi Lobat
Published: February 2020

This article reviews the biological outcome of the concentrated growth factor (CGF), a new platelet derivative used for tissue regeneration, in published articles related to the use of this product in basic and clinical studies. An electronic literature research using PubMed and SCOPUS was performed using combination of keywords: “concentrated growth factor” (OR “CGF”), AND “stem cells,” AND “cells” OR “cell proliferation” OR “cell migration” OR “cell differentiation,” AND “repair” OR “survival” OR “revitalization,” AND “tissue” OR “bone.” Forty‐five articles that were published between 2012 and 2020 met the inclusion criteria. These studies have used CGF as fresh solid form, freeze‐dried, membrane, extract, or exudate. Most studies demonstrate the positive effects of CGF in a dose‐dependent manner under certain concentrations. Studies comparing CGF with other platelet concentrates, report lower efficiency, no statistically significant differences, or better results for CGF. Combination of CGF with stem cells and biomaterials significantly improves bone regeneration and the effect of allograft or collagen membrane is better than CGF alone. For a better examination of the biological outcomes of CGF, the standardization of CGF preparation regarding the choice of the test tube material for blood collection, the required volume of blood, the necessary count of platelets in CGF, and the most appropriate type of CGF are recommended.
Heart rate variability and hematological parameters in pregnant women
Authors: Al‐Shafei Ahmad I. , Musa Shaza M. , Rayis Duria A. , Lutfi Mohamed F. , El‐Gendy Ola A. , Adam Ishag
Published: February 2020

Background

There are few researches on hematological parameters (hemoglobin, red cell distribution width [RDW], white blood cells [WBCs], mean platelets volume [MPV], and heart rate variability [HRV]). There are no published data on this concept (HRV and hematological parameters) during pregnancy.

Methods

A cross‐sectional study was conducted at Saad Abul Ela hospital in Khartoum, Sudan during the period of July to August 2018. Pregnant women with singleton, a live baby, were enrolled in this study. Clinical history and examination were performed. HRV (autonomic modulation) was assessed using time and frequency domain HRV indices.

Results

One hundred and five pregnant women were enrolled. The median (quartile) of the age, parity, and gestational age was 30.0 (25.0‐35.0) years, 1.0 (0‐3.0), and 38.0 (32.0‐39.0) weeks, respectively. While there were positive correlations between hemoglobin and low frequency (LF), RDW and high frequency (HF), WBCs and HF Norm, WBCs and LF/HF, MPV and HF Norm, LF Norm and LF/HF, there was no significant correlation between the hematological (hemoglobin, WBCs, RDW, and MPV) and HRV parameters. Linear regression analysis showed no significant association between age, parity, gestational age, body mass index, hemoglobin, RDW, and HRV variables. The Log10 WBCs were negatively associated with Log10 HF (ms2/Hz). MPV was positively associated with LF Norm and negatively associated with HF Norm.

Conclusion

The study failed to show significant associations between age, parity, gestational age, hemoglobin, RDW, and HRV variables. The WBCs were negatively associated with HF. MPV was positively associated with LF Norm, and it was negatively associated with HF Norm.
miRNA‐192 and ‐215 activate Wnt/β‐catenin signaling pathway in gastric cancer via APC
Authors: Deng Shiqi , Zhang Xiaojing , Qin Ying , Chen Wangchun , Fan Hu , Feng Xianling , Wang Jian , Yan Ruibin , Zhao Yanqiu , Cheng Yulan , Wei Yanjie , Fan Xinmin , Ashktorab Hassan , Smoot Duane , Meltzer Stephen J. , Li Song , Li Kuan , Peng Yin , Jin Zhe
Published: February 2020

Although great progress has been made in surgical techniques, traditional radiotherapy, and chemotherapy, gastric cancer (GC) is still the most common malignant tumor and has a high mortality, which highlights the importance of novel diagnostic markers. Emerging studies suggest that different microRNAs (miRNAs) are involved in tumorigenesis of GC. In this study, we found that miRNA‐192 and ‐215 are significantly upregulated in GC and promote cell proliferation and migration. Adenomatous polyposis coli (APC), a well‐known negative regulator in Wnt signaling, has been proved to be a target of miRNA‐192 and ‐215. Inhibition of miRNA‐192 or ‐215 reduced the Topflash activities and repressed the expression of Wnt signaling pathway proteins, while APC small interfering RNAs reversed the inhibitory effects, suggesting that miRNA‐192 and ‐215 activate Wnt signaling via APC. In addition, APC mediates the cell proliferation and migration regulated by miRNA‐192 and ‐215. Furthermore, APC is downregulated in GC tissues and negatively correlated with the expression of miRNA‐192 and ‐215. In summary, miRNA‐192 and ‐215 target APC and function as oncogenic miRNAs by activating Wnt signaling in GC, revealing to be potential therapeutic targets.
Influence of MRP3 Genetics and Hepatic Expression Ontogeny for Morphine Disposition in Neonatal and Pediatric Patients
Authors: Hahn David , Fukuda Tsuyoshi , Euteneuer Joshua C. , Mizuno Tomoyuki , Vinks Alexander A. , Sadhasivam Senthilkumar , Emoto Chie
Published: February 2020

