bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Aortic Dissection: Observational Lessons Learned From 11 000 Patients
Authors: Bossone Eduardo , Eagle Kim A. , Nienaber Christoph A. , Trimarchi Santi , Patel Himanshu J. , Gleason Thomas G. , Pai Chih-Wen , Montgomery Daniel G. , Pyeritz Reed E. , Evangelista Arturo , Braverman Alan C. , Brinster Derek R. , Gilon Dan , Di Eusanio Marco , Ehrlich Marek P. , Harris Kevin M. , Myrmel Truls , Isselbacher Eric M.
Published: August 2024

BACKGROUND:

Over the past 25 years, diagnosis and therapy for acute aortic dissection (AAD) have evolved. We aimed to study the effects of these iterative changes in care.

METHODS:

Patients with nontraumatic AAD enrolled in the International Registry of Acute Aortic Dissection (61 centers; 15 countries) were divided into time-based tertiles (groups) from 1996 to 2022. The impact of changes in diagnostics, therapeutic care, and in-hospital and 3-year mortality was assessed. Cochran-Armitage trend and Jonckheere-Terpstra tests were conducted to test for any temporal trend.

RESULTS:

Each group consisted of 3785 patients (mean age, ≈62 years old; ≈65.5% males); nearly two-thirds had type A AAD. Over time, the rates of hypertension increased from 77.8% to 80.4% (
P
=0.002), while smoking (34.1% to 30.6%,
P
=0.033) and atherosclerosis decreased (25.6%–16.6%;
P
<0.001). Across groups, the percentage of surgical repair of type A AAD increased from 89.1% to 92.5% (
P
<0.001) and was associated with decreased hospital mortality (from 24.1% in group 1 to 16.7% in group 3;
P
<0.001). There was no difference in 3-year survival (
P
=0.296). For type B AAD, stent graft therapy (thoracic endovascular aortic repair) was used more frequently (22.3%–35.9%;
P
<0.001), with a corresponding decrease in open surgery. Endovascular in-hospital mortality decreased from 9.9% to 6.2% (
P
=0.003). As seen with the type A AAD cohort, overall 3-year mortality for patients with type B AAD was consistent over time (
P
=0.084).

CONCLUSIONS:

Over 25 years, substantial improvements in-hospital survival were associated with a more aggressive surgical approach for patients with type A AAD. Open surgery has been partially supplanted by thoracic endovascular aortic repair for complicated type B AAD, and in-hospital mortality has decreased over the time period studied. Postdischarge survival for up to 3 years was similar over time.
Microparticle Mediated Delivery of Apelin Improves Heart Function in Post Myocardial Infarction Mice
Authors: Tang Ling , Qiu Huiliang , Xu Bing , Su Yajuan , Nyarige Verah , Li Pengsheng , Chen Houjia , Killham Brady , Liao Jun , Adam Henderson , Yang Aaron , Yu Alexander , Jang Michelle , Rubart Michael , Xie Jingwei , Zhu Wuqiang
Published: August 2024

BACKGROUND:

Apelin is an endogenous prepropeptide that regulates cardiac homeostasis and various physiological processes. Intravenous injection has been shown to improve cardiac contractility in patients with heart failure. However, its short half-life prevents studying its impact on left ventricular remodeling in the long term. Here, we aim to study whether microparticle-mediated slow release of apelin improves heart function and left ventricular remodeling in mice with myocardial infarction (MI).

METHODS:

A cardiac patch was fabricated by embedding apelin-containing microparticles in a fibrin gel scaffold. MI was induced via permanent ligation of the left anterior descending coronary artery in adult C57BL/6J mice followed by epicardial patch placement immediately after (acute MI) or 28 days (chronic MI) post-MI. Four groups were included in this study, namely sham, MI, MI plus empty microparticle-embedded patch treatment, and MI plus apelin-containing microparticle-embedded patch treatment. Cardiac function was assessed by transthoracic echocardiography. Cardiomyocyte morphology, apoptosis, and cardiac fibrosis were evaluated by histology. Cardioprotective pathways were determined by RNA sequencing, quantitative polymerase chain reaction, and Western blot.

RESULTS:

The level of endogenous apelin was largely reduced in the first 7 days after MI induction and it was normalized by day 28. Apelin-13 encapsulated in poly(lactic-co-glycolic acid) microparticles displayed a sustained release pattern for up to 28 days. Treatment with apelin-containing microparticle-embedded patch inhibited cardiac hypertrophy and reduced scar size in both acute and chronic MI models, which is associated with improved cardiac function. Data from cellular and molecular analyses showed that apelin inhibits the activation and proliferation of cardiac fibroblasts by preventing transforming growth factor-β–mediated activation of Smad2/3 (supporessor of mothers against decapentaplegic 2/3) and downstream profibrotic gene expression.

