bluuebunny/crossref_metadata_2025 huggingface dataset:
A new noninvasive and patient‐specific hemodynamic index for the severity of renal stenosis and outcome of interventional treatment
Authors: Yu Huidan , Khan Monsurul , Wu Hao , Du Xiaoping , Chen Rou , Rollins Dave M. , Fang Xin , Long Jianyun , Xu Chenke , Sawchuk Alan P.
Published: May 2022

Renal arterial stenosis (RAS) often causes renovascular hypertension, which may result in kidney failure and life‐threatening consequences. Direct assessment of the hemodynamic severity of RAS has yet to be addressed. In this work, we present a computational concept to derive a new, noninvasive, and patient‐specific index to assess the hemodynamic severity of RAS and predict the potential benefit to the patient from a stenting therapy. The hemodynamic index is derived from a functional relation between the translesional pressure indicator (TPI) and lumen volume reduction (S) through a parametric deterioration of the RAS. Our in‐house computational platform, InVascular, for image‐based computational hemodynamics is used to compute the TPI at given S. InVascular integrates unified computational modeling for both image processing and computational hemodynamics with graphic processing unit parallel computing technology. The TPI–S curve reveals a pair of thresholds of S indicating mild or severe RAS. The TPI at S = 0 represents the pressure improvement following a successful stenting therapy. Six patient cases with a total of 6 aortic and 12 renal arteries are studied. The computed blood pressure waveforms have good agreements with the in vivo measured ones and the systolic pressure is statistical equivalence to the in‐vivo measurements with p < .001. Uncertainty quantification provides the reliability of the computed pressure through the corresponding 95% confidence interval. The severity assessments of RAS in four cases are consistent with the medical practice. The preliminary results inspire a more sophisticated investigation for real medical insights of the new index. This computational concept can be applied to other arterial stenoses such as iliac stenosis. Such a noninvasive and patient‐specific hemodynamic index has the potential to aid in the clinical decision‐making of interventional treatment with reduced medical cost and patient risks.
A Single‐blind, Randomized, Single‐dose, Two‐sequence, Two‐period, Crossover Study to Assess the Bioequivalence between Two Oral Tablet Formulations of Rivaroxaban 20 mg in Healthy Mexican Volunteers
Authors: Genis‐Najera Luis , Sañudo‐Maury Maria Elena , Moquete Trinifer
Published: May 2022

The objective of this study was to demonstrate the bioequivalence of 2 oral tablet formulations of rivaroxaban 20 mg in healthy Mexican volunteers under fed conditions. This phase I, single‐blind, single‐dose, randomized, two‐sequence, two‐period crossover study included 32 volunteers. Subjects were randomly assigned to one of two sequences: test formulation (single 20 mg dose) in the first period followed by the reference formulation (single 20 mg dose) in the second, or vice versa. Blood samples were collected predose and at predefined timepoints across a 48‐hour period after drug intake. Rivaroxaban plasma concentrations were measured using a validated high‐performance liquid chromatography‐tandem mass spectrometry method. Pharmacokinetic parameters included maximum plasma concentration (Cmax), area under the plasma concentration‐time curve from time zero to last measurable concentration and to infinity (AUC0‐t, AUC0‐∞), time to reach Cmax, and half‐life. Safety was evaluated through adverse‐event monitoring using subject interviews and recording of vital signs. The 90% confidence intervals for the test/reference geometric mean ratios of Cmax (100.4%–112.7%), AUC0‐t (96.5%–111.6%), and AUC0‐∞ (95.5%–109.5%) were within the bioequivalence acceptance range (80‐125%). Two adverse events (headaches) were recorded. Both formulations of rivaroxaban 20 mg tablets were bioequivalent and well tolerated in a healthy population of Mexican volunteers under fed conditions.
Clinical Formulation Bridging of Gefapixant, a P2X3‐Receptor Antagonist, for the Treatment of Chronic Cough
Authors: Gupta Pranav , Hussain Azher , Ford Anthony P. , Smith Steven , Nussbaum Jesse C. , Stoch Aubrey , Iwamoto Marian
Published: May 2022

Gefapixant is a P2X3‐receptor antagonist being developed for treatment of refractory or unexplained chronic cough. Four phase 1 studies were conducted in healthy participants that bridged the early‐phase gefapixant formulation (F01) to the phase 3 (F04A) and intended commercial (F04B) formulations. In addition, food and proton pump inhibitor (PPI) coadministration effects on gefapixant exposure were assessed. The gefapixant free base formulation (F01) was used in the initial early‐phase clinical studies. Adding citric acid to the F01 formulation (to generate F02) enhanced drug solubilization, resulting in similar bioavailability and mitigating food and gastric pH effects. The subsequently developed gefapixant citrate salt formulation (F04) achieved exposures that were comparable to F02 in the fed state (90%CIs of geometric mean ratios for area under the plasma concentration–time curve from time 0 extrapolated to infinity and maximum observed concentration were within 0.80 and 1.25) and were not meaningfully affected by food or PPIs (90%CIs of geometric mean ratios for area under the plasma concentration–time curve from time 0 extrapolated to infinity and maximum observed concentration were within 0.80 and 1.25). Minor compositional changes were made to generate the F04A and F04B formulations. In vitro dissolution studies were used to bridge F04 to F04A, and clinical bioequivalence was then established between F04A and F04B. These data support use of the proposed commercial gefapixant formulation without significant food and PPI effects.
Data reduction and recovery in wireless communication system: An extensive experimental evaluation using PSK and QAM modulations
Authors: Panem Charanarur , Vetrekar Narayan , Gad Rajendra
Published: May 2022

