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Article: Artificial intelligence is set to transform mental health services.

Pandi-Perumal, Seithikurippu R / Narasimhan, Meera / Seeman, Mary V / Jahrami, Haitham

2023 , Page(s) 1–3

Abstract: The current development in the field of artificial intelligence and its applications has advantages and disadvantages in the digital age that we now live in. The state of the use of AI for mental health has to be assessed by stakeholders, which includes ... ...

Abstract	The current development in the field of artificial intelligence and its applications has advantages and disadvantages in the digital age that we now live in. The state of the use of AI for mental health has to be assessed by stakeholders, which includes all of us. We must comprehend the trends, gaps, opportunities, challenges, and shortcomings of this new technology. As the field evolves, rules, regulatory frameworks, guidelines, standards, and policies will develop and will progressively scale upwards. To advance the field, mental health professionals must be prepared to meet obstacles and seize possibilities presented by creative and disruptive technologies like AI. Therefore, a collaborative strategy must include multi-stakeholder participation in basic, translational, and clinical aspects of AI. Mental health practitioners need to be ready to face challenges and embrace and harness the power of innovative and disruptive technology such as AI that could offer to move the field forward.
Language	English
Publishing date	2023-09-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2008418-3
ISSN	2165-6509 ; 1092-8529
ISSN (online)	2165-6509
ISSN	1092-8529
DOI	10.1017/S1092852923002456
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Article ; Online: Toward Deploying a Deep Learning Model for Diagnosis of Rhabdomyosarcoma.

Ho, David Joon / Agaram, Narasimhan P / Frankel, Arthur O / Lathara, Melvin / Catchpoole, Daniel / Keller, Charles / Hameed, Meera R

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

2024 Volume 37, Issue 3, Page(s) 100421

MeSH term(s)	Humans ; Deep Learning ; Rhabdomyosarcoma/diagnosis ; Rhabdomyosarcoma/pathology ; Diagnosis, Differential
Language	English
Publishing date	2024-02-08
Publishing country	United States
Document type	Letter
ZDB-ID	645073-8
ISSN	1530-0285 ; 0893-3952
ISSN (online)	1530-0285
ISSN	0893-3952
DOI	10.1016/j.modpat.2024.100421
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Zs.A 2450: Show issues

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Article ; Online: GLI1 Co-Amplification in Well-differentiated/Dedifferentiated Liposarcomas: Clinicopathologic and Molecular Analysis of 92 Cases.

Sharma, Aarti E / Dickson, Mark / Singer, Samuel / Hameed, Meera R / Agaram, Narasimhan P

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

2024 , Page(s) 100494

Abstract: Background: GLI1 (12q13.3) amplification is identified in a subset of mesenchymal neoplasms with a distinct nested round cell/epithelioid phenotype. MDM2 and CDK4 genes are situated along the oncogenic 12q13-15 segment, amplification of which defines ... ...

