bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting PLIN2/PLIN5‐PPARγ: Sulforaphane Disturbs the Maturation of Lipid Droplets
Authors: Tian Sicong , Lei Peng , Teng Chunying , Sun Yao , Song Xinyue , Li Baolong , Shan Yujuan 
Published: July 2019

ScopeThe effects of sulforaphane (SFN) on the maturation of lipid droplets (LDs)—the storage units for free fatty acids and sterols as triacylglycerides (TAG) and cholesterol esters (CE)—are far from being understood, despite the fact that SFN is known to be beneficial for ameliorating lipid metabolism disorders.Methods and ResultsHigh‐fat‐intake models are established in both HHL‐5 hepatocytes and rodents. The numbers and sizes of LDs are decreased by SFN. The accumulation of lipid core components (TAG & CE) is reduced and the expression of their key synthetases, acyl‐coenzyme A: diacylglycerol acyltransferases 2 (DGAT2) and acyl‐coenzyme A: cholesterol acyltransferases 1 (ACAT1), is also inhibited. Moreover, SFN decreases LD‐associated protein PLIN2 and PLIN5 expression, but not that of PLIN1 and PLIN3, both in vivo and in vitro. Furthermore, over‐expression of peroxisome proliferator‐activated receptor gamma (PPARγ) induces the accumulation of TAG and the up‐regulation of PLIN2 and PLIN5, which are not reversed by SFN. These results suggest that PPARγ may be a target of SFN in lipid metabolism.ConclusionSFN disturbs LD maturation by inhibiting the formation of the neutral lipid core and decreases PLIN2 and PLIN5 via down‐regulation of PPARγ.
Nerve entrapments related to muscle herniation
Authors: Tong Olivia , Bieri Phyllis , Herskovitz Steven 
Published: July 2019

AbstractBackgroundMuscle herniation is a muscle protrusion through a fascial defect. It is a rarely reported cause of nerve entrapment.MethodsWe present a case of superficial fibular (peroneal) neuropathy associated with a fibularis (peroneus) brevis muscle herniation and a review of the literature on nerve entrapments secondary to muscle herniation unrelated to compartment syndrome.ResultsEleven cases of nerve entrapments secondary to muscle herniation were identified. The superficial fibular nerve (SFN) was the most commonly entrapped nerve by fibularis muscle herniation. Patients presented with pain, numbness, or paresthesias, and an often tender, small palpable mass with a Tinel sign. Muscle MRI or ultrasound identified the lesion, and patients responded well to fasciotomy.ConclusionsThe most commonly reported nerve entrapped by muscle herniation is the SFN secondary to fibularis muscle herniation. Characteristic clinical and imaging (MRI or ultrasound) features are diagnostic, and there is a salutary response to fasciotomy.
Physiological differences in sarcolemmal excitability between human muscles
Authors: Lee James H. F. , Boland‐Freitas Robert , Ng Karl 
Published: July 2019

AbstractIntroductionThe sarcolemmal resting membrane potential (RMP) affects muscle excitability, contractility, and force generation. However, there are limited In vivo data on the normal RMP of the human sarcolemma between muscles. We hypothesize that the in vivo RMP may differ between human muscles with different physiological roles.MethodsMuscle velocity recovery cycles were recorded from a proximal antigravity muscle, the rectus femoris, and compared with paired recordings from a distal non‐antigravity muscle, the tibialis anterior, in 34 normal individuals.ResultsSignificant differences in muscle relative refractory period (3.55 millseconds vs 3.87 milliseconds, P = .002), early supernormality (14.22% vs 10.50%, P < .0001), and late supernormality (5.43% vs 3.50%, P < .0001) were observed.DiscussionThe results strongly suggest a less negative RMP in tibialis anterior vs rectus femoris and attest to intermuscle differences in normal excitability and physiology. This novel finding employing an in vivo methodology highlights the need for muscle‐specific normative data in future studies.
Shifting Diets of Lake Trout in Northeastern Lake Michigan
Authors: Luo Miles K. , Madenjian Charles P. , Diana James S. , Kornis Matthew S. , Bronte Charles R. 
Published: July 2019

