Publications by authors named "Cen Zhang"

93 Publications

Systemic Inflammatory Response Syndrome is Associated with Hematoma Expansion in Intracerebral Hemorrhage.

J Stroke Cerebrovasc Dis 2021 May 30;30(8):105870. Epub 2021 May 30.

Department of Neurology, NYU Langone University School of Medicine, New York, New York, USA; Department of Neurosurgery, NYU Langone Medical Center, New York, New York, USA.

Objectives: Systemic inflammatory response syndrome (SIRS) and hematoma expansion are independently associated with worse outcomes after intracerebral hemorrhage (ICH), but the relationship between SIRS and hematoma expansion remains unclear.

Materials And Methods: We performed a retrospective review of patients admitted to our hospital from 2013 to 2020 with primary spontaneous ICH with at least two head CTs within the first 24 hours. The relationship between SIRS and hematoma expansion, defined as ≥6 mL or ≥33% growth between the first and second scan, was assessed using univariable and multivariable regression analysis. We assessed the relationship of hematoma expansion and SIRS on discharge mRS using mediation analysis.

Results: Of 149 patients with ICH, 83 (56%; mean age 67±16; 41% female) met inclusion criteria. Of those, 44 (53%) had SIRS. Admission systolic blood pressure (SBP), temperature, antiplatelet use, platelet count, initial hematoma volume and rates of infection did not differ between groups (all p>0.05). Hematoma expansion occurred in 15/83 (18%) patients, 12 (80%) of whom also had SIRS. SIRS was significantly associated with hematoma expansion (OR 4.5, 95% CI 1.16 - 17.39, p= 0.02) on univariable analysis. The association remained statistically significant after adjusting for admission SBP and initial hematoma volume (OR 5.72, 95% CI 1.40 - 23.41, p= 0.02). There was a significant indirect effect of SIRS on discharge mRS through hematoma expansion. A significantly greater percentage of patients with SIRS had mRS 4-6 at discharge (59 vs 33%, p=0.02).

Conclusion: SIRS is associated with hematoma expansion of ICH within the first 24 hours, and hematoma expansion mediates the effect of SIRS on poor outcome.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105870DOI Listing
May 2021

Determining the effects of blended learning using the community of inquiry on nursing students' learning gains in sudden patient deterioration module.

Nurs Open 2021 May 11. Epub 2021 May 11.

Department of Nursing, Stomatological Hospital of Chongqing Medical University, Chongqing, China.

Aims: To determine the effectiveness of blended learning using the community of inquiry framework on nursing students' learning gains in a sudden patient deterioration module.

Design: A quasi-experimental trial.

Methods: 233 Chinese nursing students in their fourth semester of a sudden patient deterioration learning module were assigned to control (N = 113) and experimental group (N = 120). Students in experimental group engaged in community of inquiry-based blended learning in sudden patient deterioration module, including computer-aided self-instruction, team-based topic discussion and simulation training. Control group learned similar contents through face-to-face teaching comprising of a presentation with lecture, tutorial and simulation training. Student assessment of learning gains, knowledge and practical ability was quantified after the interventions.

Results: Compared with control group, students in experimental group had improved student assessment of learning gains (p = .001, Cohen d = 0.69) and practical ability (p < .001, Cohen d = 0.48). Although no significant difference in overall knowledge score, experimental group students did better performance in application and analysis (p = .001, Cohen d = 0.45).
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http://dx.doi.org/10.1002/nop2.914DOI Listing
May 2021

Dual Antiplatelet Therapy Versus Aspirin in Patients With Stroke or Transient Ischemic Attack: Meta-Analysis of Randomized Controlled Trials.

Stroke 2021 Jun 27;52(6):e217-e223. Epub 2021 Apr 27.

Section of Interventional Cardiology and Vascular Medicine, NorthShore University Health System, Evanston, IL (A.T., M.R., A.Q.).

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http://dx.doi.org/10.1161/STROKEAHA.120.033033DOI Listing
June 2021

Effect of peer support on improving self-management ability in peritoneal dialysis patients-a randomized controlled trial.

Ann Palliat Med 2021 Mar;10(3):3028-3038

Nursing Department of Wuxi People's Hospital, Wuxi, China.

Background: Peritoneal dialysis (PD) is an ideal method for the treatment of chronic kidney disease. Its survival rate and quality of life depend on the quality of dialysis. The quality of dialysis depends on the compliance of patients with drugs and dialysis treatment, the choice of diet, the detection of complications and the monitoring and management of the disease. Therefore, the self-management of PD patients is particularly important. This study explored the role of peer support in improving the self-management ability of PD patients.

Methods: A total of 105 PD patients in a Chinese tertiary hospital were enrolled and divided into a control group (35 cases), a WeChat group (intervention group 1; 35 cases), and a face-to-face group (intervention group 2; 35 cases). During the 6-month follow-up, the control group were given individualized education, and the intervention group was given peer support.

Results: After the 6-month intervention, the self-management ability of the intervention group was significantly different from that of the control group (P<0.01). There were significant differences between the WeChat group and the face-to-face group with respect to hemoglobin and blood phosphorus (P<0.05). There were significant differences in prealbumin, hemoglobin, blood phosphorus and calcium levels between the intervention and control groups after 3 months and 6 months of intervention (P<0.01).

Conclusions: Peer support can effectively improve the self-management ability and biochemical indicators in PD patients.
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http://dx.doi.org/10.21037/apm-21-219DOI Listing
March 2021

The Interplay Between Tumor Suppressor p53 and Hypoxia Signaling Pathways in Cancer.

