bluuebunny/crossref_metadata_2025 huggingface dataset:
Increasing Clinical Trial Participation of Black Women Diagnosed with Breast Cancer
Authors: Fairley Ricki , Lillard James W. , Berk Alexandra , Cornew Sophia , Gaspero Joseph , Gillespie James , Horne LaTrisha L. , Kidane Sabrina , Munro Sandra B. , Parsons Matthew , Powers Emily R. , Rizzo Suzanne E. , Tishcler Alyson , Wohl Hope , Weiss Marisa C.
Published: June 2023

Despite racial disparities in breast cancer mortality, Black women remain underrepresented in clinical trials. In this mixed methods research, 48 Black women were engaged via focus group discussions and in-depth interviews to better understand the lived experience of women with breast cancer. The results of this qualitative study informed the development of a subsequent online survey to identify barriers, motivators, and other factors that influence decision-making by Black women diagnosed with breast cancer when considering clinical trial participation. Among the 257 Black survey participants, most (95%) were aware of clinical trials; of those, most viewed them as lifesaving (81%) and/or benefiting others (90%). Negative perceptions such as serious side effects (58%), not receiving real treatment (52%), or risk of potential harm (62%) were indicated. Barriers included financial expenses (49%), concerns that their condition could be made worse (29%), that they would receive a placebo (28%), or that treatment was unapproved (28%). Participants were more likely than their health care providers (HCPs) to initiate discussions of clinical trials (53% versus 33%), and 29% of participants indicated a need for more information about risks and benefits, even after having those conversations. The most trustworthy sources of information on clinical trials were HCPs (66%) and breast cancer support groups (64%). These results suggest that trusted communities are key for providing education on clinical trials. However, there is also a need for HCPs to proactively discuss clinical trials with patients to ensure that they are adequately informed about all aspects of participation.
Forecasting bitcoin volatility: exploring the potential of deep learning
Authors: Pratas Tiago E. , Ramos Filipe R. , Rubio Lihki
Published: June 2023

This study aims to evaluate forecasting properties of classic methodologies (ARCH and GARCH models) in comparison with deep learning methodologies (MLP, RNN, and LSTM architectures) for predicting Bitcoin's volatility. As a new asset class with unique characteristics, Bitcoin's high volatility and structural breaks make forecasting challenging. Based on 2753 observations from 08-09-2014 to 01-05-2022, this study focuses on Bitcoin logarithmic returns. Results show that deep learning methodologies have advantages in terms of forecast quality, although significant computational costs are required. Although both MLP and RNN models produce smoother forecasts with less fluctuation, they fail to capture large spikes. The LSTM architecture, on the other hand, reacts strongly to such movements and tries to adjust its forecast accordingly. To compare forecasting accuracy at different horizons MAPE, MAE metrics are used. Diebold–Mariano tests were conducted to compare the forecast, confirming the superiority of deep learning methodologies. Overall, this study suggests that deep learning methodologies could provide a promising tool for forecasting Bitcoin returns (and therefore volatility), especially for short-term horizons.
DeepSHARQ: hybrid error coding using deep learning
Authors: Gil Pereira Pablo , Vogelgesang Kai , Miodek Moritz , Schmidt Andreas , Herfet Thorsten
Published: June 2023

Cyber-physical systems operate under changing environments and on resource-constrained devices. Communication in these environments must use hybrid error coding, as pure pro- or reactive schemes cannot always fulfill application demands or have suboptimal performance. However, finding optimal coding configurations that fulfill application constraints—e.g., tolerate loss and delay—under changing channel conditions is a computationally challenging task. Recently, the systems community has started addressing these sorts of problems using hybrid decomposed solutions, i.e., algorithmic approaches for well-understood formalized parts of the problem and learning-based approaches for parts that must be estimated (either for reasons of uncertainty or computational intractability). For DeepSHARQ, we revisit our own recent work and limit the learning problem to block length prediction, the major contributor to inference time (and its variation) when searching for hybrid error coding configurations. The remaining parameters are found algorithmically, and hence we make individual contributions with respect to finding close-to-optimal coding configurations in both of these areas—combining them into a hybrid solution. DeepSHARQ applies block length regularization in order to reduce the neural networks in comparison to purely learning-based solutions. The hybrid solution is nearly optimal concerning the channel efficiency of coding configurations it generates, as it is trained so deviations from the optimum are upper bound by a configurable percentage. In addition, DeepSHARQ is capable of reacting to channel changes in real time, thereby enabling cyber-physical systems even on resource-constrained platforms. Tightly integrating algorithmic and learning-based approaches allows DeepSHARQ to react to channel changes faster and with a more predictable time than solutions that rely only on either of the two approaches.
Proportionality in International Humanitarian Law
Authors: van den Boogaard Jeroen
Published: June 2023

This book seeks to clarify the legal concept of proportionality in international humanitarian law, as it applies during armed conflict. It is argued in the book that a refocus of the interpretation of the proportionality rule is warranted to enhance the protection of civilians. More precisely, this book seeks to dissect the origins of the rule, determine how its components must be interpreted and how it is to be applied in practice. The book considers practical situations that may arise in the conduct of military operations and searches for the limits international humanitarian law sets to commanders' assessments of proportionality during armed conflict. The book concludes that proportionality is an inherently subjective and imprecise yardstick that nonetheless serves to protect civilians during armed conflict.
A History of Developmental and Behavioral Pediatrics at the University of Rochester
Authors: Davidson Philip W. , Hyman Susan L.
Published: June 2023