Abstract
Prey fish communities in Lake Michigan have been steadily changing, characterized by declines in both the quantity and quality of Alewife Alosa pseudoharengus. To evaluate concurrent changes in the diet of Lake Trout Salvelinus namaycush in northeastern Lake Michigan, we analyzed stomach contents of Lake Trout caught during gill-net surveys and fishing tournaments from May through October 2016. We then compared the composition, on a wet-weight basis, of 2016 diets with those previously described in a recent survey conducted in 2011. Overall, we found that Lake Trout diets in 2016 consisted mostly (94% by wet weight) of Alewives and Round Goby Neogobius melanostomus. Averaging across May through October, 61% of the Lake Trout diet consisted of Alewives. A clear seasonal shift was apparent: the diet was dominated by Round Goby (67%) during May–June, whereas Alewives dominated the diet (76%) during July–October. Seasonal dominance of Round Goby in spring Lake Trout diets has not been previously observed in northeastern Lake Michigan as Round Goby represented only 21% of the Lake Trout diet in spring of 2011. Diet composition of Lake Trout caught in gill nets did not significantly differ from diet composition of Lake Trout caught by anglers in either the May–June period or the July–October period. Although Lake Trout showed increased diet flexibility in 2016 compared with 2011, Alewives were still the predominant diet component during 2016, despite reduced Alewife biomass throughout Lake Michigan. Nonetheless, this further evidence of diet plasticity suggests that Lake Trout may be resilient to ongoing and future forage base changes.
Bacterial Stern layer diffusion: experimental determination with spectral induced polarization and sensitivity to nitrite toxicity
Authors: Mellage Adrian , Smeaton Christina M. , Furman Alex , Atekwana Estella A. , Rezanezhad Fereidoun , Van Cappellen Philippe 
Published: July 2019

ABSTRACTSpectral induced polarization signatures have been used as proxies for microbial abundance in subsurface environments, by taking advantage of the charged properties of microbial cell membranes. The method's applicability, however, remains qualitative, and signal interpretation ambiguous. The adoption of spectral induced polarization as a robust geo‐microbiological tool for monitoring microbial dynamics in porous media requires the development of quantitative relationships between biogeochemical targets and spectral induced polarization parameters, such as biomass density and imaginary conductivity (σ″). Furthermore, deriving cell density information from electrical signals in porous media necessitates a detailed understanding of the nature of the cell membrane surface charge dynamics. We present results from a fully saturated sand‐filled column reactor experiment where Shewanella oneidensis growth during nitrate reduction to ammonium was monitored using spectral induced polarization. While our results further confirm the direct dependence of σ″ on changing cell density, Cole–Cole derived relaxation times also record the changing surface charging properties of the cells, ascribed to toxic stress due to nitrite accumulation. Concurrent estimates of cell size yield the first measurement‐derived estimation of the apparent surface ion diffusion coefficient for cells (Ds = 5.4 ±1.3 µm2 s−1), strengthening the link between spectral induced polarization and electrochemical cell polarization. Our analysis provides a theoretical framework on which to build σ″–cell density relations using bench‐scale experiments, leading to eventual robust non‐destructive monitoring of in situ microbial growth dynamics.
Simultaneous separation and determination of hirsutine and hirsuteine by cyclodextrin‐modified micellar electrokinetic capillary chromatography
Authors: Wang Mengli , Guo Jing , Wang Zhiying , Zhang Guangbin , Yu Haixia , Chang Ruimiao , Chen Anjia 
Published: July 2019

