bluuebunny/crossref_metadata_2025 huggingface dataset:
Compliance with European Consumer Law
Authors: Pflücke Felix
Published: July 2024

European consumer law has adapted and evolved in response to the rapid growth of e-commerce in the last two decades. This monograph examines the evolving legal framework at the EU and national levels—from mandatory disclosures to unfair contract terms—and analyses the extent to which scientifically grounded evidence or theories underpin these legislative choices. It depicts the increasing use of evidence in EU consumer law and policy but highlights the lack of scientific rigour and evidence in enforcement. At the heart of the book lies an original empirical inquiry assessing compliance among e-commerce traders with consumer protection rules. The empirical analysis investigates whether 300 traders from four jurisdictions comply with their legal duties and identifies reasons for non-compliance. It translates the evidence of previously undiscovered non-compliance patterns into precise and actionable policy recommendations. The underlying objective of this monograph is to advocate for a more evidence-driven approach within European consumer law aimed at strengthening the effectiveness of the rules and fostering trader compliance. Ultimately, it serves as a foundational step, setting the stage for future empirical research in this dynamic domain.
Conclusion
Authors: Pflücke Felix
Published: July 2024

The book explored how the European Union and four selected European jurisdictions regulate e-commerce business-to-consumer transactions and whether the legislative choices have been evidence-based. For this purpose, a hand-collected dataset helped assess whether traders complied with the underlying rules, which has been unexplored to date. This chapter concludes the monograph. It summarizes the main findings, outlines some of the book’s implications, addresses unanswered questions, and offers some concluding remarks.
Rabindranath Tagore
Authors: Roy Sumana
Published: July 2024

Rabindranath Tagore’s understanding of his own culture is mediated through a belief in the Indian subcontinent as being a ‘vast land of forests’, or even a large forest. Understanding cultures through the elements, through the opposition of land and water, and through the indulgence of plant life and its related accessories of thinking and living allows Rabindranath to see cultures and collectives without vilifying them. India’s culture of leisure, of the necessity of rest, of optimism, of a natural cosmopolitanism that comes from the accommodativeness of the forest, where there is room for everyone, where no one is rejected, and of ananda, a spirit that Rabindranath understands as genetic to this place and its people, is a gift of forest living. Then there are the trees of Santiniketan, those that he carried from his visits or requested to be sent to him from various parts of the country, those he valued and asked about in his letters when he was away. These were also the trees that would turn Santiniketan into the living laboratory where he could carry out his pedagogical experiments. And there are the plants and flowers and fruits of his songs and poems, stories and novels—how they hold in them his philosophy and politics, his moral universe, and his understanding of language.
Bibhutibhushan Bandyopadhyay
Authors: Roy Sumana
Published: July 2024

Bibhutibhushan Bandyopadhyay gives us a revolutionary formulation of history in his novel Ichhamati—the history of plant life, records of its settlement on land as well as its death and evacuation from these spaces, a census of plants and trees, all these constitute our national history, not only the life of kings, queens, and the famous. Returning to his philosophy of ananda, particularly in Pather Panchali, he notes the difference between the plant and human worlds—in doing so he allows us to understand concepts like poverty and miserliness, abundance and riches, in an unexpected register. The active remnants of an Upanishadic thought system, the effect of colonial education and practice on the plant world in Bengal, the meaning and implication of a taste such as ‘sweetness’, the meaning of the forest and how man has been destroying it for millennia—these are among the many things we discover in this chapter.
Association between the incidence of functional disability and frequency of eating together among older adults living alone: a 6-year follow-up study from the Japan Gerontological Evaluation Study
Authors: Shimizu Akio , Ikeda Takaaki , Miyaguni Yasuhiro , Takeda Sho , Tamada Yudai , Aida Jun
Published: July 2024

Objective

This study aimed to determine whether the frequency of eating together is associated with the incidence of functional disability in older adults who live alone.

Methods

This 6-year observational prospective cohort study utilised self-reported questionnaires. Data were drawn from the participants of the Japan Gerontological Evaluation Study project between 2016 and 2022. The participants were independent older adults aged ≥65 years living alone in Japan. The primary outcome was the incidence of functional disability during the follow-up period, with the self-reported frequency of eating together serving as the explanatory variable. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models after adjusting for confounders associated with incident functional disability.

Results

Among the 7167 participants, the mean age at baseline was 75.3 ± 6.5 years and 69.2% were female. About, 12.8% of participants (n = 917) developed functional disabilities during the observation period. The incidence rates were 11.7% for ‘every day’, 11.3% for ‘several times a week’, 11.5% for ‘several times a month’, 12.7% for ‘several times a year’ and 19.0% for ‘seldom’. The frequency of eating together ‘seldom’ was significantly associated with an increased incidence of functional disability (HR: 1.55, 95% CI: 1.10–2.18).

Conclusion

Among older adults living alone, infrequent eating together (‘seldom’) was identified as a risk factor for developing functional disability.
Joint association of cardiovascular health and frailty with all-cause and cause-specific mortality: a prospective study
Authors: Ning Ning , Fan Xiaoting , Zhang Yuan , Wang Yingxin , Liu Yang , Li Yumeng , Zhao Hua , Jin Lina , Ma Yanan
Published: July 2024

Background

Poor cardiovascular health (CVH) and physical frailty were reported to increase mortality risk, but their joint effects have not been fully elucidated.

