bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD27 signaling inhibits tumor growth and metastasis via CD8 + T cell-independent mechanisms in the B16-F10 melanoma model
Authors: Puppala Eswara Rao , Wu Long , Fan Xiaoxuan , Cao Xuefang 
Published: August 2024

AbstractCD27 belongs to the tumor necrosis factor receptor superfamily and acts as a co-stimulatory molecule, modulating T and B cell responses. CD27 stimulation enhances T cell survival and effector functions, thus providing opportunities to develop therapeutic strategies. The current study aims to investigate the role of endogenous CD27 signaling in tumor growth and metastasis. CD8 + T cell-specific CD27 knockout (CD8Cre-CD27fl) mice were developed, while global CD27 knockout (KO) mice were also used in our studies. Flow cytometry analyses confirmed that CD27 was deleted specifically from CD8 + T cells without affecting CD4 + T cells, B cells, and HSPCs in the CD8Cre-CD27fl mice, while CD27 was deleted from all cell types in global CD27 KO mice. Tumor growth and metastasis studies were performed by injecting B16-F10 melanoma cells subcutaneously (right flank) or intravenously into the mice. We have found that global CD27 KO mice succumbed to significantly accelerated tumor growth compared to WT controls. In addition, global CD27 KO mice showed a significantly higher burden of metastatic tumor nests in the lungs compared to WT controls. However, there was no significant difference in tumor growth curves, survival, metastatic tumor nest counts between the CD8Cre-CD27fl mice and WT controls. These results suggest that endogenous CD27 signaling inhibits tumor growth and metastasis via CD8 + T cell-independent mechanisms in this commonly used melanoma model, presumably through stimulating antitumor activities of other types of immune cells.
Chimeric antigen receptor dendritic cells targeted delivery of a single tumoricidal factor for cancer immunotherapy
Authors: Duan Rong , Milton Philip , Sittplangkoon Chutamath , Liu Xin , Sui Zhining , Boyce Brendan F. , Yao Zhenqiang 
Published: August 2024

Abstract
Background
Chimeric antigen receptor (CAR)-T cells have been used to treat blood cancers by producing a wide variety of cytokines. However, they are not effective in treating solid cancers and can cause severe side-effects, including cytokine release syndrome. TNFα is a tumoricidal cytokine, but it markedly increases the protein levels of cIAP1 and cIAP2, the members of inhibitor of apoptosis protein (IAP) family of E3 ubiquitin ligase that limits caspase-induced apoptosis. Degradation of IAP proteins by an IAP antagonist does not effectively kill cancer cells but enables TNFα to strongly induce cancer cell apoptosis. It would be a promising approach to treat cancers by targeted delivery of TNFα through an inactive adoptive cell in combination with an IAP antagonist.

Methods
Human dendritic cells (DCs) were engineered to express a single tumoricidal factor, TNFα, and a membrane-anchored Mucin1 antibody scFv, named Mucin 1 directed DCs expressing TNFα (M-DCsTNF). The efficacy of M-DCsTNF in recognizing and treating breast cancer was tested in vitro and in vivo.

Results
Mucin1 was highly expressed on the surface of a wide range of human breast cancer cell lines. M-DCsTNF directly associated with MDA-MB-231 cells in the bone of NSG mice. M-DCsTNF plus an IAP antagonist, SM-164, but neither alone, markedly induce MDA-MB-231 breast cancer cell apoptosis, which was blocked by TNF antibody. Importantly, M-DCsTNF combined with SM-164, but not SM-164 alone, inhibited the growth of patient-derived breast cancer in NSG mice.

Conclusion
An adoptive cell targeting delivery of TNFα combined with an IAP antagonist is a novel effective approach to treat breast cancer and could be expanded to treat other solid cancers. Unlike CAR-T cell, this novel adoptive cell is not activated to produce a wide variety of cytokines, except for additional overexpressed TNF, and thus could avoid the severe side effects such as cytokine release syndrome.
Are We Overlooking Harms of BDDE-Cross-Linked Dermal Fillers? A Scoping Review
Authors: Wojtkiewicz Marta , Stachura Albert , Roszkowski Bartłomiej , Winiarska Natalia , Kazimierska Karolina , Stachura Kamilla 
Published: August 2024

