bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstructing Turbulent Flows Using Spatio-temporal Physical Dynamics
Authors: Chen Shengyu , Bao Tianshu , Givi Peyman , Zheng Can , Jia Xiaowei
Published: December 2023

Accurate simulation of turbulent flows is of crucial importance in many branches of science and engineering. Direct numerical simulation (DNS) provides the highest fidelity means of capturing all intricate physics of turbulent transport. However, the method is computationally expensive because of the wide range of turbulence scales that must be accounted for in such simulations. Large eddy simulation (LES) provides an alternative. In such simulations, the large scales of the flow are resolved, and the effects of small scales are modelled. Reconstruction of the DNS field from the low-resolution LES is needed for a wide variety of applications. Thus the construction of super-resolution methodologies that can provide this reconstruction has become an area of active research. In this work, a new physics-guided neural network is developed for such a reconstruction. The method leverages the partial differential equation that underlies the flow dynamics in the design of spatio-temporal model architecture. A degradation-based refinement method is also developed to enforce physical constraints and to further reduce the accumulated reconstruction errors over long periods. Detailed DNS data on two turbulent flow configurations are used to assess the performance of the model.
Conceptualizing and Measuring Trust, Mistrust, and Distrust: Implications for Advancing Health Equity and Building Trustworthiness
Authors: Richmond Jennifer , Anderson Andrew , Cunningham-Erves Jennifer , Ozawa Sachiko , Wilkins Consuelo H.
Published: December 2023

Trust is vital to public confidence in health and science, yet there is no consensus on the most useful way to conceptualize, define, measure, or intervene on trust and its related constructs (e.g., mistrust, distrust, and trustworthiness). In this review, we synthesize literature from this wide-ranging field that has conceptual roots in racism, marginalization, and other forms of oppression. We summarize key definitions and conceptual frameworks and offer guidance to scholars aiming to measure these constructs. We also review how trust-related constructs are associated with health outcomes, describe interventions in this field, and provide recommendations for building trust and institutional trustworthiness and advancing health equity. We ultimately call for future efforts to focus on improving the trustworthiness of public health professionals, scientists, health care providers, and systems instead of aiming to increase trust in these entities as they currently exist and behave.
High Sensitivity Detection of Nitrite Electrochemical Sensor Modified with MOF Composite Materials
Authors: Li Xu-Shan , Zou Xin , Chen Wen-Yi , Sun Qian , Gao En-Qing
Published: December 2023

Depositing composites of Ni-HHTP and MWCNTs on a glassy carbon electrode(GCE) have developed a sensitive and facile electrochemical sensor for nitrite detection. Ni-HHTP@MWCNTs composites were synthesized in situ using 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP), nickel acetate tetrahydrate Ni(OAc)2·4H2O and multi-walled carbon nanotubes (MWCNTs) by hydrothermal method. The composite electrode was prepared by the coating method. The synergistic combination of Ni-HHTP and MWCNTs enables the electrode to possess fast electronic conductivity and generate sensitive electrochemical signals for sodium nitrite (NaNO2). The controlled variable approach determines the best test conditions for the analyte and obtains a susceptible response signal. The composite electrode has an extensive linear response range of 1–10000 μM to NaNO2, with a detection limit of 0.95 μM and sensitivity of 0.96 mA·mM−1·cm−2, which shows excellent reproducibility and stability performance. There are no interferences from the most common ions. The electrochemical analysis method was used for nitrite detection in actual water samples with a recovery rate of 97.2%–103.7%, indicating this composite material’s practical application potential. The mechanism of the specific electrochemical process on the modified electrode was also explored. This work preliminarily explored new electrochemical sensors for high-precision nitrite detection and precise sensing in analysis tests.
Design and Fabrication of Protonic Ceramic Fuel Cells Based on BaZr0.8Y0.2O3−δ
|BaZr0.1Ce0.7Y0.1Yb0.1O3−δ
Bilayer Electrolyte
Authors: Ortiz-Corrales Julián A. , Matsuo Hiroki , Otomo Junichiro
Published: December 2023

Reducing electronic leakage is important for improving the performance of protonic ceramic fuel cells (PCFCs) because it can considerably decrease power efficiency. In this work, we explore the efficacy of bilayer electrolytes using BaZr0.8Y0.2O3−δ (BZY) and BaZr0.1Ce0.7Y0.1Yb0.1O3−δ
(BZCYYb) as the anode and cathode-side electrolytes, respectively. Theoretical calculations were used to guide the design and experimental fabrication of highly efficient cells. Computational results showed that higher efficiencies were achieved when a thin BZY layer was applied to a thicker BZCYYb layer. This configuration served as a barrier, effectively preventing electronic leakage. Subsequently, a BZY|BZCYYb cell was fabricated and tested using I-V and electrochemical impedance measurements. The results were compared with those of single-layer BZY and BZCYYb cells. The bilayer electrolyte exhibited higher open-circuit voltages, suggesting a reduction in the leakage current. Moreover, the bilayer cell exhibited the lowest ohmic resistance and highest power density. Thus, BZY|BZCYYb bilayer electrolytes can potentially improve the performance and efficiency of PCFCs.
2023 Colin Garfield Fink Postdoctoral Summer Fellowship – Summary Report: The Effect of Electrochemical Hydrogen Production and Storage in Ti3C2T
x
MXene on Cell Pressure
Authors: Wang Ruocon (John)
Published: December 2023

