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Background: Post radiation nasopharyngeal necrosis (PRNN) invading the internal carotid artery (ICA) contributes to the death of 69.2–72.7% of PRNN patients. ICA occlusion is an effective treatment to avoid fatal bleeding, while some patients are intolerant. We present a novel method that allows for these patients without interrupting blood flow through the ICA. Methodology: This study enrolled patients with PRNN-invaded ICA who were not suitable for ICA occlusion from April 2020 to November 2022. ICA stent pretreatment was performed in the 36 patients and followed the endoscopic nasopharyngectomy (ENPG) or conservative treatment for PRNN. We report the survival outcome and incidence of complications after stent implantation and compare the survival outcomes of ENPG and conservative treatment for PRNN followed by stent implantation. Results: ICA stent pretreatment was performed in the 36 enrolled patients, among which 14 underwent ENPG, and 22 received conservative treatment. 27.8% patients died after a median follow-up of 15 months. The Kaplan-Meier estimates of overall survival were higher in the ENPG group than in the conservative treatment group. Karnofsky performance status (KPS) was significantly higher in the ENPG group than in the non-ENPG group. Conclusions: The innovative application of ICA stents is a promising treatment to improve outcomes in patients with PRNN invading the ICA who are unsuitable for ICA embolization, especially when followed by endoscopic surgery. However, methods to avoid postoperative cerebral ischemia and nasopharyngeal hemorrhage still require further study.

Introduction Fibrofatty plaque burden (FFB) is a high-risk, vulnerable plaque feature comprised of an atheromatous core and fibrous cap with increased risk of coronary artery disease (CAD) [1]. Psoriasis (PSO) is a chronic inflammatory disease linked with atherosclerotic risk and premature cardiovascular disease, driven in part by vulnerable plaque rupture [2,3]. Machine learning (ML) previously showed the prognostic value of FFB in predicting 5-year risk of cardiac-related mortality in patients with CAD [4]. Whether ML can predict FFB in psoriasis is understudied. Purpose To use ML to identify top determinants of FFB by CCTA in PSO. Methods 320 consecutive participants with psoriasis were recruited as part of an ongoing cohort study, of whom 307 had FFB analyzed with coronary computed tomography angiography (CCTA) and quantified by QAngio CT (Medis, The Netherlands). 140 out of 182 potential determinants were subjected to ML algorithms analyzed by random forest and validated by 5-fold cross validation to select the top determinants based on R-square criteria. Lipid concentration and size were measured by nuclear magnetic resonance (NMR) and sdLDL-C was calculated by Sampson's formula. Results The top 21 determinants of FFB at baseline were grouped into 3 categories: cardiometabolic risk factors (BMI, sex, DBP, mean arterial pressure, exercise, heart rate, glucose, anxiety, psoriasis disease duration), clinical measurements (basophils, platelets, hemoglobin, RBC, alkaline phosphatase, ALT, creatinine, neutrophil-to-lymphocyte ratio), and lipoproteins (LDL particle size, apolipoprotein A1, apolipoprotein B-to-A1 ratio, calculated sdLDL-C). Conclusion ML confirmed that FFB strongly correlates with cardiometabolic risk factors, clinical measurements, and lipoproteins. Further investigations into these top determinants of FFB over time may provide insight into potential therapeutic interventions that decrease cardiovascular risk in patients with chronic inflammatory diseases and should be validated in larger studies. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): This study was supported by the National Heart, Lung and Blood Institute (NHLBI) IntramuralResearch Program (ZIA-HL-06193). This research was made possible through the NIH MedicalResearch Scholars Program, a public-private partnership supported jointly by the NIH andcontributions to the Foundation for the NIH from the Doris Duke Charitable Foundation,Genentech, the American Association for Dental Research, the Colgate-Palmolive Company, andother private donors.

The species Hyblaea solomonensis Buchsbaum & Chen, sp. n. is described from the Solomon Islands. The species is to be placed in the Hyblaea constellata Guenée, 1852 - species group due to its similarity in the external morphological features, as well as in the genital structures. The new species differs from all other species in this group.

