bluuebunny/crossref_metadata_2025 huggingface dataset:
Untargeted Metabolomics for Inborn Errors of Metabolism: Development and Evaluation of a Sustainable Reference Material for Correcting Inter-Batch Variability
Authors: Garrett Rafael , Ptolemy Adam S , Pickett Sara , Kellogg Mark D , Peake Roy W A
Published: October 2024

Background

Untargeted metabolomics has shown promise in expanding screening and diagnostic capabilities for inborn errors of metabolism (IEMs). However, inter-batch variability remains a major barrier to its implementation in the clinical laboratory, despite attempts to address this through normalization techniques. We have developed a sustainable, matrix-matched reference material (RM) using the iterative batch averaging method (IBAT) to correct inter-batch variability in liquid chromatography-high-resolution mass spectrometry-based untargeted metabolomics for IEM screening.

Methods

The RM was created using pooled batches of remnant plasma specimens. The batch size, number of batch iterations per RM, and stability compared to a conventional pool of specimens were determined. The effectiveness of the RM for correcting inter-batch variability in routine screening was evaluated using plasma collected from a cohort of phenylketonuria (PKU) patients.

Results

The RM exhibited lower metabolite variability between iterations over time compared to metabolites from individual batches or individual specimens used for its creation. In addition, the mean variation across amino acid (n = 19) concentrations over 12 weeks was lower for the RM (CVtotal = 8.8%; range 4.7%–25.3%) compared to the specimen pool (CVtotal = 24.6%; range 9.0%–108.3%). When utilized in IEM screening, RM normalization minimized unwanted inter-batch variation and enabled the correct classification of 30 PKU patients analyzed 1 month apart from 146 non-PKU controls.

Conclusions

Our RM minimizes inter-batch variability in untargeted metabolomics and demonstrated its potential for routine IEM screening in a cohort of PKU patients. It provides a practical and sustainable solution for data normalization in untargeted metabolomics for clinical laboratories.
Patient and Healthcare Professional Satisfaction, Acceptability, and Preference Experiences With Mirikizumab Administration for Ulcerative Colitis: An International Survey
Authors: Clemow David , Radawski Christine , Milata Joe , Alaka Karla , Gibble Theresa Hunter , Schaum Adam , Ezennia Obi , Martinez Nicholas , Szaloki Tibor , Ito Yuka , Rodriguez Danielle , Kirk Katherine
Published: October 2024

Background

There is a need to better understand ulcerative colitis (UC) patient and healthcare provider (HCP) treatment satisfaction, acceptability, and preferences.

Methods

Two international, cross-sectional, web-based surveys were conducted among participants of a phase 3 mirikizumab study (NCT03519945). The questions captured moderate-to-severe UC patients’ experience, HCPs’ perception of patients’ experience, and HCPs’ own experience with mirikizumab administration through intravenous (IV) infusions and subcutaneous (SC) injections.

Results

Respondents included 93 patients and 42 HCPs from 11 countries. The majority of patients had UC >4 years (74.2%), were bionaive (68%), in remission at the time of the survey (63%). HCPs were primarily from the United States (57%), generally nurses (41%) or gastroenterologists (26%) with ≥6 years of experience in treating UC (57%). Most patients were “very satisfied/satisfied” (IV, 83%; SC, 91%), “completely/somewhat” accepting of mirikizumab administration (IV, 87%; SC, 97%), and agreed that improvement to their UC outweighed any administration dissatisfaction (90%). HCPs’ perspectives of patients’ experiences were higher: “very satisfied/satisfied” (IV, 93%; SC, 100%); “completely/somewhat” accepting (IV, 90%; SC, 98%). HCPs themselves were “very satisfied/satisfied” (IV, 81%; SC, 95%); gastroenterologists were “very satisfied” (IV, 82%; SC, 82%) more than nurses (IV, 29%; SC, 65%) who were generally at least “satisfied” (IV, 53%; SC, 35%). Two SC and monthly SC injections were “completely acceptable” by the patients (76% and 85%) and per HCPs’ perceptions of patients’ preferences (69% and 100%).

Conclusions

Both patients and HCPs were satisfied with and accepted mirikizumab IV induction followed by monthly maintenance SC injections. UC improvement outweighed any administration dissatisfaction.
Transcatheter aortic valve replacement in a bicuspid aortic valve with membranous interventricular septum aneurysm communicating with aortic root: a case report
Authors: Xi Ziwei , Yao Jing , Song Guangyuan
Published: October 2024

Background

Membranous interventricular septum aneurysm (MISA) is a rare abnormality occurring in 0.3% of patients with congenital heart disease, which thereby increases anatomical complexity.

Case summary

Transcatheter aortic valve replacement (TAVR) procedure was planned for a 71-year-old female patient from East Asia with a type 1 bicuspid aortic valve diagnosed with severe aortic stenosis by transthoracic echocardiography (TTE). Pre-procedural multidetector computed tomography (MDCT) clearly revealed an extremely horizontal aorta and a MISA originating from the sub-annulus with the upper edge extending 7.2 mm above the annulus. A probable communicating flow between the left ventricle and the aorta was confirmed by reviewing the TTE images. Moreover, there was a calcified raphe between the left- and right-coronary cusps. A downsized balloon-expandable valve (a 23 mm Sapien 3 valve with an additional 2 mL dilation) was therefore chosen and deployed with a 100/0 aortic/ventricular ratio position. The TTE post-implantation indicated a trace perivalvular leakage. The cardiac MDCT performed post-procedure, at the 6-month, and 12-month follow-ups demonstrated complete sealing and significant healing of the aneurysm.