Objectives

We aimed to explore the separate and joint effects of CVH and frailty on mortality based on two perspectives of Life’s Essential 8 (LE8) and Framingham Risk Score (FRS).

Methods

21 062 participants in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018 were involved in this study. CVH was evaluated by the LE8 and FRS, and categorized into low, moderate and high CVH groups. Cox proportional hazard models were applied to estimate the separate and joint associations of CVH and frailty index (FI) with all-cause, cardiovascular disease (CVD) and cancer mortality.

Results

Over a median follow-up period of 87 months (95% CI: 86.0–88.0), 2036 deaths occurred. The separate linear dose–response relationships between CVH, frailty and mortality were observed (nonlinear P > .05). The combination of low CVH/frailty was negatively associated with all-cause mortality [hazard ratio (HR) and 95%CI: low LE8*FI, 5.30 (3.74, 7.52); high FRS*FI, 4.34 (3.20, 5.88)], CVD mortality [low LE8*FI, 6.57 (3.54, 12.22); high FRS*FI, 7.29 (3.92, 13.55)] and cancer mortality [low LE8*FI, 1.99 (1.14, 3.25); high FRS*FI, 2.32 (1.30, 4.15)], with high CVH/fit group as reference. Further stratified analyses showed that the combined burden of mortality from frailty and low CVH was greater among the young and females.

Conclusions

Low CVH and frailty were independently and jointly correlated with greater risk of all-cause, CVD and cancer deaths, especially among the young and females.
CCPA: cloud-based, self-learning modules for consensus pathway analysis using GO, KEGG and Reactome
Authors: Nguyen Ha , Pham Van-Dung , Nguyen Hung , Tran Bang , Petereit Juli , Nguyen Tin
Published: July 2024

This manuscript describes the development of a resource module that is part of a learning platform named ‘NIGMS Sandbox for Cloud-based Learning’ (https://github.com/NIGMS/NIGMS-Sandbox). The module delivers learning materials on Cloud-based Consensus Pathway Analysis in an interactive format that uses appropriate cloud resources for data access and analyses. Pathway analysis is important because it allows us to gain insights into biological mechanisms underlying conditions. But the availability of many pathway analysis methods, the requirement of coding skills, and the focus of current tools on only a few species all make it very difficult for biomedical researchers to self-learn and perform pathway analysis efficiently. Furthermore, there is a lack of tools that allow researchers to compare analysis results obtained from different experiments and different analysis methods to find consensus results. To address these challenges, we have designed a cloud-based, self-learning module that provides consensus results among established, state-of-the-art pathway analysis techniques to provide students and researchers with necessary training and example materials. The training module consists of five Jupyter Notebooks that provide complete tutorials for the following tasks: (i) process expression data, (ii) perform differential analysis, visualize and compare the results obtained from four differential analysis methods (limma, t-test, edgeR, DESeq2), (iii) process three pathway databases (GO, KEGG and Reactome), (iv) perform pathway analysis using eight methods (ORA, CAMERA, KS test, Wilcoxon test, FGSEA, GSA, SAFE and PADOG) and (v) combine results of multiple analyses. We also provide examples, source code, explanations and instructional videos for trainees to complete each Jupyter Notebook. The module supports the analysis for many model (e.g. human, mouse, fruit fly, zebra fish) and non-model species. The module is publicly available at https://github.com/NIGMS/Consensus-Pathway-Analysis-in-the-Cloud.

This manuscript describes the development of a resource module that is part of a learning platform named ``NIGMS Sandbox for Cloud-based Learning'' https://github.com/NIGMS/NIGMS-Sandbox. The overall genesis of the Sandbox is described in the editorial NIGMS Sandbox [1] at the beginning of this Supplement. This module delivers learning materials on the analysis of bulk and single-cell ATAC-seq data in an interactive format that uses appropriate cloud resources for data access and analyses.
A large-scale assessment of sequence database search tools for homology-based protein function prediction
Authors: Zhang Chengxin , Freddolino Lydia
Published: July 2024

Sequence database searches followed by homology-based function transfer form one of the oldest and most popular approaches for predicting protein functions, such as Gene Ontology (GO) terms. These searches are also a critical component in most state-of-the-art machine learning and deep learning-based protein function predictors. Although sequence search tools are the basis of homology-based protein function prediction, previous studies have scarcely explored how to select the optimal sequence search tools and configure their parameters to achieve the best function prediction. In this paper, we evaluate the effect of using different options from among popular search tools, as well as the impacts of search parameters, on protein function prediction. When predicting GO terms on a large benchmark dataset, we found that BLASTp and MMseqs2 consistently exceed the performance of other tools, including DIAMOND—one of the most popular tools for function prediction—under default search parameters. However, with the correct parameter settings, DIAMOND can perform comparably to BLASTp and MMseqs2 in function prediction. Additionally, we developed a new scoring function to derive GO prediction from homologous hits that consistently outperform previously proposed scoring functions. These findings enable the improvement of almost all protein function prediction algorithms with a few easily implementable changes in their sequence homolog-based component. This study emphasizes the critical role of search parameter settings in homology-based function transfer and should have an important contribution to the development of future protein function prediction algorithms.
Cholinergic modulation of interhemispheric inhibition in the mouse motor cortex
Authors: Handa Takashi , Zhang Qing , Aizawa Hidenori
Published: July 2024

