bluuebunny/crossref_metadata_2025 huggingface dataset:
The teleological modal profile and subjunctive background of organic generation and growth
Authors: Stovall Preston
Published: February 2024

Formal methods for representing the characteristic features of organic development and growth make it possible to map the large-scale teleological structure of organic activity. This provides a basis for semantically evaluating, or providing a theory of meaning for, talk of organic activity as purposive. For the processes of organic generation and growth are subjunctively robust under a variety of influences characteristic for the kind or species in question, and these subjunctive conditions can be displayed in a two-dimensional array. After motivating and introducing this array, I use its two dimensions to partially account for features of the purposiveness characterizing two sets of exemplars of the plant and animal kingdoms: ferns and cacti, and cheetah and gazelle. The result is a formal framework for interpreting talk of organic activity as purposive, able to be adapted to a range of research traditions in the philosophy of language and the philosophy of biology.
Immunohistological analysis reveals IgG1-dominant immunophenotype of tubulointerstitial nephritis unassociated with IgG4-related diseases
Authors: Hyodo Toshiki , Hara Shigeo , Goto Shunsuke , Fujii Hideki , Nishi Shinichi , Horinouchi Tomoko , Nozu Kandai , Yoshikawa Norishige , Yoshimoto Akihiro , Itoh Tomoo
Published: February 2024

Purpose

Tubulointerstitial nephritis (TIN) has various etiologies, including IgG4-related disease (IgG4-RD), autoimmune diseases, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and others. IgG4-positive plasma cell infiltration can occasionally be found in TIN unrelated to IgG4-RD. Therefore, there may be problems with usage of IgG4 immunostaining to differentiate between TIN with and TIN without IgG4-RD. This study aimed to compare the proportion of plasma cells that are positive for each IgG subclass and to clarify the predominant IgG subclass trends and clinical characteristics associated with IgG4-RD and non-IgG4-related interstitial nephritis.

Methods

The study enrolled 44 cases of TIN: 6 of IgG4-RD, 8 of autoimmune disease, 9 of AAV, and 21 of unknown disease group. In addition to clinical characteristics, IgG subclass composition of interstitial plasma cells was evaluated among 4 groups by immunohistochemistry.

Results

IgG1 was the predominant IgG subclass in TIN unrelated to IgG4-RD. In the IgG4-RD group, the IgG subclass rate was high in both IgG1 and IgG4. The rate of average IgG4-positive cells was significantly lower in the autoimmune disease group and unknown disease group compared with the IgG4-RD group.

Conclusion

The present study revealed IgG1-dominant immune profiles of TIN unrelated to IgG4-RD. Further investigation is required to elucidate the clinicopathological differences between IgG1-dominant and IgG4-dominant groups in IgG4-RD.
Effects of Non-Face-to-Face Chronic Care Management on Service Utilization and Outcomes Among US Medicare Beneficiaries with Diabetes
Authors: Hong Dongzhe , Stoecker Charles , Shao Yixue , Nauman Elizabeth , Fonseca Vivian , Hu Gang , Bazzano Alessandra N. , Kabagambe Edmond K. , Shi Lizheng
Published: February 2024

Background

Type 2 diabetes mellitus (T2DM) results in heavy economic and disease burdens in Louisiana. The Centers for Medicare and Medicaid Services has reimbursed non-face-to-face chronic care management (NFFCCM) for patients with two or more chronic conditions since 2015.

Objective

To assess the impacts of NFFCCM on healthcare utilization and health outcomes.

Design, Setting, and Participants

This retrospective cohort study included Medicare fee-for-service beneficiaries with T2DM and at least one additional chronic disease between 2014 and 2018.

Exposures

At least one record of NFFCCM Current Procedural Terminology codes.

Main Measures

The health outcomes in the study included major adverse cardiovascular events (MACE), all-cause mortality, and heart failure. The monthly service utilization and continuity of care index for primary care were also included. The propensity score method was used to balance the baseline differences between the two groups. Weighted multivariate regression models were developed using propensity score weights to assess the impacts of NFFCCM on outcomes.

Key Results

During the 5 years of study period, 8415 patients among the 118,643 Medicare beneficiaries received at least one NFFCCM. Patients receiving any NFFCCM had reduced healthcare utilization compared with patients not receiving NFFCCM, including 0.012 (95% CI − 0.014 to − 0.011; p < 0.001) fewer monthly hospital admissions, 0.017 (95% CI − 0.019 to − 0.016; p < 0.001) fewer monthly ED visits, and 0.399 (95% CI 0.375 to 0.423; p < 0.001) more monthly outpatient encounters. Patients receiving NFFCCM services had lower MACE event rates of 7.4% (95% CI 7.1 to 7.8%; p < 0.001), all-cause mortality rate of 7.8% (95% CI 7.4 to 8.1%; p < 0.001), and heart failure rate of 0.3% (95% CI 0.2 to 0.5%; p < 0.001), respectively.

