bluuebunny/crossref_metadata_2025 huggingface dataset:
Socioeconomic disparities in kidney transplant access for patients with end-stage kidney disease within the All of Us Research Program
Authors: Wang Jiayuan , Cho Kellie C , Tantisattamo Ekamol
Published: September 2024

Objectives

Disparity in kidney transplant access has been demonstrated by a disproportionately low rate of kidney transplantation in socioeconomically disadvantaged patients. However, the information is not from national representative populations with end-stage kidney disease (ESKD). We aim to examine whether socioeconomic disparity for kidney transplant access exists by utilizing data from the All of Us Research Program.

Materials and Methods

We analyzed data of adult ESKD patients using the All of Us Researcher Workbench. The association of socioeconomic data including types of health insurance, levels of education, and household incomes with kidney transplant access was evaluated by multivariable logistic regression analysis adjusted by baseline demographic, medical comorbidities, and behavioral information.

Results

Among 4078 adults with ESKD, mean diagnosis age was 54 and 51.64% were male. The majority had Medicare (39.6%), were non-graduate college (75.79%), and earned $10 000-24 999 annual income (20.16%). After adjusting for potential confounders, insurance status emerged as a significant predictor of kidney transplant access. Individuals covered by Medicaid (adjusted odds ratio [AOR] 0.45; 95% confidence interval [CI], 0.35-0.58; P-value < .001) or uninsured (AOR 0.21; 95% CI, 0.12-0.37; P-value < .001) exhibited lower odds of transplantation compared to those with private insurance.

Discussion/Conclusion

Our findings reveal the influence of insurance status and socioeconomic factors on access to kidney transplantation among ESKD patients. Addressing these disparities through expanded insurance coverage and improved healthcare access is vital for promoting equitable treatment and enhancing health outcomes in vulnerable populations.
Reliable generation of privacy-preserving synthetic electronic health record time series via diffusion models
Authors: Tian Muhang , Chen Bernie , Guo Allan , Jiang Shiyi , Zhang Anru R
Published: September 2024

Objective

Electronic health records (EHRs) are rich sources of patient-level data, offering valuable resources for medical data analysis. However, privacy concerns often restrict access to EHRs, hindering downstream analysis. Current EHR deidentification methods are flawed and can lead to potential privacy leakage. Additionally, existing publicly available EHR databases are limited, preventing the advancement of medical research using EHR. This study aims to overcome these challenges by generating realistic and privacy-preserving synthetic EHRs time series efficiently.

Materials and Methods

We introduce a new method for generating diverse and realistic synthetic EHR time series data using denoizing diffusion probabilistic models. We conducted experiments on 6 databases: Medical Information Mart for Intensive Care III and IV, the eICU Collaborative Research Database (eICU), and non-EHR datasets on Stocks and Energy. We compared our proposed method with 8 existing methods.

Results

Our results demonstrate that our approach significantly outperforms all existing methods in terms of data fidelity while requiring less training effort. Additionally, data generated by our method yield a lower discriminative accuracy compared to other baseline methods, indicating the proposed method can generate data with less privacy risk.

Discussion

The proposed model utilizes a mixed diffusion process to generate realistic synthetic EHR samples that protect patient privacy. This method could be useful in tackling data availability issues in the field of healthcare by reducing barrier to EHR access and supporting research in machine learning for health.

Conclusion

The proposed diffusion model-based method can reliably and efficiently generate synthetic EHR time series, which facilitates the downstream medical data analysis. Our numerical results show the superiority of the proposed method over all other existing methods.
Leveraging a global, federated, real-world data network to optimize investigator-initiated pediatric clinical trials: the TriNetX Pediatric Collaboratory Network
Authors: Wilson Jurran L , Betensky Marisol , Udassi Sharda , Ellison Pavithra R , Lilienthal Richard , Stahl Lindsay R , Palchuk Matvey B , Zia Ayesha , Town Deborah A , Kimble Wes , Goldenberg Neil A , Morizono Hiroki
Published: September 2024

Objective

Clinical research networks facilitate collaborative research, but data sharing remains a common barrier.

Materials and Methods

The TriNetX platform provides real-time access to electronic health record (EHR)-derived, anonymized data from 173 healthcare organizations (HCOs) and tools for queries and analysis. In 2022, 4 pediatric HCOs worked with TriNetX leadership to found the Pediatric Collaboratory Network (PCN), facilitated via a multi-institutional data-use agreement (DUA). The DUA enables collaborative study design and execution, with institutional review board-approved transfer of complete datasets for further analyses on a per-protocol basis.

Results and Discussion

Of the 41.2 million children with TriNetX records, the PCN represents nearly 10%. The PCN assisted several early-career investigators to bring study concepts from conception to an international scientific meeting presentation and journal submission.