Abstract	Background: GLI1 (12q13.3) amplification is identified in a subset of mesenchymal neoplasms with a distinct nested round cell/epithelioid phenotype. MDM2 and CDK4 genes are situated along the oncogenic 12q13-15 segment, amplification of which defines well-differentiated (WDLPS)/dedifferentiated liposarcoma (DDLPS). The 12q amplicon can occasionally include GLI1 - a gene in close proximity to CDK4. We hereby describe the first cohort of GLI1/MDM2/CDK4 co-amplified WD/DDLPS. Materials and methods: The departmental database was queried retrospectively for all cases of WD/DDLPS having undergone next generation (IMPACT) sequencing with confirmed MDM2, CDK4, and GLI1 co-amplification. Clinicopathologic data was obtained from review of the medical chart and available histologic material. Results: 486 WD/DDLPS underwent DNA sequencing, 92 (19%) of which harbored amplification of the GLI1 locus in addition to MDM2 and CDK4. These included primary tumors (n=60), local recurrences (n=29), and metastases (n=3). Primary tumors were most frequently retroperitoneal (47/60,78%) mediastinal (4/60,7%), and paratesticular (3/60, 5%). Average age was 63 years with a male: female ratio of 3:2. The cohort was comprised by DDLPS (86/92 [93%], 6 of which were comprised by WDLPS with early dedifferentiation) , and WDLPS without any longitudinal evidence of dedifferentiation (6/92, 7%%). A fifth (13/86,17%) of DDLPS cases showed no evidence of a well-differentiated component in any of the primary, recurrent, or metastatic specimens. Dedifferentiated areas mostly showed high-grade undifferentiated pleomorphic sarcoma-like (26/86, 30%),) and high-grade myxofibrosarcoma-like (13/86, 16%)) morphology. A disproportionately increased incidence of meningothelial whorls with/without osseous metaplasia was observed as the predominant pattern in 16/86 (19%), and GLI1-altered morphology as described was identified in a total of 10/86 (12%) tumors. JUN (1p32.1), also implicated in the pathogenesis of WD/DDLPS, was co-amplified with all three of MDM2, CDK4, and GLI1 in 7/91 (8%) cases. Additional loci along chromosomal arms 1p and 6q, including TNFAIP3, LATS1 and ESR1, were also amplified in a subset of cases. Conclusions: In this large-scale cohort of GLI1 co-amplified WD/DDLPS, we elucidate uniquely recurrent features including meningothelial whorls and GLI-altered morphology in dedifferentiated areas. Assessment of tumor location (retroperitoneal or mediastinal), identification of a well-differentiated liposarcoma component, and co-amplification of other spatially discrete genomic segments (1p, 6q) might aid in distinction from tumors with true driver GLI1 alterations.
Language	English
Publishing date	2024-04-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	645073-8
ISSN	1530-0285 ; 0893-3952
ISSN (online)	1530-0285
ISSN	0893-3952
DOI	10.1016/j.modpat.2024.100494
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Article ; Online: Evaluation of the drug-drug interaction potential of brigatinib using a physiologically-based pharmacokinetic modeling approach.

Hanley, Michael J / Yeo, Karen Rowland / Tugnait, Meera / Iwasaki, Shinji / Narasimhan, Narayana / Zhang, Pingkuan / Venkatakrishnan, Karthik / Gupta, Neeraj

CPT: pharmacometrics & systems pharmacology

2024 Volume 13, Issue 4, Page(s) 624–637

Abstract: Brigatinib is an oral anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of ALK-positive metastatic non-small cell lung cancer. In vitro studies indicated that brigatinib is primarily metabolized by CYP2C8 and CYP3A4 and inhibits P-gp, ...

Abstract	Brigatinib is an oral anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of ALK-positive metastatic non-small cell lung cancer. In vitro studies indicated that brigatinib is primarily metabolized by CYP2C8 and CYP3A4 and inhibits P-gp, BCRP, OCT1, MATE1, and MATE2K. Clinical drug-drug interaction (DDI) studies with the strong CYP3A inhibitor itraconazole or the strong CYP3A inducer rifampin demonstrated that CYP3A-mediated metabolism was the primary contributor to overall brigatinib clearance in humans. A physiologically-based pharmacokinetic (PBPK) model for brigatinib was developed to predict potential DDIs, including the effect of moderate CYP3A inhibitors or inducers on brigatinib pharmacokinetics (PK) and the effect of brigatinib on the PK of transporter substrates. The developed model was able to predict clinical DDIs with itraconazole (area under the plasma concentration-time curve from time 0 to infinity [AUC
MeSH term(s)	Humans ; Rifampin/pharmacokinetics ; Cytochrome P-450 CYP3A Inhibitors/pharmacology ; Itraconazole/pharmacology ; Cytochrome P-450 CYP3A/metabolism ; Carcinoma, Non-Small-Cell Lung ; ATP Binding Cassette Transporter, Subfamily G, Member 2 ; Lung Neoplasms ; Neoplasm Proteins/metabolism ; Cytochrome P-450 CYP3A Inducers/pharmacokinetics ; Drug Interactions ; Membrane Transport Proteins ; Receptor Protein-Tyrosine Kinases/metabolism ; Models, Biological ; Organophosphorus Compounds ; Pyrimidines
Chemical Substances	Rifampin (VJT6J7R4TR) ; Cytochrome P-450 CYP3A Inhibitors ; brigatinib (HYW8DB273J) ; Itraconazole (304NUG5GF4) ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; ATP Binding Cassette Transporter, Subfamily G, Member 2 ; Neoplasm Proteins ; Cytochrome P-450 CYP3A Inducers ; Membrane Transport Proteins ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1) ; Organophosphorus Compounds ; Pyrimidines
Language	English
Publishing date	2024-01-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2697010-7
ISSN	2163-8306 ; 2163-8306
ISSN (online)	2163-8306
ISSN	2163-8306
DOI	10.1002/psp4.13106
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Article: Depression: A focus on challenges, clinical controversies and collaborative care.

