bluuebunny/crossref_metadata_2025 huggingface dataset:
Bibliometric analysis for global marine microplastic pollution control from 2013 to 2022
Authors: Lou Xiaoyi , Sui Yifan , Fang Changling , Tang Yunyu , Huang Dongmei , Guo Yaoguang
Published: October 2023

The control of microplastic pollution in the marine environment has become a growing public concern in recent years. To better grasp the trends and development of microplastic pollution control in the marine environment, the published literature in Science Citation Index Expanded (SCIE) database of Web of Science Core Collection from 2013 to 2022, up to a total of 2,357 articles or reviews was analyzed through CiteSpace and VOSviewer tools. The results show an exponential growth in the number of papers related to the control of microplastic pollution in the marine environment, with China, United States, India, and Australia providing the main drivers, while China being the most active country, with Science of the Total Environment, Marine Pollution Bulletin, Environmental Pollution and Chemosphere being the most important sources for publishing relevant research. A relatively complete theoretical framework has been developed for the control of marine microplastic pollution, focusing on the quantification, traceability and collectability of microplastics. However, few papers have focused on policy implications and technological innovations in this area. The research on marine microplastic pollution control has transitioned from traceability and hazard analysis of microplastics to the impact of economic activities and synthetic fibre on microplastic pollution. Microplastics in wastewater discharged from municipal wastewater treatment plants, human consumption, man-made fibers and synthetic polymers have become the frontier of research. The present study is of significance for better understanding and supporting further research on the control of microplastic pollution in the marine environment.
Unlocking the link between company attributes and sustainability accounting in shanghai: firm traits driving corporate transparency and stakeholder responsiveness
Authors: Wang Litao
Published: October 2023

Sustainability accounting is crucial for corporate transparency and responsibility, but its relationship with firm characteristics in Shanghai, China’s financial center, remains poorly understood. This study uses a descriptive-analytical methodology to examine the impact of firm size, industry type, and profitability on sustainability accounting practices. A systematic literature review and meta-analysis of 43 studies provide insights into the extent and drivers of sustainability reporting. The findings reveal a positive association between firm size (r = 0.389) and profitability (r = 0.327) with sustainability reporting. Larger, more profitable firms, including state-owned enterprises, exhibit extensive sustainability accounting practices. However, the effect of industry type is inconclusive (r = 0.061), indicating a contingent relationship dependent on firm-specific contexts. The study suggests implementing regulations mandating minimum sustainability disclosure for large and profitable enterprises. Capacity-building initiatives for small private firms and the adoption of integrated reporting policies can enhance transparency. These outcomes contribute contemporary insights into corporate sustainability accounting in China’s evolving landscape. The implications extend to policy development and collaborative efforts to expand sustainability measurement and disclosure in Shanghai. Tailoring regulatory initiatives to firm profiles, such as size and profitability, enhances sustainability accounting practices. Targeted capacity-building programs, assurance mandates, and integrated reporting regulations improve the quality and usefulness of sustainability accounting information. Collaboration with the investor community is crucial for mainstreaming sustainability measurement and disclosure. This study deepens the understanding of sustainability accounting practices in Shanghai, an emerging economy financial hub. It provides insights for policy development, emphasizing firm and sector-specific factors driving sustainability accounting. Policymakers can promote transparency and responsibility by considering firms’ unique characteristics, fostering a more sustainable business environment.
Rhizosphere mycobiome diversity in four declining Mediterranean tree species
Authors: Diez-Hermano Sergio , Poveda Jorge , Niño-Sanchez Jonatan , Bocos-Asenjo Irene Teresa , Peix Álvaro , Martín-Pinto Pablo , Diez Julio Javier
Published: October 2023

Introduction

Forests in the Mediterranean basin are currently in decline. Their resilience has been eroded as a result of climate change and anthropogenic impacts, making them vulnerable to increasingly frequent episodes of drought, fire and the spread of pests and diseases. The impact of these natural and anthropogenic events on soil biodiversity is of particular concern, as the soil fungal community plays a key role in ecosystem homeostasis.

Objectives and methods

In order to analyse the relationship between soil health status and fungal diversity, soil samples were collected from declining Mediterranean forests of Castanea sativa (chestnut), Quercus ilex (holm oak), Quercus suber (cork oak) and Quercus pyrenaica (Pyrenean oak). A metabarcoding study was carried out by sequencing the ITS genomic region.

Results

A total of 674 fungal genera were found. It has not been possible to explain the differences in health status from the fungal genera found exclusively on declining forest soils, as none of them have been described as pathogenic. Healthy chestnut soils were characterized by a high alpha diversity and a higher abundance of the genus Metarhizium. No differentially abundant genera were found in any of the other forest species tested. Declining chestnut soils harbored more abundance of ectomycorrhizae and soil saprotrophs than healthy samples. Ectomycorrhizae were the dominant lifestyle in all oak species regardless of health status, whereas arbuscular mycorrhizae were preferentially found in declining cork oak soils.