Conclusion

The PCN facilitates EHR vendor-agnostic multicenter pediatric research on the global TriNetX platform. Continued growth of the PCN will advance knowledge in pediatric health.
Longitudinal changes in BMD in adults with cystic fibrosis
Authors: Jad Reem , Ma Xiayi , Stanojevic Sanja , Illango Abarnaa , Tullis Elizabeth , Gilmour Julie , Goss Christopher H , Strug Lisa J , Stephenson Anne L
Published: September 2024

Improved survival in people with cystic fibrosis (pwCF) presents new complexities of care, including CF-related bone disease, a common complication in older pwCF. The trajectory of bone loss with age in this population remains unclear. The objective of this study was to estimate the average rate of change in BMD in adults with CF. This retrospective study included adults with CF, aged 25-48 yr, followed between January 2000 and December 2021. Subjects with at least one DXA scan were included. Scans obtained posttransplantation, after the initiation of bisphosphonates or cystic fibrosis transmembrane conductance regulator modulator therapy was excluded. The primary outcome was BMD (g/cm2) at the LS and FN. A linear mixed-effects model with both random intercept and random slope terms was used to estimate the average annual change in BMD. A total of 1502 DXA scans in 500 adults (average age 28.4 y) were included. There was a statistically significant annual decline in BMD of −0.008 gm/cm2/yr (95% CI, −0.009 to −0.007) at the FN and −0.006 gm/cm2/yr (95% CI, −0.007 to −0.004) at the LS. Relative to BMD at age 25, there was a 18.8% decline at the FN by age 48 yr and a 11% decline at the LS. Pancreatic insufficient subjects had a faster rate of decline in BMD compared with pancreatic sufficient subjects. After adjusting for markers of disease severity, the annual rate of decline remained significant. Individuals with CF experience bone loss at an age when it is not anticipated, thereby entering early adulthood, where further bone loss is inevitable especially with the decrease in estrogen during menopause, with suboptimal BMD. As the CF population ages, it will become very important to consider interventions to maximize bone health.
Integrated viral and immune monitoring in a prospective COVID-19 cohort from India
Authors: Agrawal Sachee , Kasarpalkar Nandini , Ghosh Sayantani , Paradkar Gaurav , Daund Vaibhav , Bhowmick Shilpa , Chitalia Vidushi , Rao Priyanka , Sankpal Ashwini , Kalsurkar Varsha , Shah Karan , Khan Sameen , Patil Ashwini , Jagtap Dhanashree , Khandkar Omkar , Kaneria Mala , Mahale Smita D , Sachdeva Geetanjali , Bhor Vikrant M , Shastri Jayanthi , Patel Vainav
Published: September 2024

In this study, we report on longitudinal kinetics of cellular immune subsets following SARS-CoV-2 infection in a cohort of hospitalized individuals and evaluate the interplay of these profiles with infecting viral variants, humoral immunity including neutralizing responses, vaccination history, and clinical outcomes. A cohort of 121 SARS-CoV-2–infected individuals exhibiting varying disease states were prospectively evaluated for lymphopenic profiles, antiviral humoral responses and infecting viral variants for a period of up to 90 d spanning the period of February 2021 to January 2022 (second and third waves of infection). A total of 51 participants received at least 1 vaccine dose of indigenous vaccines (Covishield or Covaxin) prior to recruitment. When stratified in terms of mortality, B and natural killer cells, in contrast to the T cell compartment, did not recover from nadir levels in nonsurvivors who were largely unvaccinated. No discriminatory signature was identified for nonsurvivors in terms of anti-nucleocapsid or anti-S1-RBD IgG chemiluminescent immunoassay profiles including GenScript S1-RBD assays. Evaluation of sVCAM and sMAdCAM revealed opposing dynamics that correlated with disease severity and convalescence respectively. Viral variant analysis revealed Delta and Omicron variants to comprise the majority of the infections, which reflected national transmission kinetics during the period of recruitment. Our results demonstrate the importance of monitoring circulating biomarkers for convalescence as well as mortality in COVID-19 progression. Delta variants of SARS-CoV-2 clearly demonstrated increased pathogenicity and warrants sustained viral surveillance for re-emergence of these strains. Our findings with respect to vaccination advocate for continued vaccine development and administration of COVID-19 vaccines.
A comprehensive analysis of metastatic disease following surgery for clinically localized cutaneous melanoma
Authors: Boutros Christina S , Kakish Hanna , Pawar Omkar S , Loftus Alexander W , Ammori John B , Bordeaux Jeremy , Mangla Ankit , Sheng Iris , Schwartz Gary , Rothermel Luke D , Hoehn Richard S
Published: September 2024

Background

The National Comprehensive Cancer Network considers “baseline staging” (whole body computed tomography or positron emission tomography scans with or without brain magnetic resonance imaging scans) for all patients with asymptomatic melanoma who had a positive sentinel lymph node biopsy result. The true yield of these workups is unknown.

Methods

We created cohorts of adult patients with malignant melanoma using the National Cancer Database (2012-2020) to mimic 3 common scenarios: 1) clinically node-negative disease, with positive sentinel lymph node biopsy results; 2) clinically node-negative disease, with negative sentinel lymph node biopsy results; and 3) clinically node-positive disease, with confirmed lymph node metastases. Multivariable regression, supervised decision trees, and nomograms were constructed to assess the risk of metastases based on key features.

Results

In total, 10 371 patients were in scenario 1, 55 172 were in scenario 2, and 4012 were in scenario 3. The proportion of patients with any metastatic disease (brain metastases) were as follows: 1.4% (0.3%) in scenario 1, 0.3% (<0.1%) in scenario 2, and 11.6% (1.6%) in scenario 3. On multivariable regression, Breslow depth greater than 4, ulceration, and lymphovascular invasion were associated with greater risk of metastatic disease. A supervised decision tree for patients in scenarios 1 and 2 found that the only groups with more than 2% risk of metastases were groups with T4 tumors or T2/T3 tumors with ulceration and lymphovascular invasion. Most groups had a negligible risk (<0.1%) of brain metastases.

