bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthcare service use and medical outcomes of tracheostomy-dependent children: a nationwide study
Authors: Song In Gyu , Kim You Sun , Kim Min Sun , Lee Ji Weon , Cho Yoon-Min , Lim Youna , Kwon Seong Keun , Suh Dong In , Park June Dong
Published: March 2024

Background

Despite the rising trend of tracheostomies in children, there is a lack of comprehensive resources for families to navigate the challenges of living with a tracheostomy, emphasising the need for evidence-based support in understanding postoperative care and long-term adjustments. This study aimed to examine the pattern of using healthcare services and nationwide medical outcomes in children who underwent a tracheotomy before the age of 2 years.

Methods

This retrospective study used the National Health Insurance System database from 2008 to 2016 and included all children codified with tracheotomy procedure codes before their second birthday. Healthcare utilisation, such as medical costs, number of hospital visits, home healthcare nursing and medical diagnoses on readmission, in the first 2 years after tracheotomy was evaluated. Multivariable logistic regression analysis was used to determine the factors affecting mortality.

Results

In total, 813 patients were included in this study. Their use of healthcare services and the accompanying expenses were higher than the national medians for similar age groups; however, both metrics decreased in the second year. The major causes of admission within 2 years of surgery were respiratory and neurological diseases. The mortality rate within 2 years was 37.8%. Higher risks of mortality were associated with having two or more complex chronic conditions. Use of home healthcare nursing services was associated with a lower mortality risk.

Conclusion

Paediatric patients with more complex chronic conditions tended to have higher mortality rates within 2 years after surgery. However, receiving home healthcare nursing was significantly associated with a reduced risk of death. Many causes of hospitalisation may be preventable with education and supportive care. Therefore, further research for establishing an integrated care system for these patients and their caregivers is required.
Performance of GPT-4 in Membership of the Royal College of Paediatrics and Child Health-style examination questions
Authors: Armitage Richard
Published: March 2024

The large language model (LLM) ChatGPT has been shown to have considerable utility across medicine and healthcare. This paper aims to explore the capabilities of GPT-4 (Generative Pre-trained Transformer 4) in answering Membership of the Royal College of Paediatrics and Child Health (MRCPCH) written paper-style questions. GPT-4 was subjected to four publicly available sample papers designed for those preparing to sit MRCPCH theory components. The model received no specialised training or reinforcement. The average score across all four papers was 78.1%. The model provided reasoning for its answers despite this not being required by the questions. This performance strengthens the case for incorporating LLMs into supporting roles for practising clinicians and medical education in paediatrics.
Fluoroscopy-guided high-intensity focused ultrasound ablation of the lumbar medial branch nerves: dose escalation study and comparison with radiofrequency ablation in a porcine model
Authors: Gofeld Michael , Tiennot Thomas , Miller Eric , Rebhun Niv , Mobley Stephen , Leblang Suzanne , Aginsky Ron , Hananel Arik , Aubry Jean-Francois
Published: March 2024

Background

Radiofrequency ablation (RFA) is a common method for alleviating chronic back pain by targeting and ablating of facet joint sensory nerves. High-intensity focused ultrasound (HIFU) is an emerging, non-invasive, image-guided technology capable of providing thermal tissue ablation. While HIFU shows promise as a potentially superior option for ablating sensory nerves, its efficacy needs validation and comparison with existing methods.

Methods

Nine adult pigs underwent fluoroscopy-guided HIFU ablation of eight lumbar medial branch nerves, with varying acoustic energy levels: 1000 (N=3), 1500 (N=3), or 2000 (N=3) joules (J). An additional three animals underwent standard RFA (two 90 s long lesions at 80°C) of the same eight nerves. Following 2 days of neurobehavioral observation, all 12 animals were sacrificed. The targeted tissue was excised and subjected to macropathology and micropathology, with a primary focus on the medial branch nerves.

Results

The percentage of ablated nerves with HIFU was 71%, 86%, and 96% for 1000 J, 1500 J, and 2000 J, respectively. In contrast, RFA achieved a 50% ablation rate. No significant adverse events occurred during the procedure or follow-up period.

Conclusions

These findings suggest that HIFU may be more effective than RFA in inducing thermal necrosis of the nerve.
Health benefits of interval walking training
Authors: Karstoft Kristian , Thorsen Ida Kær , Nielsen Jens Steen , Solomon Thomas Phillip James , Masuki Shizue , Nose Hiroshi , Ried-Larsen Mathias
Published: March 2024

Interval walking training (IWT) is a free-living training intervention involving alternating fast and slow walking cycles. IWT is efficacious in improving physical fitness and muscle strength, and reducing factors associated with lifestyle-related diseases. In individuals with type 2 diabetes, IWT improves glycemic control directly through enhanced glucose effectiveness, challenging conventional views on mechanisms behind training-induced improvements in glycemic control. Whereas adherence to IWT in short-term studies is high, ensuring long-term adherence remains a challenge, particularly in populations with chronic diseases and/or overweight/obesity. Long-term studies in real-world settings are imperative to ascertain the widespread effectiveness of IWT and elucidate its impact on hard endpoints.
On the Opportunities and Challenges of Foundation Models for GeoAI (Vision Paper)
Authors: Mai Gengchen , Huang Weiming , Sun Jin , Song Suhang , Mishra Deepak , Liu Ninghao , Gao Song , Liu Tianming , Cong Gao , Hu Yingjie , Cundy Chris , Li Ziyuan , Zhu Rui , Lao Ni
Published: March 2024

