Effect of Kinesiology Taping on Breast Cancer-Related Lymphedema: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PURPOSE: The objective of this systematic review and meta-analysis was to evaluate the impact of kinesiology taping on individuals suffering from breast cancer-related lymphedema. METHODS AND METHODS: We conducted a comprehensive search in PubMed, Cochrane Library, and Embase databases, spanning from their inception date to December 20, 2023, to identify pertinent studies. Inclusion criteria comprised studies that (1) enrolled participants diagnosed with breast cancer-related lymphedema; (2) implemented kinesiology taping as the intervention; (3) incorporated either complete decongestive therapy, exercise, or sham taping as the control treatment; and (4) included clinical measurements such as the severity of lymphedema, upper limb function assessment, quality of life, and perceived comfort. RESULTS: Information was extracted from 14 randomized controlled trials (RCTs). The analyses demonstrated statistically significant improvement, indicating a preference for kinesiology taping in the outcomes of upper limb functional assessment (standardized mean difference [SMD] = -0.88, 95% confidence interval [CI]: [-1.22, -0.55]), quality of life (SMD = 0.50, 95% CI: [0.16, 0.84]), and perceived comfort (SMD = 0.85, 95% CI: [0.34, 1.36]). CONCLUSION: The findings suggest that kinesiology taping could be considered a viable option for individuals dealing with breast cancer-related lymphedema. Nevertheless, acknowledging certain limitations within this study, further confirmation of its benefits necessitates additional larger-scale and better-designed RCTs.

Chromosome-level genome assemblies of 2 hemichordates provide new insights into deuterostome origin and chromosome evolution.

Deuterostomes are a monophyletic group of animals that includes Hemichordata, Echinodermata (together called Ambulacraria), and Chordata. The diversity of deuterostome body plans has made it challenging to reconstruct their ancestral condition and to decipher the genetic changes that drove the diversification of deuterostome lineages. Here, we generate chromosome-level genome assemblies of 2 hemichordate species, Ptychodera flava and Schizocardium californicum, and use comparative genomic approaches to infer the chromosomal architecture of the deuterostome common ancestor and delineate lineage-specific chromosomal modifications. We show that hemichordate chromosomes (1N = 23) exhibit remarkable chromosome-scale macrosynteny when compared to other deuterostomes and can be derived from 24 deuterostome ancestral linkage groups (ALGs). These deuterostome ALGs in turn match previously inferred bilaterian ALGs, consistent with a relatively short transition from the last common bilaterian ancestor to the origin of deuterostomes. Based on this deuterostome ALG complement, we deduced chromosomal rearrangement events that occurred in different lineages. For example, a fusion-with-mixing event produced an Ambulacraria-specific ALG that subsequently split into 2 chromosomes in extant hemichordates, while this homologous ALG further fused with another chromosome in sea urchins. Orthologous genes distributed in these rearranged chromosomes are enriched for functions in various developmental processes. We found that the deeply conserved Hox clusters are located in highly rearranged chromosomes and that maintenance of the clusters are likely due to lower densities of transposable elements within the clusters. We also provide evidence that the deuterostome-specific pharyngeal gene cluster was established via the combination of 3 pre-assembled microsyntenic blocks. We suggest that since chromosomal rearrangement events and formation of new gene clusters may change the regulatory controls of developmental genes, these events may have contributed to the evolution of diverse body plans among deuterostomes.

Lithium nitrate salt-assisted CO2 absorption for the formation of corrosion barrier layer on AZ91D magnesium alloy.