AbstractIntroductionHirsutine and hirsuteine are the main pharmacological activity ingredients of Uncaria rhynchophylla (UR), playing an important role in treating mental and cardiovascular diseases, such as Alzheimerʼs disease, hypertension, Parkinson's disease, potential anti‐cancer activities and so on.ObjectiveTo develop a cyclodextrin‐modified micellar electrokinetic capillary chromatography (CD‐MEKC) method for the simultaneous separation and determination of hirsutine and hirsuteine from UR and its formulations.MethodologyThe optimal method was developed by investigating influences of significant factors on the separation, and this method was successfully applied for the determination of hirsutine and hirsuteine in UR and its formulations.ResultsThe optimal background electrolyte (BGE) consisted of 40 mM sodium dihydrogen phosphate (pH 7.0), 150 mM 2,6‐dimethyl‐β‐cyclodextrin (DM‐β‐CD), 3 mM mono‐(6‐ethylenediamine‐6‐deoxy)‐β‐cyclodextrin (ED‐β‐CD), and 30 mM sodium cholate (SC). Under these conditions, hirsutine and hirsuteine were successfully separated within 13 min at the separation voltage of 15 kV, temperature of 25°C and the detection wavelength of 224 nm. For the analytes, linear calibration curves were performed within the range 5.0–160.0 μg/mL. The limit of detection (LOD, S/N = 3) and the limit of quantitation (LOQ, S/N = 10) were 0.41, 1.42 μg/mL for hirsutine and 0.60, 2.17 μg/mL for hirsuteine, respectively. The recoveries of three samples were from 97.9% to 102.3%.ConclusionThe method was successfully applied to the determination of hirsutine and hirsuteine in UR and its formulations. Meanwhile, it provides an effective reference of the quality control of UR and its formulations.
Identifying pregnancies in insurance claims data: Methods and application to retinoid teratogenic surveillance
Authors: MacDonald Sarah C. , Cohen Jacqueline M. , Panchaud Alice , McElrath Thomas F. , Huybrechts Krista F. , Hernández‐Díaz Sonia 
Published: July 2019

AbstractPurposeThe purpose of the study is to develop an algorithm to identify pregnancies in administrative databases and apply it to assess pregnancy rates and outcomes in women prescribed isotretinoin or tretinoin.MethodsUsing the 2011 to 2015 Truven Health MarketScan Database, we identified pregnancies, including losses and terminations. In a cohort design, nonpregnant women filling a prescription for isotretinoin or tretinoin were matched to five women without either prescription. Women were followed for 365 days or until conception, medication discontinuation, or enrollment discontinuation (“prescription episode”). Rates of pregnancy, risks of pregnancy losses, and prevalence of infant malformations at birth were assessed by exposure.ResultsWe identified 2 179 192 livebirths, 8434 stillbirths, 2521 mixed births, 415 110 spontaneous abortions, 124 556 elective terminations, and 8974 unspecified abortions. There were 86 834 isotretinoin and 973 587 tretinoin episodes, matched to 5 302 105 unexposed women. Pregnancy rates were 3 (isotretinoin), 19 (tretinoin), and 34 (unexposed) per 1000 person‐years. Risk of spontaneous pregnancy losses were similar; however, terminations were more common in the isotretinoin‐exposed (28% [95% CI: 21%‐36%]) than the tretinoin‐exposed (10% [95% CI: 9%‐11%]) or unexposed pregnancies (6%). Malformations occurred in 4.5% (95% CI: 3.5%‐5.6%) of the tretinoin‐exposed pregnancies and 4.2% of the unexposed pregnancies (adjusted odds ratio: 1.16 [95% CI: 0.85‐1.58]); isotretinoin‐exposed births were too few to assess malformations.ConclusionsAdministrative databases can complement risk evaluation and mitigation strategies (REMS) for known teratogens and contribute to safety surveillance for other medications. Here, isotretinoin‐exposed pregnancy rates were low, but existent, and many pregnancies were terminated. Tretinoin exposure was not associated with a meaningfully elevated risk of losses or malformations as compared with unexposed pregnancies.
A plan to diversify a transgenic blight‐tolerant American chestnut population using citizen science
Authors: Westbrook Jared W. , Holliday Jason A. , Newhouse Andrew E. , Powell William A. 
Published: July 2019

