Publications by authors named "Gurvinder Kaur"

159 Publications

Commentary: Transcondylar Odontoid Resection and Stabilization for Craniovertebral Degenerative Compression: 2-Dimensional Operative Video.

Oper Neurosurg (Hagerstown) 2021 Jul 22. Epub 2021 Jul 22.

Department of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, Florida, USA.

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http://dx.doi.org/10.1093/ons/opab271DOI Listing
July 2021

Commentary: Infra-Occipital Supra-Tentorial Approach for Resection of Low-Grade Tumor of the Left Lingual Gyrus: 2-Dimensional Operative Video.

Oper Neurosurg (Hagerstown) 2021 Jul 16. Epub 2021 Jul 16.

Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.

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http://dx.doi.org/10.1093/ons/opab210DOI Listing
July 2021

Commentary: Interposition Grafting of the Facial Nerve After Resection of a Large Facial Nerve Schwannoma: 2-Dimensional Operative Video.

Oper Neurosurg (Hagerstown) 2021 Jul 7. Epub 2021 Jul 7.

Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.

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http://dx.doi.org/10.1093/ons/opab254DOI Listing
July 2021

Commentary: Early Experience With Virtual and Synchronized Augmented Reality Platform for Preoperative Planning and Intraoperative Navigation: A Case Series.

Oper Neurosurg (Hagerstown) 2021 Jun 25. Epub 2021 Jun 25.

Department of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, Florida, USA.

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http://dx.doi.org/10.1093/ons/opab201DOI Listing
June 2021

Perioperative Complications in Endoscopic Endonasal versus Transcranial Resections of Adult Craniopharyngiomas.

World Neurosurg 2021 Jun 18. Epub 2021 Jun 18.

Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA; Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, Florida, USA. Electronic address:

Background: Adult craniopharyngiomas are low-grade tumors of the pituitary infundibulum that can be locally aggressive and frequently present with profound visual deficits and endocrinopathies. Surgical resection remains the preferred initial treatment for these lesions, and recently endoscopic endonasal approaches (EEAs) have become increasingly used. However, minimal data exist comparing these techniques with traditional transcranial (TC) methods. The purpose of this study was to evaluate perioperative differences in EEA and TC approaches for adult craniopharyngiomas over the past several decades.

Methods: Craniopharyngioma surgeries in the Nationwide Inpatient Sample from 1998 to 2014 were identified. Complication rates, mortality rates, and annual treatment trends were stratified by procedure. Annual caseload was assessed with linear regression, and multivariate logistic regression models were created to determine predictors of inpatient mortality and perioperative complications.

Results: From 1998-2014, a significant increase in EEAs for craniopharyngiomas (+4.36/year, r = 0.80, P < 0.0001) was observed. In contrast, no increase in TC surgeries for these lesions was seen. In multivariate analysis, EEAs were more likely to experience postoperative cerebrospinal fluid leak (odds ratio = 2.61, P < 0.0001). However, EEAs were protective against all other perioperative complications including diabetes insipidus, panhypopituitarism, visual impairment, and even mortality (odds ratio = 0.41, P = 0.0007).

Conclusions: Over the past several decades, utilization of EEAs to resect adult craniopharyngiomas has increased. EEAs appear to be associated with lower rates of perioperative mortality and complications. However, long-term, prospective studies controlling for tumor size, location, and preoperative symptomatology are needed to determine when one approach should be used preferentially over the other.
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http://dx.doi.org/10.1016/j.wneu.2021.06.066DOI Listing
June 2021

Genome-wide identification of potential biomarkers in multiple myeloma using meta-analysis of mRNA and miRNA expression data.

Sci Rep 2021 May 26;11(1):10957. Epub 2021 May 26.

Laboratory Oncology Unit, Dr B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, 110029, India.

Multiple myeloma (MM) is a plasma cell malignancy with diverse clinical phenotypes and molecular heterogeneity not completely understood. Differentially expressed genes (DEGs) and miRNAs (DEMs) in MM may influence disease pathogenesis, clinical presentation / drug sensitivities. But these signatures overlap meagrely plausibly due to complexity of myeloma genome, diversity in primary cells studied, molecular technologies/ analytical tools utilized. This warrants further investigations since DEGs/DEMs can impact clinical outcomes and guide personalized therapy. We have conducted genome-wide meta-analysis of DEGs/DEMs in MM versus Normal Plasma Cells (NPCs) and derived unified putative signatures for MM. 100 DEMs and 1,362 DEGs were found deranged between MM and NPCs. Signatures of 37 DEMs ('Union 37') and 154 DEGs ('Union 154') were deduced that shared 17 DEMs and 22 DEGs with published prognostic signatures, respectively. Two miRs (miR-16-2-3p, 30d-2-3p) correlated with survival outcomes. PPI analysis identified 5 topmost functionally connected hub genes (UBC, ITGA4, HSP90AB1, VCAM1, VCP). Transcription factor regulatory networks were determined for five seed DEGs with ≥ 4 biomarker applications (CDKN1A, CDKN2A, MMP9, IGF1, MKI67) and three topmost up/ down regulated DEMs (miR-23b, 195, let7b/ miR-20a, 155, 92a). Further studies are warranted to establish and translate prognostic potential of these signatures for MM.
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http://dx.doi.org/10.1038/s41598-021-90424-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154993PMC
May 2021

Commentary: Concomitant Embolization and Microsurgical Resection of a Giant, Hypervascular Skull Base Meningioma: 2-Dimensional Operative Video.

