Related Changes Research Articles

Oral microbiome in the development of oral cancer

Oral cancer is an aggressive and rapidly progressive disease. The oral cavity is home to over 700 species of microorganisms which regulate metabolism, immune function and health. There are 3 types of mechanisms by which bacteria may participate in carcinogenesis. First, bacteria cause chronic inflammation, which stimulates the production of cytokines, including interleukins, interferons, and tumor necrosis factor. Second, bacteria can interact directly with host cells by secreting toxins or by binding to membrane receptors. Finally, the production of metabolites by bacteria may also contribute to carcinogenesis. The importance of bacteria level and composition in the transition of oral precancerous lesions to cancer has been demonstrated. The relationship of changes in microbiome composition with smoking, inflammation in healthy individuals, as well as with the development of oral cancer in patients has been studied.

The reasons for and influences of unintended teenage pregnancy in Kericho county, Kenya: a qualitative study.

Unintended teenage pregnancies are associated with greater health and socio-economic risks for teenage mothers and newborns. In Kenya, the government has declared a target for ending teenage pregnancy by 2030. However, the prevalence of teenage pregnancy has only decreased slightly, demonstrating the need for further efforts. Understanding teenage mothers' own experiences and perspectives is necessary to design appropriate interventions. A community-based qualitative study was conducted from March to May 2023. Two focus group discussions were conducted with community health volunteers and the mothers of teenage girls. Semi-structured interviews were conducted on the case histories of 19 teenage mothers and 18 key informants. Thematic analysis was subsequently performed using MAXQDA 2022. Four major reasons emerged for unintended teenage pregnancies: (1) lack of knowledge or awareness about the human reproductive system, (2) lack of knowledge about family planning (FP), (3) financial challenges, and (4) low access to FP. At the study site, cultural norms and stereotypes, such as "infertility caused by FP," "freedom of sex by promoting FP," and "cultural taboos on having sex before marriage and talking about sexuality," were observed as barriers in promoting FP to teenagers. In addition, teenagers from low socio-economic backgrounds were found to be more vulnerable because they can be easily exploited by men who can afford to provide for some of their basic needs. Regarding the influences of unintended teenage pregnancy on teenage mothers' lives, the 19 cases were classified into four categories: (1) dropping out of school, (2) financial challenges, (3) changing relationships with parents, and (4) no major influence. Crucially, unintended teenage pregnancies negatively influenced most study participants. Continuing education, supportive parental attitudes, positive perceptions of the relationship with the child's father, and having future perspectives were identified as factors mitigating the negative influences. Strengthening culturally appropriate comprehensive sexuality education and the school re-entry policy with a supportive environment may prevent unintended teenage pregnancy and mitigate its negative influences. As financial challenges can be both a reason for and a negative influence of unintended teenage pregnancy, economic empowerment interventions are necessary.

(Un)Funny Against All Odds: The Changing Landscape of Humour in Politics

The article wants to set the stage for the rest of the special issue titled ‘From resistance to legitimation: The changing role of humour in politics’ by providing an overview of some the key concepts, theories and approaches to humour. It begins by considering different concepts of and some of the theoretical approaches to the functions and implications of humour including relief, superiority and incongruity as well as carnival theory and the role of parody. From these ideas, it outlines several functions of using humour in politics which include the raising of public attention and distraction, provocation and isolation from critique, humour as a means of persuasion and anxiety management as well as the use of humour as a means of stabilizing and de-stabilizing hierarchies. Turning to the main contribution of the special issue it outlines the changing relationship of humour in politics from a means of critique of power to a means of legitimation of power. It places the contribution of the special issue in this debate and holds that humour plays an ambiguous role and calls for further research into the dark and unfunny side of humour in politics.

"I Am Forever Changed": A Phenomenological Study of the Existential Experiences of Parents of Children and Young People With Complex Care Needs.