In recent years, many researchers have taken serum ubiquitin c-terminal hydrolase (Uch-L1) as an indicator of post-traumatic brain injury and associated it with cognitive impairment. Alzheimer's disease is characterized by cognitive impairment and energy metabolism disorders. The purpose of this study was to detect whether serum Uch-L1 is related to cognition and brain energy metabolism in healthy people, and to explore whether it can be used as an early blood marker of Alzheimer's disease.In this prospective cohort study, adult outpatients from a Grade 3A hospital were recruited. They completed the 18F-FDG-PET/CT examination in the nuclear medicine department and were screened by the Mini Mental State scale (MMSE) and the Montreal Cognitive Assessment scale (MoCA). Blood samples were collected from all outpatients to detect the concentration of serum Uch-L1, and the mean standard uptake value (SUVmean) of energy metabolism in the hippocampus during PET/CT examination was collected.A total of 37 participants, 14 participants with cognitive impairment (MMSE score27) and 23 controls (MMSE score 27-30) were included. There was a significant difference in the SUVmean of the hippocampus between the cognitive impairment group and the normal control group (p0.05). There was a significant correlation between the SUVmean of the hippocampus and the total score of MMSE in all participants [r = 0.439, 95% CI: (0.139-0.668), p = 0.007]. There were also significant correlations between serum Uch-L1 and MMSE. Based on the significant differences of demographic variables between groups, we conducted a multivariate linear regression analysis of MMSE cognitive scores based on age (X1), length of education (X2) and SUVmean of hippocampus (X3). The regression equation is as follows: Y = 25.709-0.072 X1 + 0.422 X2 + 0.232 X3.Brain cognitive ability is closely related to energy metabolism and serum Uch-L1 concentration, so serum Uch-L1 may become a blood marker for extensive screening of dementia in the future. We look forward to the introduction of a more accurate and low-cost method for detecting serum Uch-L1 concentration.

The BCR recognizes foreign Ags to initiate humoral immunity that needs isotype-switched Abs generated via class switch recombination (CSR); however, stimulating the BCR in the absence of costimulation (e.g., CD40) does not induce CSR; thus, it remains elusive whether and how the BCR induces CSR mechanistically. Autoreactive B cells can maintain anergy via unresponsiveness of their BCRs to self-antigens. However, it remains unknown what molecule(s) restrict BCR signaling strength for licensing BCR-induced CSR and whether deficiency of such molecule(s) disrupts autoreactive B cell anergy and causes B cell–mediated diseases by modulating BCR signaling. In this study, we employ mouse models to show that the BCR’s capacity to induce CSR is restrained by B cell–intrinsic checkpoints TRAF3 and TRAF2, whose deletion in B cells enables the BCR to induce CSR in the absence of costimulation. TRAF3 deficiency permits BCR-induced CSR by elevating BCR-proximal signaling intensity. Furthermore, NF-κB2 is required for BCR-induced CSR in TRAF3-deficient B cells but not for CD40-induced or LPS-induced CSR, suggesting that TRAF3 restricts NF-κB2 activation to specifically limit the BCR’s ability to induce CSR. TRAF3 deficiency also disrupts autoreactive B cell anergy by elevating calcium influx in response to BCR stimulation, leading to lymphoid organ disorders and autoimmune manifestations. We showed that TRAF3 deficiency-associated autoimmune phenotypes can be rectified by limiting BCR repertoires or attenuating BCR signaling strength. Thus, our studies highlight the importance of TRAF3-mediated restraint on BCR signaling strength for controlling CSR, B cell homeostasis, and B cell–mediated disorders.

Cancer cells can evade immune recognition by losing major histocompatibility complex (MHC) class I. Hence, MHC class I-negative cancers represent the most challenging cancers to treat. Chemotherapeutic drugs not only directly kill tumors but also modulate the tumor immune microenvironment. However, it remains unknown whether chemotherapy-treated cancer cells can activate CD8 T cells independent of tumor-derived MHC class I and whether such MHC class I-independent CD8 T-cell activation can be exploited for cancer immunotherapy. Here, we showed that chemotherapy-treated cancer cells directly activated CD8 T cells in an MHC class I-independent manner and that these activated CD8 T cells exhibit virtual memory (VM) phenotypes. Consistently, in vivo chemotherapeutic treatment preferentially increased tumor-infiltrating VM CD8 T cells. Mechanistically, MHC class I-independent activation of CD8 T cells requires cell–cell contact and activation of the PI3K pathway. VM CD8 T cells contribute to a superior therapeutic effect on MHC class I-deficient tumors. Using humanized mouse models or primary human CD8 T cells, we also demonstrated that chemotherapy-treated human lymphomas activated VM CD8 T cells independent of tumor-derived MHC class I. In conclusion, CD8 T cells can be directly activated in an MHC class I-independent manner by chemotherapy-treated cancers, and these activated CD8 T cells may be exploited for developing new strategies to treat MHC class I-deficient cancers.