Mg alloy corrosion susceptibility is a major issue that limits its wide industrial application in transport, energy and medical sectors. A corrosion-resistant layer containing crystalline MgCO3 was formed on the surface of AZ91D Mg alloy by Li salt loading and thermal CO2 treatment. Compared to the uncoated AZ91D surface, the surface layer exhibited up to a ∼15-fold increase in corrosion resistance according to the electrochemical results in 3.5 wt% NaCl solution and ∼32% decrease in wear rate compared to untreated AZ91D. The improved corrosion resistance is attributed to the formation of a <10 µm thick dense layer containing Mg, O, C and Li with crystalline MgCO3 phases. The initial step was to form a porous MgO layer on the surface of AZ91D Mg alloy, followed by loading an alkali metal salt (i.e., LiNO3) onto the MgO surface. The porous MgO surface was then reconstructed into a dense insulation layer containing Mg carbonate through CO2 absorption facilitated by molten Li salt during thermal CO2 treatment at 350 °C. As a potential method to utilize excessive CO2 for beneficial outcomes, the formation of the carbonate-containing film introduced in this study opens a new pathway for protecting various existing Mg alloys for diverse industrial applications.

Challenges with computing scalar and ad-hoc implicatures in Mandarin-speaking 4-8-year-old autistic children.

INTRODUCTION: Mixed findings have been reported about the computation of scalar or/and ad-hoc implicatures in primarily school-age autistic verbal children and adolescents: while some studies reported their struggles with both implicatures, others observed their strengths in computing scalar implicatures. This study extends the previous investigation by testing the derivation of scalar (including both number and quantifier) and ad-hoc implicatures of a younger group of Mandarin-speaking autistic 4-8-year-olds; moreover, we assess the biological, linguistic, and cognitive factors affecting children's implicature acquisition. METHODS: The participants included 22 4-8-year-old autistic verbal children (mean age = 67.64 months) and 19 typically developing (TD) children who did not significantly differ in age, receptive vocabulary, and non-verbal IQ. Both groups completed a computer-based Truth Value Judgment task, assessing their knowledge of scalar (involving the number 'three' and the quantifier 'some') and ad-hoc implicatures. We also examined whether their implicature computation was linked to age, receptive vocabulary, non-verbal IQ, and Theory of Mind (ToM). RESULTS: Compared with the TD controls, autistic children derived significantly fewer scalar and ad-hoc implicatures. Specifically, TD children successfully computed number and ad-hoc implicatures, contrasting to the bimodal distribution of their pragmatic vs. logical responses to quantifier implicatures. Though autistic children performed better with number implicatures slightly above the chance level, they had difficulties in computing quantifier and ad-hoc implicatures. Further, autistic children's knowledge of the number and ad-hoc implicatures was linked to their ToM skills. CONCLUSIONS: These findings underscore the overall delayed implicature knowledge of young autistic children, and their low sensitivity to the implicatures is related to the core ToM deficits. Furthermore, our data confirm the coherent pattern of the earlier acquisition of number over quantifier implicatures and illuminate the distinct mechanisms underlying the computation of scalar vs. ad-hoc implicatures.

A prospective study of psychological adjustment during and after forehead flap nasal reconstruction.

The psychological effects of staged nasal reconstruction with a forehead flap were prospectively investigated. Thirty-three patients underwent nasal reconstruction with forehead flaps between March 2017 and July 2020. Three questionnaires were used to assess psychosocial functioning before surgery (time 1), 1 week after forehead flap transfer (time 2), 1 week after forehead flap division (time 3), and after refinement procedures (time 4). The patients were categorized into three groups according to the severity of nasal defects. Between- and within-group comparisons were conducted. All patients reported increased satisfaction with their appearance during nasal reconstruction. For most patients, levels of distress and social avoidance were highest before reconstruction (time 1). Both levels decreased as reconstruction advanced, and were significantly improved by times 3 and 4. The stage of reconstruction had a greater effect on these levels than did severity of nasal defect. Nasal reconstruction with forehead flap is beneficial physically and psychologically. Psychological evaluation before and after surgery facilitates patient-surgeon interactions and further enhances outcomes.

Predicting DSM-5 PTSD symptomatology 6 months to 2 years after burn: The role of early psychological risk factors.