Hydrogen is a clean fuel that can power vehicles with high efficiency and produce water as the only byproduct. However, hydrogen technologies face challenges that include low volumetric storage capacity. One way to increase volumetric capacity is to store hydrogen in solid state materials. MXenes represent the fastest-growing family of 2D transition metal carbides and nitrides. Owning to their attractive properties, such as redox-active surfaces, metallic conductivity, and hydrophilicity, MXenes have been intensively studied for applications in electrocatalysis and electrochemical energy storage. Recently, Ti2CTx MXene was claimed to store over 8 wt% hydrogen. Since MXenes are also electrocatalysts for hydrogen production, investigating hydrogen storage while it is produced on the same material electrode is a promising direction. In this study, we investigated the effect of electrochemical hydrogen production and storage in Ti3C2Tx MXene on cell pressure in a sulfuric acidic electrolyte.
Tech Highlights
Authors: Pile Donald , Gallaway Joshua , McNulty David , Liu Chao (Gilbert) , Liu Zenghe , Karuppaiah Chock
Published: December 2023

A collection of technology highlights pulled from recent papers published in ECS journals.
Molecular Dynamics Study of Sapphire Polishing Considering Chemical Products
Authors: Liu Xianghong , Zhong Min , Xu Wenhu
Published: December 2023

The sapphire chemical mechanical polishing (CMP) process is complicated. The silicate products such as Al2SiO5 are produced during the polishing process. This paper applies molecular dynamics (MD) to study sapphire CMP process considering chemical products. The effects of Al2SiO5 on sapphire polishing as well as the polishing depth, speed and abrasive particle’s radius on the polishing of sapphire covered with Al2SiO5 were investigated by comparing polishing force, coefficient of friction (COF), temperature, removed atoms and subsurface quality. The results show that the Al2SiO5 film is beneficial to improving the removal rate and the subsurface quality of sapphire. Increasing the polishing depth can raise the material removal rate, but will aggravate the subsurface damage. The balance of chemical products and polishing depth should be controlled to keep them equivalent during sapphire polishing to minimize subsurface damage. The temperature of the workpiece will rise and the polishing force will decline with the increasing polishing speed. The removed atoms become more but the subsurface damage fluctuates. As the radius of the particle increases, the COF decreases, and the subsurface quality first rises and then declines. The best polishing quality was obtained at 150 m s−1 and 40 Å.
Transformation of SiO2 Particles to Si Film via Al-Assisted Electrochemical Reduction in Molten CaCl2
Authors: Kim Hyeonsu , Lee Jiseok , Lim Taeho , Kim Jae Jeong
Published: December 2023

A Si film was formed from SiO2 particles in CaCl2 molten salt by electrochemical reduction using liquid Al-Si alloys. The liquid Al-Si alloys, formed from electrochemically reduced Si and metallic Al during the electrochemical reduction of the SiO2 particles, not only promoted electrochemical reduction, but also induced Si thin film formation. The Si film growth was observed by optical imaging, while the morphology and composition of the films were characterized by scanning electron microscopy and X-ray diffraction analysis. A pulse reduction technique was introduced to promote SiO2 reduction. The effect of the on/off time ratio on the Si film formation was investigated, with efficient SiO2 reduction achieved via on/off time ratio optimization. At the optimized ratio, a 0.9-mm-thick Si film with a Si purity of 96 at% was obtained. This effective Si production system might contribute to the fabrication of low-cost solar cells and Si-related electronic devices that require Si films.
Physics-Informed Optimal Experiment Design of Calendar Aging Tests and Sensitivity Analysis for SEI Parameters Estimation in Lithium-ion Batteries
Authors: Movahedi Hamidreza , Pannala Sravan , Siegel Jason B. , Stefanopoulou Anna G.
Published: December 2023

This paper focuses on sensitivity analysis and optimal experiment design for calendar aging tests tofind SEI (solid-electrolyte interface) degradation parameters. This parameterization facilitates predicting theLi-ion battery end-of-life. To this end, a physics-based model of SEI layer is used to develop a closed formsolution for loss of Lithium inventory during calendar aging. This model is shown to match experimental data.Further, the developed model is used to find the sensitivity of LLI (loss of Lithium inventory) to SEIparameters in diffusion-limited and kinetically limited SEI patterns.Through this sensitivity analysis, we show that in the kinetically limited case, performing calendar aging testsat high SOCs gives the most accurate results. For the diffusion limited case, we use optimal experiment designtechniques to find the optimal calendar aging SOCs. It is also shown that, these optimal SOC values result inhigher accuracy estimations compared to sub-optimal SOCs.
Implications for neutrophils in cardiac arrhythmias
Authors: Hegemann Niklas , Barth Lukas , Döring Yannic , Voigt Niels , Grune Jana
Published: December 2023

Cardiac arrhythmias commonly occur as a result of aberrant electrical impulse formation or conduction in the myocardium. Frequently discussed triggers include underlying heart diseases such as myocardial ischemia, electrolyte imbalances, or genetic anomalies of ion channels involved in the tightly regulated cardiac action potential. Recently, the role of innate immune cells in the onset of arrhythmic events has been highlighted in numerous studies, correlating leukocyte expansion in the myocardium to increased arrhythmic burden. Here, we aim to call attention to the role of neutrophils in the pathogenesis of cardiac arrhythmias and their expansion during myocardial ischemia and infectious disease manifestation. In addition, we will elucidate molecular mechanisms associated with neutrophil activation and discuss their involvement as direct mediators of arrhythmogenicity.
Mechanisms of reduced myocardial energetics of the dystrophic heart
Authors: Stevens Jackie A. , Dobratz Tyler C. , Fischer Kaleb D. , Palmer Alexandria , Bourdage Kira , Wong Anne J. , Chapoy-Villanueva Hector , Garry Daniel J. , Liu Julia C. , Kay Matthew W. , Kuzmiak-Glancy Sarah , Townsend DeWayne
Published: December 2023

