bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen
Authors: Sconce Elizabeth A. , Khan Tayyaba I. , Wynne Hilary A. , Avery Peter , Monkhouse Louise , King Barry P. , Wood Peter , Kesteven Patrick , Daly Ann K. , Kamali Farhad
Published: June 2005

Current dosing algorithms do not account for genetic and environmental factors for warfarin dose determinations. This study investigated the contribution of age, CYP2C9 and VKORC1 genotype, and body size to warfarin-dose requirements. Studied were 297 patients with stable anticoagulation with a target international normalized ratio (INR) of 2.0 to 3.0. Genetic analyses for CYP2C9 (*2 and *3 alleles) and VKORC1 (-1639 polymorphism) were performed and venous INR and plasma R- and S-warfarin concentrations determined. The mean warfarin daily dose requirement was highest in CYP2C9 homozygous wild-type patients, compared with those with the variant *2 and *3 alleles (P < .001) and highest in patients with the VKORC1 (position -1639) GG genotype compared with those with the GA genotype and the AA genotype (P < .001). Mean warfarin daily dose requirements fell by 0.5 to 0.7 mg per decade between the ages of 20 to 90 years. Age, height, and CYP2C9 genotype significantly contributed to S-warfarin and total warfarin clearance, whereas only age and body size significantly contributed to R-warfarin clearance. The multivariate regression model including the variables of age, CYP2C9 and VKORC1 genotype, and height produced the best model for estimating warfarin dose (R2 = 55%). Based upon the data, a new warfarin dosing regimen has been developed. The validity of the dosing regimen was confirmed in a second cohort of patients on warfarin therapy.
Primary cutaneous large B-cell lymphomas: clinicopathologic features, classification, and prognostic factors in a large series of patients
Authors: Kodama Kazuo , Massone Cesare , Chott Andreas , Metze Dieter , Kerl Helmut , Cerroni Lorenzo
Published: June 2005

In the new World Health Organization/European Organization for Research and Treatment of Cancer (WHO/EORTC) classification of cutaneous lymphomas, large B-cell lymphomas (LBCLs) are divided into 3 groups: LBCL, leg-type (LBCLLT); follicle center lymphoma, diffuse type (FCLDT); and LBCL, others (LBCLO). We studied a large number of primary cutaneous LBCLs to test the validity of the classification and to identify prognostic factors for these patients. Ninety-three cases of primary cutaneous LBCL were analyzed for clinicopathologic features, expression of several markers including Bcl-2, Bcl-6, MUM-1, and FOX-P1, in situ hybridization for Epstein-Barr virus, and molecular analyses of IGH gene rearrangement and of Borrelia burgdorferi and human herpesvirus 8 DNA. Patients were classified into the following categories: FCLDT, 44 cases; LBCLLT, 40 cases; and LBCLO, 9 cases. Statistical analyses showed that the LBCLLT and FCLDT groups were clearly distinct in terms of clinicopathologic features and survival. The LBCLO group had features in between those of LBCLLT and FCLDT. Our study shows that accurate morphologic and phenotypic analyses allow us to stratify most patients into the prognostically different categories of LBCLLT and FCLDT. The definition of a third category of LBCLO requires further studies to clarify whether these cases indeed show distinct clinicopathologic features. (Blood. 2005;106:2491-2497)
Identification of the receptor scavenging hemopexin-heme complexes
Authors: Hvidberg Vibeke , Maniecki Maciej B. , Jacobsen Christian , Højrup Peter , Møller Holger J. , Moestrup Søren K.
Published: June 2005

Heme released from heme-binding proteins on internal hemorrhage, hemolysis, myolysis, or other cell damage is highly toxic due to oxidative and proinflammatory effects. Complex formation with hemopexin, the high-affinity heme-binding protein in plasma and cerebrospinal fluid, dampens these effects and is suggested to facilitate cellular heme metabolism. Using a ligand-affinity approach, we purified the human hemopexin-heme receptor and identified it as the low-density lipoprotein receptor-related protein (LRP)/CD91, a receptor expressed in several cell types including macrophages, hepatocytes, neurons, and syncytiotrophoblasts. Binding experiments, including Biacore analysis, showed that hemopexin-heme complex formation elicits the high receptor affinity. Uptake studies of radio-labeled hemopexin-heme complex in LRP/CD91-expressing COS cells and confocal microscopy of the cellular processing of fluorescent hemopexin-heme complex established the ability of LRP/CD91 to mediate hemopexin-heme internalization resulting in cellular heme uptake and lysosomal hemopexin degradation. Uptake of hemopexin-heme complex induced LRP/CD91-dependent heme-oxygenase 1 mRNA transcription in cultured monocytes. In conclusion, hemopexin-heme complexes are removed by a receptor-mediated pathway showing striking similarities to the CD163-mediated haptoglobin-hemoglobin clearance in macrophages. Furthermore, the data indicate a hitherto unknown role of LRP/CD91 in inflammation. (Blood. 2005; 106:2572-2579)
Inferring yeast cell cycle regulators and interactions using transcription factor activities
Authors: Yang Young-Lyeol , Suen Jason , Brynildsen Mark P , Galbraith Simon J , Liao James C
Published: June 2005

Background

Since transcription factors are often regulated at the post-transcriptional level, their activities, rather than expression levels may provide valuable information for investigating functions and their interactions. The recently developed Network Component Analysis (NCA) and its generalized form (gNCA) provide a robust framework for deducing the transcription factor activities (TFAs) from various types of DNA microarray data and transcription factor-gene connectivity. The goal of this work is to demonstrate the utility of TFAs in inferring transcription factor functions and interactions in Saccharomyces cerevisiae cell cycle regulation.