Oper Neurosurg (Hagerstown) 2021 Jul;21(2):E99-E100

Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.

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http://dx.doi.org/10.1093/ons/opab164DOI Listing
July 2021

Helicase-like transcription factor-deletion from the tumor microenvironment in a cell line-derived xenograft model of colorectal cancer reprogrammed the human transcriptome-S-nitroso-proteome to promote inflammation and redirect metastasis.

PLoS One 2021 19;16(5):e0251132. Epub 2021 May 19.

Department of Cell Biology & Biochemistry, Texas Tech University Health Sciences Center, Lubbock, Texas, United States of America.

Methylation of the HLTF gene in colorectal cancer (CRC) cells occurs more frequently in men than women. Progressive epigenetic silencing of HLTF in tumor cells is accompanied by negligible expression in the tumor microenvironment (TME). Cell line-derived xenografts (CDX) were established in control (Hltf+/+) and Hltf-deleted male Rag2-/-IL2rg-/- mice by direct orthotopic cell microinjection (OCMI) of HLTF+/+HCT116 Red-FLuc cells into the submucosa of the cecum. Combinatorial induction of IL6 and S100A8/A9 in the Hltf-deleted TME with ICAM-1 and IL8 in the primary tumor activated a positive feedback loop. The proinflammatory niche produced a major shift in CDX metastasis to peritoneal dissemination compared to controls. Inducible nitric oxide (iNOS) gene expression and transactivation of the iNOS-S100A8/A9 signaling complex in Hltf-deleted TME reprogrammed the human S-nitroso-proteome. POTEE, TRIM52 and UN45B were S-nitrosylated on the conserved I/L-X-C-X2-D/E motif indicative of iNOS-S100A8/A9-mediated S-nitrosylation. 2D-DIGE and protein identification by MALDI-TOF/TOF mass spectrometry authenticated S-nitrosylation of 53 individual cysteines in half-site motifs (I/L-X-C or C-X-X-D/E) in CDX tumors. POTEE in CDX tumors is both a general S-nitrosylation target and an iNOS-S100A8/A9 site-specific (Cys638) target in the Hltf-deleted TME. REL is an example of convergence of transcriptomic-S-nitroso-proteomic signaling. The gene is transcriptionally activated in CDX tumors with an Hltf-deleted TME, and REL-SNO (Cys143) was found in primary CDX tumors and all metastatic sites. Primary CDX tumors from Hltf-deleted TME shared 60% of their S-nitroso-proteome with all metastatic sites. Forty percent of SNO-proteins from primary CDX tumors were variably expressed at metastatic sites. Global S-nitrosylation of proteins in pathways related to cytoskeleton and motility was strongly implicated in the metastatic dissemination of CDX tumors. Hltf-deletion from the TME played a major role in the pathogenesis of inflammation and linked protein S-nitrosylation in primary CDX tumors with spatiotemporal continuity in metastatic progression when the tumor cells expressed HLTF.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251132PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8133447PMC
May 2021

Commentary: The Infratemporal Retro-Eustachian Transposition of the Temporoparietal Fascial Flap for Clival Reconstruction After Endoscopic Endonasal Approach: An Anatomic Conceptual Technique.

Oper Neurosurg (Hagerstown) 2021 Jul;21(2):E171-E172

Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.

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http://dx.doi.org/10.1093/ons/opab147DOI Listing
July 2021

Commentary: Total Petrosectomy for the Total Resection of Sphenopetroclival Meningioma: 2-Dimensional Operative Video.

Oper Neurosurg (Hagerstown) 2021 06;21(1):E24-E25

Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.

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http://dx.doi.org/10.1093/ons/opab091DOI Listing
June 2021

Dietary Annatto-Extracted Tocotrienol Reduces Inflammation and Oxidative Stress, and Improves Macronutrient Metabolism in Obese Mice: A Metabolic Profiling Study.

Nutrients 2021 Apr 13;13(4). Epub 2021 Apr 13.

Department of Nutrition, University of California at Davis, Davis, CA 95616, USA.

