bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of rivaroxaban versus placebo after lower extremity bypass surgery: A post hoc analysis of a “CASPAR like” outcome from VOYAGER PAD
Authors: Bonaca Marc P. , Szarek Michael , Debus E. Sebastian , Nehler Mark R. , Patel Manesh R. , Anand Sonia S. , Muehlhofer Eva , Berkowitz Scott D. , Haskell Lloyd P. , Bauersachs Rupert M.
Published: October 2022

Background

The Clopidogrel and Acetylsalicylic Acid in Bypass Surgery for Peripheral Arterial Disease (CASPAR) trial is the only large, double‐blind, placebo‐controlled trial of dual antiplatelet therapy (DAPT) versus aspirin in patients with peripheral artery disease (PAD) after lower extremity revascularization (LER). The trial was neutral for index‐graft occlusion/revascularization, amputation or death (hazard ratio [HR] 0.98, 95% confidence interval [CI] 0.78–1.23, p = .87) with an excess of global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries moderate or severe bleeding (HR 2.84, 95% CI 1.32–6.08, p = .007).

Hypothesis and Methods

VOYAGER‐PAD demonstrated that rivaroxaban significantly reduces acute limb ischemia (ALI), major amputation, myocardial infarction (MI), stroke and CV death but increased bleeding. The relative efficacy and safety of rivaroxaban in a CASPAR like population and for similar outcomes is unknown. The current analysis is a post‐hoc exploratory analysis of a “CASPAR like” composite of ALI, unplanned index limb revascularization (UILR), amputation or CV death in surgical patients.

Results

In the 2185 who underwent surgical LER, rivaroxaban reduced the CASPAR endpoint at 1 (HR 0.76, 95% CI 0.62−0.95, p = .0133) and 3 years (HR 0.84, 95% CI 0.71−1.00, p = .0461, Figure). There were similar reductions in composites of ALI, amputation or CV death (HR 0.79, p = .0228) and ALI, UILR, amputation, MI, IS or CV death (HR 0.85, p = .0410).

Conclusions

The combination of rivaroxaban and aspirin significantly reduces ischemic outcomes in patients with PAD after LER. Although no formal head‐to‐head comparison exists, in a similar population and for similar outcomes, this regimen demonstrated benefit where trials of DAPT were neutral. These data suggest that factor Xa inhibition may provide specific benefits in this population and that DAPT should not be considered a proven substitution.
Patients with completely resected nongenitourinary low‐risk embryonal rhabdomyosarcoma are candidates for reduced duration low‐intensity chemotherapy
Authors: Bisogno Gianni , Fuchs Joerg , Dasgupta Roshni , Ferrari Andrea , Haduong Josephine H. , Rogers Timothy , Walterhouse David O. , Coppadoro Beatrice , Xue Wei , Vokuhl Christian , Hawkins Douglas S. , Seitz Guido , Merks Johannes H. M. , Sparber‐Sauer Monika , Venkatramani Rajkumar
Published: October 2022

Background

The survival of patients with localized embryonal rhabdomyosarcoma (RMS) completely resected at diagnosis is greater than 90%. Most patients have paratesticular, uterine, or vaginal RMS, limiting specific analyses of RMS localized in other anatomic regions. This international study was conducted to define the outcome for completely resected embryonal RMS at sites other than paratesticular, uterine, or vaginal primary sites.

Methods

A total of 113 patients aged 0–18 years were identified who were enrolled from January 1995 to December 2016 in Children's Oncology Group (COG) (64 patients) and European protocols (49). Genitourinary nonbladder and prostate RMS were excluded. The recommended chemotherapy was vincristine and actinomycin‐D (VA) for 24 weeks or ifosfamide plus VA in the European protocols and VA for 48 weeks or VA plus cyclophosphamide in the COG protocols.

Results

The most common primary sites were nonparameningeal head and neck (40.7%), other (23.9%), and extremities (20.4%). In the COG studies, 42% of patients received VA and 58% VA plus cyclophosphamide. In Europe, 53% received VA and 47% ifosfamide plus VA. With a median follow‐up of 97.5 months, the 5‐year progression‐free and overall survival was 80.0% (71.2%–86.4%) and 92.5% (85.6%–96.2%), respectively, without significant differences between chemotherapy regimens. Tumor size (< or >5 cm) significantly influenced overall survival: 96.2% (88.6%–98.8%) vs. 80.6% (59.5%–91.4%), respectively (p = .01).

Conclusions

Survival of patients with nonalveolar RMS completely resected at diagnosis is excellent among tumors arising from nonparatesticular, uterine, and vaginal sites, and patients may be treated successfully with low‐intensity chemotherapy. To reduce the burden of treatment, VA for 24 weeks may be considered in children with tumors <5 cm.
Covalent Organic Frameworks Based Inorganic/Organic Composite Materials for Photocatalytic Applications
Authors: Xiao Mingjiao , Wei Yanze , Yu Ranbo
Published: October 2022