We have previously reported the influences of OCT1 ontogeny and genetic variation on morphine clearance in neonatal and pediatric patients. In the latter study, plasma morphine‐glucuronide levels correlated with patient genotype for the rs4793665 single‐nucleotide polymorphism (SNP) at the locus of MRP3, an efflux transporter of morphine glucuronides between hepatocytes and circulating blood. The link between MRP3 activity and overall morphine clearance has not been thoroughly investigated however, and the developmental profile of hepatic MRP3 protein expression remains thinly defined between neonates and adults. In the current study, previously determined morphine clearance values for neonatal (24‐58 weeks postmenstrual age, N = 57) and pediatric (5‐16 years, n = 85) patients were reanalyzed for correlation to the SNP genotype of patient rs4793665. Among OCT1 wild‐type patients, pediatric morphine clearance showed a significant decreasing trend by MRP3 genotypes in the order of CC > CT > TT (P = .014), whereas for neonates, an identical but nonsignificant trend was observed. Pharmacogenetic differences in MRP3 and OCT1 ontogeny were evaluated by Western blot of hepatic membrane fractions from 50 subjects aged 1 day postnatal to 33 years old. Hepatic MRP3 protein level did not vary by rs4793665 genotype, and followed an atypical developmental pattern of increase up to 1‐2 years of age, thereafter decreasing during preadolescence before increasing again to adult levels at maturity (17‐33 years). By comparison, OCT1 expression was significantly decreased in OCT1 *1/*3 genotyped patients older than 1 year and followed a trajectory consistent with prior studies. Our results suggest that consideration of MRP3 pharmacogenetics and ontogeny may aid in identifying pediatric patients having different/atypical morphine requirements.
Development of a Physiologically Based Pharmacokinetic Model for Prediction of Pramipexole Pharmacokinetics in Parkinson's Disease Patients With Renal Impairment
Authors: You Xiang , Wu Wanhong , Xu Jing , Jiao Zheng , Ke Meng , Huang Pinfang , Lin Cuihong
Published: February 2020

Pramipexole is the first‐line medication recommended by the British National Institute for Health and Care Excellence. Pramipexole is predominantly eliminated by renal excretion. The aim was to develop a physiologically based pharmacokinetic (PBPK) model of pramipexole, providing a basis for its individualized administration. The role of glomerular filtration and organic cation transporter 2 (OCT2) in renal tubular secretion was considered. Plasma concentration‐time profiles of pramipexole were predicted and validated, first in healthy populations and then in PD patients with varied renal function. Finally, the pharmacokinetics of PD patients with different degrees of renal impairment were predicted. The simulated pharmacokinetic parameters, including maximum plasma concentration (Cmax), area under the plasma concentration‐time curve (AUC), time to maximum plasma concentration (tmax), and steady‐state trough plasma concentration values, obtained using the PBPK model were validated using fold error values, which were all smaller than 2. The successfully validated model supported that OCT2‐mediated tubular secretion was affected proportionally to changes in glomerular filtration for various degrees of renal impairment. The predicted AUC0‐inf values were increased 1.16‐, 1.76‐, 3.26‐, and 9.48‐fold in mild, moderate, and severe renal impairment and end‐stage renal disease (ESRD) subjects, resepctively, compared with PD patients with normal renal function. It appears that PD patients with mild renal impairment are unlikely to require dose adjustment (0.125 mg 3 times a day). The pramipexole dose should be reduced to approximately 0.125 mg twice daily, 0.125 mg once daily, and 0.0375 mg once daily in PD patients with moderate renal impairment, severe renal impairment, and ESRD, respectively.
Musculoskeletal adaptations to strength training in frail elderly: a matter of quantity or quality?
Authors: Aas Sigve N. , Breit Markus , Karsrud Stian , Aase Ole J. , Rognlien Simen H. , Cumming Kristoffer T. , Reggiani Carlo , Seynnes Olivier , Rossi Andrea P. , Toniolo Luana , Raastad Truls
Published: February 2020

Background

The improvement in muscle strength generally exceeds the increase in muscle size following strength training in frail elderly, highlighting the complex aetiology of strength deficit in aging. The aim of this study was to investigate the effect of heavy‐load strength training on a broad number of factors related to specific strength in frail elderly.

