An immunosuppressive vascular niche drives macrophage polarization and immunotherapy resistance in glioblastoma.

Cancer immunity is subjected to spatiotemporal regulation by leukocyte interaction with neoplastic and stromal cells, contributing to immune evasion and immunotherapy resistance. Here, we identify a distinct mesenchymal-like population of endothelial cells (ECs) that form an immunosuppressive vascular niche in glioblastoma (GBM). We reveal a spatially restricted, Twist1/SATB1-mediated sequential transcriptional activation mechanism, through which tumor ECs produce osteopontin to promote immunosuppressive macrophage (Mφ) phenotypes. Genetic or pharmacological ablation of Twist1 reverses Mφ-mediated immunosuppression and enhances T cell infiltration and activation, leading to reduced GBM growth and extended mouse survival, and sensitizing tumor to chimeric antigen receptor T immunotherapy. Thus, these findings uncover a spatially restricted mechanism controlling tumor immunity and suggest that targeting endothelial Twist1 may offer attractive opportunities for optimizing cancer immunotherapy.

Clinical outcomes of Epstein-Barr virus (EBV)-associated metastatic and locally advanced unresectable gastric cancers (GCs) in patients receiving first-line fluoropyrimidine and platinum (FP) doublet chemotherapy.

BACKGROUND: Epstein-Barr virus-associated gastric cancer (EBVaGC) is a distinct molecular subgroup showing excellent outcomes after surgery for localized disease. Prominent immune cell infiltration in EBVaGC reflects the immunogenicity of Epstein-Barr virus (EBV) and, as suggested by some investigators, responsiveness to immune checkpoint inhibitors in the palliative setting. However, few data are available on the prevalence, clinical characteristics, and prognosis of EBVaGC patients receiving palliative cytotoxic chemotherapy. METHODS: In this retrospective study, we identified 1061 patients with metastatic, recurrent, or locally advanced unresectable gastric cancer (GC) who started first-line fluoropyrimidine/platinum (FP) doublet chemotherapy with or without trastuzumab from January 2015 to August 2018. For 766 patients with available tumor tissue, the presence of EBV in cancer cells was evaluated by EBV-encoded RNA in situ hybridization and correlated with clinical characteristics and treatment outcomes. RESULTS: Among the patients evaluated (n = 766), 40 (5.0%) were EBV-positive. EBVaGC was associated with male sex (p = 0.009) and lower neutrophil-lymphocyte ratio (NLR < 2.46, p = 0.03). Efficacy of first-line FP chemotherapy, in terms of response rate ad progression-free survival (PFS), did not differ between EBVaGC and EBV-negative GC (overall response rate: 53.8% vs. 51.8%, p = 0.99; median PFS: 6.4 vs. 6.7 months, p = 0.90). However, overall survival tended to be better with EBVaGC than EBV-negative GC (16.4 vs. 14.0 months, p = 0.07). CONCLUSIONS: EBVaGC accounted for 5% of metastatic/unresectable GCs. While EBVaGC was not associated with better response to or PFS following first-line cytotoxic chemotherapy, it showed a trend toward better overall survival.

Syntactic complexity differentially affects auditory sentence comprehension performance for individuals with age-related hearing loss.

Objectives: This study examined whether older adults with hearing loss (HL) experience greater difficulties in auditory sentence comprehension compared to those with typical-hearing (TH) when the linguistic burdens of syntactic complexity were systematically manipulated by varying either the sentence type (active vs. passive) or sentence length (3- vs. 4-phrases). Methods: A total of 22 individuals with HL and 24 controls participated in the study, completing sentence comprehension test (SCT), standardized memory assessments, and pure-tone audiometry tests. Generalized linear mixed effects models were employed to compare the effects of sentence type and length on SCT accuracy, while Pearson correlation coefficients were conducted to explore the relationships between SCT accuracy and other factors. Additionally, stepwise regression analyses were employed to identify memory-related predictors of sentence comprehension ability. Results: Older adults with HL exhibited poorer performance on passive sentences than on active sentences compared to controls, while the sentence length was controlled. Greater difficulties on passive sentences were linked to working memory capacity, emerging as the most significant predictor for the comprehension of passive sentences among participants with HL. Conclusion: Our findings contribute to the understanding of the linguistic-cognitive deficits linked to age-related hearing loss by demonstrating its detrimental impact on the processing of passive sentences. Cognitively healthy adults with hearing difficulties may face challenges in comprehending syntactically more complex sentences that require higher computational demands, particularly in working memory allocation.