Immunotherapy has been applied successfully to treat B-cell lymphomas in preclinical models or clinical settings. However, immunotherapy resistance is a major challenge for B-cell lymphoma treatment. To overcome this issue, combinatorial therapeutic strategies have been pursued to achieve a better efficacy for treating B-cell lymphomas. One of such strategies is to combine immunotherapy with histone deacetylase (HDAC) inhibitors. HDAC inhibitors can potentially increase tumor immunogenicity, promote anti-tumor immune responses, or reverse immunosuppressive tumor environments. Thus, the combination of HDAC inhibitors and immunotherapy has drawn much attention in current cancer treatment. However, not all HDAC inhibitors are created equal and their net effects are highly dependent on the specific inhibitors used and the HDACs they target. Hence, we suggest that optimal treatment efficacy requires personalized design and rational combination based on prognostic biomarkers and unique profiles of HDAC inhibitors. Here, we discuss the possible mechanisms by which B-cell lymphomas acquire immunotherapy resistance and the effects of HDAC inhibitors on tumor cells and immune cells that could help overcome immunotherapy resistance.

With molecular beam epitaxy and topotactic chemical reaction, we prepared NdFeAs(O,H) epitaxial thin films with various hydrogen concentrations on 5{\deg} vicinal cut MgO substrates. By measuring the resistivities along the longitudinal and transversal directions, the ab plane and the c axis resistivities (\{rho}_ab and \{rho}_c) were obtained. The resistivity anisotropy {\gamma}_\{rho}=\{rho}_c \ \{rho}_ab of NdFeAs(O,H) with various hydrogen concentrations was compared with that of NdFeAs(O,F). At the H concentrations which led to superconducting transition temperatures Tc over 40 K, {\gamma}_\r{ho} recorded ~100-150 at 50 K. On the other hand, a low {\gamma}_\{rho} value of 9 was observed with the mostly doped sample. The exponent \{beta} of the ab plane resistivity obtained by fitting a power law expression \{rho}_{ab}(T)=\{rho}_0+AT^\{beta} to the data was close to unity down to low temperature in the vicinity where the second antiferromagnetic phase locates, which may be related to the quantum critical point discussed at the over-doped side of the phase diagram., Comment: Appeared in Physical. Rev. Materials

This study presents that ICVAX, a PD1-based DNA vaccine against HIV-1, could induce broad and polyfunctional T cell responses against different HIV-1 subtypes. ICVAX encodes a recombinant antigen consisting of the human soluble PD1 domain fused with two mosaic Gag-p41 antigens.

This study was performed to evaluate the subjective and objective functional outcomes of patients who had undergone submandibular gland-sparing neck dissection. All data were obtained from patients treated in a single hospital. Seventy-seven patients who had undergone complete submandibular gland sparing (CSGS) were included in the study. Cancer prognosis items were recorded. The subjective outcomes included patient self-evaluation of mouth dryness and the evaluation of the presence of saliva secretion following the application of digital pressure. Saliva scintigraphy served as the objective test. Self-reported xerostomia was compared between the CSGS patients and a control group of patients who had undergone unilateral submandibular gland removal (USGR; n = 74). In the CSGS group, local recurrence occurred in 3.8% of the 80 cancer sites, and neck recurrence occurred in 5.9% of neck dissection sites. Regarding the subjective measurements, 7.0% of the CSGS patients reported xerostomia and 91.9% demonstrated saliva secretion by digital pressure. Scintigraphy revealed actively secreting glands, with 42.9% of them showing normal gland function; none of the patients had severe xerostomia. The relative risk of dry mouth was significantly higher in the USGR patients than in the CSGS patients (P 0.001). Submandibular gland sparing during neck dissection was found to result in satisfactory saliva secretion, with a relatively small risk of local or neck recurrence.

Coronavirus disease 2019 (COVID-19) spread around the world in 2020. Abnormal pulmonary function and residual CT abnormalities were observed in COVID-19 patients during recovery. Appropriate rehabilitation training is around the corner. The correlation between spirometric impairment and residual CT abnormality remains largely unknown.A cross-sectional study conducted on the pulmonary function of 101 convalescent COVID-19 patients before discharge. Multivariate analysis was used to establish a scoring system to evaluate the spirometric abnormality based on residual chest CT.Lung consolidation area25% and severe-type COVID-19 were two independent risk factors for severe pulmonary dysfunction. Besides, a scoring system was established. People scoring more than 12 points have more chances (17 times) to get severe pulmonary function impairment before discharge.For the first time, a chest CT characteristics-based grading system was suggested to predict the pulmonary dysfunction of COVID-19 patients during convalescence in this study. This study may provide suggestions for pulmonary rehabilitation.

