Genomic determinants of response and resistance to inotuzumab ozogamicin in B-cell ALL.

Inotuzumab ozogamicin (InO) is an antibody-drug conjugate that delivers calicheamicin to CD22-expressing cells. In a retrospective cohort of InO-treated patients with B-cell acute lymphoblastic leukemia, we sought to understand the genomic determinants of response and resistance to InO. Pre- and post-InO patient samples were analyzed by whole genome, exome, and/or transcriptome sequencing. Acquired CD22 mutations were observed in 11% (3/27) of post-InO relapsed tumor samples, but not in refractory samples (0/16). There were multiple CD22 mutations per sample and the mechanisms of CD22 escape included epitope loss (protein truncation, protein destabilization) and epitope alteration. Two CD22 mutant cases were post-InO hypermutators resulting from error-prone DNA damage repair (non-homologous/alternative end joining, mismatch repair deficiency), suggesting hypermutation drove escape from CD22-directed therapy. CD22-mutant relapses occurred after InO and subsequent hematopoietic stem cell transplantation (HSCT), suggesting InO eliminated predominant clones, leaving subclones with acquired CD22 mutations that conferred resistance to InO and subsequently expanded. Acquired loss-of-function mutations in TP53, ATM and CDKN2A were observed, consistent with compromise of the G1/S DNA damage checkpoint as a mechanism of evading InO-induced apoptosis. Genome wide CRISPR/Cas9 screening in cell lines identified DNTT (TdT) loss as a marker of InO resistance. In conclusion, genetic alterations modulating CD22 expression and DNA damage response influence InO efficacy. Our findings highlight the importance of defining the basis of CD22 escape, and eradication of residual disease prior to HSCT. The identified mechanisms of escape from CD22-targeted therapy extend beyond antigen loss, and provide opportunities to improve therapeutic approaches and overcome resistance.

In Vivo Osteo-organoid Approach for Harvesting Therapeutic Hematopoietic Stem/Progenitor Cells.

Hematopoietic stem cell transplantation (HSCT) requires a sufficient number of therapeutic hematopoietic stem/progenitor cells (HSPCs). To identify an adequate source of HSPCs, we developed an in vivo osteo-organoid by implanting scaffolds loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) into an internal muscle pouch near the femur in mice. After 12 weeks of implantation, we retrieved the in vivo osteo-organoids and conducted flow cytometry analysis on HPSCs, revealing a significant presence of HSPC subsets within the in vivo osteo-organoids. We then established a sublethal model of hematopoietic/immune system injury in mice through radiation and performed hematopoietic stem cell transplantation (HSCT) by injecting the extracted osteo-organoid-derived cells into the peripheral blood of radiated mice. The effect of hematopoietic recovery was evaluated through hematological, peripheral blood chimerism, and solid organ chimerism analyses. The results confirmed that in vivo osteo-organoid-derived cells can rapidly and efficiently reconstruct damaged peripheral and solid immune organs in irradiated mice. This approach holds potential as an alternative source of HSPCs for HSCT, offering benefits to a larger number of patients.

SMARCA4 is a haploinsufficient B cell lymphoma tumor suppressor that fine-tunes centrocyte cell fate decisions.

SMARCA4 encodes one of two mutually exclusive ATPase subunits in the BRG/BRM associated factor (BAF) complex that is recruited by transcription factors (TFs) to drive chromatin accessibility and transcriptional activation. SMARCA4 is among the most recurrently mutated genes in human cancer, including ∼30% of germinal center (GC)-derived Burkitt lymphomas. In mice, GC-specific Smarca4 haploinsufficiency cooperated with MYC over-expression to drive lymphomagenesis. Furthermore, monoallelic Smarca4 deletion drove GC hyperplasia with centroblast polarization via significantly increased rates of centrocyte recycling to the dark zone. Mechanistically, Smarca4 loss reduced the activity of TFs that are activated in centrocytes to drive GC-exit, including SPI1 (PU.1), IRF family, and NF-κB. Loss of activity for these factors phenocopied aberrant BCL6 activity within murine centrocytes and human Burkitt lymphoma cells. SMARCA4 therefore facilitates chromatin accessibility for TFs that shape centrocyte trajectories, and loss of fine-control of these programs biases toward centroblast cell-fate, GC hyperplasia and lymphoma.