Obesity and its related complications are a world-wide health problem. Dietary tocotrienols (TT) have been shown to improve obesity-associated metabolic disorders, such as hypercholesterolemia, hyperglycemia, and gut dysbiosis. This study examined the hypothesis that the antioxidant capacity of TT alters metabolites of oxidative stress and improves systemic metabolism. C57BL/6J mice were fed either a high-fat diet (HFD control) or HFD supplemented with 800 mg annatto-extracted TT/kg (HFD+TT800) for 14 weeks. Sera from obese mice were examined by non-targeted metabolite analysis using UHPLC/MS. Compared to the HFD group, the HFD+TT800 group had higher levels of serum metabolites, essential amino acids (lysine and methionine), sphingomyelins, phosphatidylcholine, lysophospholipids, and vitamins (pantothenate, pyridoxamine, pyridoxal, and retinol). TT-treated mice had lowered levels of serum metabolites, dicarboxylic fatty acids, and inflammatory/oxidative stress markers (trimethylamine N-oxide, kynurenate, 12,13-DiHOME, and 13-HODE + 9-HODE) compared to the control. The results suggest that TT supplementation lowered inflammation and oxidative stress (oxidized glutathione and GSH/GSSH) and improved macronutrient metabolism (carbohydrates) in obese mice. Thus, TT actions on metabolites were beneficial in reducing obesity-associated hypercholesterolemia/hyperglycemia. The effects of a non-toxic dose of TT in mice support the potential for clinical applications in obesity and metabolic disease.
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http://dx.doi.org/10.3390/nu13041267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069008PMC
April 2021

Impact of C1q fixing donor-specific antibodies on renal transplant outcome.

Scand J Immunol 2021 Jul 15;94(1):e13048. Epub 2021 May 15.

Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India.

Not all anti-HLA donor-specific antibodies (HLA-DSAs) are detrimental to renal allograft. In this context, the C1q complement activating ability of antibodies appears to be an important parameter to distinguish clinically inert versus detrimental DSAs. We evaluated sera of 206 consecutive primary live donor renal transplant recipients before transplant and at post-operative day 7, 30, 90, 180 and at the time of graft dysfunction for quantifying HLA-DSAs using single antigen bead assay on a Luminex platform. Patients positive for these antibodies with an MFI >500 were further screened for C1q fixing nature of DSA. Fourteen of the 18 antibody-positive patients had C1q fixing DSA with MFI value >5000. Only 4 antibody-positive patients did not have C1q fixing DSA. The MFI values of DSA detected by C1q assay were generally higher at least by 25% than those detected by the conventional IgG-SAB assay. Twelve of the 14 patients (85.71%) with C1q+ DSA developed antibody-mediated rejection during the mean follow-up period of 21.43 ± 8.03 months as compared to none of the four C1q-negative DSA (85.71% vs 0%; P = .001). These results suggest deleterious effect of C1q+ DSA vis-à-vis C1q-negative DSA on renal allograft.
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http://dx.doi.org/10.1111/sji.13048DOI Listing
July 2021

Therapeutic application of Sertoli cells for treatment of various diseases.

Semin Cell Dev Biol 2021 Apr 25. Epub 2021 Apr 25.

Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Medical Education, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA. Electronic address:

Sertoli cells (SCs) are immune privileged cells found in the testis that function to immunologically protect maturing germ cells from immune destruction. This immune protection is due to the blood-testis-barrier, which prevents infiltration of cytotoxic immune cells and antibodies, and SC production of immunomodulatory factors, that favor a tolerogenic environment. The ability of SCs to create an immune privileged environment has led to the exploration of their potential use in the treatment of various diseases. SCs have been utilized to create a tolerogenic ectopic microenvironment, to protect co-grafted cells, and to deliver therapeutic proteins through gene therapy. To date, numerous studies have reported the potential use of SCs for the treatment of diabetes, neurodegenerative disorders, and restoration of spermatogenesis. Additionally, SCs have been investigated as a delivery vehicle for therapeutic products to treat other diseases like Laron syndrome, muscular dystrophy, and infections. This review will provide an overview of these therapeutic applications.
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http://dx.doi.org/10.1016/j.semcdb.2021.04.007DOI Listing
April 2021

C-Peptide as a Therapy for Type 1 Diabetes Mellitus.

Biomedicines 2021 Mar 8;9(3). Epub 2021 Mar 8.

Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.

Diabetes mellitus (DM) is a complex metabolic disease affecting one-third of the United States population. It is characterized by hyperglycemia, where the hormone insulin is either not produced sufficiently or where there is a resistance to insulin. Patients with Type 1 DM (T1DM), in which the insulin-producing beta cells are destroyed by autoimmune mechanisms, have a significantly increased risk of developing life-threatening cardiovascular complications, even when exogenous insulin is administered. In fact, due to various factors such as limited blood glucose measurements and timing of insulin administration, only 37% of T1DM adults achieve normoglycemia. Furthermore, T1DM patients do not produce C-peptide, a cleavage product from insulin processing. C-peptide has potential therapeutic effects in vitro and in vivo on many complications of T1DM, such as peripheral neuropathy, atherosclerosis, and inflammation. Thus, delivery of C-peptide in conjunction with insulin through a pump, pancreatic islet transplantation, or genetically engineered Sertoli cells (an immune privileged cell type) may ameliorate many of the cardiovascular and vascular complications afflicting T1DM patients.
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http://dx.doi.org/10.3390/biomedicines9030270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000702PMC
March 2021

Prospective Comparison of Angiogenesis-Specific 68Ga-RGD2 PET/CT Imaging Parameters and DAS28-ESR in Rheumatoid Arthritis.

Clin Nucl Med 2021 Jul;46(7):556-561

From the Departments of Nuclear Medicine.