Background While immune checkpoint inhibitors (ICI) were approved for head and neck squamous cell carcinomas (HNSCCs), the response rate remains relatively low. Mechanisms underlying ICI unresponsiveness versus sensitivity are not fully understood. Method To better delineate differential responses to ICI treatment, we employed mouse SCC models, termed KPPA tumors that were caused by deleting p53 and hyperactivating PIK3CA, two most frequently mutated genes in human HNSCCs. We transplanted two KPPA tumor lines (TAb2 versus TCh3) into C57BL/6 recipients and examined the immune tumor microenvironment using flow cytometry. Furthermore, we employed single-cell RNA sequencing to identify the difference in tumor infiltrating lymphocytes (TILs). Results We found that different KPPA tumors exhibited heterogeneous immune profiles pre-existing treatment that dictated their sensitivity or unresponsiveness to anti-PD-L1. Unresponsive TAb2 tumors were highly enriched with functional tumor-associated macrophages (TAMs), especially M2-TAMs. In contrast, sensitive TCh3 tumors contained more CD8 TILs with better effector functions. TAb2 tumor cells drastically expanded F4/80+ TAMs from bone marrow precursors, requiring CSF1 and VEGF. Consistently, a higher combined expression of VEGF-C and CSF1 predicts worse survival in PIK3CAAmp/TP53Mutated HNSCC patients. Unresponsive TAb2 tumors upregulated distinct signaling pathways that correlate with aggressive tumor phenotypes. While anti-PD-L1 did not affect the TME of TAb2 tumors, it significantly increased the number of CD8 TILs in TCh3 tumors. Conclusions We uncovered tumor-intrinsic differences that may underlie the differential responses to ICI by establishing and employing two SCC tumor lines, TAb2 vs. TCh3, both of which harbor TP53 deletion and PIK3CA hyperactivation. Our study indicates the limitation of stratifying cancers according to their genetic alterations and suggests that evaluating HNSCC tumor-intrinsic cues along with immune profiles in the TME may help better predict ICI responses. Our experimental models may provide a platform for pinpointing tumor-intrinsic differences underlying an immunosuppressive TME in HNSCCs and for testing combined immunotherapies targeting either tumor-specific or TAM-specific players to improve ICI efficacy.

Head and neck cancers are a heterogeneous group of tumors that are highly aggressive and collectively represent the sixth most common cancer worldwide. Ninety percent of head and neck cancers are squamous cell carcinomas (HNSCCs). The tumor microenvironment (TME) of HNSCCs consists of many different subsets of cells that infiltrate the tumors and interact with the tumor cells or with each other through various networks. Both innate and adaptive immune cells play a crucial role in mediating immune surveillance and controlling tumor growth. Here, we discuss the different subsets of immune cells and how they contribute to an immunosuppressive TME of HNSCCs. We also briefly summarize recent advances in immunotherapeutic approaches for HNSCC treatment. A better understanding of the multiple factors that play pivotal roles in HNSCC tumorigenesis and tumor progression may help define novel targets to develop more effective immunotherapies for patients with HNSCC.

Ozone has been widely used for water treatment all over the world. This study investigated the effects of pre-ozonation on N-nitrosodimethylamine (NDMA) formation from four drinking-water sources during subsequent chloramination. Moreover, relationships between NDMA and water-quality parameters (dissolved organic carbon (DOC), dissolved organic nitrogen (DON), hydrophobic fractions (HFs), positive-charged fractions (PCFs), ultraviolet absorbance at 254 nm wavelength (UV254), ammonia) were determined. The results indicated that NDMA formed directly by ozonation, but the concentrations (5.7–37.8 ng/L) were much lower than during chloramination (25.3–193 ng/L). Pre-ozonation slightly augmented NDMA formation from reservoirs, while it facilitated NDMA precursor destruction in the lake and river. The river was rich in organic matter, its DOC concentration was up to 4.97 mg/L, while the DON/DOC ratio (4.68%) was low; the lake possessed the most organic nitrogen and highest DON/DOC ratio (10.76%). HFs in reservoir #2 were low (1.27 mg/L), and the HFs/DOC ratio was especially high (73.4%). PCFs constituted 48.5–72.1% of DOC. UV254 values were in the range 0.081–0.175 cm−1. The ammonia concentration was high in the lake water (0.29 mg/L), while that in reservoir #2 was only 0.08 mg/L. There was a strong correlation between NDMA formation and the removal of ammonia, DON and PCFs.