Predicting the binding configuration and release potential of heavy metals on iron (oxyhydr)oxides: A machine learning study on EXAFS.

Heavy metals raise a global concern and can be easily retained by ubiquitous iron (oxyhydr)oxides in natural and engineered systems. The complex interaction between iron (oxyhydr)oxides and heavy metals results in various mineral-metal binding configurations, such as outer-sphere complexes and edge-sharing inner-sphere complexes, which determine the accumulation and release of heavy metals in the environment. However, traditional experimental approaches are time-consuming and inadequate to elucidate the complex binding relationships and configurations between iron (oxyhydr)oxides and heavy metals. Herein, a workflow that integrates the binding configuration data of 11 heavy metals on 7 iron (oxyhydr)oxides and then trains machine learning models to predict unknown binding configurations was proposed. The well-trained multi-grained cascade forest models exhibited high accuracy (> 90%) and predictive performance (R2 ∼ 0.75). The underlying effects of mineral properties, metal ion species, and environmental conditions on mineral-metal binding configurations were fully interpreted with data mining. Moreover, the metal release rate was further successfully predicted based on mineral-metal binding configurations. This work provides a method to accurately and quickly predict the binding configuration of heavy metals on iron (oxyhydr)oxides, which would provide guidance for estimating the potential release behavior of heavy metals and remediating heavy metal pollution in natural and engineered environments.

Subfascial Mini Muscle-Release Dual Plane Technique: A Modified Procedure for Breast Augmentation.

BACKGROUND: Each breast augmentation technique has advantages and indications, and the quest for the perfect implant pocket plane is ongoing. An ideal dual plane should meet three requirements: adequate implant coverage, optimal control of breast shape, and maximal muscle preservation. This paper reports a modified procedure for breast augmentation named subfascial mini muscle-release dual plane technique. METHODS: From an inframammary or periareolar approach, the implant pocket is dissected in a subfascial plane up to the pectoralis major. The muscle is split 3 cm above the lateral margin and then pocket dissection proceeds in the submuscular plane. A small portion of the costal origin is divided inferomedially creating a dual plane. RESULTS: A total of 178 patients with hypoplasia or breast atrophy were included, among whom 34 had breast ptosis and 20 had tubular breast deformity. The median follow-up period was 20 months. With an average implant volume of 268.8 ml and a smooth implant type of 85.4%, there was 1 case of hematoma, 2 cases of wound healing issues, 2 cases of rippling sign, 2 cases of grade III/IV capsular contracture, 5 cases of implant malposition and 12 cases of mild muscle contraction-associated deformity. Revision surgeries were performed on 2 patients. CONCLUSION: The subfascial mini muscle-release dual plane technique is an easy method for breast augmentation and is especially indicated for ptotic breasts and tubular breast deformities. This technique combines the advantages of traditional dual plane and muscle-splitting techniques, yielding a satisfactory aesthetic outcome.

Genomic and functional impact of Trp53 inactivation in JAK2V617F myeloproliferative neoplasms.

Classical myeloproliferative neoplasms (MPNs) are characterized by the proliferation of myeloid cells and the risk of transformation into myelofibrosis or acute myeloid leukemia (AML) and TP53 mutations in MPN patients are linked to AML. However, JAK2V617F has been reported to impact the TP53 response to DNA damage, suggesting potential overlapping role of TP53 inactivation in MPN. We established a mouse model showing that JAK2V617F/Vav-Cre/Trp53-/- mice displayed a similar phenotype to JAK2V617F/Vav-Cre mice, but their proliferation was outcompeted in competitive grafts. RNA-Seq revealed that half of the genes affected by JAK2V617F were affected by p53-inactivation, including the interferon pathway. To validate this finding, mice were repopulated with a mixture of wild-type and JAK2V617F (or JAK2V617F/Vav-Cre/Trp53-/-) cells and treated with pegylated interferonα. JAK2V617F-reconstituted mice entered complete hematological remission, while JAK2V617F/Vav-Cre /Trp53-/--reconstituted mice did not, confirming that p53 loss induced interferon-α resistance. KEGG and Gene Ontology analyses of common deregulated genes showed that these genes were mainly implicated in cytokine response, proliferation, and leukemia evolution, illustrating that in this mouse model, the development of MPN is not affected by TP53 inactivation. Taken together, our results show that many genetic modifications induced by JAK2V617F are influenced by TP53, the MPN phenotype may not be. Trp53 loss alone is insufficient to induce rapid leukemic transformation in steady-state hematopoiesis in JAK2V617F MPN, and Trp53 loss may contribute to interferon resistance in MPN.