CONCLUSIONS:

Poly(lactic-co-glycolic acid) microparticles prolonged the apelin release time in the mouse hearts. Epicardial delivery of the apelin-containing microparticle-embedded patch protects mice from both acute and chronic MI-induced cardiac dysfunction, inhibits cardiac fibrosis, and improves left ventricular remodeling.
The Contribution of the International Compensation Regimes to the Protection of the Ocean
Authors: Jacobsson Måns
Published: August 2024

This article discusses another means of protecting the ocean to that of the London Convention regime, which prohibits or restricts the dumping of waste at sea, namely through compensation under the existing liability and compensation regimes relating to the spills of oil and other hazardous and noxious substances. Some main features of the existing liability regimes relating to ship-source spills – namely spills from oil tankers, spills of bunker oil from other ships and releases of other hazardous and noxious substances – are presented and their advantages and weaknesses are discussed.
Ship Recycling and the Right to a Healthy Environment
Authors: Pozdnakova Alla
Published: August 2024

This article analyses the Basel Convention on the Control of Transboundary Movements of Hazardous Wastes and their Disposal and International Convention for the Safe and Environmentally Sound Recycling of Ships (Hong Kong Convention) and shows that these agreements lay down environmental obligations – and sometimes corresponding rights – for States regarding the protection of health and the environment. Predictably, they do not envisage rights for the victims of environmental violations. Despite inherent and persistent limitations of international human rights in general and environmental rights in particular, a human right to a healthy environment may contribute in several ways to better environmental protection in the ship recycling sector. Importantly, the human rights-based approach to the environmental and health standards in ship recycling may reduce the troubling divergence between the Basel and Hong Kong frameworks and increase the minimum standards for sound and safe recycling, bringing it in line with European requirements.
A systematic review of the gut microbiome, metabolites, and multi-omics biomarkers across the colorectal cancer care continuum
Authors: Wu Y. , Shen N. , Hope C. , Noh H.I. , Richardson B.N. , Swartz M.C. , Bai J.
Published: August 2024

The gut microbiome and the microbial metabolome contribute to treatment efficacy and treatment outcomes across the cancer care spectrum. This study systematically reviewed the existing literature between 2007 to March 2022 to elucidate the role of gut microbiota-metabolite biomarkers in colorectal cancer (CRC) care and treatment-related outcomes. Using Covidence, all studies identified were screened by title and abstract, followed by a full-text review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and data extraction. We analysed 13 non-experimental and 9 experimental CRC studies and found that, usually, the α-diversity of the gut microbiome and short-chain fatty acids decreased in CRC patients, while amino acids (e.g. glutamate) increased in CRC patients. Correlations between specific gut microbial taxa and metabolites were identified, with amino acids, fatty acids, and glycerol positively associated with certain gut microbes. Interventions promoting gut microbes and microbial metabolites associated with better health outcomes (e.g. Bifidobacterium, Lactobacillus, butyric acid, and bile acid) can potentially promote treatment efficacy and improve cancer care outcomes. Gut microbial metabolism should be integrated into targeted cancer interventions for CRC patients, given the confirmed role of the gut microbiome and metabolome pathways across the CRC care continuum.
The Influence of Chinese Catholic Historical Memories on Early Joseon Catholicism
Authors: Tsai Chihche
Published: August 2024

Neither the theological perspective of church history nor the “impact–response” framework can sufficiently explain why Catholicism was able to take root in Joseon. Early Joseon converts from Confucianism received a contextualized understanding of Catholicism transformed by Chinese thought. One can describe this as Confucianized or Sinicized Catholicism. The first missionary sent to the Joseon Peninsula was Zhou Wenmo, a Chinese Catholic priest whose interpretation of the development and historical memories of Chinese Catholicism significantly shaped the ways of Joseon’s early converts from Confucianism. China’s historical narrative was so profound that the converted Confucians and other early converts embraced Catholicism, and the vision was constructed from the historical memories of the late Ming and early Qing. Nevertheless, this vision of nationalizing Catholicism was shattered by consecutive persecutions after 1801.
Unraveling another of the ‘Big Fiveʹ: new species and records of Cerithiopsidae from Brazil (Caenogastropoda: Triphoroidea)
Authors: PIMENTA ALEXANDRE DIAS , FARIA RAQUEL GAROFALO DE SOUZA , FIGUEIRA RAQUEL MEDEIROS ANDRADE , FERNANDES MAURÍCIO ROMULO
Published: August 2024

