Search

Purpose: This study aimed to analyze the incidence of cancer therapy-related cardiovascular toxicity (CTRCVT) and identify the radiation dosimetric and clinical risk factors for these events in patients with HER2-positive breast cancer., Materials and Methods: Data from 1,378 patients who were treated with curative surgery and adjuvant trastuzumab for breast cancer were retrospectively analyzed. A total of 959 patients underwent postoperative radiation therapy (RT), while 419 patients were managed without RT (no-RT). CTRCVT were categorized according to the time of occurrence in relation to trastuzumab as follows: during trastuzumab cycles (CTRCVT-during T) or after completing trastuzumab (CTRCVT-after T). The cardiac radiation dose was extracted from the RT plan of each individual patient. The incidence of and contributing factors for CTRCVT-during T and -after T were evaluated., Results: After a median follow-up of 95.8 months (range, 4.3-181.1 months), 69 patients (5.0%) had experienced CTRCVT. CTRCVT-during T was detected in 41 patients (3.0%), and the 8-year rate of CTRCVT-after T was 2.2%. Of the patients developing CTRCVT-during T, 27 (2.0%) discontinued trastuzumab. The cardiac radiation doses were significantly associated with the risk of both CTRCVT-during T (odds ratio, 1.087; P = 0.001) and -after T (hazard ratio, 1.177; P <0.001). The 8-year rates of CTRCVT-after T were not significantly different between the no-RT and RT groups (2.0% vs. 2.4%, P = 0.956). However, the rate was significantly higher in patients with heart V 25Gy ≥3% compared to those with heart V 25Gy <3% (5.7% vs. 1.5%, P = 0.019). Patients who received <17 cycles of trastuzumab had worse oncological outcomes than those who received ≥17 cycles., Conclusions: Both CTRCVT-during T and -after T were associated with the cardiac radiation dose. Therefore, evaluation of the cardiac radiation dose is necessary to prevent early termination of trastuzumab treatment, which could lead to worse outcomes., Competing Interests: Declaration of competing interest JSC serves on the scientific advisory board for Oncosoft and holds stock in Oncosoft and reports a patented prediction method for normal tissue region prediction, with royalties paid from OncoSoft, Coreline Soft Co., Ltd., (Copyright © 2024. Published by Elsevier Inc.)

Malaria in pregnancy increases maternal and perinatal morbidity and mortality. Indoor residual spraying (IRS) is a core vector control strategy used to reduce transmission in endemic areas; however, its efficacy in reducing the sequelae of malaria in pregnancy is not well described. PubMed, Embase, Cochrane, and Web of Science were searched for all studies assessing IRS exposure during pregnancy. Abstracts and full texts were reviewed independently by two researchers, with discrepancies adjudicated by a third. Of 3,319 studies that met the search criteria, 17 met the inclusion criteria. Thirteen studies reported on the effect of IRS on malaria endpoints during pregnancy, five on birth outcomes, and one on a fetal anomaly. Twelve of the 13 studies exploring maternal malaria and 3 of 3 studies reporting on placental malaria demonstrated a reduction among those exposed to IRS during pregnancy. Results were more mixed for obstetric outcomes. Two of the best-quality studies showed reductions in preterm birth, low birthweight, and fetal/neonatal mortality; a third high-quality study did not demonstrate a reduction in perinatal mortality but did not evaluate preterm birth. One study found a significantly increased risk of preterm birth in those exposed to IRS, although the study was of lower quality. A final study demonstrated a small, although statistically significant, association between IRS and male urogenital birth defects. In malaria-endemic areas, the published literature suggests that IRS during pregnancy reduces the incidence of malaria parasitemia. However, without high-quality prospective studies directly examining IRS in pregnancy, the impact on birth outcomes is less clear.

Initial studies on the immunogenicity of SARS-CoV-2 (CoV-2) S glycoprotein ("spike") as a protein subunit vaccine suggested sub-optimal efficacy in mammals. Although protein engineering efforts have produced CoV-2 spike protein sequences with greatly improved immunogenicity, additional strategies for improving the immunogenicity of CoV-2 protein subunit vaccines are scaffolding and the use of adjuvants. Comparisons of the effectiveness of engineered protein-only and engineered protein-nanoparticles vaccines have been rare. To explore this knowledge gap, we inoculated mice with two doses of either sequence-optimized trimeric spike protein or one of several sequence-optimized spike nanoparticles. We measured their immune response up to two months after the first dose. We also measured the immune response and protection against live virus in hamsters inoculated with either sequence-optimized trimeric spike protein or a liposome-based sequence-optimized spike nanoparticle. We found that in the presence of adjuvant, the antibody and neutralization titers elicited by spike-nanoparticles were not significantly greater than those elicited by spike-only in mice, even at doses as low as 0.1 µg/animal. Hamsters vaccinated with spike-only or spike-nanoparticles were equally protected from live virus one month after their first inoculation. These results suggest that sequence-optimized protein subunit vaccines in the form of individual prefusion-stabilized trimers can be as effective in improving immunogenicity as scaffolded forms., (© 2024. The Author(s).)