Dystrophic hearts have poor contractile reserve that is associated with a reduction in myocardial energetics. We demonstrate that oxygen delivery does not contribute to the limited energy production of the dystrophic heart even with increased workloads. Cytochrome optical spectroscopy of the contracting heart reveals alterations in complex IV and evidence of depolarized mitochondrial membranes. We show specific alterations in the electron transport chain of the dystrophic heart that may contribute to poor myocardial energetics.
Ultrasonographic assessment of pulmonary and central venous congestion in experimental heart failure
Authors: Hegemann Niklas , Sang Pengchao , Kim Jonathan H. , Koçana Ceren , Momin Noor , Klages Jan , Kucherenko Mariya M. , Knosalla Christoph , O’Brien Benjamin , Simmons Szandor , Nahrendorf Matthias , Kuebler Wolfgang M. , Grune Jana
Published: December 2023

As thorough, noninvasive assessment of congestion is not available in small animals, we developed and validated an ultrasonography-based research tool to evaluate pulmonary and central venous congestion in experimental heart failure models.
Relationship between Coronary Artery Calcium Score and Coronary Stenosis
Authors: Chen Xinyan , Zhao Jianbin , Cai Qingqing , Chen Rong , Wu Wenhao , Wang Peng , Zhang Gaoxing , Zhen Jinhuan
Published: December 2023

Background. The coronary artery calcium score (CACS) is commonly employed to quantify the degree of calcification in coronary atherosclerosis. Indeed, increased coronary stenosis severity is associated with a progressive increase in CACS. Objectives. This study sought to explore the association between CACS and coronary stenosis of ≥50% and ≥70%. Methods. We conducted a retrospective analysis of patient data collected between July 1, 2017, and March 3, 2022, at Jiangmen Central Hospital. A total of 208 patients, presenting with both symptomatic and asymptomatic manifestations and suspected coronary artery disease (CAD), were included. Statistical analyses included ROC curve assessments, subgroup analyses based on age, and comparisons of CACS values against the presence of coronary stenosis ≥50% and ≥70%. Results. Ultimately, 208 patients were included, with a median age of 65.0 years and a median CACS of 115.7 (interquartile range: 13.7–369.4). A CACS threshold of ≥1300 demonstrated a specificity of 100% for coronary stenosis of ≥50%. Notably, the percentage of patients with obstructive CAD showing CACS = 0 was significantly higher in those under 65 years (15.1%) compared to patients over 65 years (3.8%) (

P
=
0.005

). The inflection point, at which the risk probability for coronary stenosis of ≥50% shifted from being a protective factor to a risk factor, was observed when CACS fell within the range of 63.3 to 66.0. Conclusion. CACS demonstrates good performance for the detection of coronary artery stenosis.
High Levels of Vitamin A in Plant-Based Diets for Gilthead Seabream (Sparus aurata) Juveniles, Effects on Growth, Skeletal Anomalies, Bone Molecular Markers, and Histological Morphology
Authors: Dominguez David , Montero Daniel , Zamorano Maria Jesus , Castro Pedro L. , da Silva Joseane , Fontanillas Ramon , Izquierdo Marisol
Published: December 2023

Substitution of fish-based ingredients may alter the nutritional profile of the feeds, including the vitamin contents, ultimately leading to unbalanced vitamin supply. Vitamin A plays an essential role in epithelium preservation, cell differentiation, reproduction, and vision. It also intervenes in skeletogenesis through chondrocytes development. Therefore, low levels of vitamin A may cause poor growth and abnormal bone development among other symptoms. Besides, in gilthead seabream excess vitamin A altered bone structure and homeostasis, indicating that an upper level for vitamin A in feeds for this species must be defined. For this purpose, a practical plant-based diet (FM 10% and FO 6%) containing five increasing levels of vitamin A (24,000, 26,000, 27,000, 31,000, and 37,000 IU/kg) supplemented as retinyl acetate was formulated to identify the effects of high levels of vitamin A for gilthead seabream juveniles. The trial was conducted with 450 total fish distributed into 15 tanks, where each diet was tested in triplicates for 70 days. At the end of the trial, samples were taken for analyses of vitamin A—relevant markers. At the end of the trial the high levels of vitamin A supplementation did not cause a reduction in growth, whereas no significant effect was observed for the feed efficiency, specific growth rate, and feed convertion ratio. Although not significant, retinol content in liver showed a tendency to increase with the elevation of dietary vitamin A levels. Although minor, the highest level of vitamin A dietary content (37,000 IU/kg) caused a significant increase in caudal vertebrae partial fusion as well as caudal vertebrae malformations. Increasing dietary vitamin A was related to a reduction in the occurrence of microhemorrhages in the liver and a reduction in the presence of eosinophils associated to the pancreas. Overall, the results of the present study suggested that gilthead seabream juveniles fed a plant-based diet are able to tolerate very high levels of vitamin A supplementation when supplemented as retinyl acetate. Nevertheless, further supplementation should be avoided in order to reduce the prevalence of anomalies affecting the caudal vertebrae.
Moricandia sinaica (Boiss.): A Potent Source of Hypoglycaemic and Antidiabetic Remedy
Authors: Ullah Riaz , Shahat Abdelaaty A. , Hammad Ahmed A. , Alqahtani Ali S. , Nasr Fahd A. , Alharbi Mohammed S. , Alhuzani Mohammed R. , Tariq Akash
Published: December 2023