Discussion

This work highlights the resilience of fungal communities of soil against decline and highlights the need to further investigate its relationship with the forest’s ability to cope with the challenges of climate change.
Transcriptomic and metabolomic analyses of the ovaries of Taihe black-bone silky fowls at the peak egg-laying and nesting period
Authors: Xiang Xin , Huang Xuan , Wang Jianfeng , Zhang Haiyang , Zhou Wei , Xu Chunhui , Huang Yunyan , Tan Yuting , Yin Zhaozheng
Published: October 2023

The poor reproductive performance of most local Chinese chickens limits the economic benefits and output of related enterprises. As an excellent local breed in China, Taihe black-bone silky fowl is in urgent need of our development and utilization. In this study, we performed transcriptomic and metabolomic analyses of the ovaries of Taihe black-bone silky fowls at the peak egg-laying period (PP) and nesting period (NP) to reveal the molecular mechanisms affecting reproductive performance. In the transcriptome, we identified five key differentially expressed genes (DEGs) that may affect the reproductive performance of Taihe black-bone silky fowl: BCHE, CCL5, SMOC1, CYTL1, and SCIN, as well as three important pathways: the extracellular region, Neuroactive ligand-receptor interaction and Cytokine-cytokine receptor interaction. In the metabolome, we predicted three important ovarian significantly differential metabolites (SDMs): LPC 20:4, Bisphenol A, and Cortisol. By integration analysis of transcriptome and metabolome, we identified three important metabolite-gene pairs: “LPC 20:4-BCHE”, “Bisphenol A-SMOC1”, and “Cortisol- SCIN”. In summary, this study contributes to a deeper understanding of the regulatory mechanism of egg production in Taihe black-bone silky fowl and provides a scientific basis for improving the reproductive performance of Chinese local chickens.
Learning the kernel for rare variant genetic association test
Authors: Falk Isak , Zhao Millie , Nait Saada Juba , Guo Qi
Published: October 2023

Introduction: Compared to Genome-Wide Association Studies (GWAS) for common variants, single-marker association analysis for rare variants is underpowered. Set-based association analyses for rare variants are powerful tools that capture some of the missing heritability in trait association studies.

Methods: We extend the convex-optimized SKAT (cSKAT) test set procedure which learns from data the optimal convex combination of kernels, to the full Generalised Linear Model (GLM) setting with arbitrary non-genetic covariates. We call this extended cSKAT (ecSKAT) and show that the resulting optimization problem is a quadratic programming problem that can be solved with no additional cost compared to cSKAT.

Results: We show that a modified objective is related to an upper bound for the p-value through a decreasing exponential term in the objective function, indicating that optimizing this objective function is a principled way of learning the combination of kernels. We evaluate the performance of the proposed method on continuous and binary traits using simulation studies and illustrate its application using UK Biobank Whole Exome Sequencing data on hand grip strength and systemic lupus erythematosus rare variant association analysis.

Discussion: Our proposed ecSKAT method enables correcting for important confounders in association studies such as age, sex or population structure for both quantitative and binary traits. Simulation studies showed that ecSKAT can recover sensible weights and achieve higher power across different sample sizes and misspecification settings. Compared to the burden test and SKAT method, ecSKAT gives a lower p-value for the genes tested in both quantitative and binary traits in the UKBiobank cohort.
Advances in immunotyping of colorectal cancer
Authors: Wu Yinhang , Zhuang Jing , Qu Zhanbo , Yang Xi , Han Shuwen
Published: October 2023

Immunotherapy has transformed treatment for various types of malignancy. However, the benefit of immunotherapy is limited to a minority of patients with mismatch-repair-deficient (dMMR) and microsatellite instability-high (MSI-H) (dMMR-MSI-H) colorectal cancer (CRC). Understanding the complexity and heterogeneity of the tumor immune microenvironment (TIME) and identifying immune-related CRC subtypes will improve antitumor immunotherapy. Here, we review the current status of immunotherapy and typing schemes for CRC. Immune subtypes have been identified based on TIME and prognostic gene signatures that can both partially explain clinical responses to immune checkpoint inhibitors and the prognosis of patients with CRC. Identifying immune subtypes will improve understanding of complex CRC tumor heterogeneity and refine current immunotherapeutic strategies.
Pioneer factors in viral infection
Authors: Neugebauer Eva , Bastidas-Quintero Aura M. , Weidl Daniel , Full Florian
Published: October 2023

Pioneer factors are transcription factors sharing the fascinating ability to bind to compact chromatin and thereby alter its transcriptional fate. Most pioneer factors are known for their importance during embryonic development, for instance, in inducing zygotic genome activation or cell fate decision. Some pioneer factors are actively induced or downregulated by viral infection. With this, viruses are capable to modulate different signaling pathways resulting for example in MHC-receptor up/downregulation which contributes to viral immune evasion. In this article, we review the current state of research on how different viruses (Herpesviruses, Papillomaviruses and Hepatitis B virus) use pioneer factors for their viral replication and persistence in the host, as well as for the development of viral cancer.
Osteonecrosis is associated with APOL1 variants in African Americans with systemic lupus erythematosus
Authors: Yip Kevin , Akerman Meredith , Fernandez Ruiz Ruth , Leung Nicole , Algasas Huda , Qian Yingzhi , Buyon Jill P. , Divers Jasmin , Izmirly Peter , Belmont Michael , Blazer Ashira D.
Published: October 2023

Background/purpose

African Americans (AA) with systemic lupus erythematosus (SLE) are at higher risk for both kidney disease and Osteonecrosis (ON). Two Apolipoprotein L1 (APOL1) risk variants (RV), G1 and G2, have been associated with chronic kidney disease (CKD), hypertension, and microvascular disease in AAs, which are independent risk factors for ON. Accordingly, we investigated the association between carriers of the APOL1 risk variants and the prevalence of ON in AA SLE patients.