Randomized phase III trial of a neoadjuvant regimen of four cycles of adriamycin plus cyclophosphamide followed by four cycles of docetaxel (AC4-D4) versus a shorter treatment of three cycles of FEC followed by three cycles of docetaxel (FEC3-D3) in node-positive breast cancer (Neo-shorter; NCT02001506).

PURPOSE: To determine whether six cycles of FEC3-D3 has a comparable efficacy to eight of AC4-D4. METHODS: The enrolled patients (pts) were clinically diagnosed with stage II or III breast cancer. The primary endpoint was a pathologic complete response (pCR), and the secondary endpoints were 3 year disease-free survival (3Y DFS), toxicities, and health-related quality of life (HRQoL). We calculated that 252 pts were needed in each treatment group to enable the detection of non-inferiority (non-inferiority margin of 10%). RESULTS: In terms of ITT analysis, 248 pts were finally enrolled. The 218 pts who completed the surgery were included in the current analysis. The baseline characteristics of these subjects were well balanced between the two arms. By ITT analysis, pCR was achieved in 15/121 (12.4%) pts in the FEC3-D3 arm and 18/126 (14.3%) in the AC4-D4 arm. With a median follow up of 64.1 months, the 3Y DFS was comparable between the two arms (75.8% in FEC3-D3 vs. 75.6% in AC4-D4). The most common adverse event (AE) was Grade 3/4 neutropenia, which arose in 27/126 (21.4%) AC4-D4 arm pts vs 23/121 (19.0%) FEC3-D3 arm cases. The primary HRQoL domains were similar between the two groups (FACT-B scores at baseline, P = 0.35; at the midpoint of NACT, P = 0.20; at the completion of NACT, P = 0.44). CONCLUSION: Six cycles of FEC3-D3 could be an alternative to eight of AC4-D4. Trial registration ClinicalTrials.gov NCT02001506. Registered December 5,2013. https://clinicaltrials.gov/ct2/show/NCT02001506.

Immune repertoire and responses to neoadjuvant TCHP therapy in HER2-positive breast cancer.

Background: Despite the introduction of trastuzumab, pathologic complete response (pCR) is not attained in approximately 30-40% of Human epithelial growth factor receptor-2-positive breast cancer. Tumor-infiltrating lymphocytes (TIL) have been suggested as a predictive marker of treatment response, albeit not always effective. We investigated the relationship between trastuzumab, docetaxel, carboplatin, and pertuzumab (TCHP) treatment and immune repertoire as a treatment response predictor. Design: In all, 35 cases were divided into two experimental groups: 10 and 25 cases in the preliminary and main experiments, respectively. In the preliminary experiment, the biopsy tissues before TCHP treatment and the surgical tissues after TCHP treatment were compared. In the main experiment, the biopsy tissues before TCHP treatment were compared according to the TCHP treatment response. Methods: The T-cell repertoire for TRA, TRB, TRG, and TRD, and B-cell repertoire for immunoglobulin heavy, immunoglobulin kappa, and immunoglobulin lambda were evaluated. Whole transcriptome sequencing was also performed. Results: In the preliminary experiment, the density and richness of the T-cell receptor (TCR) and B-cell receptor (BCR) repertoires decreased after treatment, regardless of TCHP response. In the main experiment, the Shannon's entropy index, density, and length of CDR3 of the TCR and BCR repertoires did not differ significantly in patients who did and did not achieve pCR. The pCR and non-pCR subgroups according to the level of TILs revealed that the non-pCR/lowTIL group had a higher proportion of low-frequency clones than the pCR/lowTIL group in TRA (non-pCR/lowTIL versus pCR/lowTIL, 0.01-0.1%, 63% versus 45.3%; <0.01%, 32.9% versus 51.8%, p < 0.001) and TRB (non-pCR/lowTIL versus pCR/lowTIL, 0.01-0.1%, 26.5% versus 14.7%; <0.01%, 72.0% versus 84.1%, p < 0.001). Conclusions: The role of the diversity, richness, and density of the TCR and BCR repertoires as predictive markers for TCHP response was not identified. Compositions of low-frequency clones could be candidates for predictive factors of TCHP response; however, validation studies and further research are necessary.

