bluuebunny/crossref_metadata_2025 huggingface dataset:
Disruption of Dcp1 leads to a Dcp2‐dependent aberrant ribosome profiles in Aspergillus nidulans
Authors: Bharudin Izwan , Caddick Mark X. , Connell Sean R. , Lamaudière Matthew T. F. , Morozov Igor Y.
Published: April 2023

There are multiple RNA degradation mechanisms in eukaryotes, key among these is mRNA decapping, which requires the Dcp1‐Dcp2 complex. Decapping is involved in various processes including nonsense‐mediated decay (NMD), a process by which aberrant transcripts with a premature termination codon are targeted for translational repression and rapid decay. NMD is ubiquitous throughout eukaryotes and the key factors involved are highly conserved, although many differences have evolved. We investigated the role of Aspergillus nidulans decapping factors in NMD and found that they are not required, unlike Saccharomyces cerevisiae. Intriguingly, we also observed that the disruption of one of the decapping factors, Dcp1, leads to an aberrant ribosome profile. Importantly this was not shared by mutations disrupting Dcp2, the catalytic component of the decapping complex. The aberrant profile is associated with the accumulation of a high proportion of 25S rRNA degradation intermediates. We identified the location of three rRNA cleavage sites and show that a mutation targeted to disrupt the catalytic domain of Dcp2 partially suppresses the aberrant profile of Δdcp1 strains. This suggests that in the absence of Dcp1, cleaved ribosomal components accumulate and Dcp2 may be directly involved in mediating these cleavage events. We discuss the implications of this.
Genetic linkage analysis of head and neck cancer in a Spanish family
Authors: Pérez‐Sayáns Mario , Chamorro‐Petronacci Cintia M. , Bravo Susana B. , Padín‐Iruegas María E. , Guitián‐Fernández Esteban , Barros‐Angueira Francisco , Quintas‐Rey Rita , García‐García Abel
Published: April 2023

Objectives

To describe the genetic variants that may be associated with the development of head and neck cancer (HNC) and functionally validating the molecular implications.

Materials and Methods

A prospective observational study was carried out on a family of 3 generations in which 3 members had developed HNC. Peripheral blood sample was taken in a routine procedure for exome sequencing in one relative and genotyping in the remaining twelve relatives. For the functional analysis all‐trans retinoic acid (atRA) was extracted from saliva and serum and measured using ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS). The presence of HPV‐DNA.

Results

None of the patients smoked or consumed alcohol. The presence of HPV DNA was not detected in any of the biopsied samples. A total amount of 6 members out of 13 (46.15%) carried out the same mutation of CYP26B1 (2p13.2; G>T). The mean plasma concentration of atRA was 3.3109 ± 1.4791 pg/mL for the study family and 4.7370 ± 1.5992 pg/mL for the controls (p = 0.042).

Conclusion

Lower levels of atRA were confirmed in the study family, which may open the way to the possible relationship between the polymorphism CYP26B1 (2p13.2; G>T) and HNC.
Transnational crimes: how nations should cooperate and why they don't*
Authors: Bac Mehmet
Published: April 2023

Chain‐form crime partnerships and intelligence sharing by national authorities to detect cross‐border partners create multiple externalities in the combat against transnational crimes and illicit trafficking. Cooperative enforcements that minimize global harms prioritize the country with lower intelligence production and/or superior detection capability. In equilibrium, as in practice, national enforcements are underbudgeted and might prioritize the wrong side – predominantly the high‐budget, high‐harm country. Governments might not share intelligence out of fear of importing enforcement burden, and harmonizing criminal sanctions alone might not be effective. Shocks on crime deterrence in a target country are first absorbed by source countries, implying weaker horizontal crime transfer effects than projected.
Once More unto the Breach: Kant and Race
Authors: Fleischacker Samuel
Published: April 2023

The last thirty years has seen an explosion of literature on Kant and race. Once overlooked essays and notes in which Kant expresses contempt for nonwhite people and support for slavery have been brought to light, and many scholars have wrestled with the question of how a philosopher who stressed the equal dignity of all human beings could hold such views. This article tries to reframe the debate over these issues. It begins by reviewing the racist texts in Kant's corpus and the responses to them proposed by scholars like Charles Mills (to whom the paper is dedicated), Robert Bernasconi, and Pauline Kleingeld. It then introduces elements of Kant's philosophical development that gave Kant reason to renounce his racism—whether or not he actually did so—from about the time of the Groundwork onward. Finally, it turns to the question of what Kant's racism can tell us about his moral philosophy—and perhaps about moral philosophy in general.
Regulation of drought tolerance in Arabidopsis involves the PLATZ4‐mediated transcriptional repression of plasma membrane aquaporin PIP2;8
Authors: Liu Miao , Wang Chunyan , Ji Zhen , Lu Junyao , Zhang Lei , Li Chunlong , Huang Jinguang , Yang Guodong , Yan Kang , Zhang Shizhong , Zheng Chengchao , Wu Changai
Published: April 2023