Conclusion

This study is the first large analysis to guide the use of imaging for cutaneous melanoma. Among patients with clinically node negative disease, metastatic disease is uncommon, and brain metastases are exceedingly rare. Further investigation could promote a tailored approach to metastatic workups guided by individual risk factors.
kpop: a kernel balancing approach for reducing specification assumptions in survey weighting
Authors: Hartman Erin , Hazlett Chad , Sterbenz Ciara
Published: September 2024

With the precipitous decline in response rates, researchers and pollsters have been left with highly nonrepresentative samples, relying on constructed weights to make these samples representative of the desired target population. Though practitioners employ valuable expert knowledge to choose what variables X must be adjusted for, they rarely defend particular functional forms relating these variables to the response process or the outcome. Unfortunately, commonly used calibration weights—which make the weighted mean of X in the sample equal that of the population—only ensure correct adjustment when the portion of the outcome and the response process left unexplained by linear functions of X are independent. To alleviate this functional form dependency, we describe kernel balancing for population weighting (kpop). This approach replaces the design matrix X with a kernel matrix, K encoding high-order information about X. Weights are then found to make the weighted average row of K among sampled units approximately equal to that of the target population. This produces good calibration on a wide range of smooth functions of X, without relying on the user to decide which X or what functions of them to include. We describe the method and illustrate it by application to polling data from the 2016 US presidential election.
Impacts of innovation school system in Korea: a latent space item response model with Neyman–Scott point process
Authors: Yi Seorim , Kim Minkyu , Park Jaewoo , Jeon Minjeong , Jin Ick Hoon
Published: September 2024

South Korea’s educational system has faced criticism for its lack of focus on critical thinking and creativity, resulting in high levels of stress and anxiety among students. As part of the government’s effort to improve the educational system, the innovation school system was introduced in 2009, which aims to develop students’ creativity as well as their non-cognitive skills. To better understand the differences between innovation and regular school systems in South Korea, we propose a novel method that combines the latent space item response model with the Neyman–Scott point process model. Our method accounts for the heterogeneity of items and students, captures relationships between respondents and items, and identifies item and student clusters that can provide a comprehensive understanding of students’ behaviours/perceptions on non-cognitive outcomes. Our analysis reveals that students in the innovation school system show a higher sense of citizenship, while those in the regular school system tend to associate confidence in appearance with social ability. A comparison with exploratory item factor analysis highlights our method’s advantages in terms of uncertainty quantification of the clustering process and more detailed and nuanced clustering results. Our method is made available to an existing R package, lsirm12pl.
Mode-wise principal subspace pursuit and matrix spiked covariance model
Authors: Tang Runshi , Yuan Ming , Zhang Anru R
Published: September 2024

This paper introduces a novel framework called Mode-wise Principal Subspace Pursuit (MOP-UP) to extract hidden variations in both the row and column dimensions for matrix data. To enhance the understanding of the framework, we introduce a class of matrix-variate spiked covariance models that serve as inspiration for the development of the MOP-UP algorithm. The MOP-UP algorithm consists of two steps: Average Subspace Capture (ASC) and Alternating Projection. These steps are specifically designed to capture the row-wise and column-wise dimension-reduced subspaces which contain the most informative features of the data. ASC utilizes a novel average projection operator as initialization and achieves exact recovery in the noiseless setting. We analyse the convergence and non-asymptotic error bounds of MOP-UP, introducing a blockwise matrix eigenvalue perturbation bound that proves the desired bound, where classic perturbation bounds fail. The effectiveness and practical merits of the proposed framework are demonstrated through experiments on both simulated and real datasets. Lastly, we discuss generalizations of our approach to higher-order data.
It’s not all that bad: associations among pain characteristics and sexual well-being in people living with chronic pain
Authors: Santos-Iglesias Pablo , Estey Justine L , Crump Lyndsay , LaChapelle Diane L , Byers E Sandra
Published: September 2024

Background

Individuals experiencing chronic pain often report adverse effects on their sexual functioning. However, other important aspects of sexual well-being (SWB), such as sexual distress and sexual self-esteem, have received little attention. This is an important omission because a SWB involves more than just good sexual function. Similarly, past research has not examined how chronic pain characteristics affect the different aspects of SWB.

Aim

The goal of this cross-sectional study was to examine the SWB of individuals living with chronic pain and to examine the extent to which SWB is associated with different chronic pain characteristics.

Methods

A total of 310 individuals (28.1% men, 70.6% women, 1.3% transgender men) with ages between 21 and 50 (M = 31.96, SD = 6.13) who were in a romantic relationship and with self-reported chronic pain for three months or longer completed an online survey.

Outcomes

The following indicators of SWB were included in the study: frequency of genital sexual activity, sexual satisfaction, sexual self-esteem, sexual desire, sexual function, genital pain, and sexual distress.

Results

The results show that most individuals with chronic pain maintain an active and satisfying sexual life and feel positive about themselves as a sexual partner. Slightly more than a fourth reported experiencing at least one sexual functioning difficulty and almost three-fourths of them found those difficulties sexually distressing. A first canonical correlation showed that more negative pain characteristics were associated with poorer SWB. The second canonical correlation showed that greater perceived partner support can offset the negative relationship between pain and some aspects of SWB.