Here, we evaluated the antidiabetic and hypoglycaemic activities of Moricandia sinaica, a species of the Brassicaceae family, for the first time. The hypoglycaemic and antidiabetic activities of the M. sinaica shoot’s methanol extract (MOR-1), butanol fraction (MOR-2), and aqueous fraction (MOR-3) were examined against streptozotocin-induced diabetes model in albino Swiss mice. The mice were divided into eight groups (each group consisted of 6 mice). MOR-1 (100 and 200 mg/kg), MOR-2 (100 and 200 mg/kg), and MOR-3 (100 and 200 mg/kg) were administered to groups III, IV, V, VI, VII, and VIII, respectively, for 15 days (daily). The blood samples were haematologically and biochemically assessed at 0 days, 7 days, and 15 days. Mice in group I were kept untreated as control while group II was treated with glibenclamide as standard. Antidiabetic effects increased with MOR-1 and MOR-2 doses in a dose-dependent manner. MOR-2 treatment (200 mg/kg) yielded the best results (29.56% and 40.07% after 7 and 15 days, respectively) compared to the results obtained at zero days. MOR-2 (200 mg/kg) showed the greatest decline in glucose levels (27.67% and 41.13% after 7 and 15 days, respectively). The results concluded that M. sinaica exhibited potential hypoglycaemic activity.
Investigating Interaction Dynamics among Nonoil Economic Growth and Its Most Important Determinants: Evidence from Saudi Arabia
Authors: Al-Abdi Badr Saleh , Badr Abdallah M. M. , Ali Faisal A. M. , Jabbar Tawfik M. A. , Al–Salwi Fahmy
Published: December 2023

Over the past decades, Saudi Arabia’s economic development has strongly depended on oil revenues fueled by the rise of oil prices and the strong global market demands for crude oils. However, the country can no longer depend on oil revenues in the face of the dynamic global market, and hence, the Saudi government’s Vision 2030 seeks to reduce this dependence and diversify the economy’s sources of income. Motivated by this, this study aims to investigate the impact of growth factors: financial innovation (FI), nonoil trade openness (TO), nonoil gross capital formation (GCF), and human capital (CH) development on the nonoil economic growth in Saudi Arabia. The goal of this investigation is to examine the dynamic symmetrical and nonsymmetrical impact of these growth factors on nonoil economic growth and policymaking in Saudi Arabia. To achieve this, this study utilizes the distributed lag symmetric and asymmetric (ARDL and NARD) approaches to assess the short- and long-term symmetric relationships among these growth variables with nonoil economic growth as well as the stationarity, cointegration, and directionality among variables with the theory of “ceteris paribus” in the error correction model (ECM), and Granger causality framework to analyze time-series data from 1980 to 2020. The findings of this study revealed that the FI, TO, GCF, and CH have an impact on the nonoil economic growth in the short and long terms. Additionally, in the long term, the NARDL technique showed that the positive adjustments of HC, FI, TO, and GCF boost the development, which have very significant effects on the nonoil GDP. They also indicate that negative movements have more influence than positive movements in FI. Meanwhile, mixed directional causation results were observed in the short-run analyses. Overall, the findings of this study provide significant insights, empirical recommendations, and implications for policymakers striving to achieve sustainable nonoil trade economic growth in Saudi Arabia and the region.
Combining the Tyrosine Kinase Inhibitor Cabozantinib and the mTORC1/2 Inhibitor Sapanisertib Blocks ERK Pathway Activity and Suppresses Tumor Growth in Renal Cell Carcinoma
Authors: Wu Yige , Chen Siqi , Yang Xiaolu , Sato Kazuhito , Lal Preet , Wang Yuefan , Shinkle Andrew T. , Wendl Michael C. , Primeau Tina M. , Zhao Yanyan , Gould Alanna , Sun Hua , Mudd Jacqueline L. , Hoog Jeremy , Mashl R. Jay , Wyczalkowski Matthew A. , Mo Chia-Kuei , Liu Ruiyang , Herndon John M. , Davies Sherri R. , Liu Di , Ding Xi , Evrard Yvonne A. , Welm Bryan E. , Lum David , Koh Mei Yee , Welm Alana L. , Chuang Jeffrey H. , Moscow Jeffrey A. , Meric-Bernstam Funda , Govindan Ramaswamy , Li Shunqiang , Hsieh James , Fields Ryan C. , Lim Kian-Huat , Ma Cynthia X. , Zhang Hui , Ding Li , Chen Feng
Published: December 2023