Synthesis and protection: a controllable electrochemical approach to polypyrrole-coated copper azide with superior safety for MEMS.

Traditional lead-based primary explosives present challenges in application to micro-energetics-on-a-chip. It is highly desired but still remains challenging to design a primary explosive for the development of powerful yet safe energetic films. Copper-based azides (Cu(N3)2 or CuN3, CA) are expected to be ideal alternatives owing to their properties such as excellent device compatibility, excellent detonation performance, and low environmental pollution. However, the significantly high electrostatic sensitivity of CA limits its use in micro-electro-mechanical systems (MEMS). This study presents an in situ electrochemical approach to preparing and modifying a CA film with excellent electrostatic safety using a Cu chip. Herein, a CA film is prepared by employing Cu nanorod arrays as precursors. Next, polypyrrole (PPy) is directly coated on the surface of the CA materials to produce a CA@PPy composite energetic film using the electrochemical process. The results show that CuN3 is first generated and gradually oxidized to Cu(N3)2, essentially forming enclosed nest-like structures during electrochemical azidation. The microstructure and composition of the product can be regulated by varying the current density and reaction time, which leads to controllable heat output of the CA from 521 to 1948 J g-1. Notably, the composite energetic film exhibits excellent electrostatic sensitivity (2.69 mJ) owing to the excellent conductivity of PPy. Thus, this study offers novel ideas for the further advances of composite energetic materials and applications in MEMS explosive systems.

Protein lysine acetyltransferase CBP/p300: A promising target for small molecules in cancer treatment.

CBP and p300 are homologous proteins exhibiting remarkable structural and functional similarity. Both proteins function as acetyltransferase and coactivator, underscoring their significant roles in cellular processes. The function of histone acetyltransferases is to facilitate the release of DNA from nucleosomes and act as transcriptional co-activators to promote gene transcription. Transcription factors recruit CBP/p300 by co-condensation and induce transcriptional bursting. Disruption of CBP or p300 functions is associated with different diseases, especially cancer, which can result from either loss of function or gain of function. CBP and p300 are multidomain proteins containing HAT (histone acetyltransferase) and BRD (bromodomain) domains, which perform acetyltransferase activity and maintenance of HAT signaling, respectively. Inhibitors targeting HAT and BRD have been explored for decades, and some BRD inhibitors have been evaluated in clinical trials for treating hematologic malignancies or advanced solid tumors. Here, we review the development and application of CBP/p300 inhibitors. Several inhibitors have been evaluated in vivo, exhibiting notable potency but limited selectivity. Exploring these inhibitors emphasizes the promise of targeting CBP and p300 with small molecules in cancer therapy.

Nerve Distribution Method is Superior to the Conventional Method in BoNT-A Treatment of Trapezius Hypertrophy: A Randomized Controlled Trial.