Clinical implications

These findings show that individuals living with chronic pain can experience positive SWB. Furthermore, the buffering effect of partner support suggests it is important to involve romantic partners in interventions aimed at improving the SWB of people living with chronic pain.

Strengths and limitations

The study examined a large number of indicators of SWB using a sample of individuals with different types of chronic pain. Limitations include potential self-selection bias and a sample that was predominantly white and highly educated.

Conclusions

The results paint a more positive picture of the SWB of individuals living with pain and show that individuals living with chronic pain can experience positive SWB. These findings can help for researchers, educators, and clinicians about how to conceptualize, understand, and improve the SWB of individuals living with chronic pain.
Differential warming at crown scale impacts walnut primary growth onset and secondary growth rate
Authors: Dusart Nicolas , Moulia Bruno , Saudreau Marc , Serre Christophe , Charrier Guillaume , Hartmann Félix P
Published: September 2024

Trees are exposed to significant spatio-temporal thermal variations, which can induce intra-crown discrepancies in the onset and dynamics of primary and secondary growth. In recent decades, an increase in late winter and early spring temperatures has been observed, potentially accelerating bud break, cambial activation, and their coordination. Intra-crown temperature heterogeneities could lead to asymmetric tree shapes unless there is a compensatory mechanism at the crown level. An original warming experiment was conducted on young Juglans regia trees in a greenhouse. The average temperature difference during the day between warmed and control parts from February to August was 4 °C. The warming treatment advanced the date of budbreak significantly, by up to 14 d. Warming did not alter secondary growth resumption but increased growth rates, leading to higher xylem cell production (by 2-fold) and to an increase in radial increment (+80% compared with control). Meristem resumptions were asynchronous without coordination in response to temperature. Buds on warmed branches began to swell 2 weeks prior to cambial division, which was 1 week earlier than on control branches. A difference in carbon and water remobilization at the end of bud ecodormancy was noted under warming. Overall, our results argue for a lack of compensatory mechanisms at the crown scale, which may lead to significant changes in tree architecture in response to intra-crown temperature heterogeneities.
‘Credulous or the naïve?’ The Irish Department of Health’s response to commercial surrogacy
Authors: O’Connell Claire
Published: September 2024

This article explores the prohibition of commercial surrogacy as currently contained within the Health (Assisted Human Reproduction) Act 2024. The 2024 Act regulates surrogacy for the first time in Irish law and creates a framework for the recognition of intending parentage arising from surrogacy agreements. This article explores the safeguards for surrogates contained within the 2024 Act against the arguments generally cited by the Department of Health against commercial surrogacy—that of commodifying children and exploitation of women. It considers Irish case law on commercial surrogacy and that of the European Court of Human Rights. It also includes passages from the O’Connell Study which was conducted within the author’s PhD thesis. The article concludes that the refusal to recognize the legal parent–child relationship based on the commercial nature of the surrogacy agreement is a violation of the child’s right to respect for private life under Article 8 of the European Convention on Human Rights (the ECHR). It also finds that the Irish Courts have found no public policy reason strong enough to justify the refusal to recognize a foreign adoption order which followed a commercial surrogacy agreement. Primarily it argues that a commercial surrogacy agreement can be ethical; but requires sufficient safeguards for those parties involved.
Molecular characterization of metastatic penile squamous cell carcinoma in developing countries and its impact on clinical outcomes: LACOG 2018 translational study
Authors: Monteiro Fernando Sabino Marques , Alencar Junior Antonio Machado , da Trindade Karine Martins , Rebelatto Taiane Francieli , Maluf Fernando C , Gazzola Antonia A , Barrios Pablo M , Bellmunt Joaquim , de Jesus Rafaela Gomes , Silva Gyl Eanes Barros , Teixeira Junior Antonio Augusto Lima , Spiess Philippe E , Fay Andre P
Published: September 2024

Background

Penile squamous cell carcinoma (PSCC) is a rare malignancy. However, in developing countries the incidence rate is higher. The understanding of molecular alterations is essential for evaluating possible targets for more effective systemic therapies.

Methods

We retrospectively collected clinical data of metastatic PSCC (mPSCC) patients who had received at least one prior systemic treatment from 3 Brazilian hospitals. Tumor samples were evaluated using the next-generation sequencing (NGS) Foundation One DX and immunohistochemistry (IHC). The objective was to identify and describe somatic genomic alterations known to be functional or pathogenic and their association with survival outcomes.

Results

Twenty-three patients were identified, 22 and 18 patients had tumor samples analyzed by IHC and NGS, respectively. PD-L1 expression (CPS ≥ 1%) was positive in 14 patients (63.6%). Regarding the genomic alterations, 16 patients (88.9%) had some clinically relevant genomic alterations. TP53, TERT, CDKN2A, PIK3CA, NOTCH1, and CDKN2B loss were identified in 66.7%, 50%, 50%, 33.3%, 27.8%, and 22.2% of the patients, respectively. No MSI or TMB high (≥10 mutations/MB) cases were identified. NOTCH1 mutation was identified only in HPV-negative patients and it was associated with worse OS (yes: 5.5 vs no: 12.8 months, P = .049) and progression-free survival (yes: 5.5 vs no: 11.7 months, P = .032).