Abstract
1,4-Butanediol ether (BDDE) is widely used as a cross-linker for hyaluronic acid in dermal fillers. The purpose of this scoping review was to determine the state of knowledge about the behaviour of cross-linked substances and safety of BDDE application. The rationale behind the review came from the clinical experience of one of the authors (KS), who noticed adverse reactions after BDDE-linked hyaluronan application. The scoping review was conducted according to PRISMA-ScR guidelines. Out of 399 articles, 52 met the inclusion criteria. Data on study design, sample/population, aims, methodology, outcomes and funding were extracted. Results were charted according to 6 subtopics: rheological properties, hydrogel stability, BDDE toxicity, immunogenicity, tissue interactions and clinical studies. In vitro, cross-linked hydrogels were characterized as effective fillers in terms of viscosity and elasticity; however, previously uncharacterized by-products of the cross-linking reaction were found. Most in vivo studies reported increased dermis regeneration, vascularization and anti-inflammatory cytokine release after implantation of BDDE-cross-linked substances. In clinical studies, BDDE was shown to sensitize subjects to 1,6-hexanediol ether and other substances found in epoxy resin systems. Occupational dermatitis and hypersensitivity reactions were documented. Our review shows that BDDE may have long-term adverse effects, which are overlooked in the safety assessment of fillers. Reviews on BDDE conducted so far have mostly been sponsored by the industry, potentially leading to incomplete reporting of adverse effects. A review of the occurrence of allergic reactions after commercial dermal filler use and analysis of possibly harmful by-products of BDDE hyaluronan degradation are needed.

Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
LGI1 encephalitis: potentially complement-activating anti-LGI1-IgG subclasses 1/2/3 are associated with the development of hippocampal sclerosis
Authors: Bien Christian G. , Rada Anna , Mertens Markus , Bien Corinna I. , Bauer Jan , Hagemann Anne , Woermann Friedrich G. 
Published: August 2024

AbstractTwo-thirds of published patients with anti-leucine rich, glioma inactivated 1 (LGI1) encephalitis develop hippocampal sclerosis (HS). It is likely that this contributes to residual cognitive long-term deficits and the risk of epilepsy. Almost all patients harbor anti-LGI1-immunoglobulin G-(IgG-) subclass 4, which is considered a “benign”, non-destructive subclass. In contrast, neuropathological case studies have suggested that the classical complement cascade may contribute to mediotemporal cell death in patients with LGI1 antibodies. IgG subclasses 1, 2, or 3 are required to initiate this cascade. We hypothesized that patients with these anti-LGI1-IgG1/2/3 in addition to IgG4 have a higher risk of developing HS than patients with anti-LGI1-IgG4 alone. We retrospectively assessed all anti-LGI1 encephalitis patients from this center with anti-LGI1-IgG-subclass information and follow-up MRI available. Nine out of 20 patients had developed HS (45%). Volumetric FreeSurfer analysis confirmed the visual HS diagnoses. HS and a lower hippocampal volume were associated with anti-LGI1-IgG1/2/3. All six patients with this IgG subclass status developed HS. There was no association with older or younger age at onset, female sex, longer latency from disease onset to start of immunotherapy, less intense immunotherapy, higher serum titers of LGI1 antibodies, LGI1 antibodies in CSF or higher LGI1-specific antibody indices. There was no association between anti-LGI1-IgG1/2/3 status and neuropsychological performance, epilepsy, or general neurological performance. This confirms our hypothesis that anti-LGI1-IgG1/2/3 in serum puts patients at risk of developing HS. If these findings can be confirmed and clinically corroborated, patients with anti-LGI1-IgG1/2/3 might become candidates for anti-complement-directed immunological treatments.
Therapeutic potential of oral alginate nanoparticles against experimental toxoplasmosis
Authors: Rashed Hoda A. , Abdel-Bary Amany , Elmorsy Eman A. 
Published: August 2024