To explore the existential lived experiences of parents of children and young people with complex care needs. An explorative qualitative design. We conducted 16 in-depth interviews with parents of children and young people with complex care needs across Norway from February to May 2022. Data collection and analysis were guided by the theoretical framework of van Manen's phenomenology of practice approach. Four distinct but interwoven themes reflecting the comprehensive and holistic nature of parents' existential lived experiences emerged: lived body: "I am forever changed"; lived space: Seeking sanctuary; lived time: "Time doesn't seem to exist"; and lived self-other: Parents' changing relationships. Parents' ongoing efforts to manage fluctuations in their daily lives profoundly affect the existential aspects of their well-being, suggesting that respectful and attentive nurse-parent relationships can nurture existential growth. There is a crucial need for a genuine nursing presence characterised by an attitude of open sensitivity and attentive listening to parents' existential experiences. Nurses should embrace the opportunity to engage in respectful and attentive dialogues with parents. Acknowledging that the insights emerging from these conversations can improve integrated and personalised nursing services worldwide. Parents of children and young people with complex care needs often experience suboptimal healthcare. Additionally, access to quality healthcare services, particularly in rural areas, is limited, creating inefficiencies and coordination challenges. This study provides nurses, other health care professionals, researchers, and decision-makers with valuable perspectives on supporting parents' existential needs which may significantly impact their overall well-being and coping abilities, contributing to a more compassionate approach to family care. Consolidated Criteria for Reporting Qualitative Research (COREQ). Parents of children and young people with complex care needs provided valuable feedback on the findings and implications of this work.

Ideas and the changing relationship between states and markets in social policy: A review essay

AbstractThis review essay takes stock of the recent literature about the role of ideas in social policy, with a particular focus on a key issue in social policy research: the changing interactions between states and markets over time. Specifically, our aim is to examine how the ideational literature discusses and explains prominent contemporary social policy evolutions: the rise of social investment and the financialization and technocratization of the welfare state. This is done based on the scholarship on state/market interactions and the role of ideas in social policy, and by utilizing key insights of scholars of ideational influences on state/market interactions. The article ends with a short agenda for future research on ideas and discourses as a crucial factor in the evolution of the welfare state as a key space in which states and markets interact.

Understanding the Relationship of Functional and Neurochemical Brain Changes in Parkinson’s Disease: First Steps With Novel Neuroimaging Approaches

Understanding the Relationship of Functional and Neurochemical Brain Changes in Parkinson’s Disease: First Steps With Novel Neuroimaging Approaches

Weight change and the risk of cardiovascular disease in patients with hypertension: A primary-care cohort study.

Weight control is a cornerstone of hypertension management. Therefore, it is important to understand the relationship of weight change to risk of cardiovascular disease (CVD) among patients with hypertension. We aimed to investigate the association of weight change with the risk of CVD, stroke, and myocardial infarction (MI) among patients with hypertension. We obtained the data from medical records of the Hypertension Health Management Program (HMPH) in Shenzhen, China. The present study included 221 454 individuals with hypertension. Weight change over two years was divided into loss ≥10%, loss 5-10%, stable (-5 ~ 5%), gain 5-10%, and gain >10%. Cox regression analyses were applied to assess the associations of weight change groups with the risk of CVD, stroke, and MI. Compared with the stable weight group (-5 ~ 5%), those with weight loss ≥10% had a higher risk of CVD (hazard ratio (HR) = 1.21; 95% confidence interval (CI) = 1.05-1.40) in the fully adjusted model. Weight gain >10% was significantly associated with a higher risk of CVD (HR = 1.17; 95% CI = 1.04-1.31). In the meanwhile, participants with weight loss ≥10% had significantly higher risks of stroke (HR = 1.20; 95% CI = 1.02-1.41). However, participants with weight gain >10% had an increased risk of MI (HR = 1.45; 95% CI = 1.15-1.82) in the fully adjusted model. Weight loss or weight gain were associated with higher risks of CVD. Management of patients with hypertension requires close monitoring and appropriate interventions to achieve optimal body weight to prevent adverse outcomes.