Conclusions and Relevance

These findings suggest that reimbursement for NFFCCM was associated with the shifting high-cost utilization to lower-cost primary health care settings among patients with diabetes in Louisiana.
Climatic implications in earlywood and latewood width indices of Chinese pine in north central China
Authors: Yang Kaixuan , Zhang Junzhou , Fan Haowen , Yan Yuan
Published: February 2024

Latewood width (LWW) indices of trees are considered a reliable proxy of summer precipitation in the Northern Hemisphere. However, the strong coupling and high correlation between earlywood width (EWW) and LWW indices often prevent registration of climate signals of the LWW index. In this study, 328-year-long earlywood width and latewood width chronologies were developed from Chinese pine at two sites in the Hasi Mountains, north central China. The climate responses of these chronologies were analyzed and the LWW index used to derive summer precipitation signals. Correlation analyses showed that LWW was particularly influenced by earlywood growth and recorded stronger climate signals of the previous year as EWW, rather than those of the current year with infrequent summer climate signals. However, after removing the effect of earlywood growth using a simple regression model, the adjusted LWW chronology (LWWadj) showed a strong relationship with July precipitation in dry years. This suggests that the LWWadj chronology has the potential to be used to investigate long-term variability in summer precipitation in drought-limited regions.
Recent Update on PET/CT Radiotracers for Imaging Cerebral Glioma
Authors: Kim Dongwoo , Lee Suk-Hyun , Hwang Hee Sung , Kim Sun Jung , Yun Mijin
Published: February 2024

Positron emission tomography/computed tomography (PET/CT) has dramatically altered the landscape of noninvasive glioma evaluation, offering complementary insights to those gained through magnetic resonance imaging (MRI). PET/CT scans enable a multifaceted analysis of glioma biology, supporting clinical applications from grading and differential diagnosis to mapping the full extent of tumors and planning subsequent treatments and evaluations. With a broad array of specialized radiotracers, researchers and clinicians can now probe various biological characteristics of gliomas, such as glucose utilization, cellular proliferation, oxygen deficiency, amino acid trafficking, and reactive astrogliosis. This review aims to provide a recent update on the application of versatile PET/CT radiotracers in glioma research and clinical practice.
Mechanisms Accounting for the Formation of the Strong Winds that Caused the Tripping Incident of Transmission Line in Eastern Inner Mongolia
Authors: Jin Shuanglong , Liu Xiaolin , Bo Wang , Song Zongpeng
Published: February 2024

Meteorological disasters pose a serious threat to the State Grid Corporation of China, which covers ~ 88% of Chinese national territory. Of these, strong winds deserve a special attention, as they often induce windage yaw discharge of transmission lines and even toppling of transmission towers, resulting in serious economic losses. On 28 June 2023, a severe tripping incident of transmission line appears in Eastern Inner Mongolia due to strong winds. In this study, we conduct comprehensive analyses to clarify the favorable background conditions and governing mechanisms for producing the strong winds. Main results are shown as follows. Synoptic analysis indicates that, the favorable background environments for the event are characterized by a strong upper-level jet associated upper tropospheric divergence; an intense middle-level warm advection ahead of a shortwave trough; and a long-lived lower-tropospheric mesoscale vortex. The strong winds that cause the tripping incident mainly occur in the southeastern quadrant of the vortex. Vorticity budget presents that the period from the mesoscale-vortex’s formation to 4 h before is crucial to the mesoscale vortex, as cyclonic vorticity increases rapidly mainly due to the lower-level convergence-related vertical stretching. In contrast, the horizontal transport mainly results in a net export of cyclonic vorticity, which is the most detrimental factor. Kinetic energy (KE) budget shows that, after the mesoscale vortex forms, the strong winds within its southeastern quadrant enhance rapidly. Overall, the positive work done by the pressure gradient force associated with the mesoscale vortex dominates the enhancement of strong winds; the horizontal transport of KE is the second dominant factor, and the vertical transport of KE (i.e., the downward momentum transportation) shows the least contribution.
Characteristics of high-temperature heat-affected zones in duplex stainless steels
Authors: Westin E. M. , Wessman S.
Published: February 2024

The level of ferritization in the high temperature heat-affected zone (HT-HAZ) affects the weldability of duplex stainless steels. The modern grades show different sensitivity and especially the nitrogen content has been proposed to control the grain growth and austenite formation. In this work, 3-, 4- and 5-mm thick UNS S32101, UNS S32304, UNS S32205 and UNS S32750 with a nitrogen range of 0.09–0.28 wt.-% were considered. Gas tungsten arc welding (GTAW) was conducted bead-on-plate with pure argon (Ar) and Ar + 2% N2 as shielding gas. Measurements of the HT-HAZ width and ferrite content were compared with values reported for welds and thermo-mechanical Gleeble® simulations in existing literature. The HT-HAZ width decreased with the material thickness and the nitrogen content in the base metal, while only the nitrogen alloying had a clear effect on the phase balance. Nitrogen additions to the shielding gas efficiently counteracted weld metal nitrogen loss and improved the austenite formation as compared to 100% Ar but had no clear effect on the HT-HAZ width nor ferrite content. A positive influence of the base material nitrogen content on the phase balance could be validated with thermodynamic simulations using Thermo-Calc and DICTRA, but the negative effect of high cooling rates was underestimated.
An agent-based modelling framework for performance assessment of search and rescue operations in the Barents Sea
Authors: Ashrafi Behrooz , Kim Gibeom , Naseri Masoud , Barabady Javad , Dhar Sushmit , Heo Gyunyoung , Baek Sejin
Published: February 2024

