bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing the bituminous pavement constructions with waste plastic materials improved the road constructions performance and their future applications
Authors: Pallavi M. Lalitha , Dey Subhashish , Veerendra Ganugula Taraka Naga , Padavala Siva Shanmukha Anjaneya Babu , Manoj Akula Venkata Phani
Published: September 2024

The yearly production of plastic garbage is rising in the current environment as a result of the fast population rise. Recycling and reusing plastic trash is essential for sustainable development. The need of the hour is to utilize waste polythene for various supporting reasons since it is not biodegradable. These materials are made of polymers like polyethylene, polypropylene, and polystyrene. Due to the enhanced performance and elimination of the environmental issue, adding plastic waste to flexible pavement has emerged as a desirable choice. A composite material known as bituminous concrete (BC) is often utilized in construction projects such as road paving, airport terminals, and stopover areas. It includes mineral aggregate and black top or bitumen, which are combined, laid down in layers, and then compacted. The bituminous mixture in this research article was combined with plastic to use a chemical stabilizer. The ideal bitumen content is replaced by 0, 15%, 27%, and 36% plastic, as well as the bitumen's weight, stability, and Marshall value to create hypothermal. A linear scale is used to compare the flow rates to the bituminous mixture. The characterization of plastics contains bituminous materials are done by the SEM–EDX, XRD, FTIR and BET analysis. There have been several studies on the addition of trash to bituminous mixes, but this one is focused on the use of plastic waste as a modification in a bitumen binder for flexible pavement. According to research, bituminous mixes containing up to 4 percent plastic waste are excellent for sustainable development.
Effects of nourished beach morphology on storm response
Authors: Cheng Jun , Wang Ping , Royer Elizabeth , Ragusa Dallas , Katwal Shalini , Nocelo Cecilia Limon
Published: September 2024

Field observations on storm induced beach changes are important to improve our effort on beach management. This study compared storm induced beach changes caused by hurricane Hermine in 2016 (4 years after a beach nourishment) and Tropical Storm Eta in 2020 (2 years after a beach renourishment) along the barrier-island coast of west-central Florida. Pre-Eta beach were 1 to 2 times wider than that of pre-Hermine. Since Hurricane Hermine and TS Eta generated a similar hydrodynamic condition for the study site, comparing beach changes induced by these two storms provides a unique opportunity to investigate the response of different antecedent beach conditions to energetic events. The shore protection effect of beach nourishment is apparently evidenced by the fact that post-Eta shoreline was located seaward of those post-Hermine at half of the beach-profile locations in the study area. The shore protection effect in the subaerial portion of the beach, however, is not obvious for the other half of beach profiles where shoreline positions were retreated to similar locations after these two storms. Instead, their shore protection effect occurred in the sub-aqueous portion of the beach and was indicated by higher sandbar crests located closer to the shoreline, which can dissipate and reduce incoming wave energy. The shoreline elevation needs to be properly defined (Mean High Water vs Mean Low Water line) as it is used as a proxy to represent beach volume loss. For Hermine induced beach change, no significant correlation exists between MHW line change and beach volume loss. While a significant correlation exists between MHW line change and beach volume loss induced by TS Eta. This correlation pattern switched if the shoreline here is defined as mean low water line. For efficient beach/shoreline management, multiple proxies (e.g., sandbar height and location of its crest and trough) in addition to shoreline change should be used to assess the performance of beach nourishment project.
Adopting health revenue cycle management best practices among public or private healthcare providers in Saudi Arabia: a pilot study
Authors: Al Yafi Ola , Albabtain Monirah A. , Arafat Amr , Bin Jassas Abdullatif
Published: September 2024

The new era of healthcare providers in Saudi Arabia where all covered beneficiaries will receive valued based medicine with cost effectiveness. Healthcare Transformation in Saudi Arabia: healthcare transformation is aiming to restructure the healthcare providers by Health Sector Transformation Program (HSTP) including revenue cycle management project; which is the core of our study. The literature lacks evidence of scoring systems for health revenue cycle management (HRCM) assessment in Saudi Arabia. We established a gap analysis scoring system to classify healthcare providers’ HRCM readiness. This pilot study aimed to assess the rate of adopting health revenue cycle management best practices among public or private healthcare providers in Saudi Arabia. This pilot study included ten healthcare providers in Saudi Arabia. The providers were assessed during the period from August 2022 to May 2023. The HRCM phases were: contract management, pre-service, time-of-service, and post-service. Contract management and preservice assessment revealed that all of the healthcare providers had missed some or most of their sub-major functions. For time-of-service, all healthcare providers required comprehensive gap analysis and the establishment of policies and procedures. Post-service was assessed in seven healthcare providers but was absent in three. All healthcare providers required training and the activation of reporting protocols and KPIs. Overall, the assessment revealed that one HCP had a low classification, seven had a moderate classification, and two had a high classification. All healthcare providers can be enhanced by training, comprehensive gap analysis, implementing policies and procedures with ongoing monitoring. Additionally, patient satisfaction research and the development of IT/technical solutions.
Morphological variation in first-formed shells of the Ordovician Paucicrura–Diceromyonia brachiopod lineage of North America
Authors: Rogal Rosemary C. C. , Sproat Colin D.
Published: September 2024