BACKGROUND: Major burn injuries may have long-term mental health consequences, such as posttraumatic stress disorder (PTSD). This study extended prior work to investigate DSM-5 PTSD symptoms at 6 months, 1 year, and 2 years post-burn as well as the contribution of two sets of early psychological risk factors to DSM-5 PTSD symptoms: Established PTSD risk factors (prior adjustment problems, past trauma, perception of life threat, peritraumatic emotions and dissociation) and theory-derived cognitive factors (negative appraisals of the trauma and its sequelae, memory disorganization, trauma-related rumination, and thought suppression). METHOD: The current study recruited a sample of 118 adult burn patients (75.4% men, mean age 41.8, mean TBSA 18.3%) consecutively admitted to a large regional burn center in Northern Taiwan, who were assessed at 6, 12, and 24 months following their burn injury. RESULTS: A total of 11.0%, 5.9%, and 7.6% met probable DSM-5 PTSD at 6 months, 1 year, and 2 years post-burn, respectively. The rates rose to 15.3%, 10.2%, and 11.0% using the cutoff method. After controlling for covariates, the regression model with theory-derived cognitive factors explained an additional significant 15.9%, 17.2%, and 17.7% of the variance in DSM-5 PTSD symptoms at 6 months, 1 year, and 2 years post-burn, respectively. In contrast, the regression model with established PTSD risk factors explained an additional significant 7.2%, 14.4%, and 10.5% of the variance in DSM-5 PTSD symptoms at 6 months, 1 year, and 2 years post-burn, respectively. Of all predictors, negative appraisals of intrusions was consistently and strongly predictive of DSM-5 PTSD symptomatology post-burn across time, followed by prior depression. CONCLUSIONS: The results underscore the role of early cognitive risk factors in the development and persistence of DSM-5 PTSD symptomatology following burn injury.

Predicting early mortality and severe intraventricular hemorrhage in very-low birth weight preterm infants: a nationwide, multicenter study using machine learning.

Our aim was to develop a machine learning-based predictor for early mortality and severe intraventricular hemorrhage (IVH) in very-low birth weight (VLBW) preterm infants in Taiwan. We collected retrospective data from VLBW infants, dividing them into two cohorts: one for model development and internal validation (Cohort 1, 2016-2021), and another for external validation (Cohort 2, 2022). Primary outcomes included early mortality, severe IVH, and early poor outcomes (a combination of both). Data preprocessing involved 23 variables, with the top four predictors identified as gestational age, birth body weight, 5-min Apgar score, and endotracheal tube ventilation. Six machine learning algorithms were employed. Among 7471 infants analyzed, the selected predictors consistently performed well across all outcomes. Logistic regression and neural network models showed the highest predictive performance (AUC 0.81-0.90 in both internal and external validation) and were well-calibrated, confirmed by calibration plots and the lowest two mean Brier scores (0.0685 and 0.0691). We developed a robust machine learning-based outcome predictor using only four accessible variables, offering valuable prognostic information for parents and aiding healthcare providers in decision-making.

Comparative Analysis of Out-of-Hospital Cardiac Arrest Outcomes in Health Clinics, Nursing Homes, and Public Places: Implications for Optimizing Automated External Defibrillator Strategies.

Purpose: Various factors, such as event location and response time, influence the outcomes of out-of-hospital cardiac arrest (OHCA). Very few studies have explored the delivery of basic life support (BLS) to patients having OHCA at health clinics or nursing homes-settings with professional BLS providers. Thus, in this study, we compared prognostic and survival outcomes between health clinics, nursing homes, and other public places (eg, workplaces and sports facilities/recreational areas) to offer insights for optimizing OHCA outcomes. Patients: This study included adults who had nontraumatic OHCA in Taoyuan City between January 2017 and December 2022. Methods: We collected data on patient characteristics, emergency medical service parameters, onsite patient management, automated external defibrillator (AED) locations, OHCA prognosis, and survival outcomes. Multivariate analyses were performed to predict survival to discharge (primary outcome) and neurological outcomes at discharge (secondary outcome). Results: During the study period, the numbers of OHCA events at health clinics, nursing homes, and other public places were 158, 208, and 1986, respectively. The mean age of OHCA in health medical clinics, nursing home and other public places were 63.4, 81.5 and 64.7, respectively (P value<0.001). The proportion of witnessed events, rate of bystander resuscitation, and frequency of AED utilization were the highest for health clinics (53.2% (84/158), 83.4% (132/158), and 13.3% (21/158), respectively, P value<0.001). The average AED-scene distances and response times were the lowest for health clinics (388.8 m and 5.4 min, respectively). In initial shockable rhythm group, the probabilities of survival to discharge at discharge were the highest for health clinics (aOR=1.41, 95% CI=1.04-1.81, P value=0.041)) and lowest for nursing homes (aOR=0.84, 95% CI=0.76-0.93, P value=0.024). Conclusion: Our research shows that OHCA patients at medical health clinics have higher rates of witnessing and bystander CPR and AED usage than other public places. However, while survival rates for patients with shockable rhythms are slightly better at health clinics, the neurological outcomes are not significantly different. The AED-scene distances are too far to be used effectively.