Societal Impact StatementOver four billion American chestnut trees have been killed as a result of an introduced pathogen, the chestnut blight fungus. Recently, transgenic blight‐tolerant American chestnut trees have been produced by inserting a gene from wheat into the American chestnut genome. Pending federal approval to use these transgenic trees for large‐scale forest restoration, this would be the first instance where a transgenic approach has been used to restore a tree species that has been rendered functionally extinct by an introduced pathogen. With the help of citizen scientists, we estimate that large‐scale forest restoration using blight‐tolerant American chestnut trees is possible within the next few decades.SummaryBreeding transgenic blight‐tolerant American chestnuts with susceptible wild‐type (WT) trees is potentially an efficient method to rescue the genetic diversity and adaptive capacity of the American chestnut population for large‐scale restoration.To develop a breeding plan to diversify a transgenic blight‐tolerant population, we simulated pedigrees to estimate inbreeding coefficients and effective population size in scenarios involving outcrossing 1–4 transgenic founders to a maximum of 1,500 WT trees over 1–5 generations. We also simulated marker‐assisted introgression scenarios to minimize the extent of the transgenic founder genome, especially on the transgene carrier chromosome.Simulations suggest that the effective population size may be increased to >500, and the average inbreeding coefficient reduced to <0.01, by outcrossing a single transgenic founder over five generations to 2, 25, 50, 150, and 450 (677 total) WT parents. Three generations of marker‐assisted introgression is predicted to decrease the length of the founder genome to between 7% and 13% of the transgene carrier chromosome length as compared to 42% with event selection (ES) only. Transgenic outcross selections may be intercrossed to select progeny homozygous for the transgene for planting in seed orchards.A diversified population of transgenic blight‐tolerant American chestnut is estimated to be available for use in large‐scale forest restoration 20–35 years after federal approval to distribute the trees. In contrast, trees from earlier generations would be available almost immediately after federal approval for personal or horticultural plantings. Methods to accelerate pollen production and outcrossing are discussed.
Design of a basigin‐mimicking inhibitor targeting the malaria invasion protein RH5
Authors: Warszawski Shira , Dekel Elya , Campeotto Ivan , Marshall Jennifer M. , Wright Katherine E. , Lyth Oliver , Knop Orli , Regev‐Rudzki Neta , Higgins Matthew K. , Draper Simon J. , Baum Jake , Fleishman Sarel J. 
Published: July 2019

AbstractMany human pathogens use host cell‐surface receptors to attach and invade cells. Often, the host‐pathogen interaction affinity is low, presenting opportunities to block invasion using a soluble, high‐affinity mimic of the host protein. The Plasmodium falciparum reticulocyte‐binding protein homolog 5 (RH5) provides an exciting candidate for mimicry: it is highly conserved and its moderate affinity binding to the human receptor basigin (KD ≥1 μM) is an essential step in erythrocyte invasion by this malaria parasite. We used deep mutational scanning of a soluble fragment of human basigin to systematically characterize point mutations that enhance basigin affinity for RH5 and then used Rosetta to design a variant within the sequence space of affinity‐enhancing mutations. The resulting seven‐mutation design exhibited 1900‐fold higher affinity (KD approximately 1 nM) for RH5 with a very slow binding off rate (0.23 h−1) and reduced the effective Plasmodium growth‐inhibitory concentration by at least 10‐fold compared to human basigin. The design provides a favorable starting point for engineering on‐rate improvements that are likely to be essential to reach therapeutically effective growth inhibition.
National culture diversity in new venture boards: The role of founders' relational demography
Authors: Balachandran Chanchal , Wennberg Karl , Uman Timur 
Published: July 2019

Abstract
Research SummaryThis study explains the conditions under which new venture boards are less or more culturally diverse in terms of their directors' country of birth. Longitudinal data on 5,515 Swedish ventures suggest that most directors are recruited from founders' proximate social settings—neighborhoods in which they reside and past workplaces—and that diversity levels in these social settings strongly predict the national culture diversity in venture boards. Given the rapid internationalization of workplaces and regions around the world, this paper provides important clues regarding how culturally diverse upper echelons are being incorporated into the organizational design of new ventures.
Managerial SummaryMost New Venture Boards exhibit limited diversity in terms of their directors' country of birth, as they are drawn from the venture founders' network. Yet, some new venture boards are indeed born diverse. Our study reveals that founders with prior exposure to culturally diverse workplaces and residential neighborhoods are much more likely to design a culturally diverse board at founding. Given the rapid internationalization of workplaces and regions in most countries around the world, our paper provides important clues regarding how national culture diversity in top management emerges and is being incorporated into the organizational design of new ventures.
Impact of model misspecification in shared frailty survival models
Authors: Gasparini Alessandro , Clements Mark S. , Abrams Keith R. , Crowther Michael J. 
Published: July 2019