First-formed shells of several species of Dalmanellidae (Brachiopoda) from the Ordovician (Katian) of North America were measured and compared: Cincinnetina multisecta, Diceromyonia tersa, Diceromyonia storeya, Paucicrura corpulenta, Paucicrura rogata, and Paucicrura sillimani. Sizes and structures of the first-formed shells suggest that members of this family had planktotrophic subadults, with some species showing indications of only an unshelled larval stage and others showing both a larval stage and a shelled juvenile stage. This differs from modern rhynchonelliformean brachiopods, which all possess only a lecithotrophic larval stage. The range of sizes of first-formed shells of most studied species are similar, but P. sillimani of Baffin Island, Canada (middle Katian), has a significantly larger first-formed shell that formed during an extended juvenile stage. This may have enabled the species to colonize newly exploitable habitats during an interval of rapid sea level rise in Laurentia during the Katian. This plasticity of developmental modes in the Dalmanellidae shows not only that using distantly related modern brachiopods as an analog for extinct Paleozoic lineages may be misleading, but also that development can vary within a single lineage and that timing of developmental stages should not be considered a reliable character for use in phylogenetic studies of brachiopods.
RADIOCARBON MORTAR DATING INTERCOMPARISON MODIS2—APPROACH FROM THE ZAGREB RADIOCARBON LABORATORY, CROATIA
Authors: Sironić Andreja , Cherkinsky Alexander , Štrukil Vjekoslav , Borković Damir , Barešić Jadranka , Krajcar Bronić Ines
Published: September 2024

The Second International Mortar Dating Intercomparison Study (MODIS2) took place in 2020. Three mortar samples from different sites and chronologies were distributed among various research groups in form of bulk mortar and grain fraction smaller than 150 µm. This is the first time the Zagreb Radiocarbon Laboratory, with support of the Center of Applied Isotope Studies, University of Georgia, took part in the international mortar intercomparison. The initial approach of the Laboratory to mortar dating was to separate 32–63 µm grain fraction and collect three CO2 gas portions by sequential dissolution with acid. After checking the 14C date trends of the gas portions, which should be ascending with later fractions, the one for the first and shortest gas portion was reported as the age of the mortar. However, the first gas portion might not be true age of the mortar, since it still might contain some “dead” carbon. Therefore, data extrapolation from the first two initial CO2 portions was also conducted on the results, but not reported to the intercomparison. Though in general, all the intercomparison reported dates fit the expected historical ages, for one sample, the extrapolated result showed a better match to the historical data.
Relationship between serum vitamin D levels and thyroid- and parathyroid-related diseases: a Mendelian randomisation study
Authors: Zhang Lirong , Hu Congting , Lin Xinmiao , Lin Huiting , Wu Wenhua , Cai Jiaqin , Sun Hong , Wei Xiaoxia
Published: September 2024

Previous studies have indicated an association between vitamin D and thyroid- and parathyroid-related diseases. However, it remains unclear whether it is a cause of the disease, a side effect of treatment or a consequence of the disease. The Mendelian randomisation (MR) study strengthens the causal inference by controlling for non-heritable environmental confounders and reverse causation. In this study, a two-sample bidirectional MR analysis was conducted to investigate the causal relationship between serum vitamin D levels and thyroid- and parathyroid-related diseases. Inverse variance weighted, weighted median and MR-Egger methods were performed, the Cochran Q test was used to evaluate the heterogeneity and the MR-PRESSO and MR-Egger intercepts were utilised to assess the possibility of pleiotropy. The Bonferroni-corrected significance threshold was 0·0038. At the Bonferroni-corrected significance level, we found that vitamin D levels suggestively decreased the risk of benign parathyroid adenoma (OR = 0·244; 95 % CI 0·074, 0·802; P = 0·0202) in the MR analyses. In the reverse MR study, a genetically predicted risk of thyroid cancer suggestively increased the risk of elevated vitamin D (OR = 1·007; 95 % CI 1·010, 1·013; P = 0·0284), chronic thyroiditis significantly increased the risk of elevated vitamin D (OR = 1·007; 95 % CI 1·002, 1·011; P = 0·0030) and thyroid nodules was significantly decreased the vitamin D levels (OR = 0·991; 95 % CI 0·985, 0·997; P = 0·0034). The findings might be less susceptible to horizontal pleiotropy and heterogeneity (P > 0·05). This study from a gene perspective indicated that chronic thyroiditis and thyroid nodules may impact vitamin D levels, but the underlying mechanisms require further investigation.
International sports federations as de facto lawmakers: Queer-feminist explorations of the gendered power of sports law
Authors: Holzer Lena
Published: September 2024

This article analyses the law-making power of international sports federations, with a specific focus on their authority of shaping global norms on gender. It explores a variety of international sporting rules from feminist and queer perspectives. These include the ban of rainbow armbands at the 2022 FIFA (Men’s) World Cup, rules on the participation of transgender persons in rugby, gendered and racialized uniform regulations in sports, and the Semenya case concerning the sports participation of women with variations in sex characteristics The analysis asserts that despite being non-state actors, international sports federations are de facto international lawmakers that disseminate hegemonic gender norms reflecting cis-hetero-sexism and white body norms. However, analysing the Semenya case and the decision of the Chamber of the European Court of Human Rights in the case shows that the law-making power of international sports federations in shaping gender norms is not absolute but embedded in a transnational network of norms. The article concludes that subjecting international sports federations to a feminist, queer, and anti-racist legal analysis assists in understanding how hegemonic norms on gender circulate transnationally and enhances knowledge on how international law works in practice.
Transcatheter occlusion of venovenous collaterals in the total cavopulmonary Fontan circulation
Authors: Baker David W. , Uthayakumaran Gajon , Polwart Ngaire , Lee Melissa G.Y. , Wilson Will , Ayer Julian , Tanous David , D’Udekem Yves , Celermajer David S. , O’Donnell Clare , Cordina Rachael
Published: September 2024