Discussion

Transcatheter aortic valve replacement utilizing a balloon-expandable valve was successfully performed for a case with membranous interventricular septum aneurysm extending above the annulus. Comprehensive imaging analysis before the procedure is crucial for TAVR with challenging anatomical conditions.
Cardiorespiratory Fitness in Childhood Cancer Survivors: A Systematic Review and Meta-Analysis
Authors: Weinkauf Kaitlyn , Fyfe Emma , Hewitt Dean , Wang Jing , Kennedy Megan , Pituskin Edith , La Gerche Andre , Foulkes Stephen J , Haykowsky Mark J
Published: October 2024

Aims

Cardiovascular disease (CVD) is a leading cause of mortality in childhood cancer survivors (CCS) that may be related to the cardiotoxic effects of radiation or chemotherapy and concomitant reductions in cardiorespiratory fitness. Therefore, we sought to compare cardiorespiratory fitness (peak oxygen uptake, V̇O2peak) between CCS and age-matched non-cancer controls (CON). Secondary outcomes included hemodynamics and resting cardiac function.

Methods

Embase, Scopus, MEDLINE, CINAHL and SPORTDiscus databases were searched from inception to June 2023 for eligible studies. Cross-sectional studies with V̇O2peak measured in CCS and CON were included. Differences in outcomes and pooled estimates for each outcome were estimated from a fixed effects meta-analysis and between group differences were reported as a weighted mean difference (WMD).

Results

Of 2026 studies identified, 18 reported V̇O2peak (CCS: n=786, 44% female, mean age: 16-years, time post-therapy: 5.8 years; CON: n=1379, 50% female, mean age: 16-years). V̇O2peak was lower in CCS (WMD: -7.08mL/kg/min, 95% CI: -7.75 to -6.42, I2: 79%, n=2,165) with no difference for peak exercise heart rate (WMD: -1.4bpm, 95% CI: -3.0 to 0.2, I2: 63%, n=741). Resting left-ventricular ejection fraction (WMD: -1.61%, 95% CI: -2.60 to -0.62, I2.: 49%, n=222) and systolic blood pressure were lower (WMD: -3.8mmHg, 95% CI: -5.7 to -1.9, I2: 25%, n=184) while resting heart rate was higher in CCS (WMD: 4.9bpm; 95% CI: 1.8 to 7.9, I2: 55%, n=262).

Conclusions

CCS have a marked reduction in cardiorespiratory fitness (7.1ml/kg/min lower than CON) that may have important prognostic implications for their future risk of CVD and mortality.
Predictive modelling of medication adherence in post-myocardial infarction patients: a Bayesian approach using beta-regression
Authors: Tannous Elias Edward , Selitzky Shlomo , Vinker Shlomo , Stepensky David , Schwarzberg Eyal
Published: October 2024

Aims

Predicting medication adherence in post-myocardial infarction (MI) patients has the potential to improve patient outcomes. Most adherence prediction models dichotomize adherence metrics and status. This study aims to develop medication adherence prediction models that avoid dichotomizing adherence metrics and to test whether a simplified model including only 90-days adherence data would perform similarly to a full multi-variable model.

Methods and results

Post-MI adult patients were followed for 1-year post the event. Data from pharmacy records were used to calculate proportion of days covered (PDC). We used Bayesian beta-regression to model PDC as a proportion, avoiding dichotomisation. For each medication group, statins, P2Y12 inhibitors and aspirin, two prediction models were developed, a full and a simplified model. 3692 patients were included for model development. The median (inter-quartile range) PDC at 1-year for statins, P2Y12 inhibitors and aspirin was 0.8 (0.33, 1.00), 0.79 (0.23, 0.99), and 0.79 (0.23, 0.99), respectively. All models showed good fit to the data by visual predictive checks. Bayesian R2 for statins, P2Y12 inhibitors and aspirin models were 61.4%, 71.2%, and 55.2%, respectively. The simplified models showed similar performance compared with full complex models as evaluated by cross validation.

Conclusion

We developed Bayesian multi-level models for statins, P2Y12 inhibitors and aspirin in post-MI patients that handled 1-year PDC as a proportion using the beta-distribution. In addition, simplified models, with 90-days adherence as single predictor, had similar performance compared with full complex models.

Lay summary

Predicting adherence to medications in patients after myocardial infarction may help focusing resources on patients with the highest need for medical attention. Medication adherence is usually calculated from prescription filling data. Most previously published prediction models categorized patients as ‘adherent’ or ‘non-adherent’ and then tried to predict to which category a certain patient would belong. We suggest here a method to avoid the need for such categorisation. This method can successfully predict the extent of prescription filling. Moreover, we found that simple prediction models, needing only information on the first 3 months prescription filling behaviour, was as good as complex models that required many predictors.
Uropathogenic Escherichia coli causes significant urothelial damage in an ex vivo porcine bladder model, with no protective effect observed from cranberry or d-mannose
Authors: Konesan Jenane , Moore Kate H , Mansfield Kylie J , Liu Lu
Published: October 2024