Results

Using gNCA, we determined 74 TFAs from both wild type and fkh1 fkh2 deletion mutant microarray data encompassing 1529 ORFs. We hypothesized that transcription factors participating in the cell cycle regulation exhibit cyclic activity profiles. This hypothesis was supported by the TFA profiles of known cell cycle factors and was used as a basis to uncover other potential cell cycle factors. By combining the results from both cluster analysis and periodicity analysis, we recovered nearly 90% of the known cell cycle regulators, and identified 5 putative cell cycle-related transcription factors (Dal81, Hap2, Hir2, Mss11, and Rlm1). In addition, by analyzing expression data from transcription factor knockout strains, we determined 3 verified (Ace2, Ndd1, and Swi5) and 4 putative interaction partners (Cha4, Hap2, Fhl1, and Rts2) of the forkhead transcription factors. Sensitivity of TFAs to connectivity errors was determined to provide confidence level of these predictions.

Conclusion

By subjecting TFA profiles to analyses based upon physiological signatures we were able to identify cell cycle related transcription factors consistent with current literature, transcription factors with potential cell cycle dependent roles, and interactions between transcription factors.
Overexpression of extracellular superoxide dismutase reduces acute radiation induced lung toxicity
Authors: Rabbani Zahid N , Anscher Mitchell S , Folz Rodney J , Archer Emerald , Huang Hong , Chen Liguang , Golson Maria L , Samulski Thaddeus S , Dewhirst Mark W , Vujaskovic Zeljko
Published: June 2005

Background

Acute RT-induced damage to the lung is characterized by inflammatory changes, which proceed to the development of fibrotic lesions in the late phase of injury. Ultimately, complete structural ablation will ensue, if the source of inflammatory / fibrogenic mediators and oxidative stress is not removed or attenuated. Therefore, the purpose of this study is to determine whether overexpression of extracellular superoxide dismutase (EC-SOD) in mice ameliorates acute radiation induced injury by inhibiting activation of TGFβ1 and downregulating the Smad 3 arm of its signal transduction pathway.

Methods

Whole thorax radiation (single dose, 15 Gy) was delivered to EC-SOD overexpressing transgenic (XRT-TG) and wild-type (XRT-WT) animals. Mice were sacrificed at 1 day, 1 week, 3, 6, 10 and 14 weeks. Breathing rates, right lung weights, total/differential leukocyte count, activated TGFβ1 and components of its signal transduction pathway (Smad 3 and p-Smad 2/3) were assessed to determine lung injury.

Results

Irradiated wild-type (XRT-WT) animals exhibited time dependent increase in breathing rates and right lung weights, whereas these parameters were significantly less increased (p < 0.05) at 3, 6, 10 and 14 weeks in irradiated transgenic (XRT-TG) mice. An inflammatory response characterized predominantly by macrophage infiltration was pronounced in XRT-WT mice. This acute inflammation was significantly attenuated (p < 0.05) in XRT-TG animals at 1, 3, 6 and 14 weeks. Expression of activated TGFβ1 and components of its signal transduction pathway were significantly reduced (p < 0.05) at later time-points in XRT-TG vs. XRT-WT.

Conclusion

This study shows that overexpression of EC-SOD confers protection against RT-induced acute lung injury. EC-SOD appears to work, in part, via an attenuation of the macrophage response and also decreases TGFβ1 activation with a subsequent downregulation of the profibrotic TGFβ pathway.
Toe spreading ability in men with chronic pelvic pain syndrome
Authors: Yilmaz Ugur , Rothman Ivan , Ciol Marcia A , Yang Claire C , Berger Richard E
Published: June 2005

Background

We examined toe-spreading ability in subjects with chronic pelvic pain syndrome (CPPS) to test the hypothesis that subjects with CPPS could have deficiencies in lower extremity functions innervated by sacral spinal roots.

Methods

Seventy two subjects with CPPS and 98 volunteer controls were examined as part of a larger study on CPPS. All the subjects underwent a detailed urologic and neurological examination including a toe-spreading examination with a quantitative scoring system. We compared the groups in terms of ability of toe-spreading as either "complete" (all toes spreading) or "incomplete" (at least one interdigital space not spreading) and also by comparing the number of interdigital spaces. For CPPS subjects only, we also analyzed the variation of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scales by toe-spreading categories.

Results

CPPS subjects were less often able to spread all toes than subjects without CPPS (p = 0.005). None of the NIH-CPSI sub-scales (pain, urinary symptoms, and quality of life), nor the total score showed an association with toe spreading ability.

Conclusion

We found toe spreading to be diminished in subjects with CPPS. We hypothesize that incomplete toe spreading in subjects with CPPS may be related to subtle deficits involving the most caudal part of the spinal segments.
Stable expression of a recombinant human antinucleosome antibody to investigate relationships between antibody sequence, binding properties, and pathogenicity
Authors: Mason Lesley J , Lambrianides Anastasia , Haley Joanna D , Manson Jessica J , Latchman David S , Isenberg David A , Rahman Anisur
Published: June 2005