Large pre-trained models, also known as
foundation models
(FMs), are trained in a task-agnostic manner on large-scale data and can be adapted to a wide range of downstream tasks by fine-tuning, few-shot, or even zero-shot learning. Despite their successes in language and vision tasks, we have not yet seen an attempt to develop foundation models for geospatial artificial intelligence (GeoAI). In this work, we explore the promises and challenges of developing multimodal foundation models for GeoAI. We first investigate the potential of many existing FMs by testing their performances on seven tasks across multiple geospatial domains, including Geospatial Semantics, Health Geography, Urban Geography, and Remote Sensing. Our results indicate that on several geospatial tasks that only involve text modality, such as toponym recognition, location description recognition, and US state-level/county-level dementia time series forecasting, the task-agnostic large learning models (LLMs) can outperform task-specific fully supervised models in a zero-shot or few-shot learning setting. However, on other geospatial tasks, especially tasks that involve multiple data modalities (e.g., POI-based urban function classification, street view image–based urban noise intensity classification, and remote sensing image scene classification), existing FMs still underperform task-specific models. Based on these observations, we propose that one of the major challenges of developing an FM for GeoAI is to address the multimodal nature of geospatial tasks. After discussing the distinct challenges of each geospatial data modality, we suggest the possibility of a multimodal FM that can reason over various types of geospatial data through geospatial alignments. We conclude this article by discussing the unique risks and challenges to developing such a model for GeoAI.
Identifying Electrocatalytic Activity Sequence of Metal Phthalocyanines for the Hydrogen Peroxide Oxidation Reaction
Authors: Shi Shufang , Yang Jie , Chen Lifang , Huang Mengxue , Liu Chang , Ding Ruimin , Yin Xi
Published: March 2024

The hydrogen peroxide oxidation reaction (HPOR) plays a vital role in the emerging H2-H2O2 cycle energy storage system, in which the rational design of HPOR electrocatalyst is essential for achieving high system efficiency. Herein, we establish the HPOR activity trends using structurally well-defined metal phthalocyanines (MPc) as model catalysts via a combined experimental and computational approach. The measured activity sequence follows the order of CoPc > FePc > MnPc > ZnPc > H2Pc > NiPc > CuPc based on their site-normalized exchange current (i
0-s). Theoretical calculations indicate that the binding free energy of hydroperoxyl intermediate, HOO*, on MPc (ΔG
HOO*) is the activity descriptor for HPOR. A volcano-type activity trend is observed by correlating the logarithm of i
0-s (logi
0-s) with the ΔG
HOO* values and agrees with the theoretical predictions. This HPOR activity trend provides insights into the design of highly active electrocatalysts for HPOR and related energy applications.
Performance of Working Memory Updating in Socially Anxious Individuals
Authors: Yuan Jing , Sun Xiran , Zhang Qin , Cui Lixia
Published: March 2024

Working memory updating plays a critical role in executive function. Few studies explored the working memory updating in socially anxious individuals. In this study, we wanted to explore the working memory updating in socially anxious individuals. We studied this issue by instructing participants to perform an emotional 2-back task, and recording their response time and accuracy. We found that high socially anxious individuals showed significant longer response time in positive word condition than that of negative and neutral words. But there was no significant difference in word type in low socially anxious group. In accuracy, we did not observe any significant difference in group, word type, and their interaction. These results indicate that socially anxious individuals have deficits in positive content updating, which have an important implication for developing method to reduce social anxiety.
Protective Effects of Astaxanthin on Post‐Thaw Sperm Quality in Normozoospermic Men
Authors: Mohammadi-Bardbori Afshin , Shadboorestan Amir , Salehi Ensieh , Rahimi Mohammad Amin , Kargar-Abarghouei Elias , Amidi Fardin , Shamseddin Jebreil , Omidi Mahmoud
Published: March 2024

Fighting against free radical accumulation during the cryopreservation process with the help of exogenous antioxidants has become an effective strategy to augment post‐thaw sperm quality. The present study explored the effects of various concentrations of astaxanthin, as a potent antioxidant, on human sperm parameters during the freeze–thaw process. Twenty‐five normozoospermic specimens were included in this prospective study. Each sample was divided into five equal parts: fresh group, and frozen–thawed groups including 0, 1, 10, and 50 μM of astaxanthin. The prepared spermatozoa were cryopreserved by rapid freezing technique. Precryopreservation and post‐thaw sperm motility parameters, sperm morphology, vitality, DNA fragmentation, reactive oxygen species (ROS) levels, and mitochondrial membrane potential (MMP) were investigated. All sperm parameters after thawing significantly decreased compared to before freezing. Treatment of spermatozoa with 50 μM of astaxanthin significantly increased their total and progressive motility, viability, DNA integrity, and MMP and decreased their intracellular ROS levels compared with the control group. In total, 10 μM of astaxanthin significantly improved total and progressive motility, DNA integrity, MMP, and decreased ROS levels, whereas, in the 1 µM group, there were significant differences only in ROS levels. As a result, we found that astaxanthin can improve sperm quality after freezing/thawing and decrease the detrimental effects of this process on sperm parameters.
Mineralization of Dentinal Lesions with Different Concentrations of Fluoride
Authors: Al-Asmar Ayah A.
Published: March 2024

