Fundamental Cause Research Articles

No Socioeconomic Inequalities in Mortality among Catholic Monks: A Quasi-Experiment Providing Evidence for the Fundamental Cause Theory.

We propose a novel approach to test the fundamental cause theory (FCT) by analyzing the association between socioeconomic status (SES), as measured by the order titles "brothers" and "padres," and mortality in 2,421 German Catholic monks born between 1840 and 1959. This quasi-experiment allows us to study the effect of SES on mortality in a population with largely standardized living conditions. Mortality analyses based on Kaplan-Meier product limit estimation show that there were no statistically significant survival differences between the high and lower SES monks. This holds for all birth cohorts, indicating that monastic life offers health protection for monks with a lower SES regardless the disease patterns, causes of death, or main risk factors in a given period. These findings support the FCT: Whereas SES-related differences in mortality are a widely confirmed finding in the general population, a context with largely standardized conditions eliminates the importance of SES-related resources.

SEM approach to assess self-efficacy and social capital of producer’s organizations in Chhattisgarh

Farmer-producer organizations are typified by farmer groupings that are structured with the intention of turning a profit by leveraging economies of scale and functioning similarly to corporate entities. The creation and advancement of farmer collectivization can offer farmers a forum for obtaining essential information, exchanging knowledge, sharing production and marketing risks, and embracing market-driven agricultural product production. Compared to the individual method, grassroots initiatives on the collectivization of marginalized rural communities can enhance their support for livelihood in terms of income, self-respect, negotiating power, etc. The current study was carried out in the state of Chhattisgarh in order to propose a model by combining two schools of thought; the function of social capital, and self-efficacy that influence the perceived performance among the members of farmer producer organizations (FPOs). This study was set out to determine and investigate the fundamental causes of the farmers' groups' performance in producer businesses that are operating quite successfully on the ground. Findings reveal that self-efficacy was a key player as a partial mediator in the social capital formation that affected FPO performance. The size of mediating effect was analysed and observed highly significant with 45.77% effect size.

Research Status of Large‐Size Carbides in High‐Carbon Chromium Bearing Steel

Metallurgical quality of bearing steel is an important foundation and guarantees for determining the performance, accuracy, service life, and reliability of bearings. Nowadays, advances in refining technology have led to a significant increase in the cleanliness of bearing steel, and the control of large‐size carbides (primary, banded, and network carbides) has become particularly important. In this article, the recent research on large‐size carbides regarding morphology, precipitation mechanism, and control methods is reviewed. Firstly, the morphological characteristics of carbides are summarized. Primary carbides appear as blocky, lamellar, or irregular shapes, while banded carbides are distributed in bands. Network carbides mainly precipitate along the austenitic grain boundaries and aggregate to form networks. Secondly, the precipitation mechanisms of carbides are summarized. Dendritic segregation is the fundamental cause of the formation of primary and banded carbides, whereas network carbides are the supersaturation precipitation of carbon at austenite grain boundaries. Finally, methods for controlling large‐size carbides are summarized, including improving dendritic segregation, high‐temperature diffusion annealing, improving rolling and cooling processes and using magnesium or rare‐earth treatments. No single method offers sufficient carbide control, and mechanism of rare‐earth refining carbides is unknown. Thus, a comprehensive approach should be used in production to effectively regulate carbides in steel.

Body Positivity, Physical Health, and Emotional Well-Being Discourse on Social Media: Content Analysis of Lizzo's Instagram.