Mycoplasma genitalium infection and resistance-associated mutations to macrolides and fluoroquinolones among high-risk patients in Taiwan.

BACKGROUND: Mycoplasma genitalium is an emerging etiology of sexually transmitted infections (STIs) with increasing resistance to antimicrobials. Surveillance on the epidemiology of M. genitalium infection and antimicrobial resistance is warranted. METHODS: Between September 2021 and August 2023, people with HIV (PWH) and people without HIV (PWoH) at risk of STIs were screened for M. genitalium infection using a multiplex polymerase-chain-reaction assay of specimens collected from the rectum, urethra, oral cavity, and vagina. The prevalences of resistance-associated mutations (RAMs) of M. genitalium to fluoroquinolones, macrolides, and tetracycline were investigated. RESULTS: During the 2-year study period, 1021 participants were enrolled, including 531 PWH and 490 PWoH. Overall, 83 (8.1%) and 34 (7.6%) participants had M. genitalium infection at baseline and during follow-up, respectively, with the rectum being the most common site of detection (61.5%). With the first course of antimicrobial treatment, 27 of 63 (42.9%) participants with M. genitalium infection were cured during follow-up, including 24 of 58 (41.4%) who received doxycycline monotherapy. The prevalence of RAMs to macrolides, fluoroquinolones, and tetracyclines at baseline were 24.3%, 22.4%, and 7.9%, respectively. Though PWH had more M. genitalium infection (10.2% vs 5.9%, p = 0.01), a higher rate of RAMs to macrolides (41.0% vs 14.7%, p < 0.01) was found in PWoH. CONCLUSIONS: Among high-risk populations, the prevalence of M. genitalium infection was 8.1%. The overall genotypic resistance of M. genitalium to macrolides and fluoroquinolones was moderately high in Taiwan. Detection of M. genitalium infection and antimicrobial resistance is warranted to ensure resistance-guided antimicrobial treatments to be administered.

Exploring the impact of hydrogen sulfide on hematologic malignancies: A review.

Hydrogen sulfide (H2S) is one of the three most crucial gaseous messengers in the body. The discovery of H2S donors, coupled with its endogenous synthesis capability, has sparked hope for the treatment of hematologic malignancies. In the last decade, the investigation into the impact of H2S has expanded, particularly within the fields of cardiovascular function, inflammation, infection, and neuromodulation. Hematologic malignancies refer to a diverse group of cancers originating from abnormal proliferation and differentiation of blood-forming cells, including leukemia, lymphoma, and myeloma. In this review, we delve deeply into the complex interrelation between H2S and hematologic malignancies. In addition, we comprehensively elucidate the intricate molecular mechanisms by which both H2S and its donors intricately modulate the progression of tumor growth. Furthermore, we systematically examine their impact on pivotal aspects, encompassing the proliferation, invasion, and migration capacities of hematologic malignancies. Therefore, this review may contribute novel insights to our understanding of the prospective therapeutic significance of H2S and its donors within the realm of hematologic malignancies.

Metabolomic Alterations in Methotrexate Treatment of Moderate-to-Severe Psoriasis.

