bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical cause of neonatal mortality in Iran: analysis of the national Iranian Maternal And Neonatal network
Authors: Habibelahi Abbas , Heidarzadeh Mohammad , Abdollahi Leila , Taheri Majzoubeh , Ghaffari-Fam Saber , Vakilian Roshanak , Daemi Amin 
Published: March 2024

BackgroundThe neonatal mortality rate is a main indicator of the health and development of a country. Having insight into the cause of neonatal deaths may be the first step to reducing it. This paper depicts the cause of newborn deaths in Iran.MethodsThis cross-sectional study was performed on data from the national Iranian Maternal And Neonatal network to investigate all neonatal deaths in the country during the year 2019. The cause of death data were reported according to categories of birth weight, gestational age (GA), death time and place.ResultsThe main causes of the 9959 neonatal deaths during the study period were respiratory distress syndrome (RDS) (37%), malformation (21%), prematurity of <26 weeks (20%), others (12%), asphyxia (7%) and infection (3%). The major causes of neonatal mortality in delivery rooms were prematurity of <26 weeks and in the inpatient wards the RDS. By increasing the GA and birth weight towards term babies, the rate of RDS gets lower, while that of malformation gets higher.ConclusionsRDS was the main cause of neonatal mortality in Iran which is seen mainly in preterm babies. Prematurity of <26 weeks was another main cause. Thus, suggestions include reducing prematurity by preconception and pregnancy care and, on the other hand, improving the care of preterm infants in delivery rooms and inpatient wards.
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

BackgroundDespite 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.MethodsThis 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.ResultsIn 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.ConclusionPaediatric 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.
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

BackgroundRadiofrequency 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.MethodsNine 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.ResultsThe 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.ConclusionsThese findings suggest that HIFU may be more effective than RFA in inducing thermal necrosis of the nerve.
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

Abstract

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

Abstract

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.
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

Abstract
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

Abstract
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.
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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 &lt; .001) and had an increased probability of 28-day mortality (OR, 5.3; 95% CI, 2.0-15.6; P &lt; .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

Abstract
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.