Generalized pustular psoriasis (GPP) is a rare, chronic, heterogeneous, and potentially life-threatening disease characterized by primary, sterile, and macroscopically visible pustules with or without systemic symptoms. There are ethnic differences in the genetic mutations associated with GPP that might affect the clinical manifestations and treatment responses. Currently, there is limited evidence from the patient population in the Asia-Pacific (APAC) region, resulting in a general paucity of information on the effective management of patients with GPP in this region. This modified Delphi panel study aimed to identify current evidence and gain advanced insights to facilitate the development of a regionally tailored APAC consensus on the management of GPP. A systematic literature review (SLR) was conducted to identify published literature and develop consensus statements on (i) definition and clinical course, (ii) diagnosis of GPP, (iii) treatment outcomes, goals, and monitoring measures, and (iv) optimal management strategies and clinical practices. Statements were rated by a panel of dermatologists in two rounds, with the threshold for consensus at ≥80% agreement. Twenty experts from the APAC region reached consensus on 106 statements that were developed based on the SLR and experts' collective expertise. The experts agreed that GPP is a rare, severe, and potentially life-threatening condition that is distinct from plaque psoriasis. This consensus emphasized the importance of a tailored treatment strategy taking into account the GPP flare severity and each patient's unique clinical circumstances. The experts reached consensus on the severity classification of GPP flares and recommended first-line and maintenance treatment options for adult GPP, childhood GPP, and GPP in pregnancy. These consensus outcomes have been synthesized into treatment algorithms to guide dermatologists in the APAC region in their clinical decision-making processes., (© 2024 The Author(s). The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Background : We primarily investigated the prognostic role of CDKN2A homozygous deletion in CNS WHO grade 4 gliomas. Additionally, we plan to examine traditional prognostic factors for grade 4 gliomas and validate the findings. Materials : We conducted a retrospective analysis of the glioma cohorts at our institute. We reviewed medical records spanning a 15-year period and examined pathological slides for an updated diagnosis according to the 2021 WHO classification of CNS tumors. We examined the IDH1/2 mutation and CDKN2A deletion using NGS analysis with ONCOaccuPanel ® . Further, we examined traditional prognostic factors, including age, WHO performance status, extent of resection, and MGMT promoter methylation status. Results : The mean follow-up duration was 27.5 months (range: 4.1-43.5 months) and mean overall survival (OS) was 20.7 months (SD, ±1.759). After the exclusion of six patients with a poor status of pathologic samples, a total of 136 glioblastoma cases diagnosed by previous WHO classification criteria were newly classified into 29 (21.3%) astrocytoma, IDH -mutant, and CNS WHO grade 4 cases, and 107 (78.7%) glioblastoma, IDH -wildtype, and CNS WHO grade 4 cases. Among them, 61 (56.0%) had CDKN2A deletions. The high-risk group with CDKN2A deletion regardless of IDH1/2 mutation had a mean OS of 16.65 months (SD, ±1.554), the intermediate-risk group without CDKN2A deletion and with IDH1/2 mutation had a mean OS of 21.85 months (SD, ±2.082), and the low-risk group without CDKN2A deletion and with IDH1/2 mutation had a mean OS of 33.38 months (SD, ±2.946). Multifactor analysis showed that age (≥50 years vs. <50 years; HR 4.645), WHO performance (0, 1 vs. 2; HR 5.002), extent of resection (gross total resection vs. others; HR 5.528), MGMT promoter methylation, (methylated vs. unmethylated; HR 5.078), IDH1/2 mutation (mutant vs. wildtype; HR 6.352), and CDKN2A deletion (absence vs. presence; HR 13.454) were associated with OS independently. Conclusions : The present study suggests that CDKN2A deletion plays a powerful prognostic role in CNS WHO grade 4 gliomas. Even if CNS WHO grade 4 gliomas have mutant IDH1/2 , they may have poor clinical outcomes because of CDKN2A deletion.

Advanced electronic semiconducting Van der Waals heterostructures (HSs) are promising candidates for exploring next-generation nanoelectronics owing to their exceptional electronic properties, which present the possibility of extending their functionalities to diverse potential applications. In this study, GeTe/MoTe 2 HS are explored for nonvolatile memory and neuromorphic-computing applications. Sputter-deposited Ag/GeTe/MoTe 2 /Pt HS cross-point devices are fabricated, and they demonstrate memristor behavior at ultralow switching voltages (V SET : 0.15 V and V RESET : -0.14 V) with very low energy consumption (≈30 nJ), high memory window, long retention time (10 4 s), and excellent endurance (10 5 cycles). Resistive switching is achieved by adjusting the interface between the Ag top electrode and the heterojunction switching layer. Cross-sectional transmission electron microscope images and conductive atomic force microscopy analysis confirm the presence of a conducting filament in the heterojunction switching layer. Further, emulating various synaptic functions of a biological synapse reveals that GeTe/MoTe 2 HS can be utilized for energy-efficient neuromorphic-computing applications. A multilayer perceptron is implemented using the synaptic weights of the Ag/GeTe/MoTe 2 /Pt HS device, revealing high pattern accuracy (81.3%). These results indicate that HS devices can be considered a potential solution for high-density memory and artificial intelligence applications., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

We estimated the seroprevalence of anti-SARS-COV-2 IgG in different island groups in Okinawa. A cross-sectional sero-survey was repeated in three periods between July 2020 and February 2021. A total of 2683 serum samples were collected from six referral medical centers, each covering a separate region in Okinawa. In the main island, the seroprevalence was 0.0% (0/392, 95% CI: 0.0-0.9), 0.6% (8/1448, 0.2-1.1), and 1.4% (8/582, 0.6-2.7) at the 1 st , 2 nd , and 3 rd sero-survey, respectively. In the remote islands, the seroprevalence was 0.0% (0/144, 95% CI: 0.0-2.5) and 1.6% (2/123, 0.2-5.8) at the 2 nd and 3 rd survey, respectively. The case detection ratio was 2.7 (95% CI: 1.3-5.3) in the main island and 2.8 (0.7-11.1) in the remote islands during the 3 rd survey. The case detection ratio was the highest in people aged 20-29 years (8.3, 95% CI: 3.3-21.4) in the main island and in those aged 50-59 years (14.1, 2.1-92.7) in the remote islands, suggesting under-reporting of clinical cases by the surveillance system in these subgroups. A sero-survey during an emerging infectious disease epidemic can be useful for validating the reliability of the surveillance system by providing the case detection ratio.

Mechanically durable transparent electrodes are essential for achieving long-term stability in flexible optoelectronic devices. Furthermore, they are crucial for applications in the fields of energy, display, healthcare, and soft robotics. Conducting meshes represent a promising alternative to traditional, brittle, metal oxide conductors due to their high electrical conductivity, optical transparency, and enhanced mechanical flexibility. In this paper, we present a simple method for fabricating an ultra-transparent conducting metal oxide mesh electrode using self-cracking-assisted templates. Using this method, we produced an electrode with ultra-transparency (97.39%), high conductance (R s  = 21.24 Ω sq -1 ), elevated work function (5.16 eV), and good mechanical stability. We also evaluated the effectiveness of the fabricated electrodes by integrating them into organic photovoltaics, organic light-emitting diodes, and flexible transparent memristor devices for neuromorphic computing, resulting in exceptional device performance. In addition, the unique porous structure of the vanadium-doped indium zinc oxide mesh electrodes provided excellent flexibility, rendering them a promising option for application in flexible optoelectronics., (© 2024. The Author(s).)