Urinary tract infections (UTIs), primarily caused by uropathogenic Escherichia coli (UPEC), have an unclear impact on bladder mucosal physiology. This study investigates UPEC’s effects on the urothelium and lamina propria using an ex vivo porcine bladder model. Bladder mucosal strips were analysed for contractile responses to acetylcholine, serotonin, and neurokinin A. Given rising antibiotic resistance, non-antibiotic agents such as cranberry and d-mannose were also evaluated for their potential to prevent UPEC-induced damage. The findings of the current study revealed that UPEC significantly compromised urothelial integrity, barrier function, and permeability, with loss of urothelial cells, uroplakins, and tight junction protein ZO-1 expression. Additionally, infected bladders exhibited a markedly enhanced contractile response to serotonin compared to uninfected controls. Notably, neither cranberry nor d-mannose offered protection against UPEC-mediated damage or mitigated the heightened serotonin-induced contractility. This study provides novel insights into how UPEC disrupts bladder cell biology and highlights the possible involvement of serotonin in the pathophysiology of UTIs.
Open Louchébem: Secrecy in the Argot of Paris Butchers
Authors: Saugera Valérie
Published: October 2024

Louchébem, the ancient trade argot of the Paris butchers, is based on a word formation (or rather deformation) process used to disguise French words according to a rule. The butchers did not invent the process but borrowed it from Largonji (a deformation of jargon). Words from this source are attested in the argot of the so-called ‘dangerous classes’, who used it to produce language opaque to the authorities. Louchébem combines a means of secrecy, an opportunity for language play and a tool for constructing craft identity. In this article, I present the linguistic and sociolinguistic details of Louchébem based on primary data collected from 233 traditional butchers. I further investigate secrecy in the modern context, when the key to Louchébem is available on the internet over 150 years after the emergence of the butchers’ argot. My research shows that both internal and external factors influence how secret Louchébem really is.
Dealing with Clashes of International Law: A Microlevel Study of Climate and Trade
Authors: Elsig Manfred , Spilker Gabriele
Published: October 2024

For years, scholars in international relations have addressed questions related to regime complexity and its effects. However, there is a lack of understanding of how individuals react to clashes of international law obligations when assessing domestic policies. In this article, we study the extent to which citizens are concerned with compliance and noncompliance with international law when their governments design domestic laws to implement international obligations. We are, in particular, interested in whether citizens’ reactions to clashes of international obligations are driven by concerns about being exposed internationally for breaching international law or concerns about tangible material costs. Our empirical analysis is based on an experiment embedded in a survey of Swiss citizens’ attitudes toward environmental issues. The experiment first shows that individuals react to both information about compliance as well as noncompliance, whereas the shifts are more notable in the case of negative information about noncompliance. Second, we find that information about the country being subject to international adjudication (what we call exposure costs) in case of noncompliance is more consequential than information about material costs (facing retaliation).
Presumptive Identification of Clinically Significant Hemoglobin Variants Hb E, Hb S, Hb D in Hb A1c Capillary Electrophoresis
Authors: Puthiyaveettil Ankitha K , Vaz Glen S , Prasad Sujay R , Putchen Deepalakshmi D
Published: October 2024

Background

The quantitation of glycated hemoglobin (Hb A1c) represents an average blood glucose level for a period of 2 to 3 months for diagnosing, monitoring, and managing diabetes mellitus. Unreliable results are reported when hemoglobin (Hb) variants are present in the sample. Patients are advised to use an alternate method due to the presence of the variant Hb and a reflex test to Hb electrophoresis to obtain precise information about the Hb variant. The present study utilizes x axis values from Hb A1c capillary electrophoresis (CE) to identify clinically significant Hb variants Hb E, S, and D.

Methods

Patient samples (n = 60) that showed a variant peak in the Hb A1c test with an x axis value of 190 to 240 were selected for the study. The migration position of the Hb variant (x axis value) and variant percent of the Hb A1c test were compared with the x axis value and variant percent in the Hb electrophoresis test to presumptively identify the variants. The identity of the variants was confirmed using mass spectrometry (MS).

Results

Out of 60 samples, 20 samples were identified as Hb E (x axis 225–227), 20 samples were identified as Hb S (x axis 210–214), and 18 samples were identified as Hb D-Punjab (x axis 200–201). Two variants with an x axis value of 194 were identified as an α variant Hb Q India using MS. There is an overall negative shift of the x axis (−1 to −13 units) and a lower variant percent (−0.2% to −8.7%) in Hb A1c CE when compared with Hb electrophoresis.

Conclusions

The present study highlights the significance of the x axis value and variant percent to identify clinically significant Hb variants in the Hb A1c CE test.
The EU Environmental Crime Directive 2024: A Revolution in EU Environmental Criminal Law?
Authors: Faure Michael G
Published: October 2024

On 11 April 2024, the European Union (EU) adopted a new Environmental Crime Directive (ECD) that departs from how the relationship between administrative law and criminal law has previously been defined in EU law. According to the revised ECD, a conduct shall be deemed unlawful when it is in ‘manifest breach of relevant substantive legal requirements’ – even when there is compliance with an administrative permit. With this, the new ECD has de facto created autonomous environmental crimes. This is revolutionary, as in most legal systems criminal liability is not possible if an operator complied with the conditions of a permit. This article argues that this legal development is welcomed as a way to ensure effective environmental criminal enforcement. The question that remains open, however, is how the concept of ‘manifest breach of relevant substantive legal requirements’ will be translated by the Member States during the transposition of the amended ECD into national law. It is argued that it is especially important to find a formulation that can be reconciled with the legality principle, requiring the conditions for criminal liability to be specified in a clear and specific manner whilst ensuring that environmental crimes are held to account.
CCR2+ monocytes are dispensable to resolve acute pulmonary Pseudomonas aeruginosa infections in WT and cystic fibrosis mice
Authors: Öz Hasan H , Braga Cassia L , Gudneppanavar Ravindra , Di Pietro Caterina , Huang Pamela H , Zhang Ping-Xia , Krause Diane S , Egan Marie E , Murray Thomas S , Bruscia Emanuela M
Published: October 2024