Objective: The aim of this study was to compare the performance of angiogenesis-specific 68Ga-RGD2 PET/CT with Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) in assessing disease activity and treatment response in rheumatoid arthritis (RA).

Methods: This was a prospective study comparing the performance of 68Ga-RGD2 PET/CT and DAS28-ESR in 30 RA patients. All of them underwent 68Ga-RGD2 PET/CT scan from head to toe and clinical examination at the baseline. A repeat scan and clinical examination were done in 27 patients after 3 months of treatment with disease-modifying antirheumatic drugs ± steroids. Three PET parameters, that is, PJC (PET-positive joint count), aSUVmax (average SUVmax), and hSUVmax (highest SUVmax), of positive joints were compared with the DAS28-ESR for disease activity assessment and response evaluation.

Results: Among the 3 PET parameters, PJC showed a significant correlation with the DAS28-ESR (0.64, P < 0.01). A significant change was observed with treatment in the DAS28-ESR and PET parameters of 27 patients at follow-up. There was significant correlation between percentage changes in DAS28-ESR and scan parameters such as PJC (0.689, P < 0.001), aSUVmax (0.712, P < 0.001), and hSUVmax (0.555, P = 0.003) values. The absolute change in aSUVmax value could accurately discriminate (area under the curve, 0.98; P = 0.001) European League Against Rheumatism responders from nonresponders.

Conclusions: 68Ga-RGD2 PET/CT is a promising tool for objective assessment of disease activity and treatment response in patients with RA.
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http://dx.doi.org/10.1097/RLU.0000000000003586DOI Listing
July 2021

Commentary: An Update of Neuroanesthesia for Intraoperative Brain Mapping Craniotomy.

Neurosurgery 2021 Mar 17. Epub 2021 Mar 17.

Department of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, Florida, USA.

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http://dx.doi.org/10.1093/neuros/nyab065DOI Listing
March 2021

Neuro-oncology practice guidelines from a high-volume surgeon at the COVID-19 epicenter.

J Clin Neurosci 2021 Mar 16;85:1-5. Epub 2020 Dec 16.

Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.

Background: During the coronavirus 19 (COVID-19) pandemic, physicians have begun adapting their daily practices to prevent transmissions. In this study we aimed to provide surgical neuro-oncologists with practice guidelines during the COVID-19 pandemic based on objective data from a high-volume brain tumor surgeon at the current COVID-19 epicenter.

Methods: All outpatient visits and surgeries performed by the senior author during the COVID-19 pandemic were compared between the initial quarantine (3/23/20-5/4/20), the plateau period following quarantine (5/5/20-6/27/20), and the second peak (6/28/20-7/20/20). In-person and telemedicine visits were evaluated for crossovers. Surgeries were subdivided based on lesion type and evaluated across the same time period.

Results: From 3/23/20-7/20/20, 469 clinic visits and 196 surgeries were identified. After quarantine was lifted, face-to-face visits increased (P < 0.01) yet no change in telehealth visits occurred. Of 327 telehealth visits, only 5.8% converted to in-person during the 4-month period with the most cited reason being patient preference (68.4%). Of the 196 surgeries performed during the pandemic, 29.1% occurred during quarantine, 49.0% during the plateau, and 21.9% occurred in the second peak. No COVID negative patients developed symptoms at follow-up. 55.6% were performed on malignant tumors and 31.6% were benign with no difference in case volumes throughout the pandemic.

Conclusions: Despite exceptional challenges, we have maintained a high-volume surgical neuro-oncology practice at the epicenter of the COVID-19 pandemic. We provide the protocols implemented at our institution in order to maximize neuro-oncology care while mitigating risk of COVID-19 exposure to both patients and providers.
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http://dx.doi.org/10.1016/j.jocn.2020.12.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834482PMC
March 2021

SLC6A14 deficiency is linked to obesity, fatty liver, and metabolic syndrome but only under conditions of a high-fat diet.

Biochim Biophys Acta Mol Basis Dis 2021 May 26;1867(5):166087. Epub 2021 Jan 26.

Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA. Electronic address:

SLC6A14 is a Na/Cl-coupled transporter for neutral/cationic amino acids, expressed in ileum and colon. A single-nucleotide polymorphism (SNP), rs2011162 (-22,510C > G), in SLC6A14 coding for the 3'-untranslated region (3'-UTR) is associated with obesity in humans. But the impact of this polymorphism on the transporter expression and its connection to obesity are not known. Our objective was to address these issues. The impact of rs2011162 (-22,510C > G) on SLC6A14 expression was monitored using a luciferase reporter. The link between Slc6a14 and obesity was investigated in wild type and Slc6a14 mice when fed a normal diet or a high-fat diet. The obesity-associated 3'-UTR polymorphism reduced SLC6A14 expression. With a high-fat diet, Slc6a14 mice gained more weight than wild type mice. With normal diet, there was no difference between the two genotypes. The gain in body weight with the high-fat diet in Slc6a14 mice was accompanied with metabolic syndrome. With the high-fat diet, Slc6a14 mice showed increased food intake, developed fatty liver, and altered plasma amino acid profile. The high-fat diet-associated hepatic steatosis in Slc6a14 mice showed male preponderance. We conclude that the 3'-UTR SNP in SLC6A14 associated with obesity decreases the expression of SLC6A14 and that the deficiency of SLC6A14 is linked to obesity. This is supported by the findings that Slc6a14 mice develop obesity, fatty liver, and metabolic syndrome. This connection is evident only with a high-fat diet. Therefore, dietary/pharmacologic interventions that induce SLC6A14 expression in the intestinal tract might have potential for obesity prevention..
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http://dx.doi.org/10.1016/j.bbadis.2021.166087DOI Listing
May 2021

Effective Organizational Justice and Organizational Citizenship Behavior Using Fuzzy Logic to Obtain the Optimal Relationship.