Current treatment approaches for renal cell carcinoma (RCC) face challenges in achieving durable tumor responses due to tumor heterogeneity and drug resistance. Combination therapies that leverage tumor molecular profiles could offer an avenue for enhancing treatment efficacy and addressing the limitations of current therapies. To identify effective strategies for treating RCC, we selected ten drugs guided by tumor biology to test in six RCC patient-derived xenograft (PDX) models. The multitargeted tyrosine kinase inhibitor (TKI) cabozantinib and mTORC1/2 inhibitor sapanisertib emerged as the most effective drugs, particularly when combined. The combination demonstrated favorable tolerability and inhibited tumor growth or induced tumor regression in all models, including two from patients who experienced treatment failure with FDA-approved TKI and immunotherapy combinations. In cabozantinib-treated samples, imaging analysis revealed a significant reduction in vascular density, and single-nucleus RNA sequencing (snRNA-seq) analysis indicated a decreased proportion of endothelial cells in the tumors. SnRNA-seq data further identified a tumor subpopulation enriched with cell-cycle activity that exhibited heightened sensitivity to the cabozantinib and sapanisertib combination. Conversely, activation of the epithelial–mesenchymal transition pathway, detected at the protein level, was associated with drug resistance in residual tumors following combination treatment. The combination effectively restrained ERK phosphorylation and reduced expression of ERK downstream transcription factors and their target genes implicated in cell-cycle control and apoptosis. This study highlights the potential of the cabozantinib plus sapanisertib combination as a promising treatment approach for patients with RCC, particularly those whose tumors progressed on immune checkpoint inhibitors and other TKIs.

Significance:

The molecular-guided therapeutic strategy of combining cabozantinib and sapanisertib restrains ERK activity to effectively suppress growth of renal cell carcinomas, including those unresponsive to immune checkpoint inhibitors.
Data from A pilot study omitting radiation in the treatment of children with newly diagnosed Wnt-activated medulloblastoma
Authors: Cohen Kenneth J. , Munjapara Vasu , Aguilera Dolly , Castellino Robert C. , Stapleton Stacie L. , Landi Daniel , Ashley David M. , Rodriguez Fausto J. , Hawkins Cynthia , Yang Edward , London Wendy , Chi Susan , Bandopadhayay Pratiti
Published: December 2023

Abstract
Purpose: Treatment of wingless (WNT)-activated medulloblastoma (WNT+MB) with surgery, irradiation (XRT) and chemotherapy results in excellent outcomes. We studied the efficacy of therapy de-intensification by omitting XRT entirely in children with WNT+MB. Patients and Methods: Tumors were molecularly screened to confirm the diagnosis of WNT+MB. Eligible children were treated within 31 days following surgery with nine cycles of adjuvant chemotherapy per ACNS0331. No XRT was planned. The primary endpoint was the occurrence of relapse, progression, or death in the absence of XRT within the first two years after study enrollment. Four events in the first 10 evaluable patients would result in early study closure. Results: Fourteen children were prescreened and nine met the protocol definition of WNT+MB. Six of the nine eligible patients consented to protocol therapy and five completed planned protocol therapy. The first two children enrolled relapsed shortly after therapy completion with local and leptomeningeal recurrences. The study was closed early due to safety concerns. Both children are surviving after XRT and additional chemotherapy. A third child relapsed at completion of therapy but died of progressive disease 35 months from diagnosis. Two children finished treatment but immediately received post-treatment XRT to guard against early relapse. The final child’s treatment was aborted in favor of a high-dose therapy/stem cell rescue approach. While OS at 5 years is 83%, no child received only planned protocol therapy with all receiving eventual XRT and/or alternative therapy. Conclusions: Radiation therapy is required to effectively treat children with WNT-altered medulloblastoma.
Facts and Hopes on Biomarkers for Successful Early Clinical Immunotherapy Trials: Innovative Patient Enrichment Strategies
Authors: Cannarile Michael A. , Karanikas Vaios , Reis Bernhard , Mancao Christoph , Lagkadinou Eleni , Rüttinger Dominik , Rieder Natascha , Ribeiro Franclim R. , Kao Henry , Dziadek Sebastian , Gomes Bruno
Published: December 2023

Despite the clinical validation and unequivocal benefit to patients, the development of cancer immunotherapies is facing some key challenges and the attrition rate in early phases of development remains high. Identifying the appropriate patient population that would benefit most from the drug is on the critical path for successful clinical development. We believe that a systematic implementation of patient enrichment strategies early in the drug development process and trial design, is the basis for an innovative, more efficient, and leaner clinical development to achieve earlier a clear proof of concept or proof of failure. In this position article, we will describe and propose key considerations for the implementation of patient enrichment strategies as an opportunity to provide decision-enabling data earlier in the drug development process. We introduce an innovative multidimensional tool for immuno-oncology drug development that focuses on facilitating the identification and prioritization of enrichment-relevant biomarkers, based on the drug mechanism of action. To illustrate its utility, we discuss patient enrichment examples and use a case in the field of cancer immunotherapy, together with technical and regulatory considerations. Overall, we propose to implement fit for purpose enrichment strategies for all investigational drugs as early as possible in the development process. We believe that this will increase the success rate of immuno-oncology clinical trials, and eventually bring new and better medicines to patients faster.
Supplementary Figures from Targeting Aggressive B-cell Lymphomas through Pharmacological Activation of the Mitochondrial Protease OMA1
Authors: Schwarzer Adrian , Oliveira Matheus , Kleppa Marc-Jens , Slattery Scott D. , Anantha Andy , Cooper Alan , Hannink Mark , Schambach Axel , Dörrie Anneke , Kotlyarov Alexey , Gaestel Matthias , Hembrough Todd , Levine Jedd , Luther Michael , Stocum Michael , Stiles Linsey , Weinstock David M. , Liesa Marc , Kostura Matthew J.
Published: December 2023