Making sense of big questions that require multiple subjects: preliminary theorisation of an integrative philosophy of knowledge and empirical indications of a lack of subject connection within school curricula

AbstractThis paper provides theorisation about a novel concept for education: an integrative philosophy of knowledge (IPK). This is proposed for school curricula to relate multiple subjects to big questions of personal and existential importance. Critical contemporary issues such as climate change education require multiple subject contributions but there is little clarity in the English education guidance on this drawing together, beyond the encouragement to do so in priority areas. Leading British thinkers have engaged the idea of the unity of knowledge, not without difficulty and criticism. The paper identifies reasons for a practical approach to consilience in school curricula. In addition to preliminary theorisation, in methodological ‘harmony’, this paper adds tentative empirical findings from a related research project that provides quantitative indications that such multi-subject connection is likely not happening. The findings are not definitive, but the perceptions of three groups of beginning and experienced teachers (secondary Religious Education (RE), secondary science and primary teachers) indicate that school curricula do not reflect an integrative approach to climate change education, and sex and relationships education, despite policy priority. A significant national survey could not detect many signs of connection. The paper speculates that RE could have a key epistemic role for the curriculum as a whole in this regard.

Association of changes and cumulative measures of triglyceride-glucose index-body mass index with hypertension risk: a prospective cohort study

BackgroundTo investigate the relationships of the dynamic changes in triglyceride glucose index-body mass index (TyG‑BMI) and cumulative TyG-BMI with the risk of hypertension among middle-aged and elderly Chinese.MethodsData were used from the China Health and Retirement Longitudinal Study (CHARLS). Participants who participated in the baseline study (2011–2012) and in subsequent surveys (2015–2018) were included in this study. The primary exposures were changes in TyG-BMI and cumulative TyG-BMI from 2012 to 2015. Changes in TyG-BMI were categorized using k-means clustering methods, while cumulative TyG-BMI was categorized into quartiles. Cox proportional hazards regression models were performed to examine the association between changes in TyG-BMI and cumulative TyG-BMI with the incidence of hypertension. Linear regression analyzes were performed to examine the association between changes in TyG-BMI and cumulative TyG-BMI with cumulative systolic blood pressure (SBP) and cumulative diastolic blood pressure (DBP).ResultsOf a total of 2,561 participants aged 56.93 ± 8.08 years old at baseline, 253 individuals (9.9%) developed hypertension during the 7-year follow-up period. The hazard ratios (HR) and 95% confidence interval (CI) for hypertension were 1.50 (1.10–2.03) for class 2 (persistently medium class) and 2.35 (1.61–3.42) for class 3 (persistently high class), compared to class 1 (persistently low class). Additionally, class 2 showed increases of 7.70 mmHg (95% CI: 5.18–10.21) in cumulative SBP and 6.53 mmHg (95% CI: 4.68–8.38) in cumulative DBP, while class 3 exhibited increases of 14.10 mmHg (95% CI: 10.56–17.64) in cumulative SBP and 12.64 mmHg (95% CI: 10.03–15.25) in cumulative DBP, compared with class 1. Regarding cumulative TyG-BMI, the HR for hypertension were 1.75 (95% CI: 1.18–2.59) for quartile 3 and 2.15 (95% CI: 1.43–3.23) for quartile 4, compared with quartile 1. In quartile 2, cumulative SBP increased by 3.99 mmHg (95% CI: 0.88–7.11) and cumulative DBP by 2.74 mmHg (95% CI: 0.45–5.02). Quartile 3 showed increases of 8.32 mmHg (95% CI: 5.09–11.54) in cumulative SBP and 7.13 mmHg (95% CI: 4.76–9.49) in cumulative DBP. Quartile 4 exhibited the highest increases, with cumulative SBP rising by 13.15 mmHg (95% CI: 9.70–16.60) and cumulative DBP by 12.20 mmHg (95% CI: 9.67–14.74). Furthermore, a linear relationship was observed between cumulative TyG-BMI and the risk of hypertension.ConclusionsChanges in TyG-BMI and cumulative TyG-BMI were associated with an increased risk of hypertension, as well as higher cumulative SBP and DBP in Chinese middle-aged and elderly population.