BACKGROUND Aberrant lipid metabolism alterations in skin tissue, blood, or urine have been implicated in psoriasis. Here, we examined lipid metabolites related to psoriasis and their association with the age of disease onset. MATERIAL AND METHODS Differences in lipid metabolites before and after methotrexate (MTX) treatment were evaluated. The discovery cohort and validation cohort consisted of 50 and 46 patients, respectively, with moderate-to-severe psoriasis. After MTX treatment, the patients were divided into response (Psoriasis Area and Severity Index [PASI] 75 and above) and non-response (PASI below 75) groups, blood was collected for serum metabolomics, and multivariate statistical analysis was performed. RESULTS We detected 1546 lipid metabolites. The proportion of the top 3 metabolites was as follows: triglycerides (TG, 34.8%), phospholipids (PE, 14.5%), phosphatidylcholine (PC, 12.4%); diglycerides (DG) (16: 1/18: 1), and DG (18: 1/18: 1) showed strong positive correlations with onset age. There were marked changes in TG (16: 0/18: 0/20: 0), TG (18: 0/18: 0/22: 0), TG (14: 0/18: 0/22: 0), TG (14: 0/20: 0/20: 0), lysophosphatidylcholine (LPC) (16: 0/0: 0), LPC (18: 0/0: 0), LPC (14: 0/0: 0), and LPC (18: 1/0: 0) levels before and after 12 weeks of MTX treatment. The glycerophospholipid metabolic pathway was implicated in psoriasis development. Of the 96 recruited patients, 35% were MTX responders and 65% non-responders. PE (34: 4) and PE (38: 1) levels were significantly different between the groups. Obvious differences in lipid metabolism were found between early-onset (<40 years) and late-onset (≥40 years) psoriasis. Significant changes in serum lipid profile before and after MTX treatment were observed. CONCLUSIONS The specific lipid level changes in responders may serve as an index for MTX treatment efficacy evaluation.

Multicomponent Synthesis of Imidazole-Based Ionizable Lipids for Highly Efficient and Spleen-Selective Messenger RNA Delivery.

The spleen emerges as a pivotal target for mRNA delivery, prompting a continual quest for specialized and efficient lipid nanoparticles (LNPs) designed to enhance spleen-selective transfection efficiency. Here we report imidazole-containing ionizable lipids (IMILs) that demonstrate a pronounced preference for mRNA delivery into the spleen with exceptional transfection efficiency. We optimized IMIL structures by constructing and screening a multidimensional IMIL library containing multiple heads, tails, and linkers to perform a structure-activity correlation analysis. Following high-throughput in vivo screening, we identified A3B7C2 as a top-performing IMIL in spleen-specific mRNA delivery via the formulated LNPs, achieving a remarkable 98% proportion of splenic transfection. Moreover, A3B7C2-based LNPs are particularly potent in splenic dendritic cell transfection. Comparative analyses revealed that A3B7C2-based LNPs achieved a notable 2.8-fold and 12.9-fold increase in splenic mRNA transfection compared to SM102 and DLin-MC3-DMA lipid formulations, respectively. Additionally, our approach yielded an 18.3-fold enhancement in splenic mRNA expression compared to the SORT method without introducing additional anionic lipids. Collectively, these IMILs highlight promising avenues for further research in spleen-selective mRNA delivery. This work offers valuable insights for the swift discovery and rational design of ionizable lipid candidates tailored for spleen-selective transfection, thereby facilitating the application of mRNA therapeutics in spleen-related interventions.

Case report: Donor-derived CLL-1 chimeric antigen receptor T-cell therapy for relapsed/refractory acute myeloid leukemia bridging to allogeneic hematopoietic stem cell transplantation after remission.

