bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of PSMA PET/CT on clinical decision-making of radical prostatectomy and pelvic lymph node dissection
Authors: Özman Oktay , Veerman Hans , Hagens Marinus J. , van Leeuwen Pim J. , Vis André N. , van der Poel Henk G. 
Published: October 2024

Objective
To evaluate the effect of prostate-specific membrane antigen (PSMA) PET/computed tomography (CT) on clinical decision-making of radical prostatectomy (RP) and pelvic lymph node dissection (PLND) after its utilization in daily clinical practice at an European high-volume cancer center.

Materials and methods
Patients who had unfavorable intermediate- and high-risk prostate cancer between 2017 and 2021 were included retrospectively and divided into two groups; those who staged using PSMA PET/CT (group 1) and those who staged using conventional modalities (group 2). Clinical decision-making of RP over nonsurgical treatments and f PLND were primary endpoints and evaluated using regression models.

Results
PSMA PET/CT claimed significantly more N1 (24.2% vs. 11.3%; P = 0.01; OR, 1.97; 95% CI, 1.18–3.28) but insignificantly more M1 disease (9.9% vs. 5.7%; P = 0.42; OR, 1.91; 95% CI, 0.39–9.23), compared with the conventional imaging modalities. miN0 stage was related to more RP decisions compared with cN0 stage (P < 0.001; OR, 1.91; 95% CI, 1.48–2.46). PLND decision-making was significantly driven by positive c\miN stage findings, which were more reliable when it was reported after a PSMA PET/CT examination (P < 0.001; OR, 35.55; 95% CI, 6.74–187.45 for conventional imaging modalities vs. P < 0.001; OR, 91.72; 95% CI, 11.25–747.56 for PSMA PET/CT).

Conclusions
Patients with no suspicion of lymph node invasion on molecular imaging (PSMA PET/CT) tended to be referred to RP more compared to radiological imaging. Also, the PLND decision was strongly driven by staging findings. Compared with conventional imaging, PSMA PET/CT findings were more reliable during PLND decision-making.
Cholesteryl ester transfer protein inhibition: a pathway to reducing risk of morbidity and promoting longevity
Authors: Davidson Michael H. , Hsieh Andrew , Kastelein John J.P. 
Published: October 2024

Purpose of review
To review the evidence and describe the biological plausibility for the benefits of inhibiting cholesteryl ester transfer protein (CETP) on multiple organ systems through modification of lipoprotein metabolism.

Recent findings
Results from observational studies, Mendelian randomization analyses, and randomized clinical trials support the potential of CETP inhibition to reduce atherosclerotic cardiovascular disease (ASCVD) risk through a reduction of apolipoprotein B-containing lipoproteins. In contrast, raising high-density lipoprotein (HDL) particles, as previously hypothesized, did not contribute to ASCVD risk reduction. There is also an expanding body of evidence supporting the benefits of CETP inhibition for safeguarding against other conditions associated with aging, particularly new-onset type 2 diabetes mellitus and dementia, as well as age-related macular degeneration, septicemia, and possibly chronic kidney disease. The latter are likely mediated through improved functionality of the HDL particle, including its role on cholesterol efflux and antioxidative, anti-inflammatory, and antimicrobial activities.

Summary
At present, there is robust clinical evidence to support the benefits of reducing CETP activity for ASCVD risk reduction, and plausibility exists for the promotion of longevity by reducing risks of several other conditions. An ongoing large clinical trial program of the latest potent CETP inhibitor, obicetrapib, is expected to provide further insight into CETP inhibition as a therapeutic target for these various conditions.
Management of pediatric thyroid carcinoma
Authors: Dimachkieh Amy L. , Mahajan Priya 
Published: October 2024

Purpose of review
The incidence of thyroid carcinoma is increasing among children and adolescents, particularly in female individuals. Children and adolescents require special considerations in management as the molecular genetics of pediatric thyroid tumors are inherently different from their adult counterparts. The increased risk of malignancy, nodal metastases, and pulmonary metastases in pediatric patients warrants pediatric-specific management recommendations and pediatric-specific multidisciplinary teams.

Recent findings
This article highlights the molecular origins of pediatric thyroid carcinoma and the implications of tumor genetics for the course of disease and treatment considerations. We highlight specific surgical considerations to optimize outcomes while minimizing lifelong risks of vocal paralysis and hypoparathyroidism. The landscape of treatment options is rapidly evolving with development of sophisticated molecular approaches to understand the genetic landscape, and this review features updated recommendations and systemic treatment options for the management of pediatric thyroid malignancy.