Background:

Venovenous collaterals are abnormal connections between the systemic and pulmonary venous systems. They are commonly seen in the Fontan circulation and may lead to significant hypoxaemia. Transcatheter closure of venovenous collaterals is a potential but controversial treatment as the long-term benefits and outcomes are not well understood.

Methods:

This retrospective cohort study utilised data from the Australian and New Zealand Fontan Registry. Patients who underwent transcatheter venovenous collateral occlusion for hypoxemia from the year 2000 onwards were included. Atriopulmonary and Kawashima-type Fontan circulations were excluded to reflect a more contemporary Fontan cohort.

Results:

Nineteen patients (age 19.3 ± 7.8 years, 53% female) underwent transcatheter venovenous collateral occlusion. Compared to baseline, mean oxygen saturation was improved at latest follow-up (90.5% vs 87.0%; p = 0.003). Nine patients achieved a clinically significant response (defined as an increase of at least 5% to 90% or greater), and this was associated with lower baseline Fontan pressures (12.9 v 15.6 mmHg; p = 0.02). No heart failure hospitalisations, arrhythmia, transplant referrals, or mortality were observed during the median follow-up period of 4 years. Two patients experienced thromboembolic events and five patients underwent re-intervention.

Conclusion:

Transcatheter occlusion of venovenous collaterals in Fontan patients with chronic hypoxaemia resulted in a modest increase in oxygenation over a median follow-up of 4 years and longer-term prognosis did not appear to be adversely affected. Lower Fontan pressures at baseline were associated with a greater improvement in oxygenation.
Subjective fitness relates to performance and can be improved by exercise in children and young adults with heart disease
Authors: Aronoff Elizabeth B. , Chin Clifford , Opotowsky Alexander R. , Rice Malloree C. , Mays Wayne A. , Knecht Sandra K. , Goessling Jennah , Powell Adam W.
Published: September 2024

Introduction:

The Duke Activity Status Index is used to assess an individual patient’s perception of their fitness abilities. It has been validated and shown to predict actual fitness in adults but has been studied less in the paediatric population, specifically those with heart disease. This study aims to assess if the Duke Activity Status Index is associated with measured markers of physical fitness in adolescents and young adults with heart disease.

Methods:

This retrospective single-centre cohort study includes patients who completed a minimum of 12 weeks of cardiac rehabilitation between 2016 and 2022. Cardiac rehabilitation outcomes included physical, performance, and psychosocial measures. A comparison between serial testing was performed using a paired t-test. Univariable and multivariable analyses for Duke Activity Status Index were performed. Data are reported as median [interquartile range].

Results:

Of the 118 participants (20 years-old [13.9–22.5], 53% male), 33 (28%) completed at least 12 weeks of cardiac rehabilitation. Median peak oxygen consumption was 60.1% predicted [49–72.8%], and Duke Activity Status Index was 32.6 [21.5–48.8]. On Pearson’s correlation assessing the Duke Activity Status Index, there were significant associations with % predicted peak oxygen consumption (r = 0.49, p < 0.0001), 6-minute walk distance (r = 0.45, p < 0.0001), Duke Activity Status Index metabolic equivalents (r = 0.45, p < 0.0001), and dominant hand grip (r = 0.48, p < 0.0001). In multivariable analysis, the % predicted peak oxygen consumption (r = 0.40, p = 0.005) and dominant hand grip (r = 0.37, p = 0.005) remained statistically significant.

Conclusions:

Duke Activity Status Index is associated with measures of physical fitness in paediatric and young adults with heart disease who complete a cardiac rehabilitation program.
Housing and Papering Over the Cracks of the Welfare State: Exploring the Role and Impact of Technology as Part of Housing Service Provision in an Era of Multi-level Precarity
Authors: McCall Vikki , Rolfe Steve , Gibson Grant , Serpa Regina , Lawrence Julia
Published: September 2024

The UK welfare landscape is increasingly challenging due to ongoing austerity involving public sector cuts, service retrenchment, and withdrawal of statutory responsibilities. This article shows that as the welfare state contracts, precarity increases and responsibility for service provision is progressively devolved to front-line individuals and service users. To illustrate, the article examines the use of assistive and everyday technologies to improve social housing residents’ quality of life based on a longitudinal mixed methods study conducted between 2020 and 2022. The findings highlight how housing providers can support person-led technology interventions for older residents, where minor improvements positively impact day-to-day living. However, interventions are often limited by practicalities, capacity, and cost. This article connects technological engagement in housing to the ongoing ‘responsibilisation’ of many areas of housing provision to social landlords and tenants. This suggests an extension of responsibility where social housing providers are papering over the cracks in the welfare state.
Do immigrants at bay keep the xenophobes away? Post-entry rights and public opposition to immigrant admission
Authors: Lutz Philipp
Published: September 2024