A history of the University of Rochester Medical Center's Developmental and Behavioral Pediatrics Division from its inception in 1947 through 2019.
How Bedfordshire Voted, 1735-1784
Authors: Collett-White James
Published: June 2023

The third volume in BHRS's series of poll books and covers the years from the fall of Walpole to the rise of William Pitt the younger.
Identifying causally significant features in three-dimensional isotropic turbulence
Authors: Encinar Miguel P. , Jiménez Javier
Published: June 2023

Flow patterns of causal significance to three-dimensional isotropic turbulence are identified through the recently introduced algorithm of Jiménez (J. Fluid Mech., vol. 854, 2018, R1). Localised perturbations are introduced at arbitrary regions of a triple-periodic decaying flow at

${Re}_\lambda \approx 190$

, and their evolution is used as a marker of the significance of said regions to the flow. Their dimensions are found to be an important parameter, with sizes of the order of the integral scale being controlled by the kinetic energy content, and sizes within the dissipative range, by the enstrophy and dissipation. The three quantities are found to be important at intermediate (inertial) scales. Prominent differences emerge between regions of high and low significance. The former typically contain strong gradients and/or kinetic energy and the latter are weak. An analysis of the structure of significant and insignificant flow patterns reveals that strain is more efficient than vorticity at propagating the contents of the perturbation to other regions of the flow. Moreover, the flow patterns of significant regions are found to be more complex, typically containing vortex clusters, while simpler vortex sheets are found in insignificant regions. The present results suggest that strategies aiming to manipulate the flow should focus on strain-dominated vortex clusters, avoiding enstrophy-dominated vortex sheets. This is confirmed through an assimilation experiment, in which greater synchronisation between two simulations is achieved when simulations share significant regions rather than insignificant ones. These conclusions have implications for both the control of turbulent flows and the making of predictions based on limited or noisy measurements.
Interface behaviour of the slow diffusion equation with strong absorption: Intermediate-asymptotic properties
Authors: King John R. , Richardson Giles W. , Foster Jamie M.
Published: June 2023

The dynamics of interfaces in slow diffusion equations with strong absorption are studied. Asymptotic methods are used to give descriptions of the behaviour local to a comprehensive range of possible singular events that can occur in any evolution. These events are: when an interface changes its direction of propagation (reversing and anti-reversing), when an interface detaches from an absorbing obstacle (detaching), when two interfaces are formed by film rupture (touchdown) and when the solution undergoes extinction. Our account of extinction and self-similar reversing and anti-reversing is built upon previous work; results on non-self-similar reversing and anti-reversing and on the various types of detachment and touchdown are developed from scratch. In all cases, verification of the asymptotic results against numerical solutions to the full PDE is provided. Self-similar solutions, both of the full equation and of its asymptotic limits, play a central role in the analysis.
Survey of Crowd Crush Disasters and Countermeasures
Authors: Wang Soon-Joo
Published: June 2023

Introduction:

On the night of October 29, 2022, a crowd crush occurred during Halloween festivities in the Itaewon neighborhood of Seoul, Korea. At least 156 people were killed and at least 173 others were injured. In this study, the author tried to learn a lesson by investigating the worldwide crowd crush disaster and analyzing the differences and results.

Method:

First, the crowd crush disasters were investigated and summarized through literature and internet searches. Second, based on this, the prevention and management of crowd crush disasters, emergency medical response, and necessary research/development contents were derived through a Delphi survey of experts.

Results:

Crowd crush disasters have been experienced from developed countries to developing countries since the 1800s. Commonly the crowd density was high, and the crowds continued to move and then the crowd collapsed above a certain limit. The biggest casualty occurred during a pilgrimage to Mecca in Saudi Arabia in 2015, but the theme of the event, such as concerts, sporting events, and funerals, was varied. Experts survey was that the manager's efforts not to increase the crowd density, and efforts to maintain order and prevent contingencies were important. They said that it is important to comply with the principles of disaster medicine, but it is difficult to access the patient in the crowd crush state, so the management of the crowd may be more important. They said that it is necessary to establish a realistic guideline and a real-time crowd density monitoring system using CCTV or drones.

Conclusion:

Crowd crush disasters can occur in any type of crowd gathering events where the crowd density increases, and prevention through crowd management and real-time crowd density monitoring should be implemented.
Education During the Covid-19 Pandemic. The Case of Romania’s Political-Administrative Decisions on Education and Health
Authors: Săgeată Radu , Geantă Nicolae , Damian Nicoleta , Persu Mihaela
Published: June 2023

This article highlights the problems faced by teachers, students, parents and authorities in Romania during the Coronavirus pandemic, as well as their management in the general context of the health crisis unfolding in this country. The documentation regarding Romania was compiled mainly on the basis of official reports and information taken from the media, due to the novelty of the subject for the case study presented. They were joined by theoretical-methodological works on the general epidemiological context and by studies on the particularities of the Romanian education system, which helped us to outline the theoretical-methodological background of the research. The authors have tried to highlight good practices, but also the errors that led to an increase in the number of cases and the imposition of restrictions, during the first four waves of the pandemic, with a major impact on educational activities in Romania. The main restrictions and advantages of online education, a first for the Romanian education system, are also highlighted.
The WTO's Multi-Party Interim Appeal Arbitration Arrangement (MPIA): What's New?
Authors: Pauwelyn Joost
Published: June 2023