When purified under rigorous conditions, some murine anti-double-stranded-DNA (anti-dsDNA) antibodies actually bind chromatin rather than dsDNA. This suggests that they may actually be antinucleosome antibodies that only appear to bind dsDNA when they are incompletely dissociated from nucleosomes. Experiments in murine models suggest that antibody–nucleosome complexes may play a crucial role in the pathogenesis of glomerulonephritis in systemic lupus erythematosus. Some human monoclonal anti-DNA antibodies are pathogenic when administered to mice with severe combined immunodeficiency (SCID). Our objective was to achieve stable expression of sequence-altered variants of one such antibody, B3, in Chinese hamster ovary (CHO) cells. Purified antibodies secreted by these cells were tested to investigate whether B3 is actually an antinucleosome antibody. The pathogenic effects of the antibodies were tested by implanting CHO cells secreting them into SCID mice. Purified B3 does not bind to dsDNA unless supernatant from cultured cells is added, but does bind to nucleosomes. The strength of binding to dsDNA and nucleosomes is dependent on the sequence of the light chain. Mice that received CHO cells secreting wild-type B3 developed more proteinuria and died earlier than control mice that received nonsecreting CHO cells or mice that received B3 with a single light chain mutation. However, none of the mice had histological changes or deposition of human immunoglobulin G in the kidneys. Sequence changes may alter the pathogenicity of B3, but further studies using different techniques are needed to investigate this possibility.
Lactate concentration gradient from right atrium to pulmonary artery
Authors: Gutierrez Guillermo , Chawla Lakhmir S , Seneff Michael G , Katz Nevin M , Zia Hasan
Published: June 2005

Introduction

We compared simultaneous measurements of blood lactate concentration ([Lac]) in the right atrium (RA) and in the pulmonary artery (PA). Our aim was to determine if the mixing of right atrial with coronary venous blood, having substantially lower [Lac], results in detectable decreases in [Lac] from the RA to the PA.

Methods

A prospective, sequential, observational study was conducted in a medical-surgical intensive care unit. We enrolled 45 critically ill adult individuals of either sex requiring pulmonary artery catheters (PACs) to guide fluid therapy. Immediately following the insertion of the PAC, one paired set of blood samples per patient was drawn in random order from the PAC's proximal and distal ports for measurement of hemoglobin concentration, O2 saturation (SO2) and [Lac]. We defined Δ[Lac] as ([Lac]ra - [Lac]pa), ΔSO2 as (SraO2 - SpaO2) and the change in O2 consumption (ΔVO2) as the difference in systemic VO2 calculated using Fick's equation with either SraO2 or SpaO2 in place of mixed venous SO2. Data were compared by paired Student's t-test, Spearman's correlation analysis and by the method of Bland and Altman.

Results

We found SraO2 > SpaO2 (74.2 ± 9.1 versus 69.0 ± 10.4%; p < 0.001) and [Lac]ra > [Lac]pa (3.9 ± 3.0 versus 3.7 ± 3.0 mmol.l-1; p < 0.001). Δ[Lac] correlated with ΔVO2 (r2 = 0.34; p < 0.001).

Conclusion

We found decreases in [Lac] from the RA to PA in this sample of critically ill individuals. We conclude that parallel decreases in SO2 and [Lac] from the RA to PA support the hypothesis that these gradients are produced by mixing RA with coronary venous blood of lower SO2 and [Lac]. The present study is a preliminary observation of this phenomenon and further work is needed to define the physiological and clinical significance of Δ[Lac].
Leptin Improves Insulin Resistance and Hyperglycemia in a Mouse Model of Type 2 Diabetes
Authors: Toyoshima Yuka , Gavrilova Oksana , Yakar Shoshana , Jou William , Pack Stephanie , Asghar Zeenat , Wheeler Michael B. , LeRoith Derek
Published: June 2005

Leptin has metabolic effects on peripheral tissues including muscle, liver, and pancreas, and it has been successfully used to treat lipodystrophic diabetes, a leptin-deficient state. To study whether leptin therapy can be used for treatment of more common cases of type 2 diabetes, we used a mouse model of type 2 diabetes (MKR mice) that show normal leptin levels and are diabetic due to a primary defect in both IGF-I and insulin receptors signaling in skeletal muscle. Here we show that leptin administration to the MKR mice resulted in improvement of diabetes, an effect that was independent of the reduced food intake. The main effect of leptin therapy was enhanced hepatic insulin responsiveness possibly through decreasing gluconeogenesis. In addition, the reduction of lipid stores in liver and muscle induced by enhancing fatty acid oxidation and inhibiting lipogenesis led to an improvement of the lipotoxic condition. Our data suggest that leptin could be a potent antidiabetic drug in cases of type 2 diabetes that are not leptin resistant.
Cholesterol and Steroid Synthesizing Smooth Endoplasmic Reticulum of Adrenocortical Cells Contains High Levels of Proteins Associated with the Translocation Channel
Authors: Black Virginia H. , Sanjay Archana , van Leyen Klaus , Lauring Brett , Kreibich Gert
Published: June 2005

Steroid-secreting cells are characterized by abundant smooth endoplasmic reticulum whose membranes contain many enzymes involved in sterol and steroid synthesis. Yet they have relatively little morphologically identifiable rough endoplasmic reticulum, presumably required for synthesis and maintenance of the smooth membranes. In this study, we demonstrate that adrenal smooth microsomal subfractions enriched in smooth endoplasmic reticulum membranes contain high levels of translocation apparatus and oligosaccharyltransferase complex proteins, previously thought confined to rough endoplasmic reticulum. We further demonstrate that these smooth microsomal subfractions are capable of effecting cotranslational translocation, signal peptide cleavage, and N-glycosylation of newly synthesized polypeptides. This shifts the paradigm for distinction between smooth and rough endoplasmic reticulum. Confocal microscopy revealed the proteins to be distributed throughout the abundant tubular endoplasmic reticulum in these cells, which is predominantly smooth surfaced. We hypothesize that the broadly distributed translocon and oligosaccharyltransferase proteins participate in local synthesis and/or quality control of membrane proteins involved in cholesterol and steroid metabolism in a sterol-dependent and hormonally regulated manner.
Six Novel Mutations in the Proopiomelanocortin and Melanocortin Receptor 4 Genes in Severely Obese Adults Living in Southern Italy
Authors: Buono Pasqualina , Pasanisi Fabrizio , Nardelli Carmela , Ieno Luigi , Capone Silvana , Liguori Rosario , Finelli Carmine , Oriani Giovannangelo , Contaldo Franco , Sacchetti Lucia
Published: June 2005

Background: The genetic characterization of obese individuals could clarify the molecular mechanisms underlying body weight regulation and lead to targeted therapy. Here we report variants of the proopiomelanocortin (POMC) and melanocortin receptor 4 (MC4R) genes detected in severely obese adults living in southern Italy.