In recent years, the increase in Arctic offshore activities has raised concerns about the search and rescue (SAR) operations as mitigative measures to ensure the safety of shipping and cruise activities. Performing SAR operations in the remote Arctic offshore environment is exceptionally challenging due to the severe environmental conditions, including low temperatures, high waves, strong winds, heavy snow showers, sea ice, spray icing, dense fog, limited visibility, and polar low pressures. Moreover, the scarcity of port infrastructure along the Arctic coastline exacerbates the difficulties faced during SAR operations. Tackling the aforementioned challenges necessitates a comprehensive modelling framework for analysis of SAR operations in the Arctic that is able to consider the dynamics and uncertain nature of Arctic harsh environmental conditions, and the constraints imposed by the limited capacity of Arctic SAR infrastructure. To this aim, this paper proposes an agent-based modelling (ABM) framework to assess the performance of SAR operations while tackling such challenges in the Arctic. A Monte Carlo simulation approach is used to model the dynamics and uncertainty of weather and sea conditions using historical data, using which some severity levels are determined. Expert judgement process is then used quantify the impacts of such severity levels on the performance of rescue agents, and thus, on the total rescue time. To validate the proposed framework, an illustrative case in the Norwegian Barents Sea is considered, where the performance of SAR infrastructure is examined under different rescue scenarios. According to the results of this paper, the total rescue time is the longest during December to February, and the shortest rescue time is associated with months May to August. Some recommendations are further proposed to improve the performance of SAR infrastructure in the Barents Sea.
Revisiting Grace de Laguna’s critiques of analytic philosophy and of pragmatism
Authors: Katzav Joel
Published: February 2024

I revisit my paper, ‘Grace de Laguna’s 1909 Critique of Analytic Philosophy’ and respond to the commentary on it. I respond to James Chase and Jack Reynolds by further analysing the difference between speculative philosophy as de Laguna conceived of it and analytic philosophy, by clarifying how her critique of analytic philosophy remains relevant to some of its more speculative forms, and by explaining what justifies the criticism of established opinion that goes along with her rejection of analytic philosophy’s epistemic conservatism. In response to Andreas Vrahimis, I contextualise my reading of de Laguna’s work in 1909. This clarifies her critique of pragmatism, distinguishes it from her critique of epistemically conservative philosophy, and shows that she was not only already aware of the full scope of the latter critique but is likely to have identified the then incipient analytic philosophy as its primary target. Also, contra Vrahimis, her argument is effective against Bertrand Russell’s later, epistemically conservative approach to philosophy. In response to Cheryl Misak, I point out that her argument that de Laguna is, despite herself, a pragmatist rests on a misunderstanding of the differences between pragmatism and idealism, and I show that de Laguna’s main early influences were Herbert Spencer and her teacher, James Edwin Creighton. I further argue that Misak’s rejection of de Laguna’s critique of pragmatism rests on a misrepresentation of the critique.
Is it time to abandon the concept of treatment-resistant depression?
Authors: Hickie Ian B. , Cuijpers Pim , Scott Elizabeth , Iorfino Frank
Published: February 2024

One of the most used, but poorly defined, terms in the management of clinical depression is that of treatment-resistant depression (TRD) (McIntyre et al., 2023). It implies that persons with major depression have received a range of appropriate psychological, medical or physical treatments (at appropriate doses and for appropriate durations) but have not experienced a significant clinical response. Intrinsically, it does not require consideration as to whether those treatments provided were relevant to their age or developmental stage, clinical phenotype, interpersonal or social context, or personal illness trajectory. These broader clinical considerations often influence initial and subsequent treatment choices.
Misperception of peer beliefs reinforces inequitable gender norms among Tanzanian men
Authors: Lawson David W. , Chen Zhian , Kilgallen Joseph A. , Brand Charlotte O. , Ishungisa Alexander M. , Schaffnit Susan B. , Kumogola Yusufu , Urassa Mark
Published: February 2024

Gender role ideology, i.e. beliefs about how genders should behave, is shaped by social learning. Accordingly, if perceptions about the beliefs of others are inaccurate this may impact trajectories of cultural change. Consistent with this premise, recent studies report evidence of a tendency to overestimate peer support for inequitable gender norms, especially among men, and that correcting apparent ‘norm misperception’ promotes transitions to relatively egalitarian beliefs. However, supporting evidence largely relies on self-report measures vulnerable to social desirability bias. Consequently, observed patterns may reflect researcher measurement error rather than participant misperception. Addressing this shortcoming, we examine men's gender role ideology using both conventional self-reported and a novel wife-reported measure of men's beliefs in an urbanising community in Tanzania. We confirm that participants overestimate peer support for gender inequity. However, the latter measure, which we argue more accurately captures men's true beliefs, implies that this tendency is relatively modest in magnitude and scope. Overestimation was most pronounced among men holding relatively inequitable beliefs, consistent with misperception of peer beliefs reinforcing inequitable norms. Furthermore, older and poorly educated men overestimated peer support for gender inequity the most, suggesting that outdated and limited social information contribute to norm misperception in this context.
Sympatric occurrence of Taenia saginata and Sarcocystis spp. in cattle from Narok County, Kenya: meat inspection findings with molecular validation
Authors: Oduori D.O. , Kitala P.M. , Wachira T.M. , Mulinge E. , Zeyhle E. , Gabriël S. , Gathura P.B.
Published: February 2024