Purpose: The role of regional node irradiation (RNI) with whole-breast irradiation (WBI) in patients with pN1 breast cancer receiving taxane-based adjuvant chemotherapy is not well defined. The KROG 1701 trial, a phase 3, multicenter, noninferiority study, aimed to compare the disease-free survival between WBI+RNI and WBI alone in this patient cohort. Comprehensive patient-reported outcomes (PROs) collected at multiple timepoints are reported., Methods and Materials: The trial (NCT03269981) enrolled patients with pN1 breast cancer after breast-conserving surgery and taxane-based adjuvant chemotherapy, allocating them to receive either WBI+RNI or WBI only. PROs were assessed using European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaires Core 30and breast cancer-specific module 23 modules at baseline, during radiation therapy, and at subsequent follow-up intervals of 3 to 6 months, and annually up to 4 years., Results: From April 2017 to December 2021, 840 patients were enrolled; 777 received intervention as assigned, and 750 completed baseline PRO questionnaires (387 in WBI+RNI, 363 in WBI only). All PRO domains showed improvements over time (P < .001). During radiation therapy, the WBI+RNI group reported greater fatigue and nausea. Higher arm symptom scores were observed in the WBI+RNI group 3 months post-treatment (P = .030). No other significant PRO domain differences, including arm/breast symptoms, were observed between the 2 groups., Conclusions: In patients with pN1 breast cancer treated with taxane-based chemotherapy, adding RNI to WBI resulted in minor, temporary declines in specific PRO domains, but these differences were not clinically significant. This indicates that overall patient experience between WBI+RNI and WBI is comparable, supporting the safety and patient tolerability of both treatments., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Exocyst is a large multisubunit tethering complex essential for targeting and fusion of secretory vesicles in eukaryotic cells. Although the assembled exocyst complex has been proposed to tether vesicles to the plasma membrane and activate soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) for membrane fusion, the key biochemical steps that exocyst stimulates in SNARE-mediated fusion are undetermined. Here we use a combination of single-molecule and bulk fluorescence assays to investigate the roles of purified octameric yeast exocyst complexes in a reconstituted yeast exocytic SNARE assembly and vesicle fusion system. Exocyst had stimulatory roles in multiple distinct steps ranging from SNARE protein activation to binary and ternary complex assembly. Importantly, exocyst had a downstream role in driving membrane fusion and full content mixing of vesicle lumens. Our data suggest that exocyst provides extensive chaperoning functions across the entire process of SNARE complex assembly and fusion, thereby governing exocytosis at multiple steps., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Purpose: This study aimed to evaluate the clinical outcomes and prognostic implications of regional nodal irradiation (RNI) after neoadjuvant chemotherapy (NAC) in patients with residual triple-negative breast cancer (TNBC)., Materials and Methods: We analyzed 152 patients with residual TNBC who underwent breast-conserving surgery after NAC between December 2008 and December 2017. Most patients (n = 133; 87.5%) received taxane-based chemotherapy. Adjuvant radiotherapy (RT) was administered at a total dose of 45-65 Gy in 15-30 fractions to the whole breast, with some patients also receiving RT to regional nodes. Survival was calculated using the Kaplan-Meier method, and prognostic factors influencing survival were analyzed using the Cox proportional-hazards model., Results: During a median follow-up of 66 months (range, 9 to 179 months), the 5-year disease-free survival (DFS) rate was 68.0%. The 5-year locoregional recurrence-free survival, distant metastasis-free survival, and overall survival rates were 83.6%, 72.6%, and 78.7%, respectively. In the univariate analysis, the cN stage, ypT stage, ypN stage, axillary operation type, and RT field were associated with DFS. Multivariate analysis revealed that higher ypT stage (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.00-3.82; p = 0.049) and ypN stage (HR = 4.7; 95% CI 1.57-14.24; p = 0.006) were associated with inferior DFS. Among clinically node-positive patients, those who received RT to the breast only had a 5-year DFS of 73.7%, whereas those who received RNI achieved a DFS of 59.6% (p = 0.164). There were no differences between the DFS and RNI., Conclusion: In patients with residual TNBC, higher ypT and ypN stages were associated with poorer outcomes after NAC. RNI did not appear to improve DFS. More intensive treatments incorporating systemic therapy and RT should be considered for these patients.

Air pollution, a global health concern, has been associated with adverse effects on human health. In particular, particulate matter (PM), which is a major contributor to air pollution, impacts various organ systems including the skins. In fact, PM has been suggested as a culprit for accelerating skin aging and pigmentation. In this study, using single-cell RNA sequencing, IL-24 was found to be highly upregulated among the differentially expressed genes commonly altered in keratinocytes and fibroblasts of ex vivo skins exposed to PM. It was verified that PM exposure triggered the expression of IL-24 in keratinocytes, which subsequently led to a decrease in type I procollagen expression and an increase in MMP1 expression in fibroblasts. Furthermore, long-term treatment of IL-24 induced cellular senescence in fibroblasts. Through high-throughput screening, we identified chemical compounds that inhibit the IL-24-STAT3 signaling pathway, with lovastatin being the chosen candidate. Lovastatin not only effectively reduced the expression of IL24 induced by PM in keratinocytes but also exhibited a capacity to restore the decrease in type I procollagen and the increase in MMP1 caused by IL-24 in fibroblasts. This study provides insights into the significance of IL-24, illuminating mechanisms behind PM-induced skin aging, and proposes IL-24 as a promising target to mitigate PM-associated skin aging., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Bioactive metal-based nanostructures, particularly zinc oxide (ZnO), are promising materials for bone tissue engineering. However, integrating them into 3D-printed polymers using traditional blending methods reduces the cell performance. Alternative surface deposition techniques often require extreme conditions that are unsuitable for polymers. To address these issues, we propose a metal-assisted hydrothermal synthesis method to modify 3D printed polycaprolactone (PCL) scaffolds with ZnO nanoparticles (NPs), facilitating the growth of ZnO nanoarrays (NAs) at a low-temperature (55 °C). Physicochemical characterizations revealed that the ZnO NPs form both physical and chemical bonds with the PCL surface; chemical bonding occurs between the carboxylate groups of PCL and Zn(OH) 2 during seed deposition and hydrothermal synthesis. The ZnO NPs and NAs grown for a longer time (18 h) on the surface of PCL scaffolds exhibit significant proliferation and early differentiation of osteoblast-like cells. The proposed method is suitable for the surface modification of thermally degradable polymers, opening up new possibilities for the deposition of diverse metals.

Nanomaterials like graphene and transition metal dichalcogenides are being explored for developing artificial photosensory synapses with low-power optical plasticity and high retention time for practical nervous system implementation. However, few studies are conducted on Tellurium (Te)-based nanomaterials due to their direct and small bandgaps. This paper reports the superior photo-synaptic properties of covalently bonded Tellurium sulfur oxide (TeSO x ) and Tellurium selenium oxide (TeSeO x )nanomaterials, which are fabricated by incorporating S and Se atoms on the surface of Te multiropes using vapor deposition. Unlike pure Te multiropes, the TeSO x and TeSeO x multiropes exhibit controllable temporal dynamics under optical stimulation. For example, the TeSO x multirope-based transistor displays a photosensory synaptic response to UV light (λ = 365 nm). Furthermore, the TeSeO x multirope-based transistor exhibits photosensory synaptic responses to UV-vis light (λ = 365, 565, and 660 nm), reliable electrical performance, and a combination of both photodetector and optical artificial synaptic properties with a maximum responsivity of 1500 AW -1 to 365 nm UV light. This result is among the highest reported for Te-heterostructure-based devices, enabling optical artificial synaptic applications with low voltage spikes (1 V) and low light intensity (21 µW cm -2 ), potentially useful for optical neuromorphic computing., (© 2024 Wiley‐VCH GmbH.)