Weight stigma is a fundamental cause of health inequality. Body positivity may be a counterbalance to weight stigma. Social media is replete with weight-stigmatizing content and is a driver of poor mental health outcomes; however, there remains a gap in understanding its potential to mitigate the prevalence and impact of harmful messaging and to promote positive effects on a large scale. We selected musical artist Lizzo, whose brand emphasizes body positivity and empowerment, for an instrumental case study on the discourse on social media and specifically Instagram. We focused on 3 domains, including body positivity, physical health, and emotional well-being. These domains challenge social norms around weight and body size and have the potential to positively affect the physical and psychological health of people with diverse body sizes. We evaluated posts by Lizzo, comments from Instagram users, and replies to comments over a 2-month period (October 11 to December 12, 2019). Two coders rated Lizzo's posts and Instagram users' comments for their sentiments on the 3 domains. Replies to Instagram users' comments were assessed for their reactions to comments (ie, did they oppose or argue against the comment or did they support or bolster the comment). Engagement metrics, including the number of "likes," were also collected. The final sample included 50 original posts by Lizzo, 250 comments from Instagram users, and 1099 replies to comments. A proportion of Lizzo's content included body positive sentiments (34%) and emotional well-being (18%); no posts dealt explicitly with physical health. A substantial amount Instagram users' comments and replies contained stigmatizing content including the use of nauseated and vomiting emojis, implications that Lizzo's body was shameful and should be hidden away, accusations that she was promoting obesity, and impeachments of Lizzo's health. In spite of the stigmatizing content, we also discovered content highlighting the beneficial nature of having positive representation of a Black woman living in a larger body who is thriving. Moreover, analysis of the discourse between users illustrated that stigmatizing expressions are being combated online, at least to some degree. This study demonstrates that Lizzo has exposed millions of social media users to messages about body positivity and provided more visibility for conversations about weight and shape. Future research should examine the extent to which body positive messages can lead to greater acceptance of individuals living in larger bodies. Instagram and other social media platforms should consider ways to reduce body-shaming content while finding ways to promote content that features diverse bodies. Shifting the landscape of social media could decrease stereotypes about weight and shape while increasing dialog about the need for greater acceptance and inclusion of people with diverse bodies.

Asking Why Is Necessary to Address Health Disparities: A Critical Approach for Solution-Oriented Environmental Epidemiological Research.

In environmental epidemiology, we use an array of tools from various, related disciplines to answer key questions about environmental exposures in relation to health outcomes. Typically, we ask questions related to what, who, where, when, and how. We value these questions because they contribute to novel scientific discovery and our understanding of disease etiology linked to environmental exposures. In addition, these questions help us better understand who might be at highest risk of exposure and subsequent risk of disease. Although necessary for the goals of environmental epidemiology, these questions are insufficient for addressing environmental health disparities. Specifically, these questions may be able to help us describe exposure-health outcome associations but are limited in their ability to move beyond identification to intervening on observed disparities to achieve environmental health equity. We sought to emphasize the need to value and routinely add the key question of "Why?" in environmental epidemiological studies. In asking this additional critical question, we can identify and incorporate the structural determinants and drivers of environmental exposure disparities and determine whether these factors are linked to existing and historically recalcitrant health disparities. Further, we can design effective studies that build on existing frameworks to address the fundamental causes of environmental health disparities. This commentary underscores the need to routinely incorporate "why" questions in the practice of environmental epidemiology. By asking and addressing "Why?" we can employ better, more solution-oriented study designs, improve data collection, and enhance our ability to collaborate with diverse study populations through trust-building and community-engaged research. Incorporating these approaches will move environmental epidemiology forward from mostly documenting to actively addressing environmental health disparities. https://doi.org/10.1289/EHP14513.

Effects of oncoming wind speed and turbulence intensity on wind characteristics of a simplified hill and ridge

Supertall buildings and long-span bridges are significantly affected by wind-induced vibrations, and the wind fields in mountainous areas are highly complex and influenced by the oncoming wind speed and turbulence intensity. To accurately determine the variation patterns of wind characteristics in mountainous areas under different oncoming wind speeds and turbulence intensities, large eddy simulation (LES) was employed to analyze wind fields over simplified hill and ridge models. By setting different basic wind speeds (5, 10, 15, and 20 m/s) and turbulence intensities (1%, 3%, 5%, and 10%) at the inlet, the variation patterns of wind characteristics over the simplified hill and ridge under atmospheric boundary layer inflow were studied, revealing wind field flow mechanisms. The results indicate that the wind characteristics on the leeward side of the simplified hill and ridge are significantly influenced by the oncoming wind speed and turbulence intensity. Increasing the oncoming wind speed and turbulence intensity leads to decreased wind profile deceleration, reduced changes in wind direction and attack angles, and increased wind speed amplification factor. In addition, the turbulence fluctuations, power spectra, and coherence function between two points on the leeward side increase with the oncoming wind speed and turbulence intensity. The turbulent integral scale decreases with an increase in the oncoming wind speed and turbulence intensity. As the wind speed and turbulence increase, the size of the recirculation bubble gradually decreases, with its center moving closer to the wall surface. In the vorticity field, the number of smaller-scale three-dimensional turbulent vortices near the hill and ridge increases. These differences in flow characteristics are the fundamental causes of the changes in wind characteristics. High wind speeds and turbulence intensities typically result in higher kurtosis and skewness, with significant non-Gaussian characteristics in the fluctuating wind. Traditional wind load design specifications for building architecture based on a Gaussian distribution may not be applicable to mountainous terrain. In practical engineering, the influences of the oncoming wind speed and turbulence intensity on wind characteristics should be fully considered.