Frequent Intraluminal Growth of Large Muscular Veins in Surgically Resected Colorectal Cancer Tissues: A 3-Dimensional Pathologic Reconstruction Study.

Although venous invasion (VI) is common in colorectal cancers (CRCs) and is associated with distant metastasis, the 3-dimensional (3D) microscopic features and associated mechanisms of VI are not well elucidated. To characterize the patterns of VI, 103 tissue slabs were harvested from surgically resected CRCs with ≥pT2. They were cleared using the modified immunolabeling-enabled 3D imaging of solvent-cleared organs method, labeled with multicolor fluorescent antibodies, including antibodies against cytokeratin 19, desmin, CD31, and E-cadherin, and visualized by confocal laser scanning microscopy. VI was classified as intravasation, intraluminal growth, and/or extravasation, and 2-dimensional and 3D microscopic features were compared. VI was detected more frequently in 3D (56/103 [54.4%]) than in conventional 2-dimensional hematoxylin and eosin-stained slides (33/103 [32%]; P < .001). When VI was present, it was most commonly in the form of intraluminal growth (51/56), followed by extravasation (13/56) and intravasation (5/56). The mean length of intraluminal growth was 334.0 ± 212.4 µm. Neoplastic cell projections extended from cancer cell clusters in the connective tissue surrounding veins, penetrated the smooth muscle layer, and then grew into and filled the venous lumen. E-cadherin expression changed at each invasion phase; intact E-cadherin expression was observed in the cancer cells in the venous walls, but its expression was lost in small clusters of intraluminal neoplastic cells. In addition, reexpression of E-cadherin was observed when cancer cells formed well-oriented tubular structures and accumulated and grew along the luminal side of the venous wall. In contrast, singly scattered cancer cells and cancer cells with poorly defined tubular structures showed loss of E-cadherin expression. E-cadherin expression was intact in the large cohesive clusters of extravasated cancer cells. However, singly scattered cells and smaller projections of neoplastic cells in the stroma outward of venous wall showed a loss of E-cadherin expression. In conclusion, VI was observed in more than half of the CRCs analyzed by 3D histopathologic image reconstruction. Once inside a vein, neoplastic cells can grow intraluminally. The epithelial-mesenchymal transition is not maintained during VI of CRCs.

Gene Expression of Prox-1 and Hif-1a in Primo Vessels Inside Lymph Vessels of the Rabbit.

The gene expression of Prox-1 and Hif-1a for the isolated primo vessels (PVs) and composite lymphatic vessels (LVs) containing PVs (LVs + PVs) was investigated by RNA-sequencing (Seq) and quantitative polymerase chain reaction (qRT-PCR) analysis. RNA-Seq on the passed 10 samples on RNA-QC for two experimental groups with PVs and PVs + LVs proceeded to the library construction stage automatically and analyzed differentially expressed genes (DEGs). From the real-time qRT-PCR analysis data, we found the marker genes of Prox-1 and Hif-1a were enriched and decreased in an isolated PVs compared to LVs, respectively. Based on mRNA transcriptional data, Prox-1 and Hif-1a were increased and decreased in PVs compared to LVs + PVs under lipopolysaccharide (LPS) treatment and relieved by acupuncture electric stimulation (AES), respectively. This finding indicates that high and low levels of Prox-1 and Hif-1a may be involved in the function of PVs and that pathophysiological and physiological condition could progress into inflamed lymphatic endothelial cells expanding the PV within the LV.

Desmin and CD31 immunolabeling for detecting venous invasion of the pancreatobiliary tract cancers.