Qual Manag Health Care 2021 Jan/Mar 01;30(1):13-20

School of Humanities & Social Science, Thapar Institute of Engineering & Technology (Deemed University), Patiala, Punjab, India (Drs Ajlouni and Kaur); and Faculty of Science and Information Technology, Jadara University, Irbid, Jordan (Dr Alomari).

Background: Organizational justice (OJ) is important for organizational success; it reflects employee perceptions of fair treatment. OJ promotes employee retention and work engagement toward high performance. Organizational citizenship behavior (OCB) is a discretionary behavior, describing how employees contribute to a smoother organizational performance. OCB enhances employee satisfaction, quality of care, patients' satisfaction with hospital performance, and the use of best hospital practices. Moreover, OJ increases employee satisfaction and is perceived as a factor that encourages workers to go "above and beyond" their responsibilities, while avoiding OCB in the workplace may reduce awareness of justice. Previous efforts have shown that perceptions of a just workplace promoted OCB at different industrial companies. Still, few studies have investigated this relationship in hospitals.

Objectives: This study addressed this gap by investigating the significant relationships of OJ and OCB in a large Jordanian hospital.

Methods: A fuzzy approach to Pearson's correlation was applied to test the formulated hypothesis, with an aim to better understand causal correlation of vague data.

Results: A statistically significant, positive correlation existed between OJ and OCB. Maximum correlations existed between distributive justice and altruism, procedural justice, courtesy, and interactional or interpersonal justice and conscientiousness. This study showed that procedural justice was the best predictor of OCB.

Conclusion: This study revealed a correlation between OJ and OCB, reflecting the diversity of these correlation relationships, which can help decision makers to form their strategic plans.
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http://dx.doi.org/10.1097/QMH.0000000000000288DOI Listing
December 2020

Commentary: Bilateral "Rescue Strip" Technique for Endoscopic Endonasal Approaches to the Clivus.

Oper Neurosurg (Hagerstown) 2021 01;20(2):E116-E117

Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida.

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http://dx.doi.org/10.1093/ons/opaa346DOI Listing
January 2021

Commentary: Glomus Vagale Tumor Resection: 2-Dimensional Operative Video.

Oper Neurosurg (Hagerstown) 2020 12;20(1):E58-E59

Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida.

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http://dx.doi.org/10.1093/ons/opaa333DOI Listing
December 2020

Neonatal Pig Sertoli Cells Survive Xenotransplantation by Creating an Immune Modulatory Environment Involving CD4 and CD8 Regulatory T Cells.

Cell Transplant 2020 Jan-Dec;29:963689720947102

Department of Cell Biology and Biochemistry, 12343Texas Tech University Health Sciences Center, Lubbock, TX, USA.

The acute cell-mediated immune response presents a significant barrier to xenotransplantation. Immune-privileged Sertoli cells (SC) can prolong the survival of co-transplanted cells including xenogeneic islets, hepatocytes, and neurons by protecting them from immune rejection. Additionally, SC survive as allo- and xenografts without the use of any immunosuppressive drugs suggesting elucidating the survival mechanism(s) of SC could be used to improve survival of xenografts. In this study, the survival and immune response generated toward neonatal pig SC (NPSC) or neonatal pig islets (NPI), nonimmune-privileged controls, was compared after xenotransplantation into naïve Lewis rats without immune suppression. The NPSC survived throughout the study, while NPI were rejected within 9 days. Analysis of the grafts revealed that macrophages and T cells were the main immune cells infiltrating the NPSC and NPI grafts. Further characterization of the T cells within the grafts indicated that the NPSC grafts contained significantly more cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8) regulatory T cells (Tregs) at early time points than the NPI grafts. Additionally, the presence of increased amounts of interleukin 10 (IL-10) and transforming growth factor (TGF) β and decreased levels of tumor necrosis factor (TNF) α and apoptosis in the NPSC grafts compared to NPI grafts suggests the presence of regulatory immune cells in the NPSC grafts. The NPSC expressed several immunoregulatory factors such as TGFβ, thrombospondin-1 (THBS1), indoleamine-pyrrole 2,3-dioxygenase, and galectin-1, which could promote the recruitment of these regulatory immune cells to the NPSC grafts. In contrast, NPI grafts had fewer Tregs and increased apoptosis and inflammation (increased TNFα, decreased IL-10 and TGFβ) suggestive of cytotoxic immune cells that contribute to their early rejection. Collectively, our data suggest that a regulatory graft environment with regulatory immune cells including CD4 and CD8 Tregs in NPSC grafts could be attributed to the prolonged survival of the NPSC xenografts.
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http://dx.doi.org/10.1177/0963689720947102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564626PMC
July 2021

Near-infrared stimulated hydrogel patch for photothermal therapeutics and thermoresponsive drug delivery.