The contour of the neck and shoulder is defined by the trapezius muscle (TM). Beyond facial procedures, botulinum toxin A (BoNT-A) injections has been increasingly adopted to create a smooth shoulder line. Several studies described the intramuscular nerve branching and the pattern of perforating branch of the accessory nerve in the trapezius muscle, providing essential information for botulinum neurotoxin injection. To this date, research groups seldom perform clinical investigations, especially randomized controlled trials, that demonstrates whether BoNT-A injections using the nerve distribution method for aesthetic purposes is more effective. Patients met the criteria for inclusion were randomized to either the Nerve Distribution group (ND group) or control group. Control group patients received injection using the conventional method while ND group patients received the nerve distribution method. Photographic and ultrasonographic evaluations were carried out at baseline, one month, three months, and six months after the procedure. Patients were also required to complete a questionnaire to evaluate their feedbacks to the injection. After screening, 30 healthy young Chinese women were included. At one-month follow-up, no statistically significant difference was observed between the two methods. At the three-month follow-up, the reduction of the TM thickness for the ND group (0.21 ± 0.09 cm) was more than that for the control group (0.27 ± 0.08 cm), with p = 0.047*. Similar differences were observed for the reduction of the shoulder area proportion (p = 0.031*) and the shoulder angle (p = 0.035*). At the six-month follow-up, the reduction in TM thickness in the ND group (0.2 ± 0.09 cm) was more than that of the control group (0.28 ± 0.06 cm), with p = 0.041*. The global aesthetic improvement scale feedbacks of the two methods showed no significant difference (3.4 ± 0.71 vs 3.8 ± 0.91, p = 0.207). The patients did not experience severe side effects. Compared to the conventional injection method, the nerve distribution method is more effective in reducing the trapezius muscle thickness, shoulder area proportion, and shoulder angle at three months, and shows longer lasting effects. The results of this study introduce unique insights into the design and tailoring of treatment protocols for shoulder-line contouring using BoNT-A.Level of Evidence I 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 .

The biomarkers associated with epithelial-mesenchymal transition in human keloids.

INTRODUCTION: A keloid is a type of benign fibrotic disease with similar features to malignancies, including anti-apoptosis, over-proliferation, and invasion. Epithelial-mesenchymal transition (EMT) is a crucial mechanism that regulates the metastatic behavior of tumors. Thus, identifying EMT biomarkers is paramount in comprehensively understanding keloid pathogenesis. METHODS: To identify the differentially expressed genes (DEGs) GSE92566 dataset, with 3 normal skin and 4 keloid tissues, was downloaded from GEO databases to identify the differentially expressed genes (DEGs). Further, EMT-related genes were downloaded from dbEMT 2.0 databases and intersected with GSE92566 DEGs to identify EMT-related-DEGs (ERDEGs). Subsequently, the ERDEGs were used for GO, KEGG, gene set enrichment analysis (GSEA), protein-protein interaction (PPI), and miRNAs-mRNAs network analysis. To predict small molecules for EMT inhibition, the ERDEGs were imported to cMAP databases, whereas hub genes were imported to DGidb databases. Finally, we carried out qRT-PCR and in vitro experiments to validate our findings. RESULTS: A total of 122 ERDEGs were identified, including 59 upregulated and 63 down-regulated genes. Moreover, enrichment analysis revealed that focal adhesion, AMPK signal pathway, Wnt signal pathway, and EMT biological process were significantly enriched. STRING databases and Cytoscape software were used to construct the PPI network and EMT-related hub genes. Further, 3 modules were explored from the PPI network using the Molecular Complex Detection (MCODE) plugin. In the Cytohubba plugin, 10 hub genes were explored, including FN1, EGF, SOX9, CDH2, PROM1, EPCAM, KRT19, ITGB1, CD24, and KRT18. These genes were then enriched for the focal adhesion pathway. We constructed a microRNA (miRNA)-mRNA network, which predicted hsa-miR-155-5p (8 edges), hsa-miR-124-3p (7 edges), hsa-miR-145-5p (5 edges), hsa-miR-20a-5p (5 edges) and hsa-let-7b-5p (4 edges) as the most connected miRNAs regulating EMT. Based on the ERDEGs and 10 hub genes mentioned above, ribavirin demonstrated high drug-targeting relevance. Subsequently, qRT-PCR confirmed that the expression of FN1, ITGB1, CDH2, and EPCAM corroborated with previous findings. qRT-PCR also showed that the expression levels of hsa-miR-124-3p and hsa-miR-145-5p were significantly lower in keloids and hsa-miR-155-5p was upregulated in keloids. Finally, by treating human keloid fibroblasts (HKFs) with ribavirin in vitro, we confirmed that ribavirin could inhibit HKFs proliferation and EMT. CONCLUSION: In summary, this work provides novel EMT biomarkers in keloids and predicts new small target molecules for keloid therapy. Our findings improve the understanding of keloid pathogenesis, providing new treatment options.