Supplementary Figures and Methods
Exploring Patients’ Perceptions on Injectable Opioid Agonist Treatment: Influences on Treatment Initiation and Implications for Practice
Authors: Friedmann Zoe , Binder Annette , Kinkel Hans-Tilmann , Kühner Claudia , Zsolnai Andreas , Mick Inge
Published: December 2023

Introduction: Injectable opioid agonist treatment (iOAT) with diacetylmorphine is an effective option for individuals previously considered non-responsive to opioid substitution treatment. Despite implementation in Canada and several European countries, relatively few eligible people choose to initiate iOAT. To better understand what encourages or deters prospective patients from initiating iOAT, the current study explores patients’ perceptions on iOAT and how these influence therapy initiation in practice. Methods: We conducted 34 semi-structured interviews with individuals currently in or eligible for iOAT in two German outpatient iOAT clinics. Transcripts were analysed following qualitative content analysis, with development of inductive categories and use of consensual coding. For member checking, we consulted individuals with lived experiences prior to data collection and publication. Results: Participants based their choice to initiate iOAT on the perceived implications of the treatment on one’s daily life and individual recovery. Participants were encouraged to initiate iOAT due to the therapy’s perceived potential in reducing cravings and substance use, its positive health consequences, and due to the image of iOAT as a path towards abstinence. Regarding deterring perceptions, participants feared a profound impairment of daily life due to factors such as the daily visits to the clinic, were concerned about whether iOAT would sufficiently promote or even impede one’s recovery, and described negative health effects. Conclusion: Perceptions found in this study profoundly influenced participants’ decisions on iOAT enrolment and contextualize the previous literature. The study reveals the dynamic coexistence of different perceptions about iOAT and sheds light on the inner-group stigmatization of iOAT. Practitioners and future research should acknowledge the complexities found in the current study in order to exploit the full potential of effective treatment modalities such as iOAT.
Turpentine Ointment for the Treatment of Folliculitis: An Open, Prospective, Randomized, Placebo- and Comparator-Controlled Multicenter Trial
Authors: Görne Rainer C. , Günnewich Nils , Huber Hilde , Wallmen Britta , Zimmermann Christian ,   On behalf of the Folliculitis Study Group
Published: December 2023

Introduction: Folliculitis is a painful infection and inflammation of the hair follicles, mostly caused by bacterial, fungal, or, more rarely, viral infections. Turpentine derivatives have been used traditionally to treat various skin infections and could thus also be effective in treating folliculitis. We carried out an open, prospective, randomized, placebo- and comparator-controlled multicenter trial to evaluate the efficacy and safety of an ointment containing pine turpentine oil, larch turpentine, and eucalyptus oil in the treatment of acute folliculitis. Methods: Seventy outpatients with acute folliculitis were treated with the turpentine ointment, a comparator (povidone iodine solution), or a placebo (Vaseline) for 7 days. Photographs of the affected skin areas were taken by the physicians at four visits and by the patients on a daily basis. Photographs were evaluated by blinded observers. Primary efficacy endpoint was the change in total hair follicle lesion counts. Secondary endpoints included the evolution of the lesion counts in the course of the study, responder rate (improvement of follicle lesions by at least one count), and the patient’s global assessment. Safety endpoints were the tolerability of the treatments and adverse event recording. Results: A decrease of follicle lesions counts was detected for both active treatments but not for placebo, but the differences among groups were not statistically significant. As for the secondary endpoints, the ointment showed statistically significant superiority over placebo for the evolution of the lesions during the course of the study (p = 0.017), the responder rate (p = 0.032), and the subjective efficacy assessment by patients (p = 0.029). All treatments were equally well tolerated, with a similar number of treatment-emergent adverse events. Conclusion: The turpentine ointment is an effective and safe option for the treatment of folliculitis.
GSK-3β as a Potential Coordinator of Anabolic and Catabolic Pathways in Hepatitis C Virus Insulin Resistance
Authors: Das Gokul C. , Hollinger F. Blaine
Published: December 2023

Introduction: Chronic hepatitis C infection can result in insulin resistance (IR). We have previously shown that it occurs through the interaction of pathways for glucose homeostasis, insulin signaling, and autophagy. But it is not known how soon the pathways are activated and how IR is related to the signals generated by catabolic and anabolic conditions occurring in infected cells. We have extended our studies to a cell culture system mimicking acute infection and to downstream pathways involving energy-sensor AMPK and nutrient-sensor mTOR that are active in catabolic and anabolic processes within the infected cells. Methods: Huh7 liver cells in culture were infected with hepatitis C virus (HCV). We performed proteomics analysis of key proteins in infected cells by Western blotting and IP experiments, with or without IFNα exposure as a component of conventional therapeutic strategy. Results: We present evidence that (a) IRS-1 Ser312, Beclin-1, protein conjugate Atg12-Atg5 or GS Ser641 are up-regulated early in infection presumably by activating the same pathways as utilized for persistent infection; (b) Bcl-XL, an inhibitor of both autophagy and apoptosis, is present in a core complex with IRS-1 Ser312 and Beclin-1 during progression of IR; (c) AMPK level remains about the same in infected cells where it is activated by phosphorylation at Thr172 concomitant with increased autophagy, a hallmark of catabolic conditions; (d) an mTOR level that promotes anabolism is increased rather than decreased under an expanded autophagy; (e) hypophosphorylation of translational repressor 4E-BP1 downstream of mTOR is suggestive of reduced protein synthesis; and (f) β-catenin, is up-regulated but not phosphorylated suggesting indirectly our previous contention that its kinase, GSK-3β, is mostly in an inactive state. Conclusion: We report that in the development of IR following chronic infection, anabolic and catabolic pathways are activated early, and the metabolic interaction occurs possibly in a core complex with IRS-1 Ser312, Beclin-1, and autophagy inhibitor Bcl-XL. Induction of autophagy is usually controlled by a two-edged mechanism acting in opposition under anabolic and catabolic conditions by AMPK/mTOR/4E-BP1 pathway with GSK-3β-mediated feedback loops. However, we have observed an up-regulation of mTOR along with an up-regulation of AMPK caused by HCV infection is a deviation from the normal scenario described above which might be of therapeutic interest.
Cooperativity, Information Gain, and Energy Cost During Early LTP in Dendritic Spines
Authors: Karbowski Jan , Urban Paulina
Published: December 2023