AbstractSide effects and low efficacy of current anti-toxoplasmosis therapeutics against encysted bradyzoites necessitate research into alternative safe therapeutic options. The safety, immunostimulatory, and antimicrobial properties of alginate nanoparticle formulation (Alg-NP) highlight its potential as an oral therapy against acute toxoplasmosis. In the current study, Alg-NP was formulated and characterized and then assessed for its anti-Toxoplasma effects using parasitological, ultrastructural, immunological, and histopathological studies. Treatment with Alg-NP significantly prolonged mice survival and reduced the parasite burden in both peritoneal fluid and tissue impression smears. In addition, it altered parasite viability and caused severe tachyzoite deformities as evidenced by ultrastructural studies. Alg-NP induced high levels of serum IFN-γ in infected mice with significant amelioration in histopathological changes in both hepatic and splenic tissue sections. In conclusion, Alg-NP could be considered a promising therapeutic agent against acute murine toxoplasmosis, and owing to its safety, it could potentially be enlisted for human use.
Genome-wide assessment of shared genetic landscape of idiopathic pulmonary fibrosis and its comorbidities
Authors: Yang Yuanhao , Sheng Yong H , Carreira Patricia , Wang Tong , Zhao Huiying , Wang Ran 
Published: August 2024

AbstractIdiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease accompanied by both local and systemic comorbidities. Genetic factors play a role in the development of IPF and certain associated comorbidities. Nevertheless, it is uncertain whether there are shared genetic factors underlying IPF and these comorbidities. To bridge this knowledge gap, we conducted a systematic investigation into the shared genetic architecture between IPF and ten prevalent heritable comorbidities (i.e., body mass index [BMI], coronary artery disease [CAD], chronic obstructive pulmonary disease [COPD], gastroesophageal reflux disease, lung cancer, major depressive disorder [MDD], obstructive sleep apnoea, pulmonary hypertension [PH], stroke, and type 2 diabetes), by utilizing large-scale summary data from their respective genome-wide association studies and multi-omics studies. We revealed significant (false discovery rate [FDR] < 0.05) and moderate genetic correlations between IPF and seven comorbidities, excluding lung cancer, MDD and PH. Evidence suggested a partially putative causal effect of IPF on CAD. Notably, we observed FDR-significant genetic enrichments in lung for the cross-trait between IPF and CAD and in liver for the cross-trait between IPF and COPD. Additionally, we identified 65 FDR-significant genes over-represented in 20 biological pathways related to the etiology of IPF, BMI, and COPD, including inflammation-related mucin gene clusters. Several of these genes were associated with clinically relevant drugs for the treatment of IPF, CAD, and/or COPD. Our results underscore the pervasive shared genetic basis between IPF and its common comorbidities and hold future implications for early diagnosis of IPF-related comorbidities, drug repurposing, and the development of novel therapies for IPF.
Timing and cortical region matter: theta power differences between teenagers affected by Major Depression and healthy controls
Authors: Gradwohl Gideon , Snipes Sophia , Walitza Susanne , Huber Reto , Gerstenberg Miriam 
Published: August 2024

AbstractIn adults affected by Major Depressive Disorder (MDD), most findings point to higher electroencephalographic (EEG) theta power during wake compared to healthy controls (HC) as a potential biomarker aiding the diagnostic process or subgrouping for stratified treatment. Besides these group differences, theta power is modulated by time of day, sleep/wake history, and age. Thus, we aimed at assessing if the time of recording alters theta power in teenagers affected by MDD or HC. Standardized wake EEG power was assessed with high-density EEG in 15 children and adolescents with MDD and in 15 age- and sex-matched HC in the evening and morning. Using a two-way ANOVA, group, time, and their interaction were tested. In patients, the current severity of depression was rated using the Children’s Depression Rating Scale. Broadband EEG power was lower in the morning after sleep, with a significant interaction (group x time) in central regions in the 4-6 Hz range. In MDD relative to HC, theta power was decreased over occipital areas in the evening and increased over frontal areas in the morning. A higher frontal theta power was correlated with more severe depressive mood in the morning but not in the evening. This was a cross-sectional study design, including patients on antidepressant medication. In conclusion, depending on time of recording, region-specific opposite differences of theta power were found between teenagers with MDD and HC. These findings stress the importance of the time of the recording when investigating theta power’s relationship to psychopathology.
Digital wear analysis and retention of poly-ether-ether-ketone retentive inserts versus conventional nylon inserts in locator retained mandibular overdentures: in-vitro study
Authors: Fayed Mahmoud Saleh , Elsherbini Nancy Nader , Mohsen Bassem , Osman Reham 
Published: August 2024

Abstract
Objective
this study aimed to digitally compare wear behavior and retention between PEEK and nylon retentive inserts used in locator-retained, mandibular implant overdentures when attachment design and size were standardized.