Phase-change random access memory represents a notable advancement in nonvolatile memory technology; however, it faces challenges in terms of thermal stability and reliability, hindering its broader application. To mitigate these issues, doping and structural modification techniques such as phase-change heterostructures (PCH) are widely studied. Although doping typically enhances thermal stability, it can adversely affect the switching speed. Structural modifications such as PCH have struggled to sustain stable performance under high atmospheric conditions. In this study, these challenges are addressed by synergizing oxygen-doped Sb 2 Te 3 (OST) with PCH technology. This study presents a novel approach in which OST significantly improves the crystallization temperature, power efficiency, and cyclability. Subsequently, the integration of the PCH technology bolsters the switching speed and further amplifies the device's reliability and endurance by refining the grain size (≈7 nm). The resultant OST-PCH devices exhibit exceptional performance metrics, including a drift coefficient of 0.003 in the RESET state, endurance of ≈4 × 10 8 cycles, an switching speed of 300 ns, and 67.6 pJ of RESET energy. These findings suggest that the OST-PCH devices show promise for integration into embedded systems, such as those found in automotive applications and Internet of Things devices., (© 2024 Wiley‐VCH GmbH.)

Immunoregulatory mechanisms established in the lymphoid organs are vital for preventing autoimmunity. However, the presence of similar mechanisms in non-lymphoid tissues remains unclear. Through transcriptomic and lipidomic analyses, we find a negative association between psoriasis and fatty acid metabolism, as well as Th2 signature. Homeostatic expression of liver X receptor (LXR) and peroxisome proliferator-activated receptor gamma (PPARγ) is essential for maintaining fatty acid metabolism and for conferring resistance to psoriasis in mice. Perturbation of signal transducer and activator of transcription 6 (STAT6) diminishes the homeostatic levels of LXR and PPARγ. Furthermore, mice lacking STAT6, interleukin 4 receptor alpha (IL-4Rα), or IL-13, but not IL-4, exhibit increased susceptibility to psoriasis. Under steady state, innate lymphoid cells (ILCs) are the primary producers of IL-13. In human skin, inhibiting tonic type 2 immunity exacerbates psoriasis-like inflammation and IL-17A, while activating LXR or PPARγ inhibits them. Hence, we propose that tonic type 2 immunity, driven by IL-13-producing ILCs, represents a crucial tissue checkpoint that represses autoimmunity and maintains lipid homeostasis in the skin., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Several fabrication methods have been developed for label-free detection in various fields. However, fabricating high-density and highly ordered nanoscale architectures by using soluble processes remains a challenge. Herein, we report a biosensing platform that integrates deep learning with surface-enhanced Raman scattering (SERS), featuring large-area, close-packed three-dimensional (3D) architectures of molybdenum disulfide (MoS 2 )-assisted gold nanoparticles (AuNPs) for the on-site screening of coronavirus disease (COVID-19) using human tears. Some AuNPs are spontaneously synthesized without a reducing agent because the electrons induced on the semiconductor surface reduce gold ions when the Fermi level of MoS 2 and the gold electrolyte reach equilibrium. With the addition of polyvinylpyrrolidone, a two-dimensional large-area MoS 2 layer assisted in the formation of close-packed 3D multistacked AuNP structures, resembling electroless plating. This platform, with a convolutional neural network-based deep learning model, achieved outstanding SERS performance at subterascale levels despite the microlevel irradiation power and millisecond-level acquisition time and accurately assessed susceptibility to COVID-19. These results suggest that our platform has the potential for rapid, low-damage, and high-throughput label-free detection of exceedingly low analyte concentrations.

Background: Atopic dermatitis (AD), a chronic inflammatory skin disease with T cell activation as a key feature, in which Th2 cell-mediated responses play a pivotal role. Regulatory T cells (Treg) are central immune cells that restrict autoimmunity and inflammation in the body. Patients with immune dysregulation, polyendocrinopathy, or enteropathy X-linked syndrome, an immune disease characterized by a deficiency in Treg, develop skin inflammation and allergic disorders, indicating that Treg play a crucial role in the development of allergic skin inflammation., Objective: we investigated the underlying mechanisms by which Treg control cutaneous allergic inflammation., Methods: An allergic skin inflammation mouse model was constructed using MC903, and Treg-depleted mouse model was constructed using diphtheria toxin. Neutralization of IFN-γ was constructed using anti-mouse-IFN-γ mouse antibody. Neutrophil infiltration was analyzed by flow cytometry and immunohistochemistry. Neutrophil extracellular traps (NETs), a process called NETosis, were detected using immunofluorescence. In vitro neutrophil stimulation and immunocytochemistry was conducted to demonstrate the effect of IFN-γ on NETosis., Results: The depletion of Foxp3 + Treg led to significantly exacerbated AD-like skin inflammation, including increased recruitment of neutrophils and expression of Th1 cytokine IFN-γ. Neutrophil infiltrating in skin of Treg-depleted mice released more NETs than wild type. Neutralization of IFN-γ abolished neutrophil infiltration and NETosis in Treg-depleted mice. Neutrophils stimulated with IFN-γ were more prone to release NETs in vitro. Finally, Foxp3 + Treg control cutaneous allergic inflammation by regulating IFN-γ-driven neutrophilic infiltration and NETosis., Conclusion: Our results highlight the previously underestimated Treg-IFN-γ-neutrophil inflammatory axis., (Copyright © 2024 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Aging-related bone loss is driven by various biological factors, such as imbalanced bone metabolism from decreased osteoblast and increased osteoclast activities. Various transcriptional and post-transcriptional factors increase osteoclast activity with aging; however, studies regarding the post-translational regulators of osteoclast activity are still limited. The ubiquitin E3 ligase Pellino-1 is a well-known post-translational regulator of inflammation. However, how Pellino-1 expression regulation affects osteoclast differentiation remains unclear. This study determined that Pellino-1 levels are reduced in bone marrow monocytes (BMMs) from 40-week-old mice compared to 4-week-old mice. Interestingly, conditional Knockout (cKO) of Pellino-1 in 6-week-old mice resulted in decreased bone mass, reduced body size, and lower weight than in Pellino-1 floxed mice; however, these differences are not observed in 20-week-old mice. The increased number of tartrate-resistant acid phosphatase (TRAP)-positive cells and serum levels of C-terminal telopeptides of type I collagen, a marker of bone resorption, in 6-week-old Pellino-1 cKO mice implied a connection between Pellino-1 and the osteoclast population. Enhanced TRAP activity and upregulation of osteoclast genes in BMMs from the cKO mice indicate that Pellino-1 deletion affects osteoclast differentiation, leading to decreased bone mass and heightened osteoclast activity. Thus, targeting Pellino-1 could be a potential gene therapy for managing and preventing osteoporosis., (© 2024 The Authors. Advanced Biology published by Wiley‐VCH GmbH.)

