bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative effectiveness and safety outcomes between denosumab and bisphosphonate in South Korea
Authors: Park ChulHyoung , Kim Chungsoo , Park Rae Woong , Jeon Ja Young
Published: May 2024

Both bisphosphonates and denosumab are the mainstays of treatment for osteoporosis to prevent fractures. However, there are still few trials directly comparing the prevention of fractures and the safety of 2 drugs in the treatment of osteoporosis. We aimed to compare the efficacy and safety between denosumab and bisphosphonates using a nationwide claims database. The database was covered with 10 million, 20% of the whole Korean population sampled by age and sex stratification of the Health Insurance Review and Assessment Service in South Korea. Among 228 367 subjects who were over 50 yr of age and taking denosumab or bisphosphonate from January 2018 to April 2022, the analysis was performed on 91 460 subjects after 1:1 propensity score matching. The primary outcome was treatment effectiveness; total fracture, major osteoporotic fracture, femur fracture, pelvic fracture, vertebral fracture, adverse drug reactions; acute kidney injury, chronic kidney disease, and atypical femoral fracture. Total fracture and osteoporotic major fracture, as the main outcomes of efficacy, were comparable in the denosumab and bisphosphonate group (HR 1.06, 95% CI, 0.98–1.15, P = .14; HR 1.13, 95% CI, 0.97–1.32, P = .12, respectively). Safety for acute kidney injury, chronic kidney disease, and atypical femoral fracture also did not show any differences between the 2 groups. In subgroup analysis according to ages, the denosumab group under 70 yr of age had a significantly lower risk for occurrences of acute kidney injury compared to the bisphosphonate group under 70 yr of age (HR 0.53, 95% CI, 0.29–0.93, P = .03). In real-world data reflecting clinical practice, denosumab and bisphosphonate showed comparable effectiveness for total fractures and major osteoporosis fractures, as well as safety regarding acute kidney injury, chronic kidney disease, and atypical femoral fracture.
The representation dynamic and the “normalization” of group differences
Authors: Carvalho Jean-Paul , Pradelski Bary S R
Published: May 2024

Intergroup inequality has been linked to differing norms of economic participation among groups. We present a theory of endogenous identity-specific norms in which the larger a group’s representation in an economic activity, the more the activity is deemed “normal” or “appropriate” for its members. This representation dynamic can arise from behavioral heuristics or be created by informational technologies such as generative artificial intelligence. Through it, the economic underrepresentation of a group becomes “normalized,” resulting in more severe inequality than in standard models. Equality of opportunity almost never results in equal outcomes, even when groups have the same productivity. Minorities and historically marginalized groups tend to be underrepresented. However, minorities with greater productivity and/or weaker group identification can become overrepresented, and even dominant. When there are multiple career stages, underrepresentation can escalate at senior levels long after “glass ceilings” have disappeared. Underrepresentation disappears as economic returns rise and/or group identification weakens.
Eosinophil specialization is regulated by exposure to the esophageal epithelial microenvironment
Authors: Dunn Julia L M , Szep Andrea , Gonzalez Galan Emily , Zhang Simin , Marlman Justin , Caldwell Julie M , Troutman Ty D , Rothenberg Marc E
Published: May 2024

Distinct subsets of eosinophils are reported in inflammatory and healthy tissues, yet the functions of uniquely specialized eosinophils and the signals that elicit them, particularly in eosinophilic esophagitis, are not well understood. Herein, we report an ex vivo system wherein freshly isolated human eosinophils were cocultured with esophageal epithelial cells and disease-relevant proinflammatory (IL-13) or profibrotic (TGF-β) cytokines. Compared with untreated cocultures, IL-13 increased expression of CD69 on eosinophils, whereas TGF-β increased expression of CD81, CD62L, and CD25. Eosinophils from IL-13–treated cocultures demonstrated increased secretion of GRO-α, IL-8, and macrophage colony-stimulating factor and also generated increased extracellular peroxidase activity following activation. Eosinophils from TGF-β–treated cocultures secreted increased IL-6 and exhibited increased chemotactic response to CCL11 compared with eosinophils from untreated or IL-13–treated coculture conditions. When eosinophils from TGF-β–treated cocultures were cultured with fibroblasts, they upregulated SERPINE1 expression and fibronectin secretion by fibroblasts compared with eosinophils that were cultured with granulocyte macrophage colony-stimulating factor alone. Translational studies revealed that CD62L was heterogeneously expressed by eosinophils in patient biopsy specimens. Our results demonstrate that disease-relevant proinflammatory and profibrotic signals present in the esophagus of patients with eosinophilic esophagitis cause distinct profiles of eosinophil activation and gene expression.
Demodex folliculorum (Trombidiformes: Demodecidae) infestation in medical students with facial dermatoses and healthy groups
Authors: Edalatkhah Hasan , Izadi Behrang , Nazari Maryam , Solgi Rahmat , Amani Ghayum Saeideh , Mohammadi-Ghalehbin Behnam , Moradi-Asl Eslam , Asfaram Shabnam , Azghani Peyman , Heidari Zahra
Published: May 2024