Summary
Pediatric thyroid carcinoma is a lifelong burden and the treatment tailored to optimize outcomes minimizes long-term risks of treatments, surgery, radiation and targeted systemic therapies. Multidisciplinary teams that treat pediatric thyroid carcinoma should focus surgical experience and use the most updated guidelines and treatments available, particularly considering the landscape of molecular genetics in pediatric thyroid carcinoma.
Superior retention of aged fat graft by supplementing young adipose-derived stromal cells in a murine model
Authors: Tran Vinh Vuong The , Jin Xian , Zhou Xin Ye , Hong Ki Yong , Chang Hak 
Published: October 2024

Background:
In 2021, a meta-analysis showed fat graft retention varied from 26 to 83%. In a retrospective study including patients with Parry-Romberg syndrome, the younger age group had higher satisfaction scores (3.8 vs. 3.0) after fat grafting. Cell-assisted lipotransfer (CAL) could be an alternative to overcome the instability of volume loss; however, no study investigated its effect on old recipients.

Methods:
In an in vitro study, adipose-derived stromal cells (ASCs) from aged and young (52- and 8-weeks old) DsRed B6 mice were characterized by proliferation rates as percentages of Ki-67-positive cells. 68-week-old wild type B6 mice received 150 µL of green fluorescent protein fat (from 69-week-old B6 mice) mixed with saline, 3 x 105 aged or young DsRed ASCs (N, A, and Y groups, respectively) on the scalp (n = 6/group). After 8 weeks, graft volumes were evaluated using micro-computed tomography. Vessel densities were tracked by percentages of CD31 using immunofluorescence staining.

Results:
Young ASCs showed higher proliferation than the aged (47.1% and 26.2%, respectively, p < 0.05). The Y group showed the highest graft retention (median: N = 41.0%, A = 52.2%, Y = 65.2%, p < 0.05) and percentage of blood vessels (median: N = 27.7%, A = 43.5%, Y = 54.7%, p < 0.05) among the three groups.

Conclusions
CAL is effective with old recipients; higher effect was observed by supplementation with younger ASCs due to higher angiogenesis stimulation. However, this is autologous grafting model, further validation of safety, toxicity, and allogenic grafting is required.

Clinical Relevance Statement:
The results suggest that it is clinically possible to conduct CAL for old adults using autologous ASCs. However, further validation of using allogenic ASCs from young donors to improve graft retention in old adults is required.
Prenatal and postnatal antiviral therapies for the prevention and treatment of congenital cytomegalovirus infections
Authors: Chandrasekaran Preethi , Lee Han-Shin , Hui Lisa , Schleiss Mark R. , Sung Valerie 
Published: October 2024

Purpose of review
Congenital cytomegalovirus infection (cCMV) is the leading infectious cause of sensorineural hearing loss and lifelong neurodevelopmental disabilities. Studies suggest antiviral therapy can prevent fetal infection after maternal primary infection, as well as halt the progression of hearing loss and neurodevelopmental disabilities in newborns with symptomatic cCMV. With growing worldwide momentum on early detection and diagnosis of cCMV, this review describes the exciting recent advances in antiviral therapies in CMV infected pregnant mothers and babies, as well as emerging evidence on anti-CMV vaccines.

Recent findings
New opportunities for prenatal and neonatal interventions have driven a rising interest in screening and identification of asymptomatic CMV infection. Routine screening of pregnant women to identify primary infection in first trimester is now advocated in Western Europe but has yet to be examined from a public health perspective in other regions. Evidence is emerging for maternal valaciclovir therapy to prevent fetal infection after a maternal primary CMV infection in the first trimester of pregnancy. For those infants who are born with symptomatic cCMV, a 6-month course of valganciclovir, started within the first 4 weeks of life, and possibly up to 13 weeks of life, is the current recommended therapy. However, there is unclear evidence for the benefit of treatment for asymptomatic cCMV and cCMV with isolated hearing loss. Research to identify more effective antivirals and an effective CMV vaccine continues.