Extravasation of CCR2-positive monocytes into tissue and to the site of injury is a fundamental immunological response to infections. Nevertheless, exuberant recruitment and/or activity of these monocytes and monocyte-derived macrophages can propagate tissue damage, especially in chronic inflammatory disease conditions. We have previously shown that inhibiting the recruitment of CCR2-positive monocytes ameliorates lung tissue damage caused by chronic neutrophilic inflammation in cystic fibrosis mouse models. A potential concern with targeting monocyte recruitment for therapeutic benefit in cystic fibrosis, however, is whether they are essential for eradicating infections such as Pseudomonas aeruginosa, a pathogen that commonly colonizes and damages the lungs of patients with cystic fibrosis. In this study, we investigated the role of CCR2-positive monocytes in the immune response to acute pulmonary P. aeruginosa infection. Our data show that the altered host immune response caused by the lack of monocyte recruitment to the lungs does not impact P. aeruginosa lung colonization, clearance, and the severity of the infection. These results also hold up in a cystic fibrosis mouse background, which has a hyperinflammatory immune response yet exhibits reduced bactericidal activity. Thus, we lay the groundwork for future studies to investigate the use of CCR2 inhibitors as a potential therapy to ameliorate lung tissue damage in cystic fibrosis. This could be given alone or as an adjunct therapy with CFTR modulators that significantly improve clinical outcomes for eligible patients but do not completely resolve the persistent infection and inflammation that drive lung tissue damage.
Book cluster: a new approach to explore the evolution of knowledge organization in ancient China
Authors: Li Wenqi , Wang Zhaoji , Yu Hanxu , Lai Qianting , Wang Jun
Published: October 2024

Chinese ancient book catalogs have persisted for over two millennia, serving as ancient knowledge organization systems and cultural heritage of great academic value. This article introduces the concept of “book cluster,” a novel approach to studying catalog classification evolution, offering a meso-level perspective that bridges books and categories. Drawing from computational methods, we identify clusters of books with similar categorization trajectories, enabling more efficient and intuitive exploration of knowledge organization trends. We review existing research on catalog classification, highlighting the traditional qualitative analysis and emerging computational methods. We then present our data source and processing methods. The concept of book cluster is defined, along with the algorithm for cluster identification and feature extraction. A case study demonstrates the potential of the book cluster concept in analyzing classification changes and knowledge inheritance. Additionally, we introduce an online analytical platform for further exploration. Through computational analysis of book clusters, we gain insights into the evolution of ancient book recording, circulation, and academic contexts. Book clusters offer clues about the content of lost books. This research lays the groundwork for future iterations. By pioneering the study of knowledge organization evolution using book clusters, we enhance our understanding of Chinese history's academic culture and knowledge preservation.
Effect of antibiotic drug use on outcome and therapy-related toxicity in patients with glioblastoma—A retrospective cohort study
Authors: Götz Linda , Ansafi Tananeh , Gerken Michael , Klinkhammer-Schalke Monika , Fischl Anna , Riemenschneider Markus J , Proescholdt Martin , Bumes Elisabeth , Kölbl Oliver , Schmidt Nils Ole , Linker Ralf , Hau Peter , Haedenkamp Tareq M
Published: October 2024

Background

Glioblastoma (GB) is the most frequent malignant brain tumor and has a dismal prognosis. In other cancers, antibiotic use has been associated with severity of chemotherapy-induced toxicity and outcome. We investigated if these mechanisms are also involved in GB.

Methods

We selected a cohort of 78 GB patients who received combined radiochemotherapy. We investigated if exposure to prediagnostic antibiotic use is associated with clinical side effects and laboratory changes during adjuvant therapy as well as overall survival (OS) and progression-free survival (PFS) using chi-square test, binary logistic regression, Kaplan–Meyer analysis, and multivariable Cox regression.

Results

Seventeen patients (21.8%) received at least one course of prediagnostic antibiotics and 61 (78.2%) received no antibiotics. We found a higher incidence of loss of appetite (23.5% vs. 4.9%; P = .018) and myelosuppression (41.2% vs. 18.0%; P = .045) in the antibiotic group. Multivariable logistic regression analysis revealed antibiotics to be a predictor for nausea (OR = 6.94, 95% CI: 1.09–44.30; P = .041) and myelosuppression (OR = 9.75, 95% CI: 1.55–61.18; P = .015). Furthermore, lymphocytopenia was more frequent in the antibiotic group (90.0% vs. 56.1%, P = .033). There were no significant differences in OS (P = .404) and PFS (P = .844). Multivariable Cox regression showed a trend toward shorter survival time (P = .089) in the antibiotic group.