Demodex folliculorum (Simon, 1842) has been associated with various dermatological conditions. This study aimed to assess the prevalence of Demodex infestation in medical students with facial dermatoses compared with healthy medical students serving as controls. A total of 250 participants were enrolled, including 150 individuals with facial dermatoses and 100 healthy controls. Sampling was performed based on the standardized skin surface biopsy method. Demographic characteristics, specifically gender and age, were not statistically different between the patient and control groups. Among the facial dermatosis patients, 25 out of 150 (16.6%) were found to have Demodex infestation, while only three out of the 100 healthy controls (3%) exhibited infestations. The only identified species was D. folliculorum. The rates of Demodex infestation were significantly higher in the patients compared to the control groups. These findings indicate a higher prevalence of Demodex infestation among medical students with facial dermatosis, particularly in those diagnosed with folliculitis, acne vulgaris, and inflammatory papule, when compared to healthy controls. A better understanding of the relationship between D. folliculorum infestation and these dermatological conditions may lead to improved diagnostic and treatment strategies in the future.
Mass-redshift dependency of supermassive black hole binaries for the gravitational wave background
Authors: Kozhikkal Musfar Muhamed , Chen Siyuan , Theureau Gilles , Habouzit Mélanie , Sesana Alberto
Published: May 2024

Studying how the black hole (BH)–(galaxy) bulge mass relation evolves with redshift provides valuable insights into the co-evolution of supermassive black holes and their host galaxies. However, obtaining accurate measurement of BH masses is challenging due to the bias towards the most massive and luminous galaxies. Instead, we focus on the BH and bulge masses as they vary with redshift using the EAGLE, Illustris, TNG100, TNG300, Horizon-AGN, and SIMBA large-scale cosmological simulations. We use an analytical astrophysical model with galaxy stellar mass function, pair fraction, merger time-scale and BH–bulge mass relation extended to include redshift evolution. The model can predict the intensity of the gravitational wave background (GWB) produced by a population of supermassive black hole binary (SMBHB) as a function of the frequency. This allows us to compare the predictions of this model with the constraints of pulsar timing array observations. Here, we employ Bayesian analysis for the parameter inference. We find that all six simulations are consistent $\le 3.5\sigma$ with a range of simulated GWB spectra. By fixing the BH–bulge mass parameters to the simulations we analyse the changes in the constraints on the other astrophysical parameters. Furthermore, we also examine the variation in SMBHB merger rate with mass and redshift between these large-scale simulations.
An arcsecond view at 1–2 GHz into the Galactic Bulge
Authors: Pattie E C , Maccarone T J , Britt C T , Heinke C O , Jonker P G , Lorimer D R , Sivakoff G R , Steeghs D , Strader J , Torres M A P , Wijnands R
Published: May 2024

We present the results of a high angular resolution (1.1 arcsec) and sensitivity (maximum of ∼0.1 mJy) radio survey at 1–2 GHz in the Galactic Bulge. This complements the X-ray Chandra Galactic Bulge Survey, and investigates the full radio source population in this dense Galactic region. Radio counterparts to sources at other wavelengths can aid in classification, as there are relatively few types of objects that are reasonably detectable in radio at kiloparsec distances, and even fewer that are detected in both X-rays and radio. This survey covers about 3 sq deg of the Galactic Bulge Survey area (spanning the Galactic coordinate range of −3° < l < +3° and +1.6° < b < +2.1°) as a first look into this region of the Galaxy with this combination of frequency, resolution, and sensitivity. Spectral indices within the observed band of 1–2 GHz were calculated for each source to assist in determining its emission mechanism. We find 1617 unique sources in the survey, 25 of which are radio counterparts to X-ray sources, and about 100 of which are steep-spectrum (α ≲ −1.4) point sources that are viable pulsar candidates. Four radio sources are of particular interest: a compact binary; an infrared transient with an inverted radio spectrum; a potential transitional millisecond pulsar candidate; and a very steep spectrum radio source with an X-ray and bright infrared counterpart. We discuss other notable sources, including possible radio transients, potential new planetary nebulae, and active galactic nuclei.
Stress fracture of the clavicle associated with sternocostoclavicular hyperostosis combined with bony ankylosis of the acromioclavicular joint and ossification of the coracoclavicular ligament
Authors: Kurose Rie , Wakai Yuji
Published: May 2024

Sternocostoclavicular hyperostosis (SCCH) has been reported in patients with pustulotic arthro-osteitis, but there are few reports of marked ossification of the lateral part of the clavicle. Here, we report a case of stress fracture in a patient with SCCH with marked ossification of the lateral part of the clavicle. In this case, the clavicular fracture was proximal and no dislocation. Conservative treatment with a clavicle band and the administration of corticosteroids resulted in rapid symptom improvement. Eight months later, the patient had no difficulty in daily life, but X-rays showed that bone fusion was not complete. Therefore, it is necessary to carefully follow-up such patients for any recurrence of symptoms and radiographic changes.
Comparative evaluation of the diagnostic and prognostic performance of CNSide™ versus standard cytology for leptomeningeal disease
Authors: Appel Haley R , Rubens Muni , Roy Mukesh , Kotecha Rupesh , Hall Matthew D , Mehta Minesh P , Mohler Alexander , Chen Zhijian , Ahluwalia Manmeet S , Odia Yazmin
Published: May 2024

Background

This retrospective study compares the real-world performance of cerebrospinal fluid (CSF) CNSide™ versus cytology in leptomeningeal disease (LMD).

Methods

Consecutive patients with suspected LMD who underwent lumbar punctures for CSF cytology and CNSide™ from January 2020 to December 2022 were reviewed. LMD was classified by EANO criteria. Descriptive statistics, confusion matrix, Kaplan–Meier curves, and Cox proportional regression were used.

