Cumulative Proportion Research Articles

Differential assessment of fracture frequency and risk in patients undergoing hemodialysis depending on the treatment of mineral and bone disorders: Prospective cohort study with historical control

The present study aimed to assess the incidence, risk, and timing of fractures in patients undergoing hemodialysis with secondary hyperparathyroidism (SHPT), following the correction of mineral and bone disorders (MBD).
 Methods. This prospective cohort open-label study involving 242 patients was conducted between 2019 and 2022. The patients were categorized into three groups based on MBD treatment. Group 1 (n=64) represented a historical cohort without modern treatment, while Group 2 (n=153) received contemporary MBD and SHPT correction. Group 3 (n=22) included patients prescribed selective vitamin D receptor activators in addition to modern therapy.Patients underwent regular assessments, including calcium, phosphorus, and parathyroid hormone measurements every three months, therapy adjustments, fracture diagnosis, and treatment over a 24-month follow-up period.
 Results. Our findings revealed a significantly higher cumulative proportion of patients without bone fractures in Group 2 compared to the historical control, with survival rates of 75.8% and 92.6%, respectively (p=0.0006). The average life expectancy before fractures in Group 2 was 695.77±10.19 days, significantly longer than the historical group (p < 0.0001), and the risk of bone fractures decreased by more than four times (HR 0.2274, 95% CI: 0.0965 – 0.5358).
 Comparing Groups 1 and 3 showed even more positive outcomes. The cumulative proportion of patients without fractures at the end of the study was 75.8% in Group 1 and 95.5% in Group 3 (p = 0.0441), with a life expectancy before fractures of 630.88±24.29 days and 724.38±5.48 days, respectively (p < 0.0001). The risk for bone fractures decreased by one-third in Group 3 (HR 0.3390, 95% CI: 0.0838 - 0.9058). The average life expectancy before fractures in Group 3 was significantly longer than in Group 2 (p < 0.0001), although the cumulative proportion of patients without fractures did not differ significantly (95.5% vs. 92.6%, p > 0.05).
 Conclusions. The study demonstrates that correcting SHPT and MBD with non-calcium phosphate binders, calcimimetics, and paricalcitol or vitamin D reduces fracture incidence and risk, and increases the treatment duration until a fracture episode occurs in patients undergoing hemodialysis.

A Prospective Phase II Dose Escalation Study Using IMRT for High Risk N0M0 Prostate Cancer.

Published data supports the use of very high dose intensity modulated radiotherapy (IMRT) in achieving high efficacy and low toxicity for high-risk prostate cancer (HRPCa). This phase II multi-institutional non-randomized prospective dose escalation study using intensity modulated radiotherapy (IMRT) for high risk N0M0 prostate cancer was designed to investigate dose escalation using 1.8 Gy increments from baseline 75.6 Gy up to maximum 81 Gy, once dose volume constraints were adhered to. Inclusion criteria were patients undergoing a radical course of RT for high and very high-risk disease, defined as one or more of the criteria ≥ T3*, ≥ Gleason 8, Prostate specific antigen (PSA) > 20ng/ml. All patients received Androgen Deprivation Therapy (ADT) and none had radiological evidence of distant metastatic disease. The primary objective was to determine if dose escalated IMRT for high risk localized prostate cancer could provide freedom from biochemical relapse (BR; PSA rising > nadir +2ng/mL or initiation of salvage hormone therapy) similar to that reported in the literature. The Kaplan-Meier method was used to estimate survival times. Secondary objectives included OS, Disease Free Survival (DFS), and the incidence and severity of Genito-urinary (GU), Gastro-intestinal (GI) and erectile dysfunction (ED) toxicities (CTCAE v.3). Toxicities and performance status were collected and graded weekly during RT, 2 months after completing RT, 8 months' post RT, and 6 monthly thereafter to year five and annually thereafter to year nine. A total of 230 evaluable patients were enrolled between April 2009 and June 2016. The median follow-up was 7.3 years. The cumulative proportion of patients surviving without BR at 5 years was 91% (95% Confidence Interval (CI): 86% to 94%). Overall survival at 5 and 7 years was 92% (88% to 95%) and 89% (83% to 92%) respectively, while the cumulative proportion of patients free from disease was 89% (84% to 93%) at 5 years and 81% (75% to 86%) at 7 years. The incidence of acute G2 and G3 toxicities were; GU; 57.8% G2, 12.6% G3, GI; 15.2% G2, 0.4% G3, ED; 30.0% G2 and 61.7% G3. The incidence of late G2, G3 and G4 toxicities were; GU; 40.9% G2, 8.7% G3, GI; 36.5% G2, 2.2% G3, 0.4% G4, ED; 11.7% G2 and 86.1% G3. The percentage of patients receiving each dose level was; 3.5% received 75.6Gy in 42 fractions, 2.2% received 77.4Gy in 43 fractions, 93% received 81Gy in 45 fractions. The findings indicate that high-dose IMRT is well tolerated and is associated with excellent long-term tumor-control outcomes in patients with localized high and very high-risk prostate cancer, with 91% of patients surviving at 5 years without biochemical relapse. The rates of long term G3 GU and GI toxicity were low at 8.7% and 0.4% respectively.

