bluuebunny/crossref_metadata_2025_split huggingface dataset:
What are the Characteristics of Oral Injuries Caused by Playground Equipment?
Authors: Yamada Miki , Hino Shunsuke , Iijima Yosuke , Horie Norio , Kaneko Takahiro 
Published: June 2024

Purpose:
Studies regarding oral injuries from playground equipment in children remain limited. This study aimed to clarify the characteristics of oral injury caused by playground equipment and identify associations with concomitant head injury.

Methods:
Children treated between 2011 and 2021 at an oral surgery clinic for oral injuries from playground equipment were retrospectively investigated. The following factors were analyzed: demographic characteristics, mechanism of injury, type of equipment causing the injury, classification of oral injury, and whether the Department of Emergency and Critical Care Medicine was consulted regarding the head injury. The data collected were statistically analyzed using the Fisher-Freeman-Halton test with significance adopted at the 5% level.

Results:
This study analyzed data from 82 children. Injuries were concentrated in age groups of 2 to 3 years (32.9%), 4 to 5 years (28.0%), and 6 to 7 years (25.6%). Regarding the mechanism of injury, falls were more common (89.0%) than impact/striking (11.0%). The type of equipment most frequently causing injury was slides (29.3%), followed by swings (23.2%) and iron bars (18.3%). Injuries were classified as soft tissue injury alone (56.1%) or tooth injury and/or jaw fracture (43.9%). Consultation with the Department of Emergency and Critical Care Medicine for head injury was uncommon (13.4%), and all consultations for brain injury diagnosed minor injuries.

Conclusion:
Oral injuries caused by playground equipment were frequent between 2 and 7 years old. The most common cause was falls, with most injuries caused by slides, swings, or iron bars. Approximately half of the oral injuries were soft tissue injuries only, while the other half were associated with tooth and/or jaw injuries. Department of Emergency and Critical Care Medicine consultations for head trauma were uncommon and consistently confirmed minor injuries.
The Lost and Variable Cause: A Systematic Review of Shunt-Related Craniosynostosis Occurrence
Authors: LaValley Myles N. , Asadourian Paul A. , Valenti Alyssa B. , Hoffman Caitlin E. , Imahiyerobo Thomas A. 
Published: June 2024

Objective:
Shunt-related craniosynostosis (SRC) is the premature fusion of cranial sutures possibly due to a loss of tension across dura and suture lines after placement of a shunt for hydrocephalus. As modifications in approaches toward shunting represent a modifiable risk factor, prior literature has investigated the determinants and outcomes. However, the data remain highly variable and are limited by single-institution studies.

Methods:
A systematic search of PubMed, Embase, and Web of Science from inception to February 2022 was conducted. Studies were screened by 2 reviewers for eligibility based on predefined inclusion/exclusion criteria.

Results:
In the 9 included articles, the average follow-up time for the entire cohort ranged from 1.5 to 4.2 years. The pooled incidence of SRC across all 9 studies was 6.5% (140/2142), with an individual range of 0.53% (1/188) to 48.8% (61/125). The average time from shunt placement to SRC diagnosis ranged from 0.25 years to 4.6 years. 61% (65/110) of cases included only one suture, 88% (25/28) of these involved the sagittal suture, and those cases with multiple fusions also had 98% involvement of the sagittal suture (45/46). Overall, 94% (1783/1888) of patients had a fixed shunt placed.

Conclusions:
Shunt-related craniosynostosis is likely an underreported complication in the treatment of hydrocephalus. Older age at shunt placement, increased number of shunt revision procedures, and lower valve pressure settings may be risk factors for SRC development. Results also indicate that craniosynostosis can develop months to years after shunting. Future quality studies with standardization of data reporting processes are warranted to investigate this clinical problem.
Extended Pharmacologic Prophylaxis for Venous Thromboembolism After Colon Cancer Surgery Is Associated With Improved Long-term Survival
Authors: Booth Alexander , Brinton Daniel , Donahue Colleen , Westfal Maggie , George Virgilio , Maxwell Pinckney J. , Simpson Kit , Mahvi David , Curran Thomas 
Published: June 2024

Objective:
This large database study assessed whether extended pharmacologic prophylaxis for venous thromboembolism after colon cancer resection was associated with improved oncologic survival.