Many citizens in liberal democracies are concerned about immigration and its impact on their countries. Governments often seek to address these concerns by restricting the post-entry rights of immigrants such as the right to permanent settlement or access to welfare benefits. Thereby, it is expected that immigrants with an inferior legal status are (perceived as) less threatening to natives and, as a result, make the latter more willing to accept new immigrants. Does this policy rationale indeed attenuate public opposition to immigrant admission and thus allow for the reconciliation of the economic need for immigrants with the political concerns of domestic constituents? This study advances the theoretical argument of a rights-conditionality in citizens’ immigration preferences and provides empirical evidence on the phenomenon. A factorial survey experiment among citizens in the United States and Switzerland tests the effect of residence and welfare rights on the public opposition to immigrant admission. The results show that restricting immigrants’ welfare rights does significantly decrease public opposition towards immigration across the two countries. In contrast, restricting immigrants’ residence rights does not, and in the context of Switzerland, even increases opposition to immigrant admission. Citizens critical of immigration are thus not per se more welcoming to immigrants if they receive an inferior legal status but seem to care about immigrants’ contributions and commitment to the receiving society. The findings highlight the importance of immigrants‘ post-entry rights in the view of citizens and show how the design of immigration policies may help to understand public immigration preferences.
What militaries need to know about data protection and the right to digital privacy/private life
Authors: Argren Rigmor
Published: September 2024

With the advent of socio-technical systems that gather and process personal data, the capacity to identify and even locate people in an automated fashion has dramatically increased. This article discusses what militaries need to know about data protection and the right to digital privacy/private life when personal data is processed. The focus in this discussion is on sensitive data that makes individuals identifiable. It is here argued that the right to data protection and the right to digital privacy/private life are distinctive and separate rights and should be treated as such, despite some overlaps. Although the law of armed conflict approaches processing of sensitive data in a topical manner, it remains firm on the delimitation between what is permissible and what becomes unlawful when it comes to processing data. This article illustrates that elements of both data protection and protection of the right to privacy/private life can be traced in the law of armed conflict. In fact, both rights remain distinctive also in times of armed conflict and must be separately protected through obligations of result as well as obligations of conduct.
Embedding constitutional rights
Authors: Taylor Whitney K.
Published: September 2024

This article details the concept of constitutional embedding and demonstrates its utility in four country-rights cases. Constitutional embedding refers to the process by which some understanding of constitutional rights comes to take root in everyday life, moving from words on paper to something that shapes expectations and behavior. The degree of constitutional embedding varies along two dimensions: social and legal, or how individuals and groups operating in the social sphere understand and relate to constitutional rights, and how those working in the formal legal sphere do so. In a global political climate defined by democratic backsliding, powerful vested interests, and backlash against moves toward equality, the status of constitutional rights and how they become and remain embedded is doubly important. The constitutional embedding framework highlights how interactions between legal elites and ordinary citizens constitute the extent to which constitutional law influences daily life. The framework has broad applicability across contexts and rights domains.
Observational Insights of Nearshore Wind Stress and Parameterizations From Gaussian Process Regressions
Authors: Benbow C. A. , MacMahan J. H.
Published: September 2024

The nearshore wind stress, , is examined using machine‐learning models for air‐ocean data collected via new flux buoys deployed across four experiments. Consistent with prior nearshore studies, existing open‐ocean models predict nearshore with a large error of 0.0152 m2/s2. Gaussian Process Regression (GPR) for nearshore is developed, reducing errors to 0.0108 m2/s2. Nearshore air‐sea parameterizations are examined with wind speed (61%) and the wind‐wave frequency of encounters (16%) being the most important. A simpler nearshore, GPR‐derived, wind‐dependent‐only model () is developed, with errors of 0.0135 m2/s2. GPRs, evaluated using identical variables, were applied to nearshore observations, and these observations modeled with open‐ocean formulations for an initial comparison of parameterizations between these two regimes. The parameterizations are similar, though with subtle nonlinear differences. The new nearshore data set and machine‐learning models enhance the accuracy of predictions and understanding of differences from the open‐ocean.
Vapor Condensates on the Most Pristine Black Beads From a Clod in Apollo Drive Tube 73001: Discovery of Lunar NaCl Nanocrystals
Authors: Liu Yang , Ma Chi
Published: September 2024

Identification of the mineral species of vapor condensates on the surface of lunar pyroclastic beads, formed during the flights of beads in the lunar volcanic plume, helps to constrain the physical and chemical conditions of the lunar volcanic plume. We conducted nanomineralogy studies of vapor condensates on the surface of pristine black beads from a clod that was extracted from the recently opened Apollo drive tube 73001. This drive tube had been sealed under vacuum since its collection on the Moon and thus represents the most pristine sample in allocatable Apollo collection. Vapor condensates observed on the surface include patches made of ZnS nanocrystals and possible rare scattered NaCl nanocrystals. ZnS nanocrystals were previously found on Apollo 15 green and yellow beads, but NaCl nanocrystals are unique to black beads. Both ZnS and NaCl nanocrystals are absent in Apollo 17 74220 orange beads. Although orange and black beads are of similar chemistry, black beads in the clod 73001, 226 could form from a different environment.
Tectonic Anatomy Reveals the Chinese Altai‐Kuerti‐Dulate Arc Amalgamation in the Southern Altaids
Authors: Gan Jingmin , Xiao Wenjiao , Mao Qigui , Wang Hao , Sang Miao , Tan Zhou , Li Rui , Ao Songjian , Song Dongfang , Zhang Zhiyong
Published: September 2024