Methods: A total of 196 unrelated nondiabetic severely obese individuals [111 females and 85 males; mean (SD) age, 32.2 (11.5) years; mean body mass index, 48.8 (8.1) kg/m2] and 100 normal-weight healthy volunteers (34 males and 66 females) entered the study. POMC and MC4R were genotyped by sequencing analysis. Leptin, insulin, glucose, and the lipid profile were measured in fasting serum samples. We used the protein truncation test to verify the stop-codon mutation. Anthropometric measurements, sitting blood pressure, and heart rate were also recorded.

Results: Of the obese participants, 1.5% had mutations in POMC exon 3 (new mutations, P231L and E244X; known, R236G) and 2.5% had MC4R mutations (new mutations, W174C, Q43X, S19fsX51, and I317V; known, A175T). These mutations were not present in the controls. Gene polymorphisms were identified in similar percentages of severely obese and nonobese individuals, i.e., respectively, 52.5% and 51% (POMC) and 1% and 2% (MC4R).

Conclusions: We detected 2 new POMC mutations and 4 new MC4R mutations in a large number of severely obese adults living in southern Italy. These mutations, not present in normal-weight individuals, are further evidence that defects in the melanocortin pathway are related to severe obesity.
Contribution of CYP3A5 to the in Vitro Hepatic Clearance of Tacrolimus
Authors: Kamdem Landry K , Streit Frank , Zanger Ulrich M , Brockmöller Jürgen , Oellerich Michael , Armstrong Victor W , Wojnowski Leszek
Published: June 2005

Background: Tacrolimus is metabolized predominantly to 13-O-demethyltacrolimus in the liver and intestine by cytochrome P450 3A (CYP3A). Patients with high concentrations of CYP3A5, a CYP3A isoenzyme polymorphically produced in these organs, require higher doses of tacrolimus, but the exact mechanism of this association is unknown.

Methods: cDNA-expressed CYP3A enzymes and a bank of human liver microsomes with known CYP3A4 and CYP3A5 content were used to investigate the contribution of CYP3A5 to the metabolism of tacrolimus to 13-O-demethyltacrolimus as quantified by liquid chromatography–tandem mass spectrometry.

Results: Demethylation of tacrolimus to 13-O-demethyltacrolimus was the predominant clearance reaction. Calculated Km and Vmax values for CYP3A4, CYP3A5, and CYP3A7 cDNA-expressed microsomes were 1.5 μmol/L and 0.72 pmol · (pmol P450)−1 · min−1, 1.4 μmol/L and 1.1 pmol · (pmol P450)−1 · min−1, and 6 μmol/L and 0.084 pmol · (pmol P450)−1 · min−1, respectively. Recombinant CYP3A5 metabolized tacrolimus with a catalytic efficiency (Vmax/Km) that was 64% higher than that of CYP3A4. The contribution of CYP3A5 to 13-O-demethylation of tacrolimus in human liver microsomes varied from 1.5% to 40% (median, 18.8%). There was an inverse association between the contribution of CYP3A5 to 13-O-demethylation and the amount of 3A4 protein (r = 0.90; P <0.0001). Mean 13-O-demethylation clearances in CYP3A5 high and low expressers, estimated by the parallel-tube liver model, were 8.6 and 3.57 mL · min−1 · (kg of body weight)−1, respectively (P = 0.0088).

Conclusions: CYP3A5 affects metabolism of tacrolimus, thus explaining the association between CYP3A5 genotype and tacrolimus dosage. The importance of CYP3A5 status for tacrolimus clearance is also dependent on the concomitant CYP3A4 activity.
Deletion of the transcription factors Hsf1, Msn2 and Msn4 in yeast uncovers transcriptional reprogramming in response to proteotoxic stress
Authors: Mühlhofer Moritz , Offensperger Felix , Reschke Sarah , Wallmann Georg , Csaba Gergely , Berchtold Evi , Riedl Maximilian , Blum Helmut , Haslbeck Martin , Zimmer Ralf , Buchner Johannes
Published: February 2024

The response to proteotoxic stresses such as heat shock allows organisms to maintain protein homeostasis under changing environmental conditions. We asked what happens if an organism can no longer react to cytosolic proteotoxic stress. To test this, we deleted or depleted, either individually or in combination, the stress‐responsive transcription factors Msn2, Msn4, and Hsf1 in Saccharomyces cerevisiae. Our study reveals a combination of survival strategies, which together protect essential proteins. Msn2 and 4 broadly reprogram transcription, triggering the response to oxidative stress, as well as biosynthesis of the protective sugar trehalose and glycolytic enzymes, while Hsf1 mainly induces the synthesis of molecular chaperones and reverses the transcriptional response upon prolonged mild heat stress (adaptation).
Sphingosine 1‐phosphate receptor modulators in multiple sclerosis treatment: A practical review
Authors: Coyle Patricia K. , Freedman Mark S. , Cohen Bruce A. , Cree Bruce A. C. , Markowitz Clyde E.
Published: February 2024