Conclusion

This study demonstrated that molecular alterations in mPSCC from developing countries are similar to those from developed countries. Predictive biomarkers for immunotherapy response such as TMB high or MSI were not identified. Specific gene mutations may identify patients with worse prognoses and open new avenues for therapeutic development.
The system building perspective for building sustainable system configurations using the German energy transition as an example
Authors: Olbrich Sarah , Bauknecht Dierk
Published: September 2024

An increasing number of countries employ net-zero decarbonization targets in their climate policies, which requires decarbonizing socio-technical systems like the energy system by mid-century. While there is a high level of agreement about net-zero targets, there remains great uncertainty as to how to meet them. At the same time, the challenges of building a new system that fulfils systemic targets such as net-zero are insufficiently reflected on in the sustainability transitions literature. With the help of a literature review building on theories of socio-technical transitions, this paper introduces system building dimensions that account for the difficulties of net-zero transitions. We identify four such dimensions: (1) competing potential system configurations with different sustainability implications; (2) a broad range of complementary system elements needed; (3) lock-ins and path dependencies in the system building process; and (4) the politics of system building. We offer the German energy transition as an empirical case study to illustrate the relevance of these system building dimensions.
An investigation of the relationship between tropical monsoon precipitation changes and stratospheric sulfate aerosol optical depth
Authors: Xavier Anu , Bala Govindasamy , Roose Shinto , KH Usha
Published: September 2024

Stratospheric aerosol geoengineering (SAG) is one of the several solar geoengineering options that have been proposed to counteract climate change. In the case of SAG, reflective aerosols injected into the stratosphere would reflect more sunlight and cool the planet. When assessing the potential efficacy and risks of SAG, the sensitivity of tropical monsoon precipitation changes should be also considered. Using a climate model, we perform several stylized simulations with different meridional distributions and amounts of volcanic sulfate aerosols in the stratosphere. Because tropical monsoon precipitation responds to global mean and interhemispheric difference in radiative forcing or temperature, we quantify the sensitivity of tropical monsoon precipitation to SAG in terms of two parameters: global mean aerosol optical depth (GMAOD) and interhemispheric AOD difference (IHAODD). For instance, we find that the simulated northern hemisphere monsoon precipitation has a sensitivity of −1.33 ± 0.95% per 0.1 increase in GMAOD and −7.62 ± 0.27% per 0.1 increase in IHAODD. Our estimated precipitation changes in terms of the two sensitivity parameters for the global mean precipitation and for the indices of tropical, northern hemisphere, southern hemisphere and Indian summer monsoon precipitation are in good agreement with the model simulated precipitation changes. Similar sensitivity estimates are also made for unit changes in global mean and interhemispheric differences in effective radiative forcing and surface temperature. Our study based on planetary energetics provides a simpler framework for understanding the tropical monsoon precipitation response to external forcing agents.
Diurnal.plant.tools in 2024: Expanding to Marchantia polymorpha and Four Angiosperms
Authors: Tan Qiao Wen , Tan Emmanuel , Mutwil Marek
Published: September 2024

Diurnal gene expression is a pervasive phenomenon occurring across all kingdoms of life, orchestrating adaptive responses to daily environmental fluctuations and thus enhancing organismal fitness. Our understanding of the plant circadian clock is primarily derived from studies in Arabidopsis, and direct comparisons are difficult due to differences in gene family sizes. To this end, the identification of functional orthologs based on diurnal and tissue expression is necessary. The diurnal.plant.tools database constitutes a repository of gene expression profiles from 17 members of the Archaeplastida lineage, with built-in tools facilitating cross-species comparisons. In this database update, we expand the dataset with diurnal gene expression from four agriculturally significant crop species and Marchantia, a plant of evolutionary significance. Notably, the inclusion of diurnal gene expression data for Marchantia enables researchers to glean insights into the evolutionary trajectories of the circadian clock and other biological processes spanning from algae to angiosperms. Moreover, integrating diurnal gene expression data with datasets from related gene co-expression databases, such as CoNekt-Plants and CoNekt-Stress, which contain gene expression data for tissue and perturbation experiments, provides a comprehensive overview of gene functions across diverse biological contexts. This expanded database serves as a valuable resource for elucidating the intricacies of diurnal gene regulation and its evolutionary underpinnings in plant biology.
N6-methyladenosine transcriptome-wide profiles of maize kernel development
Authors: Wu Jia Wen , Zheng Guang Ming , Zhang Lin , Zhao Ya Jie , Yan Ru Yu , Ren Ru Chang , Wei Yi Ming , Li Kunpeng , Zhang Xian Sheng , Zhao Xiang Yu
Published: September 2024

Maize (Zea mays L.) kernel development is a complex and dynamic process involving cell division and differentiation, into a variety of cell types. Epigenetic modifications, including DNA methylation, play a pivotal role in regulating this process. N6-methyladenosine modification is a universal and dynamic posttranscriptional epigenetic modification that is involved in the regulation of plant development. However, the role of N6-methyladenosine in maize kernel development remains unknown. In this study, we have constructed transcriptome-wide profiles for maize kernels at various stages of early development. Utilizing a combination of MeRIP-seq and RNA-seq analyses, we identified a total of 11,170, 10,973, 11,094, 11,990, 12,203, and 10,893 N6-methyladenosine peaks in maize kernels at 0, 2, 4, 6, 8, and 12 days after pollination, respectively. These N6-methyladenosine modifications were primarily deposited at the 3′-UTRs and were associated with the conserved motif-UGUACA. Additionally, we found that conserved N6-methyladenosine modification is involved in the regulation of genes that are ubiquitously expressed during kernel development. Further analysis revealed that N6-methyladenosine peak intensity was negatively correlated with the mRNA abundance of these ubiquitously expressed genes. Meanwhile, we employed phylogenetic analysis to predict potential regulatory proteins involved in maize kernel development and identified several that participate in the regulation of N6-methyladenosine modifications. Collectively, our results suggest the existence of a novel posttranscriptional epigenetic modification mechanism involved in the regulation of maize kernel development, thereby providing a novel perspective for maize molecular breeding.
Type and Distribution of Gross Motor Activity During Physical Therapy in Young Children With Cerebral Palsy
Authors: Prosser Laura A , Paremski Athylia C , Skorup Julie , Alcott Morgan , Pierce Samuel R
Published: September 2024