We investigate a mutual relationship between information and energy during the early phase of LTP induction and maintenance in a large-scale system of mutually coupled dendritic spines, with discrete internal states and probabilistic dynamics, within the framework of nonequilibrium stochastic thermodynamics. In order to analyze this computationally intractable stochastic multidimensional system, we introduce a pair approximation, which allows us to reduce the spine dynamics into a lower-dimensional manageable system of closed equations. We found that the rates of information gain and energy attain their maximal values during an initial period of LTP (i.e., during stimulation), and after that, they recover to their baseline low values, as opposed to a memory trace that lasts much longer. This suggests that the learning phase is much more energy demanding than the memory phase. We show that positive correlations between neighboring spines increase both a duration of memory trace and energy cost during LTP, but the memory time per invested energy increases dramatically for very strong, positive synaptic cooperativity, suggesting a beneficial role of synaptic clustering on memory duration. In contrast, information gain after LTP is the largest for negative correlations, and energy efficiency of that information generally declines with increasing synaptic cooperativity. We also find that dendritic spines can use sparse representations for encoding long-term information, as both energetic and structural efficiencies of retained information and its lifetime exhibit maxima for low fractions of stimulated synapses during LTP. Moreover, we find that such efficiencies drop significantly with increasing the number of spines. In general, our stochastic thermodynamics approach provides a unifying framework for studying, from first principles, information encoding, and its energy cost during learning and memory in stochastic systems of interacting synapses.
Genome-wide association study of brain functional and structural networks
Authors: Cheng Ruonan , Yin Ruochen , Zhao Xiaoyu , Wang Wei , Gong Gaolang , Chen Chuansheng , Xue Gui , Dong Qi , Chen Chunhui
Published: December 2023

Imaging genetics studies with large samples have identified many genes associated with brain functions and structures, but little is known about genes associated with brain functional and structural network properties. The current genome-wide association study examined graph theory measures of brain structural and functional networks with 497 healthy Chinese participants (17–28 years). Four genes (TGFB3, LGI1, TSPAN18, and FAM155A) were identified to be significantly associated with functional network global efficiency, and two (NLRP6 and ICE2) with structural network global efficiency. Meta-analysis of structural and functional brain network property confirmed the four functional-related genes and revealed two more (RBFOX1 and WWOX). They were reported to be significantly associated with regional brain structural or functional measurements in the UK Biobank project; and showed differential gene expression level between low and high structure–function coupling regions according to Allen Human Brain Atlas gene expression data. Taken together, our results suggest that brain structural and functional networks had shared and unique genetic bases, consistent with the notion of many-to-many structure–function coupling of the brain.
Pre-train, Prompt, and Recommendation: A Comprehensive Survey of Language Modeling Paradigm Adaptations in Recommender Systems
Authors: Liu Peng , Zhang Lemei , Gulla Jon Atle
Published: December 2023

The emergence of Pre-trained Language Models (PLMs) has achieved tremendous success in the field of Natural Language Processing (NLP) by learning universal representations on large corpora in a self-supervised manner. The pre-trained models and the learned representations can be beneficial to a series of downstream NLP tasks. This training paradigm has recently been adapted to the recommendation domain and is considered a promising approach by both academia and industry. In this paper, we systematically investigate how to extract and transfer knowledge from pre-trained models learned by different PLM-related training paradigms to improve recommendation performance from various perspectives, such as generality, sparsity, efficiency and effectiveness. Specifically, we propose a comprehensive taxonomy to divide existing PLM-based recommender systems w.r.t. their training strategies and objectives. Then, we analyze and summarize the connection between PLM-based training paradigms and different input data types for recommender systems. Finally, we elaborate on open issues and future research directions in this vibrant field.
An Efficient Self-Supervised Cross-View Training For Sentence Embedding
Authors: Limkonchotiwat Peerat , Ponwitayarat Wuttikorn , Lowphansirikul Lalita , Udomcharoenchaikit Can , Chuangsuwanich Ekapol , Nutanong Sarana
Published: December 2023