Objectives. The present study aimed to investigate the relationship between fluoride concentration and mineral distribution within the dentinal lesion body. Methods. Remineralization of artificial deep dentinal lesions with various levels of fluoride was studied using a scanning electron microscope, microhardness tests, and polarized light microscope. Human molars were exposed to demineralization at pH 5.0 for 2 weeks. Then, they were divided into different groups for remineralization with different fluoride concentrations (0.1–10.0 ppm) for 1, 2, 3, and 4 weeks. Results. The results indicated a proportional relationship between fluoride concentration and dentinal lesion remineralization from 0.1 to 10.0 ppm. In the present study, the formation of a well‐remineralized surface layer inhibited remineralization at the lesion front. On the other hand, the lesion front remineralization was found to be independent of fluoride concentration. Conclusion. Our results stated that for effective remineralization of dentinal lesions to the innermost part, fluoride levels from 1.0 to 5.0 ppm have the highest efficiency.
Rapid Thermal Processing and Improved Photocatalysis of Bi2O3-BaTiO3 Heterojunction
Authors: Bing Lina , Wu Wei , Shen Zhenjiang
Published: March 2024

Bi2O3-BaTiO3 heterojunction with high photocatalysis efficiency was directly synthesized by rapid thermal processing (RTP). Bi2O3 and BaTiO3 were mixed in ratio and treated by RTP and conventional thermal processing (CTP), respectively. RTP samples have obvious Bi2O3 diffraction peaks, while CTP samples show pure BaTiO3 tetragonal perovskite. More small particles and layered existed in RTP samples. Photodegradation of MB solutions shows that RTP can promote photocatalytic efficiency. Its main lies in the following points: RTP can remove grain boundary defects by strengthening the bond grains; RTP can limit the solution region of the two substances to a certain range to get the best built-in electric field width; and RTP can strengthen the tetragonal BaTiO3 phase to hasten ion movement. Therefore, RTP can achieve much higher photocatalytic efficiency by improving the build heterojunction. This work provides a direct and efficient route to get improvement and high performance of heterojunction.
Acromegaly, Herniation of Cerebellar Tonsils, and Arnold–Chiari 1 Malformation: The Importance of Right Definitions
Authors: Ciarloni Alessandro , Salvio Gianmaria
Published: March 2024

We present a case of acromegaly associated with Arnold–Chiari 1 malformation and a literature review regarding this association, mainly focusing on the importance of a clear distinction between Chiari malformation and herniation of cerebellar tonsils (CTH). Indeed, in many clinical cases, this distinction has not been properly made and a better description of the radiological findings could be important for the clinical management of these patients. In fact, Arnold–Chiari 1 malformation, as a congenital disease, is not caused by acquired growth hormone (GH) excess, but the latter could worsen pre-existing CTH or even induce it ex novo. Therefore, awareness of this condition in the clinical management of acromegaly appears crucial.
Phase I Trial of Viral Vector-Based Personalized Vaccination Elicits Robust Neoantigen-Specific Antitumor T-Cell Responses
Authors: D'Alise Anna Morena , Leoni Guido , Cotugno Gabriella , Siani Loredana , Vitale Rosa , Ruzza Valentino , Garzia Irene , Antonucci Laura , Micarelli Elisa , Venafra Veronica , Gogov Sven , Capone Alessia , Runswick Sarah , Martin-Liberal Juan , Calvo Emiliano , Moreno Victor , Symeonides Stefan N. , Scarselli Elisa , Bechter Oliver
Published: March 2024

Purpose:

Personalized vaccines targeting multiple neoantigens (nAgs) are a promising strategy for eliciting a diversified antitumor T-cell response to overcome tumor heterogeneity. NOUS-PEV is a vector-based personalized vaccine, expressing 60 nAgs and consists of priming with a nonhuman Great Ape Adenoviral vector (GAd20) followed by boosts with Modified Vaccinia Ankara. Here, we report data of a phase Ib trial of NOUS-PEV in combination with pembrolizumab in treatment-naïve patients with metastatic melanoma (NCT04990479).

Patients and Methods:

The feasibility of this approach was demonstrated by producing, releasing, and administering to 6 patients 11 of 12 vaccines within 8 weeks from biopsy collection to GAd20 administration.

Results:

The regimen was safe, with no treatment-related serious adverse events observed and mild vaccine-related reactions. Vaccine immunogenicity was demonstrated in all evaluable patients receiving the prime/boost regimen, with detection of robust neoantigen-specific immune responses to multiple neoantigens comprising both CD4 and CD8 T cells. Expansion and diversification of vaccine-induced T-cell receptor (TCR) clonotypes was observed in the posttreatment biopsies of patients with clinical response, providing evidence of tumor infiltration by vaccine-induced neoantigen-specific T cells.