The epidemiological picture of Taenia saginata infections in Kenya is fragmented with limited available data. Although Sarcocystis species are significant meat-borne parasites, few studies have explored their occurrence in Kenya. This study aimed to estimate the occurrence of bovine cysticercosis and screen for the presence of Sarcocystis spp. A meat inspection-based survey was conducted in ten abattoirs in Narok County, Kenya, and inspection for T. saginata cysticerci was limited to the Triceps brachii muscle. The apparent occurrence of the parasite was 5.4% (95% CI, 3.8, 7.6, n=573). Molecular confirmation of T. saginata was done via nested polymerase chain reaction targeting the mitochondrial 12S ribosomal RNA gene and restricted fragment length polymorphism. Sarcocystis species were identified using a multiplex polymerase chain reaction method targeting the 18S ribosomal RNA gene sequences and the mitochondrial cytochrome c oxidase subunit I gene. Of the 31 cystic lesions tested, 26/31 (83.9%) were confirmed to be T. saginata.Sarcocystis cruzi and S. hominis were detected in 8/31 (25.8%) and 1/31 (3.2%) of the cystic lesions, respectively. Co-infections of S. cruzi and T. saginata were found in 6/31 lesions (19.4%). The confirmation of bovine cysticercosis and S. hominis is suggestive of the presence of risky culinary and sanitation practices that facilitate transmission. This is the first report and molecular confirmation of Sarcocystis spp. in cattle in the country. The presence of both zoonotic S. hominis and pathogenic S. cruzi highlights an underexplored concern of veterinary and human health significance, warranting further epidemiological investigation.
‘Sovereignty is still the name of the game’: Indigenous theorising and strategic entanglement in Māori political discourses
Authors: Clavé-Mercier Valentin
Published: February 2024

In recent decades, sovereignty has come under increased academic scrutiny for being a Eurocentric notion antithetical to emancipatory politics, leading critical theory scholars to call for an overcoming or even abandonment of the concept. Paradoxical as it may seem, it nonetheless remains an appealing ideal for many colonised peoples. Indigenous activists and scholars have actively re-appropriated the language of sovereignty to encapsulate and advance Indigenous political aspirations. This paper discusses how Māori, Aotearoa/New Zealand’s Indigenous people, navigate their relations to the concept in their contemporary political discourses pursuing self-governance. Building on interviews with Māori leaders, scholars, and activists, it offers empirical insights into Indigenous political thought’s engagement with the idea of sovereignty. It highlights an ambivalence oscillating between rejection and rearticulation present both in Indigenous theorising and Māori politics. From an analysis of Māori contemporary conceptual strategies, this paper suggests that Yarimar Bonilla’s notion of ‘strategic entanglement’ offers a productive account to comprehend the approached Māori actors’ deployment of the sovereignty concept, and possibly that of Indigenous peoples beyond Aotearoa. This paper thus highlights the continued relevance of the sovereignty framework, both analytically and politically, to meaningfully engage with contemporary Indigenous politics.
In vitro effects of the combination of serotonin, selenium, zinc, and vitamins D and E supplementation on human sperm motility and reactive oxygen species production
Authors: Yilmazer Yasemin , Moshfeghi Elnaz , Cetin Fadime , Findikli Necati
Published: February 2024

Infertility affects 15% of all couples worldwide and 50% of cases of infertility are solely due to male factors. A decrease in motility in the semen is considered one of the main factors that is directly related to infertility. The use of supplementation to improve the overall sperm quality has become increasingly popular worldwide. The purpose of this study was to evaluate whether sperm motility was affected by the combination of serotonin (5-HT), selenium (Se), zinc (Zn), and vitamins D, and E supplementation. Semen samples were incubated for 75 min at 37°C in medium containing varying concentrations of 5-HT, Se, Zn, vitamin D, and E. 5-HT (200 μM), Se (2 μg/ml), Zn (10 μg/ml), vitamin D (100 nM), and vitamin E (2 mmol) have also been shown to increase progressive sperm motility. Three different mixtures of supplements were also tested for their combined effects on sperm motility and reactive oxygen species (ROS) production. While the total motility in the control group was 71.96%, this was found to increase to 82.85% in the first mixture. In contrast the average ROS level was 8.97% in the control group and decreased to 4.23% in the first mixture. Inclusion of a supplement cocktail (5-HT, Se, Zn, vitamins D and E) in sperm processing and culture medium could create an overall improvement in sperm motility while decreasing ROS levels during the incubation period. These molecules may enhance the success of assisted reproduction techniques when present in sperm preparation medium.
Testing the Role of Narrative Modeling on Self-Compassion
Authors: Andreeva Irina , Green Melanie
Published: February 2024

Abstract: The present research examines the effects of modeling self-compassion through a narrative. Three experimental studies ( N1 = 168, N2 = 219, N3 = 281) varied narrative self-compassion (high, low). Narrative self-compassion was manipulated through the reactions of the main character to mistakes and misfortunes. In the high self-compassion condition, the character’s response was forgiving and self-reassuring, emphasizing the main aspects of self-compassionate behaviors; in the low-self-compassion condition, the character’s response was self-critical. Contrary to expectations, there was no significant effect of story condition on self-compassionate outcomes in Studies 1 and 2. In Study 3, exposure to the low self-compassion story condition resulted in a significant decrease in self-compassion levels reported by participants. Transportation into the narrative and identification with the main character were also found to be higher in the low-self compassion story condition (Study 1), and to have a significant negative effect on self-compassion outcomes (Study 2). These findings suggest that using narrative modeling to evoke self-compassionate outcomes is ineffective, at least in a cross-sectional design. It is possible that participants did not have enough time to manage the negative emotions that may have been sparked by the narrative and grapple with long-held beliefs immediately postexposure; future research should examine longitudinal effects of self-compassion narratives.
The Value of Large‐Scale Climatic Indices for Monthly Forecasting Severity of Widespread Flooding Using Dilated Convolutional Neural Networks
Authors: Tarasova Larisa , Ahrens Bodo , Hoff Amelie , Lall Upmanu
Published: February 2024