Front Cell Dev Biol 2021 18;9:648808. Epub 2021 Feb 18.

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers-State University of New Jersey, New Brunswick, NJ, United States.

Hypoxia is a hallmark of solid tumors and plays a critical role in different steps of tumor progression, including proliferation, survival, angiogenesis, metastasis, metabolic reprogramming, and stemness of cancer cells. Activation of the hypoxia-inducible factor (HIF) signaling plays a critical role in regulating hypoxic responses in tumors. As a key tumor suppressor and transcription factor, p53 responds to a wide variety of stress signals, including hypoxia, and selectively transcribes its target genes to regulate various cellular responses to exert its function in tumor suppression. Studies have demonstrated a close but complex interplay between hypoxia and p53 signaling pathways. The p53 levels and activities can be regulated by the hypoxia and HIF signaling differently depending on the cell/tissue type and the severity and duration of hypoxia. On the other hand, p53 regulates the hypoxia and HIF signaling at multiple levels. Many tumor-associated mutant p53 proteins display gain-of-function (GOF) oncogenic activities to promote cancer progression. Emerging evidence has also shown that GOF mutant p53 can promote cancer progression through its interplay with the hypoxia and HIF signaling pathway. In this review, we summarize our current understanding of the interplay between the hypoxia and p53 signaling pathways, its impact upon cancer progression, and its potential application in cancer therapy.
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http://dx.doi.org/10.3389/fcell.2021.648808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930565PMC
February 2021

Another 'BEE'? - Brain-Eye-Ear (BEE) Disease Secondary to HbSC Disease Masquerading as Multiple Sclerosis.

J Stroke Cerebrovasc Dis 2021 Apr 20;30(4):105618. Epub 2021 Jan 20.

NYU MS Comprehensive Care Center, Department of Neurology, NYU Langone Health, New York, USA.

Recurrent episodes of neurological dysfunction and white matter lesions in a young adult raise suspicion for multiple sclerosis (MS). However, occlusive retinopathy, hearing loss and absence of CSF oligoclonal bands are atypical for MS and should make the clinician consider an alternative diagnosis. We describe a man with hearing loss, visual signs and symptoms, and an accumulating burden of brain lesions, who was treated for a clinical diagnosis of MS for nearly two decades. Genetic testing revealed a unifying diagnosis.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105618DOI Listing
April 2021

Genetic and stochastic influences upon tumor formation and tumor types in Li-Fraumeni mouse models.

Life Sci Alliance 2021 03 29;4(3). Epub 2020 Dec 29.

Rutgers Cancer Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ, USA

is the most frequently mutated gene in human cancers. Li-Fraumeni syndrome patients inheriting heterozygous mutations often have a much-increased risk to develop cancer(s) at early ages. Recent studies suggest that some individuals inherited mutations do not have the early onset or high frequency of cancers. These observations suggest that other genetic, environmental, immunological, epigenetic, or stochastic factors modify the penetrance of the cancerous mutant Tp53 phenotype. To test this possibility, this study explored dominant genetic modifiers of mutations in heterozygous mice with different genetic backgrounds. Both genetic and stochastic effects upon tumor formation were observed in these mice. The genetic background of mice carrying mutations has a strong influence upon the tissue type of the tumor produced and the number of tumors formed in a single mouse. The onset age of a tumor is correlated with the tissue type of that tumor, although identical tumor tissue types can occur at very different ages. These observations help to explain the great diversity of cancers in different Li-Fraumeni patients over lifetimes.
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http://dx.doi.org/10.26508/lsa.202000952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772779PMC
March 2021

Electrospinning of nanofibers: Potentials and perspectives for active food packaging.

Compr Rev Food Sci Food Saf 2020 03 6;19(2):479-502. Epub 2020 Feb 6.

College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China.

Electrospun nanofibers with structural and functional advantages have drawn much attention due to their potential applications for active food packaging. The traditional role of food packaging is just storage containers for food products. The changes of retailing practice and consumer demand promote the development of active packaging to improve the safety, quality, and shelf life of the packaged foods. To develop the technique of electrospinning for active food packaging, electrospun nanofibers have been covalently or non-covalently functionalized for loading diverse bioactive compounds including antimicrobial agents, antioxidant agents, oxygen scavengers, carbon dioxide emitters, and ethylene scavengers. The aim of this review is to present a concise but comprehensive summary on the progress of electrospinning techniques for active food packaging. Emphasis is placed on the tunability of the electrospinning technique, which achieves the modification of fiber composition, orientation, and architecture. Efforts are also made to provide functionalized strategies of electrospun polymeric nanofibers for food packaging application. Furthermore, the existing limitations and prospects for developing electrospinning in food packaging area are discussed.
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http://dx.doi.org/10.1111/1541-4337.12536DOI Listing
March 2020

The emerging role of leukemia inhibitory factor in cancer and therapy.

Pharmacol Ther 2021 May 28;221:107754. Epub 2020 Nov 28.