Despite being one of the most speciose marine mollusc families in the world, knowledge about the richness and distribution of Cerithiopsidae in Brazil is very limited. The present study aims to revise the occurrence of species of this family from Brazil, based on the examination of specimens in malacological collections obtained through several expeditions and surveys in the last years. All previous literature records of species from Brazil were checked, and the occurrence of Cerithiopsis gemmulosa, Cerithiopsis lata, Cerithiopsis io, Cerithiopsis fusiformis, Cerithiopsis capixaba, Cerithiopsis balaustium, Cerithiopsis aimen, Cerithiopsis prieguei, Cerithiopsis flava and Seila adamsii are confirmed; for these species, new information is presented regarding their distribution and shell morphology. The occurrence of Cerithiopsis greenii, Cerithiopsis iota, Cerithiopsis cynthiae and Horologica pupa in Brazil is rejected. Bittium brucei comb. nov. is reallocated in Cerithiopsis but considered a nomen dubium, due to the lack of features in the worn holotype, hindering its specific determination. Bittiolum guaranianum comb. nov., elsewhere considered a Cerithiopsis, is here considered to be a synonym of Bittiolum varium. Eight species, previously known from the Great Caribbean region, are recorded from Brazil: Cerithiopsis rabilleri, Cerithiopsis albovittata, Cerithiopsis hielardae, Cerithiopsis beneitoi, Cerithiopsis perigaudae, Cerithiopsis soubzmaignei comb. nov., Belonimorphis cubensis and Cubalaskeya nivea. Nine new species are proposed: Cerithiopsis pisinna sp. nov., Cerithiopsis aenea sp. nov., Cerithiopsis nimia sp. nov., Cerithiopsis claudioi sp. nov., Cerithiopsis vescula sp. nov., Cerithiopsis scobinata sp. nov., Cerithiopsis onerata sp. nov., Cerithiopsis parviscymnus sp. nov. and Cerithiopsis favus sp. nov. Besides that, Cerithiopsis cf. hielardae, Cerithiopsis cf. atalaya, Cerithiopsis sp. 1 and Dizoniopsis sp. are herein recognized as potential new species, pending acquisition of additional material for better understanding about their taxonomic status. Cerithiopsis gemmulosa, Cerithiopsis albovittata, Cerithiopsis flava (= Cerithiopsis redferni syn. nov.) and Seila adamsii are recognized as species complexes, with wide variation in shell morphology, and probably each of these complexes include various cryptic species in the western Atlantic. Summing up, 27 nominal species of Cerithiopsidae (in addition to four or five potential new species) are now recognized from Brazil, requiring further genetic investigation and additional sampling to improve the knowledge of this important group in this region.
Reassessment of the phylogenetic position of the spiny-scale pricklefish Hispidoberyx ambagiosus (Teleostei: Hispidoberycidae) based on comparative morphology
Authors: KIMURA KATSUYA
Published: August 2024

The spiny-scale pricklefish Hispidoberyx ambagiosus Kotlyar, 1981, the sole member of the family Hispidoberycidae, is known from only a few specimens collected from tropical waters of the Indo-West Pacific region. Because its phylogenetic position has not been well investigated, the present study describes the osteology, myology and other morphological features of H. ambagiosus, and reassesses the phylogenetic position of the species, and its relationships with related taxa. Many significant characters, including Tominaga’s organ, were newly discovered in H. ambagiosus and related taxa. Following a phylogenetic analysis of characters in 80 transformation series, three most parsimonious trees were obtained, with H. ambagiosus inferred as forming a monophyletic group together with Barbourisiidae, Cetomimidae, Gibberichthyidae, Rondeletiidae and Stephanoberycidae. Within this clade, H. ambagiosus was inferred as a sister taxon of a clade including the latter three of the aforementioned families. It is considered that H. ambagiosus retains many primitive features, having fewer derived characters than other species in the clade including the six families.
Atmospheric Precursors of Skillful SST Prediction in the Northeast Pacific
Authors: Cluett A. A. , Jacox M. G. , Amaya D. J. , Alexander M. A. , Scott J. D.
Published: August 2024

Forecasts of sea surface temperature anomalies (SSTAs) provide essential information to stakeholders of marine resources in coastal ecosystems, such as the California Current Large Marine Ecosystem (CCLME), at management-relevant monthly-to-annual time scales. Diagnosing dynamical sources of predictability and the mechanisms differentiating skill among forecasts is required for verification and improvement in operational forecasting systems. Using retrospective forecasts (1982–2020) from a four-member subset of the North American Multi-Model Ensemble (NMME), we evaluate the conditional skill of SSTA forecasts in the CCLME at monthly resolution for lead times up to 10.5 months. Forecasts from ensemble members with relatively small SSTA errors at shorter lead times retain higher skill at longer lead times, with the most substantial and long-lasting increases for forecasts initialized in the fall and early spring. The “best” low-error SSTA forecasts are characterized by increased skill in the prediction of North Pacific atmospheric circulation [sea level pressure (SLP) and 200-hPa geopotential height] the month prior to the evaluation of SSTA errors in the CCLME and exhibit more realistic progressions of anomalous SLP. The Pacific meridional mode (PMM) emerges as a diagnostic of skillful North Pacific atmosphere–ocean coupling, as forecasts that correctly simulate the PMM and its associated SLP variability increase the SSTA prediction skill in the CCLME in the fall through spring. Predictable coupled ocean–atmosphere modes provide a target for enhancing predictability with early detection of the onset of a deterministic progression emerging from stochastic atmospheric variability.

Significance Statement

Global forecast systems provide near-term climate predictions that inform the management of marine resources, such as those of the California Current Large Marine Ecosystem. In this study, we probe the processes which lead forecasts to succeed or fail at predicting sea surface temperatures in the California Current at seasonal time scales among retrospective forecasts from the North American Multimodel Ensemble. We demonstrate that forecasts which best simulate sea surface temperatures at the earliest lead times sustain advantages in forecast skill and find that correctly simulating extratropical atmospheric circulation increases the predictive skill of sea surface temperatures in the northeast Pacific in the following lead times. Our results offer North Pacific atmospheric circulation as a target for forecast model improvement that would additionally enhance ocean forecasts.
An analysis of SM Entertainment’s ownership structure amidst its global-local expansion
Authors: Goh Josephine Yu Qin , Ngo Sheau-Shi
Published: August 2024