The evolution of technologies in data communication system has resulted in generation of large data. With the availability of limited bandwidth and to maintain the energy efficiency of the wireless communication system, data reduction plays a significant amount of role in preserving the lifetime of wireless communication system. Considering the significance of this problem in wireless communication system, in this work, we present data reduction and recovery or reconstruction on multivariate data using principal component analysis (PCA). In general, we send the eigen coefficients from the source and use these coefficients at the destination to recover or reconstruct the original data back in wireless communication system. We employ in our work two different digital modulation techniques such as phase‐shift keying (PSK) and quadrature amplitude modulation (QAM) with seven different bit rate to demonstrate our approach. We carry the experiments independently using five different signal ensemble and four different multiple‐input, multiple‐output (MIMO) configuration along with Rayleigh fading. This work presents an extensive simulated benchmark results based on performance matrix such as root mean square error (RMSE) and bit error rate (BER) at different values of signal‐to‐noise ratio (SNR). We further validate our approach by presenting synthesis of our proposed model using Xilinx target device Virtex‐6 LX240T Field Programmable Gate Array (FPGA). The experimental results reported based on simulation, synthesis, and validation of model demonstrate the applicability of our proposed approach in real‐time scenario.
Data and pilot power controls scheme based on convolutional neural network for massive cellular system with underlaid device‐to‐device communications
Authors: Faragallah Osama S. , El‐sayed Hala S. , El‐Mashed Mohamed G.
Published: May 2022

Studying deep learning framework in massive cellular system to optimize its performance is a challenge task. In this paper, multi‐cell massive cellular system with device‐to‐device (D2D) communication is studied, where D2D pairs and cellular users can share different orthogonal pilots to overcome interference at the cellular base station (BS). We propose data and pilot power controls scheme based on deep learning framework using convolutional neural network (CNN) for cellular and D2D users. The main focus is to obtain the optimal data and pilot powers (i.e., cellular pilot power,
, cellular data power,
, D2D pilot power,
, and D2D data power,
) for maximum spectral efficiency (SE). SE optimization problem is formulated with the goal of obtaining optimal transmit powers. Also, comparison between the proposed scheme and the iterative power control schemes (i.e., weighted minimum mean square error [MMSE] technique, bisection technique, and technique‐based geometric mean per‐cell max–min fairness) is provided. Results show that the proposed scheme can increase the sum SE of multi‐cell massive cellular system with D2D communications.
Improving clinical trial efficiency using a machine learning‐based risk score to enrich study populations
Authors: Jering Karola S. , Campagnari Claudio , Claggett Brian , Adler Eric , Klein Liviu , Ahmad Faraz S. , Voors Adriaan A. , Solomon Scott , Yagil Avi , Greenberg Barry
Published: May 2022

Aims

Prognostic enrichment strategies can make trials more efficient, although potentially at the cost of diminishing external validity. Whether using a risk score to identify a population at increased mortality risk could improve trial efficiency is uncertain. We aimed to assess whether Machine learning Assessment of RisK and EaRly mortality in Heart Failure (MARKER‐HF), a previously validated risk score, could improve clinical trial efficiency.

Methods and results

Mortality rates and association of MARKER‐HF with all‐cause death by 1 year were evaluated in four community‐based heart failure (HF) and five HF clinical trial cohorts. Sample size required to assess effects of an investigational therapy on mortality was calculated assuming varying underlying MARKER‐HF risk and proposed treatment effect profiles. Patients from community‐based HF cohorts (n = 11 297) had higher observed mortality and MARKER‐HF scores than did clinical trial patients (n = 13 165) with HF with either reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). MARKER‐HF score was strongly associated with risk of 1‐year mortality both in the community (hazard ratio [HR] 1.48, 95% confidence interval [CI] 1.44–1.52) and clinical trial cohorts with HFrEF (HR 1.41, 95% CI 1.30–1.54), and HFpEF (HR 1.74, 95% CI 1.53–1.98), per 0.1 increase in MARKER‐HF. Using MARKER‐HF to identify patients for a hypothetical clinical trial assessing mortality reduction with an intervention, enabled a reduction in sample size required to show benefit.

Conclusion

Using a reliable predictor of mortality such as MARKER‐HF to enrich clinical trial populations provides a potential strategy to improve efficiency by requiring a smaller sample size to demonstrate a clinical benefit.
Redefining the epidemiology of cardiac amyloidosis. A systematic review and meta‐analysis of screening studies
Authors: Aimo Alberto , Merlo Marco , Porcari Aldostefano , Georgiopoulos Georgios , Pagura Linda , Vergaro Giuseppe , Sinagra Gianfranco , Emdin Michele , Rapezzi Claudio
Published: May 2022

Aims

An algorithm for non‐invasive diagnosis of amyloid transthyretin cardiac amyloidosis (ATTR‐CA) and novel disease‐modifying therapies have prompted an active search for CA. We examined the prevalence of CA in different settings based on literature data.