BMP5 promotes trophoblast functions upon N-glycosylation via the BMP5-SMAD1/5 signaling pathway in preeclampsia

IntroductionPreeclampsia (PE) is one of the most common pregnancy-related complications worldwide and currently lacks an effective treatment. While trophoblast cell dysfunction has been identified as the fundamental cause of PE, the underlying mechanisms remain unclear. Bone morphogenetic protein 5 (BMP5) is a secreted glycoprotein highly expressed in the placenta that is involved in cell proliferation, migration, and invasion. However, the role and mechanism of BMP5 glycosylation of trophoblast cell function remain unclear. MethodsThe expression of BMP5 and N-glycosylation in preeclamptic placental tissues was investigated. We predicted and validated the N-glycosylation sites of BMP5. Additionally, we evaluated the effect of BMP5 N-glycosylation on the proliferation, migration, invasion, and angiogenesis of human immortalized trophoblastic HTR-8/SVneo cells. Furthermore, the role of N-glycosylated BMP5 in activating the BMP5-SMAD1/5 signaling pathway and regulating trophoblastic cell functions was explored. ResultsOur study reveals that PHA-E+L (recognizing branching N-glycans) reactive N-glycans and BMP5 expression levels are lower in preeclamptic villous tissues compared to normal placental tissues. Additionally, we demonstrated that BMP5 is an N-glycosylation-modified protein. Furthermore, N-glycosylated BMP5 promoted the functional trophoblastic cells (HTR-8/SVneo). We also revealed that N-glycosylation of BMP5 regulates multiple cell functions through the BMP5-SMAD1/5 signaling pathway. ConclusionN-glycosylated BMP5 promotes trophoblast cell proliferation, migration, invasion, and angiogenesis. This study provides mechanistic insight as to how N-glycosylation of BMP5 in trophoblast cells can contribute to the pathogenesis of preeclampsia and provides a new basis for its diagnosis and treatment.

Mechanism of airfoil stall flutter: New insights from global linear stability analysis

Stall flutter is a self-excited aeroelastic vibration phenomenon that occurs in lifting systems near the stall angle of attack, characterized by the distinct single-degree-of-freedom behavior. Despite its significance, this phenomenon remains not fully understood and is often vaguely attributed to nonlinear effects. To address this gap, the present study aims to reveal the underlying fluid–structure interaction mechanisms of stall flutter through global linear stability analysis (LSA). For this purpose, a reduced-order model (ROM)-based aeroelastic stability analysis framework is established using the autoregressive with exogenous input method. The ROM-based aeroelastic model provides a low-order representation of the coupled dynamics near the equilibrium steady state and can accurately capture the stability characteristics of the fluid-elastic system. It is found that as the angle of attack approaches the static stall angle, a low-frequency weakly stable fluid mode emerges, whose frequency is sufficiently lower than that of the von Kármán vortex shedding. The interaction between this fluid mode and the structure mode ultimately leads to the instability of the aeroelastic system at high reduced velocities, which is the fundamental cause of stall flutter. Moreover, dynamic mode decomposition is employed to successfully extract the spatial coherent structures and frequency characteristics of this low-frequency fluid mode, thereby confirming the validity of the LSA results. Further analysis indicates that, as the angle of attack decreases, this low-frequency fluid mode gradually weakens and eventually degenerates into more stable non-oscillatory fluid modes, resulting in structural stabilization and the cessation of stall flutter. Overall, the linear dynamic model accurately predicts the onset of instability and the vibration frequency of the airfoil, which challenges the traditional nonlinear perspectives and supports the feasibility of using linear control theory for stall flutter suppression in future research.