As a rising class of functional porous organic materials with tunable pore structures and flexible chemical environments, covalent organic frameworks (COFs) have demonstrated their tremendous potential in numerous applications, such as adsorption, water purification, heterogeneous catalysis, and organic electronics. In the field of photocatalytic applications, the association of emerging COFs with traditional inorganic catalysts can effectively combine the functionality of COFs with the stability of their inorganic counterparts to construct efficient and stable composite photocatalysts. A rapidly growing new field has been established regarding COFs‐based inorganic/organic hybrid photocatalysts, which call for a timely review to summarize recent developments. In this contribution, we revisit this promising composite photocatalysts by emphasizing some recent breakthroughs in synthetic strategies and the enhanced performance in various photocatalytic applications. Simultaneously, the mechanisms of performance improvement are elucidated by analyzing the interactions between the inorganic and organic counterparts. We hope general tactics could be inspired for directing open considerations for the future design of photocatalysts and their practical implementations.
Pharmacokinetic and Pharmacodynamic Modeling and Simulation Analysis of Prasugrel in Healthy Male Volunteers
Authors: Kim Mi‐Jo , Kim Hyungsub , Lee Sang‐Min , Choi Hee‐Youn , Kim Yo‐Han , Choi Seung Chan , Kim Eun‐Hwa , Park Hyun‐Jung , Lim Hyeong‐Seok
Published: October 2022

This study evaluated the pharmacokinetics and pharmacodynamics of the antiplatelet agent prasugrel, and explored its optimal dose regimens via modeling and simulation using NONMEM. We measured platelet aggregation and the serial plasma concentrations of the inactive (R‐95913) and active metabolites (R‐138727) of prasugrel after a single oral dose of 10–60 mg in 20 healthy adult male volunteers. A pharmacokinetic model for R‐95913 and R‐138727, and a pharmacodynamic model between the concentration of R‐138727 and maximal platelet aggregation measured by light transmittance were constructed. The predictability of the model for platelet aggregation was evaluated by comparing the model prediction values with the observed ones not used in the construction of the model. Pharmacokinetic data were best described by a 3‐compartment models for R‐95913, a 1‐compartment model for R‐138727 with transit compartment model for absorption delay, and first‐pass metabolic conversion of R‐95913 into R‐138727 during absorption. The association–dissociation model between R‐138727 and its receptor in platelets was applied for the inhibitory effect of prasugrel on platelet aggregation. Prasugrel rapidly inhibited platelet aggregation after oral administration, with a prolonged duration of action; however, the concentration of the active metabolite decreased rapidly, which may have been due to the slow dissociation rate of R‐138727 from its target receptor in platelets. The external validation suggests that our model could be used to individualize prasugrel treatment in various clinical situations. Simulation showed rapid onset of inhibitory effect with great magnitude and consistent inhibition after therapeutic dose of prasugrel.
Deep neural network based interactive fuzzy Bayesian search algorithm for low‐cost smart farming automation model
Authors: Sivaraj Aparna , Palanisamy Valarmathie
Published: October 2022

One of the most significant factors that influence the globalized economy is agriculture. In order to address the requirement of increasing populations in terms of food necessities, modernizations and technological progressions in agriculture, it is necessary to implement a smart agricultural system. Various traditional techniques are still utilized by the farmers and their intuition in agriculture is not enough to furnish and deliver various issues namely soil management, plant disease identification, weed management, irrigation management, and so forth. Therefore, in this paper, a low‐cost smart farming automation system is evaluated and presented. Since the development of a smart farming automation system minimizes the labor cost and enhances agricultural production level, this paper proposes a deep neural network based Interactive fuzzy Bayesian search (DNN‐IFBS) algorithm for a low‐cost smart farming automation system. In addition to this, the crop water stress index (CWSI) is computed to determine the water status of the plant by employing solar irradiation, canopy temperature, and so forth. The data for analysis is collected simultaneously from three cameras containing image resolutions of about 650 × 460 pixels each. Two different plants namely the melon and sesame are utilized as datasets for experimentation. Finally, the performances of the proposed approach are determined according to the statistical performance measures namely accuracy, specificity as well as F‐measure. The comparative analysis is carried out to evaluate the effectiveness of the proposed system. From the evaluation results, the accuracy rate obtained for the proposed approach is 98.7%.
Optimal AdaBoost kernel support vector machine for monitoring arrhythmia patients utilizing Internet of Things‐cloud environment
Authors: Hemalatha M.
Published: October 2022

In general, heart disease is considered as the most severe disease that results in high mortality rate globally. An arrhythmia is one type of heart disease caused due to asymmetrical heartbeat rhythm rate (i.e., heartbeat will be too slow or too fast). The generation of IoT devices as well as ECG signals is capable of tracking the heart rhythm of the patients consistently. Even though, analyzing ECG signals using cloud‐based techniques achieves a certain accuracy level with high latency. Then by evaluating the ECG signals with fog‐based approaches minimizes the latency but the computing capability is minimum. Therefore, wearable devices and fog devices are linked directly to attain high service quality with minimum latency. To conquer such drawbacks, this article proposes a novel AdaBoost kernel support vector machine‐based remora optimization (AKSVM based RO) algorithm to analyze the ECG signals and to initiate the crisis with minimum time delay. The proposed approach predicts the ECG signals of arrhythmia affected persons from an IoT wearable device. In addition to this, the proposed AKSVM‐RO approach is more feasible to deploy in fog environment. Also, it assists in optimizing the time delay in calling the ambulance service during emergency situations. Finally, the experimental investigations are conducted for various approaches with respect to simulation measures to minimize the latency and accuracy of the proposed system.
Comparison between ozone and CHX gel application for reduction of pain and incidence of dry socket after lower third molar removal
Authors: Ahmedi Jehona , Agani Zana , Ademi Abdyli Resmije , Prekazi Loxha Mergime , Hamiti‐Krasniqi Vjosa , Rexhepi Aida , Stubljar David
Published: October 2022

Objectives

The aim of this study is to evaluate the efficacy between ozone gas and 1% chlorhexidine (CHX) gel in the incidence of dry socket after surgical extraction of impacted lower third molars.

