Realization of large-area ultraflat chiral blue phosphorene.

Blue phosphorene (BlueP), a theoretically proposed phosphorous allotrope with buckled honeycomb lattice, has attracted considerable interest due to its intriguing properties. Introducing chirality into BlueP can further enrich its physical and chemical properties, expanding its potential for applications. However, the synthesis of chiral BlueP remains elusive. Here, we demonstrate the growth of large-area BlueP films on Cu(111), with lateral size limited by the wafer dimensions. Importantly, we discovered that the BlueP is characterized by an ultraflat honeycomb lattice, rather than the prevailing buckled structure, and develops highly ordered spatial chirality plausibly resulting from the rotational stacking with the substrate and interface strain release, as further confirmed by the geometric phase analysis. Moreover, spectroscopic measurements reveal its intrinsic metallic nature and different characteristic quantum oscillations in the image-potential states, which can be exploited for a range of potential applications including polarization optics, spintronics, and chiral catalysis.

Theoretical prediction and characterization of novel two-dimensional ternary tetradymite compounds La2X2Y (X = I, Br, Cl; Y = Ge, Te) as anode materials for metal-ion batteries.

Tetradymite compounds, such as Bi2Te3, crystallizing in rhombohedral structures have triggered tremendous research interest from the scientific community because of their intriguing properties. Herein, using the state-of-the-art first-principles calculations, we identify that La2X2Y (X = I, Br, Cl; Y = Ge, Te) nanosheets exhibit a ternary tetradymite-type structure with extraordinary electrical and electrochemical properties. It is first demonstrated that the layered La2X2Y compounds exhibit weak interlayer coupling with cleavage energies in the range of ∼0.28-0.38 J m-2, allowing the ready separation of monolayers that can be synthesized by mechanical exfoliation from their bulk counterparts. Next, we predict that La2X2Ge nanosheets exhibit a semiconducting nature, and upon physical realistic strain, a Dirac cone can be realized. These findings can be exploited in the transport properties. Furthermore, we comprehensively investigated the electrochemical properties of the predicted systems to evaluate their potential use in metal-ion (Li/Na) batteries. Our detailed analyses reveal that the Li (Na) adatoms are sufficiently mobile on the surface of the studied systems. For instance, the binding energy for the Li (Na) adatom on La2I2Ge is -2.24(-1.79) eV with a diffusion barrier of as small as ∼0.31(0.20) eV. Subsequently, the maximum theoretical specific capacity for Li (Na) reaches as high as 887(1064) mA h g-1, which can be attributed to a much higher storage capacity compared to previously identified 2D anode materials. These findings substantiate that the predicted nanosheets could be synthesized to explore their potential applications in future metal-ion batteries.

Effect of Time to Thrombolysis on Clinical Outcomes in Patients With Acute Ischemic Stroke Treated With Tenecteplase Compared to Alteplase: Analysis From the AcT Randomized Controlled Trial.