A Comprehensive Review on the Significance of Cysteine in Various Metabolic Disorders; Particularly CVD, Diabetes, Renal Dysfunction, and Ischemic Stroke.

Metabolic disorders have long been a challenge for medical professionals and are a leading cause of mortality in adults. Diabetes, cardiovascular disorders (CVD), renal dysfunction, and ischemic stroke are the most prevalent ailments contributing to a high mortality rate worldwide. Reactive oxygen species are one of the leading factors that act as a fundamental root cause of metabolic syndrome. All of these disorders have their respective treatments, which, to some degree, sabotage the pathological worsening of the disease and an inevitable death. However, they pose a perilous health hazard to humankind. Cysteine, a functional amino acid shows promise for the prevention and treatment of metabolic disorders, such as CVD, Diabetes mellitus, renal dysfunction, and ischemic stroke. In this review, we explored whether cysteine can eradicate reactive oxygen species and subsequently prevent and treat these diseases.

A Review of Chatter Stability in Thin-Walled Mirror Milling

This paper addresses the chatter problem in thin-walled part milling, reviewing the advancements in mirror milling technology for thin-walled parts. It provides an in-depth discussion of the fundamental causes of chatter during thin-walled part milling. A comparative analysis of the advantages and disadvantages of empirical, finite element, and analytical models for milling force in thin-walled parts is presented. The paper also discusses the experimental methods, finite element modal analysis, and structural coupling methods used to obtain the frequency response functions of workpieces and tools, comparing their respective strengths and weaknesses. Furthermore, time-domain and frequency-domain methods for stability prediction are analyzed and compared, with a discussion on the future prospects of chatter stability prediction in mirror milling.

‘Vaping is a break from all of that’: Exploring attitudes, harm perceptions, cessation barriers and social dynamics among people who vape

Objective: Vaping, initially a smoking cessation aid, is now a widespread recreational activity sometimes associated with perceived health concerns. This study explored attitudes, harm perceptions and cessation barriers in the context of participants’ vaping behaviours, guided by the theoretical lens of fundamental social causes. Design and Setting: The study focused on a subset of 571 current adult vapers from a larger survey investigating vaping attitudes. It analysed open-text survey responses relating to vaping behaviours. To analyse the responses, we employed layered analyses, using deductive conceptual mapping to inform an inductive thematic content analysis. Results: Participants mentioned nuanced vaping risks, citing cancer and respiratory concerns, often comparing them to tobacco’s well-known harmful effects. Despite acknowledging vaping’s potential harms, participants perceived the practice to be less harmful than smoking, emphasising relative safety. Some viewed vaping positively for former smokers, contingent on regulated products. This complex attitude balance reflected the intricate interplay between health concerns and social dynamics. Recurrent vaping symbolised consistent engagement, with cravings and widespread availability associated with quitting challenges. Conclusions: Participants’ nuanced perceptions of health risks reflect a harm duopoly, resembling illicit drug harm tiering. There is a complex interplay between health knowledge and social influences in the context of vaping behaviours. Study findings underscore the need for messaging interventions discouraging vaping among those who do not smoke tobacco to consider these health and social dynamics, leveraging collaborative design.