Plant A/T‐rich protein and zinc‐binding protein (PLATZ) transcription factors play important roles in plant growth, development and abiotic stress responses. However, how PLATZ influences plant drought tolerance remains poorly understood. The present study showed that PLATZ4 increased drought tolerance in Arabidopsis thaliana by causing stomatal closure. Transcriptional profiling analysis revealed that PLATZ4 affected the expression of a set of genes involved in water and ion transport, antioxidant metabolism, small peptides and abscisic acid (ABA) signaling. Among these genes, the direct binding of PLATZ4 to the A/T‐rich sequences in the plasma membrane intrinsic protein 2;8 (PIP2;8) promoter was identified. PIP2;8 consistently reduced drought tolerance in Arabidopsis through inhibiting stomatal closure. PIP2;8 was localized in the plasma membrane, exhibited water channel activity in Xenopus laevis oocytes and acted epistatically to PLATZ4 in regulating the drought stress response in Arabidopsis. PLATZ4 increased ABA sensitivity through upregulating the expression of ABSCISIC ACID INSENSITIVE 3 (ABI3), ABI4 and ABI5. The transcripts of PLATZ4 were induced to high levels in vegetative seedlings under drought and ABA treatments within 6 and 3 h, respectively. Collectively, these findings reveal that PLATZ4 positively influences plant drought tolerance through regulating the expression of PIP2;8 and genes involved in ABA signaling.
Lessons Learned Toward Estimating the High-Pressure Turbine Inlet Temperature Profile Using Measurements Acquired at the High-Pressure Turbine Exit
Authors: Zhu Xu , Zhou Kai , Zheng Xinqian , Lou Fangyuan
Published: April 2023

To achieve higher thermal efficiency, gas turbines operate at increasingly higher turbine inlet temperatures, leading to the need for advanced cooling methods such as film cooling, impingement cooling, and passage cooling in modern high-pressure turbines (HPTs). However, accurately predicting the nonuniform temperature distribution at the HPT inlet in real-time has been a challenge, resulting in oversized cooling flow rates of up to 25% of the core engine flow. To address this issue, this paper proposes a novel approach based on discrete measurements acquired at the HPT exit to predict the turbine inlet temperature and nonuniformity magnitude. The proposed method utilizes a multiwavelet approximation technique to extract the hot-streaks-related component at the HPT exit, which is then used to approximate the HPT inlet temperature distribution based on the hot-streaks' decay rate across the HPT. This paper provides an overview of the proposed method and its potential applications in the gas turbine industry. Additionally, the impact of burner-to-burner asymmetry on the accuracy of the proposed method is analyzed, and recommendations for improving its effectiveness in such scenarios are presented.
Model Predictive Control of a Multi-Mode Suspension System Using Preview Information and Weight Optimization
Authors: Batta Nathan A. , Doscher Daniel P.
Published: April 2023

This study examines the effectiveness of a model predictive controller (MPC) on the multimode active suspension concept to reduce driver absorbed power. A multimode suspension uses additional degrees-of-freedom beyond a traditional active suspension. This allows the suspension to address disturbances with multiple frequencies when coupled with a noncausal control scheme such as MPC. A half-car model is developed by placing both active and passive components in series to mitigate high and low frequency disturbances at the tire-road interface. A stepwise MPC with preview information is applied to the model to measure an incoming disturbance. The model includes noise in state feedback and preview information. A Kalman filter addresses process and measurement noise while the preview information is filtered using an exponential moving average. Process and Measurement noise are considered to be known. Four disturbance profiles are examined: step, two-mode, three-mode, and an ISO8608 Class D profile. Weights used for the MPC process are optimized for each profile according to an objective function based on driver absorbed power. For each profile the response for uncontrolled, controlled, and controlled with preview is examined to assess effectiveness of the multimode suspension. Results demonstrate the utility of the multimode suspension supplemented with MPC for each profile. Driver absorbed power decreases by 68%, 99%, 73%, and 89% for the step, two-mode, three-mode, and ISO8608 Class D profile, respectively. Examination of the natural, disturbance, and forcing frequencies suggests that the MPC accounts for the damped natural frequencies of the system in response to incoming disturbances. The system shows potential to improve performance of vehicles traversing extreme terrain or maintaining a stable chassis for a variety of applications. Future work includes examination of the relationship between the damped natural frequencies, the disturbance, and the resulting control law.
Active control of airfoil turbulent boundary layer noise with trailing-edge blowing
Authors: Yang Chenghao , Arcondoulis Elias J. G. , Yang Yannian , Guo Jing , Maryami Reza , Bi Chuanxing , Liu Yu
Published: April 2023

Large Eddy Simulation (LES) and Ffowcs Williams-Hawkings acoustic analogy are performed to study the effect of trailing-edge blowing on airfoil self-noise. Simulations were conducted using a National Advisory Committee for Aeronautics 0012 airfoil at zero angle of attack and a chord-based Reynolds number of 4 × 10 5. The aerodynamic and aeroacoustic characteristics of the baseline airfoil were thoroughly verified by comparison with previous numerical and experimental data. The noise reduction effects of continuous and local blowing with different blowing ratios and blowing momentum coefficients were compared. A maximum noise reduction of 20 dB was achieved via trailing-edge blowing and the noise reduction mechanisms of the two blowing methods were discussed. The LES results show a pair of recirculation bubbles in the airfoil wake which are suppressed by trailing-edge blowing. As the blowing vortices convect into the wake, they stretch and stabilize the shear flows from airfoil surfaces. Instantaneous vorticity and root mean square velocity fluctuations are also weakened. There is a decrease in the spanwise coherence and an increase in the phase difference, which contribute to noise reduction. It is concluded that the suppression of turbulence fluctuations in the near wake is the main mechanism of noise reduction for airfoil trailing-edge blowing.
Developmentally programmed histone H3 expression regulates cellular plasticity at the parental-to-early embryo transition
Authors: Gleason Ryan J. , Guo Yanrui , Semancik Christopher S. , Ow Cindy , Lakshminarayanan Gitanjali , Chen Xin
Published: April 2023