BACKGROUND: The AcT (Alteplase Compared to Tenecteplase) randomized controlled trial showed that tenecteplase is noninferior to alteplase in treating patients with acute ischemic stroke within 4.5 hours of symptom onset. The effect of time to treatment on clinical outcomes with alteplase is well known; however, the nature of this relationship is yet to be described with tenecteplase. We assessed whether the association of time to thrombolysis treatment with clinical outcomes in patients with acute ischemic stroke differs by whether they receive intravenous tenecteplase versus alteplase. METHODS: Patients included were from AcT, a pragmatic, registry-linked, phase 3 randomized controlled trial comparing intravenous tenecteplase to alteplase in patients with acute ischemic stroke. Eligible patients were >18 years old, with disabling neurological deficits, presenting within 4.5 hours of symptom onset, and eligible for thrombolysis. Primary outcome was modified Rankin Scale score 0 to 1 at 90 days. Safety outcomes included 24-hour symptomatic intracerebral hemorrhage and 90-day mortality rates. Mixed-effects logistic regression was used to assess the following: (a) the association of stroke symptom onset to needle time; (b) door (hospital arrival) to needle time with outcomes; and (c) if these associations were modified by type of thrombolytic administered (tenecteplase versus alteplase), after adjusting for age, sex, baseline stroke severity, and site of intracranial occlusion. RESULTS: Of the 1538 patients included in this analysis, 1146 (74.5%; 591 tenecteplase and 555 alteplase) presented within 3 hours versus 392 (25.5%; 196: TNK and 196 alteplase) who presented within 3 to 4.5 hours of symptom onset. Baseline patient characteristics in the 0 to 3 hours versus 3- to 4.5-hour time window were similar, except patients in the 3- to 4.5-hour window had lower median baseline National Institutes of Health Stroke Severity Scale (10 versus 7, respectively) and lower proportion of patients with large vessel occlusion on baseline CT angiography (26.9% versus 18.7%, respectively). Type of thrombolytic agent (tenecteplase versus alteplase) did not modify the association between continuous onset to needle time (Pinteraction=0.161) or door-to-needle time (Pinteraction=0.972) and primary clinical outcome. Irrespective of the thrombolytic agent used, each 30-minute reduction in onset to needle time was associated with a 1.8% increase while every 10 minutes reduction in door-to-needle time was associated with a 0.2% increase in the probability of achieving 90-day modified Rankin Scale score 0 to 1, respectively. CONCLUSIONS: The effect of time to tenecteplase administration on clinical outcomes is like that of alteplase, with faster administration resulting in better clinical outcomes. REGISTRATION: URL: https://classic. CLINICALTRIALS: gov; Unique identifier: NCT03889249.

Black phosphorene/blue phosphorene van der Waals heterostructure: a potential anode material for lithium-ion batteries.

Van der Waals (vdW) heterostructure-based electrodes have invoked tremendous research interest due to their intriguing properties and their capability to break the limitations of the restricted properties of single-material systems. Herein, based on first-principles approaches, we propose that the black phosphorene/blue phosphorene (BLK-P/BLE-P) vdW heterostructure can be a capable anode material for power-driving lithium-ion batteries (LIBs), as it exhibits a large theoretical capacity, together with a relatively strong binding strength compared with the individual BLK-P and BLE-P monolayers. Our calculation results show that the Li adatom prefers to intercalate into the interlayer of the BLK-P/BLE-P vdW heterostructure due to the synergistic interfacial effect, resulting in a high binding strength and a diffusivity comparable to the BLK-P and BLE-P monolayers. Subsequently, the theoretical specific capacity is found to be as high as 552.8 mA h g-1, which can be attributed to the much higher storage capacity of Li adatoms in the BLK-P/BLE-P vdW heterostructure. Furthermore, electronic structure calculations reveal that a large amount of charge transfer assists in semiconductor to metallic transition upon lithiation, which would ensure good electrical conductivity. These simulations prove that the BLK-P/BLE-P heterostructure has great potential in LIBs and is essential for future battery design.

Disulfide HMGB1 acts via TLR2/4 receptors to reduce the numbers of oligodendrocyte progenitor cells after traumatic injury in vitro.

Traumatic brain injury (TBI) is associated with poor clinical outcomes; autopsy studies of TBI victims demonstrate significant oligodendrocyte progenitor cell (OPC) death post TBI; an observation, which may explain the lack of meaningful repair of injured axons. Whilst high-mobility group box-1 (HMGB1) and its key receptors TLR2/4 are identified as key initiators of neuroinflammation post-TBI, they have been identified as attractive targets for development of novel therapeutic approaches to improve post-TBI clinical outcomes. In this report we establish unequivocal evidence that HMGB1 released in vitro impairs OPC response to mechanical injury; an effect that is pharmacologically reversible. We show that needle scratch injury hyper-acutely induced microglial HMGB1 nucleus-to-cytoplasm translocation and subsequent release into culture medium. Application of injury-conditioned media resulted in significant decreases in OPC number through anti-proliferative effects. This effect was reversed by co-treatment with the TLR2/4 receptor antagonist BoxA. Furthermore, whilst injury conditioned medium drove OPCs towards an activated reactive morphology, this was also abolished after BoxA co-treatment. We conclude that HMGB1, through TLR2/4 dependant mechanisms, may be detrimental to OPC proliferation following injury in vitro, negatively affecting the potential for restoring a mature oligodendrocyte population, and subsequent axonal remyelination. Further study is required to assess how HMGB1-TLR signalling influences OPC maturation and myelination capacity.