Sex workers’ confidence in the police in one Canadian city under the Protection of Communities and Exploited Persons Act

ABSTRACT Confidence in the police, a significant concern of sex workers across the globe, is an important gauge of their views of the legitimacy of law enforcement and their likelihood to seek help when in harms’ way. The purpose of this study is to explore sex worker confidence in police in one Canadian city after the enactment of the dramatically revised prostitution law in 2014, the Protection of Communities and Exploited Persons Act. In 2017–2018, a cross-section of active sex workers (N = 60) from Victoria, Canada, were interviewed about their personal and work lives under the criminal code law. Thematic analysis was carried out using the participants’ answers to these questions: (1) You said you have _____ confidence in the police. Please elaborate on why you feel this way about the police; (2) You said you had _____ interactions with police in the last 12 months? What happened, when, where, why, etc.? Have your interactions with the police changed in recent years? Our findings show the police’s treatment of sex workers is influenced by intersecting stigmas and structural factors that shape the confidence sex workers’ have in law enforcement. We provide greater contextualisation related to the confidence sex workers have in police, why lack of confidence may not always be synonymous with negative experiences, and why their distrust of the ‘institution of policing’ highlights the importance of having public policies that address the fundamental causes of sex worker victimisation and stigmatisation.

Burden of diabetes mellitus in Weifang: Changing trends in prevalence and deaths from 2010 to 2021.

The objective of this study is to analyze the death characteristics and burden of disease (BOD) in diabetes mellitus (DM) patients in Weifang from 2010 to 2021. The findings will serve as a foundational data source and theoretical framework for public health administrative departments in the formulation of DM-related policies. The annual percent change (APC) and average annual percent change (AAPC) of the disability-adjusted life years (DALY), years of life lost (YLL), and years lived with disability (YLD) in DM residents from 2010 to 2021 were analyzed using the Joinpoint software to reflect the changing trend of the BOD in DM patients. Additionally, we conducted an analysis of the various causes of death among these patients and compared BOD in diabetic patients with different backgrounds. From 2010 to 2021, the burden of disease, which includes DALY, YL, and YLD, has been increasing among patients with DM in Weifang. It is noteworthy that the burden of disease is particularly pronounced among male patients and those aged 75 or above. Additionally, it is observed that widowed and illiterate DM patients have comparatively longer survival times. Furthermore, among the DM patients who have unfortunately passed away, it has been identified that unspecified DM with ketoacidosis accounts for 10.03% of the deaths as a direct cause of death. In contrast, type 2 diabetes mellitus (T2DM) with kidney complications contributes to 10.23% of the deaths as the fundamental cause of death. The city is faced with a significant challenge of diabetes, which is influenced by factors such as gender, age, cultural background, and marital status. Unspecified diabetes mellitus (DM) with ketoacidosis (10.03%) and T2DM with renal complications (0.23%) are identified as the primary direct and underlying causes of death among diabetic patients, respectively. This study serves as a valuable reference for other regions in terms of diabetes prevention, control, and the management of chronic diseases.

Examining the Effects of Status Quo Bias on Household/Individual Carbon Consumption

The research investigated the degree of influence status quo bias has on rising carbon emissions. It found that status quo bias strongly regulates the actions of households and individuals when making environmental decisions. Through transportation, individuals lack the incentive to switch to eco- friendly methods and display inertia to their original path. Consumption habits and market interactions also show individuals’ reluctance to new technologies. Results show that the status quo bias plays a significant role as one of the fundamental causes of uncontrollable carbon emissions.

Nanocarriers Targeting Circular RNA ADARB1 Boost Radiosensitivity of Nasopharyngeal Carcinoma through Synergically Promoting Ferroptosis.

Nasopharyngeal carcinoma (NPC) is a common malignant tumor of the head and neck, prevalent in regions such as Southern China and Southeast Asia. Radiotherapy serves as the primary clinical treatment for this carcinoma. However, resistance to radiotherapy is a fundamental cause of treatment failure and patient mortality, with the underlying mechanisms yet to be fully elucidated. We identified a recently characterized circular RNA, circADARB1, which is markedly upregulated in NPC tissues and closely associated with poor prognosis and radiotherapy resistance. Both in vitro and in vivo experiments demonstrated that circADARB1 inhibited ferroptosis, thereby inducing radiotherapy resistance in NPC cells. Building on these findings, we synthesized a biomimetic nanomaterial consisting of semiconducting polymer nanoparticles wrapped in cell membranes, designed to deliver both siRNA targeting circADARB1 and iron ions. The application of this nanomaterial not only efficiently suppressed the expression of circADARB1 and boosted intracellular iron concentrations, but also enhanced ferroptosis induced by radiotherapy, improving the radiosensitivity of NPC cells. Furthermore, our study revealed that circADARB1 upregulated the expression of heat shock protein HSP90B1, which repaired misfolded SLC7A11 and GPX4 proteins triggered by radiotherapy, thereby preserving their stability and biological functions. Mechanistically, SLC7A11 facilitated cysteine transportation into cells and glutathione synthesis, while GPX4 employed glutathione to mitigate intracellular lipid peroxidation induced by radiotherapy, shielding cells from oxidative damage and inhibiting ferroptosis, and ultimately leading to radiotherapy resistance in NPC cells. Our investigation elucidates molecular mechanisms with substantial clinical relevance, highlights the promising application prospects of nanotechnology in precision cancer therapy.