High-resolution mapping of carbon dioxide emissions in Guizhou Province and its scale effects

Accurate spatial distribution of carbon dioxide (CO2) emissions is essential information needed to peaking emissions and achieving carbon neutral in China. The aim of this study was to map CO2 emissions with high spatial resolution at provincial scale and then explore the scale effect on mapping results. As an example, the spatiotemporal pattern and factors influencing CO2 emissions were examined in Guizhou Province in Western China. With the proposed method, a reasonable spatial distribution of CO2 emissions with high spatial resolution was obtained, which had relatively accurate information on spatial details. The optimal resolution of CO2 emissions at the provincial scale under high spatial resolution was approximately 90 m and 1260 m. More detailed grid data can better reflect the spatial variability of CO2 emissions. Emissions of CO2 were spatially heterogeneous in Guizhou, with high emissions in centers of big cities that gradually spread and decreased from city centers. From 2009 to 2019, the spatial distribution of CO2 emissions developed from agglomeration to dispersion. Areas of high carbon emissions decreased, those of medium carbon emissions increased, and many areas changed from no emissions to carbon emissions. Industrial land had the highest emissions, followed by commercial and transportation lands. Over 10 years, changes occurred in the relation between interregional economic level of Guizhou and CO2 emissions, with the relation changing from linear into an inverted U-shaped relation. The effect of industrial structure on CO2 emissions decreased, and the linear increase between CO2 emissions and the urban scale became more evident. The results of this study will contribute to accurate monitoring and management of carbon emissions in Guizhou, as well as provide support to formulate policies related to controls on carbon emissions in different regions.

From passion to knowledge

AbstractIn this paper, I aim to situate the practical agency of the sage in an overall picture of the development of the Plotinian moral agent. This development can be seen as a gradual transition from external to internal principles of action guidance which endow the agent with autonomy and coherence in her practical actions. The transition from external to internal principles corresponds to a changing relationship between the agent's telos and particular actions. Non-virtuous agents aim at the attainment of an object of desire, while the civically virtuous person aims to perform virtuous actions irrespectively of the achievement of particular objects of desire. Finally, the telos of the sage is the contemplation of forms and she acts practically as a consequence and external activity of having achieved her goal. The analysis of Plotinus' theory of moral development shows that the sage's inward turn and detachment from external circumstances do not involve inactivity in the practical sphere but figure as a necessary condition of her making an active contribution to the order of the sensible world through her actions as opposed to passively responding to external circumstances.

MoⅣ boosted carrier density of MoO3-X for surface-enhanced Raman spectroscopy

Molybdenum oxides (MoO3-X) with the same surface plasmon resonance (SPR) effect as Au/Ag, and occupies an irreplaceable value in SERS detections. MoO3-X SERS substrates with oxygen-rich defects tend to show better SERS performance, but the preparation and characterization of tunable O defects remain challenging. It cannot be ignored that the oxidation state of metal cations is also influenced by O defects. Here, a series of MoO3-X SERS sensors with regulable Mo valence state were fabricated using magnetron sputtering technology. By changing the Mo sputtering power and the O2/Ar2 ratio, the Mo/O element ratio of the substrate can be easily regulated to readjust the O defects. The X-ray Photoelectron Spectroscopy (XPS) and Raman spectra were performed to investigate the change and related relationship between Mo mixed valence state and SERS sensitivity. The abundant incompletely coordinated electrons produced by low valence MoⅣ act as free carriers, increasing the free carrier density of MoO3-X substrates, which is beneficial for the SERS effect. It has also been proven by Hall effect measurement. The SERS measurement shows that the enhancement factor (EF) reached 3.70 × 105, which is exceedingly close to Au/Ag. The MoO2.5 substrate also exhibited a repeatable and consistent response, high stability, and repeatability, which proves the splendid application potential in complex environments.

Climate Change, Well-Being and Interpersonal Relationships Among Youth in the Caribbean [St. Kitts and Nevis

Climate Change, Well-Being and Interpersonal Relationships Among Youth in the Caribbean [St. Kitts and Nevis

Association between changes in lean mass, muscle strength, endurance, and power following resistance or concurrent training with differing high protein diets in resistance-trained young males.