Conclusions:

These findings indicate the ability of NOUS-PEV to amplify and broaden the repertoire of tumor-reactive T cells to empower a diverse, potent, and durable antitumor immune response. Finally, a gene signature indicative of the reduced presence of activated T cells together with very poor expression of the antigen-processing machinery genes has been identified in pretreatment biopsies as a potential biomarker of resistance to the treatment.
The Cross-talk Between Intestinal Microbiota and MDSCs Fuels Colitis-associated Cancer Development
Authors: Ashkenazi-Preiser Hadas , Reuven Or , Uzan-Yulzari Atara , Komisarov Sharon , Cirkin Roy , Turjeman Sondra , Even Carmel , Twaik Nira , Ben-Meir Kerem , Mikula Ivan , Cohen-Daniel Leonor , Meirow Yaron , Pikarsky Eli , Louzoun Yoram , Koren Omry , Baniyash Michal
Published: March 2024

Intestinal chronic inflammation is associated with microbial dysbiosis and accumulation of various immune cells including myeloid-derived suppressor cells (MDSC), which profoundly impact the immune microenvironment, perturb homeostasis and increase the risk to develop colitis-associated colorectal cancer (CAC). However, the specific MDSCs–dysbiotic microbiota interactions and their collective impact on CAC development remain poorly understood. In this study, using a murine model of CAC, we demonstrate that CAC-bearing mice exhibit significantly elevated levels of highly immunosuppressive MDSCs, accompanied by microbiota alterations. Both MDSCs and bacteria that infiltrate the colon tissue and developing tumors can be found in close proximity, suggesting intricate MDSC-microbiota cross-talk within the tumor microenvironment. To investigate this phenomenon, we employed antibiotic treatment to disrupt MDSC–microbiota interactions. This intervention yielded a remarkable reduction in intestinal inflammation, decreased MDSC levels, and alleviated immunosuppression, all of which were associated with a significant reduction in tumor burden. Furthermore, we underscore the causative role of dysbiotic microbiota in the predisposition toward tumor development, highlighting their potential as biomarkers for predicting tumor load. We shed light on the intimate MDSCs-microbiota cross-talk, revealing how bacteria enhance MDSC suppressive features and activities, inhibit their differentiation into mature beneficial myeloid cells, and redirect some toward M2 macrophage phenotype. Collectively, this study uncovers the role of MDSC-bacteria cross-talk in impairing immune responses and promoting tumor growth, providing new insights into potential therapeutic strategies for CAC.

Significance:

MDSCs–dysbiotic bacteria interactions in the intestine play a crucial role in intensifying immunosuppression within the CAC microenvironment, ultimately facilitating tumor growth, highlighting potential therapeutic targets for improving the treatment outcomes of CAC.
Fatigue-Related Changes of Daily Function: Most Promising Measures for the Digital Age
Authors: Maetzler Walter , Correia Guedes Leonor , Emmert Kirsten Nele , Kudelka Jennifer , Hildesheim Hanna Luise , Paulides Emma , Connolly Hayley , Davies Kristen , Dilda Valentina , Ahmaniemi Teemu , Avedano Luisa , Bouça-Machado Raquel , Chambers Michael , Chatterjee Meenakshi , Gallagher Peter , Graeber Johanna , Maetzler Corina , Kaduszkiewicz Hanna , Kennedy Norelee , Macrae Victoria , Carrasco Marín Laura , Moses Anusha , Padovani Alessandro , Pilotto Andrea , Ratcliffe Natasha , Reilmann Ralf , Rosario Madalena , Schreiber Stefan , De Sousa Dina , Van Gassen Geert , Warring Lori Ann , Seppi Klaus , van der Woude C. Janneke , Ferreira Joaquim J. , Ng Wan-Fai ,   on behalf of the IDEA-FAST project consortium
Published: March 2024

Background: Fatigue is a prominent symptom in many diseases and is strongly associated with impaired daily function. The measurement of daily function is currently almost always done with questionnaires, which are subjective and imprecise. With the recent advances of digital wearable technologies, novel approaches to evaluate daily function quantitatively and objectively in real-life conditions are increasingly possible. This also creates new possibilities to measure fatigue-related changes of daily function using such technologies. Summary: This review examines which digitally assessable parameters in immune-mediated inflammatory and neurodegenerative diseases may have the greatest potential to reflect fatigue-related changes of daily function. Key Messages: Results of a standardized analysis of the literature reporting about perception-, capacity-, and performance-evaluating assessment tools indicate that changes of the following parameters: physical activity, independence of daily living, social participation, working life, mental status, cognitive and aerobic capacity, and supervised and unsupervised mobility performance have the highest potential to reflect fatigue-related changes of daily function. These parameters thus hold the greatest potential for quantitatively measuring fatigue in representative diseases in real-life conditions, e.g., with digital wearable technologies. Furthermore, to the best of our knowledge, this is a new approach to analysing evidence for the design of performance-based digital assessment protocols in human research, which may stimulate further systematic research in this area.
Pneumocystis jirovecii Pneumonia Secondary to Blinatumomab Therapy: A Case Report
Authors: Yin Yue , Shen Kaini , Li Hanyu , Zhang Lu
Published: March 2024