Advancing Pain Understanding and Drug Discovery: Insights from Preclinical Models and Recent Research Findings

Despite major advancements in our understanding of its fundamental causes, pain—both acute and chronic—remains a serious health concern. Various preclinical investigations utilizing diverse animal, cellular, and alternative models are required and frequently demanded by regulatory approval bodies to bridge the gap between the lab and the clinic. Investigating naturally occurring painful disorders can speed up medication development at the preclinical and clinical levels by illuminating molecular pathways. A wide range of animal models related to pain have been developed to elucidate pathophysiological mechanisms and aid in identifying novel targets for treatment. Pain sometimes drugs fail clinically, causing high translational costs due to poor selection and the use of preclinical tools and reporting. To improve the study of pain in a clinical context, researchers have been creating innovative models over the past few decades that better represent pathological pain conditions. In this paper, we provide a summary of traditional animal models, including rodents, cellular models, human volunteers, and alternative models, as well as the specific characteristics of pain diseases they model. However, a more rigorous approach to preclinical research and cutting-edge analgesic technologies may be necessary to successfully create novel analgesics. The research highlights from this review emphasize new opportunities to develop research that includes animals and non-animals using proven methods pertinent to comprehending and treating human suffering. This review highlights the value of using a variety of modern pain models in animals before human trials. These models can help us understand the different mechanisms behind various pain types. This will ultimately lead to the development of more effective pain medications.

Mechanism of PD-1/PD-L1 in Regulating cTfr/cTfh Balance in Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) is frequent, an imbalance between helper cells (Th) and regulatory T cells (Treg) is the fundamental immunological cause of RA. This study investigates how recombinant human programmed cell death 1 (PD-L1) protein affects circulating T follicular helper (cTfh), circulating T follicular regulatory (cTfr), and their equilibrium. Magnetic bead sorting was used to select CD4+CXCR5+T cells from RA patients' and healthy individuals' peripheral blood mononuclear cells for in vitro growth. Recombinant human PD-L1 protein stimulated CD4+CXCR5+T cells. Cell counting kit 8 (CCK-8), flow cytometry surface labeling, ELISA, and RT-PCR were used to measure CD4+CXCR5+T cell proliferation inhibition, cTfh and cTfr frequencies, IL-21 expression, and PI3K, AKT, Bcl-6, and Blimp-1 mRNA levels. The recombinant human PD-L1 protein dose-dependently inhibited the proliferation of CD4+CXCR5+T cells in active RA peripheral blood. However, it has a weaker inhibitory effect on healthy peripheral blood CD4+CXCR5+T cells. PD-L1 protein decreased cTfh in active RA peripheral blood CD4+CXCR5+T overall cultured cells but did not affect cTfr; The cTfr/cTfh ratio increased but did not affect the frequency of cTfh and cTfr in healthy persons' cultured CD4+CXCR5+T cells. PD-L1 protein reduced IL-21 in CD4+CXCR5+T cell culture supernatant from active RA peripheral blood. Recombinant human PD-L1 protein lowered PI3K, AKT, and Bcl-6 mRNA in active RA peripheral blood CD4+CXCR5+T cell culture, including significant differences. But Blinmp-1 mRNA variations were neither substantial nor statistically different. PD-1/PD-L1 limits cTfh proliferation, differentiation, and activation via the PI3K/AKT signaling pathway regulates its immunological balance with cTfr, and corrects the cTfr/cTfh imbalance by controlling their interaction.