To preserve the functioning of WTO dispute settlement following the blockage of the Appellate Body, a sub-set of WTO Members created the Multi-Party Interim Appeal Arbitration Arrangement (MPIA). In the wake of the first appeal award rendered under the MPIA, this contribution describes how the MPIA process works and lists some of the innovations that can be found in the first MPIA procedure. More innovations can be expected as arbitration under Article 25 of the Dispute Settlement Understanding (DSU) (be it ad hoc or under the MPIA) can be adjusted and molded case-by-case by the disputing parties in their appeal arbitration agreements. In this sense, the MPIA can serve not only as an interim stop-gap to preserve WTO dispute settlement. It can also function as a laboratory to explore and test new ways of making WTO dispute settlement more efficient and in line with WTO Members' goals and interests: experimental reform by doing, rather than one-off, formal DSU review.
Moral Individualism in Modern Politics: A New Measure Inspired by Political Theory
Authors: Karpowitz Christopher F. , Patterson Kelly D.
Published: June 2023

We reexamine the concept of individualism and its political implications. While both political scientists and social psychologists agree that individualism is a core value for many Americans, political science has primarily associated the concept with views about economic mobility. Building upon insights from political theory, we argue that a narrow focus on economics overlooks key elements of individualism and its relation to political life. With the help of five distinct datasets collected between 2018 and 2022 (combinedN= 12,169), we develop a new index that emphasizes autonomy from authority, which we label moral individualism. We show how it and other dimensions of individualism explain interactions with the political world, including responses to the COVID-19 pandemic. Across multiple indicators, moral individualists were far less likely to engage in collective action or pursue other behaviors meant to assist the community. For example, even after controlling for the effects of ideology and partisanship, moral individualism reduced the probability of wearing a mask during the first year of the pandemic by approximately 30 percentage points.
Models of EU Constitutional Reform: What do we learn from the Conference on the Future of Europe?
Authors: Crum Ben
Published: June 2023

Constitutional reform in the European Union suffers from a post-functionalist dilemma: the options that are politically viable are not democratically legitimate and the options that are democratically legitimate are not politically viable. Against the background of the recent Conference on the Future of Europe and the involvement of transnational European Citizens’ Panels, this article asks whether there is any prospect of overcoming this dilemma and organizing fundamental reform of EU institutions that is both normatively legitimate and politically viable. For this, it examines four models of EU treaty reform and the way these have figured in actual EU reform processes: Intergovernmental Conference, European Convention, informal intergovernmentalism and a Citizens Convention. The article concludes that, as long as the European Union is best characterized as a ‘demoi-cracy’ in which political deliberation takes place primarily in national public spheres, the Intergovernmental Conference remains its main and inevitable forum for constitutional reform. Hence, alternative models of EU constitutional reform should be evaluated not so much on the basis of their potential to substitute the IGC but rather on their ability to catalyse the process and to pre-commit the member state governments.
Fusion of MISR Stereo Cloud Heights and Terra‐MODIS Thermal Infrared Radiances to Estimate Two‐Layered Cloud Properties
Authors: Mitra Arka , Loveridge Jesse Ray , Di Girolamo Larry
Published: June 2023

Our longest, stable record of cloud‐top pressure (CTP) and cloud‐top height (CTH) are derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) and Multi‐Angle Imaging Spectroradiometer (MISR) on Terra. Because of single cloud‐layer assumptions in their standard algorithms, they provide only single CTP/CTH retrievals in multi‐layered situations. In the predominant multi‐layered regime of thin cirrus over low clouds, MODIS significantly overestimates cirrus CTP and emissivity, while MISR accurately retrieves low‐cloud CTH. Utilizing these complementary capabilities, we develop a retrieval algorithm for accurately determining both‐layer CTP and cirrus emissivity for such 2‐layered clouds, by applying the MISR low‐cloud CTH as a boundary condition to a modified MODIS CO2‐slicing retrieval. We evaluate our 2‐layered retrievals against collocated Cloud‐Aerosol Transport System (CATS) lidar observations. Relative to CATS, the mean bias of the upper cloud CTP and emissivity are reduced by ∼90% and ∼75% respectively in the new technique, compared to standard MODIS products. We develop an error model for the 2‐layered retrieval accounting for systematic and random errors. We find up to 87% of all residuals lie within modeled 95% confidence intervals, indicating a near‐closure of error budget. This reduction in error leads to a reduction in modeled atmospheric longwave radiative flux biases ranging between 5 and 40 W m−2, depending on the position and optical properties of the layers. Given this large radiative impact, we recommend that the pixel‐level 2‐layered MODIS + MISR fusion algorithm be applied over the entire MISR swath for the 22‐year Terra record, leading to a first‐of‐its‐kind 2‐layered cloud climatology from Terra's morning orbit.
Observations of Typhoon Generated Gravity Waves From the CIPS and AIRS Instruments and Comparison to the High‐Resolution ECMWF Model
Authors: Cullens Chihoko Y. , Thurairajah Brentha , England Scott L. , Randall Cora E. , Yue Jia , Wright Corwin
Published: June 2023