Methods

A cohort of 121 adult participants of self-reported AA ancestry and meeting at least four of the American College of Rheumatology (ACR) revised criteria for SLE were recruited from a high volume urban SLE clinical site. PCR/sequencing was used to stratify participants by APOL1 genotype. Medical records, including clinical notes and imaging reports, were retrospectively reviewed for documentation of ON. Association between the number of APOL1 risk variants with time to first ON was tested.

Results

In our cohort, 18 individuals developed ON; across the APOL1 genotype groups, 2/37 0RV, 11/59 1RV, and 5/15 2RV participants were affected. The mean time to ON was 27 years, 22 years, and 18 years in 0RV, 1RV, and 2RV carriers, respectively. An adjusted Cox regression model showed that carrying the APOL1 risk variants associated with shorter ON free survival with hazard ratios (HR) of 3.1 (95% CI: 1.6–6.2) and 9.6 (95% CI 2.4–37.8) for 1RV and 2RV carriers, respectively. 2RV carriers more often exhibited multiple and bilateral joint sites affected by ON. Disease duration was longer in ON-affected participants at 20.5 years compared to 9.0 years in those unaffected (p < 0.001). In individuals who had received glucocorticoids, median cumulative prednisone equivalent dose was higher in ON-affected participants, though this did not reach statistical significance (18.7 g vs. 9.0 g; p-value = 0.3).

Conclusion

Our analysis suggests a higher risk of osteonecrosis among African American SLE patients who carry the APOL1 risk variants. In addition, disease duration increased the rate of ON. Given the high frequency of the APOL1 risk variants in African Americans, APOL1 high-risk genotype carriers may represent an ON-vulnerable subgroup within the AA population. Further work is necessary to uncover the mechanism of this association.
First estimates of population size and home range of Caribbean reef and nurse sharks using photo-identification and BRUVS
Authors: Kohler Johanna , Gore Mauvis , Ormond Rupert , Austin Timothy
Published: October 2023

The assessment of parameters population size and individual home range is important for effective conservation management of sharks. This study uses the novel application of photo identification (photo-ID) to BRUVS footage as a non-invasive alternative to tagging in order to generate individual capture histories. These were used in mark-recapture models to estimate effective population sizes and to determine home ranges. In the Cayman Islands a total of 499 shark sightings of six coastal shark species were recorded on BRUVS from 2015 - 2018, but re-sighting rates were only sufficient for the determination of population parameters for two species - Caribbean reef shark (Carcharhinus perezi) and nurse shark (Ginglymostoma cirratum). The calculated super-population sizes for Caribbean reef shark (180 ± 37 SE) and nurse shark (336 ± 61 SE) were greater than the estimates for each species based on a closed-population model (Caribbean reef shark: 128 ± 40 SE, nurse shark: 249 ± 48 SE), though both measures indicated that there were about twice as many nurse sharks (1.3 - 1.8 sharks/km2) as Caribbean reef sharks (0.7 – 1 shark/km2) within the study area. The demographic compositions included numerous immature individuals, indicating that breeding of both species takes place within the study area of 188 km2. Most recognizable individuals of both species showed linear home ranges of <20 km, but a few individuals were observed to have moved longer distances (Caribbean reef shark: 125.37 km, nurse shark: 156.07 km). The data indicate that the home ranges and long-distance movements of individual sharks observed within the islands’ marine protected areas (MPAs) often extend to areas beyond the MPA’s boundary, potentially exposing them to fishing activities. This study provides the first estimates of population size for Caribbean reef and nurse sharks in the Cayman Islands and the first estimate of a Caribbean reef shark population globally.
Low-cost UAV monitoring: insights into seasonal volumetric changes of an oyster reef in the German Wadden Sea
Authors: Hoffmann Tom K. , Pfennings Kai , Hitzegrad Jan , Brohmann Leon , Welzel Mario , Paul Maike , Goseberg Nils , Wehrmann Achim , Schlurmann Torsten
Published: October 2023