Background: Explore the efficacy and safety of donor-derived CLL-1 chimeric antigen receptor T-cell therapy (CAR-T) for relapsed/refractory acute myeloid leukemia (R/R AML) bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT) after remission. Case presentation: An adult R/R AML patient received an infusion of donor-derived CLL-1 CAR-T cells, and the conditioning regimen bridging to allo-HSCT was started immediately after remission on day 11 after CAR-T therapy upon transplantation. Then, routine post-HSCT monitoring of blood counts, bone marrow (BM) morphology, flow cytometry, graft-versus-host disease (GVHD) manifestations, and chimerism status were performed. Result: After CAR-T therapy, cytokine release syndrome was grade 1. On day 11 after CAR-T therapy, the BM morphology reached complete remission (CR), and the conditioning regimen bridging to allo-HSCT started. Leukocyte engraftment, complete donor chimerism, and platelet engraftment were observed on days +18, +23, and +26 post-allo-HSCT, respectively. The BM morphology showed CR and flow cytometry turned negative on day +23. The patient is currently at 4 months post-allo-HSCT with BM morphology CR, negative flow cytometry, complete donor chimerism, and no extramedullary relapse/GVHD. Conclusion: Donor-derived CLL-1 CAR-T is an effective and safe therapy for R/R AML, and immediate bridging to allo-HSCT after remission may better improve the long-term prognosis of R/R AML.

A retrospective study of an irradiation-based conditioning regimen and chidamide maintenance therapy in T-ALL/LBL.

OBJECTIVES: T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) are highly malignant and aggressive hematologic tumors for which there is no standard first-line treatment. Chidamide, a novel histone deacetylase inhibitor, shows great promise. We assessed the efficacy and safety of an irradiation-containing conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) and post-transplantation chidamide maintenance in patients with T-ALL/LBL. METHODS: We retrospectively analyzed the clinical data of six patients with T-ALL/LBL who underwent allo-HSCT with a radiotherapy-containing pretreatment regimen and post-transplant chidamide maintenance therapy. The endpoints were relapse, graft-versus-host disease (GVHD), transplant-related mortality (TRM), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). RESULTS: All of the patients had uneventful post-transplant hematopoietic reconstitution, and all achieved complete molecular remission within 30 days. All six patients survived, and two relapsed with a median relapse time of 828.5 (170-1335) days. The 1-year OS rate was 100%, the 2-year PFS rate was 66.7%, and the TRM rate was 0%. After transplantation, two patients developed grade I-II acute GVHD (2/6); grade III-IV acute and chronic GVHD were not observed. The most common AEs following chidamide administration were hematological AEs, which occurred to varying degrees in all patients; liver function abnormalities occurred in two patients (grade 2), and symptoms of malaise occurred in one patient (grade 1). CONCLUSION: Chidamide maintenance therapy after T-ALL/LBL transplantation is safe, but the efficacy needs to be further investigated.

Diagnostic ability of macular nerve fiber layer thickness measured by swept-source OCT in preperimetric glaucoma.

BACKGROUND: We evaluated the diagnostic ability of macula retinal nerve fiber layer (mRNFL) thickness in preperimetric glaucoma (PPG) patients. METHODS: This prospective study included 83 patients with PPG and 83 age- and refractive error-matched normal control subjects. PPG was defined as a localized RNFL defect corresponding to glaucomatous optic disc changes with a normal visual field test. We used spectral-domain (SD) OCT to measure the circumpapillary RNFL (cpRNFL) thickness and macular ganglion cell-inner plexiform layer (GCIPL) thickness. Swept-source (SS) OCT was used to measure cpRNFL thickness, macular ganglion cell layer + inner plexiform layer (IPL) thickness (GCL+), and macular ganglion cell layer + IPL+ mRNFL thickness (GCL++). The mRNFL thickness was defined as GCL++ minus GCL+. To evaluate the diagnostic power of each parameter, the area under the receiver operating characteristics curve (AUROC) was analyzed to differentiate PPG from the normal groups. RESULTS: Using SD-OCT, all GCIPL parameters and most cpRNFL parameters, except at the nasal and temporal quadrant, were significantly lower in PPG versus normal controls. PPG eyes had significantly smaller values than normal controls for all cpRNFL and GCL parameters measured by SS-OCT, except mRNFL at the superonasal area. The inferotemporal GCL++ had the largest AUROC value (0.904), followed by inferotemporal GCL+ (0.882), inferotemporal GCIPL thickness (0.871), inferior GCL++ (0.866), inferior cpRNFL thickness by SS-OCT (0.846), inferior cpRNFL thickness by SD-OCT (0.841), and inferotemporal mRNFL thickness (0.840). The diagnostic performance was comparable between inferotemporal mRNFL thickness and the best measures of GCL (inferotemporal GCL++, p = 0.098) and cpRNFL (inferior cpRNFL thickness by SS-OCT, p = 0.546). CONCLUSION: The diagnostic ability of mRNFL thickness was comparable to that of the best measures of cpRNFL and GCL analysis for eyes with PPG. Therefore, mRNFL thickness could be a new parameter to detect early structural changes in PPG.