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers-State University of New Jersey, New Brunswick, NJ 08903, USA. Electronic address:

Leukemia inhibitory factor (LIF) is a multi-functional cytokine of the interleukin-6 (IL-6) superfamily. Initially identified as a factor that inhibits the proliferation of murine myeloid leukemia cells, LIF displays a wide variety of important functions in a cell-, tissue- and context-dependent manner in many physiological and pathological processes, including regulating cell proliferation, pluripotent stem cell self-renewal, tissue/organ development and regeneration, neurogenesis and neural regeneration, maternal reproduction, inflammation, infection, immune response, and metabolism. Emerging evidence has shown that LIF plays an important but complex role in human cancers; while LIF displays a tumor suppressive function in some types of cancers, including leukemia, LIF is overexpressed and exerts an oncogenic function in many more types of cancers. Further, targeting LIF has been actively investigated as a novel strategy for cancer therapy. This review summarizes the recent advances in the studies on LIF in human cancers and its potential application in cancer therapy. A better understanding of the role of LIF in different types of cancers and its underlying mechanisms will help to develop more effective strategies for cancer therapy.
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http://dx.doi.org/10.1016/j.pharmthera.2020.107754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084904PMC
May 2021

Convex Geometry Perspective on the (Standard Model) Effective Field Theory Space.

Phys Rev Lett 2020 Nov;125(20):201601

Interdisciplinary Center for Theoretical Study, University of Science and Technology of China, Hefei, Anhui 230026, China and Peng Huanwu Center for Fundamental Theory, Hefei, Anhui 230026, China.

We present a convex geometry perspective to the effective field theory (EFT) parameter space. We show that the second s derivatives of the forward EFT amplitudes form a convex cone, whose extremal rays are closely connected with states in the UV theory. For tree-level UV completions, these rays are simply theories with all UV particles living in at most one irreducible representation of the symmetries of the theory. In addition, all the extremal rays are determined by the symmetries and can be systematically identified via group theoretical considerations. The implications are twofold. First, geometric information encoded in the EFT space can help reconstruct the UV completion. In particular, we will show that the dim-8 operators are important in reverse engineering the UV physics from the standard model EFT and, thus, deserve more theoretical and experimental investigations. Second, theoretical bounds on the Wilson coefficients can be obtained by identifying the boundaries of the cone and are, in general, stronger than the current positivity bounds. We show explicit examples of these new bounds and demonstrate that they originate from the scattering amplitudes corresponding to entangled states.
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http://dx.doi.org/10.1103/PhysRevLett.125.201601DOI Listing
November 2020

The Regulation of Ferroptosis by Tumor Suppressor p53 and its Pathway.

Int J Mol Sci 2020 Nov 9;21(21). Epub 2020 Nov 9.

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers-State University of New Jersey, New Brunswick, NJ 08903, USA.

Tumor suppressor p53 plays a key role in tumor suppression. In addition to tumor suppression, p53 is also involved in many other biological and pathological processes, such as immune response, maternal reproduction, tissue ischemia/reperfusion injuries and neurodegenerative diseases. While it has been widely accepted that the role of p53 in regulation of cell cycle arrest, senescence and apoptosis contributes greatly to the function of p53 in tumor suppression, emerging evidence has implicated that p53 also exerts its tumor suppressive function through regulation of many other cellular processes, such as metabolism, anti-oxidant defense and ferroptosis. Ferroptosis is a unique iron-dependent form of programmed cell death driven by lipid peroxidation in cells. Ferroptosis has been reported to be involved in cancer, tissue ischemia/reperfusion injuries and neurodegenerative diseases. Recent studies have shown that ferroptosis can be regulated by p53 and its signaling pathway as well as tumor-associated mutant p53. Interestingly, the regulation of ferroptosis by p53 appears to be highly context-dependent. In this review, we summarize recent advances in the regulation of ferroptosis by p53 and its signaling pathway. Further elucidation of the role and molecular mechanism of p53 in ferroptosis regulation will yield new therapeutic strategies for cancer and other diseases, including neurodegenerative diseases and tissue ischemia/reperfusion injuries.
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http://dx.doi.org/10.3390/ijms21218387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664917PMC
November 2020

Identification of Apolipoprotein E as a Potential Diagnostic Biomarker of Nasopharyngeal Carcinoma.

Cancer Manag Res 2020 24;12:8943-8950. Epub 2020 Sep 24.

The Department of Otorhinolaryngology-Head and Neck Surgery, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei, People's Republic of China.

Purpose: Apo-E, a secreted protein, is closely related to the migration and invasion of tumor cells. In this study, we aimed to analyze the expression of Apo-E in nasopharyngeal carcinoma (NPC) patients and cell lines, as well as its effects on NPC cell behavior.

Patients And Methods: Our study included 35 patients with NPC from Zhongnan Hospital. Expression levels of Apo-E in patients with NPC were examined by quantitative reverse transcription-polymerase chain reaction, Western blot, and immunohistochemical (IHC) staining. Receiver operating characteristic (ROC) curves were analyzed using the SPSS 22 software to estimate the sensitivity and specificity of the Apo-E protein in diagnosing NPC. Additionally, the level of Apo-E in NPC cell lines (NP69, 6-10B, and 5-8F) was investigated by Western blotting and IHC.

Results: Levels of Apo-E were higher in NPC patients than in controls. Moreover, ROC analysis revealed that increased Apo-E in the serum of NPC patients may act as a potential biomarker for NPC diagnosis (Area under the curve 0.917). Furthermore, similar results were also identified in NPC cancer cell lines. RNA interference technology was used to overexpress the endogenous Apo-E in the NPC cell line 6-10B. Wound healing and transwell assays indicated that the overexpression of Apo-E increased the number of cell colonies and migration ability, respectively.

Conclusion: In this study, we found that Apo-E was elevated in NPC patients and may act as a potential biomarker for NPC diagnosis. In addition, Apo-E was upregulated in NPC cell lines and promoted cell growth, migration, and invasion.
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http://dx.doi.org/10.2147/CMAR.S239479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522425PMC
September 2020

Endarterectomy for symptomatic internal carotid artery web.