Four sphingosine 1‐phosphate (S1P) receptor modulators (fingolimod, ozanimod, ponesimod, and siponimod) are approved by the US Food and Drug Administration for the treatment of multiple sclerosis. This review summarizes efficacy and safety data on these S1P receptor modulators, with an emphasis on similarities and differences. Efficacy data from the pivotal clinical trials are generally similar for the four agents. However, because no head‐to‐head clinical studies were conducted, direct efficacy comparisons cannot be made. Based on the adverse event profile of S1P receptor modulators, continued and regular monitoring of patients during treatment will be instructive. Notably, the authors recommend paying attention to the cardiac monitoring guidelines for these drugs, and when indicated screening for macular edema and cutaneous malignancies before starting treatment. To obtain the best outcome, clinicians should choose the drug based on disease type, history, and concomitant medications for each patient. Real‐world data should help to determine whether there are meaningful differences in efficacy or side effects between these agents.
Application of terminal region enlargement approach for discrete time quasi infinite horizon nonlinear model predictive control
Authors: Gupta Sowmya , Rajhans Chinmay
Published: February 2024

Ensuring nominal asymptotic stability of the nonlinear model predictive control (NMPC) controller is not trivial. Stabilizing ingredients such as terminal penalty term and Terminal Region (TR) are crucial in establishing the asymptotic stability. Approaches available in the literature provide limited degrees of freedom for the characterization of the TR for the discrete time quasi infinite horizon NMPC formulation. Current work presents alternate approaches namely arbitrary controller based approach and linear quadratic regulator (LQR) based approach, which provide larger degrees of freedom for enlarging the TR. Both the approaches are scalable to system of any dimension. Approach from the literature provides a scalar whereas proposed approaches provide two additive matrices as tuning parameters for shaping of the TR. Proposed approaches involve solving modified Lyapunov equations to compute terminal penalty term, followed by explicit characterization of the TR. Efficacy of the proposed approaches is demonstrated using benchmark two state system. TR obtained using the arbitrary controller based approach and LQR based approach are approximately 10.4723 and 9.5055 times larger by area measure when compared to the largest TR obtained using the approach from the literature. As a result, there is significant reduction in the prediction horizon length while retaining the feasibility of the controller.
Effect of Egg White Protein and Water Content on the Stabilization Mechanisms of Natural Rubber Latex Foams Obtained from Microwave Radiation
Authors: Amezúa‐Arranz Clara , Salmazo Leandra Oliveira , López‐Gil Alberto , Rodríguez‐Pérez Miguel‐Ángel
Published: February 2024

The global plastic consumption, as one of the paramount concerns of our society, opens new paths of investigation in green materials. This study presents contribution to the field with the obtention of natural rubber latex foams (NRLF using egg white powder (EW) as the biostabilizing agent. The route followed to develop these samples is based on a two‐step process, a previous aeration, followed by microwave dehydration. This synthesis route is greener and ecofriendlier than conventional ones due to the use of bio‐based bulk materials, the utilization of microwave radiation which reduces the energy consumption in comparison with conventional heating methods, and the elimination of the vulcanization process typically used when producing latex foams. Herein, a deep study of the effect of EW on NRLF obtained at three water content levels (i.e., 40, 70, 90 phr) is carried out. The density and cellular structure parameters are measured for the formulations of liquid and solid foams to comprehend the stabilization mechanisms due to the presence of the EW and the effect of water content. It has been possible to produce open‐cell natural rubber latex foams with densities as low as 53 kg m−3 and cell sizes as low as 114 μm.
Oxidation Resistance and Microstructural Analysis of Polymer‐Derived (HfxTa1−x)C/SiC Ceramic Nanocomposites
Authors: Petry Nils‐Christian , Thor Nathalie , Bernauer Jan , Ulrich Anke Silvia , Ionescu Emanuel , Riedel Ralf , Pundt Astrid , Galetz Mathias Christian , Lepple Maren
Published: February 2024

The oxidation behavior of polymer‐derived (HfxTa1−x)C/SiC nanocomposites at 1200 °C and 1400 °C for up to 100 h is investigated in this work. Overall, the chemical modification of the polycarbosilane‐based precursor with Hf and Ta leads to an improved oxidation behavior due to an increased densification. Shifting the Hf/Ta ratio from (Hf0.2Ta0.8)C/SiC to (Hf0.7Ta0.3)C/SiC results in an improved oxidation behavior due to Hf6Ta2O17 formation and the reduction of Ta2O5 formation, which reduces cracking of the samples. The formation and microstructure of SiO2 as well as the internal oxidation of (HfxTa1−x)C precipitates is explained by thermodynamic and kinetic considerations.
Review on Structural Adjustment Strategies of Titanium‐Based Metal Oxide Dimensionally Stable Anodes in Electrochemical Advanced Oxidation Technology
Authors: Qiu Fan , Wang Luyao , Fan Yang , Pan Yanan , Song Haiou , Ye Zhiwen , Zhang Shupeng
Published: February 2024