Background:
Heparin derivatives may confer an antineoplastic effect via a variety of mechanisms (eg, inhibiting angiogenesis in the tumor microenvironment). Studies evaluating the oncologic benefit of heparin and its derivatives have been limited in postsurgical patients. Multiple society guidelines recommend consideration of 30-day treatment with low molecular weight heparin to reduce venous thromboembolism risk after abdominopelvic cancer surgery. However, utilization of extended prophylaxis remains low.

Methods:
Surveillance, Epidemiology, and End Results-Medicare data were used to identify patients (age 65+) undergoing resection for nonmetastatic colon cancer from 2016 to 2017. The primary outcomes were overall and cancer-specific survival. Log-rank testing and multivariable Cox regression compared survival in patients who received extended prophylaxis versus those who did not in an inverse propensity treatment weighted cohort.

Results:
A total of 20,102 patients were included in propensity-weighting and analyzed. Eight hundred (3.98%) received extended pharmacologic prophylaxis. Overall survival and cancer-specific survival were significantly higher in patients receiving prophylaxis on log-rank tests (P=0.0017 overall, P=0.0200 cancer-specific). Multivariable Cox regression showed improved overall survival [adjusted hazard ratio 0.66 (0.56–0.78)] and cancer-specific survival [adjusted hazard ratio 0.56 (0.39–0.81)] with prophylaxis after controlling for patient, treatment, and hospital factors.

Conclusions:
Extended pharmacologic prophylaxis after colon cancer resection was independently associated with improved overall and cancer-specific survival. These results suggest a potential antineoplastic effect from heparin derivatives when used in the context of preventing postsurgical venous thromboembolism.
Adding Patient-reported Outcomes to the American College of Surgeons National Surgical Quality Improvement Program
Authors: Liu Jason B. , Pusic Andrea L. , Melucci Alexa D. , Brajcich Brian C. , Fordham Matthew J. , Lapsley Jakob C. , Ko Clifford Y. , Temple Larissa K.F. 
Published: June 2024

Objective:
To investigate the initial set of patient-reported outcomes (PROs) in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) and their associations with 30-day surgical outcomes.

Background:
PROs provide important information that can be used to improve routine care and facilitate quality improvement. The American College of Surgeons conducted a demonstration project to capture PROs into the NSQIP to complement clinical data.

Methods:
From February 2020 to March 2023, 65 hospitals collected Patient-Reported Outcomes Measurement Information System measures assessing global health, pain interference, fatigue, and physical function from patients accrued into the NSQIP. Using multivariable mixed regression, we compared the scores of patients with and without 30-day complications and further analyzed scores exceeding 1-SD worse than national benchmarks.

Results:
Overall, 33842 patients completed the Patient-Reported Outcomes Measurement Information System measures with a median of 58 days (IQR: 47–72) postoperatively. Among patients without complications (n = 31210), 33.9% had PRO scores 1-SD worse than national benchmarks. Patients with complications were 1.7 times more likely to report worse PROs (95% CI: 1.6–1.8). Patients with complications had lower scores for global physical health [adjusted mean difference (AMD): 2.6, 95% CI: 2.2–3.0], lower for global mental health (AMD: 1.8, 95% CI: 1.4–2.2), higher for pain interference (AMD: 2.4, 95% CI: 2.0–2.8), higher fatigue (AMD: 2.7, 95% CI: 2.3–3.1), and lower physical function (AMD: 3.2, 95% CI: 2.8–3.5).

Conclusions:
Postoperative complications negatively affect multiple key dimensions of patients’ health-related quality of life. PROs were well below national benchmarks for many patients, even among those without complications. Identifying solutions to improve PROs after surgery remains a tremendous quality improvement opportunity.
Recent insights into haematology and peripheral nerve disease
Authors: Tomkins Oliver , Lunn Michael P. 
Published: June 2024

Purpose of review
The association between clonal haematological disorders and peripheral nerve disease is recognized. Paraproteinaemic phenomena are the most common mechanism, but direct neural lymphomatous infiltration is seen and can be challenging to diagnose. Traditional and novel anticancer therapies have neuropathic side effects.

Recent findings
Novel studies using sensitive techniques are refining the incidence of peripheral neuropathy in patients with a monoclonal gammopathy, and the pathogenesis of IgM Peripheral neuropathy (PN) and POEMS syndrome. Recent series give insight into the characteristics and diagnostic challenges of patients with neurolymphomatosis and amyloid light chain amyloidosis. There is an increasing repertoire of effective anticancer drugs in haematological oncology, but chemotherapy-related neuropathy remains a common side effect.