J Neurosurg 2020 Aug 28:1-8. Epub 2020 Aug 28.

3Department of Neurosurgery.

Objective: The carotid web (CW) is an underrecognized source of cryptogenic, embolic stroke in patients younger than 55 years of age, with up to 37% of these patients found to have CW on angiography. Currently, there are little data detailing the best treatment practices to reduce the risk of recurrent stroke in these patients. The authors describe their institutional surgical experience with patients treated via carotid endarterectomy (CEA) for a symptomatic internal carotid artery web.

Methods: A retrospective, observational cohort study was performed including all patients presenting to the authors' institution with CW. All patients who were screened underwent either carotid artery stenting (CAS) or CEA after presentation with ischemic stroke from January 2019 to February 2020. From this sample, patients with suggestive radiological features and pathologically confirmed CW who underwent CEA were identified. Patient demographics, medical histories, radiological images, surgical results, and clinical outcomes were collected and described using descriptive statistics.

Results: A total of 45 patients with symptomatic carotid lesions were treated at the authors' institution during the time period. Twenty patients underwent CAS, 1 of them for a CW. Twenty-five patients were treated via CEA, and of these, 6 presented with ischemic strokes ipsilateral to CWs, including 3 patients who presented with recurrent strokes. The mean patient age was 55 ± 12.6 years and 5 of 6 were women. CT angiography or digital subtraction angiography demonstrated the presence of CWs ipsilateral to the stroke in all patients. All patients underwent resection of CWs using CEA. There were no permanent procedural complications and no patients had stroke recurrence following intervention at the latest follow-up (mean 6.1 ± 4 months). One patient developed mild tongue deviation most likely related to retraction, with complete recovery at follow-up.

Conclusions: CEA is a safe and feasible treatment for symptomatic carotid webs and should be considered a viable alternative to CAS in this patient population.
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http://dx.doi.org/10.3171/2020.5.JNS201107DOI Listing
August 2020

Electrospun chitosan/polycaprolactone nanofibers containing chlorogenic acid-loaded halloysite nanotube for active food packaging.

Carbohydr Polym 2020 Nov 2;247:116711. Epub 2020 Jul 2.

College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, China; Zhejiang Key Laboratory for Agro-Food Processing, Hangzhou, 310058, China; Ningbo Research Institute, Zhejiang University, Ningbo 315100, China. Electronic address:

The aim of this study was to develop chitosan (CS)/polycaprolactone (PCL) electrospun nanofibers with chlorogenic acid (CGA) loaded halloysite nanotubes (HNTs) as a carrier for CGA to provide a long-term sustained release. Results showed that the addition of [email protected] at the concentrations of 2-6 wt% resulted in continuous nanofibers with an average diameter range of 159-166 nm, with improved thermal stability caused by the formation of hydrogen bonds. The incorporation of [email protected] induced a hydrophilic surface and enhanced water vapor barrier property, but impaired the mechanical properties. However, the 2%, 4%, and 6% [email protected] incorporated fibrous mats exhibited an initial release of 18.3 %, 26.2 %, 33.1 % within 15 h, and 34.7 %, 41.4 %, 51.3 % release after 240 h, respectively, indicating a long-term sustained release with enhanced antioxidant and antimicrobial activities. These results suggested the promising applications of the prepared [email protected]/PCL/CS electrospun fibrous mats for active food packaging.
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http://dx.doi.org/10.1016/j.carbpol.2020.116711DOI Listing
November 2020

Zebrafish Crb1, Localizing Uniquely to the Cell Membranes around Cone Photoreceptor Axonemes, Alleviates Light Damage to Photoreceptors and Modulates Cones' Light Responsiveness.

J Neurosci 2020 09 14;40(37):7065-7079. Epub 2020 Aug 14.

Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, 15213 Pennsylvania

The () apical polarity genes are essential for the development and functions of epithelia. Adult zebrafish retinal neuroepithelium expresses three genes (, , and ); however, it is unknown whether and how Crb1 differs from other Crb proteins in expression, localization, and functions. Here, we show that, unlike zebrafish Crb2a and Crb2b as well as mammalian Crb1 and Crb2, zebrafish Crb1 does not localize to the subapical regions of photoreceptors and Müller glial cells; rather, it localizes to a small region of cone outer segments: the cell membranes surrounding the axonemes. Moreover, zebrafish Crb1 is not required for retinal morphogenesis and photoreceptor patterning. Interestingly, Crb1 promotes rod survival under strong white light irradiation in a previously unreported non--cell-autonomous fashion; in addition, Crb1 delays UV and blue cones' chromatin condensation caused by UV light irradiation. Finally, Crb1 plays a role in cones' responsiveness to light through an arrestin-translocation-independent mechanism. The localization of Crb1 and its functions do not differ between male and female fish. We conclude that zebrafish Crb1 has diverged from other vertebrate Crb proteins, representing a neofunctionalization in Crb biology during evolution. Apicobasal polarity of epithelia is an important property that underlies the morphogenesis and functions of epithelial tissues. Epithelial apicobasal polarity is controlled by many polarity genes, including the genes. In vertebrates, multiple genes have been identified, but the differences in their expression patterns and functions are not fully understood. Here, we report a novel subcellular localization of zebrafish Crb1 in retinal cone photoreceptors and evidence for its new functions in photoreceptor maintenance and light responsiveness. This study expands our understanding of the biology of the genes in epithelia, including retinal neuroepithelium.
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http://dx.doi.org/10.1523/JNEUROSCI.0497-20.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480234PMC
September 2020

Acute stroke care in a New York City comprehensive stroke center during the COVID-19 pandemic.