Summary
More research is needed to determine the region-specific applicability of the new European recommendations for routine CMV screening in pregnancy. Areas of uncertainty in postnatal management include timing of initiation, duration of treatment and identifying pediatric subgroups that benefit from modification of the standard treatment recommendations.
Speech Outcomes After Primary Palatoplasty and Presurgical Cleft Characteristics: Is There a Predictive Association?
Authors: Moura Lucas B. , Antoneli Melissa Z. , Passaglia Igor R.G. , Yokoyama Flavio J. , Sampaio Emily C. da Fonseca , Alonso Nivaldo 
Published: October 2024

Speech disorders related to cleft lip and palate exhibit different degrees of involvement and can occur even after primary palate repair. Hypernasality can be present as a result of velopharyngeal insufficiency, as well as nasal emission, weak pressure, articulatory errors and facial grimace, affecting speech intelligibility. Palatoplasty outcomes can be variable, and among the influencing factors are the surgical technique, the surgeon’s experience, the postoperative care, and the patient/cleft characteristics. The aim of this study was to correlate speech results after primary palate repair with surgical technique and cleft characteristics, using anthropometric measurements and speech assessment in patients diagnosed with cleft lip and palate. A longitudinal, retrospective study with patients who underwent primary palatoplasty between 2015 and 2019 and still attend Craniomaxillofacial Surgery Outpatient Clinic was conducted. Patients were operated on by a single surgeon using the intravelar technique veloplasty with maximal retropositioning of the soft palate elevator muscle. Patients who underwent primary palatoplasty after 2018 had the measurements before and immediately after palatoplasty recorded: length of palate, and the distances from cleft and uvula to posterior pharyngeal wall, and uvula to adenoid. Considering the total of 39 patients, 30 (76.9%) were male, with a mean age of 20.9 months (9–53 mo). All patients had their speech recorded between ages of 60 and 120 months. Speech samples were assessed by 3 different speech pathologists experienced in cleft speech, with an intrarater and inter-rater reliability >80%. The most frequent cleft type was unilateral complete cleft lip and palate (59%). One patient had mild hyponasality, 1 isolated obligatory disorder (nasal turbulence), and 3 patients presented compensatory articulation (2 isolated and 1 also presented obligatory disorder). Only 1 patient had marginal velopharyngeal insufficiency. Postoperatively, there was a mean increase in palate length from 5.4 to 5.6 cm, and a statistically significant decrease in the distance from the uvula to the pharynx wall, with a mean of 1.7 to 1.1 cm (P<0.001). In general, patients analyzed did not have significant alterations in speech assessment, which did not allow further comparisons and correlation. Therefore, regardless of the anatomic characteristics of the palate, it is possible to achieve good results depending on the handling experience and the technique used.
Cystobactamid off-target profiling reveals favorable safety, superoxide reduction, and SCARB1 inhibition in eukaryotes
Authors: Risch Timo , Hellwinkel Benedikt , Mostert Dietrich , Kany Andreas M. , Solga Danny , Seedorf Tim , Heimann Dominik , Hoppstädter Jessica , Kohnhäuser Daniel , Hilgers Jil-Sophie , Fries Franziska , Deschner Felix , Brönstrup Mark , Kirschning Andreas , Sieber Stephan A. , Pietschmann Thomas , Kiemer Alexandra K. , Herrmann Jennifer , Müller Rolf 
Published: October 2024

AbstractAntimicrobial resistance (AMR) poses a fundamental global threat, necessitating new strategies for effective therapies. Cystobactamids (CYS), a class of antibacterial agents targeting bacterial gyrase and topoisomerase IV, represent a non-traditional chemical scaffold with broad-spectrum activity. For toxicological de-risking, we performed a comprehensive profiling on eukaryotic cells, focusing on cytotoxicity, genotoxicity, and mitochondrial toxicity, demonstrating cellular safety and superoxide scavenging properties. Studies in zebrafish embryos assessed developmental, cardiovascular, and hepatic toxicity, indicating a favorablein vivosafety profile. Metabolism studies revealed glucuronidation and amide bond hydrolysis as key pathways, whereby CYS metabolic stability substantially improved by cobicistat co-treatment. Affinity-based protein profiling identified the cholesterol- and HCV-receptor scavenger receptor class B member 1 (SCARB1) as a primary eukaryotic off-target protein, with cystobactamids shown to inhibit SCARB1’s function, preventing hepatitis C virus pseudoparticle entry into cells. These findings suggest a high therapeutic potential for cystobactamids and highlight SCARB1 as a primary eukaryotic target.
Mapping the epigenomic landscape of post-traumatic stress disorder in human cortical neurons
Authors: Núñez-Ríos Diana L. , Nagamatsu Sheila T. , Martínez-Magaña Jose Jaime , Hurd Yasmin , Rompala Gregory , Krystal John H. ,   Traumatic Stress Brain Research Group, Montalvo-Ortiz Janitza L. 
Published: October 2024