During metazoan development, the marked change in developmental potential from the parental germline to the embryo raises an important question regarding how the next life cycle is reset. As the basic unit of chromatin, histones are essential for regulating chromatin structure and function and, accordingly, transcription. However, the genome-wide dynamics of the canonical, replication-coupled (RC) histones during gametogenesis and embryogenesis remain unknown. In this study, we use CRISPR-Cas9–mediated gene editing in
Caenorhabditis elegans
to investigate the expression pattern and role of individual RC histone
H3
genes and compare them to the histone variant,
H3.3
. We report a tightly regulated epigenome landscape change from the germline to embryos that are regulated through differential expression of distinct histone gene clusters. Together, this study reveals that a change from a H3.3- to H3-enriched epigenome during embryogenesis restricts developmental plasticity and uncovers distinct roles for individual
H3
genes in regulating germline chromatin.
Capturing what and why in healthcare innovation
Authors: Reid Benet , Davis Lori Leigh , Gordon Lisi
Published: April 2023

Understandings of innovation usually encompass multiple overlapping aspects, putting innovation terminology at risk of vagueness and overuse. However, innovation concepts are expected to remain powerful and useful in healthcare beyond the pandemic and into the future, so clarity will be helpful for effective leadership. To disentangle and disambiguate meanings within innovation, we offer a framework that captures and simplifies foundational substance within innovation concepts. Our method is an overview review of innovation literature from the 5 years preceding COVID-19. 51 sources were sampled and analysed for explicit definitions of healthcare innovation. Drawing on broad themes suggested from previous reviews, and gathering specific themes emergent from this literary dataset, we focused on categorising the nature of innovations (the what) and reasons given for them (the why). We identified 4 categories of what (ideas, artefacts, practice/process and structure) and 10 categories of why (economic value, practical value, experience, resource use, equity/accessibility, sustainability, behaviour change, specific-problem solving, self-justifying renewal and improved health). These categories reflect contrasting priorities and values, but do not substantially interfere or occlude each other. They can freely be additively combined to create composite definitions. This conceptual scheme affords insight and clarity for creating precise meanings, and making critical sense of imprecision, around innovation. Improved communication and clear shared understandings around innovative intentions, policies and practices cannot but improve the chances of enhanced outcomes. The all-inclusive character of this scheme leaves space for considering the limits of innovation, and notwithstanding well-established critiques, provides a basis for clarity in ongoing usage.
Health measurement instruments and their applicability to military veterans: a systematic review
Authors: Jomy Jane , Jani P , Sheikh F , Charide R , Mah J , Couban R J , Kligler B , Darzi A J , White B K , Hoppe T , Busse J W , Zeraatkar D
Published: April 2023

Introduction

Accurate measurement of health status is essential to assess veterans’ needs and the effects of interventions directed at improving veterans’ well-being. We conducted a systematic review to identify instruments that measure subjective health status, considering four components (ie, physical, mental, social or spiritual well-being).

Methods

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we searched CINAHL, MEDLINE, Embase, PsycINFO, Web of Science, JSTOR, ERIC, Social Sciences Abstracts and ProQuest in June 2021 for studies reporting on the development or evaluation of instruments measuring subjective health among outpatient populations. We assessed risk of bias with the Consensus-based Standards for the Selection of Health Measurement Instruments tool and engaged three veteran partners to independently assess the clarity and applicability of identified instruments.

Results

Of 5863 abstracts screened, we identified 45 eligible articles that reported health-related instruments in the following categories: general health (n=19), mental health (n=7), physical health (n=8), social health (n=3) and spiritual health (n=8). We found evidence for adequate internal consistency for 39 instruments (87%) and good test–retest reliability for 24 (53%) instruments. Of these, our veteran partners identified five instruments for the measurement of subjective health (Military to Civilian Questionnaire (M2C-Q), Veterans RAND 36-Item Health Survey (VR-36), Short Form 36, Abbreviated World Health Organization Quality of Life questionnaire (WHOQOL-BREF) and Sleep Health Scale) as clear and very applicable to veterans. Of the two instruments developed and validated among veterans, the 16-item M2C-Q considered most components of health (mental, social and spiritual). Of the three instruments not validated among veterans, only the 26-item WHOQOL-BREF considered all four components of health.

Conclusion

We identified 45 health measurement instruments of which, among those reporting adequate psychometric properties and endorsed by our veteran partners, 2 instruments showed the most promise for measurement of subjective health. The M2C-Q, which requires augmentation to capture physical health (eg, the physical component score of the VR-36), and the WHOQOL-BREF, which requires validation among veterans.
Cadaveric study investigating the femoral nerve-sparing volume for pericapsular nerve group (PENG) block
Authors: Leurcharusmee Prangmalee , Kantakam Perada , Intasuwan Pittayarat , Malatong Yanumart , Maikong Naraporn , Navic Pagorn , Kitcharanant Nitchanant , Mahakkanukrauh Pasuk , Tran De Q
Published: April 2023

Background

This cadaveric study investigated the maximum effective volume of dye in 90% of cases (MEV90) required to stain the iliac bone between the anterior inferior iliac spine (AIIS) and the iliopubic eminence (IPE) while sparing the femoral nerve during the performance of pericapsular nerve group (PENG) block.