Interhemispheric inhibition of the homotopic motor cortex is believed to be effective for accurate unilateral motor function. However, the cellular mechanisms underlying interhemispheric inhibition during unilateral motor behavior remain unclear. Furthermore, the impact of the neuromodulator acetylcholine on interhemispheric inhibition and the associated cellular mechanisms are not well understood. To address this knowledge gap, we conducted recordings of neuronal activity from the bilateral motor cortex of mice during the paw-reaching task. Subsequently, we analyzed interhemispheric spike correlation at the cell-pair level, classifying putative cell types to explore the underlying cellular circuitry mechanisms of interhemispheric inhibition. We found a cell-type pair-specific enhancement of the interhemispheric spike correlation when the mice were engaged in the reaching task. We also found that the interhemispheric spike correlation was modulated by pharmacological acetylcholine manipulation. The local field responses to contralateral excitation differed along the cortical depths, and muscarinic receptor antagonism enhanced the inhibitory component of the field response in deep layers. The muscarinic subtype M2 receptor is predominantly expressed in deep cortical neurons, including GABAergic interneurons. These results suggest that GABAergic interneurons expressing muscarinic receptors in deep layers mediate the neuromodulation of interhemispheric inhibition in the homotopic motor cortex.
Recognition patterns of acute kidney injury in hospitalized patients
Authors: Esposito Pasquale , Cappadona Francesca , Marengo Marita , Fiorentino Marco , Fabbrini Paolo , Quercia Alessandro Domenico , Garzotto Francesco , Castellano Giuseppe , Cantaluppi Vincenzo , Viazzi Francesca
Published: July 2024

Background

Acute kidney injury (AKI) during hospitalization is associated with increased complications and mortality. Despite efforts to standardize AKI management, its recognition in clinical practice is limited.

Methods

To assess and characterize different patterns of AKI diagnosis, we collected clinical data, serum creatinine (sCr) levels, comorbidities and outcomes from adult patients using the Hospital Discharge Form (HDF). AKI diagnosis was based on administrative data and according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria by evaluating sCr variations during hospitalization. Additionally, patients were categorized based on the timing of AKI onset.

Results

Among 56 820 patients, 42 900 (75.5%) had no AKI, 1893 (3.3%) had AKI diagnosed by sCr changes and coded in the HDF (full-AKI), 2529 (4.4%) had AKI reported on the HDF but not meeting sCr-based criteria (HDF-AKI) and 9498 (16.7%) had undetected AKI diagnosed by sCr changes but not coded in the HDF (KDIGO-AKI). Overall, AKI incidence was 24.5%, with a 68% undetection rate. Patients with KDIGO-AKI were younger and had a higher proportion of females, lower comorbidity burden, milder AKI stages, more frequent admissions to surgical wards and lower mortality compared with full-AKI patients. All AKI groups had worse outcomes than those without AKI, and AKI, even if undetected, was independently associated with mortality risk. Patients with AKI at admission had different profiles and better outcomes than those developing AKI later.

Conclusions

AKI recognition in hospitalized patients is highly heterogeneous, with a significant prevalence of undetection. This variability may be affected by patients’ characteristics, AKI-related factors, diagnostic approaches and in-hospital patient management. AKI remains a major risk factor, emphasizing the importance of ensuring proper diagnosis for all patients.
Daily activities of older adults before and during the COVID pandemic
Authors: Lam Jack , Garcia Joan
Published: July 2024

Objectives

This study examines how older adults’ (65 years old plus) daily activities shifted in the years around the coronavirus disease (COVID) pandemic.

Methods

Using data from American Time Use Survey, this study compares activities across the pre-pandemic (2019 to March 2020), early-pandemic (May to December 2020), and pandemic-normal (2021) periods.

Results

In the first year of the pandemic, there was less time spent on average on leisure outside the home, traveling, and with nonhousehold members, and more time alone and at home, compared with before the pandemic. Moving beyond averages, sequence and cluster analyses find 5 similar typologies of days across the three periods, characterized by days predominated by (a) housework, (b) leisure at home, (c) TV, (d) a combination of leisure at home and outside with TV, and (e) paid work. Duration of time across various daily activities differed, however, even for the same clusters. For example, in days predominated by indoor leisure, adults spent 405 min in this activity before the pandemic, 432 min during the early-pandemic period, and 549 min during the pandemic-normal period. We also observed changes in the proportion of older adults in each cluster. Across the pre-pandemic and early-pandemic periods, the proportion of days predominated by leisure at home increased (9.9%–17.9%) whereas the proportion belonging to days predominated by housework decreased (45.7%–17.6%).

Discussion

COVID-19 shifted the daily life of older adults, and our findings are consistent with selection, optimization, and compensation theory, documenting that older adult adapted across the first 2 years of the pandemic.
Aging Well With a Lifelong Disability: A Scoping Review
Authors: Smith Kimberley J , Gupta Saahil , Fortune Jennifer , Lowton Karen , Victor Christina , Burke Eilish , Carew Mark T , Livingstone Emma , Creeger Miriam , Shanahan Paul , Walsh Michael , Ryan Jennifer M
Published: July 2024

Background and Objectives

Existing literature highlights notable health and social inequalities for people aging with a lifelong disability and the need for research to better understand how we can support this group to age well. This scoping review mapped existing literature related to “aging well” in people with lifelong disabilities.