Although venous invasion (VI) is a poor prognostic factor for patients with pancreatobiliary tract cancers, its histopathologic characteristics have not been well described. We evaluated the patterns of VI and the added benefit provided by CD31, desmin, and dual CD31‒desmin immunolabeling for identification of VI. We included 120 surgically resected pancreatobiliary tract cancer cases-59 cases as a test set with known VI and 61 cases as a validation set without information of VI. VI was classified into three patterns: intraepithelial neoplasia-like (IN-like), conventional, and destructive. Hematoxylin and eosin (H&E) staining and CD31, desmin, and dual CD31‒desmin immunolabeling were performed. Foci number and patterns of VI were compared with the test and validation sets. More foci of VI were detected by single CD31 (P = 0.022) than H&E staining in the test set. CD31 immunolabeling detected more foci of the conventional pattern of VI, and desmin immunolabeling detected more foci of the destructive pattern (all, P < 0.001). Dual CD31‒desmin immunolabeling identified more foci of VI (P = 0.012) and specifically detected more foci of IN-like (P = 0.045) and destructive patterns (P < 0.001) than H&E staining in the validation set. However, dual CD31‒desmin immunolabeling was not helpful for detecting the conventional pattern of VI in the validation set. Patients with VI detected by dual CD31‒desmin immunolabeling had shorter disease-free survival (P <0.001) than those without VI. VI detected by dual CD31‒desmin immunolabeling was a worse prognostic indicator (P = 0.009). More foci of VI could be detected with additional single CD31 or dual CD31‒desmin immunolabeling. The precise evaluation of VI with dual CD31‒desmin immunolabeling can provide additional prognostic information for patients with surgically resected pancreatobiliary tract cancers.

Mycosis fungoides development after combined immune checkpoint blockade therapy in a patient with malignant melanoma: a case report.

Immune checkpoint blockade therapy can induce immune-related toxicity, but cutaneous lymphoma development has not been reported. A 56-year-old woman presented with two well-demarcated erythematous macules on the right sole and vitiligo on her extremities. Her facial melanoma had been treated with combination therapy (ipilimumab and pembrolizumab), followed by pembrolizumab monotherapy, a year prior. Microscopy revealed small-to-medium-sized lymphocytes permeating along with the basal epidermal layer. These were immuno-positive for CD2, CD3, and CD5, and showed complete CD7 loss; CD30, TCR-beta F1, and PD-1 were also detected. They exclusively expressed CD8, not CD4, and had a Ki-67 labeling index of 30-40%. Epstein-Barr virus in-situ hybridization was negative. Clonal T-cell receptor beta and gamma chain gene rearrangements were detected. Hence, the lesions were diagnosed as mycosis fungoides. This is the first report of mycosis fungoides development after anti-melanoma immunotherapy. The patient is currently on steroid ointments and phototherapy.

Analysis and Differential Expression of Primo Genes Using RNA-Seq and qRT-PCR Experiments.

Although the existence of the primo vasculature system has been shown in many species, including mice, rats, rabbits and humans, the biological role of this system, including expression of genes and proteins, has not yet been investigated. Especially the transcriptional action by mRNA, which is required for biological action, needs to be studied in primo vasculature biology. Differentially expressed genes in both isolated primo vessels and lymphatic vessels of rabbits were analyzed by RNA sequencing experiments. Primer efficiency and RNA purity of the primo vessels under lipopolysaccharides were confirmed prior to performing real-time qRT-PCR analysis following RNA extraction. We demonstrated that FLT4 was enriched in primo vessels and that several genes, including HSPH1 and EPHB2, were highly expressed in primo vessels compared with lymphatic vessels. Our data show that almost all genes, except HSPA4, were increased or sustained in isolated primo vessels compared with lymphatic vessels (FLT4 2.58 fold, HSPH1 1.83 fold, EPHB2 1.52 fold; whereas HSPA4 decreased 0.50 fold), suggesting primo vessels as a central regulator in diverse physiology. This implies that FLT4, HSPH1, and EPHB2 in high amounts may be involved in the functional activity of primo vessels. Our experimental data show that several genes are highly enriched in primo vessels in the lymphatic vessels of the rabbit.

Bilateral Metachronous Paget's Disease of the Accessory Breasts in a Male.

Bilateral axillary Paget's disease in men is a rare occurrence with limited reports on its diagnosis, treatment, and prognosis. Here, we report the case of a 55-year-old Korean male, who presented with a palpable mass and eczematous skin lesion on the left axilla. An incisional biopsy and histopathologic examination indicated invasive ductal carcinoma with Paget's disease arising in the accessory breast. Magnetic resonance imaging and positron emission tomography revealed no malignancy in the normal breast and other organs. The patient was subjected to a wide excision, wherein the left axillary lymph node was dissected, followed by the administration of adjuvant chemotherapy and radiation therapy. After 17 months of disease-free survival, the patient was diagnosed with Paget's disease of the contralateral accessory breast. He underwent wide excision surgery along with radiation therapy. To the best of our knowledge, this is the first report of bilateral extramammary Paget's disease in a male.

