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Article ; Online: Acute kidney injury is associated with higher mortality and healthcare costs in hospitalized patients with cirrhosis

Raffi Karagozian / Gaurav Bhardwaj / Dorothy B. Wakefield / Elizabeth C. Verna

Annals of Hepatology, Vol 18, Iss 5, Pp 730-

2019 Volume 735

Abstract: Introduction and Objectives: AKI is known to be associated with increased risk of mortality, however limited information is available on how AKI impacts healthcare costs and resource utilization in hospitalized patients with cirrhosis. Previous studies ... ...

Abstract	Introduction and Objectives: AKI is known to be associated with increased risk of mortality, however limited information is available on how AKI impacts healthcare costs and resource utilization in hospitalized patients with cirrhosis. Previous studies have had variable definitions of AKI, resulting in inconsistent reporting of the true impact of AKI in patients with cirrhosis. Methods: Data from the Nationwide Inpatient Sample (NIS) which contains data from 44 states and 4378 hospitals, accounting for over 7 million discharges were analyzed. The inclusion data were all discharges in the 2012 NIS dataset with a discharge diagnosis of cirrhosis. Results: A total of 32,605 patients were included in the analysis, incidence of AKI was 12.12% in patients with cirrhosis. Crude mortality was much higher for patients with cirrhosis and AKI (14.9% vs. 1.8%, OR 9.42, p < 0.001) than for patients without AKI. In addition, mean LOS was longer (8.5 vs. 4.3 days, p < 0.001) and median total hospital charges were higher for patients with AKI ($43,939 vs. $22,270, p < 0.001). In multivariate logistic regression, controlling for covariates and mortality risk score, sepsis, ascites and SBP were predictors of AKI. Conclusions: AKI is relatively common in hospitalized patients with cirrhosis. Presence of AKI results in significantly higher inpatient mortality as well as LOS and resource utilization. Median hospitalization cost was twice as high in AKI patients. Early identification of patients at high risk for AKI should be implemented to reduce mortality and contain costs. Prognosis could be enhanced by utilizing biomarkers which could rapidly detect AKI.
Keywords	Length of stay ; National inpatient sample ; Mortality ; ICD-9 ; Hospital charges ; Specialties of internal medicine ; RC581-951
Subject code	310
Language	English
Publishing date	2019-09-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Upper Gastrointestinal Bleed as a Manifestation of Poorly Differentiated Metastatic Squamous Cell Carcinoma of the Lung

Richa Bhardwaj / Gaurav Bhardwaj / Arun Gautam / Raffi Karagozian

Journal of Clinical and Diagnostic Research, Vol 11, Iss 6, Pp OD13-OD

2017 Volume 14

Abstract: Gastrointestinal (GI) metastasis from primary lung cancer is a rare clinical finding. Lung cancer most often metastasizes to the brain, bone, liver, and adrenal glands; with gastrointestinal involvement being very rare. We report a case of a 39-year-old ... ...

Abstract	Gastrointestinal (GI) metastasis from primary lung cancer is a rare clinical finding. Lung cancer most often metastasizes to the brain, bone, liver, and adrenal glands; with gastrointestinal involvement being very rare. We report a case of a 39-year-old female with a diagnosis of poorly differentiated Squamous Cell Carcinoma (SCC) of the lung presenting with dizziness and melena. Esophagogastroduodenoscopy (EGD) showed a bleeding mass in the stomach. Final biopsy report and Immunohistochemistry (IHC) of the specimen were consistent with SCC lung metastasis. While it is imperative to have a high clinical suspicion for GI metastasis in patients with primary lung cancer presenting with GI symptoms, it may be challenging to establish diagnosis. Endoscopy along with pathology and immunohistochemistry play a crucial role in differentiating primary GI malignancies from metastasis.
Keywords	gastrointestinal hemorrhage ; lung neoplasm ; metastasis ; non-small cell carcinoma lung ; Medicine ; R
Subject code	610
Language	English
Publishing date	2017-06-01T00:00:00Z
Publisher	JCDR Research and Publications Private Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Aortic aneurysm.

Mathur, Atul / Mohan, Varun / Ameta, Deepak / Gaurav, Bhardwaj / Haranahalli, Pradeep

Journal of translational internal medicine

2016 Volume 4, Issue 1, Page(s) 35–41

Language	English
Publishing date	2016-04-14
Publishing country	Poland
Document type	Journal Article
ZDB-ID	2861892-0
ISSN	2224-4018 ; 2450-131X
ISSN (online)	2224-4018
ISSN	2450-131X
DOI	10.1515/jtim-2016-0008
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Article ; Online: Protection of the Furin Cleavage Site in Low-Toxicity Immunotoxins Based on Pseudomonas Exotoxin A

Gilad Kaplan / Fred Lee / Masanori Onda / Emily Kolyvas / Gaurav Bhardwaj / David Baker / Ira Pastan

Toxins, Vol 8, Iss 8, p

2016 Volume 217

Abstract: Recombinant immunotoxins (RITs) are fusions of an Fv-based targeting moiety and a toxin. Pseudomonas exotoxin A (PE) has been used to make several immunotoxins that have been evaluated in clinical trials. Immunogenicity of the bacterial toxin and off- ... ...