Self-supervised sentence representation learning is the task of constructing an embedding space for sentences without relying on human annotation efforts. One straightforward approach is to finetune a pretrained language model (PLM) with a representation learning method such as contrastive learning. While this approach achieves impressive performance on larger PLMs, the performance rapidly degrades as the number of parameters decreases. In this paper, we propose a framework called Self-supervised Cross-View Training (SCT) to narrow the performance gap between large and small PLMs. To evaluate the effectiveness of SCT, we compare it to 5 baseline and state-of-the-art competitors on seven Semantic Textual Similarity (STS) benchmarks using 5 PLMs with the number of parameters ranging from 4M to 340M. The experimental results show that STC outperforms the competitors for PLMs with less than 100M parameters in 18 of 21 cases.1
Survival and moulting rates of larvae of Callinectes sapidus Rathbun, 1896 under different environmental circumstances (Brachyura, Portunidae)
Authors: Gencer Övgü
Published: December 2023

This study investigated the well-being and survival of larvae of the blue crab, Callinectes sapidus, under the influence of several abiotic and biotic factors, in order to collect relevant data for optimizing the larval period in the culture of this species. Aspects tested and examined were primarily: water volume, stocking density, salinity, (frequency of) moulting, starvation, mortality, cannibalism, behavioural aspects (e.g., mobility, intraspecific aggression), larval development, as well as the influence of ground colours. All aspects appeared to influence the duration and success of the larval period, from zoea-I to megalopa, but the main difference was observed to be related to the (water) volume of the culture tanks.
Spontaneous Activation of the Pacific Meridional Overturning Circulation (PMOC) in Long-Term Ocean Response to Greenhouse Forcing
Authors: Curtis Paul Edwin , Fedorov Alexey V.
Published: December 2023

The present-day deep ocean global meridional overturning circulation is dominated by the Atlantic meridional overturning circulation (AMOC), with dense water sinking in the high-latitude North Atlantic Ocean. In contrast, deep-water formation in the subarctic North Pacific is inhibited by a strong upper-ocean halocline, which prevents the development of an analogous Pacific meridional overturning circulation (PMOC). Nevertheless, paleoclimate evidence suggests that a PMOC with deep-water formation in the North Pacific was active, for instance, during the warm Pliocene epoch and possibly during the most recent deglaciation. In the present study, we describe a spontaneous activation of the PMOC in a multimillennial abrupt 4 × CO2 experiment using one of the configurations of the Community Earth System Model (CESM1). Soon after the imposed CO2 increase, the model’s AMOC collapses and remains in a weakened state for several thousand years. The PMOC emerges after some 2500 years of integration, persists for about 1000 years, reaching nearly 10 Sv (1 Sv ≡ 106 m3 s−1), but eventually declines to about 5 Sv. The PMOC decline follows the AMOC recovery in the model, consistent with an Atlantic–Pacific interbasin seesaw. The PMOC activation relies on two factors: (i) gradual warming and freshening of the North Pacific deep ocean, which reduces ocean vertical stratification on millennial time scales, and (ii) upper-ocean salinity increase in the subarctic North Pacific over several centuries, followed by a rapid erosion of the pycnocline and activation of deep-water formation. Ultimately, our results provide insights on the characteristics of global ocean overturning in warm climates.
Unrealized Integration in Education, Sociology, and Society
Authors: Carter Prudence L.
Published: December 2023

In the 2023 ASA presidential address, Prudence Carter delves into the landscape of U.S. society, tracing some of its historical progress and confronting contemporary social, economic, educational, and political challenges. Central to her argument is an exploration of the concept of “unrealized integration” and how it has hindered the nation’s march toward an inclusive, multiracial democracy. Carter describes and characterizes the current state of integration within education and society. Despite the widespread rhetoric of diversity in our organizations and institutions, she critiques its shallow application, exposing diversity’s inability to rectify imbalances of power- and resource-sharing. Incorporating the idea of “tipping points,” she discusses how civil rights movements, despite expanding representation and opportunity, have faced recurrent waves of political backlash and reversals. She contends that an erosion of social progress occurs when there is an imbalance in the pursuit of distributional equality (concerning material resources) and relational equality (involving social and cultural dynamics and processes that shape well-being). Additionally, she identifies three other crucial areas that warrant focus to pave the path toward realized integration within education and society. In a forward-looking call to arms, Carter underscores the imperative for sociologists to transcend epistemological and methodological boundaries; and she advocates for robust collaborations across the social sciences and humanities to harness the collective power of knowledge-generation and solution-building for pressing societal issues.
Foreign Body Reaction Requiring Re-Exploration After Tympanoplasty With Porcine Small Intestinal Submucosa Reconstruction
Authors: Fullerton Zoe H. , Wei Eric X. , Green Allen , Sajjadi Hamed
Published: December 2023

Objective:

We present the first published case of large foreign body reaction to Biodesign (Cook Medical, Bloomington, IN), an acellular otologic graft matrix derived from porcine small intestinal submucosa, after use in tympanoplasty surgery in a patient without previous exposure to meat products.

Methods:

A single case report of a 39-year-old female who developed tinnitus, ear drainage, and large fibrotic mass in external auditory canal and extending into middle ear after Type I medial graft tympanoplasty with Biodesign Graft. Left endoscopic microdissection and resection of the tympanic membrane and middle ear fibrotic mass were performed.

Main findings:

Surgical excision of the fibrous mass required extensive microdissection to ensure preservation of the ossicles and chorda tympani. Postoperatively, hearing improved and otalgia and otorrhea resolved.

Conclusions:

We report the first case of post-tympanoplasty reaction with the use of Biodesign acellular porcine graft in a patient with no previous known exposure to meat products. Although this presentation appears to be rare, it reinforces the need for careful patient selection and counseling around the use of porcine or other foreign grafts.