Research Design and Methods

Five scientific databases and gray literature sources were searched for studies related to “aging well” and “lifelong disability” (defined as a disability that a person had lived with since birth or early childhood).

Results

We identified 81 studies that discussed aging well with a lifelong disability, with most (70%) focusing on intellectual disabilities. Two themes captured existing research on aging well with a lifelong disability: (1) framing aging well with a lifelong disability, which included the ways that people with lifelong disability, their supporters, and existing research frame aging well for this group and (2) supporting people to age well with a lifelong disability, which involves the micro-, meso-, and macro-level factors where research suggests interventions to facilitate aging well could be situated.

Discussion and Implications

This synthesis highlights how aging well is currently framed in the literature and where interventions to improve aging well in this group could be situated. Literature highlights the importance of considering multilevel interventions to improve aging well. Evidence gaps include the lack of research conducted with groups other than those with intellectual disabilities and the need for more research examining aging well interventions.
The connections of sialic acids and diabetes mellitus: therapeutic or diagnostic value?
Authors: Ibrahim Mohammed Auwal , Isah Murtala Bindawa , Inim Mayen David , Abdullahi Aliyu Dantani , Adamu Auwal
Published: July 2024

Modulation of sialic acids is one of the important pathological consequences of both type 1 and type 2 diabetes mellitus with or without the micro- and macrovascular complications. However, the mechanistic, therapeutic and/or diagnostic implications of these observations are uncoordinated and possibly conflicting. This review critically analyses the scientific investigations connecting sialic acids with diabetes mellitus. Generally, variations in the levels and patterns of sialylation, fucosylation and galactosylation were predominant across various tissues and body systems of diabetic patients, but the immune system seemed to be most affected. These might be explored as a basis for differential diagnosis of various diabetic complications. Sialic acids are predominantly elevated in nearly all forms of diabetic conditions, particularly nephropathy and retinopathy, which suggests some diagnostic value but the mechanistic details were not unequivocal from the available data. The plausible mechanistic explanations for the elevated sialic acids are increased desialylation by sialidases, stimulation of hexosamine pathway and synthesis of acute phase proteins as well as oxidative stress. Additionally, sialic acids are also profoundly associated with glucose transport and insulin resistance in human-based studies while animal-based studies revealed that the increased desialylation of insulin receptors by sialidases, especially NEU1, might be the causal link. Interestingly, inhibition of the diabetes-associated NEU1 desialylation was beneficial in diabetes management and might be considered as a therapeutic target. It is hoped that the article will provide an informed basis for future research activities on the exploitation of sialic acids and glycobiology for therapeutic and/or diagnostic purposes against diabetes mellitus.
Fundamental diagram and stability analysis of mixed traffic considering heterogeneous car-following behaviors and platoon factors
Authors: Sun Zhanbo , Yan Qiruo , Liu Yafei , Fu Zhijian , Yang Lei
Published: July 2024

With the advancement of connected automated vehicles (CAVs), it is anticipated that mixed traffic environments, where human-driven vehicles (HVs) coexist with CAVs, will become prevalent in the future. The study aims to investigate the impact of heterogeneous car-following behaviors of HVs (e.g. aggressive, normal, and mild driving styles) and platoon factors of CAVs (i.e. platoon intensity and maximum platoon size) on the fundamental diagram and stability of mixed traffic. Firstly, a Markov chain approach is employed to describe the probability distributions of different leader-follower combinations, enabling us to construct a comprehensive mixed traffic model. Subsequently, a general modeling framework based on the mixed traffic model is established to examine the effects of heterogeneous car-following behaviors and platoon factors on the fundamental diagram and stability of mixed traffic. The results from numerical experiments reveal several findings: 1. an increase in the proportion of aggressive driving style enhances both the capacity and stability of mixed traffic; 2. larger platoon intensity and maximum platoon size contribute to improved capacity, particularly in scenarios where a large fraction of HVs exhibit aggressive driving behavior; 3. platoon intensity has a positive impact on traffic flow stability, while larger maximum platoon size leads to reduced stability; and 4. increasing CAV penetration without considering platoon intensity may lead to reduced stability compared to scenarios with a substantial proportion of aggressive drivers.
The Epidemiology of Pediatric Thermal Injury-associated Toxic Shock Syndrome: A Systematic Review
Authors: Alrasheed Mohammed Fuad , Alkhalaf Hamad , Alqahtani Alhanouf Mohammed , Alzubaidi Afnan Saad , Alasmari Abdulrahman Ali , Al-osimi Dalal Owith , Bahkali Loai Hasan , Alholais Anoud Mohammed , Basheikh Noor Ibraheem , Althaqafi Atheer Mohammed , Almousa Nourah Mansour , Al Mazrou Fatimah Hassan , Alsadiq Amal Abdulhameed , Kazzaz Yasser M
Published: July 2024