This study illustrates the evolving composition of stakeholders in SM Entertainment, a leading agency in the K-pop sector. This article aims to provide an overview of the company’s strategic growth initiatives and its adept maneuvering within the framework of global capitalism. It demonstrates the increasing mix of domestic and international entities within SM Entertainment’s ownership, analyzing how this diversified blend is influencing the power dynamics in the global entertainment industry. The research methodically gathers and analyses data from a variety of sources, including SM Entertainment’s official website, its annual financial reports, and various news outlets. The research provides concrete empirical data on the strategic balancing undertaken by SM Entertainment as it transitioned from a regional entertainment firm to an international force. It examines in detail the company’s diverse ownership composition and the intricate mechanisms driving this change. The study sheds light on the wider consequences of this transition in the entertainment sector, touching upon both cultural and business aspects, within the framework of an increasingly globalized world.
Laryngeal nodular fasciitis in a 75-year-old man: a rare case report and review of the literature
Authors: Wen Yu , Ye Shufeng , Liu Cuiping , Zhu Yiming
Published: August 2024

Nodular fasciitis (NF) is a benign and self-limiting fibroblastic proliferation that originates from the superficial fascia and extends into the subcutaneous tissue or muscle. It typically manifests in individuals aged 20 to 35 years, with rare occurrences observed in patients over the age of 60 years. We herein report a case involving a 75-year-old man with NF in the right vocal cord. The patient sought medical attention at the Department of Otolaryngology of our hospital because of a 1-month history of hoarseness and breathlessness. The diagnosis was unable to be confirmed through preoperative pathological examination. After admission to our hospital, various examinations were completed and surgical treatment was performed, and the postoperative histopathological findings revealed the presence of NF in the right vocal cord. NF of the vocal cord is a rare clinical entity. Given its rapid progression and propensity for marked infiltration, it often poses diagnostic challenges because it can mimic various malignant soft tissue tumors. Therefore, thorough exclusion of other neoplastic lesions is imperative prior to confirming the diagnosis of NF through pathological examination. Local surgical resection remains the primary treatment modality.
Regarding Statues: Whiteness, Space, and the Postcolonial European Imagination
Authors: Beebeejaun Yasminah
Published: August 2024

In recent years, there have been renewed calls to remove colonial statues in many European cities. The increased politicization of colonial heritage has become a matter of concern to urban planning as heritage disputes have erupted over the presence of specific statues and other monuments. In this paper, I argue that the retention of colonial statues is a racially charged political act that reinforces the white domination of space. I draw on critical phenomenology to demonstrate the power of material artifacts within public culture.
Health Problems Mediate the Effects of Adverse Childhood Experiences on the Frequency of Cannabis Use in a Sample of Pregnant and Breastfeeding Women
Authors: Kendall-Tackett Kathleen , Poulin Stephen R. , Garner Christine
Published: August 2024

Many health organizations recommend that mothers avoid cannabis during pregnancy and breastfeeding because they are concerned about exposing infants to Δ-9-tetrahydrocannabinol (THC), the psychoactive substance in cannabis. Yet, data collected by the U.S. Centers for Disease Control demonstrate that a small percentage of mothers continue to use cannabis despite warnings. The frequency of cannabis use is an important variable because frequent use increases THC exposure. The present study examined two variables related to the frequency of cannabis use during pregnancy and breastfeeding: health problems and adverse childhood experiences (ACEs). We examined a possible mediation effect of health problems on the relationship between ACEs and the frequency of cannabis use during pregnancy and breastfeeding. Our sample was entirely comprised of 1,343 women who used cannabis during pregnancy and breastfeeding. We collected data online. The women were recruited from a Facebook group that supports pregnant and breastfeeding mothers who use cannabis. To be included, participants needed to be at least 18 years old and to have used cannabis while pregnant or breastfeeding. The sample was 79% White, 8% Hispanic, and 14% Black, and 1,199 currently resided in the United States, 76 in Canada, 11 in the United Kingdom, and the rest resided in 13 other countries. Ninety-three percent of the sample reported at least one ACE, and 59% reported 4 or more. Ninety-six percent reported that they were using cannabis to treat a health problem, and the number of health problems ranged from 0 to 8. Two mediation analyses found that the total number of ACEs increased the risk of health problems, which increased the frequency of cannabis use. ACE total was not significantly related to the frequency of use once health problems were accounted for. ACEs are related to the frequency of cannabis use in pregnant and breastfeeding women, but indirectly through trauma’s impact on health problems. These findings suggest that practitioners might be able to lower the frequency of cannabis if they directly address health problems.
How Does Variation in AI Performance Affect Trust in AI-infused Systems: A Case Study With In-Vehicle Voice Control Systems
Authors: Gu Feiqi , Xu Haosong , He Dengbo
Published: August 2024

This study investigates how performance variation in AI-infused systems, specifically in-vehicle voice control systems, affects user trust. The frequent updates of AI-infused systems over the air raise concerns about the unstable performance of AI-infused systems, due to uncertainty and inexplicability of AIs. Employing a Wizard of Oz simulation with 27 participants, the study manipulated the accurate correct rates of voice command responses to represent system updates, measuring the perceived correct rate and trust after each update. Results suggest that the way the system evolves can impact users’ trust in the current version of the system, but this effect fades out with time. Moreover, users’ perception of performance, rather than the actual performance, has an impact on users’ trust. The research underscores the importance of managing users’ perception of system performance to maintain user trust and contributes to the knowledge of the relationship between AI evolution and user trust.
Exploring Process Performance of Envelope Opening and Ballot Extraction Options in Vote-by-Mail: A Utah Case Study
Authors: Otte Leonie S. , Macht Gretchen A.
Published: August 2024