The role of internalised HIV stigma in disclosure of maternal HIV serostatus to children perinatally HIV-exposed but uninfected: a prospective study in the United States.

Decisions to disclose HIV serostatus may be complicated by internalised HIV stigma. We evaluated the association of internalised HIV stigma in biological mothers living with HIV with disclosure of their serostatus to their children perinatally HIV-exposed but uninfected (CHEU). Mothers and their CHEU were enrolled in the United States (U.S.)-based Surveillance Monitoring for Antiretroviral Therapy (ART) Toxicities (SMARTT) study of the Pediatric HIV/AIDS Cohort Study (PHACS), a longitudinal study of outcomes related to in utero exposure to HIV and ART among CHEU. Mothers completing at least one stigma and disclosure assessment starting at the child's age 11-, 13-, 15- and/or 17-year study visits between 16 August 2016 and 1 October 2020 were eligible. Stigma was measured with the 28-item Internalised HIV Stigma Scale (IHSS). Mean stigma scores were linearly transformed to a range of 0-100, with higher scores indicating greater levels of stigma. At each visit, mothers were asked if their child was aware of their HIV diagnosis and at what age the child became aware. The Kaplan-Meier estimator evaluated the cumulative probability of disclosure at each child age. Logistic regression models with generalised estimating equations to account for repeated measures were fit to examine the association between stigma and disclosure, controlling for relevant socio-demographic variables. Included were 438 mothers of 576 children (mean age 41.5 years, 60% U.S.-born, 60% Black/African American and 37% with household income ≤$10,000). The prevalence of disclosure across all visits was 29%. Mothers whose children were aware versus not aware of their serostatus reported lower mean IHSS scores (38.2 vs. 45.6, respectively). The cumulative proportion of disclosure by age 11 was 18.4% (95% CI: 15.5%, 21.8%) and 41% by age 17 (95% CI: 35.2%, 47.4%). At all child ages, disclosure was higher among children of U.S.-born versus non-U.S.-born mothers. After adjusting for age, marital status and years since HIV diagnosis, higher IHSS scores were associated with lower odds of disclosure (OR = 0.985, 95% CI: 0.975, 0.995). Providing support to women as they make decisions about serostatus disclosure to their children may entail addressing internalised HIV stigma and consideration of community-level factors, particularly for non-U.S.-born mothers.

Complications of deep brain stimulation in Parkinson's disease: a single-center experience of 517 consecutive cases.

The number of deep brain stimulation (DBS) procedures is rapidly rising as well as the novel indications. Reporting adverse events related to surgery and to the hardware used is essential to define the risk-to-benefit ratio and develop novel strategies to improve it. To analyze DBS complications (both procedure-related and hardware-related) and further assess potential predictive factors. Five hundred seventeen cases of DBS for Parkinson's disease were performed between 2006 and 2021 in a single center (mean follow-up: 4.68 ± 2.86 years). Spearman's Rho coefficient was calculated to search for a correlation between the occurrence of intracerebral hemorrhage (ICH) and the number of recording tracks. Multiple logistic regression analyzed the probability of developing seizures and ICH given potential risk factors. Kaplan-Meier curves were performed to analyze the cumulative proportions of hardware-related complications. Mortality rate was 0.2%, while permanent morbidity 0.6%. 2.5% of cases suffered from ICH which were not influenced by the number of tracks used for recordings. 3.3% reported seizures that were significantly affected by perielectrode brain edema and age. The rate of perielectrode brain edema was significantly higher for Medtronic's leads compared to Boston Scientific's (Χ2(1)= 5.927, P= 0.015). 12.2% of implants reported Hardware-related complications, the most common of which were wound revisions (7.2%). Internal pulse generator models with smaller profiles displayed more favorable hardware-related complication survival curves compared to larger designs (X2(1)= 8.139, P= 0.004). Overall DBS has to be considered a safe procedure, but future research is needed to decrease the rate of hardware-related complications which may be related to both the surgical technique and to the specific hardware's design. The increased incidence of perielectrode brain edema associated with certain lead models may likewise deserve future investigation.

A Longitudinal Clinical Trajectory Analysis Examining the Accumulation of Co-morbidity in People with Type 2 Diabetes (T2D) Compared with Non-T2D Individuals.