We assessed the relationship of changes in upper and lower body lean mass with muscle strength, endurance and power responses following two high protein diets (1.6 or 3.2 g.kg-1.d-1) during 16 weeks of either concurrent training (CT) or resistance training (RT) in resistance-trained young males. Forty-eight resistance-trained young males (age: 26 ± 6 yr., body mass index: 25.6 ± 2.9 kg.m-2) performed 16 weeks (four sessions·wk.-1) of CT or RT with either 1.6 g.kg-1.d-1 protein (CT + 1.6; n = 12; RT + 1.6; n = 12) or 3.2 g.kg-1.d-1 protein (CT + 3.2; n = 12; RT + 3.2; n = 12). Relationships between upper (left arm + right arm + trunk lean mass) and lower body (left leg + right leg lean mass) lean mass changes with changes in muscle performance were assessed using Pearson's correlation coefficients. For upper body, non-significant weak positive relationships were observed between change in upper body lean mass and change in pull-up (r = 0.183, p = 0.234), absolute chest press strength (r = 0.159, p = 0.302), chest press endurance (r = 0.041, p = 0.792), and relative chest press strength (r = 0.097, p = 0.529) while non-significant weak negative relationships were observed for changes in absolute upper body power (r = -0.236, p = 0.123) and relative upper body power (r = -0.203, p = 0.185). For lower body, non-significant weak positive relationships were observed between the change in lower body lean mass with change in vertical jump (r = 0.145, p = 0.346), absolute lower body power (r = 0.109, p = 0.480), absolute leg press strength (r = 0.073, p = 0.638), leg press endurance (r < 0.001, p = 0.998), relative leg press strength (r = 0.089, p = 0.564), and relative lower body power (r = 0.150, p = 0.332). Changes in muscle strength, endurance and power adaptation responses following 16 weeks of either CT or RT with different high protein intakes were not associated with changes in lean mass in resistance-trained young males. These findings indicate that muscle hypertrophy has a small, or negligible, contributory role in promoting functional adaptations with RT or CT, at least over a 16-week period.

Impacts of early psychological changes on correlates of weight-loss maintenance: Seeking increased precision for sustained behavioural obesity treatment effects.

Obesity is an increasing worldwide health issue. In affluent English-speaking countries, obesity ranges from ~28% (Australia) to ~42% (United States) of the adult population. Enabling weight loss beyond an initial 6 months is an unresolved challenge. Women with obesity participated in community-based obesity treatments incorporating either cognitive-behavioural methods emphasizing self-regulatory skills development (n = 106) or typical information/education processes (n = 47). Psychosocial, behavioural, and weight changes were measured. Significant overall improvements in exercise-related self-regulation and self-efficacy, mood, physical activity/exercise (PA/exercise), diet, and weight were found from baseline-month 6 (weight-loss phase) and baseline-month 12, but not from months 6-12 (weight-loss maintenance phase). Significantly greater improvements were found in the cognitive-behavioural group. Within the weight-loss phase, changes in both PA/exercise and diet significantly contributed to the explained variance in weight loss, whereas within the weight-loss maintenance phase, only change in PA/exercise was a significant predictor. There was no significant relationship of weight loss across phases. Months 6-12 change in PA/exercise significantly mediated relationships of changes in self-regulation→weight, mood→weight, and self-efficacy→weight. Earlier scores and score changes in mood and self-efficacy significantly impacted the subsequent parallel relationships. Cognitive-behavioural methods affect psychosocial changes leading to initial changes in diet, PA/exercise, and weight. Those changes then impact subsequent changes in PA/exercise-a primary malleable correlate of maintained weight loss. SO WHAT?: This research extended previous findings to better-inform behavioural obesity-treatment foci to address the pervasive public health problem of attaining and sustaining weight loss. Findings related to PA/exercise will help impact health-promotion outcomes.

Association between weight change and serum anti-aging protein α-Klotho: a cross-sectional study in middle-aged and older adults

The relationship of weight change has extended to accelerated ageing, yet little is known about the association between weight change and anti-aging protein α-Klotho. This study included 10,972 subjects from the National Health and Nutrition Examination Survey 2007–2016. Participants were measured body weight and height at baseline and recalled weight at young adulthood and middle adulthood. α-Klotho concentrations were quantified. Generalized linear regression models were used to assess the association between weight change and α-Klotho. Across adulthood, maximal overweight, non-obese to obese, and stable obesity were consistently associated with lower serum Klotho levels. Compared with participants who remained at normal weight, from middle to late adulthood, participants experiencing maximal overweight, moving from the non-obese to obese, and maintaining obesity had 27.97 (95% CI: − 46.57 to − 9.36), 39.16 (95% CI: − 61.15 to − 17.18), and 34.55 (95% CI: − 55.73 to − 13.37) pg/ml lower α-Klotho, respectively; similarly, from young to late adulthood, those had 29.21 (95% CI: − 47.00 to − 11.42) , 34.14 (95% CI: − 52.88 to − 15.40), and 36.61 (95% CI: − 65.01 to − 8.21) lower, respectively. Interestingly, from middle to late adulthood, the absolute weight change values of 590 participants who changed from obese to non-obese were negatively associated with serum α-Klotho. Each 1 kg of weight loss during the process of changing from obese to non-obese brought about a relative increase in α-Klotho levels of 3.03 pg/ml. The findings suggest the potential role of weight management across adulthood for aging.