Thermal injury-associated toxic shock syndrome (TSS) is a life-threatening condition that can occur in children following burn injuries. The objective of this study was to describe the clinical manifestations, treatment, and outcomes of children who experienced TSS following a thermal injury. Additionally, the existing literature was systematically examined and published cases of pediatric TSS occurring after burns were compiled. In June 2023, without regard for time constraints, articles that met the criteria were searched across several electronic databases. The inclusion criteria were English-language publications, pediatric patients, and reported outcomes of interest for clinical questions. Due to the heterogeneity of the included publications and the lack of data in an appropriate format, a meta-analysis was not feasible. Our research identified 23 studies published between 1980 and 2023, including 72 cases (from multiple countries) that met the inclusion criteria. Of the 72 patients with thermal injuries complicated by TSS, 53 (73.6%) children survived, 6 (8.3%) died, and for 13 (18%) cases, the outcome was not documented. Our systematic review highlights the rarity, severity, and complexity of pediatric thermal injury-associated TSS. Key findings from the review indicate that pediatric thermal injury-associated TSS carries a high mortality rate and significant morbidity. By increasing awareness, improving diagnostic accuracy, and optimizing treatment strategies, healthcare professionals can improve patient outcomes in this challenging condition.
Discontinuation and non-publication of randomized controlled trials on cervical cancer or precancer
Authors: Lu Dongfang , Chen Xiaolin , Mu Yanmin , Kong Lingxiao , Zhang Ling , Li Juan
Published: July 2024

Background

Research waste is a considerable problem in clinical trials, with nonpublication being a significant contributor. We aimed to determine the prevalence of discontinuation and nonpublication of randomized controlled trials (RCTs) on cervical cancer or precancer.

Methods

We searched ClinicalTrials.gov for registered RCTs investigating cervical cancer or precancer that started between January 2000 and December 2020. The primary and secondary outcomes were trial nonpublication and premature discontinuation, respectively. Publication status was determined by systematic searches of peer-reviewed journals using the PubMed and Scopus databases.

Results

A total of 113 RCTs met the inclusion criteria. Among the 85 trials completed before December 2020, 44 (51.8%) were prematurely discontinued and 40 (47.1%) were unpublished. A single-center design (61.4% vs. 34.1%, P = .012) and lack of external funding (59.1% vs. 36.6%, P = .038) were significantly associated with trial discontinuation. Large-scale (target sample size >400; 46.7% vs. 17.5%, P = .004) and externally funded trials (66.7% vs. 35.0%, P = .004) were more likely to be published. Multivariate logistic analysis revealed that a large sample size [odd ratio (OR): 4.125, 95% confidence interval (CI): 1.511–11.259, P = .006] and presence of external funding (OR: 3.714, 95% CI: 1.513–9.117, P = .004) were independent positive factors for trial publication.

Conclusion

A significant proportion of RCTs related to cervical cancer or precancer were discontinued early or remain unpublished, resulting in a waste of research resources.
EP2/EP4 targeting prevents tumor-derived PGE2-mediated immunosuppression in cDC2s
Authors: Cuenca-Escalona Jorge , Bödder Johanna , Subtil Beatriz , Sánchez-Sánchez Marta , Vidal-Manrique Marcos , Sweep Mark W D , Fauerbach Jonathan A , Cambi Alessandra , Flórez-Grau Georgina , de Vries Jolanda M
Published: July 2024

Tumor-derived prostaglandin E2 (PGE2) impairs antitumor immunity by priming suppressive functions on various immune cell types, including dendritic cells (DCs). In this way, tumors mediate DC dysfunction and hamper their antitumoral activity. PGE2 is known to modulate DC function via signaling through the E-type prostanoid receptor 2 (EP2) and EP4. Preclinical studies have demonstrated the therapeutic value of targeting EP2/4 receptor signaling in DCs. Ongoing phase 1 clinical trials with EP antagonists have shown immunomodulation in cancer patients. However, the systemic drug administration leads to off-target events and subsequent side effects. To limit the off-target effects of EP targeting, EP2 and EP4 antagonists were encapsulated in polymeric nanoparticles (NPs). In this study, we evaluated the efficacy of EP2/4-specific antagonists encapsulated in NPs to protect conventional type 2 DCs (cDC2s) from suppressive effects of tumor-derived PGE2 in different tumor models. We show that tumor-derived PGE2 signals via EP2/4 to mediate the acquisition of a suppressive phenotype of cDC2s. EP2/4 antagonists encapsulated in NPs impaired the conversion of cDC2s toward a suppressive state and inhibited the occurrence of suppressive features such as interleukin-10 production or the ability to expand regulatory T cells. Importantly, the NPs abolished the transition toward this suppressive state in different tumor models: melanoma-conditioned media, ascites fluid derived from ovarian cancer patients (2-dimensional), and upon coculture with colorectal cancer patient–derived organoids (3-dimensional). We propose that targeting the PGE2-EP2/4 axis using NPs can achieve immunomodulation in the immune system of cancer patients, alleviate tumor-derived suppression, and thus facilitate the development of potent antitumor immunity in cancer patients.
Estimating sojourn time and sensitivity of screening for ovarian cancer using a Bayesian framework
Authors: Ishizawa Sayaka , Niu Jiangong , Tammemagi Martin C , Irajizad Ehsan , Shen Yu , Lu Karen H , Meyer Larissa A , Toumazis Iakovos
Published: July 2024

Background

Ovarian cancer is among the leading causes of gynecologic cancer-related death. Past ovarian cancer screening trials using combination of cancer antigen 125 testing and transvaginal ultrasound failed to yield statistically significant mortality reduction. Estimates of ovarian cancer sojourn time—that is, the period from when the cancer is first screen detectable until clinical detection—may inform future screening programs.