Methods and results

We performed a systematic search for screening studies on CA, focusing on the prevalence, sex and age distribution in different clinical settings. The prevalence of CA in different settings was as follows: bone scintigraphy for non‐cardiac reasons (n = 5 studies), 1% (95% confidence interval [CI] 0%–1%); heart failure with preserved ejection fraction (n = 6), 12% (95% CI 6%–20%); heart failure with reduced or mildly reduced ejection fraction (n = 2), 10% (95% CI 6%–15%); conduction disorders warranting pacemaker implantation (n = 1), 2% (95% CI 0%–4%); surgery for carpal tunnel syndrome (n = 3), 7% (95% CI 5%–10%); hypertrophic cardiomyopathy phenotype (n = 2), 7% (95% CI 5%–9%); severe aortic stenosis (n = 7), 8% (95% CI 5%–13%); autopsy series of ‘unselected’ elderly individuals (n = 4), 21% (95% CI 7%–39%). The average age of CA patients in the different settings ranged from 74 to 90 years, and the percentage of men from 50% to 100%. Many patients had ATTR‐CA, but the average percentage of patients with amyloid light‐chain (AL) CA was up to 18%.

Conclusions

Searching for CA in specific settings allows to identify a relatively high number of cases who may be eligible for treatment if the diagnosis is unequivocal. ATTR‐CA accounts for many cases of CA across the different settings, but AL‐CA is not infrequent. Median age at diagnosis falls in the eighth or ninth decades, and many patients diagnosed with CA are women.
Selective Deconstructive Lactamization of the Indolo[2,3‐a]quinolizine Skeleton for the Total Synthesis of (+) and (−)‐Cuscutamine
Authors: Recoba‐Torres Adriana , Cruz‐Gregorio Silvano , Quintero Leticia , Sandoval‐Lira Jacinto , Romero‐Ibañez Julio , Sartillo‐Piscil Fernando
Published: May 2022

The general approach for accessing to a tetracyclic hexahydro‐3H‐indolizino[8,7‐b]indol‐3‐one alkaloids is that what involves the construction of the γ‐lactam ring from a tricyclic precursor. Here in this report, we disclose a new synthetic strategy that permits the direct deconstruction of the tetracyclic indolo[2,3‐a]quinolizine motif into the tetracyclic hexahydroindolizin‐3‐one scaffold of the naturally occurring (+)‐cuscutamine without the use of either transition or precious metals. Additionally, the current total synthesis of both enantiomers provides structural clarification of the natural occurring alkaloid.
Mesh‐free model for Hopf's bifurcation points in incompressible fluid flows problems
Authors: Rammane Mohammed , Mesmoudi Said , Tri Abdeljalil , Braikat Bouazza , Damil Noureddine
Published: May 2022

In this article, a new numerical model is proposed to detect numerically the Hopf bifurcation point of incompressible fluid flows problems. The concept of this model consists to propose a Hopf bifurcation indicator which is solved by a high order mesh free algorithm (HO‐MFA) using the moving least squares (MLS) approximation. This numerical model is based on a strong formulation of Navier–Stokes equations. This procedure allowed us to recover the results of the literature in using only a modelization for low Reynolds number. This new model is tested on the classical flow around a cylindrical obstacle and the backward‐facing step flow to show the advantage and ability of the proposed model to detect the bifurcation points and to determinate the flow periodicity.
Digital image correlation based characterization of rubber material at large shear deformations in an extended temperature range
Authors: Kanzenbach Lars , Lehmann Thomas , Ihlemann Jörn
Published: May 2022

This contribution deals with a new shear device, which is applied for rubber measurements in simple shear in an extended temperature range. As a special feature for the loading system, no bonding technique, or vulcanization is used, but a form fit connection via pins. The measured stress–shear value curves for different temperature levels are evaluated with a standard method from GOM ARAMIS. In addition, a new approximation based evaluation method is introduced and applied for shear value determination including smoothing of the raw digital image correlation data with consideration of characteristic noise properties. This enables the analysis of noise induced error influences. It was proved by the approximation based method, that the standard ARAMIS evaluation provides shear value results, which are suitable for performed characterization tests. As a consequence, the nearly homogeneous measurement data can be used for parameter fitting of constitutive rubber models.
The changing relationship between advising and technology
Authors: Pelletier Kathe
Published: May 2022

In the past, technological tools were considered a “solution” to advising challenges. However, successful advising transformation efforts have also incorporated shifts in institutional culture and workforce in addition to the adoption of new technologies. Approaching advising redesign as a digital transformation (Dx) initiative can transform an institution's operations, strategic directions, and value propositions surrounding advising. This chapter articulates an approach to the implementation of advising technologies and the necessity to view “holistic advising redesign” as a Dx initiative for advising to reach its full potential at scale. For institutions, this means embracing not just the promise of new technology but also the investment in and attention to the critical shifts in culture and workforce.
A leadership journey: How advising shapes an institutional culture
Authors: Jones Jacquelyn , Welker Melissa , Charlton Jonikka , Arney Janna
Published: May 2022

Although we know advising can be conceptualized as a critical component of an integrated and comprehensive student success strategy on a campus, it is often difficult to implement. This chapter will provide a case study of the development and execution of a leadership initiative at an American Association of State Colleges and Universities (AASCU) institution to transform advising in service of the goals of student equity and success. The University of Texas Rio Grande Valley's advising model grew out of a convergence of a handful of key momentum points including strategic planning processes and the use of emerging data surrounding their students as a majority‐minority Hispanic‐serving institution. Through these and other momentum points and the approach from leaders, their institutional transformation reflects the importance of the role and shared responsibility for building student success and equity on campus.
Assessment of civic learning and democratic engagement
Authors: Hemer Kevin M. , Kappus Alexander
Published: May 2022