Results

Median age for 87 evaluable patients was 63 years (range: 23–93); 82 (94%) met EANO criteria for possible/probable/confirmed LMD (EANO/LMD). The commonest primary cancers were breast (36,44.0%) and lung (34,41.5%). Primary lung harbored actionable mutations in 18 (53.0%); primary breast expressed hormone receptors in 27 (75%), and HER2 amplification in 8 (22%). Uncontrolled systemic disease was detected in 35 (40%), while 25 (46%) received systemic therapy with medium/high CNS penetrance at LMD diagnosis. The median time from initial cancer to LMD diagnosis was 31 months (range: 13–73). LMD was confirmed by CSF cytology in 23/82 (28%), all identified by CNSide™. CNSide™ identified 13 additional cases (36/82, 43.9%), increasing diagnostic yield by 56.5%. Median overall survival (mOS) was 31 weeks (95%CI: 21–43), significantly worse for CNSide™ positive versus negative: 4.0 versus 16.0 weeks, respectively (HR = 0.50, P = .010). While survival since LMD diagnosis did not differ by histology, time to LMD diagnosis from initial cancer diagnosis was longer for breast (48.5 months, IQR: 30.0–87.5) versus lung (8 months, IQR:0.5–16.0) cohorts. mOS was longer for patients eligible for intrathecal chemotherapy (HR: 0.189, 95%CI: 0.053–0.672, P = .010).

Conclusions

This retrospective, real-world analysis of CNSide™ showed increased sensitivity versus cytology and provided clinically relevant molecular CSF analyses.
Digital applications for diet monitoring, planning, and precision nutrition for citizens and professionals: a state of the art
Authors: Abeltino Alessio , Riente Alessia , Bianchetti Giada , Serantoni Cassandra , De Spirito Marco , Capezzone Stefano , Esposito Rosita , Maulucci Giuseppe
Published: May 2024

The objective of this review was to critically examine existing digital applications, tailored for use by citizens and professionals, to provide diet monitoring, diet planning, and precision nutrition. We sought to identify the strengths and weaknesses of such digital applications, while exploring their potential contributions to enhancing public health, and discussed potential developmental pathways. Nutrition is a critical aspect of maintaining good health, with an unhealthy diet being one of the primary risk factors for chronic diseases, such as obesity, diabetes, and cardiovascular disease. Tracking and monitoring one’s diet has been shown to help improve health and weight management. However, this task can be complex and time-consuming, often leading to frustration and a lack of adherence to dietary recommendations. Digital applications for diet monitoring, diet generation, and precision nutrition offer the promise of better health outcomes. Data on current nutrition-based digital tools was collected from pertinent literature and software providers. These digital tools have been designed for particular user groups: citizens, nutritionists, and physicians and researchers employing genetics and epigenetics tools. The applications were evaluated in terms of their key functionalities, strengths, and limitations. The analysis primarily concentrated on artificial intelligence algorithms and devices intended to streamline the collection and organization of nutrition data. Furthermore, an exploration was conducted of potential future advancements in this field. Digital applications designed for the use of citizens allow diet self-monitoring, and they can be an effective tool for weight and diabetes management, while digital precision nutrition solutions for professionals can provide scalability, personalized recommendations for patients, and a means of providing ongoing diet support. The limitations in using these digital applications include data accuracy, accessibility, and affordability, and further research and development are required. The integration of artificial intelligence, machine learning, and blockchain technology holds promise for improving the performance, security, and privacy of digital precision nutrition interventions. Multidisciplinarity is crucial for evidence-based and accessible solutions. Digital applications for diet monitoring and precision nutrition have the potential to revolutionize nutrition and health. These tools can make it easier for individuals to control their diets, help nutritionists provide better care, and enable physicians to offer personalized treatment.
Cognitive impairment following breast cancer treatments: an umbrella review
Authors: Oliva Giulia , Giustiniani Andreina , Danesin Laura , Burgio Francesca , Arcara Giorgio , Conte Pierfranco
Published: May 2024

Objectives

Cancer-related cognitive impairment (CRCI) refers to a cognitive decline associated with cancer or its treatments. While research into CRCI is expanding, evidence remains scattered due to differences in study designs, methodologies, and definitions. The present umbrella review aims to provide a comprehensive overview of the current evidence regarding the impact of different breast cancer therapies on cognitive functioning, with a particular focus on the interplay among objective cognitive deficits (ie, measured with standardized tests), subjective cognitive concerns, (ie, self-reported), and other mediating psycho-physical factors.

Methods

The search was made in Pubmed, Embase, and Scopus for articles published until July 2023, following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis protocol.

Results

Chemotherapy and endocrine therapy appear consistently associated with CRCI in patients with breast cancer, primarily affecting memory, attention/concentration, executive functioning, and processing speed. Subjective cognitive concerns were often found weakly or not associated with neuropsychological test results, while overall CRCI seemed consistently associated with psychological distress, fatigue, sleep quality, and inflammatory and biological factors.