Type 2 diabetes mellitus (T2D) is commonly associated with an increasing complexity of multimorbidity. While some progress has been made in identifying genetic and non-genetic risk factors for T2D, understanding the longitudinal clinical history of individuals before/after T2D diagnosis may provide additional insights. In this study, we utilised longitudinal data from the DARE (Diabetes Alliance for Research in England) study to examine the trajectory of clinical conditions in individuals with and without T2D. Data from 1932 individuals (T2D n = 1196 vs. matched non-T2D controls n = 736) were extracted and subjected to trajectory analysis over a period of up to 50years (25years pre-diagnosis/25years post-diagnosis). We also analysed the cumulative proportion of people with diagnosed coronary artery disease (CAD) in their general practice (GP) record with an analysis of lower respiratory tract infection (RTI) as a comparator group. The mean age of diagnosis of T2D was 52.6 (95% confidence interval 52.0-53.4)years. In the years leading up to T2D diagnosis, individuals who eventually received a T2D diagnosis consistently exhibited a considerable increase in several clinical phenotypes. Additionally, immediately prior to T2D diagnosis, a significantly greater prevalence of hypertension (35%)/RTI (34%)/heart conditions (17%)/eye, nose, throat infection (19%) and asthma (12%) were observed. The corresponding trajectory of each of these conditions was much less dramatic in the matched controls. Post-T2D diagnosis, proportions of T2D individuals exhibiting hypertension/chronic kidney disease/retinopathy/infections climbed rapidly before plateauing. At the last follow-up by quintile of disadvantage, the proportion (%) of people with diagnosed CAD was 6.4% for quintile 1 (least disadvantaged) and 11% for quintile 5 (F = 3.4, p = 0.01 for the difference between quintiles). These findings provide novel insights into the onset/natural progression of T2D, suggesting an early phase of inflammation-related disease activity before any clinical diagnosis of T2D is made. Measures that reduce social inequality have the potential in the longer term to reduce the social gradient in health outcomes reported here.

Assessment of Human Papillomavirus Non-16/18, Type-Specific Risk for Cervical Intraepithelial Neoplasia Grade 3 or Worse Among Women With Cervical Atypical Glandular Cells.

To evaluate the risk for cervical intraepithelial neoplasia grade 3 (CIN 3) or worse (including adenocarcinoma in situ [AIS] and invasive cervical cancer) associated with non-16/18 human papillomavirus (HPV) types (other HPV) among women with atypical glandular cells (AGC) in cervical cytology. This population-based cohort study evaluates the risk of CIN 3 or worse associated with other HPV types. Human papillomavirus genotyping was performed on Pap tests collected in Sweden from 341 women with AGC that were positive for other HPV types from February 17, 2014, to December 31, 2018. The women were followed for histopathologic outcomes using comprehensive registry linkages until December 31, 2019. Cumulative incidence proportions of CIN 3 or worse by specific HPV type were calculated using 1-minus Kaplan-Meier function. Hazard ratios (HRs) for CIN 3 or worse were generated using multivariate Cox regression. Of 341 women, 134 (39.3%) had CIN 3-AIS, but there were only five (1.5%) women in the cohort with invasive cervical cancer. Human papillomavirus 45 preceded 80.0% of invasive cervical cancer cases. Among women positive for HPV33, 82.9% (95% CI 58.0-97.3%) had CIN 3 or worse during follow-up. Positivity for HPV31 conferred the highest HR for CIN 3 or worse relative to other types, both in primary cytology and primary HPV screening (HR 2.71, 95% CI 1.47-5.00 and HR 3.41, 95% CI 1.95-5.96, respectively). Among non-16/18 HPV types in AGC, HPV31 and 33 had the highest risk for CIN 3 or worse, whereas most of the women with invasive cancer were positive for HPV45. Extended HPV genotyping may be helpful for the management of AGC.

Randomized controlled field trial to assess the efficacy of an intranasal Moraxella bovis cytotoxin vaccine against naturally occurring infectious bovine keratoconjunctivitis