Methods

Thirty‐four frail elderly men (n = 18) and women (n = 16) aged 67 to 98 (86 ± 7 years) were randomized to either a group performing strength training twice a week for 10 weeks (ST) or a non‐exercising control group (CON). Knee extensor muscle strength was tested as one‐repetition maximum (1RM) and isometric maximal voluntary contraction (MVC) torque. Muscle activation was assessed by the interpolated twitch technique, and muscle density [mean Hounsfield units (HU)] and intermuscular adipose tissue (IMAT) by computed tomography scans of the quadriceps femoris. Muscle biopsies from the vastus lateralis were obtained to investigate changes in intramyocellular lipids and single‐fibre specific tension.

Results

In ST, knee extension 1RM and MVC improved by 17 and 7%, respectively. Muscle cross‐sectional area of the quadriceps femoris increased by 7%, accompanied by a 4% increase of muscle density. No changes in IMAT, voluntary activation level, single‐fibre specific tension, or lipid content were observed.

Conclusions

In contrast to several previous reports, the improvements in isometric muscle strength and muscle area were in good agreement in the present study. The training‐induced increase in muscle density was not due to changes in skeletal muscle lipid content. Instead, the increase in muscle density may reflect increased packing of contractile material or simply an increased ratio of muscle tissue relative to IMAT.
Elemental composition and moisture prediction in manure by portable X‐ray fluorescence spectroscopy using random forest regression
Authors: Sapkota Yadav , Drake Brandon Lee , McDonald Louis M. , Griggs Thomas C. , Basden Thomas J.
Published: February 2020

Manure elemental composition determination is essential to develop farm nutrient budgets and assess environmental risk. Portable X‐ray fluorescence (PXRF) spectrometers could facilitate hazardous waste‐free, rapid, and cost‐effective elemental concentration determinations. However, sample moisture is a problem for elemental concentration determination by X‐ray methods. The objective of this study was to quantify the effect of sample moisture content, predict moisture content, and correct for moisture effect on elemental concentration determinations in livestock manure. Oven‐dried manure samples (n = 40) were ground and adjusted to five moisture ranges of (w/w moisture) <10%, 10–20%, 20–30%, 40–50%, and 60–70%. Samples were scanned by PXRF for 180 s using a vacuum (<1,333 Pa) and without a filter. The presence of moisture negatively affected elemental determination in manure samples. Calibrations (n = 200) were prepared using random forest regression with detector channel counts as independent variables. A three‐step validation was performed using all the data, random cross‐validation and external validation. The back end of the spectrum (14–15 keV) had strong predictive power (r2 = .98) for moisture content. The random forest approach increased r2 between PXRF and wet chemical methods from <.66 to >.90 for P, K, and Mg and from .78 to .98 for Fe, compared with linear, nonlinear, and Lucas‐Tooth and Price equations. These results indicated that elemental concentration can accurately be measured in dried and moist manure samples using PXRF and expands the potential applications of PXRF to in situ elemental determinations for agricultural and environmental samples.
Soil surfactants influence fungicide movement in United States Golf Association putting green soil
Authors: Hutchens W.J. , Gannon T.W. , Shew H.D. , Ahmed K.A. , Kerns J.P.
Published: February 2020