Emerging organic pollutants and refractory pollutants in water bodies have caused severe harm to the ecological environment and human health. Electrochemical advanced oxidation processes (EAOPs) are currently one of the most effective oxidation methods to deal with refractory organic pollutants. Electrode materials serve as the most critical component in influencing the EAOP performance. Dimensionally stable anodes (DSAs) have the advantages of dimensional stability, structural diversity, chemical stability, low oxygen evolution potential and long service life, etc. Herein, several types of Ti‐based metal oxide DSAs (Ti/MOxDSAs) commonly used in EAOPs in the past 5 years, including Ti/IrO2, Ti/RuO2, Ti/PbO2, Ti/Sb–SnO2, and Ti/TiO2, are introduced. The modification methods including metal doping, composition adjustment, nanostructure construction, introduction of intermediate layers, compositing with carbon materials, and formation of 3D structures as well as the applications of these modified Ti‐based DSAs in EAOP for the rapid degradation of various organic pollutants are summarized and their advantages and current shortcomings of electrodes are pointed out. Finally, the Ti‐based DSA's current limitations and future development prospects are concluded.
A Therapeutic Pretargeting Strategy for Triple‐Negative Breast Cancer Based on a Bioorthogonal Reaction and a Self‐Assembled Peptide
Authors: Zhang Chen , Wang Junqiao , Chen Hui , Ouyang Muzi , Li Yuanheng , Tan Chunyan , Jiang Yuyang , Tan Ying
Published: February 2024

Triple‐negative breast cancer (TNBC), a disease with a poor prognosis and high mortality, is difficult to targeted therapy, due to the metastatic nature of TNBC cells and their lack of estrogen, progesterone, and Her‐2/Neu receptor targets. Here, a novel pretargeting strategy involving self‐assembled peptides and a bioorthogonal reaction are described. This process generates nanofibers on TNBC cell surface that prevent them migration and invasion and deliver untargeted anticancer drugs (e.g., doxorubicin) that synergistically eliminates TNBC cells. The self‐assembled peptide contains four modules: i) an aromatic group‐rich tetraphenylethylene (TPE) unit for promoting self‐assembly and nanofiber formation, ii) a GFFY peptide motif that supports self‐assembly of nanofibers into peptide scaffolds, iii) a targeting RGD motif that binding with the abundant integrin molecules present on TNBC cell surface, and iv) an azide group acting as the bioorthogonal reaction site that reacts with drugs or probes containing the dibenzocyclooctyne (DBCO) group. Results of in vitro and in vivo experiments indicate that the self‐assembled peptide inhibits tumor invasion and metastasis, while also pretargeting and killing TNBC cells with superior effectiveness and lower toxicity to that of current chemotherapies. In conclusion, this novel bioorthogonal pretargeting strategy holds promise as an effective anticancer therapeutic approach.
NIR‐Excitable POM‐Encapsulated Yb‐Bi2S3 Decorated Graphene for Wearable Photoelectrochemical Sensing
Authors: Wang Han , Li Caoling , Zhang Jingwei , Yang Zhao , Li Junjun , Cao Yu , Wu Kangbing , Liu Zhihong , Hao Junxing , Ye Xiaoxue
Published: February 2024

Transition metal sulfides have garnered significant interest in the realm of photoelectrochemical (PEC) sensors due to their remarkable optical and electrical properties. However, their intrinsic UV–vis adsorption and electron‐donor consumption severely hinder their nonirritating and in situ epidermal PEC applications. Herein, a NIR‐808 nm light‐excited heterojunction, phosphomolybdic acid‐encapsulated ytterbium‐doped bismuth sulfide (Yb‐Bi2S3/PMA), is synthesized by hydrothermal method for self‐sufficient electron donor‐based PEC sensing. Further, the Yb‐Bi2S3/PMA heterojunction is decorated on flexible and integrated laser‐induced graphene electrode arrays, providing ultrafast charge carrier transfer capacity and robust mechanical durability (300 bending cycles) for subsequent wearable PEC sensing. As a showcase, the aptamer molecular recognition‐based wearable PEC sensor for sweat trace Neuropeptide Y (NPY, a stress or depression biomarker) presents an ultra‐low detection limit (0.39 fM) and good anti‐interference ability. Moreover, the integration of wearable PEC aptasensor with signal processing and wireless communication facilitates nonirritating and in situ analysis of sweat trace NPY dynamics in various real scenarios (feeding behaviors, physiological stress, and circadian rhythm). More broadly, this research establishes the foundation for NIR‐excitable semiconductors equipped with self‐sufficient electron donor capabilities, unlocking the potential for ultrasensitive wearable PEC sensing applications.
Electron‐Assisted Generation and Straight Movement of Skyrmion Bubble in Kagome TbMn6Sn6
Authors: Li Zhuolin , Yin Qiangwei , Lv Wenxin , Shen Jun , Wang Shouguo , Zhao Tongyun , Cai Jianwang , Lei Hechang , Lin Shi‐Zeng , Zhang Ying , Shen Baogen
Published: February 2024

Topological magnetic textures are promising candidates as binary data units for the next‐generation memory device. The precise generation and convenient control of nontrivial spin topology at zero field near room temperature endows the critical advantages in skyrmionic devices but is not simultaneously integrated into one material. Here, in the Kagome plane of quantum TbMn6Sn6, the expedient generation of the skyrmion bubbles in versatile forms of lattice, chain, and isolated one by converging the electron beam, where the electron intensity gradient contributes to the dynamic generation from local anisotropy variation near spin reorientation transition (SRT) is reported. Encouragingly, by utilizing the dynamic shift of the SRT domain interface, the straight movement is actualized with the skyrmion bubble slave to the SRT domain interface forming an elastic composite object, avoiding the usual deflection from the skyrmion Hall effect. The critical contribution of the SRT domain interface via conveniently electron‐assisted heating is further theoretically validated in micromagnetic simulation, highlighting the compatible application possibility in advanced devices.
Solar Degradation and Stability of Lead‐Free Light Absorber Cs2AgBiBr6 in Ambient Conditions
Authors: Jöckel Dennis Michael , Yoon Songhak , Frebel Alexander , Neguse Samuel Meles , Rossa Jürgen Dieter , Bett Alexander Jürgen , Schubert Martin , Widenmeyer Marc , Balke–Grünewald Benjamin , Weidenkaff Anke
Published: February 2024