Vote-by-Mail (VBM) has become increasingly popular over the last decade, but the process is executed differently even between jurisdictions within the same state. Currently, most VBM literature focuses on topics from the perspective of political science, and little-to-no work features analysis of operational aspects or human-machine interactions. Depending on the jurisdiction size, these VBM process steps are executed by humans, machines, or a combination of machines supporting humans. The opening-extraction process step of envelope opening and ballot extraction is always necessary. Therefore, the literature needs to consider the process execution of VBM ballots, the possible support of machines, and human-machine interactions in the VBM tabulation processes. This study compares two opening-extraction options to open envelopes and extract ballots in the VBM tabulation process. This research demonstrates that no one system of opening-extraction is generally better than the other, but some trade-offs need to be considered.
Treating Traumatic Brain Injury with Exercise: Onset Delay and Previous Training as Key Factors Determining its Efficacy
Authors: Sánchez-Martín Tanit , Costa-Miserachs David , Coll-Andreu Margalida , Portell-Cortés Isabel , García-Brito Soleil , Torras-Garcia Meritxell
Published: August 2024

Purpose

Exercise reduces cognitive deficits in traumatic brain injury (TBI), but early post-trauma exercise is often discouraged due to potential harm. The purpose was to evaluate the interaction between pre- and post-injury physical exercise on cognition, neuronal survival and inflammation.

Methods

Rats were either sham-operated and kept sedentary (Sham) or subjected to controlled cortical impact injury and then distributed into sedentary (Tbi), pre-injury exercise (Pre-Tbi), post-injury exercise with early (24 hours, Tbi-early) or late (6 days, Tbi-late) onset, and a combination of pre- and post-injury exercise with early (Pre-Tbi-early) or late (Pre-Tbi-late) onset. Object recognition memory, hippocampal volume, neuronal survival (NeuN+) in the hippocampus and perirhinal cortex, and microglial activity (Iba-1) in the hippocampus were evaluated.

Results

All exercise conditions, except TBI-early, attenuated the significant memory impairment at 24-hour retention caused by TBI. Additionally, Pre-TBI-early treatment led to memory improvement at 3-hour retention. Pre-TBI reduced neuronal death and microglial activation in the hippocampus. TBI-late, but not TBI-early, mitigated hippocampal volume loss, loss of mature neurons in the hippocampus, and inflammation. Combining pre-injury and early-onset exercise reduced memory deficits but did not affect neuronal death or microglial activation. Combining pre-injury and late-onset exercise had a similar memory-enhancing effect than late post-injury treatment alone, albeit with reduced effects on neuronal density and neuroinflammation.

Conclusions

Pre-TBI physical exercise reduces the necessary onset delay of post-TBI exercise to obtain cognitive benefits, yet the exact mechanisms underlying this reduction require further research.
Strategies to overcome tumor microenvironment immunosuppressive effect on the functioning of CAR-T cells in high-grade glioma
Authors: Zarychta Julia , Kowalczyk Adrian , Marszołek Anna , Zawitkowska Joanna , Lejman Monika
Published: August 2024

Despite significant progress in the treatment of some types of cancer, high-grade gliomas (HGGs) remain a significant clinical problem. In the case of glioblastoma (GBM), the most common solid tumor of the central nervous system in adults, the average survival time from diagnosis is only 15–18 months, despite the use of intensive multimodal therapy. Chimeric antigen receptor (CAR)-expressing T cells, which have already been approved by the Food and Drug Administration for use in the treatment of certain hematologic malignancies, are a new, promising therapeutic option. However, the efficacy of CAR-T cells in solid tumors is lower due to the immunosuppressive tumor microenvironment (TME). Reprogramming the immunosuppressive TME toward a pro-inflammatory phenotype therefore seems particularly important because it may allow for increasing the effectiveness of CAR-T cells in the therapy of solid tumors. The following literature review aims to present the results of preclinical studies showing the possibilities of improving the efficacy of CAR-T in the TME of GBM by reprogramming the TME toward a pro-inflammatory phenotype. It may be achievable thanks to the use of CAR-T in a synergistic therapy in combination with oncolytic viruses, radiotherapy, or epigenetic inhibitors, as well as by supporting CAR-T cells crossing of the blood–brain barrier, normalizing impaired angiogenesis in the TME, improving CAR-T effector functions by cytokine signaling or by blocking/knocking out T-cell inhibitors, and modulating the microRNA expression. The use of CAR-T cells modified in this way in synergistic therapy could lead to the longer survival of patients with HGG by inducing an endogenous anti-tumor response.
Refining Insulin on Board with netIOB for Automated Insulin Delivery
Authors: Riddell Michael C. , Lewis Dana M. , Turner Lauren V. , Lal Rayhan A. , Shahid Arsalan , Zaharieva Dessi P.
Published: August 2024

Automated insulin delivery (AID) systems enhance glucose management by lowering mean glucose level, reducing hyperglycemia, and minimizing hypoglycemia. One feature of most AID systems is that they allow the user to view “insulin on board” (IOB) to help confirm a recent bolus and limit insulin stacking. This metric, along with viewing glucose concentrations from a continuous glucose monitoring system, helps the user understand bolus insulin action and the future “threat” of hypoglycemia. However, the current presentation of IOB in AID systems can be misleading, as it does not reflect true insulin action or automatic, dynamic insulin adjustments. This commentary examines the evolution of IOB from a bolus-specific metric to its contemporary use in AID systems, highlighting its limitations in capturing real-time insulin modulation during varying physiological states.
Paper 07: Race and Income Influence Patient Outcomes After Multiligament Knee Injuries
Authors: Wolfe Isabel , Chalem Isabel , Spath Alexandra , Li Zachary , Moore Michael , Alaia Michael
Published: August 2024

Objectives:

This study aimed to assess the influence of socioeconomic status (SES) variables on patient-reported outcomes and return to work following surgery for a multiligament knee injury.