Conclusion

Current evidence suggests that CRCI is common after chemotherapy and endocrine therapy for breast cancer. However, heterogeneity in study designs and the scarcity of studies on more recent treatments such as targeted therapies and immunotherapies, highlight the need for more systematic and harmonized studies, possibly taking into account the complex and multifactorial etiology of CRCI. This may provide valuable insights into CRCI’s underlying mechanisms and potential new ways to treat it.
Proteolysis in plant immunity
Authors: Liu Yanan , Jackson Edan , Liu Xueru , Huang Xingchuan , van der Hoorn Renier A L , Zhang Yuelin , Li Xin
Published: May 2024

Compared with transcription and translation, protein degradation machineries can act faster and be targeted to different subcellular compartments, enabling immediate regulation of signaling events. It is therefore not surprising that proteolysis has been used extensively to control homeostasis of key regulators in different biological processes and pathways. Over the past decades, numerous studies have shown that proteolysis, where proteins are broken down to peptides or amino acids through ubiquitin-mediated degradation systems and proteases, is a key regulatory mechanism to control plant immunity output. Here, we briefly summarize the roles various proteases play during defence activation, focusing on recent findings. We also update the latest progress of ubiquitin-mediated degradation systems in modulating immunity by targeting plant membrane-localized pattern recognition receptors, intracellular nucleotide-binding domain leucine-rich repeat receptors, and downstream signaling components. Additionally, we highlight recent studies showcasing the importance of proteolysis in maintaining broad-spectrum resistance without obvious yield reduction, opening new directions for engineering elite crops that are resistant to a wide range of pathogens with high yield.
A prion-like domain is required for phase separation and chloroplast RNA processing during cold acclimation in Arabidopsis
Authors: Legen Julia , Lenzen Benjamin , Kachariya Nitin , Feltgen Stephanie , Gao Yang , Mergenthal Simon , Weber Willi , Klotzsch Enrico , Zoschke Reimo , Sattler Michael , Schmitz-Linneweber Christian
Published: May 2024

Arabidopsis (Arabidopsis thaliana) plants can produce photosynthetic tissue with active chloroplasts at temperatures as low as 4°C, and this process depends on the presence of the nuclear-encoded, chloroplast-localized RNA-binding protein CP29A. In this study, we demonstrate that CP29A undergoes phase separation in vitro and in vivo in a temperature-dependent manner, which is mediated by a prion-like domain (PLD) located between the two RNA recognition motif domains of CP29A. The resulting droplets display liquid-like properties and are found near chloroplast nucleoids. The PLD is required to support chloroplast RNA splicing and translation in cold-treated tissue. Together, our findings suggest that plant chloroplast gene expression is compartmentalized by inducible condensation of CP29A at low temperatures, a mechanism that could play a crucial role in plant cold resistance.
A Self-Regulated Stochastic Acceleration Model of Pulsar Wind Nebulae
Authors: Tanaka Shuta J , Ishizaki Wataru
Published: May 2024

Pulsar wind nebulae (PWNe) are clouds of magnetized relativistic electron/positron plasma supplied from the central pulsar. However, the number of radio-emitting particles inside a PWN is larger than the expectation from the study of pulsar magnetospheres and their origin is still unclear. A stochastic acceleration of externally injected particles by a turbulence inside the PWN is proposed by our previous studies. In this paper, the previous stochastic acceleration model of the PWN broadband spectra is improved by taking into account the time evolution of the turbulent energy and then the total energy balance inside a PWN is maintained. The turbulent energy supplied from the central pulsar is wasted by the backreaction from the stochastic particle acceleration and the adiabatic cooling according to the PWN expansion. The model is applied to the Crab Nebula and reproduces the current broadband emission spectrum, especially the flat radio spectrum, although the time evolution of the turbulent energy (diffusion coefficient) is a bit complicated compared with our previous studies, where we assumed an exponential behavior of the diffusion coefficient.
Glycine/alginate-based piezoelectric film consisting of a single, monolithic β-glycine spherulite towards flexible and biodegradable force sensor
Authors: Lin Qiaoxia , Zhang Yonggang , Chen Luhua , Zhang Haoyue , An Chuanfeng , Li Chengze , Wang Qifan , Song Jinhui , He Wei , Wang Huanan
Published: May 2024

Development of piezoelectric biomaterials with high piezoelectric performance, while possessing excellent flexibility, biocompatibility, and biodegradability still remains a great challenge. Herein, a flexible, biocompatible and biodegradable piezoelectric β-glycine–alginate–glycerol (Gly-Alg-Glycerol) film with excellent in vitro and in vivo sensing performance was developed. Remarkably, a single, monolithic β-glycine spherulite, instead of more commonly observed multiple spherulites, was formed in alginate matrix, thereby resulting in outstanding piezoelectric property, including high piezoelectric constant (7.2 pC/N) and high piezoelectric sensitivity (1.97 mV/kPa). The Gly-Alg-Glycerol film exhibited superior flexibility, enabling complex shape-shifting, e.g. origami pigeon, 40% tensile strain, and repeated bending and folding deformation without fracture. In vitro, the flexible Gly-Alg-Glycerol film sensor could detect subtle pulse signal, sound wave and recognize shear stress applied from different directions. In addition, we have demonstrated that the Gly-Alg-Glycerol film sensor sealed by polylactic acid and beeswax could serve as an in vivo sensor to monitor physiological pressure signals such as heartbeat, respiration and muscle movement. Finally, the Gly-Alg-Glycerol film possessed good biocompatibility, supporting the attachment and proliferation of rat mesenchymal stromal cells, and biodegradability, thereby showing great potential as biodegradable piezoelectric biomaterials for biomedical sensing applications.
The impact of acute violent videogame exposure on neurocognitive markers of empathic concern
Authors: Ritchie Mary B , Compton Shannon A H , Oliver Lindsay D , Finger Elizabeth , Neufeld Richard W J , Mitchell Derek G V
Published: May 2024