This study aims to quantify the dimensions of an oyster reef over two years via low-cost unoccupied aerial vehicle (UAV) monitoring and to examine the seasonal volumetric changes. No current study investigated via UAV monitoring the seasonal changes of the reef-building Pacific oyster (Magallana gigas) in the German Wadden Sea, considering the uncertainty of measurements and processing. Previous studies have concentrated on classifying and mapping smaller oyster reefs using terrestrial laser scanning (TLS) or hyperspectral remote sensing data recorded by UAVs or satellites. This study employed a consumer-grade UAV with a low spectral resolution to semi-annually record the reef dimensions for generating digital elevation models (DEM) and orthomosaics via structure from motion (SfM), enabling identifying oysters. The machine learning algorithm Random Forest (RF) proved to be an accurate classifier to identify oysters in low-spectral UAV data. Based on the classified data, the reef was spatially analysed, and digital elevation models of difference (DoDs) were used to estimate the volumetric changes. The introduction of propagation errors supported determining the uncertainty of the vertical and volumetric changes with a confidence level of 68% and 95%, highlighting the significant change detection. The results indicate a volume increase of 22 m³ and a loss of 2 m³ in the study period, considering a confidence level of 95%. In particular, the reef lost an area between September 2020 and March 2021, when the reef was exposed to air for more than ten hours. The reef top elevation increased from -15.5 ± 3.6 cm NHN in March 2020 to -14.8 ± 3.9 cm NHN in March 2022, but the study could not determine a consistent annual growth rate. As long as the environmental and hydrodynamic conditions are given, the reef is expected to continue growing on higher elevations of tidal flats, only limited by air exposure. The growth rates suggest a further reef expansion, resulting in an increased roughness surface area that contributes to flow damping and altering sedimentation processes. Further studies are proposed to investigate the volumetric changes and limiting stressors, providing robust evidence regarding the influence of air exposure on reef loss.
Vision-force-fused curriculum learning for robotic contact-rich assembly tasks
Authors: Jin Piaopiao , Lin Yinjie , Song Yaoxian , Li Tiefeng , Yang Wei
Published: October 2023

Contact-rich robotic manipulation tasks such as assembly are widely studied due to their close relevance with social and manufacturing industries. Although the task is highly related to vision and force, current methods lack a unified mechanism to effectively fuse the two sensors. We consider coordinating multimodality from perception to control and propose a vision-force curriculum policy learning scheme to effectively fuse the features and generate policy. Experiments in simulations indicate the priorities of our method, which could insert pegs with 0.1 mm clearance. Furthermore, the system is generalizable to various initial configurations and unseen shapes, and it can be robustly transferred from simulation to reality without fine-tuning, showing the effectiveness and generalization of our proposed method. The experiment videos and code will be available at https://sites.google.com/view/vf-assembly.
Cultural adaptation and validation of the Arabic version of the short 12-item stroke-specific quality of life scale
Authors: Sakr Fouad , Dabbous Mariam , Akel Marwan , Salameh Pascale , Hosseini Hassan
Published: October 2023

Background

Given the excessive length and inconsistent validity of the existing long stroke-specific quality of life (SS-QOL) scales, there is a need to validate a shorter measuring tool. The aim of this study was to validate the Arabic version of the short 12-item SS-QOL (SS-QOL-12-AR) and examine its validity measures and psychometric properties. Additionally, the study aimed to assess the QOL after stroke and identify the sociodemographic and clinical factors that influence it in Lebanon.

Methods

A cross-sectional study was conducted. The SS-QOL-12-AR structure was validated, and its reliability and internal consistency were assessed. The scale’s specificity and sensitivity were evaluated and then compared with those of other SS-QOL scales. The correlation between each item and the overall scale were examined, and its convergent validity was evaluated.

Results

A total of 172 stroke survivors were included. The SS-QOL-12-AR structure was validated with a solution of two factors, with a Kaiser-Meyer-Olkin measure of sampling adequacy of 0.850 and a significant Bartlett’s test of sphericity (p < 0.001). The Cronbach’s alpha of the scale was 0.917. According to ROC curve analysis, the optimal cut-off point for distinguishing between lower and better QOL was 32.50. At this cut-off, the sensitivity and specificity were 70.0% and 71.2%, respectively. The area under the curve was 0.779 (95% CI 0.704–0.855, p < 0.001). The SS-QOL-12-AR demonstrated a strong and highly significant correlation with existing versions of the SS-QOL, confirming its convergent validity. 61.6% of stroke survivors had a lower QOL, which was significantly associated with poor stroke prognosis, increased physical dependence, current smoking, and alcohol abstinence.

Conclusion

The SS-QOL-12-AR exhibits strong validity and reliability, demonstrating excellent psychometric properties. The scale holds potential for application in clinical practice and research settings, enabling the measurement of stroke-related consequences and evaluation of management outcomes.
Optimal target blood pressure for the primary prevention of hemorrhagic stroke: a nationwide observational study
Authors: Shim Hwan Seok , Park Jeong-Mee , Lee Yong Jae , Kim Young-Deok , Kim Tackeun , Ban Seung Pil , Bang Jae Seung , Kwon O-Ki , Oh Chang Wan , Lee Si Un
Published: October 2023

Background

There are few reports on the preventative value of intensive blood pressure (BP) management for stroke, especially hemorrhagic stroke (HS), after new criteria for hypertension (HTN) were announced by the American College of Cardiology/American Heart Association in 2017.

Aims

This study aimed to identify the optimal BP for the primary prevention of HS in a healthy population aged between 20 and 65 years.

Methods

We conducted a 10-year observational study on the risk of HS, subclassified as intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) according to BP categories (e.g., low normal BP, high normal BP, elevated BP, stage 1 HTN, and stage 2 HTN) using the National Health Insurance Service Database.