Purpose: The locally advanced unresectable intrahepatic cholangiocarcinoma (ICC) has detrimental oncological outcomes. In this study, we aimed to investigate the efficacy of radiotherapy in patients with locally advanced unresectable ICC., Materials and Methods: Between 2001 and 2021, 116 patients were identified through medical record who underwent radiotherapy for locally advanced unresectable ICC. The resectability of ICC is determined by the multidisciplinary team at each institution. Overall survival (OS) were analyzed using the Kaplan-Meier method, and prognostic factors were analyzed using the Cox proportional hazards model., Results: The median equivalent radiotherapy dose in 2 Gy fractions (EQD2) was 52 Gy (range, 30 to 110 Gy). Forty-seven patients (40.5%) received sequential gemcitabine-cisplatin based chemotherapy (GEM-CIS CTx). Multivariate analysis identified two risk factors, EQD2 of ≥ 60 Gy and application of sequential GEM-CIS CTx for OS. Patients were grouped by these two risk factors: group 1, EQD2 ≥ 60 Gy with sequential GEM-CIS CTx (n=25); group 2, EQD2 < 60 Gy with sequential GEM-CIS CTx or fluoropyrimidine-based concurrent chemoradiotherapy (n=70); and group 3, radiotherapy alone (n=21). Curative resection was more frequently undergone in group 1 than in groups 2 or 3 (28% vs. 8.6% vs. 0%, respectively). Consequently, OS was significantly better in group 1 than in groups 2 and 3 (p < 0.05)., Conclusion: Combined high-dose radiotherapy with sequential GEM-CIS CTx improved oncologic outcomes in patients with locally advanced unresectable ICC. Further prospective studies are required to validate these findings.

The HyperArc technique is known for generating high-quality radiosurgical treatment plans for intracranial lesions or hippocampal-sparing whole-brain radiotherapy (WBRT). However, there is no reported feasibility of using the HyperArc technique in hippocampal-sparing WBRT with a simultaneous integrated boost (SIB). This study aimed to compare dosimetric parameters of 2 commercially-available volumetric-modulated arc radiotherapy techniques, HyperArc and RapidArc, when using hippocampal-sparing WBRT with a SIB to treat brain metastases. Treatment plans using HyperArc and RapidArc techniques were generated retrospectively for 19 previously treated patients (1 to 3 brain metastases). The planning target volumes for the whole brain (excluding the hippocampal avoidance region; PTV WB ) and metastases (PTV met ) were prescribed 25 and 45 Gy, respectively, in 10 fractions. Each plan included homogeneous and inhomogeneous delivery to the PTV met . Dosimetric parameters for the target (conformity index [CI], homogeneity index [HI], target coverage [D 95% ]), and nontarget organs at risk were compared for the HyperArc and RapidArc plans. For homogeneous delivery, dosimetric parameters, including mean CI, HI, and target coverage in PTV WB and PTV met , were superior for HyperArc than RapidArc plans (all p < 0.01). The PTV WB and PTV met target coverage for HyperArc plans was significantly greater than for RapidArc plans (96.17% vs 93.38%, p < 0.01; 94.02% vs 92.21%, p < 0.01, respectively). HyperArc plans had significantly lower mean hippocampal D max and D min values than RapidArc plans (D max : 15.53 Gy vs, 16.71 Gy, p < 0.01; D min : 8.33 Gy vs 8.93 Gy, p < 0.01, respectively). Similarly, inhomogeneous delivery of hyperArc produced a superior target and lower hippocampal dosimetric parameters than RapidArc, except for the HI of PTV met (all p < 0.01). HyperArc generated superior conformity and target coverage with lower hippocampal doses than RapidArc. HyperArc could be an attractive technique for hippocampal-sparing WBRT with an SIB., (Copyright © 2023 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Patient-derived organoids (PDOs) are valuable in predicting response to cancer therapy. PDOs are ideal models for precision oncologists. However, their practical application in guiding timely clinical decisions remains challenging. This study focused on patients with advanced EGFR-mutated non-small cell lung cancer and employed a cancer organoid-based diagnosis reactivity prediction (CODRP)-based precision oncology platform to assess the efficacy of EGFR inhibitor treatments. CODRP was employed to evaluate EGFR-tyrosine kinase inhibitors (TKI) drug sensitivity. The results were compared to those obtained using area under the curve index. This study validated this index by testing lung cancer-derived organoids in 14 patients with lung cancer. The CODRP index-based drug sensitivity test reliably classified patient responses to EGFR-TKI treatment within a clinically suitable 10-day timeline, which aligned with clinical drug treatment responses. This approach is promising for predicting and analyzing the efficacy of anticancer, ultimately contributing to the development of a precision medicine platform., (© 2024. The Author(s).)

Filamentous fungal mycoproteins have gained increasing attention as sustainable alternatives to animal and plant-based proteins. This comprehensive review summarizes the nutritional characteristics, toxicological aspects, and health-promoting effects of mycoproteins, focusing on those derived from filamentous fungi, notably Fusarium venenatum. Mycoproteins are characterized by their high protein content, and they have a superior essential amino acid profile compared to soybeans indicating excellent protein quality and benefits for human nutrition. Additionally, mycoproteins offer enhanced digestibility, further highlighting their suitability as a protein source. Furthermore, mycoproteins are rich in dietary fibers, which have been associated with health benefits, including protection against metabolic diseases. Moreover, their fatty acids profile, with significant proportions of polyunsaturated fatty acids and absence of cholesterol, distinguishes them from animal-derived proteins. In conclusion, the future of mycoproteins as a health-promoting protein alternative and the development of functional foods relies on several key aspects. These include improving the acceptance of mycoproteins, conducting further research into their mechanisms of action, addressing consumer preferences and perceptions, and ensuring safety and regulatory compliance. To fully unlock the potential of mycoproteins and meet the evolving needs of a health-conscious society, continuous interdisciplinary research, collaboration among stakeholders, and proactive engagement with consumers will be vital., (© 2024 Institute of Food Technologists®.)