Materials and methods
A total of sixty-four inserts (32 PEEK and 32 nylon inserts); were picked-up in implant overdentures. Overdentures of both groups were submerged in artificial saliva and mounted to chewing simulator. After 480,000 chewing cycles (equivalent to 2 years of clinical use) all inserts were scanned by scanning electron microscope (SEM), then all acquired images were digitally analyzed by software to detect and compare quantitative and qualitative changes of inserts in both groups. On the other hand, retention of both groups was measured by universal testing machine and the collected data was statistically analyzed using one-way Analysis of Variance (ANOVA) test with significance level set at P ≤ 0.05.

Results
PEEK inserts showed significantly higher mean retentive values compared to the nylon inserts in the control group. Also, PEEK retentive inserts exhibited statistically lower mean wear values than the control group P ≥ 0.000. Qualitative investigation revealed significant and more pronounced changes in the surface roughness of nylon inserts compared to PEEK ones.

Conclusions
Regarding retention, wear behavior and dimension stability, PEEK can be recommended as retentive insert material in cases of locator-retained mandibular implant overdentures.

Clinical relevance
PEEK inserts offer enhanced retention, reduced wear, and greater dimensional stability over two years time interval. Clinically, this reduces prosthodontic maintenance and adjustments, improving patient satisfaction and long-term prosthetic success.
The Tet-on system for controllable gene expression in the rock-inhabiting black fungus Knufia petricola
Authors: Erdmann Eileen A. , Brandhorst Antonia K. M. , Gorbushina Anna A. , Schumacher Julia 
Published: August 2024

AbstractKnufia petricola is a black fungus that colonizes sun-exposed surfaces as extreme and oligotrophic environments. As ecologically important heterotrophs and biofilm-formers on human-made surfaces, black fungi form one of the most resistant groups of biodeteriorating organisms. Due to its moderate growth rate in axenic culture and available protocols for its transformation and CRISPR/Cas9-mediated genome editing, K.petricola is used for studying the morpho-physiological adaptations shared by extremophilic and extremotolerant black fungi. In this study, the bacteria-derived tetracycline (TET)-dependent promoter (Tet-on) system was implemented to enable controllable gene expression in K. petricola. The functionality i.e., the dose-dependent inducibility of TET-regulated constructs was investigated by using GFP fluorescence, pigment synthesis (melanin and carotenoids) and restored uracil prototrophy as reporters. The newly generated cloning vectors containing the Tet-on construct, and the validated sites in the K. petricola genome for color-selectable or neutral insertion of expression constructs complete the reverse genetics toolbox. One or multiple genes can be expressed on demand from different genomic loci or from a single construct by using 2A self-cleaving peptides, e.g., for localizing proteins and protein complexes in the K.petricola cell or for using K. petricola as host for the expression of heterologous genes.
Process optimization in the pyroconversion of native sweet potato starch: structural and functional characterization of pyrodextrin
Authors: Tsatsop Roli Karole Tsague , Djiobie Gertrude Eléonore Tchienou , Panyoo Emmanuel Akdowa , Chendjou Stive Martial Sikandi , Oladimeji Abdulkabir Oladele , Nguimbou Richard Marcel , Ngassoum Martin Benoît 
Published: August 2024