Results

Out of 8,327,751 participants who underwent a health checkup in 2008, 949,550 were included in this study and observed from 2009 to 2018. The risk of ICH was significantly increased in men with stage 2 HTN {adjusted hazard ratio [aHR] 2.002 [95% confidence interval (CI) 1.203–3.332]} and in women with stage 1 HTN [aHR 2.021 (95% CI, 1.251–3.263)]. The risk of SAH was significantly increased in both men [aHR 1.637 (95% CI, 1.066–2.514)] and women [aHR 4.217 (95% CI, 2.648–6.715)] with stage 1 HTN. Additionally, the risk of HS was significantly increased in men with stage 2 HTN [aHR 3.034 (95% CI, 2.161–4.260)] and in women with stage 1 HTN [aHR 2.976 (95% CI, 2.222–3.986)].

Conclusion

To prevent primary HS, including ICH and SAH, BP management is recommended for adults under the age of 65 years with stage 1 HTN.
Mini review of first-in-human integrin αvβ6 PET tracers
Authors: Kimura Richard H. , Iagaru Andrei , Guo H. Henry
Published: October 2023

This mini review of clinically-evaluated integrin αvβ6 PET-tracers reveals distinct differences in human-biodistribution patterns between linear peptides, including disulfide-stabilized formats, compared to head-to-tail cyclized peptides. All PET tracers mentioned in this mini review were able to delineate disease from normal tissues, but some αvβ6 PET tracers are better than others for particular clinical applications. Each αvβ6 PET tracer was validated for its ability to bind integrin αvβ6 with high affinity. However, all the head-to-tail cyclized peptide PET-tracers reviewed here did not accumulate in the GI-tract, in striking contrast to the linear and disulfide-bonded counterparts currently undergoing clinical evaluation in cancer, IPF and long COVID. Multiple independent investigators have reported the presence of β6 mRNA as well as αvβ6 protein in the GI-tract. Currently, there remains further need for biochemical, clinical, and structural data to satisfactorily explain the state-of-the-art in human αvβ6-imaging.
Top 100 cited classical articles in sentinel lymph nodes biopsy for breast cancer
Authors: Liang Xinrui , Wang Yu , Fu Guanghua , Fan Pingmig , Ma Ke , Cao Xu-Chen , Lin Guang-Xun , Zheng Wu-ping , Lyu Peng-fei
Published: October 2023

Background

The sentinel lymph node biopsy (SLNB) takes on a critical significance in breast cancer surgery since it is the gold standard for assessing axillary lymph node (ALN) metastasis and determining whether to perform axillary lymph node dissection (ALND). A bibliometric analysis is beneficial to visualize characteristics and hotspots in the field of sentinel lymph nodes (SLNs), and it is conducive to summarizing the important themes in the field to provide more insights into SLNs and facilitate the management of SLNs.

Materials and methods

Search terms relating to SLNs were aggregated and searched in the Web of Science core collection database to identify the top 100 most cited articles. Bibliometric tools were employed to identify and analyze publications for annual article volume, authors, countries, institutions, keywords, as well as hotspot topics.

Results

The period was from 1998 to 2018. The total number of citations ranged from 160 to 1925. LANCET ONCOLOGY and JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION were the top two journals in which the above articles were published. Giuliano, AE was the author with the highest number of articles in this field with 15. EUROPEAN INST ONCOL is the institution with the highest number of publications, with 35 articles. Hotspots include the following 4 topics, false-negative SLNs after neoadjuvant chemotherapy; prediction of metastatic SLNs; quality of life and postoperative complications; and lymphography of SLNs.

Conclusion

This study applies bibliometric tools to analyze the most influential literature, the top 100 cited articles in the field of SLNB, to provide researchers and physicians with research priorities and hotspots.
Endocrine treatment near the end of life among older women with metastatic breast cancer: a nationwide cohort study
Authors: Szilcz Máté , Wastesson Jonas W. , Calderón-Larrañaga Amaia , Morin Lucas , Lindman Henrik , Johnell Kristina
Published: October 2023

Background

The appropriate time to discontinue chemotherapy at the end of life has been widely discussed. In contrast, few studies have investigated the patterns of endocrine treatment near death. In this study, we aimed to investigate the end-of-life endocrine treatment patterns of older women with metastatic breast cancer and explore characteristics associated with treatment.

Methods

A retrospective cohort study of all older women (age ≥65 years) with hormone receptor-positive breast cancer who died in Sweden, 2016 − 2020. We used routinely collected administrative and health data with national coverage. Treatment initiation was defined as dispensing during the last three months of life with a nine-month washout period, while continuation and discontinuation were assessed by previous use during the same period. We used log-binomial models to explore factors associated with the continuation and initiation of endocrine treatments.

Results

We included 3098 deceased older women with hormone receptor-positive breast cancer (median age 78). Overall, endocrine treatment was continued by 39% and initiated by 5% and of women during their last three months of life, while 31% discontinued and 24% did not use endocrine treatment during their last year of life. Endocrine treatment continuation was more likely among older and less educated women, and among women who had multi-dose drug dispensing, chemotherapy, and CDK4/6 use. Only treatment-related factors were associated with treatment initiation.