Structural Analysis of Cathode Slurry Under Flow Using New Probe for Rheo-Impedance Measurements

A battery slurry will experience a variety of shear stresses as it goes through the manufacturing process. The full characterization of a slurry for quality control is challenging due to the complex and changing relationship between active material particles, binder, and the carbon black conductive network as a function of these different shear environments. Rheology is a powerful tool for measuring suspension stability and the viscosity at different shear stresses. However, it cannot characterize the structure of the carbon black conductive network because the rheological properties are dominated by the larger active material particles. Poor distribution or aggregation of the carbon black additive will create an electrode with higher electrical resistance, resulting in more heat generation and a shorter cycle life. Electrochemical impedance spectroscopy is an information dense technique that probes the sample using an alternating current or potential at a range of frequencies. Amongst its many applications, EIS can discriminate between simultaneous events that take place over different time scales, such as the measurement of conductivity within a solid electrode vs the ionic conductivity of the electrolyte. Combining these techniques into a simultaneous measurement will characterize the rheological behavior and the structure of the carbon black conductive network under flow and temperature conditions that are relevant for a manufacturing environment. A novel probe for the simultaneous measurement of rheological properties and electrochemical impedance spectroscopy (Rheo-EIS) is herein presented. A structural analysis of Li-ion battery cathode slurries and carbon paste is used to demonstrate the technique.

Examining Employee Buy-In for Organizational Change: A Structural Equation Model

Abstract Regardless of the prevalence of change, getting employees on board is hard to achieve. While the investigation of leadership and change readiness has been done continuously, the examination of staff involvement in change and working culture, particularly of the non-western world, has been less appreciated. This article addresses this gap by analysing the connection between employee buy-in, trust, relationship, and task-oriented culture. The main data was gathered from 214 respondents. They are employees at a higher education institution in Cambodia and have experienced a technology-driven change recently. The structural equation model reveals significant relationships between trust and working relationship as well as task-oriented culture, highlighting the pivotal role of these cultural attributes in fostering trust and facilitating buy-in for change. The findings contribute to Social Exchange Theory by showcasing the reciprocal exchange between the employee relationship and support in organizational changes and portray a missing trust among Cambodian employees. Recommendations were drawn from the findings for the betterment of change practices by the managers and practitioners.

Uncovering the impacts of LUCC on ecological connectivity in suburban open-pit mining concentration areas: A pattern collection of changing relationships between ecological resistance and ecological network elements

The suburban open-pit mining concentration area couples two human activities, urban sprawl and open-pit mining, while destruction of surface vegetation and ecological restoration coexist. This has also resulted in complex land use shifts that significantly affect regional ecological connectivity. However, the impact of such complex Land use/land cover changes (LUCC) on ecological connectivity in this region is not well understood Therefore, this study takes the suburban open-pit mining concentration area of Jinan City as a case study and uses Land use/land cover (LULC) data from the years 2000, 2010, and 2020 to simulate the spatio-temporal evolution of ecological networks (ENs). Subsequently, a pattern collection of changing relationships was proposed that relate changes in ecological resistance to changes in EN elements, addressing the dynamic transmission process from "spatial field" to "spatial structure entity". Based on this approach, GeoDetector is employed to reveal the response extent of EN elements to LUCC. The results indicate: (1) In the past 20 years, the area of construction land has increased by 100 %, while mining land has increased by 69 %. This significant increase in LUCC has led to a notable enhancement in ecological resistance in the study area, driving the generation of 20 % more ecological pinch points and barriers. Additionally, it has resulted in a twofold increase in both the number and length of level 1 ecological corridors. (2) The dominant status and structure of grassland, agriculture land, and woodland remain relatively stable; however, the interflow among them has caused approximately 25 % of the ecological corridors to undergo changes such as disappearance and path alteration. (3) The implementation of ecological protection and restoration has led to a continuous increase in the area of ecological sources, particularly with the mining rehabilitation increasing by 32.7 times compared to 2000, thereby driving gradual improvement in 25 % of the ecological network elements. (4) Although the quantity and length of ecological corridors in the study area remain relatively stable, evaluation results indicate that its spatial structure is gradually deteriorating, with ecological connectivity decreasing by 7.7 %. This study highlights the importance of restoration of ecological processes in sub-urban open-pit mining concentration areas. The study results can provide a scientific basis for ecological restoration and sustainable development in resource-based cities.