Abstract	Recombinant immunotoxins (RITs) are fusions of an Fv-based targeting moiety and a toxin. Pseudomonas exotoxin A (PE) has been used to make several immunotoxins that have been evaluated in clinical trials. Immunogenicity of the bacterial toxin and off-target toxicity have limited the efficacy of these immunotoxins. To address these issues, we have previously made RITs in which the Fv is connected to domain III (PE24) by a furin cleavage site (FCS), thereby removing unneeded sequences of domain II. However, the PE24 containing RITs do not contain the naturally occurring disulfide bond around the furin cleavage sequence, because it was removed when domain II was deleted. This could potentially allow PE24 containing immunotoxins to be cleaved and inactivated before internalization by cell surface furin or other proteases in the blood stream or tumor microenvironment. Here, we describe five new RITs in which a disulfide bond is engineered to protect the FCS. The most active of these, SS1-Fab-DS3-PE24, shows a longer serum half-life than an RIT without the disulfide bond and has the same anti-tumor activity, despite being less cytotoxic in vitro. These results have significance for the production of de-immunized, low toxicity, PE24-based immunotoxins with a longer serum half-life.
Keywords	recombinant immunotoxin ; mesothelin ; Pseudomonas exotoxin A ; disulfide bond ; Medicine ; R
Subject code	500
Language	English
Publishing date	2016-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Design and structural validation of peptide–drug conjugate ligands of the kappa-opioid receptor

Edin Muratspahić / Kristine Deibler / Jianming Han / Nataša Tomašević / Kirtikumar B. Jadhav / Aina-Leonor Olivé-Marti / Nadine Hochrainer / Roland Hellinger / Johannes Koehbach / Jonathan F. Fay / Mohammad Homaidur Rahman / Lamees Hegazy / Timothy W. Craven / Balazs R. Varga / Gaurav Bhardwaj / Kevin Appourchaux / Susruta Majumdar / Markus Muttenthaler / Parisa Hosseinzadeh /

David J. Craik / Mariana Spetea / Tao Che / David Baker / Christian W. Gruber

Nature Communications, Vol 14, Iss 1, Pp 1-

2023 Volume 17

Abstract: Abstract Despite the increasing number of GPCR structures and recent advances in peptide design, the development of efficient technologies allowing rational design of high-affinity peptide ligands for single GPCRs remains an unmet challenge. Here, we ... ...

Abstract	Abstract Despite the increasing number of GPCR structures and recent advances in peptide design, the development of efficient technologies allowing rational design of high-affinity peptide ligands for single GPCRs remains an unmet challenge. Here, we develop a computational approach for designing conjugates of lariat-shaped macrocyclized peptides and a small molecule opioid ligand. We demonstrate its feasibility by discovering chemical scaffolds for the kappa-opioid receptor (KOR) with desired pharmacological activities. The designed De Novo Cyclic Peptide (DNCP)-β-naloxamine (NalA) exhibit in vitro potent mixed KOR agonism/mu-opioid receptor (MOR) antagonism, nanomolar binding affinity, selectivity, and efficacy bias at KOR. Proof-of-concept in vivo efficacy studies demonstrate that DNCP-β-NalA(1) induces a potent KOR-mediated antinociception in male mice. The high-resolution cryo-EM structure (2.6 Å) of the DNCP-β-NalA–KOR–Gi1 complex and molecular dynamics simulations are harnessed to validate the computational design model. This reveals a network of residues in ECL2/3 and TM6/7 controlling the intrinsic efficacy of KOR. In general, our computational de novo platform overcomes extensive lead optimization encountered in ultra-large library docking and virtual small molecule screening campaigns and offers innovation for GPCR ligand discovery. This may drive the development of next-generation therapeutics for medical applications such as pain conditions.
Keywords	Science ; Q
Subject code	540
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Acute Pancreatitis in a Patient with Vivax Malaria

Vishal Sharma / Alka Sharma / Amitesh Aggarwal / Gaurav Bhardwaj / Sourabh Aggarwal

JOP Journal of the Pancreas, Vol 13, Iss 2, Pp 215-

2012 Volume 216

Abstract: Context Acute pancreatitis is most commonly linked to gallstone disease or alcohol consumption. Occasionally it can followinfectious disease. Malaria, especially Plasmodium falciparum infection, has been associated with acute pancreatitis. Case report We ...