Summary
This review of the current literature focuses on recent updates and developments for the paraproteinaemic neuropathies, and the evaluation, diagnosis and treatment of peripheral nerve disease due to high-grade and low-grade lymphomas and lymphoproliferative disorders.
Altered T cell reactivity to β-amyloid-related antigens in early Alzheimer’s disease
Authors: Rickenbach Chiara , Mallone Anna , Häusle Lars , Frei Larissa , Seiter Sarina , Sparano Colin , Kirabali Tunahan , Blennow Kaj , Zetterberg Henrik , Ferretti Maria Teresa , Kulic Luka , Hock Christoph , Nitsch Roger M. , Treyer Valerie , Gietl Anton , Gericke Christoph 
Published: June 2024

AbstractThere is growing evidence that the adaptive immune system and neurodegenerative Alzheimer’s disease (AD) are intertwined in multiple ways. Recent studies have reported alterations of the adaptive immune system in early AD stages, such as preclinical AD and mild cognitive impairment (MCI) due to AD. However, the identity of specific antigenic targets and whether the respective response is beneficial or detrimental during disease progression are still open questions. Herein, we describe cross-sectional analyses of blood and cerebrospinal fluid from three different study populations covering early AD stages. We employed high-dimensional mass cytometry, single-cell RNA-sequencing,in vitroT cell secretome analysis, and antigen presentation assays to achieve a comprehensive characterization of adaptive immune cell populations. Our results show that subjects at the stage of asymptomatic, preclinical AD can mount a CD4+T helper cell response towards β- amyloid peptide and display an early enrichment of cytotoxic CD8+effector/TEMRA cells in CSF, combined with a less immunosuppressive gene signature of peripheral regulatory T cells. Conversely, in MCI due to AD, we observed increased frequencies of CD8+effector/TEMRA cells in the periphery, characterized by a pro-inflammatory gene expression profile and an overall decrease in antigen responsiveness. Our results demonstrate the complexity of adaptive immune changes in early AD and suggest that it may be beneficial in the preclinical stage to promote specific CD4+T cell responses, while in MCI it may be important to therapeutically target CD8+T cell responses if these prove to be harmful.
Increased stomach-brain coupling indexes a dimensional signature of negative mental health symptoms
Authors: Banellis Leah , Rebollo Ignacio , Nikolova Niia , Allen Micah 
Published: June 2024

AbstractVisceral rhythms orchestrate the physiological states underlying human emotion. Chronic aberrations in these brain-body interactions are implicated in a broad spectrum of mental health disorders. However, the specific contributions of the gastric-brain coupling to affective symptoms remain poorly understood. We investigated the relationship between this novel interoceptive axis and mental health symptoms in 243 participants, using a cross validated machine learning approach. We find that frontal parietal brain coupling to the gastric rhythm indexes a dimensional signature of mental health spanning anxiety, depression, stress, and well-being. Control analyses confirm the specificity of these interactions to the gastric-brain axis. Our study establishes coupling between the stomach and brain as a factor in the pathology of mental health, and offers new targets for interventions remediating aberrant brain-body coupling.
Targeting DOT1L and EZH2 synergizes in breaking the germinal center identity of Diffuse Large B Cell Lymphoma
Authors: Göbel Camiel , Niccolai Rachele , de Groot Marnix H.P. , Jayachandran Jayashree , Traets Joleen , Morris Ben , Song Ji-Ying , Azarang Leyla , Kasa Eirini , de Groot Daniel , Kreft Maaike , Kersten Marie José , Aslam Muhammad A. , van Leeuwen Fred , Jacobs Heinz 
Published: June 2024