Material and Methods

Overall, 30 patients of both genders were included in the study, with indication of surgical extraction of lower third molar, positioned similarly after being clinically and radiographically checked by X‐ray and orthopantomography. Each patient was subjected to both groups in separate sessions: treated with ozone gas and with CHX gel 1%. Data on pain intensity, number of taken analgesics‐painkillers, and dry socket were recorded for 48 h and at Day 7.

Results

Ozone gas and CHX gel effectively reduced pain intensity and prevented dry socket. The number of taken analgesics 48 h and 7 days after surgery showed no statistical significance. The same was observed for the distribution of pain. Only one patient reported the occurrence of dry socket 7 days after the surgical extraction.

Conclusions

Ozone gas and CHX 1% gel are both efficient in decreasing postoperative symptoms and incidence rates of dry socket, but in comparison to each other, the use of ozone gas is showing a bit better prevention capability.
N,N‐Diformylmescaline: A novel analogue of mescaline detected in Queensland
Authors: Gallagher Ryan , McLaughlin Maddison G. , Blakey Karen , Wermuth Urs D. , Boyd Sue , McGowan Jenny
Published: October 2022

N,N‐Diformylmescaline, a novel analogue of mescaline, has recently been detected in Australia in two unrelated seizures. To confirm the identification, a three‐step synthesis from 3,4,5‐trimethoxyphenylacetic acid was devised. However, purification of the final product proved problematic with the compound prone to degradation in solution. Analysis of the compound by LC–MS indicated that the compound was unstable under acidic and basic conditions, breaking down to N‐formylmescaline. Further degradation to mescaline was observed when the compound was dissolved in hydrochloric acid for an extended period of time suggesting that N,N‐diformylmescaline may be a prodrug for mescaline. The GC–MS, NMR and FTIR data for the seized compound are presented along with details of the synthesis and studies of the compound's stability in solution.
High predation risk decimates survival during the reproduction season
Authors: Smolinský Radovan , Hiadlovská Zuzana , Maršala Štěpán , Škrabánek Pavel , Škrobánek Michal , Martínková Natália
Published: October 2022

Predators attack conspicuous prey phenotypes that are present in the environment. Male display behavior of conspicuous nuptial coloration becomes risky in the presence of a predator, and adult males face higher predation risk. High predation risk in one sex will lead to low survival and sex ratio bias in adult cohorts, unless the increased predation risk is compensated by higher escape rate.

Here, we tested the hypothesis that sand lizards (Lacerta agilis) have sex‐specific predation risk and escape rate. We expected the differences to manifest in changes in sex ratio with age, differences in frequency of tail autotomy, and in sex‐specific survival rate.

We developed a statistical model to estimate predation risk and escape rate, combining the observed sex ratio and frequency of tail autotomy with likelihood‐based survival rate. Using Bayesian framework, we estimated the model parameters. We projected the date of the tail autotomy events from growth rates derived from capture–recapture data measurements.

We found statistically stable sex ratio in age groups, equal frequency of tail regenerates between sexes, and similar survival rate. Predation risk is similar between sexes, and escape rate increases survival by about 5%. We found low survival rate and a low number of tail autotomy events in females during months when sand lizards mate and lay eggs, indicating high predator pressure throughout reproduction. Our data show that gravid females fail to escape predation.

The risks of reproduction season in an ectotherm are a convolution of morphological changes (conspicuous coloration in males and body allometry changes in gravid females), behavior (nuptial displays), and environmental conditions which challenge lizard thermal performance. Performance of endotherm predators in cold spring months endangers gravid females more than displaying males in bright nuptial coloration.
Attenuation band impedance matched BRF for measurements of electromagnetic noise
Authors: Hayashi Jun , Nikawa Yoshio
Published: October 2022

Wireless communication devices such as wireless LANs and RFIDs are essential for smart home appliances and IoT (Internet of Things) devices in Smart Cities. When measuring the high‐frequency noise generated by devices, wireless signals of wireless communication devices and high‐frequency noise are measured at the same time. As a result, spectrum analyzers have insufficient dynamic range, or the excess signal from wireless communication devices causes harmonic distortion of the mixer inside the receiver, resulting in inaccurate measurements. Accordingly, a band rejection filter (BRF) is required to attenuate the radio signal. CISPR 16‐2‐3:2016+A1: 2019 assumes that impedances are matched for measurement, so if the impedance mismatch is large, the expanded uncertainty specified in CISPR 16‐4‐2:2011+A1:2014+A2:2018 increases. In this study, we propose a new BRF with impedance matching in the attenuation range and show its principle. As a result, the extended uncertainty could be reduced to 3.96 dB for the BRF of this study compared to 10.63 dB for the conventional BRF. In addition, the method comparison of CISPR 16‐2‐3:2016+A1: 2019 and vector network analyzer shows that the difference in attenuation of the conventional BRF was about −0.8 to 3.3 dB, whereas the BRF in this study were about −0.2 to 0.3 dB. The reduction of the expanded uncertainty and the good measurement results confirm the high usefulness of the CISPR 16‐2‐3 measurement system for the measurement of weak electromagnetic noise.
Evaluation of potential for peak demand reduction of residential buildings by household appliances with demand response
Authors: Ono Tetsushi , Hagishima Aya , Tanimoto Jun
Published: October 2022