The satellite‐based Cloud Imaging and Particle Size (CIPS) instrument and Atmospheric Infrared Sounder (AIRS) observed concentric gravity waves (GWs) generated by Typhoon Yutu in late October 2018. This work compares CIPS and AIRS nadir viewing observations of GWs at altitudes of 50–55 and 30–40 km, respectively, to simulations from the high‐resolution European Centre for Medium‐Range Weather Forecasting Integrated Forecasting System (ECMWF‐IFS) and ECMWF reanalysis v5 (ERA5). Both ECMWF‐IFS with 9 km and ERA5 with 31 km horizontal resolution show concentric GWs at similar locations and timing as the AIRS and CIPS observations. The GW wavelengths are ∼225–236 km in ECMWF‐IFS simulations, which compares well with the wavelength inferred from the observations. After validation of ECMWF GWs, five category five typhoon events during 2018 are analyzed using ECMWF to obtain characteristics of concentric GWs in the Western Pacific regions. The amplitudes of GWs in the stratosphere are not strongly correlated with the strength of typhoons, but are controlled by background wind conditions. Our results confirm that amplitudes and shapes of concentric GWs observed in the stratosphere and lowermost mesosphere are heavily influenced by the background wind conditions.
Using Machine Learning With Partial Dependence Analysis to Investigate Coupling Between Soil Moisture and Near‐Surface Temperature
Authors: Trok Jared T. , Davenport Frances V. , Barnes Elizabeth A. , Diffenbaugh Noah S.
Published: June 2023

Soil moisture (SM) influences near‐surface air temperature by partitioning downwelling radiation into latent and sensible heat fluxes, through which dry soils generally lead to higher temperatures. The strength of this coupled soil moisture‐temperature (SM‐T) relationship is not spatially uniform, and numerous methods have been developed to assess SM‐T coupling strength across the globe. These methods tend to involve either idealized climate‐model experiments or linear statistical methods which cannot fully capture nonlinear SM‐T coupling. In this study, we propose a nonlinear machine‐learning (ML)‐based approach for analyzing SM‐T coupling and apply this method to various mid‐latitude regions using historical reanalysis datasets. We first train convolutional neural networks (CNNs) to predict daily maximum near‐surface air temperature (TMAX) given daily SM and geopotential height fields. We then use partial dependence analysis to isolate the average sensitivity of each CNN's TMAX prediction to the SM input under daily atmospheric conditions. The resulting SM‐T relationships broadly agree with previous assessments of SM‐T coupling strength. Over many regions, we find nonlinear relationships between the CNN's TMAX prediction and the SM input map. These nonlinearities suggest that the coupled interactions governing SM‐T relationships vary under different SM conditions, but these variations are regionally dependent. We also apply this method to test the influence of SM memory on SM‐T coupling and find that our results are consistent with previous studies. Although our study focuses specifically on local SM‐T coupling, our ML‐based method can be extended to investigate other coupled interactions within the climate system using observed or model‐derived datasets.
Tongan Volcanic Eruption Induced Global‐Scale Thermospheric Changes Observed by the GOLD Mission
Authors: Aryal S. , Gan Q. , Evans J. S. , Laskar F. I. , Karan D. K. , Cai X. , Greer K. R. , Wang W. , McClintock W. E. , Eastes R. W.
Published: June 2023

The 2022 Tongan volcanic eruption released significant energy into the atmosphere. Tropospheric satellite images show that the eruption generated pressure waves that traveled globally. The Global Observation of the Limb and Disk (GOLD) mission observed significant wave‐like thermospheric temperature perturbations (>100 K) from 12 to 16 UT. These temperature perturbations' spatial curvatures and arrival times are initially similar to the tropospheric wave‐fronts but differ significantly with eastward propagation. The perturbations had a phase speed of ∼300–400 m/s and wavelengths greater than 2,400 km. Near‐concurrent Ionospheric Connection Explorer neutral wind measurements suggest that the eruption's effects reversed the direction of the prevailing thermospheric zonal winds around the perturbed regions. The eruption's global and whole atmospheric effects provide a unique opportunity to study how different atmospheric layers exchange energy and momentum during explosive events. GOLD's synoptic observations are uniquely positioned to study these effects in the middle thermosphere.
Efficacy and safety of isatuximab plus bortezomib, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma ineligible/with no immediate intent for autologous stem cell transplantation
Authors: Ocio Enrique M. , Perrot Aurore , Bories Pierre , San-Miguel Jesus F. , Blau Igor W. , Karlin Lionel , Martinez-Lopez Joaquin , Wang Song-Yau , Bringhen Sara , Marcatti Magda , Mateos María-Victoria , Rodriguez-Otero Paula , Oliva Stefania , Nogai Axel , Le Roux Nadia , Dong Liyan , Macé Sandrine , Gassiot Matthieu , Fitzmaurice Thomas , Oprea Corina , Moreau Philippe
Published: June 2023

Patients with newly diagnosed multiple myeloma (NDMM) ineligible for autologous stem cell transplantation (ASCT) have lower survival rates and may benefit from frontline regimens that include novel agents. This Phase 1b study (NCT02513186) evaluated preliminary efficacy, safety, and pharmacokinetics (PK) of isatuximab, an anti-CD38 monoclonal antibody, combined with bortezomib-lenalidomide-dexamethasone (Isa-VRd) in patients with NDMM ineligible for/with no intent for immediate ASCT. Overall, 73 patients received four 6-week induction cycles of Isa-VRd, then maintenance with Isa-Rd in 4-week cycles. In the efficacy population (n = 71), the overall response rate was 98.6%, with 56.3% achieving a complete response or better (sCR/CR), and 36/71 (50.7%) patients reaching minimal residual disease negativity (10−5 sensitivity). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 79.5% (58/73) of patients but TEAEs leading to permanent study treatment discontinuation were reported in 14 (19.2%) patients. Isatuximab PK parameters were within the previously reported range, suggesting that VRd does not alter the PK of isatuximab. These data support additional studies of isatuximab in NDMM, such as the Phase 3 IMROZ study (Isa-VRd vs VRd).
Co-encapsulation of curcumin and quercetin with zein/HP-β-CD conjugates to enhance environmental resistance and antioxidant activity
Authors: Qiu Chao , Zhang Zhiheng , Li Xiaojing , Sang Shangyuan , McClements David Julian , Chen Long , Long Jie , Jiao Aiquan , Xu Xueming , Jin Zhengyu
Published: June 2023