Unveiling the crucial role of iron mineral phase transformation in antimony(V) elimination from natural water.

Antimony (Sb) in natural water has long-term effects on both the ecological environment and human health. Iron mineral phase transformation (IMPT) is a prominent process for removing Sb(V) from natural water. However, the importance of IMPT in eliminating Sb remains uncertain. This study examined the various Sb-Fe binding mechanisms found in different IMPT pathways in natural water, shedding light on the underlying mechanisms. The study revealed that the presence of goethite (Goe), hematite (Hem), and magnetite (Mag) significantly affected the concentration of Sb(V) in natural water. Elevated pH levels facilitated higher Fe content in iron solids but impeded the process of removing Sb(V). To further our understanding, polluted natural water samples were collected from various locations surrounding Sb smelter sites. Results confirmed that converting ferrihydrite (Fhy) to Goe significantly reduced Sb levels (<5 µg/L) in natural water. The emergence of secondary iron phases resulted in greater electrostatic attraction and stabilized surface complexes, which was the most likely cause of the decline of Sb concentration in natural water. The comprehensive findings offer new insights into the factors governing IMPT as well as the Sb(V) behavior control.

Oncogenic and immunological values of RBM34 in osteosarcoma and its pan-cancer analysis.

RNA binding proteins (RBPs) are increasingly recognized as potential factors influencing the advancement, prognostication, and immune response in various solid tumors. Nevertheless, the comprehensive understanding of RBM34's biological mechanisms within the tumor microenvironment remains incomplete, necessitating further systematic pan-cancer investigations to ascertain its diagnostic, prognostic, and immunological significance. In this study, the TCGA, CCLE, HPA, GTEX, and TARGET databases were employed to analyze the expression abundance and subcellular localization of RBM34 in diverse tumor types. Kaplan-Meier survival analyses were used to investigate the impact of RBM34 on clinical prognosis. We implemented the TISIDB portal, CIBERSORT, and ESTIMATE algorithms to assess the correlation between RBM34 expression and immunomodulators, chemokines, and tumor-infiltrating lymphocytes (TILs) in both pan-cancer and osteosarcoma. The CGP database was applied to evaluate the half-maximal inhibitory concentrations of targeted drugs, while TMB, MSI, and MMR were utilized to predict the efficacy of tumor immunotherapy. Furthermore, an RBM34-derived prognostic index (RDPI) was constructed for osteosarcoma patients and linked to outcomes and immune status. Finally, we examined the modulation of RBM34 knockdown on osteosarcoma proliferation and migration capacity. Our results indicate that RBM34 was predominantly localized in the nucleus and differentially expressed in most human cancer types. Kaplan-Meier curve analysis and Cox regression demonstrated that RBM34 expression affected four survival metrics including overall survival (OS) in multiple tumors and was an independent prognostic factor for osteosarcoma. In immunological characterization, RBM34 expression was significantly associated with pan-cancer immunomodulator-related molecules, lymphocyte subpopulation infiltration, and biomarkers of immunotherapy response. Subsequent in vitro experiments provided additional evidence that the suppression of RBM34 impeded the migratory and invasive capabilities of osteosarcoma. Moreover, the utilization of RDPI demonstrated its reliability in prognosticating patient outcomes and estimating the individual immune landscape. Marked differences in multiple TILs (including naive B cells, CD8+ T cells, resting dendritic cells, and activated CD4+ memory T cells) and cancer-associated fibroblast proportion were observed in diverse RDPI score subgroups. Generally, RBM34 exhibited associations with clinical prognosis, immune infiltration, and immunotherapy across various cancer types, and may also serve as a viable therapeutic target for osteosarcoma.

Genomic determinants of response and resistance to inotuzumab ozogamicin in B-cell ALL.