Methods

In cadaveric hemipelvis specimens, the ultrasound transducer was placed in a transverse orientation, medial and caudal to the anterior superior iliac spine in order to identify the AIIS, the IPE and the psoas tendon. Using an in-plane technique and a lateral-to-medial direction, the block needle was advanced until its tip contacted the iliac bone. The dye (0.1% methylene blue) was injected between the periosteum and psoas tendon. Successful femoral-sparing PENG block was defined as the non-staining of the femoral nerve on dissection. Volume assignment was carried out using a biased coin design, whereby the volume of dye administered to each cadaveric specimen depended on the response of the previous one. In case of failure (ie, stained femoral nerve), the next one received a lower volume (defined as the previous volume with a decrement of 2 mL). If the previous cadaveric specimen had a successful block (ie, non-stained femoral nerve), the next one was randomized to a higher volume (defined as the previous volume with an increment of 2 mL), with a probability of b=1/9, or the same volume, with a probability of 1–b=8/9.

Results

A total of 32 cadavers (54 cadaveric hemipelvis specimens) were included in the study. Using isotonic regression and bootstrap CI, the MEV90 for femoral-sparing PENG block was estimated to be 13.2 mL (95% CI: 12.0 to 20.0). The probability of a successful response was estimated to be 0.93 (95% CI: 0.81 to 1.00).

Conclusion

For PENG block, the MEV90 of methylene blue required to spare the femoral nerve in a cadaveric model is 13.2 mL. Further studies are required to correlate this finding with the MEV90 of local anesthetic in live subjects.
A Study on the Triangular-Wave Electrodeposition of Iridium Oxide on Ti
Authors: Wu Dandan , Wang Xi , Wang Zixuan , Wu Xu
Published: April 2023

Iridium oxide is recognized as the best oxygen evolution anode material due to its excellent electrocatalytic activity and long-term stability in acidic environment. Electrodeposition, as a new method for preparing iridium oxide catalysts, has attracted extensive attention in recent years. We report a triangular-wave electrodeposition method for the preparation of iridium oxide electrodes and successfully synthesized highly active IrOx electrodes with ultralow iridium loading. The IrOx electrode prepared at 100 mV s−1 for 100 cycles exhibited a superior mass activity of 3.11 A mgIr
−1, while the IrOx electrodeposited at 20 mV s−1 for 500 cycles has the best apparent electrocatalytic activity, Tafel slope as low as 54.75 mV dec−1. Physical characterization and electrochemical experiments show that the calcination treatment plays an important role in enhancing the OER performance of the electrodes. Remarkably, the calcined IrOx-TWE/Ti can continuously catalyze OER in 0.5 M H2SO4 at 50 mA cm−2 for 150 h with a slight performance decay, demonstrating a supper large stability number of

2.78
×

10

5

.

This work provides some valuable insights into the application of electrodeposition-based iridium oxide to practical industrial systems.
Measuring the Luminescent Properties of EuD4TEA Using a Modified Thermographic Phosphor LabKit
Authors: Miller John , Hollerman William , Allison Stephen
Published: April 2023

The Thermographic Phosphor LabKit, manufactured by Emerging Measurements Company (EMCO), provides a means to determine the temperature-dependent rise times, decay times, and the total light yield for thermographic phosphors. Such phosphors are primary sensing materials for luminescence thermometry. This field is the focus of much recent innovation with applications ranging from high temperature aerodynamic surfaces to submicron thermometry for nanotechnology and biomedicine. This instrument is unique as being one of the only turn-key methods that easily measures fluorescence decay and rise time over a temperature range of -10 to 80 ˚C. The LabKit also allows the next generation of scientists and engineers to be trained using the best and most up-to-date research methods. As originally configured, the LabKit was not designed to take spectral measurements. This current work describes modification of the LabKit to measure emission spectra for a sample of triethylammonium tetrakis (dibenzoylmethide) europate (III), more commonly known as europium tetrakis (EuD4TEA). To analyze this data, a program called Spectrum Reader was developed. In addition, a new program called Double Decay was written to allow users to quickly analyze large batches of time-resolved data, making the enhanced LabKit a more useful instrument for a wide variety of research applications. Comparison of results using the LabKit to previous measurements of La2O2S:Eu yielded good results, with error bars less than 5% of the earlier measured values. This paper will present an overview of the enhanced LabKit hardware, the new analysis software, and how this was used to analyze EuD4TEA.
Successful Treatment of a Case of Metallo-Beta-Lactamase-Producing Raoultella ornithinolytica Bacteremia by Antimicrobial Stewardship Team Intervention and Therapeutic Drug Monitoring-Based Amikacin Treatment
Authors: Koishi Noriko , Sasano Hiroshi , Yoshizawa Toshihiro , Shikuri Mika , Matsumoto Hiroshi , Suzuki Mai , Fukui Yukiko , Chonan Masayoshi , Kimura Toshimi , Ichida Hirofumi , Saiura Akio , Naito Toshio
Published: April 2023

An 80-year-old woman underwent pancreatoduodenectomy. Post-operation, she experienced a fever, and a culture of blood revealed metallo-beta-lactamase-producing Raoultella ornithinolytica. For treatments with aminoglycoside antimicrobial agents, a therapeutic drug monitoring-based dosing design can lower the risk of adverse events and enable appropriate treatment. Key Clinical Message. When aminoglycoside antimicrobial agents are administered for MBL-producing bacteremia, prescription suggestions based on TDM by antimicrobial stewardship team can reduce the occurrence of adverse events and enable appropriate treatment.
Cedrus deodara: In Vivo Investigation of Burn Wound Healing Properties
Authors: Rastegari Arezoo , Manayi Azadeh , Akbarzadeh Tahmineh , Hojjatifard Reza , Samadi Nasrin , Khanavi Mahnaz , Niknam Somayeh , Saeedi Mina
Published: April 2023