Research examining the purported association between violent gaming and aggression remains controversial due to concerns related to methodology, unclear neurocognitive mechanisms, and the failure to adequately consider the role of individual differences in susceptibility. To help address these concerns, we used fMRI and an emotional empathy task to examine whether acute and cumulative violent gaming exposure were associated with abnormalities in emotional empathy as a function of trait-empathy. Emotional empathy was targeted given its involvement in regulating not only aggression, but also other important social functions such as compassion and prosocial behaviour. We hypothesized that violent gaming exposure increases the risk of aberrant social behaviour by altering the aversive value of distress cues. Contrary to expectations, neither behavioural ratings nor empathy-related brain activity varied as a function of violent gaming exposure. Notably, however, activation patterns in somatosensory and motor cortices reflected an interaction between violent gaming exposure and trait empathy. Thus, our results are inconsistent with a straightforward relationship between violent gaming exposure and reduced empathy. Furthermore, they highlight the importance of considering both individual differences in susceptibility and other aspects of cognition related to social functioning to best inform public concern regarding safe gaming practices.
Multi-omics explores the potential regulatory role of acetylation modification in flavonoid biosynthesis of Ginkgo biloba
Authors: Liu Xiaomeng , Ye Jiabao , Zhang Xiaoxi , Yang Ke , Zheng Jiarui , Cheng Shuiyuan , Zhang Weiwei , Xu Feng
Published: May 2024

Flavonoids are crucial medicinal active ingredients in Ginkgo biloba L. However, the effect of protein post-translational modifications on flavonoid biosynthesis remains poorly explored. Lysine acetylation, a reversible post-translational modification, plays a crucial role in metabolic regulation. This study aims to investigate the potential role of acetylation in G. biloba flavonoid biosynthesis. Through comprehensive analysis of transcriptomes, metabolomes, proteomes and acetylated proteins in different tissues, a total of 11,788 lysine acetylation sites were identified on 4324 acetylated proteins, including 89 acetylation sites on 23 proteins. Additionally, 128 types of differentially accumulated flavonoids were identified among tissues, and a dataset of differentially expressed genes related to the flavonoid biosynthesis pathway was constructed. Twelve (CHI, C3H1, ANR, DFR, CCoAOMT1, F3H1, F3H2, CCoAOMT2, C3H2, HCT, F3′5′H and FG2) acetylated proteins that might be involved in flavonoid biosynthesis were identified. Specifically, we found that the modification levels of CCoAOMT1 and F3′5′H sites correlated with the catalytic production of homoeriodictyol and dihydromyricetin, respectively. Inhibitors of lysine deacetylase (trichostatin A) impacted total flavonoid content in different tissues and increased flavonoid levels in G. biloba roots. Treatment with trichostatin A revealed that expression levels of GbF3′5′H and GbCCoAOMT1 in stems and leaves aligned with total flavonoid content variations, while in roots, expression levels of GbC3H2 and GbFG2 corresponded to total flavonoid content changes. Collectively, these findings reveal for the first time the important role of acetylation in flavonoid biosynthesis.
Harnessing Generative Artificial Intelligence for Medical Education
Authors: Lie Margaret , Rodman Adam , Crowe Byron
Published: May 2024

Generative artificial intelligence (AI) tools powered by large language models (LLMs) are poised to transform medical education. Generative AI’s broad knowledge base and powerful natural language processing allow educators to use it for numerous tasks that previously required significant human effort. In this AM Last Page, we provide several examples of tasks that AI can accomplish as well as a basic framework for educators to develop their own prompts.
Cannabidiol-Only Product Use in Pregnancy in the United States and Canada
Authors: Bhatia Devika , Battula Sharonya , Mikulich-Gilbertson Susan , Sakai Joseph , Hammond David
Published: May 2024

This study aimed to characterize pregnant individuals’ use of cannabidiol (CBD). Data are from the International Cannabis Policy Study (2019–2021), a repeated cross-sectional survey of individuals aged 16–65 years in the United States and Canada (N=66,457 women, including 1,096 pregnant women). The primary analysis compared pregnant and nonpregnant women's CBD-only product use patterns and reasons for use. The prevalence of CBD-only use in pregnant women was 20.4% compared with 11.3% among nonpregnant women, P<.001. Reasons for CBD use among pregnant women included anxiety (58.4%), depression (40.3%), posttraumatic stress disorder (32.1%); pain (52.3%), headache (35.6%), and nausea or vomiting (31.9%). Thus, CBD-only product use was prevalent in this large sample, with one in five pregnant women reporting use. Characterization of prenatal CBD use is an important first step to exploring potential risks to exposed offspring.
Long-Term Risk of Type 2 Diabetes After Preterm Delivery or Hypertensive Disorders of Pregnancy
Authors: Crump Casey , Sundquist Jan , Sundquist Kristina
Published: May 2024

OBJECTIVE:

To examine long-term diabetes risk after preterm delivery or hypertensive disorders of pregnancy in a large population-based cohort.