Inotuzumab ozogamicin (InO) is an antibody-drug conjugate that delivers calicheamicin to CD22-expressing cells. In a retrospective cohort of InO treated patients with B-cell acute lymphoblastic leukemia, we sought to understand the genomic determinants of response to InO. Acquired CD22 mutations were observed in 11% (3/27) of post-InO relapsed tumor samples. There were multiple CD22 mutations per sample and the mechanisms of CD22 escape included protein truncation, protein destabilization, and epitope alteration. Hypermutation by error-prone DNA damage repair (alternative end-joining, mismatch repair deficiency) drove CD22 escape. Acquired loss-of-function mutations in TP53 , ATM and CDKN2A were observed, suggesting compromise of the G1/S DNA damage checkpoint as a mechanism of evading InO-induced apoptosis. In conclusion, genetic alterations modulating CD22 expression and DNA damage response influence InO efficacy. The escape strategies within and beyond antigen loss to CD22-targeted therapy elucidated in this study provide insights into improving therapeutic approaches and overcoming resistance. KEY POINTS: We identified multiple mechanisms of CD22 antigen escape from inotuzumab ozogamicin, including protein truncation, protein destabilization, and epitope alteration.Hypermutation caused by error-prone DNA damage repair was a driver of CD22 mutation and escape.

Comparison of stereotactic aspiration surgery and conventional treatment for primary brainstem haemorrhage.

OBJECTIVE: To explore the effect of stereotactic aspiration surgery and conventional treatment for primary brainstem haemorrhage. METHODS: The clinical data of 137 patients with primary brain stem haemorrhage (haematoma volume > 3 ml) from August 2014 to August 2022 at the First Hospital of Hebei Medical University were reviewed. Sixty-five patients were treated with stereotactic haematoma aspiration, and 72 patients were treated with conventional therapy. We followed up on patient survival after 30 days and the recovery of neurological function after 90 days. The recovery of neurological function was evaluated by the modified Rankin Scale (mRS) 90 days after treatment. The mortality and neurological recovery rates of the two treatments were compared and analysed. RESULTS: There was a significant difference in the 30-day mortality rate between the two treatment groups (p < 0.05). There was a significant difference in neurological function improvement after 90 days between the two treatment groups (P < 0.05). There was no significant difference between stereotactic aspiration and routine treatment in the prognosis of primary brainstem haemorrhage patients at 90 days after treatment (P > 0.05). CONCLUSION: Stereotactic aspiration surgery for primary brain stem haemorrhage can significantly reduce mortality and improve the neurological function of some patients.

Effect of Language Arousal Nursing Combined with Thermal Insulation Nursing on MAP, SPO2, NRS and Adverse Reactions in Elderly Patients Undergoing Spinal Fracture Surgery Under General Anesthesia.

Objective: To evaluate the effects of language awakening nursing and thermal insulation nursing on anesthesia in elderly patients undergoing spinal fracture surgery. Methods: Randomized control method was used in this study, 200 elderly patients who underwent spinal fracture surgery under general anesthesia between January and December 2022. Among the patients, 100 cases were selected as the observation group, and the other 100 cases were included in the control group by the random number table method. The control group was treated with thermal insulation nursing, and the observation group was given language arousal nursing (a type of care that helps patients regain consciousness after surgery or anesthesia) combined with thermal insulation nursing (A nursing method for maintaining a patient's body temperature in a medical setting). Results: After the intervention, the observation group showed shorter extubation time, awaking time, eye-opening time, and respiratory recovery time compared to the control group (P < .05). Systolic, diastolic, and MAP decreased in both groups after the intervention, with the observation group showing lower values (P < .05). Heart rate at 5 and 10 minutes after extubation decreased in both groups, with the observation group having a lower heart rate than the control group (P < .05). There were no significant differences in SPO2 between the groups after intervention (P > .05). The observation group reported milder pain and a lower incidence of anesthesia-related adverse reactions (P < .05). These findings suggest that language arousal nursing combined with heat preservation nursing improves anesthesia recovery in elderly patients undergoing spinal fracture surgery, leading to better outcomes and reduced adverse events. Conclusion: Combining language arousal and thermal insulation nursing enhances anesthesia recovery in elderly spinal fracture surgery patients, leading to optimized blood pressure, heart rate, reduced pain, and fewer anesthesia-related adverse events.

Free Superficial Circumflex Iliac Artery/Superficial Inferior Epigastric Artery Adipofascial Flaps for Facial Reconstruction of Linear Scleroderma.