The Erqis tectonic belt, situated at the junction of the Chinese Altai‐East Junggar, originated through the subduction of the Ob‐Zaisan Ocean, playing a pivotal role in unraveling the tectonic evolution of the southern Altaids. Tectonic and provenance analyses discern three distinct arcs: the Chinese Altai in the north exhibits a protracted history from the late Cambrian to early Permian with a slender accretionary complex (AC) termed the Supute AC; the Kuerti intra‐oceanic arc in the middle emerged during the Silurian to Devonian coevally with a minor AC known as the Tesibahan AC; and the Dulate arc in the south predominantly evolved from the Middle Devonian to Permian, giving rise to the Fuyun AC that independently developed on its northern margin at least until ∼273 Ma. Our findings indicate the existence of multiple arcs within the Ob‐Zaisan Ocean, forming an archipelago paleogeography in the Paleo‐Asian Ocean. Provenance studies lead us to propose that cryptic sutures demarcating the Chinese Altai, Kuerti, and Dulate lie approximately along the Kuerti and Tesibahan faults, respectively, and that the oceanic branches between these arcs subducted northward beneath the Chinese Altai and Kuerti arcs and southward beneath the Dulate arc. Additionally, our work demonstrates the closure of the Ob‐Zaisan Ocean most probably postdates ∼273 Ma. Combining our data with previous research, we present a novel tectonic evolution model, elucidating several arc amalgamations with multiple subduction polarities between Chinese Altai and East Junggar throughout the late Cambrian to Permian.
The Changing Hydrology of an Irrigated and Dammed Yangtze River: Streamflow, Extremes, and Lake Hydrodynamics
Authors: Hao Haoran , Dong Ningpeng , Yang Mingxiang , Wei Jianhui , Zhang Xuejun , Xu Shiqin , Yan Denghua , Ren Liliang , Leng Guoyong , Chen Lu , Zhou Xudong , Wang Hao , Song Lijuan , Kunstmann Harald
Published: September 2024

Understanding the role of anthropogenic activities in the hydrological cycle is critical to support sustainable water management for the Yangtze River Basin (YRB), which experiences extensive dam operation, irrigation and water withdrawal. However, this remains challenging due to insufficient accuracies of existing process‐based models for fully depicting anthropogenic activities as part of the hydrological cycle. To this end, this study enhances a national‐scale coupled land surface‐hydrologic‐hydrodynamic model (CLHMS) with a dynamic irrigation scheme for distinct crops, an extended reservoir operation scheme incorporating both water storage anomalies and water demand anomalies, and a cost‐function‐based approach to link water demands with reservoir operation. The enhanced model is extensively validated against historical streamflow, water storage of 90 reservoirs, and irrigation water withdrawal in the YRB, and the water level and storage of the Poyang Lake (PYL). By setting up controlled experiments in the YRB, we show that the streamflow decreases by 2%–6% due to irrigation and water withdrawal, and manifests an attenuated seasonality due to reservoir operation. At the basin scale, the increasing trend of extreme flood peaks exhibits a reversal under human activities, with the flood mitigation effect of irrigation and water withdrawal accounting for up to 50% of that of reservoir operation. The hydrodynamics of the PYL also exhibits considerable human‐induced alterations, with a 1.79 m‐decrease in the water level at the end of flood season. Our study sheds light on quantifying anthropogenic hydrologic impacts at basin scales, with important implications for understanding the co‐evolution between anthropogenic activities and the hydrological cycle.
Integrated stress response plasticity governs normal cell adaptation to chronic stress via the PP2A-TFE3-ATF4 pathway
Authors: A. Avelar Rita , Gupta Riya , Carvette Grace , da Veiga Leprevost Felipe , Jasti Medhasri , Colina Jose , Teitel Jessica , Nesvizhskii Alexey I. , O’Connor Caitlin M. , Hatzoglou Maria , Shenolikar Shirish , Arvan Peter , Narla Goutham , DiFeo Analisa
Published: September 2024

The integrated stress response (ISR) regulates cell fate during conditions of stress by leveraging the cell’s capacity to endure sustainable and efficient adaptive stress responses. Protein phosphatase 2A (PP2A) activity modulation has been shown to be successful in achieving both therapeutic efficacy and safety across various cancer models. However, the molecular mechanisms driving its selective antitumor effects remain unclear. Here, we show for the first time that ISR plasticity relies on PP2A activation to regulate drug response and dictate cellular survival under conditions of chronic stress. We demonstrate that genetic and chemical modulation of the PP2A leads to chronic proteolytic stress and triggers an ISR to dictate whether the cell lives or dies. More specifically, we uncovered that the PP2A-TFE3-ATF4 pathway governs ISR cell plasticity during endoplasmic reticular and cellular stress independent of the unfolded protein response. We further show that normal cells reprogram their genetic signatures to undergo ISR-mediated adaptation and homeostatic recovery thereby avoiding toxicity following PP2A-mediated stress. Conversely, oncogenic specific cytotoxicity induced by chemical modulation of PP2A is achieved by activating chronic and irreversible ISR in cancer cells. Our findings propose that a differential response to chemical modulation of PP2A is determined by intrinsic ISR plasticity, providing a novel biological vulnerability to selectively induce cancer cell death and improve targeted therapeutic efficacy.
Characterization of regulated cancer cell death pathways induced by the different modalities of non-thermal plasma treatment
Authors: Biscop Eline , Baroen Jana , De Backer Joey , Vanden Berghe Wim , Smits Evelien , Bogaerts Annemie , Lin Abraham
Published: September 2024