Recalibrating the role of higher education in higher education is no small task. Assessment is vital to understand which efforts prove fruitful and which do not. This chapter discusses the importance of thoughtful framing and design of CLDE learning outcomes, methodological pluralism, and the opportunities available by sharing assessment findings.
Our labor of love: Socially just leadership education as civic leadership development
Authors: Collins Jasmine D. , Manning‐Ouellette Amber , Neal Brandi , Daglaris Megan
Published: May 2022

The chapter authors argue there is a distinct relationship between socially just leadership education and civic engagement, which transforms inequitable work to interrupt and reconstruct unjust systems and organizations through curricular learning and engagement. To cultivate advocacy, activism, and engaged citizenry, higher education administrators, faculty, and staff have a responsibility to engage practices for socially just leadership learning and development of college students through curricular and co‐curricular experiences.
Socioeconomic status and COVID‐19‐related cases and fatalities in the world: A cross‐sectional ecological study
Authors: Faramarzi Ahmad , Javan‐Noughabi Javad , Mousavi Sayed Ali , Bahrami Asl Farshad , Shabanikiya Hamidreza
Published: May 2022

Background and Aims

The COVID‐19 pandemic poses an extraordinary threat to global public health. We designed an ecological study to explore the association between socioeconomic factors and the COVID‐19 outcomes in 184 countries, using the geographic map and multilevel regression models.

Methods

We conducted a cross‐sectional ecological study in 184 countries. We performed regression analysis to assess the association of various socioeconomic variables with COVID‐19 outcomes in 184 countries, using ordinary least squares and multilevel modeling analysis. We performed two‐level analyses with countries at Level 1 and geographical regions at Level 2 in multilevel modeling analysis, using the same set of predictor variables used in ordinary least squares.

Results

There was a significant relationship between COVID‐19 cases rate (Log) per 100,000 inhabitants‐day at risk with human development index (HDI), percentage of the urban population, unemployment, and cardiovascular disease prevalence. The results displayed that the variances are varied between Level 1 (country level) and Level 2 (World Health Organization [WHO] regions), meaning that the geographic distribution represented a proportion of the changes in the COVID‐19 outcomes.

Conclusion

The study suggests that in addition to the socioeconomic status affects the COVID‐19 outcomes, countries' geographical location makes a part of changes in outcomes of diseases. Therefore, health policy‐makers could overcome morbidity and mortality in COVID‐19 by controlling the socioeconomics factors.
The coupled electrocatalyst synergy fabrication for the electrochemical oxygen evolution reaction: From electrode to green energy system
Authors: Mugheri Abdul Qayoom , Qamer Syeda Fatima , Otho Aijaz Ali , Mahmoud Mohamed H. , Fouad Hassan , Akhtar M. Shaheer
Published: May 2022

Advanced, functional, and novel electrocatalytic material for the electrochemical water splitting is core to the renewable energy sector. Herein, we fabricated CoCu oxide functional material on the nickel foam by a hydrothermal method that is highly rich in copper nanoparticles. The composite material showed superfast electrocatalytic performance in the oxygen evolution reaction (OER). A distinguished durability test was obtained; the Tafel slope is relatively weak on an overpotential at 10 mA/cm2 obtained potential 270 mV and was determined for the developed electrocatalyst, which is very closer to the RuO/C. The attractive features of the newly developed material are high abundance in nature, environment‐friendly, cost‐effectiveness, and superior for the OER activity being non‐precious material. The developed catalyst revealed good stability and durability, which indicate its practical applications and long‐term stability. This strategy offered to effectively hierarchical low‐cost and best structural properties for the electrocatalyst containing rare‐earth metals.
The moderating role of sexual minority status in the associations of the experience and tolerance of shame‐related emotions to suicide risk
Authors: Mann Adam J. D. , Kurtz Andrew J. , Tull Matthew T. , Gratz Kim L.
Published: May 2022

Objective

This study examined the associations of the experience and tolerance of shame‐related emotions to suicide risk, as well as the moderating role of sexual minority status.

Methods

Community adults (N = 360) were recruited via MTurk and completed self‐report questionnaires. Hierarchical regression analyses examined the main and interactive associations of sexual minority status and shame‐related variables to suicide risk.

Results

Results revealed significant positive associations between self‐disgust and suicide risk for sexual minority and heterosexual participants, although the magnitude was greater for sexual minority participants. Additionally, tolerance of shame was significantly negatively related to suicide risk only among sexual minority participants. Finally, exploratory analyses examining the three‐way interaction of self‐disgust, shame tolerance, and sexual minority status revealed a significant negative association between shame tolerance and suicide risk only among sexual minority participants with high levels of self‐disgust.