METHODS:

This retrospective cohort study included all women with a singleton delivery in Sweden during 1973–2015 and no preexisting diabetes mellitus. Participants were followed up for development of type 2 diabetes identified from nationwide outpatient and inpatient diagnoses through 2018. Cox regression was used to compute hazard ratios (HRs) for the association between preterm delivery or hypertensive disorders of pregnancy and type 2 diabetes with adjustment for gestational diabetes and other maternal factors. Co-sibling analyses assessed for confounding by shared familial (genetic or environmental) factors.

RESULTS:

Overall, 2,184,417 women were included. Within 10 years after delivery, adjusted HRs for type 2 diabetes associated with specific pregnancy outcomes were as follows: any preterm delivery (before 37 weeks of gestation), 1.96 (95% CI, 1.83–2.09); extremely preterm delivery (22–27 weeks), 2.53 (95% CI, 2.03–3.16); and hypertensive disorders of pregnancy, 1.52 (95% CI, 1.43–1.63). All HRs remained significantly elevated (1.1–1.7-fold) 30–46 years after delivery. These findings were largely unexplained by shared familial factors.

CONCLUSION:

In this large national cohort, preterm delivery and hypertensive disorders of pregnancy were associated with increased risk for type 2 diabetes up to 46 years later. Women with these pregnancy complications are candidates for early preventive actions and long-term monitoring for type 2 diabetes.
The Presence of Blood in a Strain Gauge Pressure Transducer Has a Clinical Effect on the Accuracy of Intracranial Pressure Readings
Authors: Nairon Emerson B. , Joseph Jeslin , Kamal Abdulkadir , Busch David R. , Olson DaiWai M.
Published: May 2024

IMPORTANCE:

Patients admitted with cerebral hemorrhage or cerebral edema often undergo external ventricular drain (EVD) placement to monitor and manage intracranial pressure (ICP). A strain gauge transducer accompanies the EVD to convert a pressure signal to an electrical waveform and assign a numeric value to the ICP.

OBJECTIVES:

This study explored ICP accuracy in the presence of blood and other viscous fluid contaminates in the transducer.

DESIGN:

Preclinical comparative design study.

SETTING:

Laboratory setting using two Natus EVDs, two strain gauge transducers, and a sealed pressure chamber.

PARTICIPANTS:

No human subjects or animal models were used.

INTERVENTIONS:

A control transducer primed with saline was compared with an investigational transducer primed with blood or with saline/glycerol mixtures in mass:mass ratios of 25%, 50%, 75%, and 100% glycerol. Volume in a sealed chamber was manipulated to reflect changes in ICP to explore the impact of contaminates on pressure measurement.

MEASUREMENTS AND MAIN RESULTS:

From 90 paired observations, ICP readings were statistically significantly different between the control (saline) and experimental (glycerol or blood) transducers. The time to a stable pressure reading was significantly different for saline vs. 25% glycerol (< 0.0005), 50% glycerol (< 0.005), 75% glycerol (< 0.0001), 100% glycerol (< 0.0005), and blood (< 0.0005). A difference in resting stable pressure was observed for saline vs. blood primed transducers (0.041).

CONCLUSIONS AND RELEVANCE:

There are statistically significant and clinically relevant differences in time to a stable pressure reading when contaminates are introduced into a closed drainage system. Changing a transducer based on the presence of blood contaminate should be considered to improve accuracy but must be weighed against the risk of introducing infection.
Combination treatment with PD1/PDL-1 inhibitors for sarcomas: state of the art, next questions
Authors: Martin-Broto Javier , Hindi Nadia , Moura David S.
Published: May 2024

Purpose of review

Only a small fraction of sarcomas exhibit recognized parameters of immune sensitivity, such as tumor mutational burden, PDL-1 expression, or microsatellite instability. Combined strategies aimed to modulate tumor microenvironment to increase the efficacy of PD1/PDL-1 inhibitors in sarcoma. Most explored prospective studies were based on combinations of PD1/PDL-1 inhibitors with antiangiogenics, other immune checkpoints, or chemotherapy.

Recent findings

Results on 6-month PFS rate, median PFS, and ORR in trials using PD1/PDL-1 inhibitors plus antiangiogenics ranged respectively as 46.9–55%, 4.7–7.8 months and 21–36.7%. In combination with other immune checkpoint inhibitors, the results of median PFS and ORR ranged from 2.8–4.1 months and 10–16%, respectively. In combination with chemotherapy, the best results were obtained with doxorubicin-based regimens compared to other agents. Duplet-based chemotherapy plus anti-PD1/PDL-1 obtained the highest ORR (56.2%) compared with doxorubicin (19–36.7%). Currently, the most robust predictive biomarker for anti-PD1/PDL-1 efficacy is the presence of tertiary lymphoid structures (TLS) with mature dendritic cells.

Even when direct comparisons between PD1/PDL-1 inhibitor-based combinations and single agents have not been performed yet in sarcoma, some combinations appear promising. Studies controlling heterogeneity by biomarker or histotype selection contribute to an increase in efficacy or knowledge crucial for future comparative trials.
Sarculator: how to improve further prognostication of all sarcomas
Authors: Borghi Alessandra , Gronchi Alessandro
Published: May 2024

Purpose of review

Prognostication of soft tissue sarcomas is challenging due to the diversity of prognostic factors, compounded by the rarity of these tumors. Nomograms are useful predictive tools that assess multiple variables simultaneously, providing estimates of individual likelihoods of specific outcomes at defined time points. Although these models show promising predictive ability, their use underscores the need for further methodological refinement to address gaps in prognosis accuracy.