AbstractDifferentiation of antigen-activated B cells into pro-proliferative germinal center (GC) B cells depends on the activity of the transcription factor MYC and the epigenetic writers DOT1L and EZH2. GCB-like Diffuse Large B Cell Lymphomas (GCB-DLBCLs) arise from GC B cells and closely resemble their cell of origin. Given the dependency of GC B cells on DOT1L and EZH2, we investigated the role of these epigenetic regulators in GCB-DLBCL cell lines and observed that GCB-DLBCLs synergistically depend on the combined activity of DOT1L and EZH2. Mechanistically, inhibiting both enzymes led to enhanced derepression of PRC2 target genes compared to EZH2 single treatment, along with the suppression of MYC target genes. The sum of all these alterations results in a ‘cell-identity crisis,’ wherein GCB-DLBCLs lose their pro-proliferative GC identity and partially undergo plasma cell differentiation, a state associated with poor survival. In support of this model, combined epi-drugging of DOT1L and EZH2 prohibited the outgrowth of human GCB-DLBCL xenograftsin vivo. We conclude that the malignant behavior of GCB-DLBCLs strictly depends on DOT1L and EZH2 and that combined targeting of both epigenetic writers may provide an alternative differentiation-based treatment modality for GCB-DLBCL.Key pointsMYC-driven GCB-DLBCL depends on DOT1L and EZH2 and combined targeting provides an alternative differentiation-based therapy.DOT1L and EZH2 cooperatively repress PRC2 target genes which is essential for acquiring a plasma cell-like state in GC B cell-like DLBCL.
New insight in cyclic monoterpenoids mechanism of action: an in silico approach
Authors: Pezzola Silvia , Sabuzi Federica , Galloni Pierluca , Conte Valeria , Venanzi Mariano , Bocchinfuso Gianfranco 
Published: June 2024

AbstractClarifying the mechanism of action of natural terpenoids is challenging. Further, their efficacy is inspiring in developing new antimycotic agents. Among all, thymol, carvacrol and thymyl acetate are largely scrutinized, while the new brominate thymol, namely bromothymol (4-bromo-2-isopropyl-5-methylphenol), needs deeper investigation. Here its antimycotic efficacy was evaluated and, in parallel, a careful in silico investigation of the mechanism of action was proposed. In vivo experiments, on species of acclaimed resistance, demonstrated that bromothymol had a Minimum Inhibitory Concentration (MIC) equal ∼40 μg/ml, 6 times more active than thymol. Partition coefficient (LogP) in heptane, determined through density functional theory (DFT), and Molecular Dynamics (MD) simulations, based on a Minimum Bias Approach, in the presence of neutral bilayers, indicated that bromothymol inserts into cellular membrane, such as thymol, carvacrol, and Thymyl acetate. Monoterpenoids bearing the hydroxyl group induces a shrinkage of the membrane thickness, while only thymol affected membrane density of the leaflets in which it inserted. Thymol, carvacrol, and bromothymol interacted with the polar head of the lipids causing an electrostatic imbalance into the membrane, justifying their biological activity. For the first time a detailed in silico characterization on the mechanism of these compounds is afforded, returning a coherent and clear picture of their mechanism of action.
Beta-adrenergic signaling and T-lymphocyte-produced catecholamines are necessary for interleukin 17A synthesis
Authors: Lauten Tatlock H. , Elkhatib Safwan K. , Natour Tamara , Reed Emily C. , Jojo Caroline N. , Case Adam J. 
Published: June 2024

AbstractBackgroundPost-traumatic stress disorder (PTSD) is a debilitating psychological disorder that also presents with neuroimmune irregularities. Patients display elevated sympathetic tone and are at an increased risk of developing secondary autoimmune diseases. Previously, using a preclinical model of PTSD, we demonstrated that elimination of sympathetic signaling to T-lymphocytes specifically limited their ability to produce pro-inflammatory interleukin 17A (IL-17A); a cytokine implicated in the development of many autoimmune disorders. However, the mechanism linking sympathetic signaling to T-lymphocyte IL-17A production remained unclear.MethodsUsing a modified version of repeated social defeat stress (RSDS) that allows for both males and females, we assessed the impact of adrenergic receptor blockade (genetically and pharmacologically) and catecholamine depletion on T-lymphocyte IL-17A generation. Additionally, we explored the impact of adrenergic signaling and T-lymphocyte-produced catecholamines on both CD4+ and CD8+ T-lymphocytes polarized to IL-17A-producing phenotypes ex vivo.ResultsOnly pharmacological inhibition of the beta 1 and 2 adrenergic receptors (β1/2) significantly decreased circulating IL-17A levels after RSDS, but did not impact other pro-inflammatory cytokines (e.g., IL-6, TNF-α, and IL-10). This finding was confirmed using RSDS with both global β1/2 receptor knock-out mice, as well as by adoptively transferring β1/2 knock-out T-lymphocytes into immunodeficient hosts. Furthermore, ex vivo polarized T-lymphocytes produced significantly less IL-17A with the blockade of β1/2 signaling, even in the absence of exogenous sympathetic neurotransmitter supplementation, which suggested T-lymphocyte-produced catecholamines may be involved in IL-17A production. Indeed, pharmacological depletion of catecholamines both in vivo and ex vivo abrogated T-lymphocyte IL-17A production demonstrating the importance of immune-generated neurotransmission in pro-inflammatory cytokine generation.ConclusionsOur data depict a novel role for β1/2 adrenergic receptors and autologous catecholamine signaling during T-lymphocyte IL-17A production. These findings provide a new target for pharmacological therapy in both psychiatric and autoimmune diseases associated with IL-17A-related pathology.
Fecal microbiota and metabolite composition associates with stool consistency in young children
Authors: Aatsinki Anna-Katariina , Isokääntä Heidi , Kråkström Matilda , Lahti Leo , Lukkarinen Minna , Munukka Eveliina , Karlsson Hasse , Karlsson Linnea , Oresic Matej , Dickens Alex M , Lamichhane Santosh 
Published: June 2024