Safety and efficacy of subcutaneous iscalimab (CFZ533) in two distinct populations of patients with Sjögren's disease (TWINSS): week 24 results of a randomised, double-blind, placebo-controlled, phase 2b dose-ranging study

Sjögren's disease is a chronic autoimmune disease with an unmet need for targeted therapies. The aim of the TWINSS study is to evaluate the safety and efficacy of iscalimab, a monoclonal antibody against CD40, in patients with active Sjögren's disease. This randomised, double-blind, placebo-controlled, phase 2b study, conducted at 71 sites in 23 countries, enrolled patients aged 18 years or older fulfilling the American College of Rheumatology/European Alliance of Associations for Rheumatology (EULAR) 2016 criteria. In the dose-ranging cohort 1, patients with a EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score of 5 or higher and a EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score of 5 or higher were randomly assigned (1:1:1:1) to subcutaneous iscalimab 150 mg, 300 mg, 600 mg, or placebo. In the proof-of-concept cohort 2, patients with an ESSDAI score of less than 5, ESSPRI (dryness or fatigue) score of 5 or higher, and Impact of Dry Eye on Everyday Life score of 30 or higher were randomly assigned (1:1) to iscalimab 600 mg or placebo. The sponsor, investigator, site personnel, and patients were masked to the treatment assignment. The primary objectives were to demonstrate a dose-response relationship of iscalimab based on the change in ESSDAI from baseline to week 24 in cohort 1 by Multiple Comparison Procedure-Modelling (MCP-Mod), and to assess the effect of iscalimab 600 mg on ESSPRI at week 24 in cohort 2. All the efficacy analyses included all patients who were randomly assigned, and safety analysis included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT03905525), and is complete. Between Oct 1, 2019, and Feb 28, 2022, 460 patients were screened; 173 patients were assigned to cohort 1 (44 to iscalimab 150 mg, 43 to 300 mg, 43 to 600 mg, and 43 to placebo) and 100 to cohort 2 (50 to each group). In cohort 1, the MCP step showed a significant dose-response relationship for placebo-adjusted ESSDAI change from baseline in one of four models (Linlog model, one-sided p=0·0041). ESSDAI decreased from baseline to week 24 with all three doses of iscalimab; 150 mg and 600 mg doses showed statistically significant improvement (placebo-adjusted least squares [LS] mean difference -3·0 [95% CI -4·9 to -1·1]; p=0·0025 for 150 mg and -2·9 [-4·9 to -1·0]; p=0·0037 for 600 mg). In cohort 2, ESSPRI showed a trend towards improvement with iscalimab 600 mg (placebo-adjusted LS mean change from baseline -0·57 points [95% CI -1·30 to 0·15]; p=0·12). Serious adverse events were reported in nine patients in cohort 1 (one [2%] of 43 in the placebo group, one [2%] of 44 in the iscalimab 150 mg group, three [7%] of 42 in the 300 mg group, four [9%] of 44 in the 600 mg group) and four patients in cohort 2 (two [4%] of 50 in each group). No deaths occurred over the 24-week period. The study met the primary objective of demonstrating a significant dose-response relationship with iscalimab in terms of disease activity at week 24. Iscalimab was well tolerated and showed initial clinical benefit over placebo in two distinct populations of patients with Sjögren's disease, to be confirmed in larger trials. Novartis Pharma.