Spatially co‐occurring floods pose a threat to the resilience and recovery of the communities. Their timely forecasting plays a crucial role for increasing flood preparedness and limiting associated losses. In this study we investigated the potential of a dilated Convolutional Neural Network (dCNN) model conditioned on large‐scale climatic indices and antecedent precipitation to forecast monthly severity of widespread flooding (i.e., spatially co‐occurring floods) in Germany with 1 month lead time. The severity was estimated from 63 years of daily streamflow series as the sum of concurrent exceedances of at‐site 2‐year return periods within a given month across 172 mesoscale catchments (median area 516 km2). The model was trained individually for the whole country and three diverse hydroclimatic regions to provide insights on heterogeneity of model performance and flood drivers. Our results showed a considerable potential for forecasting widespread flood severity using dCNN especially as the length of training series increases. However, event‐based evaluation of model skill indicates large underestimation for rainfall‐generated floods during dry conditions despite overall lower severity of these events compared to the rain‐on‐snow floods. Feature attribution and wavelet coherence analyses both indicated considerable difference in the major flood drivers in three regions. While the flooding in North‐Eastern region is strongly affected by the Baltic Sea, the North‐Western region is affected more by global patterns associated with the El‐Niño activity. In the Southern region in addition to global patterns we detected the effect of the Mediterranean Sea, while antecedent precipitation plays a less important role in this region.
Vegetation Greening and Climate Warming Increased the Propagation Risk From Meteorological Drought to Soil Drought at Subseasonal Timescales
Authors: Ma Feng , Yuan Xing
Published: February 2024

Subseasonal droughts including flash droughts have occurred frequently in recent years, which are accompanied by heatwaves or wildfires that raise a wide concern on environmental risk. However, the changing characteristics of subseasonal drought propagation, and the possible climate and environmental drivers remain unknown. This study quantifies the propagation characteristics from meteorological drought to soil drought using a Copula‐based Bayesian framework, and shows that higher propagation risks mainly occur in more humid regions with denser vegetation cover. Trends in drought propagation risk vary regionally, with a global increase of 2%/decade (p < 0.01) during 1980–2022. Vegetation greening and climate warming are the key drivers over >71% of the global vegetated lands, with mean contribution rates of 39.5% and 36.5% respectively. Other climatic factors including vapor pressure deficit and precipitation also paly critical roles, which closely correlate with temperature and vegetation. These findings highlight the importance of vegetation greening on subseasonal drought propagation dynamics.
Can Geometric Parameters Enable Direct Prediction of Non‐Fickian Transport in Rock Fractures Across Diverse Flow Regimes?
Authors: Zhou Jia‐Qing , Guo Li‐Guo , Jiao Jiu Jimmy , Jiang Xin‐Yu , Luo Xin
Published: February 2024

Anomalous solute migrations in fractured rocks are governed by geometric characteristics and flow regimes. Although existing inverse models can describe this behavior, the underlying physics for quantifying key transport coefficients remains largely unexplored. Here, we investigate the quantitative impacts of geometric heterogeneity and flow regimes on solute transport in rock fractures. We conduct numerical experiments to simulate water flow and conservative solute transport in 3D fractures with varying geometric features and Reynolds numbers. Our results show that the non‐Fickian transport is prevalent across the entire flow regime, with Darcy flows attributed to geometric heterogeneity and non‐Darcian flows influenced by additional eddy zones. We employ the mobile‐immobile (MIM) domain model and continuous time random walk (CTRW) model to inversely model simulated breakthrough curves. Inverse analyses demonstrate that both models effectively characterize anomalous transport behaviors. The fitted transport coefficients of the MIM model exhibit stronger quantitative relationships with aperture and roughness parameters, as well as Reynolds number, compared to the CTRW model. By incorporating parameterized transport coefficients, we propose physics‐ and statistics‐based models to directly predict anomalous transport behaviors under different flow regimes. These prediction models accurately reproduce solute transport processes of all simulated cases with acceptable errors. The feasibility of directly predicting solute transport under varying flow regimes using geometric information is thus validated. Our study not only supports the study of substance migration based on geometric structure features, but also serves as a foundation for investigating geological activities based on substance migration information.
Estimating the Energy Flux of Internal Tides in the Northern South China Sea Using Underwater Gliders
Authors: Gao Zhiyuan , Chen Zhaohui , Huang Xiaodong , Yang Haiyuan , Wang Yanhui , Ma Wei , Luo Chenyi
Published: February 2024

The characteristics of the energy flux of internal tides in the northern South China Sea (SCS) were explored by analyzing a fleet of underwater gliders. It was found that the low‐mode diurnal internal tides with ∼300 km wavelength in the middle basin are generated predominantly in the Luzon Strait (LS) and propagate over 1,000 km to the western SCS. However, the semidiurnal internal tides are generated in multiple regions, including the LS in the east part, the continental shelf, and the islands in the west. The energy flux of the mode‐1 diurnal internal tides attenuated rapidly within 450 km of the LS and was less pronounced after that. The estimated dissipation rate based on the mode‐1 energy flux is about 10−8 W/kg, underling the significant role of mode‐1 diurnal internal tides in bolstering far‐field mixing. This study provides a unique view of the spatial pattern, energy flux, and energy sink of the internal tides in the northern SCS, which could supplement the altimetry‐based results and improve the parameterization in ocean models.
Modeling Quality and Price Perception in the Choice of Drinking Water in France: A Hybrid Choice Model Approach
Authors: Beaumais Olivier , Crastes dit Sourd Romain
Published: February 2024