ABSTRACTStool consistency explains a large proportion of inter-individual variation in gut microbiota and represents a useful measure of gut transit time, which is pivotal for bacterial metabolism andvice versa. However, in infants and small children, a detailed understanding of how gut microbiota and the metabolome associate with stool consistency is lacking. We analyzed both stool microbiota and metabolome of 2.5 (n=360), 6 (n=229), 14 (n=274), and 30-month-old children (n=169) from the FinnBrain Birth Cohort Study using 16s rRNA sequencing and mass spectrometry-based targeted techniques. We used stool water content and parent-reported stool consistency as proxies for stool consistency. We found that microbiota community composition as well as the relative abundance of specific genera such asClostridium,Hungatella, andLactobacilluswere associated with stool consistency. Of the metabolites, lower concentrations of conjugated bile acids and acetic acid were associated with having constipation and lower water content. Branched short-chain fatty acid concentrations were negatively associated with stool water content. The findings reflect a shift in bacterial saccharolytic to proteolytic metabolism in the gut. Parental crude reports agreed with the objective measure of child stool consistency, and associated with similar features in the stool metabolome. Overall, our findings support the concept that stool consistency and total water content associate with gut microbiota composition and metabolic activity in infants and young children.
Effect of TIMPs and Their Minimally Engineered Variants in Blocking Invasion and Migration of Brain Cancer Cells
Authors: Taheri Elham , Raeeszadeh-Sarmazdeh Maryam 
Published: June 2024

ABSTRACTMatrix metalloproteinases (MMPs) play a pivotal role in extracellular matrix (ECM) remodeling, influencing various aspects of cancer progression including migration, invasion, angiogenesis, and metastasis. Overexpression of MMPs, particularly MMP-2 and MMP-9, is notably pronounced in glioblastoma multiforme (GBM), a highly aggressive primary brain tumor characterized by diffuse and infiltrative behavior. Previous attempts to develop small molecule MMP inhibitors have failed in clinical trials, necessitating the exploration of more stable and selective alternatives. Tissue inhibitors of metalloproteinases (TIMPs), endogenous human proteins, offer promising potential due to their stability and broader interaction interfaces compared to small molecule inhibitors. In this study, we examined the effectiveness of wild-type human TIMP-1 and TIMP-3, alongside engineered minimal TIMP variants (mTC1 and mTC3), specifically designed for targeted MMP inhibition to reduce the migratory and invasive capabilities of GBM cells. Our investigation focused on these minimal TIMP variants, which provide enhanced tissue penetration and cellular uptake due to their small molecular weight, aiming to validate their potential as therapeutic agents. The results demonstrated that mTC1 and mTC3 effectively inhibit MMP activity, a critical factor in GBM aggressiveness, thereby highlighting their promise in controlling tumor spread. Given the lethality of GBM and the limited effectiveness of current treatments, the application of engineered TIMP variants represents a novel and potentially transformative therapeutic approach. By offering targeted MMP inhibition, these variants may significantly improve patient outcomes, providing new avenues for treatment and enhancing the survival and quality of life for patients with this devastating disease.