The management of root and crown diseases of turfgrasses is challenging. To manage these diseases, golf course superintendents and other turfgrass managers often spray fungicides at a high carrier volume and irrigate after application to move fungicides into the root zone. Furthermore, previous research has demonstrated that soil surfactants can increase fungicide movement and distribution in soil. Two laboratory experiments were conducted using lysimeters, which were coated with sand on their inner walls to prevent preferential flow and contained 90/10% sand/peat moss (v/v), to determine the effects of soil surfactants on movement of selected fungicides in soil. The soil surface in the first experiment was treated three times at 2‐wk intervals with one of three soil surfactants: Aquifer (propoxylated polyethylene glycols), Fleet (polyoxyalkylene polymers), and Revolution (modified alkylated polyol). The soil in the second experiment was treated with only Revolution four times at 2‐ to 3‐wk intervals. Immediately after the final surfactant application, soil columns were treated with 14C‐labeled fungicide. 14C‐Myclobutanil was applied in the first experiment, and 14C‐azoxystrobin and 14C‐propiconazole were applied in the second experiment. In the first experiment, 14 percent units more of the recovered 14C‐myclobutanil was detected in the 5‐ to 7.6‐cm sampling depth, and >4 percent units more was detected in the 7.6‐ to 10.2‐cm depth after soil surfactant application compared with the fungicide‐alone treatment. Each soil surfactant also yielded >28% more leachate than the nontreated control. In the second experiment, the total recovered 14C‐azoxystrobin and 14C‐propiconazole in the 7.6‐ to 10.2‐cm depth increased by 2.8 and 1.9 percent units, respectively, compared with soil treated with fungicide alone. These data indicate that soil surfactant inclusion may increase fungicide distribution in soil, which may enhance the efficacy of fungicides in suppressing root and crown diseases.
Characteristics and course of patients treated with Kampo Medicine in the Department of General Medicine
Authors: Takayama Shin , Akaishi Tetsuya , Nozaki Hiroyuki , Suzuki Satoko , Arita Ryutaro , Saito Natsumi , Tanaka Junichi , Numata Takehiro , Kikuchi Akiko , Ohsawa Minoru , Abe Michiaki , Ishii Tadashi
Published: February 2020

Background

A recent investigation reported that 92.7% Japanese family physicians have prescribed Kampo medicine (KM). KM can treat a wide variety of conditions from mental disorders to physical weaknesses. However, the characteristics and course of patients treated with KM at the Department of General Medicine remain unclear.

Aims

To investigate the characteristics and course of patients treated with KM in our hospital.

Methods

Data on medical history, complaints, course after Kampo treatment, and Hamilton Depression Rating Scale (HAM‐D) scores were retrogradely collected. The background of patients who received Kampo treatment was compared to that of patients who did not.

Result

Of 362 patients, 51 were treated with KM. Symptoms for which KM was prescribed included pain, general malaise, or sensory disturbance of extremities. All patients treated with KM were screened and initially diagnosed with a functional disorder or noncritical condition. KM including a crude drug of saiko such as hochuekkito, shigyakusan, shosaikoto, and yokukansan, was frequently prescribed for patients. Subjective symptoms showed improvement (53%) and no change (47%), while worsening was not observed in any patient. HAM‐D scores showed that patients treated with KM had higher anxiety levels and related symptoms as well as a higher frequency of mental disorders prior to presenting at the hospital.

Conclusion

Most complaints of the patients treated with KM were pain, general malaise, and sensory disturbance. KM is more likely to be prescribed in patients with health‐related anxiety or a history of mental disorders.
Synthesis and evaluation of novel 4H‐pyrazole and thiophene derivatives derived from chalcone as potential anti‐proliferative agents, Pim‐1 kinase inhibitors, and PAINS
Authors: Megally Abdo Nadia Y. , Samir Eman M. , Mohareb Rafat M.
Published: February 2020

The chalcone derivatives 3a‐d reacted with either malononitrile or ethyl cyanoacetate in ethanol in the presence of catalytic amount of ammonium acetate in an oil bath at 120°C to give the Knowevenagel condensation products 5a‐h. The latter compounds reacted with hydrazine hydrate and afforded the 4H‐pyrazole derivatives 7a‐h, respectively. The reaction of compounds 7a‐h with ethyl cyanoacetate in dimethylformamide under refluxing condition afforded the cyanoacetamido derivatives 8a‐h, respectively. When compounds 8a‐h reacted with elemental sulfur and either of malononitrile or ethyl cyanoacetate in ethanol containing triethylamine, the thiophene derivatives 9a‐h and 10a‐h, respectively, were obtained. The structure of the newly synthesized compounds was established by the analytical and spectral data. All the newly synthesized compounds were evaluated against the six cancer cell lines: A549, HT‐29, MKN‐45, U87MG, and SMMC‐7721 and H460. Compounds 3c, 5h, 7g, 7h, 8f, 9e, 9g, and 10g were selected to examine their Pim‐1 kinase inhibition activity as these compounds showed high inhibition toward the c‐Met kinase and the tested cancer cell lines. Furthermore, compounds 3b, 3c, 5g, 5h, 7f, 7g, 7h, 8e, 8f, 8g, 8h, 9e, 9f, 9g, 9h, 10g and 10h were selected to be tested for pan‐assay interference compounds analysis (PAINS). Almost all the tested compounds showed zero PAINS alert and can be used as drug compounds in the future.