Introduction: With the increasing use of blinatumomab in relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL), including minimal residual disease (MRD)-positive cases, awareness of its adverse effects has gradually improved. Pneumocystis jirovecii pneumonia (PCP) associated with blinatumomab therapy is rare. Case Presentation: We present a case of PCP in a patient undergoing blinatumomab therapy. A 70-year-old female diagnosed with Philadelphia-like CRLF2 overexpression B-cell precursor ALL received blinatumomab as consolidation therapy after achieving complete remission with prior induction chemotherapy. On the second day of blinatumomab infusion, she developed intermittent low-grade fever, and chest computed tomography (CT) revealed subtle infiltrates and nodules. Despite empiric trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis, she progressed to significant shortness of breath and type I respiratory failure, with increased lactate dehydrogenase and β-D-glucan assays. Chest CT showed diffuse ground-glass opacities with scattered small nodules. The dry cough prompted next-generation sequencing of peripheral blood, which tested positive for pneumocystis jirovecii without evidence of other pathogens. Consequently, the patient was diagnosed with PCP. The first cycle of blinatumomab had to be discontinued, and therapeutic dosages of TMP-SMX and dexamethasone were administered, resulting in full recovery and stable condition during follow-ups. Conclusion: PCP is rare in B-cell precursor ALL patients receiving blinatumomab therapy but manifests with early onset and rapid disease progression. Despite prophylaxis, PCP infection cannot be ignored during blinatumomab therapy. Therefore, heightened attention is warranted when using blinatumomab therapy.
Histórias de medo para crianças como primeiras leituras de terror e a viagem assustadora de Huguinho, Zezinho e Luisinho
Authors: Campos Felipe Ribeiro
Published: March 2024

In the Duckscares series, Donald Duck’s famous nephews Huey, Dewey and Louie travel to several European countries, where they face numerous supernatural dangers. In Brazil, the comics were published in 2021 as a compilation containing four stories, each being split in two parts. The object of research is ‘The Nightmare Formula’ story. It dialogs with elements from fairy tales connected to characters and conventions commonly found in fear narratives, as expected, and aims at observing the strategies used by both verbal and non-verbal texts with the intention of causing fear to the reader. This publication is an example of how terror can also please younger readers when it is created with this public in mind; it is also a first point of contact with the genre that can potentially increase the number of adult readers interested in it. This research is based on the theoretical works of Carlos Reis, Paulo Ramos, Stephen King and Thierry Groensteen.
As faces da morte e o lado descarnado da vida segundo Benett
Authors: Viana Raí Garcia Mihi Barbalho , Borges Maria Isabel
Published: March 2024

This research sought to highlight and study the representations of death in the productions of Brazilian cartoonist Alberto Benett. The criteria selection for the corpus was as followed: productions published on the Facebook page “Benett Apavora”; comic strips and political cartoons; c) productions that highlighted the theme of death through recognizable visual symbols (skull, reaper, skeleton). The survey resulted in 52 texts about death – 42 political cartoons, 10 comic strips. In this work, two samples were chosen for analysis, two comic strips and three political cartoons. The theoretical support consisted of studies on death symbols (Chevalier, Gheerbrant, 2015; Calabritto, Daly, 2014; Ariès, 2012; Guthke, 1999; Lousa, 2016), language and genres of comics (Cagnin, 2014; Eisner, 2010; Borges, 2022; Carmelino, Possenti, 2023; Miani, 2023; Romualdo, 2000; Ramos, 2012, 2011, 2017). The analysis proved a preference for the skull and the reaper, for their suggestive evocation of death, but the effect generated can change from text to text.
Mediating and moderating function of corporate governance on the relationship between tax planning and tax disclosure
Authors: Mgammal Mahfoudh , Al-Absy Mujeeb Saif Mohsen
Published: March 2024

This study analyzes the moderating, mediating, and direct effects of corporate governance (CG) proxy mechanisms on the relationship between tax planning (TP), measured by effective tax rate components, and tax disclosure (TD). We tested the hypotheses using a 4-step hierarchical regression with Malaysian-listed non-financial companies using a balanced sample of 858 observations. We found that companies positively assessed their TP activities. Inspection of the implications of CG mechanisms as moderation on TP-TD association displayed the absence of an important constant correlated to any of the interactive variables. This makes it difficult to understand the nature of this relationship. The results illustrate the high and significant mediated impact of board compensation (BCOMS) on the TP-TD association. We further studied the sensitivity of the results and the outcomes were examined for the robustness and strength of the model specification using OLS effect estimators and the absence of TP-related factors. These test findings show no effect on the TP-TD association. This study shows that firms try to avoid taxation as far as possible by disclosing relevant tax information. These results suggest that firms express a trade-off between tax advantages and TD when choosing their TP. It meaningfully subsidizes the argument about TD concerning “comply-or-explain”, as the CG Code proposes.
The Battle over Proportionality and Essentiality: Limitations to Freedom of Religion or Belief During the Pandemic in Brazil
Authors: Carvalho Felipe Augusto Lopes
Published: March 2024

Emergency responses to the Covid-19 pandemic have generated debates over the scope and reach of government powers in the exercise of freedom of religion or belief (FoRB) and the compliance with international and constitutional provisions. This article argues that the standards used by the Brazilian Supreme Court to scrutinize the limitations imposed on religious activities were incomplete because they focused on the temporality of the restrictions and the factual situation of hospitals’ capacity. Although these are fundamental factors, the Court should have assessed the principle of proportionality between the objectives pursued and the means adopted. Furthermore, the unilateral “essentiality strategy”, used both at federal and state levels was problematic and generated more problems than solutions vis-à-vis religious groups. Instead, a collaboration-driven approach that stays away from debating whether or not a religious activity is essential should be used in the event of future health outbreaks.
Of Cakes, Websites and Faith-Based Complaints: the Fine Art of Crafting Religion as Speech
Authors: Corsalini Matteo
Published: March 2024