Primary Rhabdomyosarcoma of the Breast: Study of Three Cases at One Institution with a Review of Primary Breast Sarcomas.

BACKGROUND: Primary breast sarcoma (PBS) is rare, comprising approximately 1% of breast malignancies. Rhabdomyosarcoma (RMS) accounts for an extremely small proportion of PBSs, often leading to delayed histologic confirmation. METHODS: Upon reviewing Asan Medical Center's pathology database between 2000 and 2018, 41 PBS cases were retrieved, including three cases of primary RMS of the breast. Their clinicopathological features were analyzed, and the literature related to PBS and primary RMS of the breast was reviewed. RESULTS: We identified three primary breast RMS cases from our institution database, comprising 7.3% of PBS: one case each of spindle cell/sclerosing RMS (ssRMS), alveolar RMS (aRMS), and embryonal RMS (eRMS). All cases involved adolescents or young adults (14, 16, and 25 years, respectively) who underwent mastectomy or radiotherapy and were confirmed using immunohistochemical testing for myogenin, desmin, and myogenic differentiation. The ssRMS patient experienced recurrence at the operation site 4 months post-surgery despite undergoing concurrent chemoradiotherapy. The aRMS patient had multiple metastases at diagnosis and showed FAX3-FOXO1 fusion transcripts; she died 22 months after the diagnosis. The eRMS patient had enlarged axillary lymph nodes; post-radiotherapy, the lesion recurred as multiple metastases to the bone and lung. She died 18 months post-diagnosis. CONCLUSIONS: Our experience on RMS cases suggests that spindle cell or small round cell malignancy in breasts of young female should raise suspicion for the possibility of primary or secondary RMS. To our knowledge, this is the second report of primary breast ssRMS and it may help clinicians who encounter this rare disease in the future.

Expression of Genes in Primo Vasculature Floating in Lymphatic Endothelium Under Lipopolysaccharide and Acupuncture Electric Stimulation.

It is known that the primo vascular system (PVS) includes the primo nodes and vessels. However, the relevant genes in the PVS system for both pathologic and physiologic condition are poorly understood. Here, we first examined the gene expression in primo vessels (PVs) floating in lymphatic endothelium by isolation of PVS and lymphatic vessels (LVs) containing PVS. To investigate therapeutic effects, both PVs and LVs containing PVS were isolated after lipopolysaccharide injection and acupuncture electric stimulation at two acupoints Joksamni (ST36) and Hapgok (LI04) following lipopolysaccharide injection. We used reverse transcriptase-polymerase chain reaction to examine expression of lymphatic endothelial cell markers and inflammatory related genes. We found that lymphatic endothelial cell markers such as fms-related tyrosine kinase 4 (Flt4), lymphatic vessel endothelial receptor (Lyve-1), prospero homeobox protein 1 (Prox-1), and podoplanin (Pdpn) were highly expressed in PV compared to that of lymphatic endothelium, suggesting pivotal roles of PV in LV under inflammation. Furthermore, lymphatic-related genes including metal-response element-binding transcription factor 2 (Mtf2), hypoxia inducible factor (Hif1a), angiotensin II type 1 receptor (Agtr1), and angiotensin II type 2 receptor (Agtr2) were also overall increased in PV, and remarkably increased and these genes except peroxisome proliferator-activated receptor gamma (Pparg) after acupuncture electric stimulation in two acupoints implying central role of PV by gene activation.

Differential Gene Expression by RNA-Seq Analysis of the Primo Vessel in the Rabbit Lymph.