外科在初治鼻咽癌中的价值一直以来存在争议。初治鼻咽癌的外科发展经历了3个阶段：鼻外径路外科辅助治疗、微创外科辅助治疗、微创外科根治治疗。前2个阶段是在放化疗之前，先进行鼻咽原发灶切除术，目的是提高疗效或通过术后减量放射治疗降低放射毒性。第3阶段指针对拒绝放射治疗的“极早期”Ⅰ期鼻咽癌患者施行微创手术，彻底切除鼻咽原发灶，术后一般不进行放化疗，避免了放射性损伤，使“极早期”鼻咽癌多一个治疗选择。.

OBJECTIVE: To investigate the effects of multi-walled carbon nanotubes (MWCNTs) with different length or chemical modification on endothelial cell activation and to explore the role of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. METHODS: MWCNTs were characterized by dynamic light scattering (DLS) after being suspended in culture medium. The immortalized mouse cerebral microvascular endothelial cell line b.End3 was treated with short MWCNTs (S-MWCNT, 0.5 to 2 μm), long MWCNTs (L-MWCNT, 10 to 30 μm) and the above long MWCNTs functionalized by carboxyl-(L-MWCNT-COOH), amino-(L-MWCNT-NH(2)) or hydroxyl-(L-MWCNT-OH) modification. Cytotoxicity of MWCNTs in b.End3 cells was determined by cell counting kit-8 (CCK-8) assay and lactate dehydrogenase (LDH) release assay, and non-toxic low dose was selected for subsequent experiments. Effects of all types of MWCNTs on the endothelial activation of b.End3 were determined by the measurement of vascular cell adhesion molecule-1 (VCAM-1) concentration in cell supernatant and adhesion assay of human monocytic cell line THP-1 to b.End3.To further elucidate the mechanism involved, the protein expressions of nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3(NLRP3) in cells treated with S-MWCNT, L-MWCNT and L-MWCNT-COOH were measured by Western blot. RESULTS: At a higher concentration (125 μg/cm(2)) and treated for 24 h, all types of MWCNTs significantly inhibited viability of b.End3 cells. At a sub-toxic concentration (6.25 μg/cm(2)), all types of MWCNTs treated for 12 h significantly induced the activation of b.End3 cells, as evidenced by the elevated VCAM-1 release and THP-1 adhesion. Compared with S-MWCNT, L-MWCNT significantly promoted endothelial cell activation. L-MWCNT and L-MWCNT-COOH activated b.End3 cells to a similar extent. Furthermore, treatment with S-MWCNT, L-MWCNT and L-MWCNT-COOH increased NLRP3 expression in a time-dependent manner at 6.25 μg/cm(2). Compared with S-MWCNT, cells treated with L-MWCNT for 4 h and 12 h exhibited significantly increased protein expressions of NLRP3. However, no significant differences were detected in the level of NLRP3 protein in cells treated with L-MWCNT and L-MWCNT-COOH. CONCLUSION: Compared with the surface chemical modification, length changes of MWCNTs exerted more influence on endothelial cell activation, which may be related to the activation of NLRP3 inflammasome. Our study contributes further understanding of the impact of MWCNTs on endothelial cells, which may have implications for the improvement of safety evaluation of MWCNTs.

HIV-1 functional cure requires sustained viral suppression without antiretroviral therapy. While effector-memory CD8+ T lymphocytes are essential for viremia control, few vaccines elicit such cellular immunity that could be potently recalled upon viral infection. Here, we investigated a program death-1 (PD1)-based vaccine by fusion of simian immunodeficiency virus capsid antigen to soluble PD1. Homologous vaccinations suppressed setpoint viremia to undetectable levels in vaccinated macaques following a high-dose intravenous challenge by the pathogenic SHIVSF162P3CN. Poly-functional effector-memory CD8+ T cells were not only induced after vaccination, but were also recalled upon viral challenge for viremia control as determined by CD8 depletion. Vaccine-induced effector memory CD8+ subsets displayed high cytotoxicity-related genes by single-cell analysis. Vaccinees with sustained viremia suppression for over two years responded to boost vaccination without viral rebound. These results demonstrated that PD1-based vaccine-induced effector-memory CD8+ T cells were recalled by AIDS virus infection, providing a potential immunotherapy for functional cure., Author summary HIV-1/AIDS remains a major global pandemic although treatment regimen has improved. Identifying efficacious vaccines and therapeutics to achieve long-term viral control with very low/undetectable plasma viral loads in the absence of antiretroviral therapy, a status known as functional cure, would be highly beneficial. We previously demonstrated that antigens fused to a soluble program death-1 (PD1) domain could effectively bind and be cross-presented by dendritic cells that constitutively expressed PD1 ligands. When applied in the form of DNA vaccination, this antigen-targeting strategy was highly immunogenic in mice. Here, we investigated the efficacy of the PD1-based DNA vaccine approach against pathogenic simian-human immunodeficiency virus challenge in rhesus monkeys. Our results showed that homologous PD1-based DNA vaccinations induced highly functional effector-memory CD8+ T cells carrying a unique cytotoxicity gene expression profile. These T cells actively supressed viremia in monkeys and were re-activated via boost vaccination at 2 years after viral challenge without viral rebound. In summary, our study demonstrates the potential application of PD1-based DNA vaccination to control AIDS virus infection.