Objective. Cedrus deodara (Roxb. Ex Lamb.) G. Don possesses various biological activities, which have been documented in modern and traditional medicine. In this study, burn wound healing activity of the methanol extract of C. deodara wood was evaluated via a burn wound model in Wistar rats. Methods. The methanol extract of C. deodara was evaluated for the contents of phenolic compounds, flavonoids, and tannins. Also, its antioxidant activity was determined using the DPPH assay. Then, a topical ointment containing the methanol extract of C. deodara (10%) was used to evaluate the healing effects on a model of second‐degree thermal burn in 4 groups of 7 rats within 21 days. In this respect, average wound surface area, wound closure, and various histological features were examined. Results. Our findings revealed that the wounds treated with the methanol extract of C. deodara showed higher wound contraction (33.6, 87.1, and 93.4% on days 7, 14, and 21, respectively) compared with the positive control (27.6, 80.7, and 88.3% on days 7, 14, and 21, respectively) and the negative control (20.1, 77.9, and 80.2% on days 7, 14, and 21, respectively). According to the results from epitheliogenesis score, the number of inflammatory cells, neovascularization, and collagen density, good burn wound healing activity of the methanol extract of C. deodarawas demonstrated. Conclusion. Using the methanol extract of C. deodara in an ointment formulation can be developed to prevent or reduce burn injury progression.
Finite Element Analysis of a Reinforced Concrete Dapped-End Beam under the Effects of Impact Velocity and Dapped-End Beam Cross-Section Geometry
Authors: Melesse Getinet , Behailu Tekalign , Kaske Kassa Hibretu
Published: April 2023

This study focuses on the behavior of a three-dimensional reinforced concrete dapped-end beam subjected to the effects of impact velocity and dapped-end beam cross-section geometry by numerical simulation using ABAQUS (V6.14) software under a constant impact load. The finite element software ABAQUS is utilized to simulate and analyze the drop impact to obtain accurate and detailed results. A sudden drop impact is a short-duration dynamic load that could involve very large deformations and damage to the reinforced concrete dapped-end beam. The finite element analysis has been completed by creating the geometry, material properties, boundary conditions, and loading conditions. In this study, a total of seven analyzes were conducted with different parameters, i.e., the effect of the velocity of the impact load and the geometry of the dapped-end beam cross-section. From the finite element analysis results, it can be concluded that as the impact velocity increases, the impact force and mid-span displacement of the reinforced concrete dapped-end beam also increases. The higher the impact velocity, the greater the amount of damage caused throughout the RC beam. When the recess length increases from 200 mm to 500 mm, the deflection increases by 13%. The depth of the nib has a great influence on the impact response and deflection of the reinforced concrete dapped end beam. The ABAQUS output shows that increasing the dapped end beam nib depth from 260 mm to 450 mm reduces the impact load by 50%, from 22733.6 N to 13640.16 N. On the other hand, the nib depth increased from 260 mm to 450 mm, and the maximum deflection was reduced from 1.10245 mm to 0.6892 mm, i.e., a 46.1% reduction.
Supplementary Tables S1-S12 from Gene-Level Germline Contributions to Clinical Risk of Recurrence Scores in Black and White Patients with Breast Cancer
Authors: Patel Achal , García-Closas Montserrat , Olshan Andrew F. , Perou Charles M. , Troester Melissa A. , Love Michael I. , Bhattacharya Arjun
Published: April 2023

Supplementary Tables S1-S12
Supplementary Methods, Figures S1 - S7, and References from Gene-Level Germline Contributions to Clinical Risk of Recurrence Scores in Black and White Patients with Breast Cancer
Authors: Patel Achal , García-Closas Montserrat , Olshan Andrew F. , Perou Charles M. , Troester Melissa A. , Love Michael I. , Bhattacharya Arjun
Published: April 2023

Supplementary Methods, Figures S1-S7, and References
Supplementary Table S3 from Precision Cut Lung Slices as a Preclinical Model for Non–Small Cell Lung Cancer Chemoprevention
Authors: Sompel Kayla , Smith Alex J. , Hauer Caroline , Elango Alamelu P. , Clamby Eric T. , Keith Robert L. , Tennis Meredith A.
Published: April 2023

Supplementary Table S3 lists antibody combinations used for immune cell detection in Figure 5.
Supplementary Table S2 from Precision Cut Lung Slices as a Preclinical Model for Non–Small Cell Lung Cancer Chemoprevention
Authors: Sompel Kayla , Smith Alex J. , Hauer Caroline , Elango Alamelu P. , Clamby Eric T. , Keith Robert L. , Tennis Meredith A.
Published: April 2023

Supplementary Table S2 lists antibody information for immunofluorescence in Figure 5.
Suppl. Table 7 from The DNA Damage Response and Inflammation in Cancer
Authors: Klapp Vanessa , Álvarez-Abril Beatriz , Leuzzi Giuseppe , Kroemer Guido , Ciccia Alberto , Galluzzi Lorenzo
Published: April 2023

Other DDR pathways in inflammation and cancer
Suppl. Table 6 from The DNA Damage Response and Inflammation in Cancer
Authors: Klapp Vanessa , Álvarez-Abril Beatriz , Leuzzi Giuseppe , Kroemer Guido , Ciccia Alberto , Galluzzi Lorenzo
Published: April 2023

DDR signaling and inflammation in cancer
Suppl. Table 4 from The DNA Damage Response and Inflammation in Cancer
Authors: Klapp Vanessa , Álvarez-Abril Beatriz , Leuzzi Giuseppe , Kroemer Guido , Ciccia Alberto , Galluzzi Lorenzo
Published: April 2023