In this study, composite nanoparticles consisting of zein and hydroxypropyl beta-cyclodextrin were prepared using a combined antisolvent co-precipitation/electrostatic interaction method. The effects of calcium ion concentration on the stability of the composite nanoparticles containing both curcumin and quercetin were investigated. Moreover, the stability and bioactivity of the quercetin and curcumin were characterized before and after encapsulation. Fluorescence spectroscopy, Fourier Transform infrared spectroscopy, and X-ray diffraction analyses indicated that electrostatic interactions, hydrogen bonding, and hydrophobic interactions were the main driving forces for the formation of the composite nanoparticles. The addition of calcium ions promoted crosslinking of the proteins and affected the stability of the protein–cyclodextrin composite particles through electrostatic screening and binding effects. The addition of calcium ions to the composite particles improved the encapsulation efficiency, antioxidant activity, and stability of the curcumin and quercetin. However, there was an optimum calcium ion concentration (2.0 mM) that provided the best encapsulation and protective effects on the nutraceuticals. The calcium crosslinked composite particles were shown to maintain good stability under different pH and simulated gastrointestinal digestion conditions. These results suggest that zein–cyclodextrin composite nanoparticles may be useful plant-based colloidal delivery systems for hydrophobic bio-active agents.
Microstructural brain tissue changes contribute to cognitive and mood deficits in adults with type 2 diabetes mellitus
Authors: Roy Bhaswati , Choi Sarah E , Freeby Matthew J. , Kumar Rajesh
Published: June 2023

Type 2 diabetes mellitus (T2DM) patients show brain tissue changes in mood and cognitive regulatory sites, but the nature and extent of tissue injury and their associations with symptoms are unclear. Our aim was to examine brain tissue damage in T2DM over controls using mean diffusivity (MD) computed from diffusion tensor imaging (DTI), and assess correlations with mood and cognitive symptoms in T2DM. We collected DTI series (MRI), mood, and cognitive data, from 169 subjects (68 T2DM and 101 controls). Whole-brain MD-maps were calculated, normalized, smoothed, and compared between groups, as well as correlated with mood and cognition scores in T2DM subjects. Type 2 diabetes patients showed altered cognitive and mood functions over control subjects. Multiple brain sites in T2DM patients showed elevated MD values, indicating chronic tissue changes, including the cerebellum, insula, and frontal and prefrontal cortices, cingulate, and lingual gyrus. Associations between MD values and mood and cognition scores appeared in brain sites mediating these functions. Type 2 diabetes patients show predominantly chronic brain tissue changes in areas mediating mood and cognition functions, and tissue changes from those regions correlate with mood and cognitive symptoms suggesting that the microstructural brain changes may account for the observed functional deficits.
Cancer-associated fibroblast-derived exosome microRNA-21 promotes angiogenesis in multiple myeloma
Authors: Miaomiao Sun , Xiaoqian Wang , Yuwei Shou , Chao Chen , Chenbo Yang , Yinghao Liang , Yichen Hong , Jiao Shu , Kuisheng Chen
Published: June 2023

Multiple myeloma (MM) is the second most common hematological malignancy, and angiogenesis determines its progression. In the tumor microenvironment, normal fibroblasts (NFs) are transformed into cancer-associated fibroblasts (CAFs), which can promote angiogenesis. Microribonucleic acid-21 (miR-21) is highly expressed in various tumors. However, research on the relationship between tumor angiogenesis and miR-21 is rare. We analyzed the relationship between miR-21, CAFs, and angiogenesis in MM. NFs and CAFs were isolated from the bone marrow fluids of patients with dystrophic anemia and newly-diagnosed MM. Co-culturing of CAF exosomes with multiple myeloma endothelial cells (MMECs) showed that CAF exosomes were able to enter MMECs in a time-dependent manner and initiate angiogenesis by promoting proliferation, migration, and tubulogenesis. We found that miR-21 was abundant in CAF exosomes, entering MMECs and regulating angiogenesis in MM. By transfecting NFs with mimic NC, miR-21 mimic, inhibitor NC, and miR-21 inhibitor, we found that miR-21 significantly increased the expression of alpha-smooth muscle actin and fibroblast activation protein in NFs. Our results showed that miR-21 can transform NFs into CAFs, and that CAF exosomes promote angiogenesis by carrying miR-21 into MMECs. Therefore, CAF-derived exosomal miR-21 may serve as a novel diagnostic biomarker and therapeutic target for MM.
Starvation hardiness as preadaptation for life in subterranean habitats
Authors: Kozel Peter , Novak Tone , Janžekovič Franc , Lipovšek Saška
Published: June 2023