J Stroke Cerebrovasc Dis 2020 Sep 20;29(9):105068. Epub 2020 Jun 20.

Department of Neurology, New York Langone Health, New York, NY, United States. Electronic address:

Background And Purpose: The coronavirus disease-2019 (COVID-19) pandemic caused unprecedented demand and burden on emergency health care services in New York City. We aim to describe our experience providing acute stroke care at a comprehensive stroke center (CSC) and the impact of the pandemic on the quality of care for patients presenting with acute ischemic stroke (AIS).

Methods: We retrospectively analyzed data from a quality improvement registry of consecutive AIS patients at New York University Langone Health's CSC between 06/01/2019-05/15/2020. During the early stages of the pandemic, the acute stroke process was modified to incorporate COVID-19 screening, testing, and other precautionary measures. We compared stroke quality metrics including treatment times and discharge outcomes of AIS patients during the pandemic (03/012020-05/152020) compared with a historical pre-pandemic group (6/1/2019-2/29/2020).

Results: A total of 754 patients (pandemic-120; pre-pandemic-634) were admitted with a principal diagnosis of AIS; 198 (26.3%) received alteplase and/or mechanical thrombectomy. Despite longer median door to head CT times (16 vs 12 minutes; p = 0.05) and a trend towards longer door to groin puncture times (79.5 vs. 71 min, p = 0.06), the time to alteplase administration (36 vs 35 min; p = 0.83), door to reperfusion times (103 vs 97 min, p = 0.18) and defect-free care (95.2% vs 94.7%; p = 0.84) were similar in the pandemic and pre-pandemic groups. Successful recanalization rates (TICI≥2b) were also similar (82.6% vs. 86.7%, p = 0.48). After adjusting for stroke severity, age and a prior history of transient ischemic attack/stroke, pandemic patients had increased discharge mortality (adjusted OR 2.90 95% CI 1.77 - 7.17, p = 0.021) CONCLUSION: Despite unprecedented demands on emergency healthcare services, early multidisciplinary efforts to adapt the acute stroke treatment process resulted in keeping the stroke quality time metrics close to pre-pandemic levels. Future studies will be needed with a larger cohort comparing discharge and long-term outcomes between pre-pandemic and pandemic AIS patients.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305900PMC
September 2020

Gain-of-function mutant p53 in cancer progression and therapy.

J Mol Cell Biol 2020 09;12(9):674-687

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers-State University of New Jersey, New Brunswick, NJ 08903, USA.

p53 is a key tumor suppressor, and loss of p53 function is frequently a prerequisite for cancer development. The p53 gene is the most frequently mutated gene in human cancers; p53 mutations occur in >50% of all human cancers and in almost every type of human cancers. Most of p53 mutations in cancers are missense mutations, which produce the full-length mutant p53 (mutp53) protein with only one amino acid difference from wild-type p53 protein. In addition to loss of the tumor-suppressive function of wild-type p53, many mutp53 proteins acquire new oncogenic activities independently of wild-type p53 to promote cancer progression, termed gain-of-function (GOF). Mutp53 protein often accumulates to very high levels in cancer cells, which is critical for its GOF. Given the high mutation frequency of the p53 gene and the GOF activities of mutp53 in cancer, therapies targeting mutp53 have attracted great interest. Further understanding the mechanisms underlying mutp53 protein accumulation and GOF will help develop effective therapies treating human cancers containing mutp53. In this review, we summarize the recent advances in the studies on mutp53 regulation and GOF as well as therapies targeting mutp53 in human cancers.
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http://dx.doi.org/10.1093/jmcb/mjaa040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749743PMC
September 2020

LIF is essential for ISC function and protects against radiation-induced gastrointestinal syndrome.

Cell Death Dis 2020 07 27;11(7):588. Epub 2020 Jul 27.

Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, 08903, NJ, USA.

Leukemia inhibitory factor (LIF) is a cytokine essential for maintaining pluripotency of mouse embryonic stem cells. However, its role in adult intestinal stem cells (ISCs) is unclear. The adult intestinal epithelium has a high self-renewal rate driven by ISCs in crypts. Here, we find that LIF is present in the ISC niche in crypts and critical for the function of ISCs in maintaining the intestinal epithelial homeostasis and regeneration. Mechanistically, LIF maintains β-catenin activity through the AKT/GSK3β signaling to regulate ISC functions. LIF deficiency in mice impairs the renewal of the intestinal epithelium under the physiological condition. Further, LIF deficiency in mice impairs the regeneration of intestinal epithelium in response to radiation and shortens the lifespan of mice after high doses of radiation due to gastrointestinal (GI) syndrome, which can be rescued by administering recombinant LIF (rLIF). Importantly, LIF exhibits a radioprotective role in wild-type (WT) mice by protecting mice from lethal radiation-induced GI syndrome; administering rLIF promotes intestinal epithelial regeneration and prolongs survival in WT mice after radiation. These results reveal a previously unidentified and a crucial role of LIF in ensuring ISC function, promoting regeneration of the intestinal epithelium in response to radiation and protecting against radiation-induced GI syndrome.
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http://dx.doi.org/10.1038/s41419-020-02790-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385639PMC
July 2020

Stroke Treatment Delay Limits Outcome After Mechanical Thrombectomy: Stratification by Arrival Time and ASPECTS.