HR and inflammation in cancer
Suppl. Table 3 from The DNA Damage Response and Inflammation in Cancer
Authors: Klapp Vanessa , Álvarez-Abril Beatriz , Leuzzi Giuseppe , Kroemer Guido , Ciccia Alberto , Galluzzi Lorenzo
Published: April 2023

NHEJ and inflammation in cancer
Suppl. Table 2 from The DNA Damage Response and Inflammation in Cancer
Authors: Klapp Vanessa , Álvarez-Abril Beatriz , Leuzzi Giuseppe , Kroemer Guido , Ciccia Alberto , Galluzzi Lorenzo
Published: April 2023

MMR and inflammation in cancer
Suppl. Table 1 from The DNA Damage Response and Inflammation in Cancer
Authors: Klapp Vanessa , Álvarez-Abril Beatriz , Leuzzi Giuseppe , Kroemer Guido , Ciccia Alberto , Galluzzi Lorenzo
Published: April 2023

BER and inflammation in cancer
High Inner Centromere Protein Expression Correlates with Aggressive Features and Predicts Poor Prognosis in Patients with Invasive Breast Cancer
Authors: Ibrahim Asmaa , Miligy Islam M. , Toss Michael S. , Green Andrew R. , Rakha Emad A.
Published: April 2023

Introduction: Inner centromere protein (INCENP) is a member of the chromosomal passenger complex and plays a key role in mitosis and cell proliferation. This study aimed to evaluate the clinical and prognostic significance of INCENP in invasive breast cancer (BC). Methods: INCENP expression was evaluated on a tissue microarray of a large BC cohort (n = 1,295) using immunohistochemistry. At the mRNA level, INCENP expression was assessed using the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (n = 1,980) and The Cancer Genome Atlas (TCGA) BC cohorts (n = 854). The correlations between INCENP expression, clinicopathological parameters, and patient outcome were investigated. Results: INCENP expression was detected in the nucleus and cytoplasm of the tumour cells. Its expression was significantly associated with features characteristic of aggressive BC behaviour including high tumour grade, larger tumour size, and high Nottingham prognostic index scores. High INCENP nuclear expression was a predictor of shorter BC-specific survival in the whole cohort, as well as in the luminal subtype (p < 0.001). High INCENP nuclear expression was predictive of poor prognosis in BC patients who received hormone treatment or chemotherapy. Conclusion: High INCENP expression is a poor prognostic biomarker in BC with potential therapeutic benefits.
St. Gallen/Vienna 2023: Optimization of Treatment for Patients with Primary Breast Cancer – A Brief Summary of the Consensus Discussion
Authors: Balic Marija , Thomssen Christoph , Gnant Michael , Harbeck Nadia
Published: April 2023

The St. Gallen Consensus Conference on early breast cancer treatment 2023 was again a live event and took place in Vienna, Austria. After 4 years and one virtual event due to the pandemic, more than 2,800 participants from over 100 countries came together in Vienna, and the 2023 St. Gallen/Vienna conference was a great success. Over 3 days, the global faculty reviewed the most important evidence published during the last 2 years and debated over controversial topics, and finally, the consensus votes aimed to define the impact of the new data on everyday routine practice. Focuses of this year’s conference were radiotherapy and local management of the axilla, genetics, and their impact on treatment, as well as the role of the immune system and tumor-infiltrating lymphocytes in pathological reports and treatment decision-making. The traditional panel votes were moderated for the first time by Harold Burstein from Boston, and with questions previously voted on and live voting, the panel managed for the most part to clarify the critical questions. This report by editors of BREAST CARE summarizes the results of the 2023 international panel votes with respect to locoregional and systemic treatment as a brief news update but does not intend to replace the official St. Gallen Consensus publication that not just reports but also interprets the panel votes and will follow shortly in a major oncological journal. The next (19th) St. Gallen International Breast Cancer Conference will again take place in Vienna (save the date: March 12–15, 2025).
Activation of the High Mobility Group Box 1/Receptor for Advanced Glycation Endproducts /NOD‐like Receptor Family Pyrin Domain‐Containing 3 Axis Under Chronic Intermittent Hypoxia Induction Promotes the Progression of Atherosclerosis in ApoE
−/−
Mice
Authors: Tan Haoqu , Hu Jinfang , Zuo Wei , Huang Yun , Cui Jian , Gong Fei , Bai Wei
Published: April 2023

Background

Chronic intermittent hypoxia (CIH) has been regarded as an important cause of atherosclerotic disease. In our study, we set out to investigate whether CIH regulated the high mobility group box 1/receptor for advanced glycation endproducts/NOD‐like receptor family pyrin domain‐containing 3 (HMGB1/RAGE/NLRP3) axis to affect the progression of atherosclerosis.

Methods and Results

Initially, peripheral blood samples were collected from patients with single obstructive sleep apnea, atherosclerosis complicated with obstructive sleep apnea, and healthy volunteers. In vitro cell experiments were conducted using human monocyte cell line THP‐1 and human umbilical vein endothelial cells to explore the role of HMGB1 in cell migration, apoptosis, adhesion, and transendothelial migration. In addition, a CIH‐induced atherosclerosis mouse model was established for further identifying the critical role of the HMGB1/RAGE/NLRP3 axis in atherosclerosis. Upregulated HMGB1 and RAGE were found in patients with atherosclerosis complicated with obstructive sleep apnea. CIH induction increased HMGB1 expression by inhibiting HMGB1 methylation, activating the RAGE/NLRP3 axis. After inhibition of the HMGB1/RAGE/NLRP3 axis, monocyte chemotaxis and adhesion were repressed, and macrophage‐derived foam cell formation was inhibited, accompanied by suppression of endothelial and foam cell apoptosis and inflammatory factor secretion. In vivo animal experiments also noted that the progression of atherosclerosis was prevented by inhibition of the HMGB1/RAGE/NLRP3 axis in CIH‐induced ApoE
−/−
mice.