Abstract	Context Acute pancreatitis is most commonly linked to gallstone disease or alcohol consumption. Occasionally it can followinfectious disease. Malaria, especially Plasmodium falciparum infection, has been associated with acute pancreatitis. Case report We present the case of a 17-year-old male who presented with a history of fever, abdominal pain and hypotension and revealing acute pancreatitis associated with infection by Plasmodium vivax. Conclusion Acute pancreatitis can accompany malaria, including Plasmodium vivax.
Keywords	Malaria ; Pancreatitis ; Plasmodium vivax ; Medicine ; R ; Internal medicine ; RC31-1245 ; Specialties of internal medicine ; RC581-951 ; Diseases of the digestive system. Gastroenterology ; RC799-869
Publishing date	2012-03-01T00:00:00Z
Publisher	E S Burioni Ricerche Bibliografiche
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Pterygium - a study which was done on a rural based population.

Veena M S, Bhardwaj / Alaka Priyadarshani, Das / Gaurav, Bhardwaj

Journal of clinical and diagnostic research : JCDR

2013 Volume 7, Issue 9, Page(s) 1936–1937

Abstract: Introduction: Pterygium is a fibrous growth seen in bulber conjunctiva.It is a non malignant growth which may cause visual impairment.: Material and methods: Pterygium study was done on rural population in out patient department of NIMS Hospital and ... ...

Abstract	Introduction: Pterygium is a fibrous growth seen in bulber conjunctiva.It is a non malignant growth which may cause visual impairment. Material and methods: Pterygium study was done on rural population in out patient department of NIMS Hospital and medical college, Jaipur, Rajasthan, India.Two hundred patients with 300 eyes which had Pterygium who attended the Eye OPD during 01/06/2011 to 01/03/2012 were taken for study. A detailed history, Visual Acuity, Refractive Status, Size of Pterygium and duration of the work which was done outdoors were recorded. All other physical illness were ruled out. The aim of the study is to find the incidence of Pterygium, male/female ratio, Comparison of size of Pterygium with duration of working hours in the outfield. Conclusion: The maximum number of patients of pterygium were seen in the age group 20-60 years and there is no difference in male/female ratio.The size of pterygium depends on their duration of working hours in outfield.
Language	English
Publishing date	2013-09-10
Publishing country	India
Document type	Journal Article
ZDB-ID	2775283-5
ISSN	0973-709X ; 2249-782X
ISSN (online)	0973-709X
ISSN	2249-782X
DOI	10.7860/JCDR/2013/6107.3361
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Article ; Online: Molecular dynamic simulations reveal the structural determinants of Fatty Acid binding to oxy-myoglobin.

Sree V Chintapalli / Gaurav Bhardwaj / Reema Patel / Natasha Shah / Randen L Patterson / Damian B van Rossum / Andriy Anishkin / Sean H Adams

PLoS ONE, Vol 10, Iss 6, p e

2015 Volume 0128496

Abstract: The mechanism(s) by which fatty acids are sequestered and transported in muscle have not been fully elucidated. A potential key player in this process is the protein myoglobin (Mb). Indeed, there is a catalogue of empirical evidence supporting direct ... ...

Abstract	The mechanism(s) by which fatty acids are sequestered and transported in muscle have not been fully elucidated. A potential key player in this process is the protein myoglobin (Mb). Indeed, there is a catalogue of empirical evidence supporting direct interaction of globins with fatty acid metabolites; however, the binding pocket and regulation of the interaction remains to be established. In this study, we employed a computational strategy to elucidate the structural determinants of fatty acids (palmitic & oleic acid) binding to Mb. Sequence analysis and docking simulations with a horse (Equus caballus) structural Mb reference reveals a fatty acid-binding site in the hydrophobic cleft near the heme region in Mb. Both palmitic acid and oleic acid attain a "U" shaped structure similar to their conformation in pockets of other fatty acid-binding proteins. Specifically, we found that the carboxyl head group of palmitic acid coordinates with the amino group of Lys45, whereas the carboxyl group of oleic acid coordinates with both the amino groups of Lys45 and Lys63. The alkyl tails of both fatty acids are supported by surrounding hydrophobic residues Leu29, Leu32, Phe33, Phe43, Phe46, Val67, Val68 and Ile107. In the saturated palmitic acid, the hydrophobic tail moves freely and occasionally penetrates deeper inside the hydrophobic cleft, making additional contacts with Val28, Leu69, Leu72 and Ile111. Our simulations reveal a dynamic and stable binding pocket in which the oxygen molecule and heme group in Mb are required for additional hydrophobic interactions. Taken together, these findings support a mechanism in which Mb acts as a muscle transporter for fatty acid when it is in the oxygenated state and releases fatty acid when Mb converts to deoxygenated state.
Keywords	Medicine ; R ; Science ; Q
Subject code	540
Language	English
Publishing date	2015-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Adaptive-BLAST