Residential appliances remotely controlled by IoT for demand response has attracted much attention for effective peak demand reduction of the uncertainty of consumers’ behaviors. To promote the technology development of such appliances, estimation of the potential for peak demand reduction according to the type of appliances is strongly needed. With this background, the authors conducted a data analysis of demand curves of not only the entire household but also the branches acquired at 496 dwellings in Osaka. Based on this analysis, the potential of peak reduction of aggregated demand of various groups with different dwelling size were quantified for major five appliances, namely air conditioners, microwave ovens, refrigerators, washing machines, and dish washers.
Grassland management actions influence soil conditions and plant community responses to winter climate change
Authors: Henn Jonathan J. , Damschen Ellen I.
Published: October 2022

Restoring ecosystems in a changing climate requires understanding how management interventions interact with climate conditions. In tallgrass prairies, disturbance through fire, mowing, or grazing is a critical force in maintaining herbaceous plant diversity. However, unlike historical fire regimes that occurred throughout the growing season, management actions like prescribed fire and mowing are commonly limited to the spring or fall seasons. Warming winters are resulting in less snow, causing overwintering plants to experience reduced insulation from snow and these more extreme winter conditions may be exacerbated or ameliorated depending on the timing of management actions. Understanding this novel interaction between the timing of management actions and snow depth is critical for managing and restoring grassland ecosystems. Here, we applied experimental management treatments (spring and fall burn and fall mow) in combination with snow depth manipulations to test whether the type and timing of commonly implemented disturbances interact with snow depth to affect restored prairie plant diversity and composition. Overall, snow manipulations and management actions influenced soil temperature while only management actions influenced spring thaw timing. Burning in the fall, which removes litter prior to winter resulted in colder soils and earlier spring thaw timing. However, plant communities were mostly resistant to these effects. Instead, plants responded to management actions such that burning and mowing, regardless of timing, increased plant diversity and spring burning increased flowering structure cover while reducing weedy cool season grass cover. Together these results suggest that grassland plant communities are resistant to winter climate change over the short term and that burning or mowing is critical to promoting plant diversity in tallgrass prairies.
Right ventricular dysfunction in patients with new‐onset heart failure: longitudinal follow‐up during guideline‐directed medical therapy
Authors: Ansari Ramandi Mohammad Mostafa , van Melle Joost P. , Gorter Thomas M. , Hoendermis Elke S. , van Veldhuisen Dirk J. , Nauta Jan F. , van der Wal Martje H.L. , Warink‐Riemersma Janke , Voors Adriaan A. , Dickinson Michael G.
Published: October 2022

Aims

Improvement in left ventricular ejection fraction (LVEF) after up‐titration of guideline‐directed medical therapy (GDMT) has been well described in heart failure (HF) patients. Less is known about the prevalence and clinical course of right ventricular dysfunction (RVD) in patients with new‐onset HF.

Methods and results

From 2012 to 2018, 625 patients with a recent (<3 months) diagnosis of HF were referred to a specialized nurse‐led HF clinic for protocolized up‐titration of GDMT. RVD, defined as tricuspid annular plane systolic excursion (TAPSE) <17 mm, was assessed at baseline and at the follow‐up visit. Patients were followed for the combined endpoint of all‐cause mortality and HF hospitalization for a mean of 3.3 ± 1.9 years. Of the 625 patients, 241 (38.6%) patients had RVD at baseline. Patients with RVD were older, more symptomatic, had a lower LVEF, and more often had a history of cardiothoracic surgery and atrial fibrillation. After a median follow‐up of 9 months, right ventricular function normalized in 49% of the patients with baseline RVD. RVD at baseline was associated with a higher risk of the combined endpoint (hazard ratio [HR] 1.62, 95% confidence interval [CI] 1.21–2.18). Right ventricular function normalization was associated with a lower risk for the combined endpoint (HR 0.56, 95% CI 0.31–0.99), independent of baseline TAPSE, age, sex, and LVEF.

Conclusion

More than one‐third of patients with new‐onset HF have RVD. RVD is associated with a higher risk of all‐cause mortality and HF hospitalization. Recovery of RVD regularly occurs during up‐titration of GDMT and is associated with improved clinical outcomes.
Acute cytomegalovirus infection modulates the intestinal microbiota and targets intestinal epithelial cells
Authors: Le‐Trilling Vu Thuy Khanh , Ebel Jana‐Fabienne , Baier Franziska , Wohlgemuth Kerstin , Pfeifer Kai Robin , Mookhoek Aart , Krebs Philippe , Determann Madita , Katschinski Benjamin , Adamczyk Alexandra , Lange Erik , Klopfleisch Robert , Lange Christian M. , Sokolova Viktoriya , Trilling Mirko , Westendorf Astrid M.
Published: October 2022

Primary and recurrent cytomegalovirus (CMV) infections frequently cause CMV colitis in immunocompromised as well as inflammatory bowel disease (IBD) patients. Additionally, colitis occasionally occurs upon primary CMV infection in patients who are apparently immunocompetent. In both cases, the underlying pathophysiologic mechanisms are largely elusive ‐ in part due to the lack of adequate access to specimens. We employed the mouse cytomegalovirus (MCMV) model to assess the association between CMV and colitis. During acute primary MCMV infection of immunocompetent mice, the gut microbial composition was affected as manifested by an altered ratio of the Firmicutes to Bacteroidetes phyla. Interestingly, these microbial changes coincided with high‐titer MCMV replication in the colon, crypt hyperplasia, increased colonic pro‐inflammatory cytokine levels, and a transient increase in the expression of the antimicrobial protein Regenerating islet‐derived protein 3 gamma (Reg3γ). Further analyses revealed that murine and human intestinal epithelial cell lines, as well as primary intestinal crypt cells and organoids represent direct targets of CMV infection causing increased cell death. Accordingly, in vivo MCMV infection disrupted the intestinal epithelial barrier and increased apoptosis of intestinal epithelial cells. In summary, our data show that CMV transiently induces colitis in immunocompetent hosts by altering the intestinal homeostasis.
Synthesis and Reactivity of Weiss Diketone Derivative Bearing Four Phenylsulfanyl Groups
Authors: Yasui Kosuke , Isogai Ryosuke , Fukazawa Aiko
Published: October 2022