J Neuroimaging 2020 09 27;30(5):625-630. Epub 2020 Jun 27.

Department of Neurology, New York Langone Medical Center, New York, NY.

Background And Purpose: Mechanical thrombectomy (MT) has helped many patients achieve functional independence. The effect of time-to-treatment based in specific epochs and as related to Alberta Stroke Program Early CT Score (ASPECTS) has not been established. The goal of the study was to evaluate the association between last known normal (LKN)-to-puncture time and good functional outcome.

Methods: We conducted a retrospective cohort study of prospectively collected acute ischemic stroke patients undergoing MT for large vessel occlusion. We used binary logistic regression models adjusted for age, Modified Treatment in Cerebral Ischemia score, initial National Institutes of Health Stroke Scale, and noncontrast CT ASPECTS to assess the association between LKN-to-puncture time and favorable outcome defined as Modified Rankin Score 0-2 on discharge.

Results: Among 421 patients, 328 were included in analysis. Increased LKN-to-puncture time was associated with decreased probability of good functional outcome (adjusted odds ratio [aOR] ratio per 15-minute delay = .98; 95% confidence interval [CI], .97-.99; P = .001). This was especially true when LKN-puncture time was 0-6 hours (aOR per 15-minute delay = .94; 95% CI, .89-.99; P = .05) or ASPECTS 8-10 (aOR = .98; 95% CI, .97-.99; P = .002) as opposed to when LKN-puncture time was 6-24 hours (aOR per 15-minute delay = .99; 95% CI, .97-1.00; P = .16) and ASPECTS <8 (aOR = .98; 95% CI, .93-1.03; P = .37).

Conclusion: Decreased LKN-groin puncture time improves outcome particularly in those with good ASPECTS presenting within 6 hours. Strategies to decrease reperfusion times should be investigated, particularly in those in the early time window and with good ASPECTS.
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http://dx.doi.org/10.1111/jon.12729DOI Listing
September 2020

Parkin ubiquitinates phosphoglycerate dehydrogenase to suppress serine synthesis and tumor progression.

J Clin Invest 2020 06;130(6):3253-3269

Rutgers Cancer Institute of New Jersey, Rutgers State University of New Jersey, New Brunswick, New Jersey, USA.

Phosphoglycerate dehydrogenase (PHGDH), the first rate-limiting enzyme of serine synthesis, is frequently overexpressed in human cancer. PHGDH overexpression activates serine synthesis to promote cancer progression. Currently, PHGDH regulation in normal cells and cancer is not well understood. Parkin, an E3 ubiquitin ligase involved in Parkinson's disease, is a tumor suppressor. Parkin expression is frequently downregulated in many types of cancer, and its tumor-suppressive mechanism is poorly defined. Here, we show that PHGDH is a substrate for Parkin-mediated ubiquitination and degradation. Parkin interacted with PHGDH and ubiquitinated PHGDH at lysine 330, leading to PHGDH degradation to suppress serine synthesis. Parkin deficiency in cancer cells stabilized PHGDH and activated serine synthesis to promote cell proliferation and tumorigenesis, which was largely abolished by targeting PHGDH with RNA interference, CRISPR/Cas9 KO, or small-molecule PHGDH inhibitors. Furthermore, Parkin expression was inversely correlated with PHGDH expression in human breast cancer and lung cancer. Our results revealed PHGDH ubiquitination by Parkin as a crucial mechanism for PHGDH regulation that contributes to the tumor-suppressive function of Parkin and identified Parkin downregulation as a critical mechanism underlying PHGDH overexpression in cancer.
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http://dx.doi.org/10.1172/JCI132876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260041PMC
June 2020

Gain of function mutant p53 protein activates AKT through the Rac1 signaling to promote tumorigenesis.

Cell Cycle 2020 06 10;19(11):1338-1351. Epub 2020 Apr 10.

Rutgers Cancer Institute of New Jersey; Rutgers University , New Brunswick, NJ, USA.

Tumor suppressor p53 is the most frequently mutated gene in human cancer. Mutant p53 (mutp53) not only loses the tumor suppressive activity of wild type p53, but often gains new oncogenic activities to promote tumorigenesis, defined as mutp53 gain of function (GOF). While the concept of mutp53 GOF is well-established, its underlying mechanism is not well-understood. AKT has been suggested to be activated by mutp53 and contribute to mutp53 GOF, but its underlying mechanism is unclear. In this study, we found that the activation of the Rac1 signaling by mutp53 mediates the promoting effect of mutp53 on AKT activation. Blocking Rac1 signaling by RNAi or a Rac1 inhibitor can inhibit AKT activation by mutp53. Importantly, targeting Rac1/AKT can greatly compromise mutp53 GOF in tumorigenesis. Results from this study uncover a new mechanism for AKT activation in tumors, and reveal that activation of AKT by mutp53 the Rac1 signaling contributes to mutp53 GOF in tumorigenesis. More importantly, this study provides Rac1 and AKT as potential targets for therapy in tumors containing mutp53.
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http://dx.doi.org/10.1080/15384101.2020.1749790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469461PMC
June 2020

Education Research: Teaching and assessing communication and professionalism in neurology residency with simulation.

Neurology 2020 02 20;94(5):229-232. Epub 2020 Jan 20.