Fibroepithelial Lesions in the Breast of Adolescent Females: A Clinicopathological Study of 54 Cases.

Fibroepithelial lesions (FELs) are the most frequent breast tumors in adolescent females. The pubertal hormonal surge could impact the growth and microscopic appearance of FELs in this age group. In this study, we evaluate the morphology and clinical behavior of FELs in adolescents. We searched the 1992-2012 pathology data base for FELs in females 18 years old or younger (F ≤18 years). Seven FELs from 1975 to 1983 were also included. Three pathologists reviewed all available material. Patient (pt) characteristics and follow-up information were obtained from electronic medical records. Forty-eight F ≤18 years had 54 FELs with available slides. Thirty (67%) pts were Caucasian, 12 (27%) African-American, two (4%) Hispanic, one (2%) Asian; three were of unknown race/ethnicity. Median age at diagnosis was 16 years. Median age at menarche was 12 years; most (96%) FELs occurred after menarche (median interval 48 months). All patients underwent lumpectomy; one required subsequent mastectomy. The FELs were 34 fibroadenomas (FAs) (11 usual, 23 juvenile), and 20 phyllodes tumors (PTs) (16 benign, one borderline and three malignant). Eight (35%) juvenile FAs showed slight intratumoral heterogeneity. The mean mitotic rate was 1.3 mitoses/10 high-power fields (HPFs) (range, 0-6) in usual FAs, 1.8/10 HPFs in juvenile FAs, 3.1/10 HPFs in benign PTs, 10/10 HPFs in the borderline PT and 17/10 HPFs in malignant PTs. The mean follow-up for 29 pts with 33 FELs was 44 months. Two (10%) PTs recurred locally (a benign PT at 18 months, and a borderline PT at 11 months). Both recurrent PTs had microscopic margins <1 mm. Mitotic activity in FAs from adolescents can be substantial and this finding should be interpreted cautiously. Awareness of the morphologic features of FELs in adolescents is important to avoid overdiagnosis of PTs, which can lead to additional unnecessary and potentially disfiguring surgery.

Prevalence of the polar vessel sign in parathyroid adenomas on the arterial phase of 4D CT.

BACKGROUND AND PURPOSE: The "polar vessel" sign has been previously described on sonography of parathyroid adenomas. We estimated the 4D CT prevalence of the polar vessel sign and determined features of parathyroid adenomas that are associated with this sign. MATERIALS AND METHODS: Twenty-eight consecutive patients with parathyroid adenomas underwent 4D CT between 2008 and 2012 at 2 institutions. 4D CT images were reviewed for the presence of the polar vessel sign and a second vascular finding of an enlarged ipsilateral inferior thyroid artery. The polar vessel sign was correlated with adenoma weight and size and arterial phase CT attenuation. RESULTS: Thirty-two parathyroid adenomas in 28 patients were studied, with a mean adenoma weight of 0.66 ± 0.65 g, a mean maximal CT diameter of 11.1 ± 4.9 mm, and a mean arterial attenuation of 148 ± 47 HU. The polar vessel sign was seen in 20/32 (63%) adenomas. Adenomas with a polar vessel had higher arterial phase attenuation than adenomas without a polar vessel (163 and 122 HU, respectively, P < .01). Size and weight were not significantly different for adenomas with and without polar vessels. An enlarged inferior thyroid artery was seen in only 2/28 (7%) patients with unilateral disease. CONCLUSIONS: The polar vessel sign was present in nearly two-thirds of parathyroid adenomas on 4D CT and was more likely to be present in adenomas that had greater arterial phase enhancement. This sign can be used along with enhancement characteristics to increase the radiologist's confidence that a visualized lesion is a parathyroid adenoma rather than a thyroid nodule or lymph node.