A bicyclo[3.3.0]octane‐3,7‐dione, bearing four phenylsulfanyl (PhS) groups at the diagonal α‐positions of the carbonyls, was synthesized as a key intermediate useful for exploring the regioselective transformations of symmetrical Weiss diketone. Tetra‐PhS‐substituted bicyclo[3.3.0]octane‐3,7‐dione was prepared by deprotonation of the Weiss diketone, using LDA in the presence of PhSSO2Ph. The tetra‐PhS‐substituted derivative thus obtained served as a scaffold for further regioselective base‐promoted enolization. Furthermore, the tetra‐PhS‐substituted Weiss diketone underwent an unexpected base‐promoted rearrangement to form isomeric tetra‐PhS‐substituted bicyclo[3.3.0]octane‐3,7‐dione through migration of PhS groups, likely through an interrupted Favorskii rearrangement.
Soil erosion rates during the Holocene continuity in a forest‐steppe landscape
Authors: Püntener Dario , Šamonil Pavel , Tikhomirov Dmitry , Daněk Pavel , Christl Marcus , Roleček Jan , Egli Markus
Published: October 2022

Despite a long‐term human impact, Central and Eastern Europe exhibit patches of steppe ecosystems having the highest plant species diversity worldwide. These unique ecosystems have persisted over millennia even though the local climatic conditions would support the formation of a closed forest. Several sources of disturbances have contributed to the persistence of the forest‐steppe landscape such as grazing, fire events and human impact. These disturbances have been recorded in local erosion rates. To gain a deeper understanding of the soil dynamics we aimed at deciphering the long‐ and short‐term erosion rates and the age of the soil mantle.

The steppes in Transylvania, Romania, were studied to find evidence of a Holocene continuity of grasslands. Long‐term (millennia) average erosion rates were determined using meteoric 10Be in soils and in situ 10Be of rock outcrops (scarp). Long‐term rates were also estimated by the percolation theory. Short‐term (last few decades) erosion rates were obtained from 239+240Pu in soils. The soils started to form prior to the Last Glacial Maximum, probably during the Eemian Interglacial. The average, long‐term erosion rates varied between 0.18 and 0.63 t ha−1 yr−1. These rates are slightly elevated compared to expected soil erosion rates. The soils of the Transylvanian Plain formed over a long period and reached a quasi‐steady state (soil production equals denudation) that contributed to the maintenance of a biodiversity‐rich forest‐steppe landscape. The slightly elevated erosion rates are an effect of factors that contributed to the Holocene continuity (fire, grazing) and indicate open rather than a forested character of the landscape during soil development. During the last few decades, the erosion rates increased by a factor of 5–10, with values in the range of 1.31–4.05 t ha−1 yr−1. These large differences are caused by changes in human management of the soils. The biodiversity‐rich forest‐steppe landscapes are now under threat.
Inferring cultural reproduction from lithic data: A critical review
Authors: Liu Cheng , Stout Dietrich
Published: October 2022

The cultural reproduction of lithic technology, long an implicit assumption of archaeological theories, has garnered increasing attention over the past decades. Major debates ranging from the origins of the human culture capacity to the interpretation of spatiotemporal patterning now make explicit reference to social learning mechanisms and cultural evolutionary dynamics. This burgeoning literature has produced important insights and methodological innovations. However, this rapid growth has sometimes led to confusion and controversy due to an under‐examination of underlying theoretical and methodological assumptions. The time is thus ripe for a critical assessment of progress in the study of the cultural reproduction of lithic technology. Here we review recent work addressing the evolutionary origins of human culture and the meaning of artifact variation at both intrasite and intersite levels. We propose that further progress will require a more extended and context‐specific evolutionary approach to address the complexity of real‐world cultural reproduction.
Computational homogenization of unsteady flows with obstacles
Authors: Shakoor Modesar , Park Chung Hae
Published: October 2022

Modeling flows in domains containing obstacles becomes challenging when the obstacles are very small compared to the domain. This problem is often known as modeling flow through permeable or porous media. Darcy's law is well known to provide a robust solution to this problem for viscous flows, given that the permeability of the medium can be characterized. Solutions for inertial flows have not been proposed yet. In this article, a principle multiscale virtual power is formulated for the computational homogenization of unsteady incompressible flows in domains containing small obstacles. In this theory, the coarse scale of the domain is separated from the fine scale of the obstacles. The finite element (FE) implementation of this theory is developed in the form of a parallel (FE) algorithm with two‐way coupling between the two scales. The incompressibility constraint is handled with special care by introducing an independent pressure variable at both scales and relying on the Taylor–Hood P2/P1 pair. Simulations are conducted to analyze the accuracy and efficiency of the proposed multiscale approach. The results show that the method is robust and interesting from both the points of view of computational cost and accuracy when the ratio between the domain size and the obstacle size is larger than 100.
Ursolic acid enhances the effect of exercise training on vascular aging by reducing oxidative stress in aged type 2 diabetic rats
Authors: Kazemi Pordanjani Masume , Banitalebi Ebrahim , Roghani Mehrdad , Hemmati Roohullah
Published: October 2022