AbstractThis work aims to produce dextrin from sweet potato (Ipomoea batatas) starch by pyroconversion. The effect of dextrinization process (roasting time, temperature, and hydrochloric acid concentration) on properties (structural and functional) of starch have been studied using central composite design of experiment. Reaction conditions included: roasting time (55 and 94 min), temperature (127 and 152 °C), and hydrochloric acid concentration (0.17 and 0.43 M). The temperature (quadratic effect X22) is highly significant on the three measured responses (p < 0.05) (Color Index (CI), Turbidity (Turb), and Saccharification Percentage (SP)). Also, the findings indicated that the two most important parameters influencing the pyroconversion of sweet potato starch in the current study were temperature (X2) and hydrochloric acid concentration (X3). The optimal conditions for dextrin production obtained are 94 min, 127 °C and 0.43 M for roasting time, temperature, and hydrochloric acid concentration respectively having 97% of solubility. The FTIR analysis revealed that OH, C-H, C-O, C–C and C-O–H were the main functional groups. These functional groups remained unaffected by the pyroconversion, since the bands extend and the spectrums of all native and pyrodextrin were similar. X-Ray Diffractometry analysis results of dextrin showed that the thermal treatment reduces the crystallinity of starch. Also, this analysis shows starch has CA-type XRD patterns. Scanning Electron Microscopy (SEM) analysis results showed that the defined optimal production maintains the morphology of starch. Differential scanning calorimetry (DSC) used for thermal analysis helps to obtain the glass transition temperature of modified starch equals to 139 °C. Optimal conditions of production of pyrodextrins from sweet potato granule starches could be easily produced with improved physicochemical properties to be used as encapsulating agent or additives in food and chemical industries.
Novel enzymatic route to the synthesis of C-8 hydroxyflavonoids including flavonols and isoflavones
Authors: Dulak Kinga , Sordon Sandra , Matera Agata , Wilczak Aleksandra , Huszcza Ewa , Popłoński Jarosław 
Published: August 2024

AbstractFlavin-dependent monooxygenases (FMOs) are a valuable group of biocatalysts that can regioselectively introduce a hydroxy group for the targeted modification of biologically active compounds. Here, we present the fdeE, the FMO from Herbaspirillum seropedicae SmR1 that is a part of the naringenin degradation pathway and is active towards a wide range of flavonoids—flavanones, flavones, isoflavones, and flavonols. Bioinformatics and biochemical analysis revealed a high similarity between the analyzed enzyme and other F8H FMOs what might indicate convergent evolutionary mechanism of flavonoid degradation pathway emergence by microorganism. A simple approach with the manipulation of the reaction environment allowed the stable formation of hydroxylation products, which showed very high reactivity in both in vivo and in vitro assays. This approach resulted in an 8-hydroxyquercetin—gossypetin titer of 0.16 g/L and additionally it is a first report of production of this compound.
Clear Masks Do Not Prevent Gains During Dynamic Temporal and Tactile Cueing Treatment: An Explanatory Sequential Mixed Methods Pilot Study
Authors: Iuzzini-Seigel Jenya , Murray Elizabeth , Velleman Shelley L. , Bricker-Katz Geraldine , Thomas Donna 
Published: August 2024

Purpose:
This study aimed to determine the outcomes and impact of Dynamic Temporal and Tactile Cueing (DTTC) treatment when clear vinyl masks were worn. DTTC is one of the few evidence-based treatments for children with childhood apraxia of speech (CAS). Given that DTTC relies on visual, auditory, and tactile cues, it was unknown if treatment gains would be demonstrated when masks were worn and how masking would impact the therapy experience for clinicians and caregivers.

Method:
A sequential mixed methods design was used to study the efficacy of DTTC treatment in children with CAS when clear masks were worn. The quantitative phase used a multiple-baseline across-participants design. Four children (each 4 years of age) participated in the treatment protocol in which 24 sessions of DTTC were provided over 8 weeks while clear vinyl face masks were worn by participants and clinicians. Whole word accuracy on treated items and generalization to easy and hard untreated items were assessed during baseline, treatment, and follow-up. Semistructured interviews were conducted with clinicians and caregivers following treatment to explore the experience of masks being worn during treatment. Qualitative data were analyzed using descriptive thematic analysis.

Results:
Three children completed the treatment protocol. Visual and statistical analyses revealed that two participants demonstrated significant treatment effects, with one also demonstrating generalization. The remaining participant demonstrated marginal treatment gains. Qualitative findings revealed two main themes: “mask wearing was inconvenient but did not prevent therapy gains” and “in-person therapy with face masks was preferable to teletherapy.”

Conclusions:
Masks did not prohibit treatment gains during DTTC therapy, with treatment effects of varying degrees shown for the three participants who completed the protocol. Together, quantitative and qualitative results indicate that mask wearing was, for most, a minor inconvenience that did not substantially interfere with the efficacy of DTTC treatment.

Supplemental Material:

https://doi.org/10.23641/asha.26408854