BackgroundInfectious bovine keratoconjunctivitis (IBK; pinkeye) is generally considered to be caused by corneal infections with Moraxella bovis. Previous studies demonstrated that M. bovis cytotoxin-specific mucosal immune responses in the bovine eye can be stimulated by intranasal vaccination with a recombinant M. bovis cytotoxin subunit adjuvanted with polyacrylic acid. MethodsA randomized controlled field trial (two-arm parallel design with blinding) was conducted in beef steers in Northern California to determine if this vaccine could prevent naturally occurring IBK and/or reduce morbidity rates associated with this disease. Beef steers were vaccinated intranasally on days 0 and 21 with either a recombinant M. bovis cytotoxin subunit adjuvanted with polyacrylic acid (Vaccine group) or adjuvant alone (Control group). Eye examinations were performed on all steers every 7 days for 16 weeks to document the occurrence of IBK and to determine sizes of corneal ulcers. Serum and tear samples were collected on days 0, 42, and 112 from a subset of animals to measure changes in systemic and ocular immune responses to M. bovis cytotoxin. ResultsThe cumulative proportion of steers that developed IBK after 16 weeks did not differ between groups. Variables related to disease severity were numerically lower in steers that received the experimental vaccine. IBK-affected Vaccine group steers had a significantly lower number of observation weeks with severe ulcers versus Control group steers. Cytotoxin-specific tear IgA was significantly higher in Vaccine group compared to Control group steers on day 112. Conclusion: Although the proportion of animals that developed corneal ulcers associated with IBK did not differ between groups, the lowered metrics of disease severity in vaccinated steers suggests that intranasal vaccination with recombinant M. bovis cytotoxin can reduce the severity of IBK in cattle.

Inequality Measure of Leaf Area Distribution for a Drought-Tolerant Landscape Plant.

Measuring the inequality of leaf area distribution per plant (ILAD) can provide a useful tool for quantifying the influences of intra- and interspecific competition, foraging behavior of herbivores, and environmental stress on plants' above-ground architectural structures and survival strategies. Despite its importance, there has been limited research on this issue. This paper aims to fill this gap by comparing four inequality indices to measure ILAD, using indices for quantifying household income that are commonly used in economics, including the Gini index (which is based on the Lorenz curve), the coefficient of variation, the Theil index, and the mean log deviation index. We measured the area of all leaves for 240 individual plants of the species Shibataea chinensis Nakai, a drought-tolerant landscape plant found in southern China. A three-parameter performance equation was fitted to observations of the cumulative proportion of leaf area vs. the cumulative proportion of leaves per plant to calculate the Gini index for each individual specimen of S. chinensis. The performance equation was demonstrated to be valid in describing the rotated and right shifted Lorenz curve, given that >96% of root-mean-square error values were smaller than 0.004 for 240 individual plants. By examining the correlation between any of the six possible pairs of indices among the Gini index, the coefficient of variation, the Theil index, and the mean log deviation index, the data show that these indices are closely related and can be used interchangeably to quantify ILAD.

Socioeconomic inequalities in modern contraceptive use among women in Benin: a decomposition analysis

BackgroundContraceptive use is crucial to achieving Sustainable Development Goal 3. Evidence of socioeconomic inequality in the use of modern contraceptives is essential to address the developing inequality in its utilisation given the low prevalence of contraceptive use among women in Benin. This study examined the socioeconomic inequalities in modern contraceptive use among women in Benin.MethodsWe performed a cross-sectional analysis of the 2017-18 Benin Demographic and Health Survey data. A weighted sample of 7,360 sexually active women of reproductive age was included in the study. We used a concentration curve to plot the cumulative proportion of women using modern contraception. Decomposition analysis was conducted to determine factors accounting for the socioeconomic disparities in modern contraceptive use.ResultsWe noted that the richest women had higher odds of modern contraceptive use (adjusted odds ratio [aOR] = 1.67, CI = 1.22–2.30) compared to the poorest women. Other factors that showed significant associations with modern contraception use were age, marital status, religious affiliation, employment status, parity, women’s educational level, and ethnicity. We found that modern contraceptive use is highly concentrated among the rich, with rich women having a higher propensity of using modern contraception relative to the poor. Also, the disadvantaged to modern contraceptive use included the poor, those aged 45–49, married women, those working, those with four or more live births, rural residents, and women of Bariba and related ethnicity. Conversely, favourable concentration in modern contraceptive use was found among the rich, women aged 20–24, the divorced, women with two live births, the highly educated, those with media exposure, and women of Yoruba and related ethnicity.ConclusionThe study has shown that wealthy women are more likely to utilize contraceptives than the poor. This is because wealthy women could afford both the service itself and the travel costs to the health facility, hence overcoming any economic barriers to using modern contraception. Other factors such as age, marital status, religion, employment status, parity, mother’s educational level, and ethnicity were associated with contraceptive use in Benin. The Benin government and other stakeholders should develop family planning intercession techniques that address both the supply and demand sides of the equation, with a focus on reaching the illiterate and under-resourced population without admittance to modern contraception.