For the connectome of primo vascular system, some long-type primo vessels dyed with Alcian blue injected into inguinal nodes, abdominal node, and axially nodes were visualized, which passed over around the vena cava of the rabbit. The Alcian blue dye revealed primo vessels and colored blue in the rabbit lymph vessels. The length of long-type primo vessels was 18 cm on average, of which diameters were about 20-30 µm, and the lymph vessels had diameters of 100-150 µm. Three different tissues of pure primo vessel, mixed primo + lymph vessel, and only lymph vessel were made to undergo RNA-Seq analysis by next-generation sequencing. We also analyzed differentially expressed genes (DEGs) from the RNA-Seq data, in which 30 genes of the primo vessels, primo + lymph vessels, and lymph vessels were selected for primo marker candidates. From the plot of DEG analysis, 10 genes had remarkably different expression pattern on the Group 1 (primo vessel) vs Group 3 (lymph vessel). With Fragments Per Kilobase of exon per Million the cutoff p-value for each gene was < 0.05. Fragments Per Kilobase of exon per Million of the 10 genes such as IGHM, HLA-DRA, HIST1H41, LPL, CD36, SRGN, DGAT2, SNCG, CD48, and GPD1 for primo vessels compared with those of lymph vessels increased twice or thrice. These results suggest that the selected genes could be used for the specific marker to construct primo connectome of circuit system in the rabbit.

WITHDRAWN:Primary Rhabdomyosarcoma of the Breast: A Report of Two Cases and Literature Review.

Ahead of Print article withdrawn by publisher.

Targeted sensory enrichment interventions protect against behavioral and neuroendocrine consequences of early life stress.

Both basic and clinical research support the use of tactile stimulation to rescue several neurobiobehavioral consequences that follow early life stress. Here, using a translational rodent model of the neonatal intensive care unit (NICU), we tested the individual prophylactic potential of a variety of sensory interventions including tactile (brushing pups with a paint brush to mimic maternal licking), auditory (a simulated lactating rat dam heart beat), and olfactory (a series of aroma therapy scents) stimulation. The NICU model was developed to mimic not only the reduced parental contact that sick infants receive (by isolating rat pups from their litters), but also the nosocomial infections and medical manipulations associated with this experience (by utilizing a dual lipopolysaccharide injection schedule). Each of the neurobiobehavioral consequences observed were dissociable between isolation and inflammation, or required a combined presentation ('two hits') of the neonatal stressors. Sprague-Dawley rats exposed to these early life stressors presented with sex-specific disruptions in both separation-induced ultrasonic vocalization (USV) distress calls (males & females) and juvenile social play USVs (males only). All three sensory enhancement interventions were associated with the rescue of potentiated distress calls while olfactory stimulation was protective of social vocalizations. Female rats exposed to early life stress experienced precocious puberty and shifts in the hypothalamic GnRh axis; sensory enrichment counter-acted the advanced pubertal onset. Animals that underwent the NICU protocol also displayed maturational acceleration in terms of the loss of the rooting reflex in addition to hyperalgesia, a reduced preference for a novel conspecific, blunted basal plasma corticosterone and reduced hippocampal glucocorticoid receptor expression. These alterations closely simulated the clinical effects of early life adversity in terms of disruptions in the hypothalamic pituitary "stress" axis, social communication and engagement, tactile system processing, and accelerated maturation. Moreover, sensory enrichment attenuated many of these behavioral and neurophysiological alterations, and even slowed maturation. Overall, this supports the translatability of our novel rodent model and its potential utility in understanding how brain maturation and quality of early life experiences may interact to shape the integrity of stress and sensory system development. Future work must determine the appropriate modalities and parameters (e.g. patterning, timing) for effective sensory enrichment interventions.

Complex Environmental Rearing Enhances Social Salience and Affects Hippocampal Corticotropin Releasing Hormone Receptor Expression in a Sex-Specific Manner.

Methods for understanding the neurocircuitry of ethologically relevant behaviors have advanced substantially; however renovations to standard animal laboratory housing, in the form of enhanced enrichment, have lagged behind. This is despite evidence that environmental enrichment (EE) reduces stress, stereotypy, and promotes healthy species typical behaviors. While many scientists express interest for increased EE as a standard for animal caging systems, there are concerns that its effects on brain, behavior, and cognition are not well characterized. In the present study, male and female Sprague-Dawley rats were housed for six weeks in either EE, Colony Nesting (CN), or Standard Housing (SD) conditions. We show that adolescent exposure to environmental complexity changed the dynamics of social interactions, sensory processing, and underlying basal stress neurocircuitry, in a sex- and enrichment-type-dependent manner. Specifically, EE and CN increased prosocial engagement and the social saliency of male and female rats while the profile of hippocampal Crhr2 expression was affected only in EE males. Hippocampal Crh was associated with anxiety-like behavior in SD males - this did not extend to EE or CN groups, nor to females. Observations such as these are an important consideration for the validity of translational research investigating the neurocircuitry of stress resiliency, and for understanding the mechanisms of psychiatric disorders. Future work must focus on characterizing how individual environmental enhancements (e.g. novelty, social enrichment, physical activity) shape phenotypic differences, how they vary as a function of species, strain and sex, and (if warranted) how to meaningfully implement this knowledge into biomedical research designs.