The Fan-out Panel Level Packaging model after the molding process is established. We simplify the complex curing reaction of epoxy molding compound with equivalent thermal expansion coefficient method. We successfully use finite element method to build different geometric Fan-out Panel Level Packaging model as training dataset for machine learning. In the end, we used the modified Convolution Neural Network to estimate the amount of fan-out panel-level package warpage under different geometries. To avoid local minimum, Particle Swarm Optimization, PSO, is introduced for neural network parameter.

Introduction/Objective Pancreatic metastases are rare, and the most common neoplasms are carcinomas from the kidney, lung, and breast. Methods/Case Report We present four cases of breast ductal carcinoma in patients with metastases to the pancreas diagnosed by endoscopic ultrasound guided fine needle aspiration (EUS-FNA). The four female patients ranged from 37 to 64 years in age. Three patients had breast cancer histories, ranging from 1 to 21 years. The patient without cancer history was found to have breast mass also. Two patients had triple negative breast ductal carcinoma. The breast cancer biomarkers on the other two patients showed ER+, PR-, Her2 3+, and ER-, PR-, Her2 3+, respectively. Two patients had histories of metastatic breast cancer involving bone, liver and brain. All patients presented with symptoms associated with pancreatic mass. By imaging, solitary pancreatic head masses were found in three patients, ranging from 2.4 to 3.7 cm. One patient had two pancreatic masses (head, 2.6 cm; body, 2.9 cm). EUS-FNAs targeting the pancreatic head masses were performed on the four patients. Cell blocks were available for all except one (due to limited cells), which had subsequent histology diagnosis. Results (if a Case Study enter NA) FNAs demonstrated loosely cohesive tumor cells with enlarged, hyperchromatic nuclei, occasional prominent nucleoli, and occasional intracytoplasmic vacuoles, morphologically and immunohistochemically (CK7 +, GCDFP-15 focally +, CA19.9 -, biomarkers similar to primary tumors) consistent with breast primary. Follow-up revealed three patients expired one month, 2.5 years, and 5 years post-diagnosis, respectively. One patient without prior cancer history has been stable for 7 years. Conclusion Our study demonstrates the clinicopathological features of four cases of breast ductal carcinoma metastasized to the pancreas. We emphasize the important role of EUS-FNA for diagnoses of pancreas metastases. The finding of two of four cases with triple negative biomarkers may raise the importance of close follow-up in these patients for pancreatic metastasis.

BackgroundIn contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity.Methods and resultsCLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia, and Africa in 2009–2010, and followed up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischaemia, or prior revascularization procedure.Among 32 694 patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to ∼60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome (cardiovascular death, myocardial infarction, or stroke) with an adjusted hazard ratio of 1.28 (95% confidence interval 1.18, 1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest.ConclusionIn patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes.ClinicalTrials identifierISRCTN43070564