Early Relative Growth Rate of Abdominal Aortic Aneurysms and Future Risk of Rupture or Repair

This study aimed to test whether the relative growth rate of subthreshold abdominal aortic aneurysms (AAAs) in the first 24 months of surveillance predicts the risk of future rupture or repair. This was a single centre retrospective observational analysis of all small (< 45 mm diameter) and medium (45 - 54 mm in men, 45 - 50 mm in women) AAAs entered into ultrasound surveillance between January 2002 and December 2019, which received ≥ 24 months of surveillance. Relative growth rates were calculated from measurements taken in the first 24 months of surveillance. The Kaplan-Meier method was used to estimate intervention and rupture free proportions five years following diagnosis for AAAs growing by < 5% and by ≥ 5% in the first 24 months of surveillance. Multivariable Cox regression analysis was used to further analyse this relationship by adjusting for factors found to be significantly associated with outcome in univariable analysis. A total of 556 patients with AAAs (409 men, 147 women) were followed for ≥ 24 months. This included 431 small AAAs. Of these, 109 (25.3%) grew by < 5% in the first 24 months of surveillance and had a cumulative event free proportion of 0.98 ± 0.05 at five years compared with 0.78 ± 0.05 for the ≥ 5% growth group (p < .001). Of 125 medium AAAs, 26 (20.8%) grew by < 5% in the first 24 months of surveillance and had a cumulative event free proportion of 0.73 ± 0.11 at five years compared with 0.29 ± 0.13 for the ≥ 5% growth group (p= .024). Baseline diameter and early relative growth rate were strongly and independently predictive of future intervention or rupture with hazard ratios of 9.16 (95% CI 5.98 - 14.03, p < .001) and 4.46 (95% CI 2.45 - 8.14, p < .001), respectively. The results suggest that slow expansion of small (< 45 mm) AAAs observed over an isolated 24 month period is indicative of a very low risk of rupture or repair in the medium term. Isolated growth rates may be a useful tool with which to triage low risk AAAs and prevent unnecessary surveillance.

Reintervention Before Bidirectional Cavopulmonary Shunt and Intermediate Outcomes in Children with Single Ventricle Who Underwent Main Pulmonary Artery Banding.

Unplanned reinterventions following pulmonary artery banding (PAB) in single ventricle patients are common before stage 2 palliation (S2P) but associated risk factors are unknown. We hypothesized that reintervention is more common when PAB is placed at younger age and with a looser band, reflected by lower PAB pressure gradient. Retrospective single center study of single ventricle patients undergoing PAB between Jan 2000 and Dec 2020. The association with reintervention and successful S2P was modeled using exploratory cause-specific hazard regression. A multivariable model was developed adjusting for clinical and statistically relevant predictors. The cumulative proportion of patients undergoing reintervention were summarized using a competing risk model. 77 patients underwent PAB at median (IQR) 47 (24-66) days and 3.73 (3.2-4.5) kg. Within18 months of PAB, 60 (78%) reached S2P, 9 (12%) died, 1 (1%) transplanted and 7 (9%) were alive without S2P. Within 18months of PAB 10 (13%) patients underwent reintervention related to pulmonary blood flow modification: PAB adjustment (n = 6) and conversion to Damus-Kaye-Stansel/Blalock-Taussig-Thomas shunt (n = 4). 6/10 (60%) reached S2P following reintervention. A trend toward higher intervention in patients with a genetic syndrome (p-0.06) and weight < 3kg (p-0.057) at time of PAB was noted. Only genetic syndrome was a risk factor associated with poor outcome (p-0.025). PAB has a reasonable outcome in SV patients with unobstructed systemic and pulmonary blood flow, but with a high reintervention rate. Only a quarter of patients with genetic syndromes reach S2P and further study is required to explore the benefits from an alternative palliative strategy.

Bacterial sexually transmitted infections are concentrated in subpopulations of men who have sex with men using HIV pre-exposure prophylaxis.

Studies have shown varying trends in incidence of sexually transmitted infections (STIs) among individuals using HIV pre-exposure prophylaxis (PrEP). Characterization of individuals at increased risk for STIs may offer an opportunity for targeted STI screening. Group-based trajectory modeling. We screened participants from the AMPrEP demonstration project (2015-2020) for urogenital, anal, and pharyngeal chlamydia and gonorrhea, and syphilis every 3 months and when needed. We identified trajectories of STI incidence within individuals over time and determinants of belonging to a trajectory group. We calculated cumulative proportions of STIs within STI trajectory groups. Three hundred and sixty-six participants with baseline and at least one screening visit during follow-up were included (median follow-up time = 3.7 years [interquartile range, IQR = 3.5-3.7]). We identified three trajectories of STI incidence: participants with a mean of approximately 0.1 STIs per 3 months ('low overall', 52% of the population), participants with a mean 0.4 STI per 3 months ('medium overall', 43%), and participants with high and fluctuating (between 0.3 and 1 STIs per 3 months) STI incidence ('high and fluctuating', 5%). Participants in the 'low overall' trajectory were significantly older, and reported less chemsex and condomless anal sex with casual partners than participants in the other trajectories. Participants in the 'high and fluctuating' and 'medium overall' groups accounted for respectively 23 and 64% of all STIs observed during follow-up. STI incidence was concentrated in subpopulations of PrEP users who were younger, had more chemsex and condomless anal sex. Screening frequency for STIs could be reduced for subpopulations with low risk for incident STIs.