Ursolic acid (UA) mediates the vasorelaxant activity via nitric oxide (NO) release, and upregulation of endothelial nitric oxide synthase (eNOS) in endothelial cells (ECs) in disease conditions with increased oxidative stress (OS). The present study aimed to reflect on the impact of 8 weeks of a combination of UA supplementation and resistance/endurance training in old male Wistar rats having a high‐fat diet and/or low‐dose streptozotocin‐induced type 2 diabetes (HFD/STZ‐induced T2D), with an emphasis on Sirtuin 1 (SIRT1)–endothelial nitric oxide synthase (eNOS) axis and OS indices in their aortic tissues. A total number of56 21‐month‐old male Wistar rats with HFD/STZ‐induced T2D were randomized into seven groups (n = eight animals per group): (1) sedentary old nondiabetic (Control [C]); (2) sedentary HFD/STZ‐induced T2D (Diabetic [D]); (3) sedentary HFD/STZ‐induced T2D plus UA (Diabetic + Ursolic Acid [DU]); (4) endurance‐trained HFD/STZ‐induced T2D (Diabetic + Endurance Training [DE]); (5) resistance‐trained HFD/STZ‐induced T2D (Diabetic + Resistance Training [DR]); (6) endurance‐trained HFD/STZ‐induced T2D plus UA (Diabetic + Endurance Training + Ursolic Acid [DEU]); and (7) resistance‐trained STZ–diabetic plus UA (Diabetic + Resistance Training + Ursolic Acid [DRU]) rats. The ladder‐based resistance training group performed the ladder resistance training at 60% of the maximum voluntary carrying capacity (MVCC), 14–20 climbs in each session, with a one‐min rest between each two trials, 5 days a week. The treadmill‐based endurance exercise training protocol consisted of repeated bouts of high‐ and low‐intensity training with 60–75% maximal running speed and 30%–40% maximal running speed in the course of 8 weeks, respectively. The animals in the supplement groups also took 500 mg of UA/kg of high‐fat diet/day, resulting in a daily UA intake of approximately 250 mg UA per kg of body weight rat/day. The resistance/endurance training plus the UA consumption could partially reverse the levels of malondialdehyde (MDA), nitric oxide (NO), as well as total antioxidant capacity (TAC). It was concluded that oral 0.5% UA supplementation can prevent vascular aging biomarkers in a HFD/STZ‐induced T2D model. Further studies are also required to clarify how chronic consumption of UA with/without training protocols reverses vascular aging process.
Clinical and demographic predictors of survival for fibrolamellar carcinoma patients—A patient community, registry‐based study
Authors: Berkovitz Amichai , Migler Rachael D. , Qureshi Adam , Rosemore Carly , Torbenson Michael S. , Vaughan Roger , Marcotte Erin , Simon Sanford M.
Published: October 2022

Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary liver cancer that affects primarily adolescents and young adults. It is associated with a poor overall prognosis. There is a need to better define risk factors, but small sample size has limited such studies. An FLC patient registry now provides data sufficient for statistically robust inferences. We leveraged a unique patient community–based FLC registry to analyze the prognostic impact of demographic and clinical characteristics evident at diagnosis. Variables were analyzed using Cox proportional hazards regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). In multivariable models of 149 patients (88 females and 61 males), female gender was associated with statistically significant improved survival with HR of 0.52 (95% CI 0.29–0.93). Factors evident at diagnosis that are associated with worse survival included the presence of 10 or more tumors within the liver (HR 7.1; 95% CI 2.4–21.04), and metastases at diagnosis (HR 2.17; 95% CI 1.19–3.94). Positive lymph nodes at diagnosis, despite being found significantly associated with worse survival in a univariate analysis, did not remain significant when adjusted for covariates in a multivariable analysis. We found no statistically significant effect of age at diagnosis nor tumor size at diagnosis on survival. Female gender may confer a favorable prognosis in FLC. Established high‐risk prognostic factors that we confirmed in this Registry included the diagnostic presence of numerous intrahepatic tumors, and metastases. This is the first study derived from a FLC patient community–based registry, and highlights how registries of rare tumors can empower patients to meaningfully advance clinical and scientific discoveries.
Late toxicity comparison of alkylating‐based maintenance regimen with cyclophosphamide (VAC) vs ifosfamide (VAI) in Ewing sarcoma survivors treated in the randomized clinical trial Euro‐EWING99‐R1 in France
Authors: Corvest Victoria , Marec‐Bérard Perrine , Lervat Cyril , Pacquement Hélène , Toulmonde Maud , Gentet Jean‐Claude , Laurence Valérie , Cleirec Morgane , Mansuy Ludovic , Bompas Emmanuelle , Castex Marie‐Pierre , Taque Sophie , Filhon Bruno , Tabone Marie‐Dominique , Verité Cécile , Entz‐Werle Natacha , Saumet Laure , Guimard Gregory , Pondrom Morgane , Chevreau Christine , Flandrin Jennifer , Duranteau Lise , Rousset‐Jablonski Christine , Brugières Laurence , Jimenez Marta , Le Deley Marie‐Cécile , Gaspar Nathalie , Fresneau Brice
Published: October 2022