Conclusion

Results highlight the relevance of shame‐related experiences to suicide risk among sexual minorities.
Cardiac glycosides stimulate endocytosis of GLUT1 via intracellular Na+,K+‐ATPase α3‐isoform in human cancer cells
Authors: Fujii Takuto , Katoh Mizuki , Ootsubo Manami , Nguyen Oanh T. T. , Iguchi Mayumi , Shimizu Takahiro , Tabuchi Yoshiaki , Shimizu Yasuharu , Takeshima Hiroshi , Sakai Hideki
Published: May 2022

Glucose transporter GLUT1 plays a primary role in the glucose metabolism of cancer cells. Here, we found that cardiac glycosides (CGs) such as ouabain, oleandrin, and digoxin, which are Na+,K+‐ATPase inhibitors, decreased the GLUT1 expression in the plasma membrane of human cancer cells (liver cancer HepG2, colon cancer HT‐29, gastric cancer MKN45, and oral cancer KB cells). The effective concentration of ouabain was lower than that for inhibiting the activity of Na+,K+‐ATPase α1‐isoform (α1NaK) in the plasma membrane. The CGs also inhibited [3H]2‐deoxy‐
d‐glucose uptake, lactate secretion, and proliferation of the cancer cells. In intracellular vesicles of human cancer cells, Na+,K+‐ATPase α3‐isoform (α3NaK) is abnormally expressed. Here, a low concentration of ouabain inhibited the activity of α3NaK. Knockdown of α3NaK significantly inhibited the ouabain‐decreased GLUT1 expression in HepG2 cells, while the α1NaK knockdown did not. Consistent with the results in human cancer cells, CGs had no effect on GLUT1 expression in rat liver cancer dRLh‐84 cells where α3NaK was not endogenously expressed. Interestingly, CGs decreased GLUT expression in the dRLh‐84 cells exogenously expressing α3NaK. In HepG2 cells, α3NaK was found to be colocalized with TPC1, a Ca2+‐releasing channel activated by nicotinic acid adenine dinucleotide phosphate (NAADP). The CGs‐decreased GLUT1 expression was significantly inhibited by a Ca2+ chelator, a Ca2+‐ATPase inhibitor, and a NAADP antagonist. The GLUT1 decrease was also attenuated by inhibitors of dynamin and phosphatidylinositol‐3 kinases (PI3Ks). In conclusion, the binding of CGs to intracellular α3NaK elicits the NAADP‐mediated Ca2+ mobilization followed by the dynamin‐dependent GLUT1 endocytosis in human cancer cells.
Subdimensions of social‐communication behavior in autism—A replication study
Authors: Stroth Sanna , Niehaus Hauke , Wolff Nicole , Poustka Luise , Roessner Veit , Kamp‐Becker Inge , Endres Dominik
Published: May 2022

Introduction

In order to identify more refined dimensions of social‐communication impairments in autism spectrum disorder (ASD) a previous study applied exploratory and confirmatory factor analyses to diagnostic algorithm scores of the autism diagnostic observation schedule (ADOS), Module 3. A three‐factor model consisting of repetitive behaviors, impairments in ‘Basic Social‐Communication’ and in ‘Interaction quality’ (IQ) was established and confirmed. The current study aimed to replicate this model in an independent sample. To advance our understanding of the latent structure of social communication deficits, previous work was complemented by a probabilistic approach.

Methods

Participants (N = 1363) included verbally fluent children and young adults, diagnosed as ASD or non‐ASD based on “gold standard” best‐estimate clinical diagnosis. Confirmatory factor analysis examined the factor structure of algorithm items from the ADOS Module 3 and correlations with individual characteristics (cognitive abilities, age) were analyzed. Linear Regressions were used to test the contribution of each latent factor to the prediction of an ASD diagnosis. To tackle large inter‐correlations of the latent factors, a Bayesian exploratory factor analysis (BEFA) was applied.

Results

Results confirmed the previously reported observation of three latent dimensions in the ADOS algorithm reflecting ‘Restricted, Repetitive Behaviors’, ‘Basic Social‐Communication’ behaviors and ‘Interaction Quality’. All three dimensions contributed independently and additively to the prediction of an ASD diagnosis.

Conclusion

By replicating previous findings in a large clinical sample our results contribute to further conceptualize the social‐communication impairments in ASD as two dimensional.
Therapeutic potential of deuterium‐stabilized (R)‐pioglitazone—PXL065—for X‐linked adrenoleukodystrophy
Authors: Monternier Pierre‐Axel , Singh Jaspreet , Parasar Parveen , Theurey Pierre , DeWitt Sheila , Jacques Vincent , Klett Eric , Kaur Navtej , Nagaraja Tavarekere N. , Moller David E. , Hallakou‐Bozec Sophie
Published: May 2022