Global screening of base excision repair in nucleosome core particles

DNA damage is a fundamental molecular cause of genomic instability. Base excision repair (BER) is one line of defense to minimize the potential mutagenicity and/or toxicity derived from damaged nucleobase lesions. However, BER in the context of chromatin, in which eukaryotic genomic DNA is compacted through a hierarchy of DNA-histone protein interactions, is not fully understood. Here, we investigate the activity of BER enzymes at 27 unique geometric locations in a nucleosome core particle (NCP), which is the minimal unit of packaging in chromatin. The BER enzymes include uracil DNA glycosylase (UDG), AP endonuclease 1 (APE1), DNA polymerase β (Pol β), and DNA ligase IIIα complexed with X-ray repair cross complementing group 1 (LigIIIα/XRCC1). This global analysis of BER reveals that initiation of the repair event by UDG is dictated by the rotational position of the lesion. APE1 has robust activity at locations where repair is initiated whereas the repair event stalls at the Pol β nucleotide incorporation step within the central ∼45 bp of nucleosomal DNA. The final step of the repair, catalyzed by LigIIIα/XRCC1, is achieved only in the entry/exit regions of the NCP when nick sites are transiently exposed by unwrapping from the histones. Kinetic assays further elucidate that the location of the damaged lesion modulates enzymatic activity. Notably, these data indicate that some of the BER enzymes can act at a significant number of locations even in the absence of chromatin remodelers or other cellular factors. These results inform genome wide maps of DNA damage and mutations and contribute to our understanding of mutational hotspots and signatures.

Study on the mechanical properties and microscopic evolution mechanisms of weathered granite soil

Studying the effects of weathering on the mechanical properties and microscopic evolution of weathered granite soil (WGS) is essential for connecting microstructure with macroscopic behavior. This study conducts systematic monotonic and cyclic triaxial tests, along with a series of microscopic tests on WGS samples, to explore the influence of weathering on WGS mechanical properties and the mechanism of granite weathering. Results indicate that both effective internal friction angle and effective cohesion decrease progressively with increased weathering. Completely weathered granite (CWG) exhibits greater dynamic strength compared to granite residual soil (GRS). Additionally, as weathering progresses, quartz fragments are lost, while feldspar and biotite weather to form secondary minerals such as kaolinite and illite, leading to an overall enrichment in aluminum and iron in the granite. Weathering causes structural deterioration of WGS. Finally, the mechanical parameters of WGS and their chemical weathering indices show a coefficient of determination ranging from 60 to 99%. This study helps elucidate the fundamental causes of performance changes in WGS, thereby optimizing engineering design and enhancing disaster prediction accuracy, while providing new research perspectives and experimental evidence for WGS.

Reconsidering inequalities in COVID-19 vaccine uptake in Germany: a spatiotemporal analysis combining individual educational level and area-level socioeconomic deprivation

Combining the frameworks of fundamental causes theory and diffusion of innovation, scholars had anticipated a delayed COVID-19 vaccination uptake for people in lower socioeconomic position depending on the socioeconomic context. We qualify these propositions and analyze educational differences in COVID-19 vaccination status over the first ten months of Germany’s vaccination campaign in 2021. Data from the study “Corona Monitoring Nationwide” (RKI-SOEP-2), collected between November 2021 and February 2022, is linked with district-level data of the German Index of Socioeconomic Deprivation (GISD). We estimated the proportion of people with at least one vaccination dose stratified by educational groups and within different settings of regional socioeconomic deprivation at three time points. Logistic multilevel regression models were applied to adjust for multiple covariates and to test cross-level-interactions between educational levels and levels of area-level socioeconomic deprivation. Vaccination rates were lower among respondents with lower education. With increasing area-level socioeconomic deprivation, educational differences were larger due to particularly low vaccination rates in groups with low education levels. The analysis of vaccination timing reveals that educational gaps and gaps by area-level socioeconomic deprivation had appeared early in the vaccination campaign and did not close completely before the 4th wave of COVID-19 infections