In 303 Creative LLC v. Elenis (2023), for the first time ever, the United States Supreme Court (USSC) explicitly recognised that business commercials now enjoy constitutional, First Amendment-based religious exemptions from providing services to same-sex customers. Not even in its much-maligned decision in Burwell v. Hobby Lobby (2014), which extended in an unprecedented way to for-profit companies statutory (but not constitutional) rights heretofore confined to churches, the Court went this far. But more than this, the decision in 303 Creative LLC also appears to be the symbol of something new: a definitive shift to the Free Speech Clause to the U.S. Constitution as an alternative tool to the Free Exercise Clause for protecting religious liberty. This article explains why this shift in doctrine has happened, why it matters, and how enhanced protections for business religious free speech fits with the agenda of conservative constitutional politics in America.
Musical Genre Preferences among School Students: The Role of the Family Background and Musical Instruments Learning
Authors: Szabó Norbert , Földi Fanni , Oo Tun Zaw , Csizmadia Gábor , Józsa Krisztián
Published: March 2024

The study presents the results of research that examines the popularity of videos representing four different musical styles among students aged 9–19 ( N = 1159). The measuring instrument was a self-developed online questionnaire that explores students’ musical genre opinions based on four types of music videos: street music, rock music, classical music, and folk music. In relation to the musical pieces, we inquired about background aspects, with a specific focus on engagement in instrument presentations and the viewing of music programs. We analyze the data considering the context of learning a musical instrument and attitudes toward instrument training and family background. Findings show that the perception of genres varies significantly between students who play instruments and those who do not, as well as based on their family background. Among the seven groups of students, encompassing both instrument learners and non-learners, a distinct pattern emerges those who neither learn nor have a desire to learn an instrument exhibit notably lower fondness for musical compositions. Furthermore, significant differences are apparent among the students based on the educational level of their parents. The implication of this study lies in its revelation of how instrument training and parental education significantly shape students’ musical opinions, underscoring the need for targeted interventions to enhance music education experiences and enrich young individuals’ musical tastes.
Multiomic profiling of human clonal hematopoiesis reveals genotype and cell-specific inflammatory pathway activation
Authors: Heimlich J. Brett , Bhat Pawan , Parker Alyssa C. , Jenkins Matthew T. , Vlasschaert Caitlyn , Ulloa Jessica , Van Amburg Joseph C. , Potts Chad R. , Olson Sydney , Silver Alexander J. , Ahmad Ayesha , Sharber Brian , Brown Donovan , Hu Ningning , van Galen Peter , Savona Michael R. , Bick Alexander G. , Ferrell P. Brent
Published: March 2024

Clonal hematopoiesis (CH) is an age-associated phenomenon that increases the risk of hematologic malignancy and cardiovascular disease. CH is thought to enhance disease risk through inflammation in the peripheral blood.1 Here, we profile peripheral blood gene expression in 66 968 single cells from a cohort of 17 patients with CH and 7 controls. Using a novel mitochondrial DNA barcoding approach, we were able to identify and separately compare mutant Tet methylcytosine dioxygenase 2 (TET2) and DNA methyltransferase 3A (DNMT3A) cells with nonmutant counterparts. We discovered the vast majority of mutated cells were in the myeloid compartment. Additionally, patients harboring DNMT3A and TET2 CH mutations possessed a proinflammatory profile in CD14+ monocytes through previously unrecognized pathways such as galectin and macrophage inhibitory factor. We also found that T cells from patients with CH, although mostly unmutated, had decreased expression of GTPase of the immunity associated protein genes, which are critical to T-cell development, suggesting that CH impairs T-cell function.
Differentiation syndrome associated with treatment with IDH2 inhibitor enasidenib: pooled analysis from clinical trials
Authors: Montesinos Pau , Fathi Amir T. , de Botton Stéphane , Stein Eytan M. , Zeidan Amer M. , Zhu Yue , Prebet Thomas , Vigil Carlos E. , Bluemmert Iryna , Yu Xin , DiNardo Courtney D.
Published: March 2024

Treatment with enasidenib, a selective mutant isocitrate dehydrogenase isoform 2 (IDH2) inhibitor, has been associated with the development of differentiation syndrome (DS) in patients with acute myeloid leukemia (AML). Studies on the incidence and clinical features of DS are limited in this setting, and diagnosis is challenging because of nonspecific symptoms. This study assessed the incidence, diagnostic criteria, risk factors, and correlation with clinical response of DS based on the pooled analysis of 4 clinical trials in patients with IDH2-mutated AML treated with enasidenib as monotherapy, or in combination with azacitidine or with chemotherapy. Across the total AML population, 67 of 643 (10.4%) had ≥1 any-grade DS event, with highest incidence in patients who received enasidenib plus azacitidine and lowest incidence in patients who received enasidenib plus chemotherapy (13/74 [17.6%] and 2/93 [2.2%]). The most common symptoms of DS were dyspnea/hypoxia (80.6%) and pulmonary infiltrate (73.1%). Median time to onset of first DS event across all studies was 32 days (range, 4-129). Most patients (88.1%) received systemic steroids for treatment of DS. Evaluation of baseline risk factors for DS identified higher levels of bone marrow blasts and lactate dehydrogenase as independent factors associated with increased grade 3 to 5 DS risk. Overall, these results suggest that DS associated with IDH inhibition is manageable, given the benefits of enasidenib treatment in IDH2-mutated AML. We further characterized enasidenib-related DS in these patients and identified risk factors, which could be used for DS management in clinical practice. These trials were registered at www.ClinicalTrials.gov as # NCT01915498, NCT02577406, NCT02677922, and NCT02632708.
Dissecting causal links between gut microbiota, inflammatory cytokines, and DLBCL: a Mendelian randomization study
Authors: Jiang Peiyao , Yu Fangfang , Zhou Xiao , Shi Huizhong , He Qiaomei , Song Xianmin
Published: March 2024