In Euro‐EWING99‐R1 randomized trial, cyclophosphamide was shown to be noninferior to ifosfamide in the consolidation of standard‐risk Ewing sarcoma (SR‐EWS) after a common induction with VIDE (vincristine‐ifosfamide‐doxorubicin‐etoposide). We present the results of the late effects analysis of VAC (vincristine‐dactinomycin‐cyclophoshamide) vs VAI (vincristine‐dactinomycin‐ifosfamide) conducted in Euro‐EWING99‐R1 French cohort. Of 267 French randomized patients, 204 were alive and free‐of‐relapse at 5‐years including 172 with available long‐term follow‐up data concerning cardiac, renal and/or gonadal functions (sex‐ratio M/F = 1.3, median age at diagnosis = 14 years): 84 randomized in VAC (median cumulative doses: cyclophosphamide = 9.7 g/m2, ifosfamide = 59.4 g/m2) and 88 in VAI (ifosfamide = 97.1 g/m2). With a median follow‐up of 10 years (range = 5‐17), five late relapses and five second malignancies were recorded. The 10‐year event‐free survival among 5‐year free‐of‐relapse survivors was similar between VAC and VAI (93% vs 95%, P = .63). We estimated the 10‐year cumulative probabilities of cardiac and kidney toxicities at 4.4% (95% confidence interval [95% CI] = 1.1%‐7.6%) and 34.8% (95% CI = 26.8%‐42.0%), respectively. Cardiac toxicity cumulative probability was similar in both arms, whereas kidney toxicity was higher in VAI (at 10 years, 43.0% vs 25.7%, P = .02), resulting from significant difference in glomerular toxicity (31.1% vs 13.1%, P < .01). At 10 years, gonadal toxicity was observed in 27% and 28% of pubertal men and women, respectively, without significant difference between VAC and VAI. Kidney and gonadal toxicities represent major issues in Euro‐EWING99‐R1, with significantly higher risk of kidney toxicities with VAI, without significant gonadal toxicity reduction. These results support the need to limit cumulative doses of both alkylating agents and to use mixed regimen as in VIDE‐VAC or VDC/IE (vincristine‐doxorubicin‐cyclophoshamide/ifosfamide‐etoposide).
Co‐constructing meaning: Parents and children navigating digital literacies together
Authors: Turner Kristen Hawley , Stevens Elizabeth Years , Paciga Kathleen , O'Byrne W. Ian
Published: October 2022

This article documents a collaborative inquiry between four parent–child dyads. Adopting an approach of duoethnography, the collaborative explored the question, “What happens when parents and children co‐construct meaning regarding the challenges and opportunities in using digital technologies?” By positioning youth as co‐researchers, the teams disrupted traditional hierarchical power structures in their homes. The inquiry uncovered a process of building mutual trust through open communication and mediated decision making that empowered adolescents to critique adults' and peers' technology practices while reflecting on their own literacy development.
Photonic sensor to detect rapid changes in CRP levels
Authors: Szczerska Małgorzata , Kosowska Monika , Viter Roman , Wityk Paweł
Published: October 2022

One of the most important biomarkers used to determine inflammation is C‐reactive protein (CRP). Its level, when it is within the range that does not define inflammation, informs about the risk of cardiovascular events. If the norm is exceeded and inflammation is detected in the body, CRP level can increase 1000 times within a few hours. The type of infection can also be determined based on the level of elevated CRP. All this makes CRP a very important element of diagnostics. A sensor based on low coherence interference is presented. Preliminary studies have shown that its sensitivity is 5.65 μg/L and the measurement time is short, <10 min. The entire system is built of commercially available components, which allow production cost minimalization. In addition, the user‐friendly operation allows it to be operated by unqualified people. Due to these features, our solution is a promising alternative to commercially used enzyme‐linked immunosorbent assay, which needs trained personnel to perform time‐consuming measurement procedures.
In vitro and in vivo evaluation of surface functionalization of titanium with H2O2 hydrothermal treatment and FGF‐2
Authors: Yoneyama Yuya , Matsuno Tomonori , Fujioka‐Kobayashi Masako , Satomi Takafumi
Published: October 2022

The goals of the study were to investigate the effects on bone bioactivity of a titanium dioxide layer formed by hydrothermal oxidation of a titanium surface with hydrogen peroxide (H2O2) and loading with fibroblast growth factor‐2 (FGF‐2) in vitro and in vivo. Ti‐6Al‐4V discs were hydrothermally oxidized with H2O2 and then loaded with FGF‐2. After cytotoxicity testing, Ti‐6Al‐4V mini‐implants were subjected to the same treatment, and their osteogenic potential was evaluated histologically in a rat model. H2O2 hydrothermal oxidation resulted in a dense porous network structure and hydrophilic changes, which improved retention of FGF‐2. Morphologically, the cell density was higher, cell elongation was more pronounced, and the cell adhesion area was significantly higher in FGF‐2‐loaded cells than in those without FGF‐2. In a cell proliferation assay using mouse osteoblast‐like cells, absorbance tended to increase over time, especially in the FGF‐2 group after 7 and 14 days, and in a bone differentiation assay based on ALP activity, there was a significant increase in the FGF‐2 group after 14 days. In the rat model, H2O2 hydrothermal oxidation and FGF‐2 loading both resulted in more laminar bone tissue in the bone marrow around the mini‐implant. These results suggest that titanium surface functionalization by H2O2 hydrothermal oxidation and FGF‐2 may promote initial cell adhesion, proliferation, and osteodifferentiation, and enhance bone bioactivity. These effects all contribute to early bonding of an implant with the surrounding bone.
Detection of interstitial pneumonia with autoimmune features and idiopathic pulmonary fibrosis are enhanced by involvement of matrix metalloproteinases levels and clinical diagnosis
Authors: Liu Mingtao , Xue Mingshan , Zhang Teng , Lin Runpei , Guo Baojun , Chen Youpeng , Cheng Zhangkai J. , Sun Baoqing
Published: October 2022

Background

Higher detection of interstitial pneumonia with autoimmune features (IPAF), and idiopathic pulmonary fibrosis (IPF), has significant diagnostic and therapeutic implications. Some matrix metalloproteinases (MMPs) have become reliable diagnostic biomarkers in IPAF and IPF in previous studies, yet relevant reliability remains to be recognized.