The water resources literature usually discards the important price difference between bottled water and tap water as a predictor of drinking water choice. In France, bottled water is about 100 times more expensive than tap water. Using 4,003 survey responses, we model water resources quality (mis)‐perception and water price (mis)‐perceptions by means of a hybrid choice model. We show that respondents who are more likely to consider the quality of water resources as “very poor” or “poor” are less likely to drink tap water. Furthermore, we find that respondents who do not report the correct price difference between tap water and bottled water are more likely to drink bottled water, which is a novel finding, as significant price effects of this type have never been reported in the literature on drinking water choice.
Leveraging ICESat, ICESat‐2, and Landsat for Global‐Scale, Multi‐Decadal Reconstruction of Lake Water Levels
Authors: Yao Fangfang , Livneh Ben , Rajagopalan Balaji , Wang Jida , Yang Kehan , Crétaux Jean‐François , Wang Chao , Minear J. Toby
Published: February 2024

Lakes provide important water resources and many essential ecosystem services. Some of Earth's largest lakes recently reached record‐low levels, suggesting increasing threats from climate change and anthropogenic activities. Yet, continuous monitoring of lake levels is challenging at a global scale due to the sparse in situ gauging network and the limited spatial or temporal coverage of satellite altimeters. A few pioneering studies used water areas and hypsometric curves to reconstruct water levels but suffered from large uncertainties due to the lack of high‐quality hypsometry data. Here, we propose a novel proxy‐based method to reconstruct multi‐decadal water levels from 1992 to 2018 for both large and small lakes using Landsat images and ICESat (2003–2009) and recently launched ICESat‐2 (2018+) laser altimeters. Using the new method, we evaluate reconstructed levels of 342 lakes worldwide, with sizes ranging from 1 to 81,844 km2. Reconstructed water levels have a median root‐mean‐square error (RMSE) of 0.66 m, equivalent to 57% of the standard deviation of monthly level variability. Compared with two recently reconstructed water level data sets, the proposed method reduces the median RMSE by 27%–32%. The improvement is attributable to the new method's robust construction of high‐quality hypsometry, with a median R2 value of 0.92. Most reconstructed water level time series have a bi‐monthly or higher frequency. Given that ICESat‐2 and Landsat can observe hundreds of thousands of water bodies, this method can be applied to conduct an improved global inventory of time‐varying lake levels and thus inform water resource management more broadly than existing methods.
Helicobacter pylori CagA-mediated ether lipid biosynthesis promotes ferroptosis susceptibility in gastric cancer
Authors: Peng Yanmei , Lei Xuetao , Yang Qingbin , Zhang Guofan , He Sixiao , Wang Minghao , Ling Ruoyu , Zheng Boyang , He Jiayong , Chen Xinhua , Li Fengping , Zhou Qiming , Zhao Liying , Ye Gengtai , Li Guoxin
Published: February 2024

Helicobacter pylori, particularly cytotoxin-associated gene A (CagA)-positive strains, plays a key role in the progression of gastric cancer (GC). Ferroptosis, associated with lethal lipid peroxidation, has emerged to play an important role in malignant and infectious diseases, but the role of CagA in ferroptosis in cancer cells has not been determined. Here, we report that CagA confers GC cells sensitivity to ferroptosis both in vitro and in vivo. Mechanistically, CagA promotes the synthesis of polyunsaturated ether phospholipids (PUFA-ePLs), which is mediated by increased expression of alkylglycerone phosphate synthase (AGPS) and 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3), leading to susceptibility to ferroptosis. This susceptibility is mediated by activation of the MEK/ERK/SRF pathway. SRF is a crucial transcription factor that increases AGPS transcription by binding to the AGPS promoter region. Moreover, the results demonstrated that CagA-positive cells are more sensitive to apatinib than are CagA-negative cells, suggesting that detecting the H. pylori CagA status may aid patient stratification for treatment with apatinib.
The contribution of sodium reduction and potassium increase to the blood pressure lowering observed in the Salt Substitute and Stroke Study
Authors: Huang Liping , Li Qiang , Wu Jason HY , Tian Maoyi , Yin Xuejun , Yu Jie , Liu Yishu , Zhang Xinyi , Wu Yangfeng , Paige Ellie , Trieu Kathy , Marklund Matti , Rodgers Anthony , Neal Bruce
Published: February 2024

The Salt Substitute and Stroke Study (SSaSS) demonstrated significant reductions in systolic blood pressure (SBP), and the risk of stroke, major cardiovascular events and total mortality with the use of potassium-enriched salt. The contribution of sodium reduction versus potassium increase to these effects is unknown. We identified four different data sources describing the association between sodium reduction, potassium supplementation and change in SBP. We then fitted a series of models to estimate the SBP reductions expected for the differences in sodium and potassium intake in SSaSS, derived from 24-h urine collections. The proportions of the SBP reduction separately attributable to sodium reduction and potassium supplementation were calculated. The observed SBP reduction in SSaSS was −3.3 mmHg with a corresponding mean 15.2 mmol reduction in 24-h sodium excretion and a mean 20.6 mmol increase in 24-h potassium excretion. Assuming 90% of dietary sodium intake and 70% of dietary potassium intake were excreted through urine, the models projected falls in SBP of between −1.67 (95% confidence interval: −4.06 to +0.73) mmHg and −5.33 (95% confidence interval: −8.58 to −2.08) mmHg. The estimated proportional contribution of sodium reduction to the SBP fall ranged between 12 and 39% for the different models fitted. Sensitivity analyses assuming different proportional urinary excretion of dietary sodium and potassium intake showed similar results. In every model, the majority of the SBP lowering effect in SSaSS was estimated to be attributable to the increase in dietary potassium rather than the fall in dietary sodium.
Prognostic factors in 448 newly diagnosed multiple myeloma receiving bortezomib-based induction: impact of ASCT, transplant refusal and high-risk MM
Authors: Tang Hoi Ki Karen , Fung Chi Yeung , Hwang Yu Yan , Lee Harold , Lau Grace , Yip Sze Fai , Kho Bonnie , Lau Chi Kuen , Leung Kwan Hung , Au Elaine , Tse Eric , Sim Joycelyn , Kwong Yok Lam , Chim Chor Sang
Published: February 2024