As numerous studies on highly efficient perovskite solar cells have been conducted on lead‐based light absorbers, such as MAPbI3 and FAPbI3, increasing concerns are rising regarding toxicity and stability issues. One of the most prominent and promising lead‐free alternatives is the double‐perovskite Cs2AgBiBr6, which is well‐suited for multi‐junction solar cells considering its relatively large indirect bandgap of around 1.95–2.05 eV. Despite distinctive reports on its performance under ambient conditions, the demonstrated stability has not yet been conclusively clarified. Within this study, the degradation behavior of Cs2AgBiBr6 single crystals is investigated under different ambient environments, such as AM1.5g solar irradiation, aquatic conditions, and humidity. The corresponding samples are analyzed by using Raman, UV–vis, energy‐dispersive X‐Ray, and micro‐photoluminescence spectroscopies together with X‐Ray diffraction. High intrinsic stability of Cs2AgBiBr6 in ambient conditions and severe degradation in aquatic conditions are observed. Furthermore, surface morphology alterations are found during the simulated solar irradiation indicating photo‐accelerated degradation behavior. In the results of this study, it is clearly implied that intense research efforts need to be put into sealing the Cs2AgBiBr6 layer in solar cells with the goal of protecting it from humidity and water intrusion simultaneously, therefore avoiding photo‐accelerated degradation.
Modulation of Oxygen Content and Ferroelectricity in Sputtered Hafnia‐Zirconia by Engineering of Tungsten Oxide Bottom Electrodes
Authors: Wang Xuetao , Slesazeck Stefan , Mikolajick Thomas , Grube Matthias
Published: February 2024

The well‐developed high‐k technologies ease the integration complexity for HfO2‐based ferroelectric (FE) devices in the complementary metal‐oxide semiconductor processes. Sputtered HfxZr(1‐x)O2(HZO) FEs have proven their thermal compatibility in back‐end‐of‐line (BEOL) integration processes with high remanent polarization (Pr) and a high cycling endurance. With the help of a tungsten oxide (WOx) bottom electrode, the sputtered HZO's FE properties are further advanced in this work. WOxis used to tune the oxygen content in the HZO film, providing an FE performance with a maximum 2Prof 46 µC cm−2and an endurance of 108cycles. Based on this, sputtered HZO can compete with the atomic layer deposited HZO in the BEOL processes. In addition, WOxbottom electrodes enhance the FE capacitor behavior in a broad processing window, which relaxes the manufacturing restrictions.
Does the advertising of plant‐based burgers attract meat consumers? The influence of new product advertising on consumer responses
Authors: Wang Lingxiao , Li Wenying , Zheng Yuqing
Published: February 2024

The “meat” marketing of new plant‐based burgers distinguished them from traditional vegan burgers, yet it is still unknown if and to what extent this advertising appeals to meat consumers. We employ a novel digital advertisement dataset from Nielsen Ad Intel to investigate the market entry and advertising patterns of the Impossible Burger, one of the leading brands in the plant‐based meat market. By merging weekly ad views at the DMA market level with Nielsen Homescan Panel, we find that prior purchases of meat burgers reduce the likelihood of consumers buying the new plant‐based burger, whereas past vegan burger purchases elevate this probability. While advertising did boost the average purchasing likelihood for the Impossible Burger, the enhancement in purchase probability for meat burger consumers is approximately one fifth of that observed for vegan burger consumers. These findings have implications to effectively marketing plant‐based meat products to different consumer groups [EconLit Citations: D12, M37, M31, L66].
The impacts of extreme heat on wage losses: Evidence from the Chinese agri‐food industry
Authors: Zhu Xiaoke , Deng Qiyun
Published: February 2024

This paper investigates the effects of extremely high temperatures on wage losses for workers in the Chinese agri‐food industry. Our estimated results suggest extreme heat is associated with a decrease in worker wages, and that these welfare losses could be attributed to the adverse impacts of extremely hot days on worker productivity. We also observe that, compared to male workers, female workers are more likely to bear wage losses when exposed to extremely hot weather. Furthermore, workers in private firms may experience more wage losses due to extremely hot days than those in other ownership types. Regarding the industry‐level heterogeneity analysis, we find that wage losses in the agri‐food manufacturing industry are more severe than those in the agri‐food processing industry, while no significant wage losses are observed in the beverages and alcohol industry. In the long term, wage losses induced by climate change are projected to rise by 10.93% under RCP8.5, if no extra adaptation actions are implemented. [EconLit Citations: O13, P46, Q54]
Hyper‐Versatile Gripping: Synergizing Mechanical and Machine Intelligence of a Hybrid Robotic Gripper
Authors: Khin Phone May , Yeow Chen‐Hua , Ang Marcelo H. Jr.
Published: February 2024

Integration of robotic solutions in manufacturing sector is growing. However, it is still concentrated in certain industries (i.e., electronics and automotive) where standardization of product physical form is high. Current state‐of‐the‐art gripping solutions fall short when they need to accommodate items with high variability in physical form. This challenging scenario for automation can be found in a few industries (i.e., e‐commerce). Automation of pick‐and‐place processes in this area requires a more versatile gripping solution. To resolve this challenge, this article proposes a novel way to improve grip‐versatility by synergizing the mechanical and machine intelligence of a hybrid robotic gripper (HRG). Comparative analysis with commercial grippers shows that HRG can pick a more diverse range of items with success rate 94.78%. Visual perception‐based picking strategy is developed to automate the reconfiguration of HRG into a stable grasp pose for different objects. Using the proposed reconfigurable picking strategy, the efficacy of HRG in pick‐and‐place tasks is evaluated using three parameters—mean pick per hour (MPPH), successful execution over total attempts (SETA), and average cycle time (AVGCT). HRG can effectively pick items in cluttered workspace with MPPH of 98.54 ± 15.49, SETA of 0.93 ± 0.11, and AVGCT of 34.76 ± 3.31 s.
Smut fungus (Langdonia walkerae) incidence is lower in two bunchgrass species (Aristida stricta and A. beyrichiana) after fires early in the year
Authors: Fill Jennifer M. , Meadows Inga , Walker Joan L. , Crandall Raelene M. , Kerrigan Julia L.
Published: February 2024