Effect of post-fusion holding time, orientation and position of somatic cell-cytoplasts during electrofusion on the development of handmade cloned embryos in buffalo (Bubalus bubalis).

The present study was conducted primarily to optimize electrofusion conditions for efficient production of zona-free nuclear transfer embryos in buffalos (Bubalus bubalis). We found that 4V AC current for proper triplet alignment and single step fusion method, using a single DC pulse of 3.36 kV/cm for 4-µs duration, produced the most convincing results for efficient reconstitution of zona-free cloned embryos. Lysis rate was very high (84.28 ± 2.59%) when triplets were in physical contact with negative electrode after applying DC current, however, cleavage rate and blastocyst rate were found to be similar when the triplets were not in physical contact with either positive or negative electrodes or when they were in physical contact with the positive electrode. Significant improvement in blastocyst production was observed when the somatic cell faced the positive electrode than when it faced the negative electrode (39.17 ± 2.74% vs. 25.91 ± 2.00%, respectively) during electrofusion. Similarly, the blastocyst rate (52.0 ± 3.4%) was found to be significantly higher when reconstructed embryos were activated 6 h post electrofusion as compared to 0, 2, 4 and 8 h (16.04 ± 6.3%; 18.36 ± 1.4%; 22.44 ± 3.7% and 30.02 ± 4.6%, respectively). This study establishes the application of zona-free nuclear transfer procedures for the production of handmade cloned buffalo embryos through optimization of electrofusion parameters and post fusion holding time for enhancing their preimplantation development.

Inhibition of Polo-like kinase 1 prevents the growth of metastatic breast cancer cells in the brain.

Few therapeutic strategies exist for the treatment of metastatic tumor cells in the brain because the blood-brain barrier (BBB) limits drug access. Thus the identification of molecular targets and accompanying BBB permeable drugs will significantly benefit brain metastasis patients. Polo-like kinase 1 (Plk1) is an attractive molecular target because it is only expressed in dividing cells and its expression is upregulated in many tumors. Analysis of a publicly available database of human breast cancer metastases revealed Plk1 mRNA expression was significantly increased in brain metastases compared to systemic metastases (P = 0.0018). The selective Plk1 inhibitor, GSK461364A, showed substantial uptake in normal rodent brain. Using a breast cancer brain metastatic xenograft model (231-BR), we tested the efficacy of GSK461364A to prevent brain metastatic colonization. When treatment was started 3 days post-injection, GSK461364A at 50 mg/kg inhibited the development of large brain metastases 62% (P = 0.0001) and prolonged survival by 17%. GSK461364A sensitized tumor cells to radiation induced cell death in vitro. Previously, it was reported that mutations in p53 might render tumor cells more sensitive to Plk1 inhibition; however, p53 mutations are uncommon in breast cancer. In a cohort of 41 primary breast tumors and matched brain metastases, p53 immunostaining was increased in 61% of metastases; 44% of which were associated with primary tumors with low p53. The data suggest that p53 overexpression occurs frequently in brain metastases and may facilitate sensitivity to Plk1 inhibition. These data indicate Plk1 may be a new druggable target for the prevention of breast cancer brain metastases.

Elevations of diffusion anisotropy are associated with hyper-acute stroke: a serial imaging study.