X‐linked adrenoleukodystrophy (ALD) results from ABCD1 gene mutations which impair Very Long Chain Fatty Acids (VLCFA; C26:0 and C24:0) peroxisomal import and β‐oxidation, leading to accumulation in plasma and tissues. Excess VLCFA drives impaired cellular functions (e.g. disrupted mitochondrial function), inflammation, and neurodegeneration. Major disease phenotypes include: adrenomyeloneuropathy (AMN), progressive spinal cord axonal degeneration, and cerebral ALD (C‐ALD), inflammatory white matter demyelination and degeneration. No pharmacological treatment is available to‐date for ALD. Pioglitazone, an anti‐diabetic thiazolidinedione, exerts potential benefits in ALD models. Its mechanisms are genomic (PPARγ agonism) and nongenomic (mitochondrial pyruvate carrier—MPC, long‐chain acyl‐CoA synthetase 4—ACSL4, inhibition). However, its use is limited by PPARγ‐driven side effects (e.g. weight gain, edema). PXL065 is a clinical‐stage deuterium‐stabilized (R)‐enantiomer of pioglitazone which lacks PPARγ agonism but retains MPC activity. Here, we show that incubation of ALD patient‐derived cells (both AMN and C‐ALD) and glial cells from Abcd1‐null mice with PXL065 resulted in: normalization of elevated VLCFA, improved mitochondrial function, and attenuated indices of inflammation. Compensatory peroxisomal transporter gene expression was also induced. Additionally, chronic treatment of Abcd1‐null mice lowered VLCFA in plasma, brain and spinal cord and improved both neural histology (sciatic nerve) and neurobehavioral test performance. Several in vivo effects of PXL065 exceeded those achieved with pioglitazone. PXL065 was confirmed to lack PPARγ agonism but retained ACSL4 activity of pioglitazone. PXL065 has novel actions and mechanisms and exhibits a range of potential benefits in ALD models; further testing of this molecule in ALD patients is warranted.
Dorsal root ganglia, neural crest migration, and spinal cord form in snakes
Authors: Cundall David , Deufel Alexandra
Published: May 2022

The classic view of the vertebrate dorsal root ganglion is that it arises from trunk neural crest cells that migrate to positions lateral to the spinal cord, sending axons dorsally into the spinal cord and dendrites ventrally to meet with motor axons in the ventral root to form spinal nerves. As a result, the ganglion ends up lying in the dorsal root of the spinal nerve. Serial histological sections of parts of the trunk of juveniles of different snake species revealed that the ganglia lie distal to the junction of dorsal and ventral roots of spinal nerves and outside the neural canal. The anatomical position of spinal ganglia in snakes suggests that regulation of trunk neural crest migration in snakes differs from that in the model endotherms in which it has been most thoroughly explored. Dorsal roots have no distinct rootlets and the span of root entry to the spinal cord is short compared to that of ventral rootlets in the same segment. Comparing early developmental stages to juvenile spinal cords shows an increased separation of spinal nerve root sites and ventral migration of the ganglion in later development. Dorsal rami of the spinal nerves leave directly from the dorsal edge of the ganglion, and the ventral ramus leaves from the ventral tip of the ganglion. How these features relate to the developmental regulation of ganglion form and position and the extraordinary locomotor capabilities of the snake trunk are unclear.
Survival benefit of l‐carnitine supplementation in patients with cirrhosis
Authors: Miwa Takao , Hanai Tatsunori , Nishimura Kayoko , Sakai Yuko , Imai Kenji , Suetsugu Atsushi , Takai Koji , Shiraki Makoto , Katsumura Naoki , Shimizu Masahito
Published: May 2022

Background

l‐Carnitine supplementation is effective in improving muscle cramps, hyperammonemia, and hepatic encephalopathy in patients with cirrhosis. However, limited evidence is available on the effect of
l‐carnitine supplementation on the survival of patients with cirrhosis.

Methods

In this retrospective study, 674 patients with cirrhosis admitted to Gifu University Hospital or Chuno Kosei Hospital between October 2011 and December 2018 were enrolled. l‐carnitine supplementation was defined as the use of
l‐carnitine for >30 consecutive days during the follow‐up period. Propensity score matching was applied to create comparable groups between
l‐carnitine–treated and untreated patients. Mortality was evaluated using the Cox proportional hazards model.

Results

Among the patients, 93 were excluded. Of the remaining 581 patients, 71 (12%) received l‐carnitine supplementation. Propensity matching identified 189 patients (63
l‐carnitine–treated and 126 untreated patients) with comparable baseline characteristics in both groups. Of the matched patients, 33 (52%)
l‐carnitine–treated and 74 (59%) untreated patients died during the median follow‐up period of 36.3 months. Overall survival was significantly higher in
l‐carnitine–treated patients than in untreated patients (hazard ratio [HR], 0.66; 95% CI, 0.43–0.99). A subgroup analysis showed that the survival benefit of
l‐carnitine supplementation was prominent in patients with Child‐Pugh Class B or C (HR, 0.39; 95% CI, 0.23–0.68), serum albumin levels ≤3.5 g/dl (HR, 0.59; 95% CI, 0.37–0.95), and ammonia levels ≥90 mcg/dl (HR, 0.50; 95% CI, 0.26–0.97), and in those without sarcopenia (HR, 0.56; 95% CI, 0.35–0.90).

Conclusion

l‐Carnitine supplementation may improve survival in patients with cirrhosis.
Opportunity recognition and knowledge transfer in the champagne industry: A conceptual analysis
Authors: Atwal Glyn , Hultén Peter , Williams Alistair , Kaiser Maya
Published: May 2022

The distinctive advantage in an entrepreneurial venture derives from the adoption of embedded knowledge to create and renew cultural capital. Champagne houses pursue a knowledge transfer strategy to achieve a competitive advantage related to the cultural and managerial orientation of the defined champagne house cluster. The distinctive advantage in an entrepreneurial setup derives from adopting embedded knowledge within the organization to create and renew cultural capital.
Reflections on defining a standard for computable expression of scientific knowledge: What teach us Yoda can
Authors: Alper Brian S.
Published: May 2022