Non-thermal plasma (NTP) has shown promising anti-cancer effects, but there is still limited knowledge about the underlying cell death mechanisms induced by NTP and inherent differences between NTP treatment modalities. This study aimed to investigate four major regulated cell death (RCD) pathways, namely apoptosis, pyroptosis, necroptosis, and ferroptosis, in melanoma cancer cells following NTP treatment, and to provide an overview of molecular mechanistic differences between direct and indirect NTP treatment modalities. To discriminate which cell death pathways were triggered after treatment, specific inhibitors of apoptosis, pyroptosis, necroptosis, and ferroptosis were evaluated. RCD-specific molecular pathways were further investigated to validate the findings with inhibitors. Both direct and indirect NTP treatment increased caspase 3/7 and annexin V expression, indicative of apoptosis, as well as lipid peroxidation, characteristic of ferroptosis. Pyroptosis, on the other hand, was only induced by direct NTP treatment, evidenced by increased caspase 1 activity, whereas necroptosis was stimulated in a cell line-dependent manner. These findings highlight the molecular differences and implications of direct and indirect NTP treatment for cancer therapy. Altogether, activation of multiple cell death pathways offers advantages in minimizing treatment resistance and enhancing therapeutic efficacy, particularly in a combination setting. Understanding the mechanisms underlying NTP-induced RCD will enable the development of strategic combination therapies targeting multiple pathways to achieve cancer lethality.
N6-methyladenosine-modified TRIM37 augments sunitinib resistance by promoting the ubiquitin-degradation of SmARCC2 and activating the Wnt signaling pathway in renal cell carcinoma
Authors: Luo Qiang , Dai Ting , Dong Yihong , Liang Jianpeng , Xu Zhipeng , Sun Zhixia
Published: September 2024

Tripartite motif-containing 37 (TRIM37) is reportedly a key member of the superfamily of TRIM proteins. Emerging evidence underscores the close association between dysregulated TRIM37 expression and the progression of various human malignancies. However, the precise biological functions and regulatory mechanisms of TRIM37 remain elusive. This study aimed to elucidate the impact of TRIM37 on the chemotherapy sensitivity of renal cell carcinoma (RCC) and uncover its specific molecular regulatory role. Using RT-qPCR and western blot assays, we assessed TRIM37 expression in both RCC patients and RCC cells. Through in vitro and in vivo experiments, we investigated the effects of TRIM37 silencing and overexpression on RCC cell proliferation, stemness capacity, and chemotherapy sensitivity using colony formation and sphere formation assays. Additionally, a co-immunoprecipitation (Co-IP) experiment was conducted to explore putative interacting proteins. Our results revealed elevated TRIM37 expression in both RCC patient tumor tissues and RCC cells. Functional experiments consistently demonstrated that TRIM37 silencing reduced proliferation and stemness capacity while enhancing chemotherapy sensitivity in RCC cells. Furthermore, we discovered that TRIM37 mediates the degradation of SMARCC2 via ubiquitin-proteasome pathways, thereby further activating the Wnt signaling pathway. In conclusion, this study not only sheds light on the biological role of TRIM37 in RCC progression but also identifies a potential molecular target for therapeutic intervention in RCC patients.
Computerized cognitive training improves cognitive function in primary breast cancer survivors
Authors: Kleinknecht Karl R. , Bierend Mira , Keim Lisa-Maria , Bartels Frederik , Lampit Amit , Finke Carsten
Published: September 2024