FOXO1 reshapes neutrophils to aggravate acute brain damage and promote late depression after traumatic brain injury.

BACKGROUND: Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury (TBI). However, the heterogeneity, multifunctionality, and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood. METHODS: Using the combined single-cell transcriptomics, metabolomics, and proteomics analysis from TBI patients and the TBI mouse model, we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests. We also characterized the underlying mechanisms both in vitro and in vivo through molecular simulations, signaling detections, gene expression regulation assessments [including dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays], primary cultures or co-cultures of neutrophils and oligodendrocytes, intracellular iron, and lipid hydroperoxide concentration measurements, as well as forkhead box protein O1 (FOXO1) conditional knockout mice. RESULTS: We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model. Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI, aggravating acute brain inflammatory damage and promoting late TBI-induced depression. In the acute stage, FOXO1 upregulated cytoplasmic Versican (VCAN) to interact with the apoptosis regulator B-cell lymphoma-2 (BCL-2)-associated X protein (BAX), suppressing the mitochondrial translocation of BAX, which mediated the antiapoptotic effect companied with enhancing interleukin-6 (IL-6) production of FOXO1high neutrophils. In the chronic stage, the "FOXO1-transferrin receptor (TFRC)" mechanism contributes to FOXO1high neutrophil ferroptosis, disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein, which contributes to the progression of late depression after TBI. CONCLUSIONS: FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI, which provides insight into the heterogeneity, reprogramming activity, and versatility of neutrophils in TBI.

Neonatal Filaggrin Genetic Screening and Counseling to Prevent Atopic Dermatitis in High-Risk Infants.

Background: Mutations in filaggrin (FLG), the gene that codes for the skin barrier protein, have been shown to be associated with atopic dermatitis (AD). Objective: The objectives of this study were to determine the effects of genetic counseling and parental education on infants at a high risk of AD. Methods: We enrolled 7521 newborns in Taiwan from January 1, 2016, to March 30, 2020, and all of them received genetic testing encompassing 20 known FLG mutations. The genetic counseling and AD prevention and care team consisted of pediatricians, dermatologists, social workers, and genetic counselors. The counseling was arranged for at least 30 minutes within 45 days after delivery. Results: A total of 2963 high-risk infants (39.4%) were identified. Homozygous c.1432C>T was the most commonly identified mutation. A total of 418 neonates' parents were stratified into counseling and noncounseling groups, where the effect of parental education was evaluated. The genetically stratified parental education program was effective in preventing AD development by 63.3% in high-risk infants before 12 months of life (P < 0.0001). Conclusion: Genetic stratification and parental education are effective in preventing the development of AD in high-risk infants before 12 months of life.

Tracing the evolutionary origin of chordate somites in the hemichordate Ptychodera flava.