Conclusions

Taken together, CIH induction can upregulate HMGB1 through inhibition of HMGB1 methylation, which activates the RAGE/NLRP3 axis to promote inflammatory factor secretion, thereby promoting the progression of atherosclerosis.
Health‐Related Quality of Life and Its Association With Outcomes in Adults With Congenital Heart Disease and Heart Failure: Insight From FRESH‐ACHD Registry
Authors: Ly Reaksmei , Karsenty Clément , Amedro Pascal , Cohen Sarah , Domanski Olivia , Godart Francois , Radojevic Jelena , Vaksmann Guy , Naccache Nicole , Boubrit Anissa , Bataille Vincent , Hascoet Sébastien , Ladouceur Magalie
Published: April 2023

Background

Quality of Life (QoL) is a prognostic factor in heart failure (HF) of patients with acquired cardiac disease. The aim of this study was to determine the predictive value of QoL on outcomes in adults with congenital heart disease (ACHD) and HF.

Methods and Results

Quality of life of 196 adults with congenital heart disease with clinical heart failure (HF) (mean age: 44.3±13.8 years; 51% male; 56% with complex congenital heart disease; 47% New York Heart Association class III/IV) included in the prospective multicentric registry FRESH‐ACHD (French Survey on Heart Failure−Adult with Congenital Heart Disease) was assessed using the 36‐Item Short Form Survey (SF‐36), a patient‐reported survey. The primary end point was defined by all‐cause death, HF‐related hospitalization, heart transplantation, and mechanical circulatory support. At 12 months, 28 (14%) patients reached the combined end point. Patients with low quality of life experienced major adverse events more frequently (logrank
P
=0.013). On univariate analysis, lower score at physical functioning (hazard ratio [HR], 0.98 [95% CI, 0.97–0.99];
P
=0.008), role limitations related to physical health (HR, 0.98 [95% CI, 0.97–0.99];
P
=0.008), and general health dimensions of the SF‐36 (HR, 0.97 [95% CI, 0.95–0.99];
P
=0.002) were significantly predictive of cardiovascular events. However, after multivariable analysis, SF‐36 dimensions were no longer significantly associated with the primary end point.

Conclusions

Patients with congenital heart disease with HF and poor quality of life experience severe events more frequently, making quality of life assessment and rehabilitation programs essential to alter their trajectory.
Improvement of Symptoms and Quality of Life After Successful Percutaneous Coronary Intervention for Chronic Total Occlusion in Elderly Patients
Authors: Zhao Shuai , Wang Jiayi , Chen Yan , Wang Wei , Hu Wentao , Zou Yiming , Zhu Boda , Yang Li , Chen Genrui , Yu Tiantong , Han Peng , Ma Bingqi , Wang Huan , Xia Chenhai , Wang Rutao , Tan Zhijun , Zhai Zhongjie , Li Rong , Gao Haokao , Lian Kun , Li Chengxiang
Published: April 2023

Background

Data regarding the impact of successful chronic total occlusion treated with percutaneous coronary intervention (CTO‐PCI) on symptoms and quality of life (QOL) in elderly patients (≥75 years) are unknown. This prospective study aimed to assess whether successful CTO‐PCI could improve the symptoms and QOL in elderly patients (≥75 years).

Methods and Results

Consecutive patients who underwent elective CTO‐PCI were prospectively enrolled and subdivided into 3 groups based on age: age<65 years, 65 years≤age<75 years, and age≥75 years. The primary outcomes included symptoms, as assessed with the New York Heart Association functional class and Seattle Angina Questionnaire, and QOL, as assessed with the 12‐Item Short‐Form Health Survey questionnaire, at baseline, 1 month, and 1 year after successful CTO‐PCI. Of 1076 patients with CTO, 101 were age≥75 years (9.39%). Hemoglobin, estimated glomerular filtration rate, and left ventricular ejection fraction levels all decreased with increasing age, and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) increased. The proportion of dyspnea and coronary lesions, including multivessel disease, multi‐CTO lesion, and calcification were higher in elderly patients. Procedural success rate, intraprocedural complications, and in‐hospital major adverse cardiac events were not statistically different in the 3 groups. Importantly, symptoms, including dyspnea and angina, were markedly improved regardless of age at 1‐month and 1‐year follow‐up (
P
<0.05). Likewise, successful CTO‐PCI significantly improved QOL at 1‐month and 1‐year follow‐up (
P
<0.01). Additionally, the incidence of major adverse cardiac events and all‐cause mortality at 1‐month and 1‐year follow‐up was not statistically different in the 3 groups.