From the Departments of Neurology (A.M.K., A.L., P.P., S.K.R., A.N., C.Z., K.I., L.J.B.), Neurosurgery (A.L.), Medicine (S.Z.), Ophthalmology (L.J.B., S.L.G.), and Population Health (L.J.B.), New York University School of Medicine.

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http://dx.doi.org/10.1212/WNL.0000000000008895DOI Listing
February 2020

Multiple Administrations of Intravenous Thrombolytic Therapy to a Stroke Mimic.

J Emerg Med 2020 Mar 3;58(3):e133-e136. Epub 2019 Dec 3.

Department of Neurology, New York University School of Medicine, New York, New York.

Background: Patients who present emergently with focal neurological deficits concerning for acute ischemic stroke can be extremely challenging to diagnose and treat. Unnecessary administration of thrombolytics to potential stroke patients whose symptoms are not caused by an acute ischemic stroke-stroke mimics-may result in patient harm, although the overall risk of hemorrhagic complications among stroke mimics is low.

Case Report: We present a case of a stroke mimic patient with underlying psychiatric disease who was treated with intravenous alteplase on four separate occasions in four different emergency departments in the same city. Although he did not suffer hemorrhagic complications, this case highlights the importance of rapid exchange of health information across institutions to improve diagnostic quality and safety. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Increased awareness of stroke mimics by emergency physicians may improve diagnostic safety for a subset of high-risk patients. Establishing rapid cross-institutional communication pathways that are integrated into provider's workflows to convey essential patient health information has potential to improve stroke diagnostic decision-making and thus represents an important topic for health systems research in emergency medicine.
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http://dx.doi.org/10.1016/j.jemermed.2019.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200287PMC
March 2020

Possible Empirical Evidence of Glymphatic System on Computed Tomography After Endovascular Perforations.

World Neurosurg 2020 Feb 23;134:e400-e404. Epub 2019 Oct 23.

Department of Radiology, NYU Langone Health, New York, New York, USA; Department of Neurosurgery, NYU Langone Health, New York, New York, USA.

Background: The glial-lymphatic pathway is a fluid-clearance pathway consisting of a para-arterial route for the flow of cerebrospinal fluid along perivascular spaces and subsequently toward the brain interstitium. In this case series, we aim to investigate an empirical demonstration of glymphatic clearance of extravasated iodine following perforation incurred during endovascular therapy on serial computed tomography.

Methods: Six consecutive cases of endovascular perforation during thrombectomy performed between 2005 and 2018 were retrospectively collected by searching our internal database of total 446 thrombectomies. Two cases were excluded because care was withdrawn shortly following the procedure and no follow-up imaging was available. One case was excluded because a ventricular drain was placed. Three cases were hence included in this analysis.

Results: All 3 cases demonstrated progressive absorption of contrast by the brain parenchyma with eventual contrast disappearance.

Conclusions: We described a likely in vivo computed tomography correlate of the glymphatic system in a cohort of patients who sustained intraprocedural extravasation during thrombectomy for acute ischemic stroke.
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http://dx.doi.org/10.1016/j.wneu.2019.10.089DOI Listing
February 2020

Sequential electrospinning of multilayer ethylcellulose/gelatin/ethylcellulose nanofibrous film for sustained release of curcumin.

Food Chem 2020 Mar 16;308:125599. Epub 2019 Oct 16.

College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China; Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang University, Hangzhou 310058, China; Ningbo Research Institute, Zhejiang University, Ningbo 315100, China. Electronic address:

In this work, sequential electrospinning was utilized to fabricate a multilayer film with ethylcellulose nanofibers as the outer layer and curcumin-loaded gelatin nanofibers as the inner layer. Field-emission scanning electronic microscopy observations showed that the outer and inner layers had a smooth surface and clear boundary. The hydrophobic outer layers decreased the water vapor permeability and improved the water contact resistance of the hydrophilic inner layer, and the intimate interactions of hydrogen bonds between two adjacent layers enhanced the thermal stability. The multilayer film exhibited a sustained release manner of the encapsulated curcumin for 96 h, compared to the burst release within 30 min from the gelatin film. In addition, the antioxidant activities of the released curcumin from the multilayer film were well retained within 96 h. These results suggested that the multilayer nanofibrous film fabricated by sequential electrospinning has potential applications in bioactive encapsulation and controlled release.
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http://dx.doi.org/10.1016/j.foodchem.2019.125599DOI Listing
March 2020

Cerebrospinal Fluid in Posterior Reversible Encephalopathy Syndrome: Implications of Elevated Protein and Pleocytosis.

Neurohospitalist 2019 Apr 27;9(2):58-64. Epub 2018 Sep 27.

Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Background And Purpose: Patients with posterior reversible encephalopathy syndrome (PRES) sometimes undergo analysis of cerebrospinal fluid (CSF) to exclude alternative diagnoses. This study's objectives were to describe the CSF characteristics in patients with PRES and to identify clinical and radiologic findings associated with distinct CSF abnormalities.

Methods: We identified a retrospective cohort of patients with PRES. We compared clinical and radiographic characteristics of those who did versus did not undergo lumbar puncture, described the observed range of CSF findings, and analyzed clinical and radiographic features associated with specific CSF abnormalities.

Results: A total of 188 patients were included. Patients with (n = 77) and without (n = 111) CSF analysis had similar clinical and radiographic characteristics. Cerebrospinal fluid protein was elevated in 46 (60%) of 77, with median CSF protein 53 mg/dL (upper limit of normal 45 mg/dL). Protein elevation was significantly associated with radiographic severity ( = .0058) but not with seizure, time from symptom onset, radiographic evidence of diffusion restriction, or contrast enhancement. Five (7%) patients had elevated CSF white blood cells, all of whom had infarction and/or hemorrhage on neuroimaging, and 4 of whom had eclampsia.