Objective

Physical therapists routinely deliver and prescribe motor practice to improve function. The ability to select optimal practice regimens is limited by a current lack of detail in the measurement of motor practice. The objective of this study was to quantify the type, amount, and timing of gross motor practice during physical therapist sessions.

Methods

A secondary video coding analysis of physical therapist sessions from the iMOVE clinical trial (NCT02340026) in young children with cerebral palsy (CP) was conducted. The 37 children who completed the treatment phase were included (mean age = 22.1 months). Children could initiate pulling to stand but were unable to walk. Videos of randomly selected therapy sessions were coded for gross motor activity (422 videos total). The 10 gross motor activity codes included lying, sitting, four point, crawling, kneeling, knee walking, standing, walking, transitions between floor postures, and transitions to/from an upright posture. Twenty percent of each video was double coded for reliability. Time per session, number of bouts, and median time per bout were calculated for each gross motor activity and for 2 aggregate measures: movement time and upright time.

Results

Participants spent more than half of therapy time in sitting and standing combined (60.3%). Transitions occurred more frequently than any other motor activity (49.3 total transitions per session). Movement time accounted for 16.3% of therapy time. Upright time accounted for 53.3% of therapy time.

Conclusions

Critical practice time to gain motor skill is not equivalent to chronological time or time spent in therapy. Toddlers with CP spent a small amount of therapy time moving. Future work should explore the relations between motor practice and rehabilitation outcomes.

Impact

Physical therapists are ideally suited to detail the content of motor practice and ultimately to prescribe optimal patterns of motor practice. We report the characteristics of gross motor practice during therapy in children with CP.
Impact of high rheumatoid factor levels on treatment outcomes with certolizumab pegol and adalimumab in patients with rheumatoid arthritis
Authors: Smolen Josef S , Taylor Peter C , Tanaka Yoshiya , Takeuchi Tsutomu , Hashimoto Motomu , Cara Carlos , Lauwerys Bernard , Tilt Nicola , Ufuktepe Baran , Xavier Ricardo M , Balsa Alejandro , Curtis Jeffrey R , Mikuls Ted R , Weinblatt Michael
Published: September 2024

Objectives

To assess the impact of baseline RF level on drug concentrations and efficacy of certolizumab pegol [CZP; TNF inhibitor (TNFi) without a crystallizable fragment (Fc)] and adalimumab (ADA; Fc-containing TNFi) in patients with RA.

Methods

The phase 4 EXXELERATE study (NCT01500278) was a 104-week, randomized, single-blind (double-blind until week 12; investigator-blind thereafter), head-to-head study of CZP vs ADA in patients with RA. In this post hoc analysis, we report drug concentration and efficacy outcomes stratified by baseline RF quartile (≤Q3 or >Q3).

Results

Baseline data by RF quartiles were available for 453 CZP-randomized and 454 ADA-randomized patients (≤Q3: ≤204 IU/ml; >Q3: >204 IU/ml). From week 12, the area under the curve (AUC) of ADA concentration was lower in patients with RF >204 IU/ml vs patients with RF ≤204 IU/ml; the AUC of CZP concentration was similar in patients with RF ≤204 IU/ml and >204 IU/ml. For patients with RF ≤204 IU/ml, disease activity score (DAS28)-CRP was similar between CZP- and ADA-treated patients through week 104. For patients with RF >204 IU/ml, mean DAS28-CRP was lower in CZP- vs ADA-treated patients at week 104. The proportion of patients with RF >204 IU/ml achieving DAS28-CRP low disease activity at week 104 was greater in CZP- vs ADA-treated patients.

Conclusion

CZP was associated with maintained drug concentration and efficacy in patients with RA and high RF and may therefore be a more suitable therapeutic option than TNFis with an Fc fragment in these patients.

Trial registration

Clinicaltrials.gov, http://clinicaltrials.gov, NCT01500278
Evaluating CA-125 and PET/CT for cancer detection in idiopathic inflammatory myopathies
Authors: Wang XingYao , Albayda Jemima , Paik Julie J , Tiniakou Eleni , Adler Brittany , Mammen Andrew L , Christopher-Stine Lisa , Mecoli Christopher A
Published: September 2024

Objective

This study aims to evaluate the diagnostic accuracy of CA-125 and PET/CT in detecting cancer among adult patients with idiopathic inflammatory myopathy (IIM).

Methods

We conducted a retrospective study of a single-centre cohort of adult IIM patients enrolled from 2003 to 2020. Data on CA-125 and PET/CT tests conducted within five years of IIM symptom onset were extracted from electronic medical records. The outcomes assessed included true-positive, false-positive, true-negative and false-negative results.