BACKGROUND: Linear scleroderma is an autoimmune connective disorder characterized by a saber-shaped facial deformity. The superficial circumflex iliac artery/superficial inferior epigastric artery (SCIA/SIEA) adipofascial flap is versatile for facial reconstruction, providing excellent aesthetic outcomes and minimal donor-site morbidity. Thus, this study aimed to share our experience of successfully treating linear scleroderma using single-stage SCIA/SIEA adipofascial flap microsurgery transplantation. METHODS: To correct asymmetric facial malformations, the SCIA/SIEA adipofascial flap transplantation was performed on 5 individuals with linear scleroderma. The flap was harvested based on SCIA or SIEA patterns and diameters. Donor and recipient vessels, postoperative complications, aesthetic outcomes, and patient satisfaction were recorded. RESULTS: All flaps survived with zero necrosis. Regarding the donor artery, SIEA was performed on 1 patient (1 of 5) and SCIA on 2 patients (2 of 5), and the remaining 2 patients (2 of 5) used the common trunk. Patients maintained a satisfactory facial counter-correction 6 to 10 years postoperatively. The complications included localized desquamate and hypotrichosis. CONCLUSIONS: Free SCIA/SIEA adipofascial flaps improved facial linear scleroderma's long-term functional and morphological outcomes. This SCIA/SIEA adipofascial flap offers low mortality, invisible scars, and stable aesthetic outcomes compared with anterolateral thigh flap, parascapular flaps, and fat transplantation.

Enhancing Char Formation and Flame Retardancy of Ethylene-Vinyl Acetate Copolymer (EVA)/Aluminum Hydroxide (ATH) Composites by Grafting Ladder Phenyl/Vinyl Polysilsesquioxane (PhVPOSS).

The ladder phenyl/vinyl polysilsesquioxane (PhVPOSS) was used to improve the flame-retardancy performances of ethylene-vinyl acetate copolymer (EVA)/aluminum hydroxide (ATH) composites due to the reactivity of its vinyl groups. FTIR, XPS, 1H NMR, and SEM-EDS data demonstrated the PhVPOSS grafting onto EVA molecular chains. The PhVPOSS improved the thermal stability of EVA/ATH composites, as shown by the thermogravimetric analysis (TGA). Furthermore, with the cone calorimeter (CONE) experiments, EVA/ATH/PhVPOSS showed better fire safety than the EVA/ATH composites, with the PHRR, PSPR, and PCOP reduced by 7.89%, 57.4%, and 90.9%, respectively. The mechanism investigations of flame retardancy revealed that the charring behaviors of the EVA/ATH/PhVPOSS composites were improved by the formation of Si-C bonds and Si-O bonds, and a more compact and denser char layer can contribute more to the barrier effect.

Deciphering the role of NETosis-related signatures in the prognosis and immunotherapy of soft-tissue sarcoma using machine learning.

Background: Soft-tissue sarcomas (STSs) are a rare type of cancer, accounting for about 1% of all adult cancers. Treatments for STSs can be difficult to implement because of their diverse histological and molecular features, which lead to variations in tumor behavior and response to therapy. Despite the growing importance of NETosis in cancer diagnosis and treatment, researches on its role in STSs remain limited compared to other cancer types. Methods: The study thoroughly investigated NETosis-related genes (NRGs) in STSs using large cohorts from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and Support Vector Machine Recursive Feature Elimination (SVM-RFE) were employed for screening NRGs. Utilizing single-cell RNA-seq (scRNA-seq) dataset, we elucidated the expression profiles of NRGs within distinct cellular subpopulations. Several NRGs were validated by quantitative PCR (qPCR) and our proprietary sequencing data. To ascertain the impact of NRGs on the sarcoma phenotype, we conducted a series of in vitro experimental investigations. Employing unsupervised consensus clustering analysis, we established the NETosis clusters and respective NETosis subtypes. By analyzing DEGs between NETosis clusters, an NETosis scoring system was developed. Results: By comparing the outcomes obtained from LASSO regression analysis and SVM-RFE, 17 common NRGs were identified. The expression levels of the majority of NRGs exhibited notable dissimilarities between STS and normal tissues. The correlation with immune cell infiltration were demonstrated by the network comprising 17 NRGs. Patients within various NETosis clusters and subtypes exhibited different clinical and biological features. The prognostic and immune cell infiltration predictive capabilities of the scoring system were deemed efficient. Furthermore, the scoring system demonstrated potential for predicting immunotherapy response. Conclusion: The current study presents a systematic analysis of NETosis-related gene patterns in STS. The results of our study highlight the critical role NRGs play in tumor biology and the potential for personalized therapeutic approaches through the application of the NETosis score model in STS patients.