J Photochem Photobiol B 2020 Sep 14;210:111960. Epub 2020 Jul 14.

Central Scientific Instruments Organization (CSIR-CSIO), Chandigarh 160030, India; Academy of Scientific and Innovative Research, CSIR-CSIO, Chandigarh 160030, India.

Nanotechnology driven cancer theranostics hold potential as promising future clinical modalities. Currently, there is a strong emphasis on the development of combinational modalities, especially for cancer treatment. In this study, we present a topical hydrogel patch for nanomaterial-assisted photothermal therapeutics as well as for on-demand drug delivery application. The patch was derived from interpenetrating networks (IPNs) of alginate (Alg) and polyacrylamide (PAAm) in weight ratio 8:1 by free radical polymerization. The patch interiors were composed of hybrid nanostructures derived from gold nanorods (AuNRs) anchored onto polyvinylpyrrolidone (PVP) functionalized graphene oxide (PVP-nGO) to form [email protected] hybrids. Field emission scanning electron microscopy (FE-SEM) images revealed the porous nature of the hybrid hydrogel patch with an average pore size of ~28.60 ± 3.10 μm. Besides, functional characteristics of the hybrid patch, such as mechanical strength, viscoelastic and swelling behavior, were investigated. Under near-infrared (NIR) radiation exposure, the hybrid patch exhibited photothermal properties such as surface temperature rise to 75.16 ± 0.32 °C, sufficient to ablate cancer cells thermally. Besides, the heat generated in the hybrid patch could be transmitted to an underlying hydrogel (mimicking skin tissue) when stacked together without much loss. Under cyclic photothermal heating, the patch could retain its photothermal stability for four cycles. Furthermore, the hybrid patch demonstrated NIR stimulated drug release, which was evaluated using methotrexate (MTX, water-insoluble anticancer drug) and rhodamine B (RhB, water-soluble dye). Taken together, this work provides a new dimension towards the development of externally placed hydrogel patches for thermal destruction of localized solid tumors and tunable delivery of chemotherapeutic drugs at the target site.
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http://dx.doi.org/10.1016/j.jphotobiol.2020.111960DOI Listing
September 2020

Clinical relevance of major histocompatibility complex class I chain-related molecule A (MICA) antibodies in live donor renal transplantation - Indian Experience.

Scand J Immunol 2020 Nov 3;92(5):e12923. Epub 2020 Aug 3.

Department of Transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India.

Antibody-mediated rejections (AMR) in the absence of circulating anti-HLA-DSA have highlighted the role of non-HLA antibodies, particularly those directed against endothelial cells. Of these, MICA (major histocompatibility complex class I chain-related molecule A) antibodies are the most notable and important because of their potential in promoting graft rejections. Limited studies have focused on the impact of MICA donor-specific antibodies (DSA) on graft outcome as compared to those that are not donor-specific (NDSA). We evaluated pre- and post-transplant sera at POD 7, 30, 90, 180 and the time of biopsy from 206 consecutive primary live donor renal transplant recipients for anti-MICA and anti-HLA antibodies using single antigen bead assay on a Luminex platform. Recipients who developed MICA antibodies and their donors were phenotyped for MICA alleles. For the purpose of antibody analysis, patients were categorized into three major groups: biopsy-proven AMR, acute cellular rejection (ACR) and those with no rejection episodes (NRE). During the mean follow-up period of 17.37 ± 6.88 months, 16 of the 206 recipients developed AMR, while ACR was observed in only 13 cases. A quarter (25%) of the AMR cases had anti-MICA antibodies as compared to 7.7% of those experiencing ACR and 6.2% of the NRE group. Allelic typing revealed that all MICA Ab +ve AMR cases were due to the presence of donor-specific antibodies. MICA-DSA even in the absence of HLA-DSA was significantly associated with AMR but not with ACR when compared with the NRE group (P = <.01).
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http://dx.doi.org/10.1111/sji.12923DOI Listing
November 2020

Metabolic benefits of annatto-extracted tocotrienol on glucose homeostasis, inflammation, and gut microbiome.

Nutr Res 2020 05 17;77:97-107. Epub 2020 Apr 17.