Conclusions

Our study suggests that antibiotic use affects symptoms and lab values in GB patients. Larger prospective studies are required to investigate if prediagnostic antibiotic use could be a prognostic factor in GB patients.
Development of the pediatric neuro-oncology services assessment aid: An assessment tool for pediatric neuro-oncology service delivery capacity
Authors: Rajagopal Revathi , Diaz Coronado Rosdali , Hamid Syed Ahmer , Navarro Martin del Campo Regina , Boop Frederick , Bag Asim , Benito Reséndiz Alma Edith , Bhat K Vasudeva , Campos Danny , Chang Kenneth , Cirt Ramona , Dhyani Rahmartani Ludi , Foo Jen Chun , Hoveyan Julieta , Lucas Jr John T , Ngcana Thandeka , Ul Ain Rahat , Omran Nuha , Osorio Diana S , Qureshi Bilal Mazhar , Sabin Noah D , Schandorf Ernestina , Bankah Patrick , Dadzie Mary-Ann , Gbadamos Hafisatu , Sharafeldin Hend , Somathilaka Mahendra , Yang Peiyi , Atteby Jean-Jacques Yao , Zhang Anan , Salman Zeena , Gonzalez Miriam , Friedrich Paola , Rodriguez-Galindo Carlos , Qaddoumi Ibrahim , Moreira Daniel C
Published: October 2024

Background

To enhance the quality of care available for children with central nervous system (CNS) tumors across the world, a systematic evaluation of capacity is needed to identify gaps and prioritize interventions. To that end, we created the pediatric neuro-oncology (PNO) resource assessment aid (PANORAMA) tool.

Methods

The development of PANORAMA encompassed 3 phases: operationalization, consensus building, and piloting. PANORAMA aimed to capture the elements of the PNO care continuum through domains with weighted assessments reflecting their importance. Responses were ordinally scored to reflect the level of satisfaction. PANORAMA was revised based on feedback at various phases to improve its relevance, usability, and clarity.

Results

The operationalization phase identified 14 domains by using 252 questions. The consensus phase involved 15 experts (6 pediatric oncologists, 3 radiation oncologists, 2 neurosurgeons, 2 radiologists, and 2 pathologists). The consensus phase validated the identified domains, questions, and scoring methodology. The PANORAMA domains included national context, hospital infrastructure, organization and service integration, human resources, financing, laboratory, neurosurgery, diagnostic imaging, pathology, chemotherapy, radiotherapy, supportive care, and patient outcomes. PANORAMA was piloted at 13 institutions in 12 countries, representing diverse patient care contexts. Face validity was assessed by examining the correlation between the estimated score by respondents and calculated PANORAMA scores for each domain (r = 0.67, P < .0001).

Conclusions

PANORAMA was developed through a systematic, collaborative approach, ensuring its relevance to evaluate core elements of PNO service capacity. Distribution of PANORAMA will enable quantitative service evaluations across institutions, facilitating benchmarking and the prioritization of interventions.
Rapid extraction of trace benzene by a crown-ether-based metal-organic framework
Authors: Chen Zhonghang , Fang Peiyu , Li Jiangnan , Han Xue , Huang Wenhao , Cui Wenyue , Liu Zhiwei , Warren Mark R , Allan David , Cheng Peng , Yang Sihai , Shi Wei
Published: October 2024

Due to almost identical boiling points of benzene and cyclohexane, the extraction of trace benzene from cyclohexane is currently performed via the energy-intensive extractive distillation method. Their adsorptive separation by porous materials is hampered by their similar dimensions. Metal-organic frameworks (MOFs) with versatile pore environments are capable of molecular discrimination, but the separation of trace substrates in liquid-phase remains extremely challenging. Herein, we report a robust MOF (NKU-300) with triangular channels decorated with crown ether that can discriminate trace benzene from cyclohexane, exhibiting an unprecedented selectivity of 8615(10) for the mixture of benzene/cyclohexane (v/v = 1/1000). Remarkably, NKU-300 demonstrates exceptional selectivities for the extraction of benzene from cyclohexane over a wide range of concentrations of 0.1%–50% with ultrafast sorption kinetics and excellent stability. Single-crystal X-ray diffraction and computational modelling reveal that multiple supramolecular interactions cooperatively immobilise benzene molecules in the triangular channel, enabling superior separation performance. This study will promote the application of advanced sorbents with tailored binding sites for challenging industrial separations.
A high-velocity star recently ejected by an intermediate-mass black hole in M15
Authors: Huang Yang , Li Qingzheng , Liu Jifeng , Dong Xiaobo , Zhang Huawei , Lu Youjun , Du Cuihua
Published: October 2024

The existence of intermediate-mass black holes (IMBHs) is crucial for understanding various astrophysical phenomena, yet their existence remains elusive, except for the LIGO-Virgo detection. We report the discovery of a high-velocity star J0731+3717, whose backward trajectory about 21 Myr ago intersected that of globular cluster M15 within the cluster tidal radius. Both its metallicity [Fe/H] and alpha-to-iron abundance ratio [$\alpha$/Fe] are consistent with those of M15. Furthermore, its location falls right on the fiducial sequence of cluster M15 on the color-absolute magnitude diagram, suggesting similar ages. These findings support the notion that J0731+3717 was originally associated with M15 at a confidence level of ‘seven nines’. We find that such a high-velocity star ($V_{\rm ej} = 548^{+6}_{-5}$ km s$^{-1}$) was most likely tidally ejected from as close as one astronomical unit to the center of M15, confirming an IMBH ($\ge 100 M_{\odot }$ with a credibility of 98%) as the exclusive nature of the central unseen mass proposed previously.
Opportunities and challenges of diffusion models for generative AI
Authors: Chen Minshuo , Mei Song , Fan Jianqing , Wang Mengdi
Published: October 2024