Most epigenetic research on post-traumatic stress disorder (PTSD) has primarily focused on DNA methylation (5mC) in peripheral tissues, particularly at CpG sites. DNA hydroxymethylation (5hmC) has been found to be highly enriched in the mammalian brain, while 5mC at non-CpG sites shows high enrichment in neurons. However, little is known about their role in PTSD. Here, we characterize genome-wide differential 5mC and 5hmC at both CpG and non-CpG sites in postmortem orbitofrontal neurons from PTSD cases and controls. Utilizing reduced-representation oxidative bisulfite sequencing, we found that genome-wide significant (GWS) differential CpGs were primarily hyper-5mC/5hmC, whereas GWS differential non-CpGs were hypo-5mC/5hmC. Compared with 5mC, we show that 5hmC is a more sensitive epigenetic mark in PTSD, with a higher number of differential 5hmC sites and a stronger significance in enriched pathways. Integrating other -omics data highlighted developmental processes as significant convergent pathways and revealed overlap of our GWS 5hmC findings with 50 previously reported PTSD-associated genes, including potential therapeutic targets such as CRHR1 and DRD4. This study underscores the importance of evaluating 5hmC in the human brain and our multi-omics integration provides insights into potential target genes for future therapeutic interventions in PTSD.Graphical abstractThe study conducted a comprehensive genome-wide analysis of differential 5mC and 5hmC modifications at both CpG and non-CpG sites in postmortem orbitofrontal neurons from 25 PTSD cases and 13 healthy controls. It was observed that PTSD patients exhibit a greater number of differential 5hmC sites compared to 5mC sites. Specifically, individuals with PTSD tend to show hyper-5mC/5hmC at CpG sites, particularly within CpG islands and promoter regions, and hypo-5mC/5hmC at non-CpG sites, especially within intragenic regions. Functional enrichment analysis indicated distinct yet interconnected roles for 5mC and 5hmC in PTSD. The 5mC marks primarily regulate cell-cell adhesion processes, whereas 5hmC marks are involved in embryonic morphogenesis and cell fate commitment. By integrating published PTSD findings from central and peripheral tissues through multi-omics approaches, several biological mechanisms were prioritized, including developmental processes, HPA axis regulation, and immune responses. Based on the consistent enrichment in developmental processes, we hypothesize that if epigenetic changes occur during early developmental stages, they may increase the risk of developing PTSD following trauma exposure. Conversely, if these epigenetic changes occur in adulthood, they may influence neuronal apoptosis and survival mechanisms.
Fine-tuning and pre-training improve the predictive accuracy of large language models for rheumatoid arthritis disease activity
Authors: Honda Suguru , Ikari Katsunori , Fujisaki Mayuko , Tanaka Eiichi , Harigai Masayoshi 
Published: October 2024