In Hong Kong, newly diagnosed multiple myeloma (NDMM) receives bortezomib-based triplet induction. Upfront autologous stem cell transplant (ASCT) is offered to transplant eligible (TE) patients (NDMM ≤ 65 years of age), unless medically unfit (TE-unfit) or refused (TE-refused). Data was retrieved for 448 patients to assess outcomes. For the entire cohort, multivariate analysis showed that male gender (p = 0.006), international staging system (ISS) 3 (p = 0.003), high lactate dehydrogenase (LDH) (p = 7.6 × 10−7) were adverse predictors for overall survival (OS), while complete response/ near complete response (CR/nCR) post-induction (p = 2.7 × 10−5) and ASCT (p = 4.8 × 10−4) were favorable factors for OS. In TE group, upfront ASCT was conducted in 252 (76.1%). Failure to undergo ASCT in TE patients rendered an inferior OS (TE-unfit p = 1.06 × 10−8, TE-refused p = 0.002) and event free survival (EFS) (TE-unfit p = 0.00013, TE-refused p = 0.002). Among TE patients with ASCT, multivariate analysis showed that age ≥ 60 (p = 8.9 × 10−4), ISS 3 (p = 0.019) and high LDH (p = 2.6 × 10−4) were adverse factors for OS. In those with high-risk features (HR cytogenetics, ISS 3, R-ISS 3), ASCT appeared to mitigate their adverse impact. Our data reaffirmed the importance of ASCT. The poor survival inherent with refusal of ASCT should be recognized by clinicians. Finally, improved outcome with ASCT in those with high-risk features warrant further studies.
HMGA1 drives chemoresistance in esophageal squamous cell carcinoma by suppressing ferroptosis
Authors: Yang Jing-Yu , Lei Xin-Yuan , He Kai-Yue , Guo Jin-Rong , Liu Meng-Jie , Li Jun-Qi , Li Qiu-Tong , Jiang Zhi-Hao , Zhang Lei , Wu Dan-Hui , Li Yu-Jia , Sun Qian-Hui , Jian Yong-Ping , Xu Zhi-Xiang
Published: February 2024

Chemotherapy is a primary treatment for esophageal squamous cell carcinoma (ESCC). Resistance to chemotherapeutic drugs is an important hurdle to effective treatment. Understanding the mechanisms underlying chemotherapy resistance in ESCC is an unmet medical need to improve the survival of ESCC. Herein, we demonstrate that ferroptosis triggered by inhibiting high mobility group AT-hook 1 (HMGA1) may provide a novel opportunity to gain an effective therapeutic strategy against chemoresistance in ESCC. HMGA1 is upregulated in ESCC and works as a key driver for cisplatin (DDP) resistance in ESCC by repressing ferroptosis. Inhibition of HMGA1 enhances the sensitivity of ESCC to ferroptosis. With a transcriptome analysis and following-up assays, we demonstrated that HMGA1 upregulates the expression of solute carrier family 7 member 11 (SLC7A11), a key transporter maintaining intracellular glutathione homeostasis and inhibiting the accumulation of malondialdehyde (MDA), thereby suppressing cell ferroptosis. HMGA1 acts as a chromatin remodeling factor promoting the binding of activating transcription factor 4 (ATF4) to the promoter of SLC7A11, and hence enhancing the transcription of SLC7A11 and maintaining the redox balance. We characterized that the enhanced chemosensitivity of ESCC is primarily attributed to the increased susceptibility of ferroptosis resulting from the depletion of HMGA1. Moreover, we utilized syngeneic allograft tumor models and genetically engineered mice of HMGA1 to induce ESCC and validated that depletion of HMGA1 promotes ferroptosis and restores the sensitivity of ESCC to DDP, and hence enhances the therapeutic efficacy. Our finding uncovers a critical role of HMGA1 in the repression of ferroptosis and thus in the establishment of DDP resistance in ESCC, highlighting HMGA1-based rewiring strategies as potential approaches to overcome ESCC chemotherapy resistance.
Modification of BCLX pre-mRNA splicing has antitumor efficacy alone or in combination with radiotherapy in human glioblastoma cells
Authors: Dou Zhihui , Lei Huiwen , Su Wei , Zhang Taotao , Chen Xiaohua , Yu Boyi , Zhen Xiaogang , Si Jing , Sun Chao , Zhang Hong , Di Cuixia
Published: February 2024