Survival models incorporating random effects to account for unmeasured heterogeneity are being increasingly used in biostatistical and applied research. Specifically, unmeasured covariates whose lack of inclusion in the model would lead to biased, inefficient results are commonly modeled by including a subject‐specific (or cluster‐specific) frailty term that follows a given distribution (eg, gamma or lognormal). Despite that, in the context of parametric frailty models, little is known about the impact of misspecifying the baseline hazard or the frailty distribution or both. Therefore, our aim is to quantify the impact of such misspecification in a wide variety of clinically plausible scenarios via Monte Carlo simulation, using open‐source software readily available to applied researchers. We generate clustered survival data assuming various baseline hazard functions, including mixture distributions with turning points, and assess the impact of sample size, variance of the frailty, baseline hazard function, and frailty distribution. Models compared include standard parametric distributions and more flexible spline‐based approaches; we also included semiparametric Cox models. The resulting bias can be clinically relevant. In conclusion, we highlight the importance of fitting models that are flexible enough and the importance of assessing model fit. We illustrate our conclusions with two applications using data on diabetic retinopathy and bladder cancer. Our results show the importance of assessing model fit with respect to the baseline hazard function and the distribution of the frailty: misspecifying the former leads to biased relative and absolute risk estimates, whereas misspecifying the latter affects absolute risk estimates and measures of heterogeneity.
Antichagasic profile of a Series of Mannich Base‐Type Derivatives: Design, Synthesis, in vitro Evaluation, and Computational Studies Involving Iron Superoxide Dismutase
Authors: Paucar Rocío , Martín‐Escolano Rubén , Moreno‐Viguri Elsa , Cirauqui Nuria , Marín Clotilde , Sánchez‐Moreno Manuel , Pérez‐Silanes Silvia 
Published: July 2019

AbstractChagas disease is a silent disease that continues to endanger millions of people and, due to its insufficient current chemotherapy, urgently requires the development of more effective drugs. With this objective, twenty‐six Mannich base derivatives were synthesized, and their in vitro activity was evaluated against Trypanosoma cruzi. Three out of the twenty‐six compounds showed interesting results, including IC50 values<10 μM and a selectivity index >20 in amastigote forms of Arequipa and SN3 T. cruzi strains. In addition, these compounds showed similar infection rates in Vero cells compared to those of benznidazole at 50 μM. Finally, some studies were performed to investigate the possible mechanism of action; moreover, computational studies proposed a binding mode of these derivatives to Fe‐SOD. This new series of compounds has an encouraging antichagasic profile with a simplified structure and synthetic routes. Therefore, the most active compounds should be considered as leads for further optimization of the antichagasic activity.
Machine learning approaches to facial and text analysis: Discovering CEO oral communication styles
Authors: Choudhury Prithwiraj , Wang Dan , Carlson Natalie A. , Khanna Tarun 
Published: July 2019

Abstract
Research SummaryWe demonstrate how a novel synthesis of three methods—(a) unsupervised topic modeling of text data to generate new measures of textual variance, (b) sentiment analysis of text data, and (c) supervised ML coding of facial images with a cutting‐edge convolutional neural network algorithm—can shed light on questions related to CEO oral communication. With videos and corresponding transcripts of interviews with emerging market CEOs, we use this synthesis of methods to discover five distinct communication styles that incorporate both verbal and nonverbal aspects of communication. Our data comprises interviews that represent unedited expressions and content, making them especially suitable as data sources for the measurement of an individual's communication style. We then perform a proof‐of‐concept analysis, correlating CEO communication styles to M&A outcomes, highlighting the value of combining text and videographic data to define styles. We also discuss the benefits of using our methods versus current research methods.
Managerial SummaryCEOs spend most of their time communicating to investors, customers, and partners with the aim of influencing these various stakeholders. To what extent though does their effectiveness as leaders depend on a mixture of what they say and how they say it? We use cutting‐edge machine learning approaches to measure a CEO's communication style, which can give clues about the major strategic decisions a CEO's firm must make. With a collection of video interviews with 61 organizational leaders from emerging markets, we use textual analysis and facial image expression recognition to code whether CEOs are “excitable,” “stern,” “dramatic,” “rambling,” and “melancholy” in their communication styles. As a proof‐of‐concept, we also show that CEOs who were more dramatic in expressing themselves were also less likely to oversee major acquisitions. Therefore, not only can CEO communication styles help predict a firm's ability to grow, adapt to change, and reallocate existing assets, styles can also be coded more intuitively by using our new method, representing a vast improvement over previous methods in both accessibility and interpretability.