Conclusion: The CSF of most patients with PRES shows a mild protein elevation commensurate with radiographic severity. Cerebrospinal fluid pleocytosis may mark a distinct subtype of PRES with predisposition toward infarction and/or hemorrhage. These findings help clinicians interpret CSF findings in these patients and generate new hypotheses about the pathophysiology of this syndrome.
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http://dx.doi.org/10.1177/1941874418802061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429675PMC
April 2019

Tumor suppressor p53 and metabolism.

J Mol Cell Biol 2019 04;11(4):284-292

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, State University of New Jersey, New Brunswick, NJ, USA.

p53 plays a key role in tumor suppression. The tumor suppressive function of p53 has long been attributed to its ability to induce apoptosis, cell cycle arrest, and senescence in cells. However, recent studies suggest that other functions of p53 also contribute to its role as a tumor suppressor, such as its function in metabolic regulation. p53 regulates various metabolic pathways to maintain the metabolic homeostasis of cells and adapt cells to stress. In addition, recent studies have also shown that gain-of-function (GOF) mutant p53 proteins drive metabolic reprogramming in cancer cells, contributing to cancer progression. Further understanding of p53 and its GOF mutants in metabolism will provide new opportunities for cancer therapy.
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http://dx.doi.org/10.1093/jmcb/mjy070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487777PMC
April 2019

Formation and Stability of Core-Shell Nanofibers by Electrospinning of Gel-Like Corn Oil-in-Water Emulsions Stabilized by Gelatin.

Authors:
Cen Zhang Hui Zhang

J Agric Food Chem 2018 Nov 16;66(44):11681-11690. Epub 2018 Oct 16.

National Engineering Laboratory of Intelligent Food Technology and Equipment, Key Laboratory for Agro-Products Postharvest Handling of Ministry of Agriculture, Key Laboratory for Agro-Products Nutritional Evaluation of Ministry of Agriculture, Zhejiang Key Laboratory for Agro-Food Processing, Fuli Institute of Food Science, College of Biosystems Engineering and Food Science , Zhejiang University , Hangzhou 310058 , China.

Core-shell nanofibers were fabricated by electrospinning of gel-like corn oil emulsions stabilized by gelatin. The oil-in-water (O/W) emulsions satisfied the Herschel-Bulkley rheological model and showed shear-thinning and predominantly elastic gel behaviors. The increasing oil fractions (φ) ranging from 0 to 0.6 remarkably increased the apparent viscosity and then led to an increase in the average diameter and encapsulation efficiency of electrospun fibers. Core-shell structured fibers by emulsion electrospinning were observed in transmission electron microscopy (TEM) images. The encapsulated oil was found to randomly distribute as core, especially inside the beads. The binding of corn oil to gelatin was mainly driven by noncovalent forces. These core-shell fibers at various φ values (φ = 0.2, 0.4, 0.6, and 0.8) showed a high thermal decomposition stability upon heating to 250 °C, and the denaturation temperatures were 85.32 °C, 77.97 °C, 82.99 °C, and 87.25 °C, respectively. The corn oil encapsulated in emulsion-based fiber mats had good storage stability during 5 days. These results contributed to a good understanding of emulsion electrospinning of food materials for potential applications in bioactive encapsulation, enzyme immobilization, and active food packaging.
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http://dx.doi.org/10.1021/acs.jafc.8b04270DOI Listing
November 2018

The Auger process in multilayer WSe crystals.

Nanoscale 2018 Sep;10(37):17585-17592

Division of Nanophotonics, CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.

Multilayer WSe2 with a larger optical density of states and absorbance is regarded as a better candidate than its monolayer counterpart for next generation optoelectronic devices, however insight into carrier dynamics is still lacking. Herein, we experimentally observed an anomalous PL quenching with decreasing temperature for multilayer WSe2. At a low temperature (77 K), the Auger processes govern carrier recombination in multilayer WSe2, which are induced by a phonon bottleneck effect and strong photon absorption, and lead to PL quenching. From transient absorption spectroscopy, two distinct Auger processes are observed: a fast one (1-2 ps) and a slow one (>190 ps), which are caused by two different deep midgap defect-levels in WSe2. Based on the Auger recombination model, these two Auger rates are quantitatively estimated at ∼6.69 (±0.05) × 10-2 and 1.22 (±0.04) × 10-3 cm2 s-1, respectively. Our current observations provide an important supplement for optimizing the optical and electric behaviors in multilayer WSe2 based devices.
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http://dx.doi.org/10.1039/c8nr02567cDOI Listing
September 2018

Parkinson's disease-associated protein Parkin: an unusual player in cancer.

Cancer Commun (Lond) 2018 06 26;38(1):40. Epub 2018 Jun 26.

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, State University of New Jersey, New Brunswick, NJ, 08903, USA.

The mutation of the Parkin gene is a cause of familial Parkinson's disease. A growing body of evidence suggests that Parkin also functions as a tumor suppressor. Parkin is an ubiquitin E3 ligase, and plays important roles in a variety of cellular processes implicated in tumorigenesis, including cell cycle, cell proliferation, apoptosis, metastasis, mitophagy and metabolic reprogramming. Here we review the role and mechanism of Parkin in cancer.
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http://dx.doi.org/10.1186/s40880-018-0314-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020249PMC
June 2018