Outdoor Scene Classrooms to Arrest Myopia: Design and Baseline Characteristics.

This study aimed to investigate the impact on childhood myopia of classrooms with spatial properties of classrooms resembling those of outdoor environments. This article describes the design, baseline characteristics, and the acceptability of this strategy. Classrooms had custom-made wallpaper installed with forest and sky scenes that had spatial frequency spectra comparable with outdoor environments (i.e., outdoor scene classrooms). Acceptability of this strategy was evaluated by questionnaires. Outcomes to access the efficacy include cumulative proportion of myopia, change of cycloplegic spherical equivalent refractive error, and axial length. Ten classes, comprising 520 students, were randomly assigned into outdoor scene or tradition classrooms. There was no difference in refractive status between two groups (myopia/emmetropia/hyperopia, 16.3% vs. 49.4% vs. 34.2% in outdoor scene classrooms, 18.3% vs. 49.0% vs. 32.7% in traditional classrooms; P = .83). Compared with the traditional classrooms, 88.9% of teachers and 87.5% of students felt the outdoor scene classrooms enjoyable, 22.2% of teachers and 75.3% of students reported higher concentration, and 77.8% of teachers and 15.2% of students reported no change. In addition, 44.4% of teachers and 76.0% of students reported higher learning efficiency in the outdoor scene classrooms, and 55.6% of teachers and 18.3% of students reported no change. Outdoor scene classrooms are appealing to teachers and students. Outcomes of the study will inform the efficacy of this strategy in Chinese children.

Counterparty Risk Contagion Model of Carbon Quota Based on Asset Price Reduction

Driven by the “double carbon” goal, the sale of financial assets at reduced prices by firms due to carbon emission constraints is bound to aggravate the uncertainty and volatility of carbon trading among firms, and potentially create counterparty risk contagion. In view of this, this paper considers the sensitivity of the transaction of corporate financial assets, the transaction price of carbon quotas, and corporate carbon performance; constructs a network model for the risk contagion of carbon quota counterparties; theoretically discusses the risk formation and infection mechanism of carbon quota counterparties; and calculates and simulates the evolutionary characteristics of the risk contagion of carbon quota counterparties. The main research conclusions are as follows. (1) In the interfirm debt network, the sensitivity to the price of selling the financial asset, the probability of credit risk contagion of carbon quotas among firms, the cumulative proportion of assets sold, and the proportion of rational investors in the financial market exert a decreasing phenomenon on the risk of carbon quota counterparties. In addition, the corporate carbon performance shows a marginal increasing phenomenon. (2) When multiple factors intersect, the proportion of rational investors in the financial market has the greatest influence on the formation of the carbon quota counterparty risk, whereas the effect of corporate carbon performance has the least. Corporate carbon risk awareness has the greatest effect on the risk contagion of carbon quota counterparties, whereas the trading price of the carbon quota has the least influence. In addition, the total score of the interfirm assessment has a great impact on the trend and range of the risk contagion of carbon quota counterparties. (3) Corporate carbon risk awareness and the carbon quota trading price have a marginally decreasing effect on the risk contagion of carbon quota counterparties, and corporate carbon performance and the total score of interfirm assessment have a marginally increasing effect. This study has important theoretical and practical significance for preventing interfirm counterparty risk contagion under the double carbon target.

Seasonal differences in the timing of flight between the invasive winter moth and native Bruce spanworm promotes reproductive isolation.

The European winter moth, Operophtera brumata L. (Lepidoptera: Geometridae), was accidentally introduced to North America on at least 4 separate occasions, where it has been hybridizing with the native Bruce spanworm, O. bruceata Hulst, at rates up to 10% per year. Both species are known to respond to the same sex pheromones and to produce viable offspring, but whether they differ in the seasonal timing of their mating flights is unknown. Therefore, we collected adult male moths weekly along 2 transects in the northeastern United States and genotyped individuals using polymorphic microsatellite markers as males of these 2 species cannot be differentiated morphologically. Along each transect, we then estimated the cumulative proportions (i.e., the number of individuals out of the total collected) of each species on each calendar day. Our results indicate that there are significant differences between the species regarding their seasonal timing of flight, and these allochronic differences likely are acting to promote reproductive isolation between these 2 species. Lastly, our results suggest that the later flight observed by winter moth compared to Bruce spanworm may be limiting its inland spread in the northeastern United States because of increased exposure to extreme winter events.