Diffusion models, a powerful and universal generative artificial intelligence technology, have achieved tremendous success and opened up new possibilities in diverse applications. In these applications, diffusion models provide flexible high-dimensional data modeling, and act as a sampler for generating new samples under active control towards task-desired properties. Despite the significant empirical success, theoretical underpinnings of diffusion models are very limited, potentially slowing down principled methodological innovations for further harnessing and improving diffusion models. In this paper, we review emerging applications of diffusion models to highlight their sample generation capabilities under various control goals. At the same time, we dive into the unique working flow of diffusion models through the lens of stochastic processes. We identify theoretical challenges in analyzing diffusion models, owing to their complicated training procedure and interaction with the underlying data distribution. To address these challenges, we overview several promising advances, demonstrating diffusion models as an efficient distribution learner and a sampler. Furthermore, we introduce a new avenue in high-dimensional structured optimization through diffusion models, where searching for solutions is reformulated as a conditional sampling problem and solved by diffusion models. Lastly, we discuss future directions about diffusion models. The purpose of this paper is to provide a well-rounded exposure for stimulating forward-looking theories and methods of diffusion models.
Non-hygroscopic ionogel-based humidity-insensitive iontronic sensor arrays for intra-articular pressure sensing
Authors: Shi Junli , Xie Sai , Liu Zhiguang , Cai Minkun , Guo Chuan Fei
Published: October 2024

Implanted pressure sensors can provide pressure information to assess localized health conditions of specific tissues or organs, such as the intra-articular pressure within knee joints. However, the prerequisites for implanted sensors pose greater challenges than those for wearables or for robots: aside from biocompatibility and tissue-like softness, they must also exhibit humidity insensitivity and high-pressure resolution across a broad pressure spectrum. Iontronic sensors can provide superior sensing properties, but they undergo property degradation in wet environments due to the hygroscopic nature of their active component: ionogels. Herein, we introduce a humidity-insensitive iontronic sensor array based on a hydrophobic and tough ionogel polymerized in a hydrophobicity transition yielding two hydrophobic phases: a soft liquid-rich phase that enhances ionic conductivity and ductility, and a stiff polymer-rich phase that contributes to superior toughness. We demonstrate the in vivo implantation of these sensor arrays to monitor real-time intra-articular pressure distribution in a sheep model, while assessing knee flexion with an angular resolution of 0.1° and a pressure resolution of 0.1%. We anticipate that this sensor array will find applications in various orthopedic surgeries and implantable medical devices.
Mobile signals, patterning, and positional information in root development
Authors: Cohen Itay , Efroni Idan
Published: October 2024

Multicellular organisms use mobile intercellular signals to generate spatiotemporal patterns of growth and differentiation. These signals, termed morphogens, arise from localized sources and move by diffusion or directional transport to be interpreted at target cells. The classical model for a morphogen is where a substance diffuses from a source to generate a concentration gradient that provides positional information across a field. This concept, presented by Wolpert and popularized as the “French Flag Model,” remains highly influential, but other patterning models, which do not rely on morphogen gradients, also exist. Here, we review current evidence for mobile morphogenetic signals in plant root development and how they fit within existing conceptual frameworks for pattern formation. We discuss how the signals are formed, distributed, and interpreted in space and time, emphasizing the regulation of movement on the ability of morphogens to specify patterns. While significant advances have been made in the field since the first identification of mobile morphogenetic factors in plants, key questions remain to be answered, such as how morphogen movement is regulated, how these mechanisms allow scaling in different species, and how morphogens act to enable plant regeneration in response to damage.
Variation of brain natriuretic peptide assists with volume management and predicts prognosis of hemodialysis patients
Authors: Hu Nan , Wang Jinwei , Chen Yuqing
Published: October 2024

Purpose

The objective of this study was to elucidate the spectrum of brain natriuretic peptide (BNP) expression in hemodialysis patients with euvolemic status and investigate its prognostic significance.

Methods

Patients on chronic hemodialysis were enrolled. The normal range of BNP was measured and analyzed in patients with euvolemic status defined by systolic blood pressure and overhydration. Hemodialysis patients were stratified into groups according to BNP expression at baseline and followed up for 57 months, with all-cause mortality and cardiovascular disease-related death being assessed as primary outcomes.

Results

BNP significantly correlated with overhydration in all patients (r = 0.255, P = .004). In patients with euvolemic state, the average BNP level was 701 (±645) pg/ml, with a 95% confidence interval (CI) of 500–902 pg/ml. In patients with BNP < 902 pg/ml, systolic blood pressure significantly correlated with overhydration. Elevated BNP expression correlated with an increased risk of cardiovascular mortality (HR = 1.871, per 782 pg/ml increase, P = .008). The patients with continuously high levels of BNP showed significantly increased risk of cardiovascular disease-related death during follow-up (HR = 12.845, P = .005).

Conclusion

Predialysis measured BNP levels correlate with volume status, and the common range is from 500 to 902 pg/ml in dialysis patients with euvolemic status. Patients with upregulated BNP expression showed an increased risk of cardiovascular death.