Causal relationships between gut microbiota, inflammatory cytokines, and diffuse large B-cell lymphoma (DLBCL) remain elusive. In addressing this gap, our Mendelian randomization (MR) study used data from the MiBioGen consortium encompassing 211 microbiota taxa (n = 18 340), genome-wide association study meta-analyses of 47 inflammatory cytokines, and DLBCL cases and controls from the FinnGen consortium (cases, n = 1010; controls, n = 287 137). Through bidirectional MR analyses, we examined the causal links between gut microbiota and DLBCL and used mediation analyses, including 2-step MR and multivariable MR (MVMR), to identify potential mediating inflammatory cytokines. Our findings revealed that 4 microbiota taxa were causally associated with DLBCL, and conversely, DLBCL influenced the abundance of 20 taxa. Specifically, in the 2-step MR analysis, both the genus Ruminococcaceae UCG-002 (odds ratio [OR], 1.427; 95% confidence interval [CI], 1.011-2.015; P = .043) and the inflammatory cytokine monokine induced by gamma (MIG) (OR, 1.244; 95% CI, 1.034-1.487; P = .020) were found to be causally associated with an increased risk of DLBCL. Additionally, a positive association was observed between genus Ruminococcaceae UCG-002 and MIG (OR, 1.275; 95% CI, 1.069-1.520; P = .007). Furthermore, MVMR analysis indicated that the association between genus Ruminococcaceae UCG-002 and DLBCL was mediated by MIG, contributing to 14.9% of the effect (P = .005). In conclusion, our MR study provides evidence that supports the causal relationship between genus Ruminococcaceae UCG-002 and DLBCL, with a potential mediating role played by the inflammatory cytokine MIG.
Microclots, as defined by amyloid-fibrinogen aggregates, predict risks of disseminated intravascular coagulation and mortality
Authors: Schofield Jeremy , Abrams Simon T. , Jenkins Rosalind , Lane Steven , Wang Guozheng , Toh Cheng-Hock
Published: March 2024

Microclots have been associated with various conditions, including postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection. They have been postulated to be amyloid-fibrin(ogen) aggregates, but their role as a prognostic biomarker remains unclear. To examine their possible clinical utility, blood samples were collected for the first 96 hours from critically ill patients (n = 104) admitted to the intensive care unit (ICU). Detection was by staining platelet-poor plasma samples with thioflavin T and visualized by fluorescent microscopy. Image J software was trained to identify and quantify microclots, which were detected in 44 patients (42.3%) on ICU admission but not in the remaining 60 (57.7%) or the 20 healthy controls (0.0%). Microclots on admission to ICU were associated with a primary diagnosis of sepsis (microclots present in sepsis, 23/44 [52.3%] vs microclots absent in sepsis, 19/60 [31.7%]; P = .044). Multicolor immunofluorescence demonstrated that microclots consisted of amyloid-fibrinogen aggregates, which was supported by proteomic analysis. Patients with either a high number or larger-sized microclots had a higher likelihood of developing disseminated intravascular coagulation (odds ratio [OR], 51.4; 95% confidence interval [CI], 6.3-6721.1; P < .001) and had an increased probability of 28-day mortality (OR, 5.3; 95% CI, 2.0-15.6; P < .001). This study concludes that microclots, as defined by amyloid-fibrin(ogen) aggregates, are potentially useful in identifying sepsis and predicting adverse coagulopathic and clinical outcomes.
Implementation and external validation of the Cambridge Multimorbidity Score in the UK Biobank cohort
Authors: Harrison Hannah , Ip Samantha , Renzi Cristina , Li Yangfan , Barclay Matthew , Usher-Smith Juliet , Lyratzopoulos Georgios , Wood Angela , Antoniou Antonis C.
Published: March 2024

Background

Patients with multiple conditions present a growing challenge for healthcare provision. Measures of multimorbidity may support clinical management, healthcare resource allocation and accounting for the health of participants in purpose-designed cohorts. The recently developed Cambridge Multimorbidity scores (CMS) have the potential to achieve these aims using primary care records, however, they have not yet been validated outside of their development cohort.

Methods

The CMS, developed in the Clinical Research Practice Dataset (CPRD), were validated in UK Biobank participants whose data is not available in CPRD (the cohort used for CMS development) with available primary care records (n = 111,898). This required mapping of the 37 pre-existing conditions used in the CMS to the coding frameworks used by UK Biobank data providers. We used calibration plots and measures of discrimination to validate the CMS for two of the three outcomes used in the development study (death and primary care consultation rate) and explored variation by age and sex. We also examined the predictive ability of the CMS for the outcome of cancer diagnosis. The results were compared to an unweighted count score of the 37 pre-existing conditions.

Results

For all three outcomes considered, the CMS were poorly calibrated in UK Biobank. We observed a similar discriminative ability for the outcome of primary care consultation rate to that reported in the development study (C-index: 0.67 (95%CI:0.66–0.68) for both, 5-year follow-up); however, we report lower discrimination for the outcome of death than the development study (0.69 (0.68–0.70) and 0.89 (0.88–0.90) respectively). Discrimination for cancer diagnosis was adequate (0.64 (0.63–0.65)). The CMS performs favourably to the unweighted count score for death, but not for the outcomes of primary care consultation rate or cancer diagnosis.