Squamous cell carcinoma (SCC) is the second commonest type of skin cancer, and SCCs make up about 90% of head and neck cancers (HNSCCs). HNSCCs harbor two frequent molecular alterations, namely, gain-of-function alterations of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and loss-of-function mutations of tumor protein p53 (TP53). However, it remains poorly understood whether HNSCCs harboring different genetic alterations exhibit differential immune tumor microenvironments (TME). It also remains unknown whether PIK3CA hyperactivation and TP53 deletion can lead to SCC development spontaneously. Here, we analyzed the Cancer Genome Atlas (TCGA) datasets of HNSCCs and found that patients with both PIK3CA and TP53 alterations exhibited worse survival, significantly lower CD8 tumor infiltrating lymphocytes (TILs) and higher M0 macrophages than other controls. To better model human tumorigenesis, we deleted TP53 and constitutively activated PIK3CA in mouse keratin-15-expressing stem cells, which leads to the spontaneous development of multilineage tumors including SCCs, termed Keratin-15-p53-PIK3CA (KPPA) tumors. KPPA tumors were heavily infiltrated with myeloid-derived suppressor cells (MDSCs), with a drastically increased ratio of polymorphonuclear-MDSC (PMN-MDSC) versus monocytic-MDSC (M-MDSC). CD8 TILs expressed more PD-1 and reduced their polyfunctionality. Overall, we established a genetic model to mimic human HNSCC pathogenesis, manifested with an immunosuppressive TME, which may help further elucidate immune evasion mechanisms and develop more effective immunotherapies for HNSCCs.

Surgical treatment for stage IV breast cancer remains controversial. Therefore, we aimed to further explore the impact of surgery on survival in patients with stage IV breast cancer using the Surveillance, Epidemiology, and End Results (SEER) database. We selected 3,822 patients diagnosed with stage IV breast cancer from 2010 to 2012 in the SEER database who were divided into surgery and non-surgery groups. We assessed the breast cancer-specific survival (BCSS) and overall survival (OS) of the two groups using Kaplan-Meier plots and Cox proportional hazard regression models. In addition, we performed stratification analyses of breast subtype, tumor size and status of distant metastasis to identify the effects of these factors on surgical outcomes. The median survival times were 30 and 24 months in the surgery and non-surgery groups, respectively. The Kaplan-Meier curves showed that the surgery group survived longer than the non-surgery group. The hazard ratios (HR) of the surgery group were 0.504 for BCSS and 0.507 for OS (P Citation Format: Song C-G, Lin Y-X, Zhang J, Zeng Q, Chen M-Y, Chen L-L, Wang X-X, Chen Q-X. Impact of surgery on survival in patients with stage IV breast cancer: A population-based study from the SEER database [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-27.

Background Referrals from primary care to rheumatology services have increased significantly in recent years. Many of these patients have non-inflammatory conditions, usually with pain, and may require specialist treatment such as physiotherapy or psychological intervention. If patients could be effectively triaged at the point of referral, clinical services could be better aligned to patients’ needs, but referrals do not always contain enough information to triage patients effectively. Validated patient-completed questionnaires are available which are designed to aid patient identification, for instance for fibromyalgia and inflammatory back pain. We designed an electronic questionnaire for patients to complete prior to their first attendance to inform the clinical consultation and to explore whether they could be more appropriately triaged to specialist clinics. Methods We constructed a questionnaire consisting of the modified ACR diagnostic questionnaire for fibromyalgia, the ASAS screening questionnaire for inflammatory back pain, a validated questionnaire for identification of patients with inflammatory arthritis, PHQ8 (depression) and GAD 7 (anxiety). The questionnaire contained conditional branching to ensure that only relevant questions were answered. A user-centred design approach was taken to optimise patient experience and response rates. A link to the questionnaire was sent via SMS to unselect new patients shortly after receipt of a referral from their GP. Completed questionnaires were imported into the hospital record. Results Initial response rates were around 35%. Through a process of continuous iteration informed by user feedback this increased to 80% over a 4 months period. Key factors in optimisation were the appearance of the text (displaying from ‘NHS’ rather than an apparently random number), the language which was used to maximise patients perception of the value of completion, the use of patients’ first names in the SMS and the content and timing of automated reminder messages. Over a 4 month after optimisation 664 patients completed the questionnaire. Of these 38% and 25% scored in the moderate-severe ranges for depression and anxiety respectively. 74% of patients met the paper criteria for fibromyalgia (which is not diagnostic in itself prior to clinical assessment). Of those patients scoring in the moderate-severe ranges for depression and anxiety, 92% and 88% respectively met the questionnaire criteria for fibromyalgia. Conclusion This work suggests that collecting information prior to the first appointment can add value to the process. In our department screening tools for psychological distress, widespread pain and somatisation are used to inform the consultation. We are currently analysing this data against the patients’ final diagnoses. Combination of screening tools may enable patients to be stratified with enough predictive value into specific pathways for inflammatory and non-inflammatory conditions, some of which could be community-based. We will be applying machine learning tools to determine the optimum predictive value of these questionnaires in combination. Disclosures W. Chen None. M. Thrower None. T. Garrood None.