Key messages What is already known on this topic  The volume management of hemodialysis patients should be judged comprehensively by clinical manifestations and objective examinations. The parameters involved in the evaluation need to be further optimized. What this study adds  In hemodialysis patients, BNP serves as an indicator of volume status. Properly hydrated hemodialysis patients typically exhibit BNP levels ranging from 500 to 902 pg/ml, while persistent BNP elevation is associated with increased mortality. How this study might affect research, practice, or policy  In clinical practice, BNP can be routinely monitored in hemodialysis patients to provide information for volume adjustment and to identify patients with high mortality risk. The potential advantages of implementing targeted BNP management warrant further investigation through intervention studies.
TMD Relations: Insights from a Light-Front Quark–Diquark Model
Authors: Sharma Shubham , Puhan Satyajit , Kumar Narinder , Dahiya Harleen
Published: October 2024

In this work, we have established the relations between the T-even proton transverse-momentum-dependent parton distributions (TMDs) at all twist levels up to twist-4 using the light-front quark–diquark model. From the parameterization equations of TMDs, we have found that there are multiple ways by which a particular TMD can be expressed in terms of the initial and final helicity states of the proton. For the first time, we have presented a parameterization table that can be applied to the derivation and recognition of proton TMDs based on their helicity. We have constructed the linear and quadratic relationships of TMDs at the intra- and intertwist levels within the same model. We have also looked at the inequality relations that TMDs follow. Additionally, to provide easy access to the calculations, amplitude matrices have been expressed in the form of TMDs over all the possible helicities of the diquark.
Prevalence and influencing factors of suicidal ideation among doctors and nurses during the surge period of the COVID-19 pandemic in China: a multicenter cross-sectional study
Authors: Jing Shu , Dai Zhenwei , Liu Xiaoyang , Liu Xin , Zhang Ling , Wu Yijin , Ren Tianrui , Fu Jiaqi , Chen Xu , Wang Wenjun , Gu Xiaofen , Ma Li , Zhang Shaokai , Yu Yanqin , Li Li , Su Xiaoyou , Qiao Youlin
Published: October 2024

Background

From November 2022 to February 2023, China has experienced a surge period of COVID-19 pandemic and doctors and nurses working in hospitals have suffered from serious psychological crisis because of the medical crowding, which may result in the occurrence of suicidal ideation (SI). This study aims to explore the prevalence and influencing factors of SI during this surge phase.

Methods

A multicenter cross-sectional study was conducted in China from 5 January 2023 to 9 February 2023. Data were collected by online questionnaires, with SI measured by a single item. Ordinal logistic regression analysis and stratified analyses were preformed to identify influencing factors.

Results

A total of 5696 doctors and nurses were retained for further analysis, with 25.28% reporting SI during the COVID-19 surge phase. Participants experiencing anxiety symptoms or supporting other departments treating COVID-19 patients were more likely to report SI. Additionally, higher levels of resilience, mindfulness, and perceived social support were protective factors against SI.

Conclusion

During the COVID-19 surge phase, over a quarter of doctors and nurses in China suffered from SI, which should be of great concern. Tailored interventions should be implemented to alleviate SI among doctors and nurses when new infectious diseases outbreak in the future.
Support needs of gout patients and suitability of eHealth to address these needs
Authors: van der Ven Jeffrey , van den Bemt Bart J F , Ariaans Floor , Vriezekolk Johanna E , Flendrie Marcel , Verhoef Lise M
Published: October 2024

Objectives

To investigate the support needs of patients with gout regarding information, communication, treatment and disease monitoring, and patients’ views on and preferences for eHealth applications to address these needs.

Methods

A focus group study using purposive sampling was conducted. Three focus group sessions with a duration of 2 h per group were held with in total of 23 patients using urate-lowering therapy, recruited from primary and secondary care. Audio recordings were transcribed, and data were analysed using thematic analysis.

Results

Eight themes were identified. Five themes addressed support needs of gout patients and suitability of eHealth in addressing those needs: (1) Timely access to healthcare, especially during flares; (2) (personalized) information regarding diagnosis, medication, and diet; (3) insight into uric acid levels and medication side effects through blood monitoring; (4) better coordination across primary and secondary care; and (5) self-management and shared responsibility over care for maintaining health. Three themes addressed eHealth in general: (1) receptive towards eHealth in gout care; (2) the preference for eHealth to have a complementary role (i.e. not replacing face-to-face) contact with healthcare providers; and (3) preferences on eHealth use and functionalities.

Conclusion

Patients expressed various needs regarding their disease management and projected a supporting role for eHealth in (self)management of gout. Addressing the needs and preferences of patients could enhance their understanding of the disease and treatment, self-management, and possibly health outcomes.
Non-invasive fast assessment of hepatic injury through computed tomography imaging with renal-clearable Bi-DTPA dimeglumine
Authors: Ma Li , Pan Jinbin , Shu Gang , Pan Haiyan , Li Jingang , Li Dong , Sun Shaokai
Published: October 2024