Methods:

We retrospectively reviewed patients at our institution who underwent multi-ligament knee reconstruction between 2012 and 2022. SES variables of interest included median household income, occupation, race, sex, and marital status. International Knee Documentation Committee (IKDC) scores were used to assess clinical outcomes. Patients reported whether they had returned to work at final follow-up. Data was available for each SES variable for a subset of the cohort. Chi-square tests and Fisher exact tests were used to compare the proportion of patients who returned to work by race, sex, income, marital status, and job type (sedentary vs. nonsedentary) and to compare the proportion of patients with sedentary jobs within each demographic variable. Mann-Whitney U tests were used to compare the distribution of IKDC scores at final follow-up across the same demographic variables.

Results:

There were 144 patients with multiligament knee injuries for whom data on at least 1 SES variable was available with a median final follow-up of 3.2 years. Patients were 73.2% male with an average age of 38.8 years. Overall, 26.8% of patients were married and 56.1% of patients had sedentary jobs. Of the patients who were working before surgery (63% of the total cohort), 56.0% returned to work after surgery. There was a significant difference in the proportion of patients who had sedentary jobs by income (12.5% low income vs. 50.7% high income, p<.001) and who returned to work postoperatively (16.7% low income vs. 75.0% high income, p=.016). Median IKDC scores for white patients were 78.0 versus 65.5 for Black/African American patients; the score distributions in the two groups differed significantly (p=.045). Patient reported outcomes were not significantly different by sex or marital status.

Conclusions:

Only about half of patients returned to work after multiligament knee injury surgery. White race and higher income were predictive of better patient-reported outcomes following surgery for multiligament knee injuries. Determining the extent to which SES variables influence these outcomes may lead to improvements in rehabilitation and follow-up for diverse patients. Studies with larger cohorts are needed for a more comprehensive comparison of SES variables.
Behavioural and neurodevelopmental characteristics of SYNGAP1
Authors: Bednarczuk Nadja , Housby Harriet , Lee Irene O. , Consortium IMAGINE , Skuse David , Wolstencroft Jeanne
Published: August 2024

Background

SYNGAP1 variants are associated with varying degrees of intellectual disability (ID), developmental delay (DD), epilepsy, autism, and behavioural difficulties. These features may also be observed in other monogenic conditions. There is a need to systematically compare the characteristics of SYNGAP1 with other monogenic causes of ID and DD to identify features unique to the SYNAGP1 phenotype. We aimed to contrast the neurodevelopmental and behavioural phenotype of children with SYNGAP1-related ID (SYNGAP1-ID) to children with other monogenic conditions and a matched degree of ID.

Methods

Participants were identified from the IMAGINE-ID study, a UK-based, national cohort study of neuropsychiatric risk in children with ID of known genetic origin. Thirteen children with SYNGAP1 variants (age 4–16 years; 85% female) were matched (2:1) with 26 controls with other monogenic causes of ID for chronological and mental age, sex, socio-economic deprivation, adaptive behaviour, and physical health difficulties. Caregivers completed the Development and Wellbeing Assessment (DAWBA) and physical health questionnaires.

Results

Our results demonstrate that seizures affected children with SYNGAP1-ID (84.6%) more frequently than the ID-comparison group (7.6%; p =  < 0.001). Fine-motor development was disproportionally impaired in SYNGAP1-ID, with 92.3% of children experiencing difficulties compared to 50% of ID-comparisons(p = 0.03). Gross motor and social development did not differ between the two groups. Children with SYNGAP1-ID were more likely to be non-verbal (61.5%) than ID-comparisons (23.1%; p = 0.01). Those children able to speak, spoke their first words at the same age as the ID-comparison group (mean = 3.25 years), yet achieved lower language competency (p = 0.04). Children with SYNGAP1-ID compared to the ID-comparison group were not more likely to meet criteria for autism (SYNGAP1-ID = 46.2%; ID-comparison = 30.7%; p = .35), attention-deficit hyperactivity disorder (15.4%;15.4%; p = 1), generalised anxiety (7.7%;15.4%; p = .49) or oppositional defiant disorder (7.7%;0%; p = .15).

Conclusion

For the first time, we demonstrate that SYNGAP1-ID is associated with fine motor and language difficulties beyond those experienced by children with other genetic causes of DD and ID. Targeted occupational and speech and language therapies should be incorporated early into SYNGAP1-ID management.
β-Aminobutyric acid promotes stress tolerance, physiological adjustments, as well as broad epigenetic changes at DNA and RNA nucleobases in field elms (Ulmus minor)
Authors: Hoenicka Hans , Bein Susanne , Starczak Marta , Graf Wolfgang , Hanelt Dieter , Gackowski Daniel
Published: August 2024

Background

β-Aminobutyric acid (BABA) has been successfully used to prime stress resistance in numerous plant species; however, its effectiveness in forest trees has been poorly explored thus far. This study aimed to investigate the influence of BABA on morphological, physiological, and epigenetic parameters in field elms under various growth conditions. Epigenetic changes were assessed in both DNA and RNA through the use of reversed-phase ultra-performance liquid chromatography (UPLC) coupled with sensitive mass spectrometry.