Materials and Methods

In this study, 36 ILDs patients, including 31 IPAF patients (Mean ± SD, 50.20 ± 5.10 years; 16 [51.6%] females) and five IPF patients (Mean ± SD, 61.20 ± 6.73 years; one [20.0%] females) were retrospectively enrolled. Serial serum samples were collected from patients with IPAF and IPF between January 2019 and December 2020. Notably, Serum MMPs levels were measured by U‐PLEX Biomarker Group 1(Human) Multiplex Assays (MSD, USA).

Results

A combination of MMPs and combinatorial biomarkers was strongly associated with clinical subjects in this study (AUC, 0.597 for Stability vs. Improvement and 0.756 for Stability vs. Exacerbation). Importantly, the AUC of MMP‐12 reaches 0.730 (p < 0.05, Stability AUC vs. Improvement AUC) while MMP‐13 reaches 0.741 (p < 0.05, Stability AUC vs. Exacerbation AUC) showed better performance than other MMPs in two comparisons.

Conclusions

Clinical risk factors and MMPs are strongly associated with either stratification of the disease of progression of IPAF or in two IPAF and IPF independent cohorts. To our knowledge, this is the first to illustrate that MMP‐12 and MMP‐13 may be expected to become typical promising biomarkers in Improvement – IPAF and Exacerbation – IPAF, respectively.
Socioeconomic status and access to psychotherapy
Authors: Niemeyer Helen , Knaevelsrud Christine
Published: October 2022

Objective

Individuals with low socioeconomic status (SES) have significantly higher prevalence rates of mental disorders than those with higher SES, but are less likely to receive treatment. Studies from the United States show that individuals with higher SES are more likely to be offered a therapy place than those with low SES. In Germany, where the public health care system is without financial barriers, studies on access to treatment are lacking.

Method

The present study investigated whether the SES of persons seeking psychotherapeutic help in Germany influences psychotherapists' decision to provide access to treatment. For this purpose, 504 licensed outpatient psychological psychotherapists participated in an online study, in which they read a series of case vignettes and rated how likely they would be to offer treatment in each case. SES was operationalized by occupation and language use. Additionally, we investigated whether treatment offers were affected by the disorder and the gender of the help seeker, the therapists' socioeconomic background, and other characteristics in interaction with SES. Bonferroni‐corrected multifactorial repeated measures analysis of variances (ANOVAs) and mixed ANOVAs were calculated.

Results

Help seekers with low SES were 4.1% less likely to be offered treatment than those with moderate to high SES (F (1, 503) = 115.64; p = 0.000; η² =  0.187). The influence of SES on the probability of a therapy place offer varied significantly depending on the patient's disorder (p = 0.000): SES had a greater effect for bulimia than for depression and social anxiety disorder. Overall, the effect was small (η² = 0.026). No significant interaction between the gender of potential clients and SES was found (p = 0.062). The influence of SES on treatment accessibility varied depending on the therapeutic method for which the therapist was licensed and on the social status of the district in which the therapist's practice was located. The therapist's socioeconomic background (parental SES) did not interact with the potential client's SES.

Conclusion

Therapist biases contributing to unequal access to treatment for individuals with low SES and other characteristics can aggravate mental health care disparities. Even though the effects we found were relatively modest, awareness of the association between SES and offers of therapy places might help practitioners to reflect on their own selection practices.
The JMJD6/HURP axis promotes cell migration via NF‐κB‐dependent centrosome repositioning and Cdc42‐mediated Golgi repositioning
Authors: Huang Yun‐Ru Jaoying , Chiu Shao‐Chih , Tseng Jeng‐Sen , Chen Jo‐Mei Maureen , Wei Tong‐You Wade , Chu Chen‐Yu , Kao Hsu‐Ting Eric , Yang Chieh‐Yun Oprah , Shih Yong‐Chun Erin , Yang Tsung‐Ying , Chiu Kun‐Yuan , Teng Chieh‐Lin Jerry , Yu Chang‐Tze Ricky
Published: October 2022

Golgi apparatus (GA) and centrosome reposition toward cell leading end during directional cell migration in a coupling way, thereby determining cell polarity by transporting essential factors to the proximal plasma membrane. The study provides mechanistic insights into how GA repositioning (GR) is regulated, and how GR and centrosome repositioning (CR) are coupled. Our previous published works reveals that PRMT5 methylates HURP at R122 and the HURP m122 inhibits GR and cell migration by stabilizing GA‐associated acetyl‐tubulin and then rigidifying GA. The current study further shows that the demethylase JMJD6‐guided demethylation of HURP at R122 promotes GR and cell migration. The HURP methylation mimicking mutant 122 F blocks JMJD6‐induced GR and cell migration, suggesting JMJD6 relays GR stimulating signal to HURP. Mechanistic studies reveal that the HURP methylation deficiency mutant 122 K promotes GR through NF‐κB‐induced CR and subsequently CR‐dependent Cdc42 upregulation, where Cdc42 couples CR to GR. Taken together, HURP methylation statuses provide a unique opportunity to understand how GR is regulated, and the GA intrinsic mechanism controlling Golgi rigidity and the GA extrinsic mechanism involving NF‐κB‐CR‐Cdc42 cascade collectively dictate GR.