An O 2p itinerant-electron model for magnetic oxides, which is similar to the O 2p hole-carrier model proposed by Alexandrov et al. [Phys. Rev. Lett. 96 (2006) 117003], was used to explain the magnetic and electrical-transport properties of two series of samples with the nominal composition La 1− y Ba y Mn 1 − x Fe x O 3 (0.00 ≤ x ≤ 0.20; y = 0.15, 0.40). The samples were prepared using the sol–gel method, and X-ray diffraction patterns showed that all samples were single-phase ABO 3 perovskite structures. The magnetic and electrical-transport properties of the samples were characterized. Interesting phenomena were observed for the magnetic moment, μ obs , of the samples at 10 K: μ obs of the samples with y = 0.15 decreased approximately linearly when the Fe-doping level was increased from zero to x = 0.2. However, there was a characteristic Fe-doping level, x C = 0.10, for the samples with y = 0.40. When x ≤ x C , μ obs decreased very slowly; when x > x C , μ obs decreased rapidly. These interesting phenomena suggest that the samples had a canted magnetic structure, but the cant angle of the samples with y = 0.15 was smaller than that of the samples with y = 0.40. These magnetic structures were further confirmed by the electrical-transport properties of the samples.

Chirality is a fundamental property of biochemical molecules and often dictates their functionality. Conventionally, molecular chirality is studied by linear optical activity effects. However, poor contrast and artifacts due to anisotropy limit such studies to purified molecules not in their original microenvironments, potentially modifying their conformations. Here, we demonstrate that resonant second-harmonic-generation circular dichroism (SHG-CD) microscopy provides not only tissue imaging with improved chiral contrast, but also molecular chirality information of collagen, the most abundant protein in mammals, at its native state. Gradual protein denaturation shows that the resonant SHG-CD is dominated by the microscopic chirality related to collagen structures smaller than the spatial resolution of the microscope, i.e. to the protein conformation and microfibril organization, while the effects due to fiber orientation/anisotropy are mostly responsible of the non-resonant part. This result agrees well with a simple and intuitive model we propose to explain the resonant behavior and the consequent numerical SHG-CD simulations. Our results demonstrate the possibility to study molecular chirality in intact bio-tissues with nearly-unity contrast and sub-micrometer resolution, which will be useful in a broad range of biological and biochemical applications acceptedVersion

Powder samples of TixCo1−xFe2O4 (0.0 ≤ x ≤ 0.4) and TixMn1−xFe2O4 (0.0 ≤ x ≤ 0.3) were synthesized using a conventional method for preparing ceramics. X-ray diffraction analysis confirmed that the samples consisted of a single phase with a cubic (A)[B]2O4 spinel structure. The average molecular magnetic moment (μexp) measured at 10 K decreased monotonically with increasing x for two series of samples. According to previous investigations, Ti2+ and Ti3+ cations are present in these ferrites, but there are no Ti4+ cations; the magnetic moments of the Ti2+, Ti3+, and Mn3+ cations are assumed to couple antiferromagnetically with those of the Mn2+, Co2+, Co3+, Fe2+, and Fe3+ cations whenever they are at the (A) or [B] sublattice. The dependence of μexp of the two series of samples on the doping level x was fitted using a quantum-mechanical potential barrier, and the cation distributions in the two series of samples were obtained.

A model with two channels of electrical transport (TCET) for perovskite manganites is proposed, and it is described by an equivalent device with two current-carrier channels. In one channel, there is a spin-independent resistor (R3) with an equivalent resistivity of ρ3. In the other channel, there are two spin-dependent resistors in series (R1 and R2) with an equivalent resistivity of ρ1 + ρ2. The component ρ1 includes residual resistivity and the resistivity contributed by crystal-lattice scattering. The other component of the equivalent resistivity, ρ2, originates from the spin orientations of the itinerant electrons and the local electrons of the outer O 2p and Mn 3d orbits that deviate from the orientation of their ground states when the test temperature is close to the Curie temperature. Using this model, we fitted the experimental curves of the resistivity versus test temperature for single-crystalline La1−xSrxMnO3 (0.00 ≤ x ≤ 0.40) and polycrystalline La0.6Sr0.4Mn1−xFexO3 (0.00 ≤ x ≤ 0.30). In addition, we investigated the effects of the fraction of the antiferromagnetic phase, scattering at the crystallite interfaces, and the crystal-cell constants on the samples' resistivity. The physical mechanism of the TCET model was explained using an O 2p itinerant-electron model, which has been used in other studies to explain the magnetic ordering of several series of spinel ferrites and perovskite manganites.