Center of Excellence for Integrative Health, Texas Tech University Health Sciences Center, Lubbock, TX; Obesity Research Institute, Texas Tech University, Lubbock, TX; Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX. Electronic address:

Emerging evidence suggests that the gut microbiome plays an important role in the pathophysiology of both obesity and type 2 diabetes mellitus. We previously reported that dietary annatto-extracted tocotrienol exerts beneficial effects by modulating inflammatory responses in mice fed a high-fat diet (HFD). The purpose of this study was to test the hypothesis that tocotrienol supplementation when combined with an HFD would result in an altered gut microbiota composition. For 14 weeks, forty-eight male C57BL/6J mice were assigned to 4 groups-low-fat diet, HFD, HFD supplemented with annatto-extracted tocotrienol at 800 mg/kg diet (AT), and HFD supplemented with metformin at 200 mg/kg diet. Glucose homeostasis was assessed by glucose and insulin tolerance tests, serum and pancreas insulin levels, and histological assessments of insulin and glucagon in pancreatic tissue. The concentrations of adipokines were measured in white adipose tissues. For the gut microbiome analysis, cecal content was collected, DNA was extracted, and 16S rRNA gene sequencing was performed. AT supplementation improved glucose homeostasis and lowered resistin, leptin, and interleukin-6 levels in white adipose tissue. Relative to the HFD group, AT-supplemented mice showed a decrease in the Firmicutes to Bacteroidetes ratio and had a lower abundance of Ruminococcus lactaris, Dorea longicatena, and Lachnospiraceae family. The relative abundance of Akkermansia muciniphila was increased in the AT group compared to the low-fat diet group. The association between the metabolic improvements and the identified bacterial taxa suggests a potential metabolic modulation caused by AT supplementation through the gut microbiota composition in mice fed an HFD.
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http://dx.doi.org/10.1016/j.nutres.2020.04.001DOI Listing
May 2020

Imputation of Gene Expression Data in Blood Cancer and Its Significance in Inferring Biological Pathways.

Front Oncol 2019 8;9:1442. Epub 2020 Jan 8.

Laboratory Oncology Unit, Dr. B.R.A. IRCH, AIIMS, New Delhi, India.

Gene expression data generated from microarray technology is often analyzed for disease diagnostics and treatment. However, this data suffers with missing values that may lead to inaccurate findings. Since data capture is expensive, time consuming, and is required to be collected from subjects, it is worthwhile to recover missing values instead of re-collecting the data. In this paper, a novel but simple method, namely, DSNN (Doubly Sparse DCT domain with Nuclear Norm minimization) has been proposed for imputing missing values in microarray data. Extensive experiments including pathway enrichment have been carried out on four blood cancer dataset to validate the method as well as to establish the significance of imputation. A new method, namely, DSNN, was proposed for missing value imputation on gene expression data. Method was validated on four dataset, CLL, AML, MM (Spanish data), and MM (Indian data). All the dataset were downloaded from GEO repository. Missing values were introduced in the original data from 10 to 90% in steps of 10% because method validation requires ground truth. Quantitative results on normalized mean square error (NMSE) between the ground truth and imputed data were computed. To further validate and establish the significance of the proposed imputation method, two experiments were carried out on the data imputed with the proposed method, data imputed with the state-of-art methods, and data with missing values. In the first experiment, classification of normal vs. cancer subjects was carried out. In the second experiment, biological significance of imputation was ascertained by identifying top candidate tumor drivers using the existing state-of-the-art SPARROW algorithm, followed by gene list enrichment analysis on top candidate drivers. Quantitative NMSE results of the DSNN method were compared with three state-of-the-art imputation methods. DSNN method was observed to perform better compared to these other methods both at high as well as low observable data. Experiment-1 demonstrated superior results on classification with imputation compared to that performed on missing data matrix as well as compared to classification on imputed data with existing methods. In experiment-2, cancer affected pathways were discovered with higher significance in the data imputed with the proposed method compared to those discovered with the missing data matrix. Missing value problem in microarray data is a serious problem and can adversely influence downstream analysis. A novel method, namely, DSNN is proposed for missing value imputation. The method is validated quantitatively on the application of classification and biologically by performing pathway enrichment analysis.
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http://dx.doi.org/10.3389/fonc.2019.01442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960109PMC
January 2020

RNA-Seq profiling of deregulated miRs in CLL and their impact on clinical outcome.

Blood Cancer J 2020 01 13;10(1). Epub 2020 Jan 13.

Laboratory Oncology Unit, Dr. B.R.A.IRCH, All India Institute of Medical Sciences, New Delhi, India.

Abnormal expression patterns of regulatory small non-coding RNA (sncRNA) molecules such as microRNAs (miRs), piwi-interacting RNAs (piRNAs), and small nucleolar RNAs (snoRNAs) play an important role in the development and progression of cancer. Identification of clinically relevant sncRNA signatures could, therefore, be of tremendous translational value. In the present study, genome-wide small RNA sequencing identified a unique pattern of differential regulation of eight miRs in Chronic Lymphocytic Leukemia (CLL). Among these, three were up-regulated (miR-1295a, miR-155, miR-4524a) and five were down-regulated (miR-30a, miR-423, miR-486*, let-7e, and miR-744) in CLL. Altered expression of all these eight differentially expressed miRs (DEMs) was validated by RQ-PCR. Besides, seven novel sequences identified to have elevated expression levels in CLL turned out to be transfer RNA (tRNA)/piRNAs (piRNA-30799, piRNA-36225)/snoRNA (SNORD43) related. Multivariate analysis showed that miR-4524a (HR: 1.916, 95% CI: 1.080-3.4, p value: 0.026) and miR-744 (HR: 0.415, 95% CI: 0.224-0.769, p value: 0.005) were significantly associated with risk and time to first treatment. Further investigations could help establish the scope of integration of these DEM markers into risk stratification designs and prognostication approaches for CLL.
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http://dx.doi.org/10.1038/s41408-019-0272-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957689PMC
January 2020

Maternal exercise before and during pregnancy alleviates metabolic dysfunction associated with high-fat diet in pregnant mice, without significant changes in gut microbiota.