Premise

In frequently burned southeastern USA pine‐grassland communities, wiregrass (Aristida stricta and A. beyrichiana) are dominant bunchgrasses whose flowers are infected during flowering by a smut fungus (Langdonia walkerae). We hypothesized that because prescribed fire timing affects wiregrass flowering patterns, it could affect smut incidence (occurrence of smut on plants) and severity of infection in inflorescences and spikelets. Because soil order could influence plant susceptibility, we hypothesized that these patterns would differ between soil orders. We hypothesized differences between species as representative of geographic variation in this ecosystem.

Methods

We surveyed the incidence and severity of L. walkerae in wiregrass populations (85 populations at 14 sites) that had been prescription burned at different times during the previous year. We used binomial regressions to test whether incidence and severity differed by burn day, soil order, or species, with site as a random effect.

Results

Fires that occurred in the winter were associated with significantly lower incidence than fires later in the year (as the months progressed into summer). Plants growing on Spodosol soils were significantly less likely to be infected than those on other soils. More variation in incidence, however, was explained by site, suggesting that site‐specific characteristics were important. Smut severity in inflorescences and spikelets was greater overall in populations of A. stricta than in southern populations (A. beyrichiana).

Conclusions

Our findings indicate that fire timing and soil order affect L. walkerae incidence in wiregrass plants, but neither appears to be associated with greater severity. Patterns of smut infection are related to site history and geographic variation.
Common epilepsy variants from the general population are not associated with epilepsy among individuals with tuberous sclerosis complex
Authors: Richard Melissa A. , Lupo Philip J. , Ehli Erik A. , Sahin Mustafa , Krueger Darcy A. , Wu Joyce Y. , Bebin Elizabeth M. , Au Kit Sing , Northrup Hope , Farach Laura S. ,   TACERN Study Group
Published: February 2024

Common genetic variants identified in the general population have been found to increase phenotypic risks among individuals with certain genetic conditions. Up to 90% of individuals with tuberous sclerosis complex (TSC) are affected by some type of epilepsy, yet the common variants contributing to epilepsy risk in the general population have not been evaluated in the context of TSC‐associated epilepsy. Such knowledge is important to help uncover the underlying pathogenesis of epilepsy in TSC which is not fully understood, and critical as uncontrolled epilepsy is a major problem in this population. To evaluate common genetic modifiers of epilepsy, our study pooled phenotypic and genotypic data from 369 individuals with TSC to evaluate known and novel epilepsy common variants. We did not find evidence of enhanced genetic penetrance for known epilepsy variants identified across the largest genome‐wide association studies of epilepsy in the general population, but identified support for novel common epilepsy variants in the context of TSC. Specifically, we have identified a novel signal in SLC7A1 that may be functionally involved in pathways relevant to TSC and epilepsy. Our study highlights the need for further evaluation of genetic modifiers in TSC to aid in further understanding of epilepsy in TSC and improve outcomes.
Health care disparities and chronic rhinosinusitis: Does neighborhood disadvantage impact outcomes in sinonasal disease?
Authors: Gill Amarbir S. , Tullis Benton , Mace Jess C. , Massey Conner , Pandrangi Vivek C. , Gutierrez Jorge A. , Ramakrishnan Vijay R. , Beswick Daniel M. , Soler Zachary M. , Smith Timothy L. , Alt Jeremiah A.
Published: February 2024

Objective

Socioeconomic status (SES) is linked to health outcomes but has not been well studied in patients with chronic rhinosinusitis (CRS). The area deprivation index (ADI) is a comprehensive measure of geographic SES that ranks neighborhood disadvantage. This investigation used ADI to understand the impact of neighborhood disadvantage on CRS treatment outcomes.

Methods

A total of 642 study participants with CRS were prospectively enrolled and self‐selected endoscopic sinus surgery (ESS) or continued appropriate medical therapy as treatment. The 22‐item SinoNasal Outcome Test (SNOT‐22) and Medical Outcomes Study Questionnaire Short‐Form 6‐D (SF‐6D) health utility value scores were recorded pre‐ and post‐treatment. Using residence zip codes, national ADI scores were retrospectively assigned to patients. Spearman's correlation coefficients (Rs) and Cramer's V effect size (φc) with 95% confidence interval (CI) were calculated.

Results

A history of ESS was associated with significantly worse ADI scores compared to no history of ESS (φc = 0.18; 95% CI: 0.10, 0.25; p < 0.001). Baseline total SNOT‐22 (Rs = 0.14; 95% CI: 0.06, 0.22; p < 0.001) and SF‐6D values (Rs = −0.20; 95% CI: −0.27, −0.12; p < 0.001) were significantly negatively correlated with national ADI rank. No significant correlations between ADI and within‐subject improvement, or achievement of >1 minimal clinically important difference, in SNOT‐22 or SF‐6D scores after treatment were found.

Conclusions

Geographic socioeconomic deprivation was associated with worse baseline disease severity and history of prior surgical intervention. However, ADI did not correlate with improvement in disease‐specific outcomes. The impact of socioeconomic deprivation on outcomes in CRS requires further investigation.