Narasimhan, Meera

Asian journal of psychiatry

2010 Volume 3, Issue 3, Page(s) 95

Language	English
Publishing date	2010-09
Publishing country	Netherlands
Document type	Editorial
ZDB-ID	2456678-0
ISSN	1876-2026 ; 1876-2018
ISSN (online)	1876-2026
ISSN	1876-2018
DOI	10.1016/j.ajp.2010.08.009
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Article ; Online: Brigatinib pharmacokinetics in patients with chronic hepatic impairment.

Hanley, Michael J / Kerstein, David / Tugnait, Meera / Narasimhan, Narayana / Marbury, Thomas C / Venkatakrishnan, Karthik / Gupta, Neeraj

Investigational new drugs

2023 Volume 41, Issue 3, Page(s) 402–410

Abstract: Brigatinib is an anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of ALK-positive non-small cell lung cancer. This open-label, parallel-group study investigated the effect of chronic hepatic impairment on the pharmacokinetics (PK) of ...

Abstract	Brigatinib is an anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of ALK-positive non-small cell lung cancer. This open-label, parallel-group study investigated the effect of chronic hepatic impairment on the pharmacokinetics (PK) of brigatinib to inform dosing recommendations for these patients. Participants with hepatic impairment classified according to Child-Pugh categories of mild (A), moderate (B), or severe (C) and matched-healthy participants with normal hepatic function received a single oral dose of 90-mg brigatinib. Plasma samples were collected for the determination of brigatinib plasma protein binding and estimation of plasma PK parameters. Twenty-seven participants were enrolled (Child-Pugh A-C, n = 6 each; matched-healthy participants, n = 9). The mean fraction of free plasma brigatinib was comparable for the Child-Pugh A (11.1%), Child-Pugh B (10.8%), and healthy participant groups (8.5%); free brigatinib was higher in the Child-Pugh C group (23.1%). There were no clinically meaningful effects of mild or moderate hepatic impairment on unbound systemic exposures (area under the plasma concentration-time curve [AUC]) of brigatinib (geometric least-squares mean ratios [90% CI] of 89.32% [69.79%-114.31%] and 99.55% [77.78%-127.41%], respectively). In the severe hepatic impairment group, brigatinib unbound AUC was approximately 37% higher (geometric least-squares mean ratio [90% CI] of 137.41% [107.37%-175.86%]) compared with healthy participants with normal hepatic function. Brigatinib was well tolerated in healthy participants and in participants with hepatic impairment. No dose adjustment is required for patients with mild or moderate hepatic impairment. The brigatinib dose should be reduced by approximately 40% for patients with severe hepatic impairment.
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung ; Area Under Curve ; Lung Neoplasms ; Liver Diseases/metabolism ; Protein Kinase Inhibitors/adverse effects ; Protein Kinase Inhibitors/pharmacokinetics ; Receptor Protein-Tyrosine Kinases
Chemical Substances	brigatinib (HYW8DB273J) ; Protein Kinase Inhibitors ; Receptor Protein-Tyrosine Kinases (EC 2.7.10.1)
Language	English
Publishing date	2023-04-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	604895-x
ISSN	1573-0646 ; 0167-6997
ISSN (online)	1573-0646
ISSN	0167-6997
DOI	10.1007/s10637-023-01339-6
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Zs.A 1823: Show issues

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Article ; Online: Untying the Gordian knot of composite hemangioendothelioma: Discovery of novel fusions.