Results

The presented results confirm the influence of BABA on the development, physiology, and stress tolerance in field elms. However, the most important findings are related to the broad epigenetic changes promoted by this amino acid, which involve both DNA and RNA. Our findings confirm, for the first time, that BABA influences not only well-known epigenetic markers in plants, such as 5-methylcytosine, but also several other non-canonical nucleobases, such as 5-hydroxymethyluracil, 5-formylcytosine, 5-hydroxymethylcytosine, N6-methyladenine, uracil (in DNA) and thymine (in RNA). The significant effect on the levels of N6-methyladenine, the main bacterial epigenetic marker, is particularly noteworthy. In this case, the question arises as to whether this effect is due to epigenetic changes in the microbiome, the plant genome, or both.

Conclusions

The plant phenotype is the result of complex interactions between the plant’s DNA, the microbiome, and the environment. We propose that different types of epigenetic changes in the plant and microbiome may play important roles in the largely unknown memory process that enables plants to adapt faster to changing environmental conditions.
Ultrasound evaluation of cardiac and diaphragmatic function at different positions during a spontaneous breathing trial predicting extubation outcomes: a retrospective cohort study
Authors: Luo Ling , Li Yidan , Wang Lifang , Sun Bing , Tong Zhaohui
Published: August 2024

Background

The ratio (E/Ea) of mitral Doppler inflow velocity to annular tissue Doppler wave velocity by transthoracic echocardiography and diaphragmatic excursion (DE) by diaphragm ultrasound have been confirmed to predict extubation outcomes. However, few studies focused on the predicting value of E/Ea and DE at different positions during a spontaneous breathing trial (SBT), as well as the effects of △E/Ea and △DE (changes in E/Ea and DE during a SBT).

Methods

This study was a reanalysis of the data of 60 difficult-to-wean patients in a previous study published in 2017. All eligible participants were organized into respiratory failure (RF) group and extubation success (ES) group within 48 h after extubation, or re-intubation (RI) group and non-intubation (NI) group within 1 week after extubation. The risk factors for respiratory failure and re-intubation including E/Ea and △E/Ea, DE and △DE at different positions were analyzed by multivariate logistic regression, respectively. The receiver operating characteristic (ROC) curves of E/Ea (septal, lateral, average) and DE (right, left, average) were compared with each other, respectively.

Results

Of the 60 patients, 29 cases developed respiratory failure within 48 h, and 14 of those cases required re-intubation within 1 week. Multivariate logistic regression showed that E/Ea were all associated with respiratory failure, while only DE (right) and DE (average) after SBT were related to re-intubation. There were no statistic differences among the ROC curves of E/Ea at different positions, nor between the ROC curves of DE. No statistical differences were shown in △E/Ea between RF and ES groups, while △DE (average) was remarkably higher in NI group than that in RI group. However, multivariate logistic regression analysis showed that △DE (average) was not associated with re-intubation.

Conclusions

E/Ea at different positions during a SBT could predict postextubation respiratory failure with no statistical differences among them. Likewise, only DE (right) and DE (average) after SBT might predict re-intubation with no statistical differences between each other.
Risk profiling of tobacco epidemic and estimated number of smokers living in China: a cross-sectional study based on PBICR
Authors: Liu Siyuan , Zhou Haozheng , He Wenjun , Yang Jiao , Yin Xuanhao , Shalayiding Sufelia , Ren Na , Zhou Yan , Rao Xinyi , Zhang Nuofan , Xiong Man , Wang Yueying , Yang Wenfu , Wu Yibo , Chen Jiangyun
Published: August 2024

Background

Evidence on the prevalence of smoking in China remains insufficient, with most previous studies focusing on a single region. However, smoking prevalence exhibits significant inequalities across the entire country. This study aimed to evaluate the risk of tobacco prevalence across the country, taking into account spatial inequalities.

Methods

The data used in this study were collected in 23 provinces, 5 autonomous regions, and 4 municipalities directly under the central government in 2022. Large population survey data were used, and a Bayesian geostatistical model was employed to investigate smoking prevalence rates across multiple spatial domains.

Findings

Significant spatial variations were observed in smokers and exposure to secondhand smoke across China. Higher levels of smokers and secondhand smoke exposure were observed in western and northeastern regions. Additionally, the autonomous region of Tibet, Shanghai municipality, and Yunnan province had the highest prevalence of smokers, while Tibet, Qinghai province, and Yunnan province had the highest prevalence of exposure to secondhand smoke.

Conclusion

We have developed a model-based, high-resolution nationwide assessment of smoking risks and employed rigorous Bayesian geostatistical models to help visualize smoking prevalence predictions. These prediction maps provide estimates of the geographical distribution of smoking, which will serve as strong evidence for the formulation and implementation of smoking cessation policies.