Assessing Patterns in Childhood Obesity Patient Education: A Quality of Online Health Information and Google Trends Analysis.

Background: Childhood obesity (CO) is rapidly increasing in prevalence and developing into a health crisis of developed nations. The condition is associated with increased risk of developing various comorbidities later in life. Current treatment algorithms primarily target family education. Thus, this study aims to understand the quality of information online regarding CO and common comorbidities, determine the readability of online information, and report patterns in public interest over time using Google Trends. Methods: Four validated quality of information tools and 6 readability tools were implemented across 36 websites derived from 4 Google searches. Pearson's correlation coefficient was used to determine the associations between Google Trends' relative search volumes (RSVs) and biennial BMI-based cumulative proportion of CO. Results: Results showed variable information quality among the websites as scores ranged from "fair" to "very poor." Using six readability formulas, no website scored at or below the sixth grade reading level recommended by the American Medical Association. Google Trends' RSVs for the term "Childhood Obesity" were repeatedly increased in the months that fall in the US academic school year (October-November and February-May), and decreased within months in the US vacation periods (December-January and June-September). Search volumes were also negatively correlated with CO and pediatric type 2 diabetes prevalence. Conclusions: In summary, while Google Trends analysis showed that schools may play a role in increasing interest and awareness online, quality of information and readability analysis displayed that the information and its accessibility are far too variable to be reliable.

Temporal trends in mortality in patients with rheumatoid arthritis: a Danish population-based matched cohort study.

To investigate the 5-year all-cause mortality in patients with RA compared with the general population. This was a nationwide population-based matched cohort study. RA patients diagnosed between 1996 and the end of 2015 were identified using administrative heath registries and followed until the end of 2020 allowing 5 years of follow-up. Patients with incident RA were matched 1:5 on year of birth and sex with non-RA individuals from the Danish general population. Time-to-event analyses were performed using the pseudo-observation approach. Compared with matched controls in 1996-2000, the risk difference for RA patients ranged from 3.5% (95% CI 2.7%, 4.4%) in 1996-2000 to -1.6% (95% CI -2.3%, -1.0%) in 2011-15, and the relative risk from 1.3 (95% CI 1.2, 1.4) in 1996-2000 to 0.9 (95% CI 0.8, 0.9) in 2011-15. The age-adjusted 5-year cumulative incidence proportion of death for a 60-year-old RA patient decreased from 8.1% (95% CI 7.3%, 8.9%) when diagnosed in 1996-2000 to 2.9% (95% CI 2.3%, 3.5%) in 2011-15, and for matched controls from 4.6% (95% CI 4.2%, 4.9%) to 2.1% (95% CI 1.9%, 2.4%). Excess mortality persisted in women with RA throughout the study period, while the mortality risk for men with RA in 2011-15 was similar to their matched controls. Enhanced improvement in mortality was found in RA patients compared with matched controls, but for sex-specific differences excess mortality was only persistent in women with RA.

Comparison of the Effectiveness and Safety of Mycophenolate Mofetil and Cyclophosphamide in Lupus Nephritis: Evidence from a Real-World Study.

Both mycophenolate mofetil (MMF) and intravenous cyclophosphamide (CYC) have been recommended in the induction therapy of lupus nephritis (LN) for years; nevertheless, their effectiveness and safety in a real-world setting are extremely lacking. Therefore, we decided to conduct this real-world study. A total of 195 Chinese patients with LN who were initially treated with MMF (n = 98), or intravenous CYC (n = 97) as induction therapy were enrolled. All of the patients were followed up to 12months. Complete renal remission (CRR) was defined as 24-h urinary protein (24h-UTP) < 0.5g, and partial renal remission (PRR) was defined as ≥ 50% reduction in 24h-UTP to the subnephrotic level, however > 0.5g, both with a change of serum creatinine (SCr) within 10% from baseline. The proportions of CRR, PRR, and total renal remission (TRR), as well as adverse events, were compared by Chi-square test and Kaplan-Meier analysis (log-rank test). Inverse probability of treatment weighting (IPTW) was used for propensity score matching and multivariable logistic regression analyses were employed. The cumulative proportion of TRR in 6months (79.4 vs. 63.8%, p = 0.026) and CRR in 12months (72.8 vs. 57.6%, p = 0.049) in MMF group were significantly higher than CYC group, and the above conclusions were further confirmed by IPTW. The proportions of PRR, CRR, and TRR at other time points were equivalent between two groups. Further subgroup analysis in 111 patients with biopsy-proven III-V LN also showed a significantly higher proportion of TRR at 6months in the MMF group than in the CYC group (78.3 vs. 56.9%, p = 0.026). In the Kaplan-Meier analysis and after IPTW, the MMF group showed better TRR and CRR responses than CYC group in 12months. Multivariable logistic regression analyses revealed that MMF use was the only predictor of CRR (HR 2.12, 95% CI 1.90-4.09, p = 0.026), while low complement level was also a predictor, albeit risk was reduced (HR 0.38, 95% CI 0.17-0.86, p = 0.019). Moreover, compared to the CYC group, MMF group patients were more likely to have significantly lower SCr (μmol/l) [72.5 (62.5, 86.5) vs. 79.0 (71.1, 97.5), p = 0.001] and daily dose of prednisone (mg/day) (15.7 ± 5.2 vs. 18.6 ± 11.3, p = 0.022) at 6months; lower 24h-UTP (g) [0.1 (0.1, 0.3) vs. 0.2 (0.1, 0.9), p = 0.005] and daily dose of prednisone (mg/day) (9.6 ± 3.3 vs. 11.2 ± 5.5, p = 0.023) at 12months. Infection was the most common adverse event. Pneumonia and gastrointestinal discomfort were more frequently observed in the CYC group. Real-world data are a key component of the evidence supporting the effectiveness of drugs and are of interest to all stakeholders. Our comparative study demonstrated the effectiveness of MMF in LN induction therapy was at least equivalent to intravenous CYC, with superior tolerance.