Metameric somites are a novel character of chordates with unclear evolutionary origins. In the early branching chordate amphioxus, anterior somites are derived from the paraxial mesodermal cells that bud off the archenteron (i.e., enterocoely) at the end of gastrulation. Development of the anterior somites requires FGF signaling, and distinct somite compartments express orthologs of vertebrate non-axial mesodermal markers. Thus, it has been proposed that the amphioxus anterior somites are homologous to the vertebrate head mesoderm, paraxial mesoderm and lateral plate mesoderm. To trace the evolutionary origin of somites, it is essential to study the chordates' closest sister group, Ambulacraria, which includes hemichordates and echinoderms. The anterior coeloms of hemichordate and sea urchin embryos (respectively called protocoel and coelomic pouches) are also formed by enterocoely and require FGF signals for specification and/or differentiation. In this study, we applied RNA-seq to comprehensively screen for regulatory genes associated with the mesoderm-derived protocoel of the hemichordate Ptychodera flava. We also used a candidate gene approach to identify P. flava orthologs of chordate somite markers. In situ hybridization results showed that many of these candidate genes are expressed in distinct or overlapping regions of the protocoel, which indicates that molecular compartments exist in the hemichordate anterior coelom. Given that the hemichordate protocoel and amphioxus anterior somites share a similar ontogenic process (enterocoely), induction signal (FGF), and characteristic expression of orthologous genes, we propose that these two anterior coeloms are indeed homologous. In the lineage leading to the emergence of chordates, somites likely evolved from enterocoelic, FGF-dependent, and molecularly compartmentalized anterior coeloms of the deuterostome last common ancestor.

Combining Blood-Based Biomarkers and Structural MRI Measurements to Distinguish Persons with and without Significant Amyloid Plaques.

Background: Amyloid-ß (Aß) plaques play a pivotal role in Alzheimer's disease. The current positron emission tomography (PET) is expensive and limited in availability. In contrast, blood-based biomarkers (BBBMs) show potential for characterizing Aß plaques more affordably. We have previously proposed an MRI-based hippocampal morphometry measure to be an indicator of Aß plaques. Objective: To develop and validate an integrated model to predict brain amyloid PET positivity combining MRI feature and plasma Aß42/40 ratio. Methods: We extracted hippocampal multivariate morphometry statistics from MR images and together with plasma Aß42/40 trained a random forest classifier to perform a binary classification of participant brain amyloid PET positivity. We evaluated the model performance using two distinct cohorts, one from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and the other from the Banner Alzheimer's Institute (BAI), including prediction accuracy, precision, recall rate, F1 score, and AUC score. Results: Results from ADNI (mean age 72.6, Aß+ rate 49.5%) and BAI (mean age 66.2, Aß+ rate 36.9%) datasets revealed the integrated multimodal (IMM) model's superior performance over unimodal models. The IMM model achieved prediction accuracies of 0.86 in ADNI and 0.92 in BAI, surpassing unimodal models based solely on structural MRI (0.81 and 0.87) or plasma Aß42/40 (0.73 and 0.81) predictors. CONCLUSIONS: Our IMM model, combining MRI and BBBM data, offers a highly accurate approach to predict brain amyloid PET positivity. This innovative multiplex biomarker strategy presents an accessible and cost-effective avenue for advancing Alzheimer's disease diagnostics, leveraging diverse pathologic features related to Aß plaques and structural MRI.

Structural Reversibility of Nanoscaled Sn Anodes.

Alloying-type anode materials provide high capacity for lithium-ion batteries; however, they suffer pulverization problems resulting from the volume change during cycling. Realizing the cycling reversibility of these anodes is therefore critical for sustaining their electrochemical performance. Here, we investigate the structural reversibility of Sn NPs during cycling at atomic-level resolution utilizing in situ high-resolution TEM. We observed a surprisingly near-perfect structural reversibility after a complete cycle. A three-step phase transition happens during lithiation, accompanied by the generation of a significant number of defects, grain boundaries, and up to 202% volume expansion. In subsequent delithiation, the volume, morphology, and crystallinity of the Sn NPs were restored to their initial state. Theoretical calculations show that compressive stress drives the removal of vacancies generated within the NPs during delithiation, therefore maintaining their intact morphology. This work demonstrates that removing vacancies during cycling can efficiently improve the structural reversibility of high-capacity anode materials.