Enhanced computed tomography (CT) imaging with iodinated imaging probes is widely utilized for the diagnosis and evaluation of various liver diseases. However, these iodine-based imaging probes face intractable limitations including allergic reactions and contraindications. Herein, we propose the utilization of renal-clearable iodine-free bismuth chelate (Bi-DTPA dimeglumine) for the non-invasive fast assessment of hepatic ischemia–reperfusion injury (HIRI) via CT imaging for the first time. Bi-DTPA dimeglumine offers several advantages such as simple synthesis, no purification requirement, a yield approaching 100%, large-scale production capability (laboratory synthesis > 100 g), excellent biocompatibility and superior CT imaging performance. In a normal rat model, the administration of Bi-DTPA dimeglumine resulted in a significant 63.79% increase in liver CT value within a very short time period (30 s). Furthermore, in a HIRI rat model, Bi-DTPA dimeglumine enabled the rapid differentiation between healthy and injured areas based on the notable disparity in liver CT values as early as 15 min post-reperfusion, which showed a strong correlation with the histopathological analysis results. Additionally, Bi-DTPA dimeglumine can be almost eliminated from the body via the kidneys within 24 h. As an inherently advantageous alternative to iodinated imaging probes, Bi-DTPA dimeglumine exhibits promising prospects for application in liver disease diagnosis.
CD44: a stemness driver, regulator, and marker—all in one?
Authors: Sonnentag Steffen J , Ibrahim Nagwa S M , Orian-Rousseau Veronique
Published: October 2024

Although the concept of cancer stem cells is still controversial, previous studies have shown that blood cancers, as well as specific types of solid cancers such as colorectal cancer, rely on stem cells during the onset of tumor growth and further tumor development. Moreover, resistance to therapeutic treatment in leukemias such as acute myeloid leukemia and in colorectal cancer can be attributed to a small population of cells with stemness properties known as minimal residual disease. In this review, we look back on the discovery of cancer stem cells and the contribution of the findings in blood cancer to a parallel discovery in solid cancers. We focus on CD44 as a stem cell marker, both in blood cancers and in several types of solid cancers, particularly of the gastrointestinal tract. This review highlights newly discovered molecular mechanisms of action of CD44 which indicate that CD44 has indeed a function in stemness, stem cell maintenance, and drug resistance. We attempt here to make the link between the functions of CD44 isoforms in stemness and their involvement in specific steps of tumor growth and metastasis.
Erectile dysfunction as a holistic indicator of well-being: a narrative review
Authors: Saffati Gal , Seyan Zheyar , Rendon Daniela Orozco , Almuhaideb Mana , Hinojosa-Gonzalez David E , Kronstedt Shane , Khera Mohit
Published: October 2024

Introduction

Erectile dysfunction (ED), affecting around 52% of men aged 40–70, is a significant marker of overall health and a potential warning sign of multiple conditions like cardiovascular diseases (CVDs), diabetes, and mental health disorders. Recognizing and addressing ED through a holistic approach involving nutrition, physical activity, sleep, and stress management can improve both erectile and overall health outcomes.

Aims

To provide a narrative review of the available literature on the relationship between ED and overall health, elaborate on the possible mechanisms explaining this association, and discuss the effects of lifestyle on ED.

Methods

A search of the medical literature was carried out in PubMed and Medline, focusing on original research and systematic reviews of original research on ED and overall health.

Results

Due to shared pathophysiological mechanisms like endothelial dysfunction, ED is a significant indicator of overall health, particularly related to CVD and diabetes mellitus. Multiple studies have shown that ED frequently precedes cardiovascular events and is associated with increased cardiovascular risk, especially in younger men and those with diabetes. It also has a profound, bidirectional relationship with mental health conditions like depression and anxiety, creating a vicious cycle where each exacerbates the other. The four health pillars of nutrition, physical activity, sleep, and stress management play significant roles in erectile function and overall sexual health.

Conclusion

ED is not just a condition affecting sexual function but a critical indicator of broader health issues. By adopting an integrative approach that combines nutrition, physical activity, sleep, and stress management, healthcare providers can offer holistic and effective management strategies for this condition.
Binary and Nonbinary Transgender Patient Experiences Accessing Gender-affirming Top Surgery
Authors: Raner Gavin A. , Shapiro Jordan S. , Tse Tiffany , Armstrong Kathleen , Potter Emery
Published: October 2024

Background:

Transgender and gender diverse (TGD) individuals face barriers when seeking top surgery, or bilateral mastectomies, as part of surgical transition, leading to delayed care and adverse health outcomes. Understanding differential experiences between nonbinary and binary patients is crucial for improving TGD patient care, but this distinction is seldom made in the current literature.

Methods:

This single-center cross-sectional mixed-methods survey study conducted between 2022 and 2023 enrolled all consecutive TGD patients undergoing top surgery. Significant differences between datasets were determined by two-sample unpaired t tests. Summative content analysis and descriptive analysis were performed for free-text responses.

Results:

Thirty-seven binary and 71 nonbinary patients completed the survey. Lack of funding, long wait times within the healthcare system, and long wait times to access surgery were the three most impactful barriers for both cohorts. Nonbinary patients were more impacted by a lack of TGD-friendly surgeons and community physicians, prejudice from surgical center staff and community doctors, and employment concerns. More binary patients desired a “masculine chest” and to stop using a binder. The nonbinary group more frequently desired a “smaller chest” and had greater variability of surgical goals.

Conclusions:

Binary and nonbinary TGD patients both experience barriers to top surgery; however nonbinary patients may experience distinct barriers and have differential surgical goals. It is important to discuss specific surgery goals and offer top surgery options beyond bilateral mastectomy with nipple grafting, especially with nonbinary patients.