Science advances at a slow pace but can be accelerated with a standard for computable expression of scientific knowledge, more precisely a technical standard for electronic data exchange of machine‐interpretable data expressing scientific knowledge. Efforts to achieve this vision include Evidence‐Based Medicine on Fast Healthcare Interoperability Resources (EBMonFHIR), COVID‐19 Knowledge Accelerator (COKA), Computable Publishing LLC, Scientific Knowledge Accelerator Foundation, and the Fast Evidence Interoperability Resources (FEvIR) Platform. The vision for communicating scientific research results to be instantly found, viewed, sent, received, and incorporated into thousands of system is a Just‐in‐time Evidence Dissemination and Integration (JEDI) vision. Reflections on JEDI teachings in a fun way helps explain the focus on the “Resource” to make science computable, how a precise specification of evidence changes perspectives, the need to reset standard terminologies, the inclusive nature of efforts to achieve the vision, and the critical demand to realize the vision.
Mechanofluorochromic Difluoroboron β‐Diketonates Based Polymer Composites: Toward Multi‐Stimuli Responsive Mechanical Stress Probes
Authors: Poggi Benjamin , Lopez Elliot , Métivier Rémi , Bodelot Laurence , Allain Clémence
Published: May 2022

Developing mechano‐responsive fluorescent polymers that exhibit distinct responses to distinct mechanical stresses requires a careful design of the fluorophore in order to tune its interactions with the polymer. A series of mechanofluorochromic (MFC) polymer composites are prepared by dispersing difluoroboron diketonates complexes with various alkyl side‐chain lengths (DFB‐alkyl) in linear low‐density polyethylene. Observation of the resulting polymer composites under a microscope reveals different aggregate sizes of the three DFB‐alkyls, thus confirming the functionalization by alkyl side chains as a powerful approach to control the aggregation process in a polymer. Besides, the three polymer composite samples are shown to be sensitive to both stretching and scratching, thereby consisting in the first reported example of MFC polymer responding to these two distinct mechanical stimuli. To establish a structure–property relationship, the strategy consisted in applying controlled tensile or friction forces while simultaneously monitoring fluorescence changes. Interestingly, the intensity of the MFC response to both stretching and scratching depends on the alkyl chain length and thus on the aggregation properties of the fluorophore. According to a time‐resolved fluorescence study, the emission is found to originate from different species following the type of applied stress (tensile or friction force).
Transcriptome profiling reveals that VNPP433‐3β, the lead next‐generation galeterone analog inhibits prostate cancer stem cells by downregulating epithelial–mesenchymal transition and stem cell markers
Authors: Thomas Elizabeth , Thankan Retheesh S. , Purushottamachar Puranik , Huang Weiliang , Kane Maureen A. , Zhang Yuji , Ambulos Nicholas , Weber David J. , Njar Vincent C. O.
Published: May 2022

Cancer stem cells (CSCs) virtually present in all tumors albeit in small numbers are primarily responsible for driving cancer progression, metastasis, drug resistance, and recurrence. Prostate cancer (PCa) is the second most frequent cancer in men worldwide, and castration resistant prostate cancer (CRPC) remains a major challenge despite the tremendous advancements in medicine. Currently, none of the available treatment options are effective in treating CRPC. We earlier reported that VNPP433‐3β, the lead next‐generation galeterone analog is effective in treating preclinical in vivo models of CRPC. In this study using RNA‐seq, cytological, and biochemical methods, we report that VNPP433‐3β inhibits prostate CSCs by targeting key pathways critical to stemness and epithelial–mesenchymal transition. VNPP433‐3β inhibits CSCs in PCa, presumably by degrading the androgen receptor (AR) thereby decreasing the AR‐mediated transcription of several stem cell markers including BMI1 and KLF4. Transcriptome analyses by RNA‐seq, Ingenuity Pathway Analysis, and Gene Set Enrichment Analysis demonstrate that VNPP433‐3β inhibits transcription of several genes and functional pathways critical to the prostate CSCs thereby inhibiting CSCs in PCa besides targeting the bulk of the tumor.
Air temperature dependencies on the structure of thermometer screens in summer at Daejeon, South Korea
Authors: Park Jae‐Woo , Kim Joo‐Wan , Lee Sungjun , Kim Yong‐Gyoo
Published: May 2022

Results and accuracy of air temperature measurements made by meteorological thermometers hosted in thermometer screens strongly depend on the structure of the thermometer screen itself. In this study, the experiment was designed and conducted to understand the effect of radiation on air temperature observation. In order to control radiation sensitivity of thermometer screen, an umbrella made of Al alloy was installed over the thermometer screen (KTU). Air temperatures measured from five thermometer screens have been studied for several weather conditions using a 2‐month field experiment at Korea Research Institute of Standards and Science (KRISS). The experiments comprised two version of KRISS type, which artificially ventilated thermometer screen (KTE and KTU) and three naturally ventilated round‐shaped multi‐plate thermometer screens (BT1, BT2, VT). The results showed that the air temperature of the KTU was approximately 0.10–0.50°C lower than the other group of thermometer screens without an umbrella, which blocked direct solar radiation. During the night, the umbrella minimizes the longwave energy from the KTU to the atmosphere. So the air temperature was roughly 0.10–0.18°C higher than that of the other group without the umbrella. It is confirmed that the umbrella installed over the thermometer screen minimizes the radiation sensitivity of the thermometer screen, and it has a significant effect on air temperature measurements.
Existence of solution for a nonlinear fractional elliptic system at resonance and nonresonance
Authors: Dob Sara , Lekhal Hakim , Maouni Messaoud
Published: May 2022