Conclusion

More than a third of women with metastatic breast cancer continue endocrine treatments potentially past the point of benefit, whereas late initiation is less frequent. Further research is warranted to determine whether our results reflect overtreatment at the end of life once patients’ preferences and survival prognosis are considered.
Incessant ovulation: a review of its importance in predicting cancer risk
Authors: Cramer Daniel W.
Published: October 2023

Estrous cycles are recurring changes in therian mammals induced by estrogen, progesterone, and other hormones culminating in endometrial proliferation, ovulation, and implantation if fertilization occurred. In women, the estrous cycle is the menstrual cycle; but, unlike most mammals, the end of an infertile cycle is marked by endometrial sloughing and the start of another without an anestrous phase. Women stop cycling at menopause, while in most mammals, cycles continue until death. Epidemiologic studies identified menarche, menopause, births, lactation, and oral contraceptive (OC) use as key risk factors for ovarian, breast, and endometrial cancers. A composite variable was created to estimate the number of cycles not interrupted by events that stop ovulation. Captured by the phrase “incessant ovulation”, repetitive cycles were first postulated to affect ovarian cancer risk and later extended to breast and endometrial cancers. These associations could be explained by cumulative effects of repetitive tissue changes within reproductive organs, immune consequences of repetitive ovulation through the glycoprotein mucin 1, and residual effects of past ovulations that enhance ovarian production of testosterone. The latter two pathways could affect the risk for cancers in other organs not considered “reproductive”.
Prevalence and risk factors for high-risk human papillomavirus infection among women from three southern geopolitical zones of Nigeria
Authors: Onwuamah Chika Kingsley , Feng Ning , Momoh Abidemi Esther , Uwandu Mabel , Ahmed Rahaman Ademolu , Idigbe Ifeoma , Vincent Grace Deborah , Ogbu Chinenye Angela , Okonkwo Nkem , Sokei Judith , Abimbola Bowofoluwa Sharon , Ojopagogo Temiloluwa , Okoli Leona Chika , Adesina Mary , Ezemelue Priscilla Ngozi , Sowunmi Omowunmi , Okwuzu Jane , Labo−Popoola Olaoniye Habeebat , Shaibu Joseph Ojonugwa , Ohihoin Greg Aigbe , Nzeribe Emily , David Agatha , Olaleye Olufemi , Ofotokun Ighovwerha , Dong Xiao−ping , Ezechi Oliver Chukwujekwu
Published: October 2023

Introduction

Human Papillomavirus (HPV) infection is a risk factor for cervical cancer, the fourth most common cancer among women globally. Its burden is the highest in sub-Saharan Africa, with over 90% mortality. Interventions may fail without evidence-based data on stratified prevalence and risk factors among most at-risk women across Nigeria.

Methods

A cross-sectional comparative study, with participants recruited from the Nigerian Institute of Medical Research’s Clinics, NGO outreaches, a cancer screening centre and a university teaching hospital. Questionnaires were self-administered. Trained medics performed sampling at healthcare facilities, and self-sampling was used at outreaches.

Results

Nine hundred eighty-five study participants were recruited. About 37% and 27% of the women knew about HPV and its vaccines, respectively, but only 6% confirmed vaccination with HPV vaccines. HPV prevalence was highest among women with unknown marital status (35.9%), single women (33.8%), widowed/divorced/separated women (30.3%), and married/cohabiting women (19.6%). HPV infection was significantly higher among women who take alcohol (odds=1.7 [95% CI: 1.2-2.4]) and women who smoke (odds=2.6 [95% CI: 1.4 - 4.6]. HPV strains detected included HPV16 (1.3%), HPV18 (1.5%), Low Risk (0.2%) and Other High-Risk groups (19.7%).

Conclusion

The inverse relationship between prevalence and education suggests interventions improving awareness and prevention would be impactful. Such interventions could also target HIV-positive women, women presenting with sexually-transmitted infections, who smoke and frequently drink alcohol.
The kynurenine pathway presents multi-faceted metabolic vulnerabilities in cancer
Authors: León-Letelier Ricardo A. , Dou Rongzhang , Vykoukal Jody , Sater Ali Hussein Abdel , Ostrin Edwin , Hanash Samir , Fahrmann Johannes F.
Published: October 2023

The kynurenine pathway (KP) and associated catabolites play key roles in promoting tumor progression and modulating the host anti-tumor immune response. To date, considerable focus has been on the role of indoleamine 2,3-dioxygenase 1 (IDO1) and its catabolite, kynurenine (Kyn). However, increasing evidence has demonstrated that downstream KP enzymes and their associated metabolite products can also elicit tumor-microenvironment immune suppression. These advancements in our understanding of the tumor promotive role of the KP have led to the conception of novel therapeutic strategies to target the KP pathway for anti-cancer effects and reversal of immune escape. This review aims to 1) highlight the known biological functions of key enzymes in the KP, and 2) provide a comprehensive overview of existing and emerging therapies aimed at targeting discrete enzymes in the KP for anti-cancer treatment.
Assessing real-world safety concerns of Sacituzumab govitecan: a disproportionality analysis using spontaneous reports in the FDA adverse event reporting system
Authors: Gui Xiujuan , Zhao Jianli , Ding Linxiaoxiao , Chai Jie , Lai Hongna , Cai Yangyang , Luo Simin , Zeng Yinduo , Wu Wenjing , Chen Haizhu , Yao Herui , Wang Ying
Published: October 2023

Aim

The aim of this study was to identify potential safety concerns associated with Sacituzumab Govitecan (SG), an antibody-drug conjugate targeting trophoblastic cell-surface antigen-2, by analyzing real-world safety data from the largest publicly available worldwide pharmacovigilance database.