Recent findings

Ongoing efforts focus on improving prognostic tools by either enhancing existing models based on established parameters or integrating novel prognostic markers, such as radiomics, genomic, proteomic, and immunologic factors. Artificial intelligence is a new field that is starting to be explored, as it has the capacity to combine and analyze vast and intricate amounts of relevant data, ranging from multiomics information to real-time patient outcomes.

The integration of these innovative markers and methods could enhance the prognostic ability of nomograms such as Sarculator and ultimately enable more accurate and individualized healthcare. Currently, clinical variables continue to be the most significant and effective factors in terms of predicting outcomes in patients with STS. This review firstly introduces the rationale for developing and employing nomograms such as Sarculator, secondly, reflects on some of the latest and ongoing methodological refinements, and provides future perspectives in the field of prognostication of sarcomas.
Secular trend and projection of overweight and obesity among Chinese children and adolescents aged 7–18 years from 1985 to 2019: Rural areas are becoming the focus of investment
Authors: Dang Jiajia , Liu Yunfei , Cai Shan , Zhong Panliang , Shi Di , Chen Ziyue , Zhang Yihang , Dong Yanhui , Ma Jun , Song Yi
Published: May 2024

Background:

The urban–rural disparities in overweight and obesity among children and adolescents are narrowing, and there is a need for long-term and updated data to explain this inequality, understand the underlying mechanisms, and identify priority groups for interventions.

Methods:

We analyzed data from seven rounds of the Chinese National Survey on Students Constitution and Health (CNSSCH) conducted from 1985 to 2019, focusing on school-age children and adolescents aged 7–18 years. Joinpoint regression was used to identify inflection points (indicating a change in the trend) in the prevalence of overweight and obesity during the study period, stratified by urban/rural areas and sex. Annual percent change (APC), average annual percent change (AAPC), and 95% confidence interval (CI) were used to describe changes in the prevalence of overweight and obesity. Polynomial regression models were used to predict the prevalence of overweight and obesity among children and adolescents in 2025 and 2030, considering urban/rural areas, sex, and age groups.

Results:

The prevalence of overweight and obesity in urban boys and girls showed an inflection point of 2000, with AAPC values of 10.09% (95% CI: 7.33–12.92%, t = 7.414, P <0.001) and 8.67% (95% CI: 6.10–11.30%, t = 6.809, P <0.001), respectively. The APC for urban boys decreased from 18.31% (95% CI: 4.72–33.67%, t = 5.926, P = 0.027) to 4.01% (95% CI: 1.33–6.75%, t = 6.486, P = 0.023), while the APC for urban girls decreased from 13.88% (95% CI: 1.82–27.38%, t = 4.994, P = 0.038) to 4.72% (95% CI: 1.43–8.12%, t = 6.215, P = 0.025). However, no inflection points were observed in the best-fit models for rural boys and girls during the period 1985–2019. The prevalence of overweight and obesity for both urban and rural boys is expected to converge at 35.76% by approximately 2027. A similar pattern is observed for urban and rural girls, with a prevalence of overweight and obesity reaching 20.86% in 2025.

Conclusions:

The prevalence of overweight and obesity among Chinese children and adolescents has been steadily increasing from 1985 to 2019. A complete reversal in urban–rural prevalence is expected by 2027, with a higher prevalence of overweight and obesity in rural areas. Urgent action is needed to address health inequities and increase investments, particularly policies targeting rural children and adolescents.
Radiotherapy enhances efficacy of PD-1 inhibitors in advanced hepatocellular carcinoma: A propensity-matched real-world study
Authors: Hsu Shujung , Chao Yencheng , Hu Yong , Zhang Yang , Hong Weifeng , Chen Yixing , Chen Rongxin , Zeng Zhaochong , Du Shisuo
Published: May 2024

Background:

To address the need for immunotherapy in patients with advanced primary hepatocellular carcinoma (HCC), combination with radiotherapy (RT) has emerged as a promising strategy. In preclinical studies, irradiated tumors released tumor antigens to synergistically increase the antitumor effect of immunotherapy. Hence, we investigated whether RT enhances the efficacy of anti-programmed death receptor-1 (PD-1) inhibitors in advanced HCC in real-world practice.

Methods:

Between August 2018 and June 2021, 172 patients with advanced primary HCC were enrolled in the tertiary center (Zhongshan Hospital of Fudan University); 95 were treated with a combination of RT and the inhibitor of PD-1 (RT-PD1 cohort), and 77 were administered anti-PD-1 therapy (PD1 cohort). The first cycle of PD-1 inhibitors was administered within 60 days or concurrently with RT. Propensity score matching for bias reduction was used to evaluate the clinical outcomes.

Results:

Among 71 propensity-matched pairs, median progression-free survival was 5.7 months in the RT-PD1 cohort vs. 2.9 months in the PD1 cohort (P <0.001). Median overall survival was 20.9 months in the RT-PD1 cohort vs. 11.2 months in the PD1 cohort (P = 0.018). Compared with patients in the PD1 cohort, patients in the RT-PD1 cohort had significantly higher objective response rates (40.8%, 29/71 vs. 19.7%, 14/71, P = 0.006) and disease control rates (62.0%, 44/71 vs. 31.0%, 22/71, P <0.001). The incidences of toxic effects were not significantly different between the two cohorts.