Most subterranean habitats, especially caves, are considered extreme environments, mainly because of the limited and erratic food supply and constant darkness. In temperate regions, many climatic conditions, such as temperature and air humidity, are periodically less adverse or even more favourable in caves than the harsh seasonal weather on the surface. Accordingly, many animal species search for hibernacula in caves. These overwintering, non-specialized subterranean species (non-troglobionts) show various modes of dormancy and ongoing development. Since they do not feed, they all undergo periodic starvation, a preadaptation, which might evolve in permanent starvation hardiness, such as found in most specialized subterranean species (troglobionts). To this end, we performed a comparative analysis of energy-supplying compounds in eleven most common terrestrial non-troglobiont species during winter in central European caves. We found highly heterogeneous responses to starvation, which are rather consistent with the degree of energetic adaptation to the habitat than to overwintering mode. The consumption of energy-supplying compounds was strongly higher taxa-dependant; glycogen is the main energy store in gastropods, lipids in insects, and arachnids rely on both reserve compounds. We assume that permanent starvation hardiness in specialized subterranean species might evolved in many different ways as shown in this study.
Relationship between circulating tumour DNA and skeletal muscle stores at diagnosis of pancreatic ductal adenocarcinoma: a cross-sectional study
Authors: Hanna Lauren , Sellahewa Rav , Huggins Catherine E. , Lundy Joanne , Croagh Daniel
Published: June 2023

Low skeletal muscle index (SMI) and low skeletal muscle radiodensity (SMD) are associated with reduced survival time in pancreatic ductal adenocarcinoma (PDAC). The negative prognostic impact of low SMI and low SMD is often reported as independent of cancer stage when using traditional clinical staging tools. Therefore, this study sought to explore the relationship between a novel marker of tumour burden (circulating tumour DNA) and skeletal muscle abnormalities at diagnosis of PDAC. A retrospective cross-sectional study was conducted in patients who had plasma and tumour tissue samples stored in the Victorian Pancreatic Cancer Biobank (VPCB) at diagnosis of PDAC, between 2015 and 2020. Circulating tumour DNA (ctDNA) of patients with G12 and G13 KRAS mutations was detected and quantified. Pre-treatment SMI and SMD derived from analysis of diagnostic computed tomography imaging was tested for its association to presence and concentration of ctDNA, as well as conventional staging, and demographic variables. The study included 66 patients at PDAC diagnosis; 53% female, mean age 68.7 years (SD ± 10.9). Low SMI and low SMD were present in 69.7% and 62.1% of patients, respectively. Female gender was an independent risk factor for low SMI (OR 4.38, 95% CI 1.23–15.55, p = 0.022), and older age an independent risk factor for low SMD (OR 1.066, 95% CI 1.002–1.135, p = 0.044). No association between skeletal muscle stores and concentration of ctDNA (SMI r = − 0.163, p = 0.192; SMD r = 0.097, p = 0.438) or stage of disease according to conventional clinical staging [SMI F(3, 62) = 0.886, p = 0.453; SMD F(3, 62) = 0.717, p = 0.545] was observed. These results demonstrate that low SMI and low SMD are highly prevalent at diagnosis of PDAC, and suggest they are comorbidities of cancer rather than related to the clinical stage of disease. Future studies are needed to identify the mechanisms and risk factors for low SMI and low SMD at diagnosis of PDAC to aid screening and intervention development.
Cisplatin-induced increase in heregulin 1 and its attenuation by the monoclonal ErbB3 antibody seribantumab in bladder cancer
Authors: Steele Thomas M. , Tsamouri Maria Malvina , Siddiqui Salma , Lucchesi Christopher A. , Vasilatis Demitria , Mooso Benjamin A. , Durbin-Johnson Blythe P. , Ma Ai-Hong , Hejazi Nazila , Parikh Mamta , Mudryj Maria , Pan Chong-xian , Ghosh Paramita M.
Published: June 2023

Cisplatin-based combination chemotherapy is the foundation for treatment of advanced bladder cancer (BlCa), but many patients develop chemoresistance mediated by increased Akt and ERK phosphorylation. However, the mechanism by which cisplatin induces this increase has not been elucidated. Among six patient-derived xenograft (PDX) models of BlCa, we observed that the cisplatin-resistant BL0269 express high epidermal growth factor receptor, ErbB2/HER2 and ErbB3/HER3. Cisplatin treatment transiently increased phospho-ErbB3 (Y1328), phospho-ERK (T202/Y204) and phospho-Akt (S473), and analysis of radical cystectomy tissues from patients with BlCa showed correlation between ErbB3 and ERK phosphorylation, likely due to the activation of ERK via the ErbB3 pathway. In vitro analysis revealed a role for the ErbB3 ligand heregulin1-β1 (HRG1/NRG1), which is higher in chemoresistant lines compared to cisplatin-sensitive cells. Additionally, cisplatin treatment, both in PDX and cell models, increased HRG1 levels. The monoclonal antibody seribantumab, that obstructs ErbB3 ligand-binding, suppressed HRG1-induced ErbB3, Akt and ERK phosphorylation. Seribantumab also prevented tumor growth in both the chemosensitive BL0440 and chemoresistant BL0269 models. Our data demonstrate that cisplatin-associated increases in Akt and ERK phosphorylation is mediated by an elevation in HRG1, suggesting that inhibition of ErbB3 phosphorylation may be a useful therapeutic strategy in BlCa with high phospho-ErbB3 and HRG1 levels.
A ROCK inhibitor suppresses the transforming growth factor-beta-2-induced endothelial–mesenchymal transition in Schlemm’s canal endothelial cells
Authors: Fujimoto Tomokazu , Inoue-Mochita Miyuki , Inoue Toshihiro
Published: June 2023