Conclusions

Successful PCI was beneficial and feasible to improve symptoms and QOL in patients ≥75 years of age with CTO.
Is research funding always beneficial? A cross-disciplinary analysis of U.K. research 2014–20
Authors: Thelwall Mike , Kousha Kayvan , Abdoli Mahshid , Stuart Emma , Makita Meiko , Font-Julián Cristina I. , Wilson Paul , Levitt Jonathan
Published: April 2023

Although funding is essential for some types of research and beneficial for others, it may constrain academic choice and creativity. Thus, it is important to check whether it ever seems unnecessary. Here we investigate whether funded U.K. research tends to be higher quality in all fields and for all major research funders. Based on peer review quality scores for 113,877 articles from all fields in the U.K.’s Research Excellence Framework (REF) 2021, we estimate that there are substantial disciplinary differences in the proportion of funded journal articles, from Theology and Religious Studies (16%+) to Biological Sciences (91%+). The results suggest that funded research is likely to be of higher quality overall, for all the largest research funders, and for 30 out of 34 REF Units of Assessment (disciplines or sets of disciplines), even after factoring out research team size. There are differences between funders in the average quality of the research supported, however. Funding seems particularly associated with higher research quality in health-related fields. The results do not show cause and effect and do not take into account the amount of funding received but are consistent with funding either improving research quality or being won by high-quality researchers or projects.
Xunzi and Zhuangzi on Music: Two Ways of Modeling the Ethical Significance of Art
Authors: Kreis Guido
Published: April 2023

This paper analyses two early Chinese ways of modeling the ethical significance of art using music as an example. I shall focus on the Xunzi 《荀子》 as a paradigmatic statement of Confucian views, and selected passages from the Zhuangzi 《莊子》 as an exemplary manifestation of Daoist aesthetics. I argue that the Xunzi opts for a direct ethical impact of music, while it does not rely on an independent aesthetic conception of the goodness of music. By contrast, I argue that the Zhuangzi discusses music on the grounds of an independent aesthetic conception of its goodness, while music can only claim an indirect ethical significance. Both models are mutually exclusive. This gives reason to believe that the Xunzi and the Zhuangzi present us with the two systematically possible ways of modeling the ethical impact of art.
Heart and Beyond: Following Emotion Farther Out
Authors: Casey Edward S.
Published: April 2023

Urgent times such as ours call for a reexamination of human emotional life, a life we tend to take for granted in calmer times. Philosophy, and phenomenology in particular, should have something to say about our emotional bearings or their lack in this dürftiger Zeit, a time of collective crisis and personal desperation. My hope is that a careful assessment of emotion will be of value to those of us living through what Hannah Arendt called “dark times.” As a phenomenologist, my aim is a mainly descriptive one that seeks to arrive at a more precise sense of the emergence of emotion, not as construed causally but as felt experientially. Accordingly, I shall pursue the paths traced by certain manifestations of emotion: paths that have been largely neglected in recent treatments. Being on this road (and there is no other) amounts to living with the consequences of the manifestation of emotions, what I have come to call them periphaneity.
Tissue Inhibitors of Metalloproteinases 1 Confers 5-Fluorouracil Resistance and Stemness of Gastric Cancer Cells via the Up-Regulation of Hypoxia-Inducible Factor-1α
Authors: Jiang Jinxia , He Xiaogu , Shuang Fen , Fang Xiangming , Zhu Feng
Published: April 2023

The role and potential mechanism of TIMP1 in resistance to 5-Fluorouracil (5-Fu) and stem properties in gastric cancer (GC) were investigated. The expressions of HIF-1α and TIMP1, as well as the chemosensitivity of the 5-Fu in GC cell lines (GCCL) (e.g., MGC-803, BGC-823,
SGC-7901, HGC-27 and AGS) upon normoxia or hypoxia were analyzed by means of RT-PCR and CCK-8 assay, respectively. Meanwhile, the population of stem cells was determined by using sphere formation assay, while stem cell markers (SCM) (Oct4 and CD44) were detected by western blot to evaluate
stem properties. Hypoxia led to upregulated expression of HIF-1α and TIMP1, and enhanced resistance to 5-Fu, sphere formation capability, and expression of SCM in GC cells (GCCs). Indeed, the expressions of TIMP1 and HIF-1α were positively related to each other. The
protein levels of both HIF-1α and TIMP1 were increased and decreased by overexpressing and silencing TIMP1, respectively. Under hypoxia conditions, overexpression of TIMP1 conferred 5-Fu-resistance and stem properties to MGC-803 and AGS cells, as revealed by increased IC50 value
of 5-Fu, enhanced sphere formation, and up-regulation of Oct4 and CD44; silencing TIMP1 caused the contrary results. TIMP1 is an effective regulator of HIF-1 and plays a critical role in resistance to 5-Fu and stem properties in GCCs upon hypoxia.
The Effect of Thyroxin on the Biological Effects of High Glucose-Induced Human Retinal Endothelial Cells and B-Cell Lymphoma 2/Bcl-2 Associated X
Authors: Liu Lei , Yuan Xiaoyong , Gao Yanlin
Published: April 2023

This study intends to assess the biological effect of TTR on human retinal endothelial cells under high glucose. Cells were assigned into normal group, high glucose (HG) group and TTR intervention group followed by analysis of cell biological activity and protein expression. The retinal
endothelial cell proliferation rate was significantly promoted in HG group (P < 0.05) and inhibited in intervention group (P < 0.05). The HG group had significantly higher cell migration number than normal group (P < 0.05). However, migrated cell number in intervention
group was reduced significantly (P < 0.05). In addition, high glucose also significantly enhanced the invasion of retinal endothelial cells (P < 0.05), which was inhibited after TTR intervention (P < 0.05). Moreover, Bcl-2 protein was significantly downregulated
and Bax was upregulated in HG group compared to normal group (P < 0.05). Interestingly, their levels were normalized after TTR intervention without difference compared to their levels in normal group (P < 0.05). Consistently, the mRNA level of Bcl-2 and Bax showed similar
expression profiles to the protein expression in different groups (P < 0.05). In conclusion, TTR can inhibit the retinal endothelial cell proliferation, migration and invasion ability and regulate Bcl-2/Bax expression.