Dysregulation of anti-apoptotic and pro-apoptotic protein isoforms arising from aberrant splicing is a crucial hallmark of cancers and may contribute to therapeutic resistance. Thus, targeting RNA splicing to redirect isoform expression of apoptosis-related genes could lead to promising anti-cancer phenotypes. Glioblastoma (GBM) is the most common type of malignant brain tumor in adults. In this study, through RT-PCR and Western Blot analysis, we found that BCLX pre-mRNA is aberrantly spliced in GBM cells with a favored splicing of anti-apoptotic Bcl-xL. Modulation of BCLX pre-mRNA splicing using splice-switching oligonucleotides (SSOs) efficiently elevated the pro-apoptotic isoform Bcl-xS at the expense of the anti-apoptotic Bcl-xL. Induction of Bcl-xS by SSOs activated apoptosis and autophagy in GBM cells. In addition, we found that ionizing radiation could also modulate the alternative splicing of BCLX. In contrast to heavy (carbon) ion irradiation, low energy X-ray radiation-induced an increased ratio of Bcl-xL/Bcl-xS. Inhibiting Bcl-xL through splicing regulation can significantly enhance the radiation sensitivity of 2D and 3D GBM cells. These results suggested that manipulation of BCLX pre-mRNA alternative splicing by splice-switching oligonucleotides is a novel approach to inhibit glioblastoma tumorigenesis alone or in combination with radiotherapy.
Advanced oxidation protein products attenuate the autophagy-lysosome pathway in ovarian granulosa cells by modulating the ROS-dependent mTOR-TFEB pathway
Authors: Zhou Xing-Yu , Lai Yun-Hui , Zhang Jun , Li Ying , Wu Xiao-Min , Yang Yi-Zhen , Zhang Xiao-Fei , Ma Lin-Zi , Zheng Ke-Ming , Liu Yu-Dong , Wang Zhe , Chen Shi-Ling
Published: February 2024

Oxidative stress dysfunction has recently been found to be involved in the pathogenesis of premature ovarian insufficiency (POI). Previously, we found that advanced oxidation protein products (AOPPs) in plasma were elevated in women with POI and had an adverse effect on granulosa cell proliferation. However, the mechanism underlying the effects of AOPPs on autophagy-lysosome pathway regulation in granulosa cells remains unclear. In this study, the effect of AOPPs on autophagy and lysosomal biogenesis and the underlying mechanisms were explored by a series of in vitro experiments in KGN and COV434 cell lines. AOPP-treated rat models were employed to determine the negative effect of AOPPs on the autophagy-lysosome systems in vivo. We found that increased AOPP levels activated the mammalian target of rapamycin (mTOR) pathway, and inhibited the autophagic response and lysosomal biogenesis in KGN and COV434 cells. Furthermore, scavenging of reactive oxygen species (ROS) with N-acetylcysteine and blockade of the mTOR pathway with rapamycin or via starvation alleviated the AOPP-induced inhibitory effects on autophagy and lysosomal biogenesis, suggesting that these effects of AOPPs are ROS-mTOR dependent. The protein expression and nuclear translocation of transcription factor EB (TFEB), the key regulator of lysosomal and autophagic function, were also impaired by the AOPP-activated ROS-mTOR pathway. In addition, TFEB overexpression attenuated the AOPP-induced impairment of autophagic flux and lysosomal biogenesis in KGN and COV434 cells. Chronic AOPP stimulation in vivo also impaired autophagy and lysosomal biogenesis in granulosa cells of rat ovaries. The results highlight that AOPPs lead to impairment of autophagic flux and lysosomal biogenesis via ROS-mTOR-TFEB signaling in granulosa cells and participate in the pathogenesis of POI.
Endothelial Robo4 suppresses endothelial-to-mesenchymal transition induced by irradiation and improves hematopoietic reconstitution
Authors: Adzraku Seyram Yao , Cao Can , Zhou Qi , Yuan Ke , Hao Xiaowen , Li Yue , Yuan Shengnan , Huang Yujin , Xu Kailin , Qiao Jianlin , Ju Wen , Zeng Lingyu
Published: February 2024

Bone marrow ablation is routinely performed before hematopoietic stem cell transplantation (HSCT). Hematopoietic stem and progenitor cells (HSPCs) require a stable bone marrow microenvironment to expand and refill the peripheral blood cell pool after ablation. Roundabout guidance receptor 4 (Robo4) is a transmembrane protein exclusive to endothelial cells and is vital in preserving vascular integrity. Hence, the hypothesis is that Robo4 maintains the integrity of bone marrow endothelial cells following radiotherapy. We created an endothelial cell injury model with γ-radiation before Robo4 gene manipulation using lentiviral-mediated RNAi and gene overexpression techniques. We demonstrate that Robo4 and specific mesenchymal proteins (Fibronectin, Vimentin, αSma, and S100A4) are upregulated in endothelial cells exposed to irradiation (IR). We found that Robo4 depletion increases the expression of endoglin (CD105), an auxiliary receptor for the transforming growth factor (TGF-β) family of proteins, and promotes endothelial-to-mesenchymal transition (End-MT) through activation of both the canonical (Smad) and non-canonical (AKT/NF-κB) signaling pathways to facilitate Snail1 activation and its nuclear translocation. Endothelial Robo4 overexpression stimulates the expression of immunoglobulin-like adhesion molecules (ICAM-1 and VCAM-1) and alleviates irradiation-induced End-MT. Our coculture model showed that transcriptional downregulation of endothelial Robo4 reduces HSPC proliferation and increases HSC quiescence and apoptosis. However, Robo4 overexpression mitigated the damaged endothelium’s suppressive effects on HSC proliferation and differentiation. These findings indicate that by controlling End-MT, Robo4 preserves microvascular integrity after radiation preconditioning, protects endothelial function, and lessens the inhibitory effect of damaged endothelium on hematopoietic reconstitution.