A mechanistic insight into the potential anti-cancerous property of Nigella sativa on breast cancer through micro-RNA regulation: An in vitro & in vivo study

Cancer continues to threat mortal alongside scientific community with burgeoning grasp. Most efforts directed to tame Cancer such as radiotherapy or chemotherapy, all came at a cost of severe side effects. The plant derived bioactive compounds on the other hand carries an inevitable advantage of being safer, bioavailable & less toxic compared to contemporary chemotherapeutics. Our strategic approach employed solvent extraction of Black Seed Oil (BSO) to highlight the orchestrated use of its oil soluble phytochemicals – Thymoquinone, Carvacrol & Trans-Anethole when used in cohort. These anti-cancer agents in unbelievably modest amounts present in BSO shows better potential to delineate migratory properties in breast cancer cells as compared to when treated individually. BSO was also observed to have apoptotic calibre when investigated in MDA-MB-231 and MCF-7 cell lines. We performed chemical characterization of the individual phytochemical as well as the oil in-whole to demonstrate the bioactive oil-soluble entities present in whole extract. BSO was observed to have significant anti-cancerous properties in cumulative proportion that is reportedly higher than the individual three components. Besides, this study also reports micro-RNA regulation on BSO administration, thereby playing a pivotal role in breast cancer alleviation. Thus, synergistic action of the integrants serves better combat force against breast cancer in the form of whole extract, hence aiming at a more lucrative paradigm while significantly regulating microRNAs associated with breast cancer migration and apoptosis.

Proportion of Non-severe Ischemic Stroke Patients Returning to Work

OBJECTIVE To explore the proportion of non-severe ischemic stroke patients returning to work (RTW) and to examine the association of demographic, clinical, and evaluative information with RTW outcomes. METHODS This observational study included non-severe ischemic stroke patients at the stroke ward, Srinagarind Hospital, Khon Kaen, Thailand between September 2021 and November 2022. Patients included were over 18-year-old, had NIHSS scores not exceeding 14, were currently employed and wanted to RTW. Patients were assessed at the discharged time, 2-week-follow-up, and 3-month-follow-up. Bivariate analysis was conducted using either Chi-square or Fisher’s exact test. RESULTS Sixty-four patients were recruited of whom 4 dropped out, leaving a total of 60. The cumulative proportions of successful RTW patients at the discharged time, 2-week-follow-up, 1-month-follow-up, and 3-month-follow-up were 26.7%, 51.7%, 70%, and 76.7% (95%CI 16.8-38.8, 39.2-64.0, 57.7-80.5, 64.9-86.0), respectively. Most patients could RTW in the first month, then the number plateaued at 3 months. More successful RTW patients included those in cognitive demand occupations, evaluated as normal to minor neurological severity, motor power graded 4-5 at discharge, passed MoCA or MMSE test, and who were rated as independent by either the mRS or the BI. Bivariate analysis revealed statistically significant association between RTW proportion and occupation type, neurological severity, motor power, and ADL disability. CONCLUSIONS Most non-severe ischemic stroke patients could RTW within 3 months after discharge. Occupational type, neurological severi-ty, motor power, and ADL associated with the proportion of RTW (3-month-follow-up). RTW evaluation of non-severe stroke patients should be assessed at short intervals for 3 months after discharge. KEYWORDS return to work, ischemic stroke, occupation, cognition, activities of daily living