Medical school, residency, and fellowship occur during peak reproductive years for most trainees. This poses certain challenges for medical trainees as they approach family-building decisions. While the demands of residency have been well-elucidated, attempts at mitigating these demands alongside parenthood have long been neglected across various specialties. These challenges are perhaps most pronounced in Obstetrics and Gynecology residency programs, which are made-up of an 85% female-identifying workforce and whose training focuses on prenatal and postpartum health. Recent literature suggests an improvement in attitudes and policies towards parental leave during medical graduate education, however, there remains a lack of uniformity across specialties and programs. Through a recently developed Parental Leave Task Force made up of Obstetrics and Gynecology Trainees, we sought to conduct a review of the literature examining parental leave policies and their implications across various specialties as a call for uniform parental leave policies for all residents., (Copyright © 2024 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

A pterygium is a common conjunctival degeneration and inflammatory condition. It grows onto the corneal surface or limbus, causing blurred vision and cosmetic issues. Ultraviolet is a well-known risk factor for the development of a pterygium, although its pathogenesis remains unclear, with only limited understanding of its hereditary basis. In this study, we collected RNA-seq from both pterygial tissues and conjunctival tissues (as controls) from six patients (a total of twelve biological samples) and retrieved publicly available data, including eight pterygium samples and eight controls. We investigated the intrinsic gene regulatory mechanisms closely linked to the inflammatory reactions of pterygiums and compared Asian (Korea) and the European (Germany) pterygiums using multiple analysis approaches from different perspectives. The increased expression of antioxidant genes in response to oxidative stress and DNA damage implies an association between these factors and pterygium development. Also, our comparative analysis revealed both similarities and differences between Asian and European pterygiums. The decrease in gene expressions involved in the three primary inflammatory signaling pathways-JAK/STAT, MAPK, and NF-kappa B signaling-suggests a connection between pathway dysfunction and pterygium development. We also observed relatively higher activity of autophagy and antioxidants in the Asian group, while the European group exhibited more pronounced stress responses against oxidative stress. These differences could potentially be necessitated by energy-associated pathways, specifically oxidative phosphorylation.

Background/Objectives : Diabetic foot ulcers are one of the complications in patients with diabetes, which can be caused by infection, neuropathy, and blood vessel disorder. Among them, infection is the most common cause, and if it becomes worse, amputation may be necessary. So, it is important to detect and treat infections early, and determining indicators that can confirm infection is also important. Known infection markers include white blood cells (WBCs), the erythrocyte sediment rate (ESR), C-reactive protein (CRP), and procalcitonin, but they are not specific to diabetic foot ulcers. Presepsin, also known as soluble CD14, is known to be an early indicator of sepsis. Recent studies have reported that presepsin can be used as an early indicator of infection. This study investigated whether presepsin could be used as an early marker of severe infection in patients with diabetic foot ulcers. Methods: We retrospectively studied 73 patients who were treated for diabetic foot ulcerations from January 2021 to June 2023 at Yeungnam University Hospital. Results: Out of a total of 73 patients, 46 patients underwent amputations with severe infections, and the WBC level, ESR, and CRP, procalcitonin, and presepsin levels were significantly higher in the group of patients who underwent amputations. The cutoff of presepsin, which can predict serious infections that need amputation, was 675 ng/mL. A regression analysis confirmed that presepsin, HbA1c, and osteomyelitis significantly increased the risk of severe infections requiring amputation. Conclusions: Presepsin will be available as an early predictor of patients with severe infections requiring amputations for diabetic foot ulcerations.

Background: The use of electric scooters (e-scooters) continues to increase as a simple, inexpensive means of transport, resulting in a sharp increase in the incidence of scooter-related accidents. No study to date has closely examined the injury extent to the lower leg, joints, and extremities from e-scooter-related accidents. Here, we investigated the epidemiology and injury patterns of such accidents, focusing on injuries to the ankle and foot., Methods: Based on data from a single tertiary hospital's database, the demographics of 563 patients with scooter-associated injuries were analyzed retrospectively. Among the patients, 229 patients who were injured by e-scooter riding were further investigated. Based on the data, the general demographics of whole scooter-associated injuries and the injury characteristics and fracture cases of the lower leg, ankle, and foot were analyzed., Results: During the 4-year study period, the number of patients injured by e-scooters increased every year. Lower extremities were the most common injury site (67.2%) among riders, whereas injuries to the head and neck (64.3%) were more common in riders of non-electric scooters. Among the lower leg, ankle, and foot injuries of riders (52 cases), the ankle joint (53.8%) was the most commonly injured site, followed by the foot (40.4%) and lower leg (21.2%). The fracture group scored significantly higher on the Abbreviated Injury Scale than the non-fracture group ( p < 0.001). Among the fracture group (20 cases), ankle fractures (9 cases) were most common, including pronation external rotation type 4 injuries (4 cases) and pilon fractures (2 cases). Five patients (25%) had open fractures, and 12 patients (60%) underwent surgical treatment., Conclusions: The ankle and foot are the most common injury sites in e-scooter-related accidents. Given the high frequency and severity of e-scooter-related ankle and foot injuries, we suggest that more attention be paid to preventing these types of injuries with greater public awareness of the dangers of using e-scooters., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean Orthopaedic Association.)