Cancer-related cognitive impairment has a significant impact on the quality of life and perceived cognitive ability of breast cancer patients and frequently affects attention, working memory, and executive function. Several interventional approaches to treat these deficits have been studied, including web-based cognitive training, but methods and timing in relation to cancer treatment are heterogeneous. Only few interventions start early after primary breast cancer treatment, a time when many patients report the greatest impairments in quality of life and cognition. In this randomized controlled pilot study, 31 breast cancer survivors with subjective cognitive deficits and a mean post-treatment duration of 6.6 months (SD = 9.3) were assigned to either 14 weeks of a web-based cognitive training program (training group, n = 16) or a control group (n = 15). All patients underwent detailed neuropsychological assessment, evaluation of patient-reported outcomes (PROMs), and neurological examination before (baseline, T1) and after (follow-up, T2) the intervention. Longitudinal (T1 vs. T2) and cross-sectional (T2) cognitive performance was assessed for both groups. Overall cognitive impairment significantly improved in the training group following training (56% vs 25%; p = 0.03, Phi = 0.51), but not in the control group (73% vs. 73%; p = 1) in the longitudinal analysis (T1 vs. T2). Specifically, the training group showed statistically significant improvement of executive functions (p = 0.004, Phi = 0.32). No effects of training on subjective cognitive deficits or PROMs were observed. Comparing cross-sectional cognitive performance at follow-up (T2), the training group showed a significantly lower rate of cognitive impairment overall (p = 0.007, Phi = 0.48) and a better cognitive performance for executive function (p = 0.04, Phi = 0.32) compared to the control group. In this prospective pilot study, web-based cognitive training was efficacious in improving overall cognitive performance and executive function. Importantly, this study investigated a web-based cognitive training for the immediate post-treatment phase, when up to 75% of breast cancer patients experience cognitive decline. These results indicate that cognitive training may improve neuropsychological outcomes for patients with breast cancer.
Mosaic HIV-1 vaccine and SHIV challenge strain V2 loop sequence identity and protection in primates
Authors: Vanshylla Kanika , Tolboom Jeroen , Stephenson Kathryn E. , Feddes-de Boer Karin , Verwilligen Annemiek , Rosendahl Huber Sietske Karla , Rutten Lucy , Schuitemaker Hanneke , Zahn Roland C. , Barouch Dan H. , Wegmann Frank
Published: September 2024

The failure of human vaccine efficacy trials assessing a mosaic HIV-1 vaccine calls into question the translatability of preclinical SHIV challenge studies that demonstrated high efficacy of this vaccine in primates. Here we present a post hoc immune correlates analysis of HIV-1 Env peptide-binding antibody responses from the NHP13-19 study identifying the V2 loop as the principal correlate of protection in primates. Moreover, we found high V2 loop sequence identity between the Mos1 vaccine component and the SHIV challenge strain, while the vaccine showed considerably lower V2 identity to globally circulating HIV-1 sequences. Thus, the induction of immune responses against the V2 epitope, which had exceptional identity between the vaccine and challenge Env strains, may have contributed to the high protection in primates.
Large-scale analysis of CDH1 mutations defines a distinctive molecular subset with treatment implications in gastric cancer
Authors: Wang Jingyuan , Xiu Joanne , Battaglin Francesca , Arai Hiroyuki , Soni Shivani , Zhang Wu , Goldberg Richard M. , Philip Philip A. , Seeber Andreas , Hwang Jimmy J. , Shields Anthony F. , Marshall John L. , Astaturov Igor , Liu Tianshu , Lockhart A. Craig , Korn W. Michael , Shen Lin , Lenz Heinz-Josef
Published: September 2024

Although histological and molecular classifications have been extensively studied for gastric cancer (GC), targeted therapies for GC remain limited. CDH1 mutations (MT) are characteristic of genomically stable GC and are associated with poor prognosis, but lack effective or targeted therapies. Here, we showed the overall mutation frequency of CDH1 was 9.7% (155 of 1596). CDH1-MT GC showed significantly lower rates of PD-L1 positivity (CPS score ≥1) than CDH1-wildtype (WT) GC (56.7% vs. 73.3%, p < 0.05). Compared to CDH1-WT GC, mutations of ARID1A, WRN, POT1, CDK12, and FANCC were significantly higher, while TP53 and APC were significantly lower in CDH1-MT GC (p < 0.05); The rates of KRAS and HER2 amplifications were significantly lower, while CRKL and IGF1R amplifications were significantly higher in CDH1-MT GC, compared to CDH1-WT GC (p < 0.05). Frequently altered genes in CDH1-MT GC were especially enriched in DNA damage repair and cell cycle checkpoint pathways. Inhibition of E-cadherin sensitized GC cell lines to PARP and Wee1 inhibitors by disrupting DNA damage repair pathway and cell cycle checkpoint. This is the largest study to investigate the distinct genomic landscape of CDH1-MT GC. Our data indicated GC patients with CDH1 mutations could potentially benefit from agents targeting PARP and Wee1.
Integrated multi-omics assessment of lineage plasticity in a prostate cancer patient with brain and dural metastases
Authors: Ludwig Megan L. , Moline David , Horrmann Alec , Boytim Ella , Larson Gabrianne , Arafa Ali T. , Sayeda Masooma , Lozada John R. , Bergom Hannah E. , Day Abderrahman , Dasaraju Sandhyarani , Dehm Scott M. , Murugan Paari , Hwang Justin , Drake Justin M. , Antonarakis Emmanuel S.
Published: September 2024

Metastases to the brain are rare in prostate cancer. Here, we describe a patient with two treatment-emergent metastatic lesions, one to the brain with neuroendocrine prostate cancer (NEPC) histology and one to the dural membrane of adenocarcinoma histology. We performed genomic, transcriptomic, and proteomic characterization of these lesions and the primary tumor to investigate molecular features promoting these metastases. The two metastatic lesions had high genomic similarity, including TP53 mutation and PTEN deletion, with the most striking difference being the additional loss of RB1 in the NEPC lesion. Interestingly, the dural lesion expressed both androgen receptor and neuroendocrine markers, suggesting amphicrine carcinoma (AMPC). When analyzing pioneer transcription factors, the AMPC lesion exhibited elevated FOXA1 activity while the brain NEPC lesion showed elevated HOXC10, NFYB, and OTX2 expression suggesting novel roles in NEPC formation or brain tropism. Our results highlight the utility of performing multi-omic characterization, especially in rare cancer subtypes.
Overcoming biases of individual level shopping history data in health research
Authors: Skatova Anya
Published: September 2024