Faster Return to Daily Activities and Better Pain Control: A Prospective Study of Enhanced Recovery After Surgery Protocol in Breast Augmentation.

BACKGROUND: Enhanced recovery after surgery (ERAS) has been proven to decrease the amount of opioid use and reduce postoperative pain for a variety of surgeries, including breast reconstruction. However, data on ERAS in breast augmentation is lacking. OBJECTIVES: This study aims to investigate the effectiveness and safety of ERAS for breast augmentation. METHODS: A standardized ERAS protocol was established with full consideration of all aspects of perioperative care. Patients undergoing implant-based breast augmentation were prospectively recruited between December 2020 and January 2023, and assigned to either the ERAS or non-ERAS group randomly. The primary outcome was the activity of daily living after surgery. The secondary was postoperative pain and other outcomes included time to freely elevation, vomiting frequency, the use of analgesics, and complications. RESULTS: A total of 122 patients were included, with 70 in the ERAS group and 52 in the non-ERAS group. Compared to non-ERAS patients, ERAS patients had a shorter time to freely elevation of upper limbs (2.3 d vs. 5.5 d, P < 0.001). For ERAS patients, the pain scores were significantly lower on postoperative days 1 to 3, the activity of daily living index was significantly higher on postoperative days 1 to 3 and the opioids consumption was decreased (7.1 mg vs. 46.2 mg, P = 0.018). No difference was observed in complication and hospital costs between the two groups. CONCLUSION: The ERAS protocol significantly reduced postoperative pain and the use of opioids and promoted a return to daily activities without increasing complications in breast augmentation. LEVEL OF EVIDENCE IV: 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 .

How Camera-to-Subject Distance and Height Affect Breast Measurement and Follow-Up Assessment in Plastic Surgery.

BACKGROUND: Due to several factors that affect photograph quality, bias is inevitably present in two-dimensional (2D) breast photography. The principal variables affecting image performance at a fixed focus length are the distance between the camera and the subjects and the photography angles. OBJECTIVE: This study aimed to investigate the effects of camera-to-subject distances and camera height on breast measurement parameters to understand the trend of breast deformation and provide guidance for the accurate evaluation of planar follow-up. METHODS: We enlisted 16 volunteers with various breast cup sizes (A-D). Frontal and lateral photos were obtained with a steady focus of 50 mm at distances between 1.10 m and 2.20 m and at heights between 30 cm above the nipple and 30 cm below the nipple at intervals of 10 cm. Two researchers independently evaluated each volunteer's breast aesthetic parameters, including 11 linear parameters, 3 area parameters, and 3 ratio parameters, using Vernier calipers and Photoshop. RESULTS: The correlation coefficient of the two investigators ranged from 0.922 to 0.999. The results measured by Photoshop were 29.67 ± 5.23% greater than those of the Vernier caliper (p < 0.01). In contrast to ratio parameters, which showed no significant changes in each distance group (p = 1.00), linear parameters and area parameters significantly increased as object distance decreased (p < 0.05). The lower pole of the breast grew wider and flatter and occupied a larger proportion of the breast as height declined. CONCLUSION: Camera-to-subject distances of 1.5-1.7 m are recommended for stabilized and uniform breast photography. Varying shooting height affects breast distortion. Quantifying the relationship between photographic conditions and breast morphology enables plastic surgeons to conduct more comprehensive and accurate assessments. LEVEL OF EVIDENCE IV: 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. Bullet point list: 1. The breast morphology will get more distortion with a smaller camera-to-subject distance. 2. Camera-to-subject distances of 1.5~1.7m are recommended for stabilized and uniform breast photography. 3. Height rather than distance affects the breast proportion.