Methods

We modeled ovarian cancer progression as a continuous time Markov chain and estimated screening modality–specific sojourn time and sensitivity using a Bayesian approach. Model inputs were derived from the screening arms (multimodal and ultrasound) of the UK Collaborative Trial of Ovarian Cancer Screening and the Prostate, Lung, Colorectal and Ovarian cancer screening trials. We assessed the quality of our estimates by using the posterior predictive P value. We derived histology-specific sojourn times by adjusting the overall sojourn time based on the corresponding histology-specific survival from the Surveillance, Epidemiology, and End Results Program.

Results

The overall ovarian cancer sojourn time was 2.1 years (posterior predictive P value = .469) in the Prostate, Lung, Colorectal and Ovarian studies, with 65.7% screening sensitivity. The sojourn time was 2.0 years (posterior predictive P value = .532) in the United Kingdom Collaborative Trial of Ovarian Cancer Screening’s multimodal screening arm and 2.4 years (posterior predictive P value = .640) in the ultrasound screening arm, with sensitivities of 93.2% and 64.5%, respectively. Stage-specific screening sensitivities in the Prostate, Lung, Colorectal and Ovarian studies were 39.1% and 82.9% for early-stage and advanced-stage disease, respectively. The histology-specific sojourn times ranged from 0.8 to 1.8 years for type II ovarian cancer and 2.9 to 6.6 years for type I ovarian cancer.

Conclusions

Annual screening is not effective for all ovarian cancer subtypes. Screening sensitivity for early-stage ovarian cancers is not sufficient for substantial mortality reduction.
Pain with orgasm in endometriosis: potential etiologic factors and clinical correlates
Authors: Ding Avrilynn , Noga Heather , Bouchard Katrina N , Bedaiwy Mohamed A , Lee Caroline , Allaire Catherine , Orr Natasha L , Yong Paul J
Published: July 2024

Background

Pelvic pain worsened by orgasm is a poorly understood symptom in patients with endometriosis.

Aim

To assess the prevalence of pelvic pain worsened by orgasm in patients with endometriosis and explore its association with potential etiologic factors, including pelvic floor myalgia, uterine tenderness and adenomyosis, and central nervous system sensitization.

Methods

An analysis was done of a prospective data registry based at a tertiary referral center for endometriosis. Eligible participants were patients aged 18 to 50 years who were referred between January 1, 2018, and December 31, 2019, diagnosed with endometriosis, and subsequently underwent surgery at the center. Clinical features were compared between participants reporting worsening pelvic pain with orgasm and those without worsening pain with orgasm, including patient-reported variables, physical examination findings, and anatomic phenotyping at the time of surgery. Pelvic floor myalgia and uterine tenderness were assessed by palpation on pelvic examination, adenomyosis by ultrasound, and central nervous system sensitization via the Central Sensitization Inventory (range, 0-100).

Outcomes

Outcomes included pelvic or lower abdominal pain in the last 3 months that worsened with orgasm (yes/no).

Results

Among 358 participants with endometriosis, 14% (49/358) reported pain worsened by orgasm while 86% (309/358) did not. Pain with orgasm was significantly associated with pelvic floor myalgia (55% [27/49] vs 35% [109/309]; Cohen’s h = 0.40, P = .01) and higher scores on the Central Sensitization Inventory (mean ± SD, 53.3 ± 17.0 vs 42.7 ± 18.2; Cohen’s d = 0.60, P < .001) but not with uterine tenderness or adenomyosis. Other clinical features associated with pain with orgasm were poorer sexual health (higher scores: deep dyspareunia, Cohen’s h = 0.60; superficial dyspareunia, Cohen’s h = 0.34; and Female Sexual Distress Scale–Revised, Cohen’s d = 0.68; all P < .05) and poorer mental health (higher scores: Patient Health Questionnaire–9, 12.9 ± 6.7 vs 9.1 ± 6.3, Cohen’s d = 0.59, P < .001; Generalized Anxiety Disorder–7, 9.4 ± 5.6 vs 6.8 ± 5.5, Cohen’s d = 0.48, P = .002). Anatomic findings at the time of surgery did not significantly differ between the groups.

Clinical Implications

Interventions targeting pelvic floor myalgia and central nervous system sensitization may help alleviate pain worsened by orgasm in patients with endometriosis.

Strengths and Limitations

A strength is that pain worsened by orgasm was differentiated from dyspareunia. However, pain with orgasm was assessed by only a binary question (yes/no). Also, the study is limited to a single center, and there were limited data on sexual function.