Methods

All data obtained from the FDA Adverse Event Reporting System (FAERS) database from the second quarter of 2020 to the fourth quarter of 2022 underwent disproportionality analysis and Bayesian analysis to detect and assess the adverse event signals of SG, considering statistical significance when the lower limit of the 95% CI >1, based on at least 3 reports.

Results

Total of 1072 cases were included. The main safety signals were blood and lymphatic system disorders [ROR(95CI)=7.23 (6.43-8.14)], gastrointestinal disorders [ROR(95CI)=2.01 (1.81-2.22)], and relative infection adverse events, such as neutropenic sepsis [ROR(95CI)=46.02 (27.15-77.99)] and neutropenic colitis [ROR(95CI)=188.02 (120.09-294.37)]. We also noted unexpected serious safety signals, including large intestine perforation [ROR(95CI)=10.77 (3.47-33.45)] and hepatic failure [ROR(95CI)=3.87 (1.45-10.31)], as well as a high signal for pneumonitis [ROR(95CI)=9.93 (5.75-17.12)]. Additionally, age sub-group analysis revealed that geriatric patients (>65 years old) were at an increased risk of neutropenic colitis [ROR(95CI)=282.05 (116.36-683.66)], neutropenic sepsis [ROR(95CI)=101.11 (41.83-244.43)], acute kidney injury [ROR(95CI)=3.29 (1.36-7.94)], and atrial fibrillation [ROR(95CI)=6.91 (2.86-16.69)].

Conclusion

This study provides crucial real-world safety data on SG, complementing existing clinical trial information. Practitioners should identify contributing factors, employ monitoring and intervention strategies, and focus on adverse events like neutropenic sepsis, large intestine perforation, and hepatic failure. Further prospective studies are needed to address these safety concerns for a comprehensive understanding and effective management of associated risks.
Single cell transcriptomics identifies distinct choroid cell populations involved in visually guided eye growth
Authors: Summers Jody A. , Jones Kenneth L.
Published: October 2023

Introduction

Postnatal ocular growth is regulated by a vision-dependent mechanism, termed emmetropization, which acts to minimize refractive error through coordinated growth of the ocular tissues. The choroid participates in the emmetropization process via the production of scleral growth regulators that control ocular elongation and refraction.

Methods

To elucidate the role of the choroid in emmetropization, we used single-cell RNA sequencing (scRNA-seq) to characterize the cell populations in the chick choroid and compare gene expression changes in these cell populations when the eye is undergoing emmetropization. Emmetropization was modeled by inducing form deprivation myopia in 3 -4 day old chicks via application of translucent occluders to one eye for a period of 10 days followed by 24 hrs of unrestricted vision (by removing the occluder). Numerous studies have previously shown that visual form deprivation stimulates axial elongation and myopia, and upon removal of the occluder, the myopic chick eye rapidly slows its rate of axial elongation to recover from the induced myopia and regain emmetropia. The contralateral, untreated eyes served as controls.

Results

UMAP clustering analysis identified 24 distinct cell clusters in all chick choroids. 7 clusters were identified as fibroblast subpopulations; 5 clusters represented different populations of endothelial cells; 4 clusters were CD45+ macrophages, T cells and B cells; 3 clusters were Schwann cell subpopulations; and 2 clusters were identified as melanocytes. Additionally, single populations of RBCs, plasma cells and neuronal cells were identified. Significant changes in gene expression between control and treated choroids were identified in 17 cell clusters, representing 95% of total choroidal cells. The majority of gene expression changes were relatively small (< 2 fold). The greatest changes in gene expression were identified in a rare cell population (0.11% - 0.49% of total choroidal cells). This population expressed neuron-specific genes as well as several opsin genes suggestive of a rare neuronal cell population that is potentially light sensitive.

Discussion

Our results, for the first time, provide a comprehensive profile of the major choroidal cell types and their gene expression changes during the process of emmetropization and provide insights into the canonical pathways and upstream regulators that coordinate postnatal ocular growth.
Clinical outcomes of nephrocalcinosis in preschool-age children: association between nephrocalcinosis improvement and long-term kidney function
Authors: Woo Hyun Ah , Lee Hyeonju , Choi Young Hun , Min Jeesu , Kang Hee Gyung , Ahn Yo Han , Lee Hyun Kyung
Published: October 2023

Background

We evaluated the long-term clinical outcomes of nephrocalcinosis (NC) according to etiology and grade in preschool-age children with NC.

Methods

We retrospectively analyzed the clinical outcomes and disease grade of children with NC classified into three groups according to etiology: prematurity, tubular disorders, and others.