AbstractObjectiveTo evaluate whether the performance of the large language model (LLM) Llama2 improves with pre-training and fine-tuning, and to compare its predictive accuracy with that of a linear regression model for rheumatoid arthritis (RA) disease activity.MethodsClinical data from 11,865 patients in the cohort were used to predict disease activity at two years on four indices (Disease Activity Score (DAS) 28-Erythrocyte sedimentation rate (ESR), DAS28-C-reactive protein (CRP), Clinical Disease Activity Index (CDAI) or Japanese Health Assessment Questionnaire (J-HAQ)). Logistic regression was employed for the linear model for comparison. The predictive performance was assessed using area under the curve (AUC). Additional performance metrics including precision, recall, and F1 score were calculated.ResultsPre-training significantly improved AUC of Meditron (Llama2 pre-trained with medical data) for DAS28-ESR >5.1, DAS28-ESR <2.6, DAS28-CRP <2.3, J-HAQ score >2.5, and J-HAQ score <0.5 (P<0.05). Fine-tuning resulted in significant improvements in AUC for Llama2 across all indices (P<0.05) except CDAI >22, and for Meditron in DAS28-ESR <2.6, DAS28-CRP >4.1, DAS28-CRP <2.3 and CDAI ≤2.8 (P<0.05). Both LLMs significantly outperformed linear regression in predicting DAS28-ESR <2.6, DAS28-CRP >4.1, DAS28-CRP <2.3, J-HAQ score >2.5, and J-HAQ score <0.5 (P<0.05). Furthermore, DAS28-CRP >4.1, DAS28-CRP <2.3, J-HAQ score >2.5 and J-HAQ score <0.5, Llama2 or Meditron consistently outperformed linear regression across all performance metrics.ConclusionBoth pre-training and fine-tuning significantly improved the performance of Llama2. Both LLMs outperformed the linear regression model in predicting 5 out of the 8 categories of indices.
A Feasibility Study of Thermography for Detecting Pressure Injuries Across Diverse Skin Tones
Authors: Asare-Baiden Miriam , Sonenblum Sharon Eve , Jordan Kathleen , Chung Andrew , Gichoya Judy Wawira , Hertzberg Vicki Stover , Ho Joyce C 
Published: October 2024

AbstractPressure injury (PI) detection is challenging, especially in dark skin tones, due to the unreliability of visual inspection. Thermography may serve as a viable alternative as temperature differences in the skin can indicate impending tissue damage. Although deep learning models hold considerable promise toward reliably detecting PI, existing work fails to evaluate performance on diverse skin tones and varying data collection protocols. We collected a new dataset of 35 participants focused on darker skin tones where temperature differences are induced through cooling and cupping protocols. The dataset includes different cameras, lighting, patient pose, and camera distance. We compare the performance of three convolutional neural network (CNN) models trained on either the thermal or the optical images on all skin tones. Our results suggest thermography-based CNN is robust to data collection protocols. Moreover, the visual explanation often captures the region of interest without requiring explicit bounding box labels.
Non-lytic replicating viral delivery of an IL15 superagonist enhances antitumor immunity and extends survival in glioblastoma
Authors: Haddad Alexander F. , Saha Atul , Spatz Jordan , Collins Sara A. , Lovalvo Isabella , Gill Sabraj , Montoya Megan L. , Shukla Poojan , Hong Jinpyo , Wang Elaina , Chuntova Pavlina , Lad Meeki , Osorio Robert , Chen Jia-Shu , Jain Saket , Chalif Eric , Kasahara Noriyuki , Aghi Manish K. 
Published: October 2024

AbstractGlioblastoma (GBM) is the most lethal primary brain neoplasm due to its highly immunosuppressive microenvironment and resistance to conventional therapies. To overcome this challenge, we engineered a replicating retrovirus (RRV) to deliver a superagonist interleukin-15 receptor-linked fusion protein (RLI) directly to tumor cells, engineering them into local immunotherapy biofactories. This strategy leverages the tumor-selective replication of RRV to achieve localized and sustained RLI expression within the tumor microenvironment. In two orthotopic poorly immunogenic GBM mouse models, intratumoral administration of RRV RLI significantly reduced tumor growth and prolonged survival compared to controls, with some mice achieving long-term remission and demonstrating immunologic memory upon rechallenge. Transcriptomic and flow cytometric analyses revealed that RRV RLI treatment enhanced infiltration and activation of CD8⁺ T cells, NK cells, and upregulated antigen presentation pathways within the tumor microenvironment. Depletion studies indicated that the therapeutic efficacy of RRV RLI is dependent on both CD4⁺ and CD8⁺ T cells. Notably, combining RRV RLI with the GBM standard of care chemotherapeutic agent temozolomide (TMZ) synergistically improved survival outcomes. Subsequent single-cell RNA and T cell receptor sequencing identified enhanced effector cell activation, antigen presentation, and clonal T cell expansion in the combination therapy group. Further T cell receptor analysis and clustering implied a tumor- specific immune response rather than one targeting the viral delivery vehicle, suggesting that this therapeutic approach could be reapplied without eliciting anti-vector immunity. Our findings suggest that RRV-mediated delivery of RLI effectively transforms GBM tumors into immunostimulatory hubs, eliciting a potent anti-tumor immune response. This novel viral immunotherapy holds significant promise for clinical translation in the treatment of GBM and other difficult-to-treat solid tumors.