Conclusion

Pelvic pain exacerbated by orgasm in people with endometriosis may be related to concurrent pelvic floor myalgia and central sensitization.
Spectro-photometric follow-up of the outbursting AM CVn system ASASSN-21br
Authors: Painter S , Aydi E , Motsoaledi M , Sokolovsky K V , Strader J , Buckley D A H , Kochanek C S , Maccarone T J , Mukai K , Shappee B J , Stanek K Z
Published: July 2024

We report on spectroscopic and photometric observations of the AM Canum Venaticorum (AM CVn) system ASASSN-21br, which was discovered in outburst by the All-Sky Automated Survey for Supernovae in 2021 February. The outburst lasted for around three weeks, and exhibited a pronounced brightness dip for $\approx$4 d, during which the spectra showed a sudden transition from emission- to absorption-line dominated. Only $\approx$60 AM CVn systems with derived orbital periods are found in the Galaxy, therefore increasing the sample of AM CVn systems with known orbital periods is of tremendous importance to (1) constrain the physical mechanisms of their outbursts and (2) establish a better understanding of the low-frequency background noise of future gravitational wave surveys. Time-resolved photometry taken during the outburst of ASASSN-21br showed modulation with a period of around 36.65 min, which is likely the superhump or orbital period of the system. Time-resolved spectroscopy taken with the Southern African Large Telescope did not show any sign of periodicity in the He i absorption lines. This is possibly due to the origin of these lines in the outbursting accretion disc, which makes it challenging to retrieve periodicity from the spectral lines. Future follow-up spectral observations during quiescence might allow us better constrain the orbital period of ASASSN-21br.
Constraining gravitational wave velocities using gravitational and electromagnetic wave observations of white dwarf binaries
Authors: Cao Tian-Yong , Kumar Ankit , Yi Shu-Xu
Published: July 2024

Although the general theory of relativity (GR) predicts that gravitational waves (GWs) have exactly the same propagation velocity as electromagnetic (EM) waves, many theories of gravity beyond GR expect otherwise. Accurate measurement of the difference in their propagation speed, or a tight constraint on it, could be crucial to validate or put limits on theories beyond GR. The proposed future space-borne GW detectors are poised to detect a substantial number of Galactic white dwarf binaries (GWDBs), which emit the GW as semimonochromatic signals. Concurrently, these GWDBs can also be identified as optical variable sources. Here we proposed that allocating a GWDB’s optical light curve and contemporaneous GW signal can be used to trace the difference between the velocity of GW and EM waves. Simulating GW and EM wave data from 14 verification binaries (VBs), our method constrains propagation-originated phase differences, limiting the discrepancy between the speed of light (c) and GW ($c_{GW}$). Through the utilization of LISA’s design sensitivity and the current precision in optical observation on GWDB, our study reveals that a four-year observation of the 14 recognized VBs results in a joint constraint that confines $\Delta c/c$ ($\Delta c = c_{\mathrm{GW}} - c$) to the range of $-2.1\times 10^{-12}$ and $4.8\times 10^{-12}$. Additionally, by incorporating this constraint on $c_{\mathrm{GW}}$, we are able to establish boundaries for the mass of the graviton, limiting it to $m_{\mathrm{g}}\le 3\times 10^{-23}\, e\mathrm{V}\,c^{-2}$, and for the parameter associated with local Lorentz violation, $\bar{s}_{00}$, constrained within the range of $-3.4\times 10^{-11}\le \bar{s}_{00}\le 1.5\times 10^{-11}$.
A two-phase model of galaxy formation – II. The size–mass relation of dynamically hot galaxies
Authors: Chen Yangyao , Mo Houjun , Wang Huiyuan
Published: July 2024

In Paper-I, we developed a two-phase model to connect dynamically hot galaxies (such as ellipticals and bulges) with the formation of self-gravitating gas clouds (SGCs) associated with the fast assembly of dark matter haloes. Here, we explore the implications of the model for the size–stellar mass relation of dynamically hot galaxies. Star-forming sub-clouds resulting from the fragmentation of the turbulent SGC inherit its spatial structure and dynamical hotness, producing a ‘homologous’ relation, $r_{\rm f}\approx \, 100\, r_{\rm bulge}$, between the size of a dynamically hot galaxy ($r_{\rm bulge}$) and that of its host halo assembled in the fast regime ($r_{\rm f}$), independent of redshift and halo mass. This relation is preserved by the ‘dry’ expansion driven by dynamical heating when a galaxy becomes gas-poor due to inefficient cooling, and is frozen due to the stop of bulge growth during the slow assembly regime of the halo. The size–stellar mass relation is thus a simple combination of the galaxy–halo homology and the non-linear stellar mass–halo mass relation. Using a set of halo assembly histories, we reproduce all properties in the observed size–mass relation of dynamically hot galaxies, including the flattening in the low-mass end and the upturn in the massive end. The prediction matches observational data currently available to $z \approx 4$, and can be tested in the future at higher z. Our results indicate that the sizes of dynamically hot galaxies are produced by the dissipation and collapse of gas in haloes to establish SGCs in which stars form.
Numerical relativity simulations of black hole and relativistic jet formation
Authors: Kuroda Takami , Shibata Masaru
Published: July 2024