Diffusion tensor imaging (DTI) studies of human ischemic stroke within 24 h of symptom onset have reported variable findings of changes in diffusion anisotropy. Serial DTI within 24 h may clarify these heterogeneous results. We characterized longitudinal changes of diffusion anisotropy by analyzing discrete ischemic white matter (WM) and gray matter (GM) regions during the hyperacute (2.5-7 h) and acute (21.5-29 h) scanning phases of ischemic stroke onset in 13 patients. Mean diffusivity (MD), fractional anisotropy (FA) and T2-weighted signal intensity were measured for deep and subcortical WM and deep and cortical GM areas in lesions outlined by a > or =30% decrease in MD. Average reductions of approximately 40% in relative (r) MD were observed in all four brain regions during both the hyperacute and acute phases post stroke. Overall, 9 of 13 patients within 7 h post symptom onset showed elevated FA in at least one of the four tissues, and within the same cohort, 11 of 13 patients showed reduced FA in at least one of the ischemic WM and GM regions at 21.5-29 h after stroke. The fractional anisotropy in the lesion relative to the contralateral side (rFA, mean+/-S.D.) was significantly elevated in some patients in the deep WM (1.10+/-0.11, n=4), subcortical WM (1.13+/-0.14, n=4), deep GM (1.07+/-0.06, n=1) and cortical GM (1.22+/-0.13, n=5) hyperacutely (< or =7 h); however, reductions of rFA at approximately 24 h post stroke were more consistent (rFA= 0.85+/-0.12).

Eye position information on CT increases the identification of acute ischemic hypoattenuation.

BACKGROUND AND PURPOSE: It is possible that identification of eye deviation may sensitize a scan reader to early brain hypodensity associated with an arterial occlusive process. Our aim was to investigate the value of observing eye deviation on blinded CT identification of early hypoattenuation following ischemic infarct. MATERIALS AND METHODS: Two staff and 2 fellow neuroradiologists reviewed 75 brain CT scans obtained within 3 hours of acute ischemia from subjects in the Interventional Management of Stroke Study. Films were reviewed 3 months apart, the first time with tape over the eyes on the images, the second with the eyes visible. Readers were asked if early hypoattenuation in the middle cerebral artery (MCA) distribution or if a hyperattenuated MCA was present. kappa statistics were calculated to determine agreement among the 4 readers and between each of the 2 readings by the same reader, not only for the original interpretation of the blinded study neuroradiologist but also for the Alberta Stroke Program Early CT Score (ASPECTS) for each subject assigned by an unblinded expert panel. A generalized estimating equations modeling approach was used to look at the overall effect of including eye information for agreement between interpretations. RESULTS: Eye information availability was associated with improved agreement for detection of early ischemic hypoattenuation not only among the 4 readers but also between the 4 readers and both the blinded study neuroradiologist (P = .02) and the unblinded expert ASPECTS panel. When comparing first and second readings for hypoattenuation, we also noted increased mean values for sensitivity (46.8% first, 56.5% second), specificity (78.2%, 80.2%), positive predictive value (72.0%, 80.7%), negative predictive value (55.5%, 61.0%), and percentage agreement (61.0%, 67.5%). CONCLUSION: Observation of CT eye deviation significantly improves reader identification of acute ischemic hypoattenuation.

Time-resolved spinal MR angiography: initial clinical experience in the evaluation of spinal arteriovenous shunts.

BACKGROUND AND PURPOSE: Spinal arteriovenous shunts usually require digital subtraction angiography (DSA) for evaluation. We report a unique time-resolved spinal MR angiographic (TRSMRA) technique with a temporal resolution of 3-6 seconds and spatial resolution of approximately 1 mm(3) that has the potential to noninvasively detect, localize, and follow-up these cases. MATERIALS AND METHODS: Eleven patients with clinical presentation and/or MR findings suspicious for a spinal arteriovenous shunt were referred for TRSMRA. Patients subsequently underwent spinal DSA to confirm the presence or absence of a shunt or were followed clinically until an alternative diagnosis was found. TRSMRA was also used to predict the level of the shunt in the positive cases. In addition, 2 of these patients as well as a 12th patient referred to us posttreatment received a follow-up TRSMRA to assess treatment outcome. RESULTS: Early venous shunting was identified by using TRSMRA in 6 cases. All 6 were confirmed to have an AV shunt on subsequent spinal DSA. The shunt level predicted by TRSMRA consistently correlated with DSA to within 1 vertebral level. In the 5 patients with a negative screening TRSMRA, DSA or clinical outcome confirmed the absence of an arteriovenous shunt in all of the cases. Posttreatment TRSMRA in 3 patients accurately assessed the success or failure of treatment. CONCLUSION: Combining acceleration techniques to achieve high frame rate TRSMRA provides sufficient temporal and spatial resolution to identify, localize, and follow patients suspected of having a spinal arteriovenous shunt. Further study in a larger population is warranted to assess the accuracy of this technique.