Results

Among 1432 patients with IIM, 250 CA-125 tests were conducted on 205 patients within the first five years of symptom onset, yielding a false-positive rate of 3.1% and a false-negative rate of 14.3%. Most false-positives were associated with endometriosis or uterine fibroids, but additional medical procedures were often carried out to investigate the false-positive results. For PET/CT, 149 tests were performed on 139 patients, resulting in a false-positive rate of 5.5% and a false-negative rate of 28.6%. Lymphadenopathy and lung nodules were the predominant causes of false-positives, while melanoma, low-stage breast cancer and prostate cancer were the most frequent cancers missed (false-negatives).

Conclusion

False-positive and false-negative results are prevalent in cancer antigen 125 (CA-125) and PET/CT testing for adult patients with newly diagnosed idiopathic inflammatory myopathy. Understanding the causes of these inaccuracies can aid clinicians in making informed decisions during patient care.
Association between interleukin-12 p40 subunit and risk of primary Sjögren’s disease: a Mendelian randomization study
Authors: Zuckerman Benjamin P , Yang Zijing , Warwick Alasdair , Wincup Chris , Russell Mark D , Galloway James B , Zhao Sizheng Steven
Published: September 2024

Objectives

IL-12 signalling was proposed in the immunopathogenesis of primary Sjögren’s disease. The efficacy of therapies targeting this pathway is currently unclear. Herein, we investigated the associations between circulating proteins involved in the IL-12 and IL-23 signalling pathways on primary Sjögren’s disease using Mendelian randomization.

Methods

We selected single nucleotide polymorphisms from protein quantitative trait loci of IL12A, IL12B, IL12Rβ1, IL12Rβ2 and IL23R to examine the association between alterations in their levels and risk of primary Sjögren’s disease. Genetic association data for proteins were taken from studies ranging from 3301 to 54 306 in sample size, and from 3232 cases of primary Sjögren’s disease and 17 481 controls. The Wald ratio or inverse variance weighted methods estimated causal effects. We applied colocalization and pleiotropy-robust methods as sensitivity analyses for confounding.

Results

There was a negative association between genetically predicted IL-12p40 (encoded by IL12B) and primary Sjögren’s disease. In the two independent exposure datasets odds ratio (OR), 0.79 (95% CI 0.68–0.93; P-value = 0.004) and OR 0.86 (95% CI 0.78–0.95; P-value = 0.003) per S.D. decrease in genetically predicted IL-12p40. Neither IL-12Rβ2 nor IL-23R met the threshold P-value after Mendelian randomization analyses (P-value < 0.01) for colocalization assessment. No variants for the IL12A gene met prerequisite thresholds for weak instrument bias.

Conclusion

This study provides genetic evidence that IL-12p40 has a causal role in primary Sjögren’s disease pathogenesis. Our data suggest that decreasing levels of IL-12p40 may be deleterious. We would not suggest selecting this drug target as a therapeutic option.
An fMRI study on alexithymia and affective state recognition in the Reading the Mind in the Eyes Test
Authors: Gosch Sophie , Puhlmann Lara M C , Lauckner Mark E , Förster Katharina , Kanske Philipp , Wiesmann Charlotte Grosse , Preckel Katrin
Published: September 2024

Recognizing others’ affective states is essential for successful social interactions. Alexithymia, characterized by difficulties in identifying and describing one’s own emotions, has been linked to deficits in recognizing emotions and mental states in others. To investigate how neural correlates of affective state recognition are affected by different facets of alexithymia, we conducted a functional magnetic resonance imaging study with 53 healthy participants (aged 19–36 years, 51% female) using the Reading the Mind in the Eyes Test (RMET) and three different measures of alexithymia [Toronto Structured Interview for Alexithymia (TSIA), Toronto Alexithymia Scale (TAS-20), and Bermond–Vorst Alexithymia Questionnaire]. In addition, we examined brain activity during the RMET and replicated previous findings with task-related brain activation in the inferior frontal and temporal gyri, as well as the insula. No association was found between alexithymia and behavioral performance in the RMET, possibly due to the low number of participants with high alexithymia levels. Region of interest based analyses revealed no associations between alexithymia and amygdala or insula activity during the RMET. At the whole-brain level, both a composite alexithymia score and the unique variance of the alexithymia interview (TSIA) were associated with greater activity in visual processing areas during the RMET. This may indicate that affective state recognition performance in alexithymia relies on a higher compensatory activation in visual areas.
Mechanistic insights into Retama raetam’s anti-proliferative and pro-apoptotic effects in A549 lung cancer cells: targeting PI3K/Akt pathway and ROS production
Authors: Alshehri Mohammed Ali , Seyed Mohamed Ali , Panneerselvam Chellasamy , Sayed Samy M , Shukry Mustafa
Published: September 2024