Introduction: Indirect reduction of minimally invasive plate osteosynthesis (MIPO) can often result in delayed union in tibia fractures. This study evaluated several factors in MIPO in relation to bone union., Hypothesis: We hypothesized that the fracture gap, plate - tibia distance, or working length would have a substantial effect on the tibia union rate., Materials and Methods: Forty-one patients with simple diaphyseal or distal metaphyseal tibia fractures who underwent internal fixation surgery using the MIPO technique were divided into two groups: patients with delayed union and patients without delayed union. Non-actionable factors involving AO/OTA classification, fibula fracture and actionable factors including postoperative fracture gap, plate - tibia distance, working length in relation to parameters of bone union were compared between the two groups. Also cumulative rates of bone union and risk factors of delayed union according to variables of interest were investigated., Results: AO/OTA classification, site of fibula fracture, postoperative fracture gap, working length, and bone union rate of the two groups significantly differed (p<0.05). The cumulative rate of bone union during 1-year follow-up according to 43A tibia fracture, distal fibula fracture, fracture gap, and working length significantly differed between the two groups (p<0.05). By univariate Cox proportional hazards model, 43A tibia fracture, distal fibula fracture, facture gap, and short working length were risk factors for delayed union (p<0.05)., Discussion: Non-actionable factors involving AO/OTA classification, distal fibula fracture and actionable factors including postoperative fracture gap, working length were significant factors affecting bone union after MIPO. The present study indicated that small fracture gap and long working length during MIPO might facilitate bone healing in tibia fracture., Level of Evidence: IV; single-center retrospective cohort study., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background and Objective: This study proposes an unsupervised sequence-to-sequence learning approach that automatically assesses the motion-induced reliability degradation of the cardiac volume signal (CVS) in multi-channel electrical impedance-based hemodynamic monitoring. The proposed method attempts to tackle shortcomings in existing learning-based assessment approaches, such as the requirement of manual annotation for motion influence and the lack of explicit mechanisms for realizing motion-induced abnormalities under contextual variations in CVS over time., Method: By utilizing long-short term memory and variational auto-encoder structures, an encoder-decoder model is trained not only to self-reproduce an input sequence of the CVS but also to extrapolate the future in a parallel fashion. By doing so, the model can capture contextual knowledge lying in a temporal CVS sequence while being regularized to explore a general relationship over the entire time-series. A motion-influenced CVS of low-quality is detected, based on the residual between the input sequence and its neural representation with a cut-off value determined from the two-sigma rule of thumb over the training set., Result: Our experimental observations validated two claims: (i) in the learning environment of label-absence, assessment performance is achievable at a competitive level to the supervised setting, and (ii) the contextual information across a time series of CVS is advantageous for effectively realizing motion-induced unrealistic distortions in signal amplitude and morphology. We also investigated the capability as a pseudo-labeling tool to minimize human-craft annotation by preemptively providing strong candidates for motion-induced anomalies. Empirical evidence has shown that machine-guided annotation can reduce inevitable human-errors during manual assessment while minimizing cumbersome and time-consuming processes., Conclusion: The proposed method has a particular significance in the industrial field, where it is unavoidable to gather and utilize a large amount of CVS data to achieve high accuracy and robustness in real-world applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In this study, well-defined tungsten oxide (WO 3 ) nanowall (NW) thin films were synthesized via a controlled hot filament chemical vapor deposition (HFCVD) technique and applied for electrochemical detection of methylamine toxic substances. Herein, for the thin-film growth by HFCVD, the temperature of tungsten (W) wire was held constant at ~1450 °C and gasification was performed by heating of W wire using varied substrate temperatures ranging from 350 °C to 450 °C. At an optimized growth temperature of 400 °C, well-defined and extremely dense WO 3 nanowall-like structures were developed on a Si substrate. Structural, crystallographic, and compositional characterizations confirmed that the deposited WO 3 thin films possessed monoclinic crystal structures of high crystal quality. For electrochemical sensing applications, WO 3 NW thin film was used as an electrode, and cyclic voltammetry (CV) and linear sweep voltammetry (LSV) were measured with a wide concentration range of 20 μM~1 mM of methylamine. The fabricated electrochemical sensor achieved a sensitivity of ~183.65 μA mM -1 cm -2 , a limit of detection (LOD) of ~20 μM and a quick response time of 10 s. Thus, the fabricated electrochemical sensor exhibited promising detection of methylamine with considerable stability and reproducibility.

Background: Distal femur fractures are known to have challenging nonunion rates. Despite various available treatment methods aimed to improve union, optimal interventions are yet to be determined. Importantly, there remains no standard agreement on what defines radiographic union. Although various proposed criteria of defining radiographic union exist in the literature, there is no clear consensus on which criteria provide the most precise measurement. The use of inconsistent measures of fracture healing between studies can be problematic and limits their generalizability. Therefore, this systematic review aims to identify how fracture union is defined based on radiographic parameters for surgically treated distal femur fractures in current literature., Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, Medline, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science Core Collection databases were searched from inception to October 2022. Studies that addressed surgically treated distal femur fractures with reported radiographic union assessment were included. Outcomes extracted included radiographic definition of union; any testing of validity, reliability, or responsiveness; reported union rate; reported time to fracture union; and any functional outcomes correlated with radiographic union., Results: Sixty articles with 3,050 operatively treated distal femur fractures were included. Operative interventions included lateral locked plate (42 studies), intramedullary nail (15 studies), dynamic condylar screw or blade plate (7 studies), dual plate or plate and nail construct (5 studies), distal anterior-posterior/posterior-anterior screws (1 study), and external fixation with a circular frame (1 study). The range of mean follow-up time reported was 4.3 to 44 months. The most common definitions of fracture union included "bridging or callus formation across 3 of 4 cortices" in 26 (43%) studies, "bony bridging of cortices" in 21 (35%) studies, and "complete bridging of cortices" in 9 (15%) studies. Two studies included additional assessment of radiographic union using the Radiographic Union Scale in Tibial fracture (RUST) or modified Radiographic Union Scale in Tibial fracture (mRUST) scores. One study included description of validity, and the other study included reliability testing. The reported mean union rate of distal femur fractures was 89% (range 58%-100%). The mean time to fracture union was documented in 49 studies and found to be 18 weeks (range 12-36 weeks) in 2,441 cases. No studies reported correlations between functional outcomes and radiographic parameters., Conclusion: The current literature evaluating surgically treated distal femur fractures lacks consistent definition of radiographic fracture union, and the appropriate time point to make this judgement is unclear. To advance surgical optimization, it is necessary that future research uses validated, reliable, and continuous measures of radiographic bone healing and correlation with functional outcomes., Level of Evidence: Level IV. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/B65)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Although early life colonization of commensal microbes contributes to long-lasting immune imprinting in host tissues, little is known regarding the pathophysiological consequences of postnatal microbial tuning of cutaneous immunity. Here, we show that postnatal exposure to specific skin commensal Staphylococcus lentus (S. lentus) promotes the extent of atopic dermatitis (AD)-like inflammation in adults through priming of group 2 innate lymphoid cells (ILC2s). Early postnatal skin is dynamically populated by discrete subset of primed ILC2s driven by microbiota-dependent induction of thymic stromal lymphopoietin (TSLP) in keratinocytes. Specifically, the indole-3-aldehyde-producing tryptophan metabolic pathway, shared across Staphylococcus species, is involved in TSLP-mediated ILC2 priming. Furthermore, we demonstrate a critical contribution of the early postnatal S. lentus-TSLP-ILC2 priming axis in facilitating AD-like inflammation that is not replicated by later microbial exposure. Thus, our findings highlight the fundamental role of time-dependent neonatal microbial-skin crosstalk in shaping the threshold of innate type 2 immunity co-opted in adulthood., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: User engagement is crucial for digital therapeutics (DTx) effectiveness; due to variations in the conceptualization of engagement and intervention design, assessment and retention of engagement remain challenging., Objective: We investigated the influence of the perceived acceptability of experimental intervention components and satisfaction with core intervention components in DTx on user engagement, while also identifying potential barriers and facilitators to user engagement., Methods: We conducted a mixed methods study with a 2 × 2 factorial design, involving 12 outpatients with atopic dermatitis. Participants were randomized into 4 experimental groups based on push notification ("basic" or "advanced") and human coach ("on" or "off") experimental intervention components. All participants engaged in self-monitoring and learning courses as core intervention components within an app-based intervention over 8 weeks. Data were collected through in-app behavioral data, physician- and self-reported questionnaires, and semistructured interviews assessed at baseline, 4 weeks, and 8 weeks. Descriptive statistics and thematic analysis were used to evaluate user engagement, perceived acceptability of experimental intervention components (ie, push notification and human coach), satisfaction with core intervention components (ie, self-monitoring and learning courses), and intervention effectiveness through clinical outcomes., Results: The primary outcome indicated that group 4, provided with "advanced-level push notifications" and a "human coach," showed higher completion rates for self-monitoring forms and learning courses compared to the predetermined threshold of clinical significance. Qualitative data analysis revealed three key themes: (1) perceived acceptability of the experimental intervention components, (2) satisfaction with the core intervention components, and (3) suggestions for improvement in the overall intervention program. Regarding clinical outcomes, the Perceived Stress Scale and Dermatology Life Quality Index scores presented the highest improvement in group 4., Conclusions: These findings will help refine the intervention and inform the design of a subsequent randomized trial to test its effectiveness. Furthermore, this design may serve as a model for broadly examining and optimizing overall engagement in DTx and for future investigation into the complex relationship between engagement and clinical outcomes., Trial Registration: Clinical Research Information Service KCT0007675; http://tinyurl.com/2m8rjrmv., (©Hyerim Lee, Eung Ho Choi, Jung U Shin, Tae-Gyun Kim, Jooyoung Oh, Bokyoung Shin, Jung Yeon Sim, Jaeyong Shin, Meelim Kim. Originally published in JMIR Formative Research (https://formative.jmir.org), 09.02.2024.)