Conclusions:

RT plus anti-PD-1 therapy is well tolerated. RT enhances the efficacy of anti-PD-1 therapy in patients with advanced primary HCC by improving survival outcomes without increased toxic effects.
CYP1A2 Polymorphism and Drug Co-administration Affect the Blood Levels and Adverse Effects of Pirfenidone
Authors: Yang Xuerong , Wei Jingxia , Yang Yong , He Yuanyuan , Guo Lu , He Xing , Zhang Lijuan , Chen Lu
Published: May 2024

Background:

Mutations in metabolic enzymes and co-administration of drugs may affect the blood concentration of pirfenidone effective in pulmonary fibrosis. To provide a basis for the precise clinical use of pirfenidone, the authors analyzed the correlation between steady-state pirfenidone trough concentration and adverse drug reactions (ADRs) and examined the impact of CYP1A2*1C (rs2069514) and *1F (rs762551) variants and co-administration on pirfenidone blood concentrations and ADRs.

Methods:

Forty-four patients were enrolled. The blood concentration of pirfenidone was determined using high-performance liquid chromatography. CYP1A2*1C and *1F genotypes were determined using direct SNP sequencing. Additional information related to drug associations was collected to screen factors affecting drug metabolism.

Results:

The highest predictive value of ADRs was observed when the steady-state trough concentration of pirfenidone was 3.18 mcg·mL−1 and the area under the receiver operating characteristic curve was 0.701 (P = 0.024). The pirfenidone concentration-to-dose ratio (C/D) in CYP1A2*1F homozygous AA mutants was lower than that in C carriers (CC+AC) (1.28 ± 0.85 vs. 2.03 ± 1.28 mcg·mL−1; P = 0.036). Adverse drug reaction (ADR) incidence in the homozygous AA mutant group (28.0%) was significantly lower than that in the C carriers (CC+AC) (63.2%; P = 0.020), and ADR incidence in the A carriers (AC+AA) was considerably lower than that in the CC group (85.7%; P = 0.039). The C/D value of the combined lansoprazole/rabeprazole group was lower than that of the noncombination group (P < 0.05).

Conclusions:

The ADR incidence was positively correlated with pirfenidone blood concentration. The CYP1A2 (rs762551) AA genotype is associated with lower pirfenidone concentrations and fewer ADRs. Lansoprazole/rabeprazole co-administration reduced pirfenidone concentrations. Randomized controlled trials should further explore personalized dosing of pirfenidone and combination therapies.
A polygenic risk score for alcohol-associated cirrhosis among heavy drinkers with European ancestry
Authors: Schwantes-An Tae-Hwi , Whitfield John B. , Aithal Guruprasad P. , Atkinson Stephen R. , Bataller Ramon , Botwin Greg , Chalasani Naga P. , Cordell Heather J. , Daly Ann K. , Darlay Rebecca , Day Christopher P. , Eyer Florian , Foroud Tatiana , Gawrieh Samer , Gleeson Dermot , Goldman David , Haber Paul S. , Jacquet Jean-Marc , Lammert Craig S. , Liang Tiebing , Liangpunsakul Suthat , Masson Steven , Mathurin Philippe , Moirand Romain , McQuillin Andrew , Moreno Christophe , Morgan Marsha Y. , Mueller Sebastian , Müllhaupt Beat , Nagy Laura E. , Nahon Pierre , Nalpas Bertrand , Naveau Sylvie , Perney Pascal , Pirmohamed Munir , Seitz Helmut K. , Soyka Michael , Stickel Felix , Thompson Andrew , Thursz Mark R. , Trépo Eric , Morgan Timothy R. , Seth Devanshi ,   for the GenomALC Consortium
Published: May 2024

Background:

Polygenic Risk Scores (PRS) based on results from genome-wide association studies offer the prospect of risk stratification for many common and complex diseases. We developed a PRS for alcohol-associated cirrhosis by comparing single-nucleotide polymorphisms among patients with alcohol-associated cirrhosis (ALC) versus drinkers who did not have evidence of liver fibrosis/cirrhosis.

Methods:

Using a data-driven approach, a PRS for ALC was generated using a meta-genome-wide association study of ALC (N=4305) and an independent cohort of heavy drinkers with ALC and without significant liver disease (N=3037). It was validated in 2 additional independent cohorts from the UK Biobank with diagnosed ALC (N=467) and high-risk drinking controls (N=8981) and participants in the Indiana Biobank Liver cohort with alcohol-associated liver disease (N=121) and controls without liver disease (N=3239).

Results:

A 20-single-nucleotide polymorphisms PRS for ALC (PRSALC) was generated that stratified risk for ALC comparing the top and bottom deciles of PRS in the 2 validation cohorts (ORs: 2.83 [95% CI: 1.82 -4.39] in UK Biobank; 4.40 [1.56 -12.44] in Indiana Biobank Liver cohort). Furthermore, PRSALC improved the prediction of ALC risk when added to the models of clinically known predictors of ALC risk. It also stratified the risk for metabolic dysfunction -associated steatotic liver disease -cirrhosis (3.94 [2.23 -6.95]) in the Indiana Biobank Liver cohort -based exploratory analysis.

Conclusions:

PRSALC incorporates 20 single-nucleotide polymorphisms, predicts increased risk for ALC, and improves risk stratification for ALC compared with the models that only include clinical risk factors. This new score has the potential for early detection of heavy drinking patients who are at high risk for ALC.