In the normal eye, most of the aqueous humor drains through the trabecular meshwork (TM) and Schlemm’s canal (SC). The concentration of transforming growth factor beta 2 (TGF-β2) is increased in the aqueous humor of primary open angle glaucoma patients. TGF-β2 increases outflow resistance by affecting the TM and SC, and endothelial–mesenchymal transition (EndMT) of SC cells is involved in these changes. Here, we investigated the effect of a ROCK inhibitor on TGF-β2-induced EndMT in SC cells. The ROCK inhibitor Y-27632 suppressed the TGF-β2-induced increase in the trans-endothelial electrical resistance (TER) and proliferation of SC cells. Y-27632 suppressed the expression of α-SMA, N-cadherin, and Snail, which are upregulated by TGF-β2. Moreover, TGF-β2 decreased mRNA levels of bone morphogenetic protein (BMP) 4 and increased those of the BMP antagonist gremlin (GREM1), but Y-27632 significantly suppressed these changes. Y-27632 also inhibited TGF-β2-induced phosphorylation of p-38 mitogen-activated protein kinase (MAPK). BMP4 and the p-38 MAPK inhibitor SB203580 suppressed the TGF-β2-induced TER elevation in SC cells. Moreover, SB203580 suppressed TGF-β2-induced upregulation of fibronectin, Snail, and GREM1. These results indicate that a ROCK inhibitor inhibited the TGF-β2-induced EndMT in SC cells, implying the involvement of p38 MAPK and BMP4 signaling.
Biological calcium carbonate enhanced the ability of biochar to passivate antimony and lead in soil
Authors: Wu Can , Yang Yi , Zhong Yaping , Guan Yan , Chen Qingqing , Du Wenping , Liu Guo
Published: June 2023

The unique organic nitrogen-containing functional groups in bio-CaCO3 can form a strong complex with lead and antimony in soil.
Microscopic strain mapping in polymers equipped with non-covalent mechanochromic motifs
Authors: Traeger Hanna , Kiebala Derek , Calvino Céline , Sagara Yoshimitsu , Schrettl Stephen , Weder Christoph , Clough Jess M.
Published: June 2023

We present a generalisable methodology based on fluorescent non-covalent mechanophores for producing quantitative maps of local strain around defects within three-dimensional polymeric matrices.
Mechanistic investigation of the transfer hydrogenation of alkynes catalysed by an MLC catalyst with multiple ancillary ligand sites
Authors: Zhang Yuan , Li Lan-Yu , Hou Cheng
Published: June 2023

This study reveals the mechanistic details of the transfer hydrogenation catalyzed by an MLC catalyst with multiple ancillary ligand sites.
AFM-based spherical indentation of a brush-coated soft material: modeling the bottom effect
Authors: Argatov Ivan , Jin Xiaoqing , Mishuris Gennady
Published: June 2023

A mathematical model for determining the intrinsic effective elastic modulus of a single brush-coated cell from the force–indentation curve with the bottom effect taken into account is developed.
Sex, sepsis and the brain: defining the role of sexual dimorphism on neurocognitive outcomes after infection
Authors: Polcz Valerie E. , Barrios Evan L. , Chapin Benjamin , Price Catherine C. , Nagpal Ravinder , Chakrabarty Paramita , Casadesus Gemma , Foster Thomas , Moldawer Lyle L. , Efron Philip A.
Published: June 2023

Sexual dimorphisms exist in multiple domains, from learning and memory to neurocognitive disease, and even in the immune system. Male sex has been associated with increased susceptibility to infection, as well as increased risk of adverse outcomes. Sepsis remains a major source of morbidity and mortality globally, and over half of septic patients admitted to intensive care are believed to suffer some degree of sepsis-associated encephalopathy (SAE). In the short term, SAE is associated with an increased risk of in-hospital mortality, and in the long term, has the potential for significant impairment of cognition, memory, and acceleration of neurocognitive disease. Despite increasing information regarding sexual dimorphism in neurologic and immunologic systems, research into these dimorphisms in sepsis-associated encephalopathy remains critically understudied. In this narrative review, we discuss how sex has been associated with brain morphology, chemistry, and disease, sexual dimorphism in immunity, and existing research into the effects of sex on SAE.
A monocular image depth estimation method based on weighted fusion and point‐wise convolution
Authors: Lei Chen , Zhengyou Liang , Yu Sun
Published: June 2023

The existing monocular depth estimation methods based on deep learning have difficulty in estimating the depth near the edges of the objects in an image when the depth distance between these objects changes abruptly and decline in accuracy when an image has more noises. Furthermore, these methods consume more hardware resources because they have huge network parameters. To solve these problems, this paper proposes a depth estimation method based on weighted fusion and point‐wise convolution. The authors design a maximum‐average adaptive pooling weighted fusion module (MAWF) that fuses global features and local features and a continuous point‐wise convolution module for processing the fused features derived from the (MAWF) module. The two modules work closely together for three times to perform weighted fusion and point‐wise convolution of features of multi‐scale from the encoder output, which can better decode the depth information of a scene. Experimental results show that our method achieves state‐of‐the‐art performance on the KITTI dataset with δ1 up to 0.996 and the root mean square error metric down to 8% and has demonstrated the strong generalisation and robustness.
Compton-thick AGN in the NuSTAR Era X: Analysing seven local CT-AGN candidates
Authors: Sengupta D. , Marchesi S. , Vignali C. , Torres-Albà N. , Bertola E. , Pizzetti A. , Lanzuisi G. , Salvestrini F. , Zhao X. , Gaspari M. , Gilli R. , Comastri A. , Traina A. , Tombesi F. , Silver R. , Pozzi F. , Ajello M.
Published: June 2023

Context. We present the broad-band X-ray spectral analysis (0.6–50 keV) of seven Compton-thick active galactic nuclei (CT-AGN; line-of-sight (LOS) column density > 1024 cm−2) candidates selected from the Swift-BAT 100 month catalogue using archival NuSTAR data.