Results

Overall, 67 children were diagnosed with NC [median age, 0.76 years; interquartile range (IQR) 0.46–2.14 years]. The etiologies of NC included prematurity (28.4%), tubular disorders (25.4%), and others (46.3%). Moreover, 56 (83.6%) children were asymptomatic and diagnosed accidentally through kidney ultrasonography. Newly diagnosed underlying diseases were greater in the tubular disorders group than in the other two groups (P = 0.001). Significantly more newly diagnosed NCs were grade 3 than grade 1 (P = 0.003). The median estimated glomerular filtration rate (eGFR) changed from 96.1 (IQR 68.8–119.2) ml/min/1.72 m2 at diagnosis to 90.9 (IQR 76.4–106.4) ml/min/1.72 m2 at the last follow-up, without a significant difference (P = 0.096). Changes in the kidney function did not differ according to etiology. However, patients without improvement in NC grade showed a decrease in eGFR from 98.1 (IQR 71.1–132.9) to 87.4 (IQR 74.0–104.1) ml/min/1.73 m2 (P = 0.023), while patients with improved NC grade did not show any change in the kidney function.

Conclusions

Early recognition, especially in NC grade 3, can help uncover further diagnoses, such as tubular disorders. Long-term kidney function depends on whether the NC grade improves.
New pricing models for generic medicines to ensure long-term sustainable competition in Europe
Authors: Francois Clement , Gawlik Gabriela , Mestre-Ferrandiz Jorge , Pana Adrian , Perelman Julian , Yfantopoulos John , Simoens Steven
Published: October 2023

Background: Price erosion of generic medicines over time as a result of existing pricing policies in combination with increasing operational costs of these products due to high inflation, undermine long-term sustainable competition in European off-patent medicines markets. Therefore, the aim of this study is to identify new potential pricing models for retail generic medicines in Europe, examine their pros and cons, and illustrate them with examples inside or outside the pharmaceutical sector.

Methods: A targeted literature review, one-to-one interviews and a joint advisory board meeting with experts from five European countries were carried out to assess potential pricing models for generic medicines.

Results: We identified ten pricing models that can be applied to generic medicines. The tiered pricing model is viewed as a sustainable solution ensuring competitiveness, but requires market monitoring using a supportive IT infrastructure. De-linking the price of generic medicines from that of the off-patent originator medicine prevents the originator from forcing generic medicines’ prices to unsustainable levels. Higher costs due to inflation can be compensated in the automatic indexation model. Other pricing models that have less implementation potential include the one-in-one/multiple-out model, tax credits, value-based pricing, volume for savings and guaranteed margin/fee models. The hypothecated tax and cost allocation models, which add a patient fee to generic medicines prices, are not likely to be socially acceptable.

Conclusion: When considering a new pricing model for generic medicines, the impact on innovative medicines and the characteristics of the healthcare system in a given country need to be taken into account. Also, there is a need to continuously follow up the level of competition in off-patent medicines markets and to identify sustainability risks.
The role of microbial interactions on rhizobial fitness
Authors: Granada Agudelo Margarita , Ruiz Bryan , Capela Delphine , Remigi Philippe
Published: October 2023

Rhizobia are soil bacteria that can establish a nitrogen-fixing symbiosis with legume plants. As horizontally transmitted symbionts, the life cycle of rhizobia includes a free-living phase in the soil and a plant-associated symbiotic phase. Throughout this life cycle, rhizobia are exposed to a myriad of other microorganisms that interact with them, modulating their fitness and symbiotic performance. In this review, we describe the diversity of interactions between rhizobia and other microorganisms that can occur in the rhizosphere, during the initiation of nodulation, and within nodules. Some of these rhizobia-microbe interactions are indirect, and occur when the presence of some microbes modifies plant physiology in a way that feeds back on rhizobial fitness. We further describe how these interactions can impose significant selective pressures on rhizobia and modify their evolutionary trajectories. More extensive investigations on the eco-evolutionary dynamics of rhizobia in complex biotic environments will likely reveal fascinating new aspects of this well-studied symbiotic interaction and provide critical knowledge for future agronomical applications.
Reactivity of the triple task on writing processes and product in adults with dyslexia
Authors: Olujić Tomazin Marina , Kuvač Kraljević Jelena , Alves Rui A.
Published: October 2023

Introduction

The triple task (TT) is a method for assessing the dynamics of writing processes. It involves three tasks in one: writing a text, responding to a sound, and reporting the process. Previous research has mostly shown that the TT does not affect the writing process or the product. However, individuals with dyslexia often show difficulties in tasks that require organization, automation, integration of multiple processes, inhibition, and shifting/cognitive flexibility. The aim of this study was therefore to investigate whether TT affects the writing process and written product differently in adults with dyslexia compared to a control group of adults with typical reading skills.

Methods

Two groups of adult native Croatian speakers were included in this study: 20 adults with developmental dyslexia and 20 adults with typical reading skills; evenly distributed by: age (18–38 years), gender (13 males, 7 females per group), educational level, and nonverbal cognitive abilities. All participants wrote one text with a TT and another without. The writing of the text was tracked with a keystroke logging program – Inputlog. The two texts were compared at process and product level.

Results and discussion

The results showed that measures of writing processes and text quality in the groups of adults with dyslexia and adults with typical reading skills were unlikely to be differentially affected by TT. However, in the condition without TT, the total number of characters per minute was higher, more keys were typed per minute and more words were deleted. As expected, adults with dyslexia produced shorter texts of lower quality and with more errors; they also produced fewer characters per minute, used fewer keystrokes and typed fewer.

Conclusion

The study suggests that TT is unlikely to have a different impact on the writing process or written product in adults with dyslexia compared to adults with typical reading skills.