Conclusions

In the UK Biobank, CMS discriminates reasonably for the outcomes of death, primary care consultation rate and cancer diagnosis and may be a valuable resource for clinicians, public health professionals and data scientists. However, recalibration will be required to make accurate predictions when cohort composition and risk levels differ substantially from the development cohort. The generated resources (including codelists for the conditions and code for CMS implementation in UK Biobank) are available online.
Developing a clinical decision support system software prototype that assists in the management of patients with self-harm in the emergency department: protocol of the PERMANENS project
Authors: Mortier Philippe , Amigo Franco , Bhargav Madhav , Conde Susana , Ferrer Montse , Flygare Oskar , Kizilaslan Busenur , Latorre Moreno Laura , Leis Angela , Mayer Miguel Angel , Pérez-Sola Víctor , Portillo-Van Diest Ana , Ramírez-Anguita Juan Manuel , Sanz Ferran , Vilagut Gemma , Alonso Jordi , Mehlum Lars , Arensman Ella , Bjureberg Johan , Pastor Manuel , Qin Ping
Published: March 2024

Background

Self-harm presents a significant public health challenge. Emergency departments (EDs) are crucial healthcare settings in managing self-harm, but clinician uncertainty in risk assessment may contribute to ineffective care. Clinical Decision Support Systems (CDSSs) show promise in enhancing care processes, but their effective implementation in self-harm management remains unexplored.

Methods

PERMANENS comprises a combination of methodologies and study designs aimed at developing a CDSS prototype that assists clinicians in the personalized assessment and management of ED patients presenting with self-harm. Ensemble prediction models will be constructed by applying machine learning techniques on electronic registry data from four sites, i.e., Catalonia (Spain), Ireland, Norway, and Sweden. These models will predict key adverse outcomes including self-harm repetition, suicide, premature death, and lack of post-discharge care. Available registry data include routinely collected electronic health record data, mortality data, and administrative data, and will be harmonized using the OMOP Common Data Model, ensuring consistency in terminologies, vocabularies and coding schemes. A clinical knowledge base of effective suicide prevention interventions will be developed rooted in a systematic review of clinical practice guidelines, including quality assessment of guidelines using the AGREE II tool. The CDSS software prototype will include a backend that integrates the prediction models and the clinical knowledge base to enable accurate patient risk stratification and subsequent intervention allocation. The CDSS frontend will enable personalized risk assessment and will provide tailored treatment plans, following a tiered evidence-based approach. Implementation research will ensure the CDSS’ practical functionality and feasibility, and will include periodic meetings with user-advisory groups, mixed-methods research to identify currently unmet needs in self-harm risk assessment, and small-scale usability testing of the CDSS prototype software.

Discussion

Through the development of the proposed CDSS software prototype, PERMANENS aims to standardize care, enhance clinician confidence, improve patient satisfaction, and increase treatment compliance. The routine integration of CDSS for self-harm risk assessment within healthcare systems holds significant potential in effectively reducing suicide mortality rates by facilitating personalized and timely delivery of effective interventions on a large scale for individuals at risk of suicide.
Distribution of internal medicine rotations among resident physicians in Japan: a nationwide, multicenter, cross-sectional study
Authors: Shikino Kiyoshi , Sekine Miwa , Nishizaki Yuji , Yamamoto Yu , Shimizu Taro , Fukui Sho , Nagasaki Kazuya , Yokokawa Daiki , Watari Takashi , Kobayashi Hiroyuki , Tokuda Yasuharu
Published: March 2024

Background

In Japan, postgraduate clinical training encompasses a 2-year residency program, including at least 24 weeks of internal medicine (IM) rotations. However, the fragmented structure of these rotations can compromise the training’s quality and depth. For example, a resident might spend only a few weeks in cardiology before moving to endocrinology, without sufficient time to deepen their understanding or have clinical experience. This study examined current patterns and lengths of IM rotations within the Japanese postgraduate medical system. It scrutinized the piecemeal approach—whereby residents may engage in multiple short-term stints across various subspecialties without an overarching, integrated experience—and explored potential consequences for their clinical education.

Methods

This nationwide, multicenter, cross-sectional study used data from self-reported questionnaires completed by participants in the 2022 General Medicine In-Training Examination (GM-ITE). Data of 1,393 postgraduate year (PGY) one and two resident physicians who participated in the GM-ITE were included. We examined the IM rotation duration and number of IM subspecialties chosen by resident physicians during a 2-year rotation.

Results

Approximately half of the participants chose IM rotation periods of 32–40 weeks. A significant proportion of participants rotated in 5–7 internal medicine departments throughout the observation period. Notable variations in the distribution of rotations were observed, characterized by a common pattern where resident physicians typically spend 4 weeks in each department before moving to the next. This 4-week rotation is incrementally repeated across different subspecialties without a longer, continuous period in any single area. Notably, 39.7% of participants did not undertake general internal medicine rotations. These results suggest a narrowed exposure to medical conditions and patient care practices.

Conclusions

Our study highlights the need to address the fragmented structure of IM rotations in Japan. We suggest that short, specialized learning periods may limit the opportunity to gain broad in-depth knowledge and practical experience. To improve the efficacy of postgraduate clinical education, we recommend fostering more sustained and comprehensive learning experiences.