In this article, we study the existence of a weak solutions for the nonlinear fractional elliptic systems with Dirichlet boundary conditions in three cases. We use the Leray–Schauder degree and some sufficient conditions for the solvability of a resonance and non‐resonance systems with respect to the spectrum of the fractional Laplacian.
Electric Current Detection Based on the MR Signal Magnitude Decay
Authors: Serša Igor
Published: May 2022

Purpose

Conventional current density imaging method, which relies on the detection of the magnetic field induced by the current in an image phase, is demanding and difficult to perform. In this study, a much simpler signal‐magnitude‐decay (SMD)–based current detection method is proposed.

Methods

Conductive test and biological samples were imaged at various TE times using the gradient‐ or spin‐echo imaging sequences with superimposed constant or bipolar currents, respectively. The SMD curve was sampled for each image voxel, which enabled voxel‐vise current density calculation by fitting an appropriate SMD model curve to the measured SMD curve. Effect of the voxel size on the signal decay and precision of the current density calculation was studied as well.

Results

It was shown theoretically, as well as verified by experiments on test and biological samples, that the current flowing though the sample creates an inhomogeneous magnetic field, which, as a consequence has a faster signal decay. Estimated current density from the measured signal decay increase agreed reasonably well with the actual current density, especially with the larger voxel sizes and longer times to signal acquisition. The sensitivity of the SMD method is up to the sensitivity of the current density imaging method.

Conclusion

SMD method of current detection is not limited to any particular sample orientation or geometry, and any pulse sequence capable of acquisition of the current‐induced signal evolution in a voxel can be used for it. This widens the scope of its application from tissues to in vivo studies on animals and humans.
One‐pot synthesis of high‐capacity silicon anodes via on‐copper growth of a semiconducting, porous polymer
Authors: Huang Jieyang , Martin Andréa , Urbanski Anna , Kulkarni Ranjit , Amsalem Patrick , Exner Moritz , Li Guiping , Müller Johannes , Burmeister David , Koch Norbert , Brezesinski Torsten , Pinna Nicola , Uhlmann Petra , Bojdys Michael J.
Published: May 2022

Silicon‐based anodes with lithium ions as charge carriers have the highest predicted theoretical specific capacity of 3579 mA h g−1 (for Li15Si4). Contemporary electrodes do not achieve this theoretical value largely because conventional production paradigms rely on the mixing of weakly coordinated components. In this paper, a semiconductive triazine‐based graphdiyne polymer network is grown around silicon nanoparticles directly on the current collector, a copper sheet. The porous, semiconducting organic framework (1) adheres to the current collector on which it grows via cooperative van der Waals interactions, (2) acts effectively as conductor for electrical charges and binder of silicon nanoparticles via conjugated, covalent bonds, and (3) enables selective transport of electrolyte and Li‐ions through pores of defined size. The resulting anode shows extraordinarily high capacity at the theoretical limit of fully lithiated silicon. Finally, we combine our anodes in proof‐of‐concept battery assemblies using a conventional layered Ni‐rich oxide cathode.

Key Points

We present a Si‐based anode with superior‐performance close to the limits of theoretical capacities with an advantage of factor ×10 over any hitherto produced, commercial electrode system.

Our electrodes sustain physical bending without surface reconstruction or crack formation, and heat shocks without loss of capacity and overall cycling performance.

The critical, novelty that enables the extraordinary performance increase and durability of our anodes is a class of semi‐conducting porous organic polymers that replaces all conventional additives in battery ink formulations.
Prone burials and evidence of interpersonal violence: A case study from early medieval Bavaria, Germany
Authors: Lee Ja Young , Zink Albert , Päffgen Bernd , Wolfseder‐Freitag Angelika , Harbeck Michaela , Trautmann Bernd
Published: May 2022

In early medieval times, the people of the Baiuvarii inhabited large parts of modern Bavaria (Germany). Among other evidence, about 10,000 graves dating from this time provide evidence of an exceptional level of settlement activity. These graves were arranged predominately in multiple parallel rows, so‐called Reihengräber, whereby the bodies were placed in stretched, supine positions. Burials that deviate from this custom are rarely found. For this reason, the excavation of a male skeleton at the cemetery of Aying‐Großhelfendorf (seventh to eighth centuries) attracted particular attention. The skeleton with label number 115 was found in a prone position and appears to have sustained four separate instances of sharp force trauma. The grave included a number of metal grave goods including a spatha and an iron shield boss. One focus of the study was on the macroscopic examination of the violence‐related lesions found on skeleton 115. They were located on the femur, the humerus, the frontal bone, and the maxilla on the right side of the body. The shape of the lesions indicates the insertion of a heavy, sharp, or bladed instrument. There is no evidence of healing detectable, leading to the conclusion that the individual was most likely involved in fight with fatal outcome. Subsequently, the victim was buried in a prone position alongside 17 other individuals in an otherwise regular graveyard. A possible interpretation of this difference in burial treatment is the fear of the victim's dependents of an unexpected or violent death or an expression of foreign origin. The aim of the paper is to present the most likely interpretation of the evidence in correlation with the anthropological and archaeological data.