Background: Psoriasis is a chronic inflammatory skin disease with a Th17-skewed immune phenotype. Although it has been generally accepted that regulatory T cells (Tregs) in lesional psoriatic skin have functional impairment due to the local inflammatory microenvironment, the molecular properties of skin-homing psoriatic Tregs have not been well explored., Methods: We designed an extensive 39 marker mass cytometry (CyTOF) panel to deeply profile the immune landscape of skin-homing Tregs from 31 people with psoriasis stratified by psoriasis area severity index score as mild (n = 15) to moderate-severe (n = 16) and 32 healthy controls. We further validated the findings with an in-vitro chemokine-mediated Treg migration assay, immunofluorescent imaging of normal and psoriatic lesional skin and analysed public single-cell RNA-sequencing datasets to expand upon our findings into the local tissue microenvironments., Findings: We discovered an overall decrease in CLAhi Tregs and specifically, CLAhiCCR5+ Tregs in psoriasis. Functional markers CD39 and FoxP3 were elevated in psoriatic Tregs. However, CCR7 expression was significantly increased while CCR4 and CLA expression was reduced in psoriatic Tregs and CLAhi Tregs, which was associated with disease severity. Moreover, psoriatic Tregs revealed increased migratory capacity towards CCR7's ligands, CCL19/CCL21. Interrogation of public single-cell RNA sequencing data confirmed reduced expression of skin-trafficking markers in lesional-skin Tregs compared to non-lesioned skin, further substantiated by immunofluorescent staining., Interpretation: Psoriatic circulating Tregs showed an impaired skin-trafficking phenotype thus leading to insufficient suppression of ongoing inflammation in the lesional skin, expanding upon our current understanding of the impairment of Treg-mediated immunosuppression in psoriasis., Funding: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science and Information and Communications Technology (2020R1C1C1014513, 2021R1A4A5032185, 2020R1F1A1073692); and the new faculty research seed money grant of Yonsei University College of Medicine for 2021 (2021-32-0033)., Competing Interests: Declaration of interests The authors declare that they have no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: To quantify interobserver variation (IOV) in target volume and organs-at-risk (OAR) contouring across 31 institutions in breast cancer cases and to explore the clinical utility of deep learning (DL)-based auto-contouring in reducing potential IOV., Methods and Materials: In phase 1, two breast cancer cases were randomly selected and distributed to multiple institutions for contouring six clinical target volumes (CTVs) and eight OAR. In Phase 2, auto-contour sets were generated using a previously published DL Breast segmentation model and were made available for all participants. The difference in IOV of submitted contours in phases 1 and 2 was investigated quantitatively using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). The qualitative analysis involved using contour heat maps to visualize the extent and location of these variations and the required modification., Results: Over 800 pairwise comparisons were analysed for each structure in each case. Quantitative phase 2 metrics showed significant improvement in the mean DSC (from 0.69 to 0.77) and HD (from 34.9 to 17.9 mm). Quantitative analysis showed increased interobserver agreement in phase 2, specifically for CTV structures (5-19 %), leading to fewer manual adjustments. Underlying IOV differences causes were reported using a questionnaire and hierarchical clustering analysis based on the volume of CTVs., Conclusion: DL-based auto-contours improved the contour agreement for OARs and CTVs significantly, both qualitatively and quantitatively, suggesting its potential role in minimizing radiation therapy protocol deviation., (Copyright © 2023. Published by Elsevier Ltd.)

This study aimed to determine the optimal combination of three anti-inflammatory materials [i.e., Cervus nippon Temminck (CT), Angelica gigas Nakai (AN), and Rehmannia glutinosa (RG)] for the strongest anti-inflammatory potential. Eighteen combinations of the three materials were tested in LPS-stimulated RAW264.7 cells via assessing nitric oxide (NO). The best combination from in vitro studies was administered to LPS-treated C57BL/6J mice for five days. Subsequently, plasma metabolites were profiled by bioinformatics analyses and validations. As results, 2, 20, and 50 µg/mL of CT, AN, and RG (TM) were the most effective combination suppressing inflammation. In mice, TM mitigated hepatic inflammatory markers. Similarly, the metabolomics indicated that TM may suppress NF-κB signaling pathway, thereby alleviating hepatic inflammation. TM also decreased systemic and hepatic pro-inflammatory cytokines. Collectively, we found the optimal combination of TM for mitigating inflammation; thus further studies on safety, mechanisms, and clinical models are warranted for human applications., Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01476-x., Competing Interests: Competing interestsThe authors have no conflict of interest to disclose., (© The Korean Society of Food Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)