Highly uniform and vertically aligned SnO2 nanochannel arrays for photovoltaic applications.

Nanostructured electrodes with vertical alignment have been considered ideal structures for electron transport and interfacial contact with redox electrolytes in photovoltaic devices. Here, we report large-scale vertically aligned SnO2 nanochannel arrays with uniform structures, without lateral cracks fabricated by a modified anodic oxidation process. In the modified process, ultrasonication is utilized to avoid formation of partial compact layers and lateral cracks in the SnO2 nanochannel arrays. Building on this breakthrough, we first demonstrate the photovoltaic application of these vertically aligned SnO2 nanochannel arrays. These vertically aligned arrays were directly and successfully applied in quasi-solid state dye-sensitized solar cells (DSSCs) as photoanodes, yielding reasonable conversion efficiency under back-side illumination. In addition, a significantly short process time (330 s) for achieving the optimal thickness (7.0 µm) and direct utilization of the anodized electrodes enable a simple, rapid and low-cost fabrication process. Furthermore, a TiO2 shell layer was coated on the SnO2 nanochannel arrays by the atomic layer deposition (ALD) process for enhancement of dye-loading and prolonging the electron lifetime in the DSSC. Owing to the presence of the ALD TiO2 layer, the short-circuit photocurrent density (Jsc) and conversion efficiency were increased by 20% and 19%, respectively, compared to those of the DSSC without the ALD TiO2 layer. This study provides valuable insight into the development of efficient SnO2-based photoanodes for photovoltaic application by a simple and rapid fabrication process.

Highly ordered and vertically oriented TiO2/Al2O3 nanotube electrodes for application in dye-sensitized solar cells.

The surface of long TiO2 nanotube (NT) electrodes in dye-sensitized solar cells (DSSCs) was modified without post-annealing by using atomic layer deposition (ALD) for the enhancement of photovoltage. Vertically oriented TiO2 NT electrodes with highly ordered and crack-free surface structures over large areas were prepared by a two-step anodization method. The prepared TiO2 NTs had a pore size of 80 nm, and a length of 23 µm. Onto these TiO2 NTs, an Al2O3 shell of a precisely controlled thickness was deposited by ALD. The conformally coated shell layer was confirmed by high-resolution transmission electron microscopy, energy-dispersive x-ray spectroscopy, and x-ray photoelectron spectroscopy. The open-circuit voltage (V(oc)) of the DSSCs was gradually enhanced as the thickness of the Al2O3 shell of the TiO2/Al2O3 NT electrodes was increased, which resulted from the enhanced electron lifetime. The enhanced electron lifetime caused by the energy barrier effect of the shell layer was measured quantitatively by the open-circuit voltage decay technique. As a result, 1- and 2-cycle-coated samples showed enhanced conversion efficiencies compared to the bare sample.

A Case of Esophageal Fibrovascular Polyp That Induced Asphyxia during Sleep.

Esophageal fibrovascular polyps are rare, benign, submucosal tumors of the upper digestive tract that usually have an indolent course until the lesion attains a very large size. The most frequent complaints associated with these tumors include dysphagia and foreign body sensation. However, a long pedunculated polyp can regurgitate into the pharynx or oral cavity and cause asphyxia and sudden death if the larynx is occluded. We describe the case of a 51-year-old man who experienced snoring and occasional asphyxia during sleep. Upper endoscopy was performed, which indicated the presence of a pedunculated esophageal polyp that regurgitated into the vocal cords. The polyp was removed using a polypectomy snare and was confirmed to be a fibrovascular polyp based on pathologic examination findings. Three months after the excision of the polyp, the patient was found to be doing well without any further occurrence of asphyxia or sleep disturbances.