We investigate impacts of stellar rotation and magnetic fields on black hole (BH) formation and its subsequent explosive activities, by conducting axisymmetric radiation-magnetohydrodynamics simulations of gravitational collapse of a 70 $\mathrm{M}_\odot$ star with two-moment multi energy neutrino transport in full general relativity for the first time. Due to its dense stellar structure, all models cannot avoid the eventual BH formation even though a strongly magnetized model experiences the so-called magnetorotational explosion prior to the BH formation. One intriguing phenomenon observed in the strongly magnetized model is the formation of a relativistic jet in the post-BH formation. The relativistic jet is the outcome of a combination of strong magnetic fields and low-density materials above the BH. The jet further enhances the explosion energy beyond $\sim 10^{52}$ erg, which is well exceeding the gravitational overburden ahead of the shock. Our self-consistent supernova models demonstrate that rotating magnetized massive stars at the high-mass end of supernova progenitors could be a potential candidate of hypernova and long gamma-ray burst progenitors.
Ribosomal protein RPL39L is an efficiency factor in the cotranslational folding of a subset of proteins with alpha helical domains
Authors: Banerjee Arka , Ataman Meric , Smialek Maciej Jerzy , Mookherjee Debdatto , Rabl Julius , Mironov Aleksei , Mues Lea , Enkler Ludovic , Coto-Llerena Mairene , Schmidt Alexander , Boehringer Daniel , Piscuoglio Salvatore , Spang Anne , Mittal Nitish , Zavolan Mihaela
Published: July 2024

Increasingly many studies reveal how ribosome composition can be tuned to optimally translate the transcriptome of individual cell types. In this study, we investigated the expression pattern, structure within the ribosome and effect on protein synthesis of the ribosomal protein paralog 39L (RPL39L). With a novel mass spectrometric approach we revealed the expression of RPL39L protein beyond mouse germ cells, in human pluripotent cells, cancer cell lines and tissue samples. We generated RPL39L knock-out mouse embryonic stem cell (mESC) lines and demonstrated that RPL39L impacts the dynamics of translation, to support the pluripotency and differentiation, spontaneous and along the germ cell lineage. Most differences in protein abundance between WT and RPL39L KO lines were explained by widespread autophagy. By CryoEM analysis of purified RPL39 and RPL39L-containing ribosomes we found that, unlike RPL39, RPL39L has two distinct conformations in the exposed segment of the nascent peptide exit tunnel, creating a distinct hydrophobic patch that has been predicted to support the efficient co-translational folding of alpha helices. Our study shows that ribosomal protein paralogs provide switchable modular components that can tune translation to the protein production needs of individual cell types.
Decoding ribosome complexity: role of ribosomal proteins in cancer and disease
Authors: Fuentes Pedro , Pelletier Joffrey , Gentilella Antonio
Published: July 2024

The ribosome is a remarkably complex machinery, at the interface with diverse cellular functions and processes. Evolutionarily conserved, yet intricately regulated, ribosomes play pivotal roles in decoding genetic information into the synthesis of proteins and in the generation of biomass critical for cellular physiological functions. Recent insights have revealed the existence of ribosome heterogeneity at multiple levels. Such heterogeneity extends to cancer, where aberrant ribosome biogenesis and function contribute to oncogenesis. This led to the emergence of the concept of ‘onco-ribosomes’, specific ribosomal variants with altered structural dynamics, contributing to cancer initiation and progression. Ribosomal proteins (RPs) are involved in many of these alterations, acting as critical factors for the translational reprogramming of cancer cells. In this review article, we highlight the roles of RPs in ribosome biogenesis, how mutations in RPs and their paralogues reshape the translational landscape, driving clonal evolution and therapeutic resistance. Furthermore, we present recent evidence providing new insights into post-translational modifications of RPs, such as ubiquitylation, UFMylation and phosphorylation, and how they regulate ribosome recycling, translational fidelity and cellular stress responses. Understanding the intricate interplay between ribosome complexity, heterogeneity and RP-mediated regulatory mechanisms in pathology offers profound insights into cancer biology and unveils novel therapeutic avenues targeting the translational machinery in cancer.
Predicting COVID 19–Associated Pulmonary Aspergillosis Risk in Low- and Middle-Income Countries: A Matched Case-Control Study
Authors: Moni Merlin , Sathyapalan Dipu T , Edathadathil Fabia , Razak M Abdul , Nair Sivapriya G , Nair Chithira V , Samban Swathy S , Prasanna Preetha , Kulirankal Kiran G , Purushothaman Shyam Sundar , Gutjahr Georg , Ying Jiang , John Teny M
Published: July 2024

Background

Coronavirus disease 2019 (COVID-19)–associated pulmonary aspergillosis (CAPA) is a life-threatening fungal infection. Studies focusing on CAPA in low- and middle-income countries are limited.

Methods

This retrospective matched case-control study was conducted at a tertiary care center in South India. Cases of CAPA were classified using the 2020 European Confederation of Medical Mycology/International Society for Human and Animal Mycology consensus criteria. A total of 95 cases were matched 1:1 with COVID-19 patients without CAPA. Matching was done based on age and period of admission. Inverse probability weighting was used to account for imbalances in COVID-19 severity and intensive care unit (ICU) admission. Data on demographics, clinical details, microbiologic and radiologic data, and treatment outcomes were collected. A predictive score for CAPA was developed from baseline risk factors.

Results

The predictive score identified lymphopenia, European Organisation for Research and Treatment of Cancer risk factors, and broad-spectrum antibiotic use as the main risk factors for CAPA. Positivity for bacterial pathogens in blood or bronchoalveolar lavage samples reduced the risk of CAPA. The predictive model performed well in cross-validation, with an area under the curve value of 82%. CAPA diagnosis significantly increased mortality and shift to ICU.

Conclusions

The predictive model derived from the current study offers a valuable tool for clinicians, especially in high-endemic low- and middle-income countries, for the early identification and treatment of CAPA. With further validation, this risk score could improve patient outcomes.