Nutr Res 2019 09 8;69:42-57. Epub 2019 Aug 8.

Department of Kinesiology, Health, and Nutrition, University of Texas at San Antonio, San Antonio, TX.

Although maternal exercise before and during pregnancy is beneficial, the effects of exercise on microbiota changes during pregnancy are unknown. Here we tested the hypothesis that maternal exercise before and during pregnancy would positively affect glucose homeostasis, pancreatic cell function, and gut microbiota dysbiosis in high-fat diet (HFD) fed dams. Female C57BL/6 mice were fed either a HFD or a low-fat diet (LFD) for 12 weeks. The HFD mice were split into two groups for 4 weeks prior to pregnancy initiation and throughout the pregnancy: sedentary (HFD) or exercised (HFD + Ex). Food intake, body weight, body composition, and glucose and insulin tolerance were measured. At gestation day 19, blood, pancreas, gonadal visceral and subcutaneous fat, plantaris muscle, and cecum were collected for analysis. Both HFD and HFD + Ex mice had impaired glucose clearance compared to LFD mice at 15 days of gestation. No changes were found in pancreatic α- or β-cell health. HFD + Ex mice had significantly reduced visceral fat mass, serum insulin, and leptin levels and increased high-density lipoprotein levels, compared to HFD-fed mice. In contrast to our hypothesis, microbiota diversity and composition were not different among groups. The relative abundance of five bacterial phyla, such as Firmicutes, Bacteroidetes, Verrucomicrobia, Deferribacteres, and Actinobacteria, were not significantly altered with diet or exercise during pregnancy. Our findings suggest that maternal exercise prevents excess visceral fat accumulation, hyperinsulinemia, and hyperleptinemia associated with a HFD, but not through the alterations of gut microbiota composition or diversity during pregnancy.
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http://dx.doi.org/10.1016/j.nutres.2019.08.002DOI Listing
September 2019

Progress in 3D bioprinting technology for tissue/organ regenerative engineering.

Biomaterials 2020 01 11;226:119536. Epub 2019 Oct 11.

Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, CT, USA; Department of Orthopedic Surgery, UConn Health, Farmington, USA; Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, UConn Health, Farmington, USA; Department of Materials Science and Engineering, University of Connecticut, Storrs, USA; Department of Biomedical Engineering, University of Connecticut, Storrs, USA; Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, USA. Electronic address:

Escalating cases of organ shortage and donor scarcity worldwide are alarming reminders of the need for alternatives to allograft tissues. Within the last three decades, research efforts in the field of regenerative medicine and tissue engineering continue to address the unmet need for artificial tissues and organs for transplant. Work in the field has evolved to create what we consider a new field, Regenerative Engineering, defined as the Convergence of advanced materials science, stem cell science, physics, developmental biology and clinical translation towards the regeneration of complex tissues and organ systems. Included in the regenerative engineering paradigm is advanced manufacturing. Three-dimensional (3D) bioprinting is a promising and innovative biofabrication strategy to precisely position biologics, including living cells and extracellular matrix (ECM) components, in the prescribed 3D hierarchal organization to create artificial multi-cellular tissues/organs. In this review, we outline recent progress in several bioprinting technologies used to engineer scaffolds with requisite mechanical, structural, and biological complexity. We examine the process parameters affecting bioprinting and bioink-biomaterials and review notable studies on bioprinted skin, cardiac, bone, cartilage, liver, lung, neural, and pancreatic tissue. We also focus on other 3D bioprinting application areas including cancer research, drug testing, high-throughput screening (HTS), and organ-on-a-chip models. We also highlight the current challenges associated with the clinical translation of 3D bioprinting and conclude with the future perspective of bioprinting technology.
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http://dx.doi.org/10.1016/j.biomaterials.2019.119536DOI Listing
January 2020

Characterization of biological variation of peripheral blood immune cytome in an Indian cohort.

Sci Rep 2019 10 14;9(1):14735. Epub 2019 Oct 14.

National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.

Immune parameters show characteristic normal baseline levels and variance in the population. We characterised the degree of inter-individual and within-individual variation over one-year time period in 33 immune cell subsets by flow cytometry in peripheral blood mononuclear cells from 43 healthy young adult volunteers. Our analysis revealed that immune subsets that showed low variability between individuals also showed low short-term fluctuations within-individuals, as well as concordance in siblings. However, when baseline levels and degree of fluctuation were considered together, individuals failed to cluster into discreet groups. Together, the data reveal complex inter-relationships between immune subsets in individuals, and provide insights into the observed heterogeneity between individuals and between multiple immune subsets.
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http://dx.doi.org/10.1038/s41598-019-51294-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6791881PMC
October 2019
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