Aims. We aim to obtain a complete census of the heavily obscured AGN in the local Universe (z < 0.05).

Methods. This work is in continuation of the ongoing research of the Clemson-INAF group to classify CT-AGN candidates at redshift z < 0.05 using physically motivated torus models.

Results. Our results confirm that three out of seven targets are bona fide CT-AGN. Adding our results to the previously analysed sources using NuSTAR data, we increase the population of bona fide CT-AGN by ∼9%, bringing the total number to 35 out of 414 AGN. We also performed a comparative study using MYTorus and borus02 on the spectra in our sample, finding that both physical models are strongly consistent in the parameter space of LOS column density and photon index. Furthermore, we also investigate the clumpiness of the torus clouds by separately computing the LOS and average torus column densities in each of the seven sources. Adding our results to all the previous 48 CT-AGN candidates analysed by the Clemson-INAF research team for which NuSTAR observations are available, we find that 78% of the sources are likely to have a clumpy distribution of the obscuring material surrounding the accreting supermassive black hole.
A detailed look at the thermal and nonthermal X-ray emission from the Vela supernova remnant with SRG/eROSITA
Authors: Mayer Martin G. F. , Becker Werner , Predehl Peter , Sasaki Manami
Published: June 2023

Context. The Vela supernova remnant (SNR) is one of the most nearby and extended objects in the X-ray sky. It constitutes a unique laboratory for studying the thermal and nonthermal X-ray emission from an evolved SNR and its central plerion at an unprecedented level of detail.

Aims. Our goal is to characterize the hot ejecta and shocked interstellar medium (ISM) associated with the Vela SNR, as well as the synchrotron-emitting relativistic electrons injected into the ambient medium by the central pulsar. To achieve this, we analyzed the dataset of Vela acquired by SRG/eROSITA during its first four all-sky surveys.

Methods. We present and analyze the energy-dependent morphology of Vela using X-ray images extracted in multiple energy bands. A quantitative view of the physical parameters affecting the observed thermal and nonthermal emission is obtained by performing spatially resolved X-ray spectroscopy of over 500 independent regions using multicomponent spectral models.

Results. Imaging demonstrates that the X-ray emission of the Vela SNR consists of at least three morphologically and energetically distinct components, with shell-like structures dominating below 0.6 keV, radial outward-directed features becoming apparent at medium energies, and the pulsar wind nebula (PWN) dominating the hard emission above 1.4 keV. Our spectroscopy reveals a highly structured distribution of X-ray absorption column densities, which intriguingly appears to lack any correlation with optical extinction measurements, possibly due to dust destruction or a clumpy ISM. The shock-heated plasma in Vela is found to be comparatively cool, with a median temperature of 0.19 keV, but exhibits several, often ejecta-rich, warmer regions. Within the observed ejecta clumps, we find an unexpectedly high concentration of neon and magnesium relative to oxygen, when compared to nucleosynthetic predictions. This includes the bright “shrapnel D”, in which we can separate shocked ISM in the soft bow-shock from a hot, ejecta-rich clump at its apex, based on the new data. Finally, we find an extremely extended, smoothly decreasing distribution of synchrotron emission from the PWN, which extends up to three degrees (14 pc) from the pulsar. The integrated X-ray luminosity of the PWN in the 0.5–8.0 keV energy band corresponds to 1.5 × 10−3 of the pulsar’s present-day spin-down power. The extended PWN emission likely traces the diffusion of a high-energy electron population in an ISM-level magnetic field, which requires the existence of a TeV counterpart powered by inverse Compton radiation.
Combustion synthesis of KZnPO4: RE (RE = Dy3+and Sm3+) Phosphors for n-UV based w-LEDs
Authors: Nandanwar Chandrahasya M. , Kokode Namdeo S. , Yerpude Atul N. , Dhoble Sanjay J.
Published: June 2023

In this work, KZnPO4:Dy3+and KZnPO4:Sm3+phosphors are synthesized using the Combustion technique. The phosphor XRD and photoluminescence properties were studied. The XRD was used to confirm the orthorhombic phase with the space group P n a 21. The PL emission spectra of the synthesized KZnPO4:Dy3+phosphor shows a strong emission at 482 and 574 nm under 350 nm excitation, which is ascribed due to4F9/2→6H15/2and4F9/2→6H13/2electronic transitions of the Dy3+ions, respectively. When the KZnPO4:Sm3+phosphor was excited at 402 nm, the emission spectra exhibited prominent bands located at 562 and 597 nm. The CIE coordinates show that the current phosphors have high colour purity. The KZnPO4:Dy3+and Sm3+phosphors provide an excellent candidate for n-UV-based w-LEDs.