Lung cancer, particularly non-small cell lung cancer (NSCLC), is a leading cause of cancer-related deaths worldwide. This study investigates the molecular mechanisms behind the anti-cancer effects of the tropical desert plant Retama raetam (R. raetam) on the A549 NSCLC cell line. The research examined R. raetam's anti-proliferative effects, cytotoxicity, apoptosis, reactive oxygen species (ROS) generation, mitochondrial membrane potential, and cell morphology in NSCLC A549 and L-132 cells. In addition, the influence of R. raetam on DNA fragmentation, apoptotic signaling, and PI3K/Akt pathways for its anti-cancer mechanism was examined. Our results indicated that R. raetam's effects were dose- and time-dependent to exhibit anti-proliferative effects on A549 cells. R. raetam treatment promoted apoptotic cell death cycle arrest, increased apoptotic cells, depolarized the mitochondrial membrane, and induced morphological alterations in cells and nuclei. It also inhibited A549 cell migration (P < 0.05), colonization, and invasiveness. Moreover, the study demonstrated that R. raetam treatment resulted in the upregulation of Bax expression, downregulation of Bcl-2 expression, and apoptotic fragmented DNA in A549 cells. The top five bioactive compounds derived from R. raetam exhibited molecular interactions that inhibit PIK3CA and AKT1. This inhibition leads to an increased frequency of apoptosis and subsequent death of cancer cells. Additionally, R. raetam extract induced an increase in ROS formation and cytochrome c levels, indicating that its toxic effects on A549 cells involve both ROS-dependent cytotoxicity through the disruption of mitochondrial transmembrane potential ΔΨm and ROS-independent cell cycle arrest through downregulation BCL-2, PARP, E-Cadherin, PI3K, and Akt expressions pathways.
Clinical-radiomics combination model for predicting the short-term efficacy of bipolar transurethral enucleation of the prostate in patients with benign prostatic hyperplasia
Authors: Zhang Tianyou , Mo Zijun , Huang Jiayu , Wang Jun , Tao Yiran , Ye Lei , Zhong Wenwen , Yao Bing , Qu Hu , Ma Bo , Wang Dejuan , Mo Jiahui , Ye Chunwei , Zhu Junying , Qiu Jianguang
Published: September 2024

Background

Bipolar transurethral enucleation of the prostate (B-TUEP) is a well-established surgical treatment for benign prostatic hyperplasia (BPH); however, its efficacy may vary depending on patient characteristics. Magnetic resonance imaging (MRI) with radiomics analysis can offer comprehensive and quantitative information about prostate characteristics that may relate to surgical outcomes. This study aimed to explore the value of MRI and radiomics analysis in predicting the short-term efficacy of B-TUEP for BPH.

Materials and methods

A total of 137 patients with BPH who underwent B-TUEP at 2 institutions were included. Radiological features were measured in the MRIs, and the radiomics score was developed from 1702 radiomics features extracted from the prostate and transitional zone regions of interest. Three prediction models were developed and validated based on clinical-radiological features, radiomic features, and their combinations. The models were evaluated using the area under the receiver operating characteristic curve, calibration curve, and decision curve analysis.

Results

The combination model exhibited the highest area under curve in both the training set (0.838) and the external validation set (0.802), indicating superior predictive performance and robustness. Furthermore, the combination model demonstrated good calibration (p > 0.05) and optimal clinical utility. The combination model indicated that a higher maximum urine flow rate, lower transitional zone index, and higher radiomics score were associated with an increased risk of poor efficacy.

Conclusions

Magnetic resonance imaging with radiomic analysis can offer valuable insights for predicting the short-term efficacy of B-TUEP in patients with BPH. A combination model based on clinical and radiomics features can assist urologists in making more precise clinical decisions.
White-coat effect and masked hypertension in patients with high-normal office blood pressure: results of the Hungarian ABPM Registry
Authors: Nemcsik János , Takács Johanna , Kekk Zsófia , Farsang Csaba , Simon Attila , Páll Dénes , Torzsa Péter , Dolgos Szilveszter , Habony Norbert , Koller Ákos , Pásztor Dorottya , Járai Zoltán
Published: September 2024

Objective:

Blood pressure (BP) lowering therapy in hypertension can markedly reduce the risk of cardiovascular diseases. In case of high-normal office blood pressure (oBP), the initiation of antihypertensive medication is recommended by guidelines in patients with very high cardiovascular risk. The aims of this study were to evaluate the presence of white-coat high-normal BP (WhHNBP) and masked hypertension in high-normal oBP and to explore the prevalence of untreated very high cardiovascular risk patients.

Methods:

Data of the Hungarian Ambulatory Blood Pressure Monitoring (ABPM) Registry between September 2020 and November 2023 were used in our analysis.

Results:

From 38 720 uploaded ABPM curves with clinical data, 4300 individuals were categorized as having high-normal oBP. Among those, 3285 (76.4%) were on antihypertensive treatment. Based on the ABPM recordings, high-normal BP was confirmed in 20.5% (n = 881), while WhHNBP was present in 27.6% (n = 1188) and masked hypertension in 51.9% (n = 2231). Similar results were found in treated and untreated subjects or patients as well. Independent predictors of WhHNBP were age [odds ratio (OR) 1.02 (95% confidence interval, 95% CI: 1.01–1.02), P < 0.001], female sex [OR: 1.59 (1.32–1.92), P < 0.001] and snoring [OR: 0.70 (0.57–0.86), P < 0.001]. Independent predictors of masked hypertension were male sex [OR: 1.31 (1.12–1.54), P < 0.001] and obesity [OR: 1.71 (1.39–2.09), P < 0.001]. Five hundred and two individuals had very high cardiovascular risk with high-normal oBP and only 25 of them were untreated.

Conclusion:

In high-normal oBP, WhHNBP or masked hypertension is present in three out of four individuals. Most of the patients with high-normal oBP and very high cardiovascular risk are already treated with antihypertensive drugs.