Novel sources of population data, especially administrative and medical records, as well as the digital footprints generated through interactions with online services, present a considerable opportunity for advancing health research and policymaking. An illustrative example is shopping history records that can illuminate aspects of population health by scrutinizing extensive sets of everyday choices made in the real world. However, like any dataset, these sources possess specific limitations, including sampling biases, validity issues, and measurement errors. To enhance the applicability and potential of shopping data in health research, we advocate for the integration of individual-level shopping data with external datasets containing rich repositories of longitudinal population cohort studies. This strategic approach holds the promise of devising innovative methodologies to address inherent data limitations and biases. By meticulously documenting biases, establishing validated associations, and discerning patterns within these amalgamated records, researchers can extrapolate their findings to encompass population-wide datasets derived from national supermarket chain. The validation and linkage of population health data with real-world choices pertaining to food, beverages, and over-the-counter medications, such as pain relief, present a significant opportunity to comprehend the impact of these choices and behavioural patterns associated with them on public health.
STAT1 as a tool for non-invasive monitoring of NK cell activation in cancer
Authors: Min Jin Young , Kim Hye Min , Lee Hyunseung , Cho Mi Young , Park Hye Sun , Lee Sang-Yeop , Park Min Sung , Ha Sang Keun , Kim Donghwan , Jeong Hye Gwang , Kim Tae-Don , Hong Kwan Soo , Han Eun Hee
Published: September 2024

Natural killer (NK) cells play a crucial role in immunotherapy for cancer due to their natural ability to target and destroy cancer cells. However, current methods to visualize NK cells’ activity against tumors in live organisms are limited. We introduce an imaging method that non-invasively tracks NK cell activation by cancer cells through the STAT1 protein. To achieve this, we modified NK cells to include a specific genetic sequence that binds to STAT1 when activated. These engineered NK cells (GAS-NK) demonstrate their functionality through various biological tests and analysis. Observations of changes in cancer environments and patient-derived cancer organoid models further confirm the effectiveness of this approach. Our method provides a way to monitor NK cell activity, which could improve the prediction and effectiveness of NK cell-based cancer therapies, contributing to advances in cancer treatment.
Gate tunable edge magnetoplasmon resonators
Authors: Frigerio Elric , Rebora Giacomo , Ruelle Mélanie , Souquet-Basiège Hubert , Jin Yong , Gennser Ulf , Cavanna Antonella , Plaçais Bernard , Baudin Emmanuel , Berroir Jean-Marc , Safi Inès , Degiovanni Pascal , Fève Gwendal , Ménard Gerbold C.
Published: September 2024

Quantum Hall systems are platforms of choice to study topological properties of condensed matter systems and anyonic exchange statistics. In this work we have developed a tunable radiofrequency edge magnetoplasmonic resonator controlled by both the magnetic field and a set of electrostatic gates, meant to serve as a versatile platform for future interferometric devices designed to evidence non-abelian anyons. In our device, gates allow us to change both the size of the resonant cavity and the electronic density of the two-dimensional electron gas. We show that we can continuously control the frequency response of our resonator, making it possible to develop an edge magnetoplasmon interferometer. As we reach smaller sizes of our resonator, finite size effects caused by the measurement probes manifest. In the future, such device will be a valuable tool to investigate the properties of non-abelian anyons in the fractional quantum Hall regime.
Correction of a widespread bias in pooled chemical genomics screens improves their interpretability
Authors: Kim Lili M , Todor Horia , Gross Carol A
Published: September 2024

Chemical genomics is a powerful and increasingly accessible technique to probe gene function, gene–gene interactions, and antibiotic synergies and antagonisms. Indeed, multiple large-scale pooled datasets in diverse organisms have been published. Here, we identify an artifact arising from uncorrected differences in the number of cell doublings between experiments within such datasets. We demonstrate that this artifact is widespread, show how it causes spurious gene–gene and drug–drug correlations, and present a simple but effective post hoc method for removing its effects. Using several published datasets, we demonstrate that this correction removes spurious correlations between genes and conditions, improving data interpretability and revealing new biological insights. Finally, we determine experimental factors that predispose a dataset for this artifact and suggest a set of experimental and computational guidelines for performing pooled chemical genomics experiments that will maximize the potential of this powerful technique.
Mass Spectrometry and Chemical Biology Approaches for Deconvoluting Epigenetic Targets
Authors: Burton Antony J. , Hamza Ghaith M. , Iannetta Anthony A. , Miele Eric , Zhang Andrew X.
Published: September 2024

Epigenetic proteins modulate a critical process in the cell that affects gene and subsequently protein expression. Analyzing epigenetic proteins at the proteome-wide level can provide critical insights into their biological mechanisms, particularly generating hypotheses around their relevance to diseases. This chapter provides an overview of the advances and application of chemical biology and mass spectrometry-based methods to interrogate complex epigenetic biology and accelerate drug development against these challenging targets. We discuss chemoproteomics, CESTA (Cellular Thermal Shift Assay), AP-MS (affinity purification mass spectrometry), interactomics, and global proteomic analysis including charting post-translation modifications, in the context of their impact on epigenetic drug discovery.