Highlights

Our study investigated the prevalence of smokers and exposure to secondhand smoke in different spatial areas of China and explored various factors influencing the smoking prevalence. For the first time, our study applied Bayesian geostatistical modeling to generate a risk prediction map of smoking prevalence, which provides a more intuitive and clear understanding of the spatial disparities in smoking prevalence across different geographical regions, economic levels, and development status. We found significant spatial variations in smokers and secondhand smoke exposure in China, with higher rates in the western and northeastern regions.
Comprehensive identification of ubiquitin-like 3 (UBL3)-interacting proteins in the mouse brain
Authors: Ageta Hiroshi , Nishioka Tomoki , Yamaguchi Hisateru , Tsuchida Kunihiro , Ageta-Ishihara Natsumi
Published: August 2024

Discovery of novel post-translational modifications provides new insights into changes in protein function, localization, and stability. They are also key elements in understanding disease mechanisms and developing therapeutic strategies. We have previously reported that ubiquitin-like 3 (UBL3) serves as a novel post-translational modifier that is highly expressed in the cerebral cortex and hippocampus, in addition to various other organs, and that 60% of proteins contained in small extracellular vesicles (sEVs), including exosomes, are influenced by UBL3. In this study, we generated transgenic mice expressing biotinylated UBL3 in the forebrain under control of the alpha-CaMKII promoter (Ubl3Tg/+). Western blot analysis revealed that the expression of UBL3 in the cerebral cortex and hippocampus was 6- to 7-fold higher than that in the cerebellum. Therefore, we performed immunoprecipitation of protein extracts from the cerebral cortex of Ubl3+/+ and Ubl3Tg/+ mice using avidin beads to comprehensively discover UBL3 interacting proteins, identifying 35 new UBL3 interacting proteins. Nine proteins were annotated as extracellular exosomes. Gene Ontology (GO) analysis suggested a new relationship between sEVs and RNA metabolism in neurodegenerative diseases. We confirmed the association of endogenous UBL3 with the RNA-binding proteins FUS and HPRT1—both listed in the Neurodegenerative Diseases Variation Database (NDDVD)—and with LYPLA1, which is involved in Huntington’s disease, using immunoprecipitation (IP)-western blotting analysis. These UBL3 interacting proteins will accelerate the continued elucidation of sEV research about proteins regulated by novel post-translational modifications by UBL3 in the brain.
Discovering novel germline genetic variants linked to severe fluoropyrimidine-related toxicity in- and outside DPYD
Authors: Knikman Jonathan E. , Zhai Qinglian , Lunenburg Carin A. T. C. , Henricks Linda M. , Böhringer Stefan , van der Lee Maaike , de Man Femke M. , Offer Steven M. , Shrestha Shikshya , Creemers Geert-Jan , Baars Arnold , Dezentjé Vincent O. , Imholz Alexander L. T. , Jeurissen Frank J. F. , Portielje Johanna E. A. , Jansen Rob L. H. , Hamberg Paul , Droogendijk Helga J. , Koopman Miriam , Nieboer Peter , van de Poel Marlène H. W. , Mandigers Caroline M. P. W. , van Schaik Ron H. N. , Gelderblom Hans , Mathijssen Ron H. J. , Schellens Jan H. M. , Cats Annemieke , Guchelaar Henk-Jan , Swen Jesse J.
Published: August 2024

Background

The Alpe-DPD study (NCT02324452) demonstrated that prospective genotyping and dose-individualization using four alleles in DPYD (DPYD*2A/rs3918290, c.1236G > A/rs75017182, c.2846A > T/rs67376798 and c.1679 T > G/rs56038477) can mitigate the risk of severe fluoropyrimidine toxicity. However, this could not prevent all toxicities. The goal of this study was to identify additional genetic variants, both inside and outside DPYD, that may contribute to fluoropyrimidine toxicity.

Methods

Biospecimens and data from the Alpe-DPD study were used. Exon sequencing was performed to identify risk variants inside DPYD. In silico and in vitro analyses were used to classify DPYD variants. A genome-wide association study (GWAS) with severe fluoropyrimidine-related toxicity was performed to identify variants outside DPYD. Association with severe toxicity was assessed using matched-pair analyses for the exon sequencing and logistic, Cox, and ordinal regression analyses for GWAS.

Results

Twenty-four non-synonymous, frameshift, and splice site DPYD variants were detected in ten of 986 patients. Seven of these variants (c.1670C > T, c.1913 T > C, c.1925 T > C, c.506delC, c.731A > C, c.1740 + 1G > T, c.763 − 2A > G) were predicted to be deleterious. The carriers of either of these variants showed a trend towards a 2.14-fold (95% CI, 0.41–11.3, P = 0.388) increased risk of severe toxicity compared to matched controls (N = 30). After GWAS of 942 patients, no individual single nucleotide polymorphisms achieved genome-wide significance (P ≤ 5 × 10−8), however, five variants were suggestive of association (P < 5 × 10−6) with severe toxicity.

Conclusions

Results from DPYD exon sequencing and GWAS analysis did not identify additional genetic variants associated with severe toxicity, which suggests that testing for single markers at a population level currently has limited clinical value. Identifying additional variants on an individual level is still promising to explain fluoropyrimidine-related severe toxicity. In addition, studies with larger samples sizes, in more diverse cohorts are needed to identify potential clinically relevant genetic variants related to severe fluoropyrimidine toxicity.