Yoojin Hong / Sree V Chintapalli / Gaurav Bhardwaj / Zhenhai Zhang / Randen L. Patterson / Damian B. van Rossum

Journal of Integrated OMICS, Vol 1, Iss 1, Pp 88-

A User-defined Platform for the Study of Proteins

2011 Volume 101

Abstract: Profile-based protein-sequence analysis algorithms comprise some of the most powerful and user-friendly methods for exploring protein se-quences to determine their structure, function, and/or evolution (1-4). PSI-BLAST (5, 6) and rps-BLAST (7) are two of ...

Abstract	Profile-based protein-sequence analysis algorithms comprise some of the most powerful and user-friendly methods for exploring protein se-quences to determine their structure, function, and/or evolution (1-4). PSI-BLAST (5, 6) and rps-BLAST (7) are two of the most popular pro-file-based algorithms (~1,120 references to date), and have exceptional utility in the identification of homology between proteins, particularly for biological scientists who do not specialize in computational approaches. However, when the performance of these algorithms is compared to other methods [e.g. support-vector machine learning (SVM) (8), hidden-Markov models (HMMs) (9)], they often underperform in identifying the aforementioned protein properties (3, 9-11). We have previously demonstrated that the utility of BLAST algorithms can be significantly improved by: (i) adaptations to the profile libraries employed, (ii) adjustments to output formats, and (iii) alterations to BLAST algorithm itself (4, 6, 12-14). We present here Adaptive-BLAST (Ada-BLAST), which provides a simple user-defined platform for measuring and analyzing primary amino acid sequences. Within this platform, we developed a series of local BLAST applications (apps) that take advantage of the speed and sensitivity afforded by BLAST, while allowing for maximal user-definitions and flexible visualization. We tested the efficacy of these apps in control experiments, studying fold-recognition, in which we obtained >90% accuracy in highly divergent sequences (>25% identity). In addition, these same apps were proficient in classifying transmembrane proteins, identifying structural/functional determinants of ion-channels/receptors, and informing structural modeling algorithms. Indeed, these Ada-BLAST informed-structural models were useful in guid-ing our experimental research on the N-terminus of Transient Receptor Potential ion-channels (TRPs). Taken together, we propose that Ada-BLAST provides a powerful computational tool that is accessible to bench-scientists and computational biologists alike. The codes for Ada-BLAST are publicly available at: http://empathy.rcc.psu.edu/.
Keywords	BLAST ; Ada-BLAST ; rps-BLAST ; PSI-BLAST ; twilight-zone ; TRP channels ; ankyrin repeats ; transmembrane prediction ; protein function ; protein evolution ; protein structure ; homology modeling ; TRPC3 ; TRPV4 ; TRP_2 ; VAMP ; SNARE ; fusogenic ; lipid-binding ; Biology (General) ; QH301-705.5 ; Science ; Q ; DOAJ:Biology ; DOAJ:Biology and Life Sciences
Subject code	006
Language	English
Publishing date	2011-02-01T00:00:00Z
Publisher	Scientific Society Proteomass
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Predicting protein folds with fold-specific PSSM libraries.

Yoojin Hong / Sree Vamsee Chintapalli / Kyung Dae Ko / Gaurav Bhardwaj / Zhenhai Zhang / Damian van Rossum / Randen L Patterson

PLoS ONE, Vol 6, Iss 6, p e

2011 Volume 20557

Abstract: Accurately assigning folds for divergent protein sequences is a major obstacle to structural studies. Herein, we outline an effective method for fold recognition using sets of PSSMs, each of which is constructed for different protein folds. Our analyses ... ...

Abstract	Accurately assigning folds for divergent protein sequences is a major obstacle to structural studies. Herein, we outline an effective method for fold recognition using sets of PSSMs, each of which is constructed for different protein folds. Our analyses demonstrate that FSL (Fold-specific Position Specific Scoring Matrix Libraries) can predict/relate structures given only their amino acid sequences of highly divergent proteins. This ability to detect distant relationships is dependent on low-identity sequence alignments obtained from FSL. Results from our experiments demonstrate that FSL perform well in recognizing folds from the "twilight-zone" SABmark dataset. Further, this method is capable of accurate fold prediction in newly determined structures. We suggest that by building complete PSSM libraries for all unique folds within the Protein Database (PDB), FSL can be used to rapidly and reliably annotate a large subset of protein folds at proteomic level. The related programs and fold-specific PSSMs for our FSL are publicly available at: http://ccp.psu.edu/download/FSLv1.0/.
Keywords	Medicine ; R ; Science ; Q
Subject code	612
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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