Profile of lung cancer in Kashmir, India: a five-year study.

AIM: To study the clinico-pathological aspects of lung cancer, and the outcome of various treatment modalities. METHODS: A retrospective review of histopathologically confirmed lung cancer patients who were registered and treated at our institution over a period of five years was carried out. RESULTS: A total of 321 patients were studied. There was a preponderance of males (91.9%) as compared to females (8.1%). Smoking history was present in 88% of the male patients. Cough was the main presenting feature in 71.6% of patients. Diagnosis was established by bronchoscopy in 94% of cases. Squamous cell carcinoma was observed in 77.3%, while 17.1% had small cell carcinoma. Radiotherapy formed the main treatment modality alone (22.4%) and in combination (27%). Out of the 321 patients, 206 were evaluable on follow-up. Local failure and distant metastasis were seen in 9.2% and 19.9% of cases, respectively. The overall survival rate of 2, 3 and 5 years was 19.9%, 13.59% and 6.79%, respectively. CONCLUSIONS: . The outcome of lung cancer is poor. Increased survival is possible if the disease is detected early, treated adequately with multi modality approach.

The morphological variants of papillary carcinoma of the thyroid: a clinico-pathological study--AFIP experience. Armed Forces Institute of Pathology.

Many variants of papillary carcinoma of thyroid have been described. Identification of some of these may have prognostic implications. Eighty-two cases of papillary carcinoma of the thyroid diagnosed at Armed Forces Institute of Pathology, Rawalpindi over a six year period were reviewed with the aim of identifying these variants. Fifty-eight (70.7%) were classical papillary carcinoma. Thirteen (15.9%) had follicular variant, 6 (7.3%) columnar cell variant and 3 (3.7%) had tall cell variant. The mean age at diagnosis was 27 years for classical papillary carcinoma, 46 years for follicular variant, 61 years for columnar cell variant and 52 years for tall cell variant. The columnar cell variant had a more aggressive clinical presentation than others. Tall cell, columnar cell and diffuse sclerosing variant have a poor prognosis. An effort should be made to identify them on histopathology so that specific therapy can be planned.

Morphological study of liver in patients of chronic hepatitis C treated with interferon.

The effect of interferon therapy on liver morphology was assessed in ten patients with serologically proven chronic hepatitis C. All these patients received 3 million units of alpha interferon three times a week. Six patients received therapy for 6 months, two patients for 12 months, one patient each for 3 and 9 months. All patients underwent a second liver biopsy 1 to 6 months after cessation of therapy. Alanine aminotransferase levels were determined before, during and after therapy. Each biopsy was assessed histologically by revised classification of chronic hepatitis proposed by Desmet et al and Kondell histological activity index was determined. Four patients showed significant reduction in the necroinflammatory activity with decrease in the HAI and normalisation of ALT level. Three patients showed partial reduction in the necroinflammatory activity with partial reduction of ALT levels. Two patients did not show any change in the grade of disease while one patient showed worsening of necroinflammatory activity with rising ALT levels. One patient showed a significant reduction in fibrosis with conversion of early developing cirrhosis into bridging fibrosis. A second liver biopsy is extremely useful for assessing the response of interferon treatment, however, it must be done at a suitable time after cessation of therapy.