Linos, Konstantinos / Dermawan, Josephine K / Pulitzer, Melissa / Hameed, Meera / Agaram, Narasimhan P / Agaimy, Abbas / Antonescu, Cristina R

Genes, chromosomes & cancer

2023 Volume 63, Issue 1, Page(s) e23198

Abstract: Composite hemangioendothelioma is a rare, locally aggressive, and rarely metastasizing vascular neoplasm which affects both children and adults. Recently, a number of gene fusions including YAP1::MAML2, PTBP1::MAML2, and EPC1::PHC2 have been detected in ... ...

Abstract	Composite hemangioendothelioma is a rare, locally aggressive, and rarely metastasizing vascular neoplasm which affects both children and adults. Recently, a number of gene fusions including YAP1::MAML2, PTBP1::MAML2, and EPC1::PHC2 have been detected in a small subset of cases with or without neuroendocrine expression. Herein, we present four additional cases with novel in-frame fusions. The cohort comprises two females and two males with a wide age range at diagnosis (24-80 years). Two tumors were deep involving the right brachial plexus and mediastinum, while the remaining were superficial (right plantar foot and abdominal wall). The size ranged from 1.5 to 4.8 cm in greatest dimension. Morphologically, all tumors had an admixture of at least two architectural patterns including retiform hemangioendothelioma, hemangioma, epithelioid hemangioendothelioma, or angiosarcoma. The tumors were positive for endothelial markers CD31 (3/3), ERG (4/4), and D2-40 (1/4, focal), while SMA was expressed in 2/3 highlighting the surrounding pericytes. Synaptophysin showed immunoreactivity in 2/3 cases. One patient had a local recurrence after 40 months, while two patients had no evidence of disease 4 months post-resection. Targeted RNA sequencing detected novel in-frame fusions in each of the cases: HSPG2::FGFR1, YAP1::FOXR1, ACTB::MAML2, and ARID1B::MAML2. The two cases with neuroendocrine expression occurred as superficial lesions and harbored YAP1::FOXR1 and ARID1B::MAML2 fusions. Our study expands on the molecular spectrum of this enigmatic tumor, further enhancing our current understanding of the disease.
MeSH term(s)	Adult ; Male ; Child ; Female ; Humans ; Young Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Hemangioendothelioma/pathology ; Hemangioendothelioma, Epithelioid/genetics ; Hemangioma ; Base Sequence ; Diagnosis, Differential ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Heterogeneous-Nuclear Ribonucleoproteins ; Polypyrimidine Tract-Binding Protein
Chemical Substances	Biomarkers, Tumor ; PTBP1 protein, human ; Heterogeneous-Nuclear Ribonucleoproteins ; Polypyrimidine Tract-Binding Protein (139076-35-0)
Language	English
Publishing date	2023-09-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	1018988-9
ISSN	1098-2264 ; 1045-2257
ISSN (online)	1098-2264
ISSN	1045-2257
DOI	10.1002/gcc.23198
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Zs.A 2966: Show issues

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Article ; Online: Effect of severe renal impairment on the pharmacokinetics of brigatinib.

Gupta, Neeraj / Hanley, Michael J / Kerstein, David / Tugnait, Meera / Narasimhan, Narayana / Marbury, Thomas C / Venkatakrishnan, Karthik

Investigational new drugs

2021 Volume 39, Issue 5, Page(s) 1306–1314

Abstract: Background Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, targets activated, mutant forms of ALK and overcomes mechanisms of resistance to the ALK inhibitors crizotinib, ceritinib, and alectinib. Brigatinib is approved in ... ...

Abstract	Background Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, targets activated, mutant forms of ALK and overcomes mechanisms of resistance to the ALK inhibitors crizotinib, ceritinib, and alectinib. Brigatinib is approved in multiple countries for treatment of patients with ALK-positive non-small cell lung cancer. Based on population pharmacokinetic (PK) analyses, no dosage adjustment is required for patients with mild or moderate renal impairment. Methods An open-label, single-dose study was conducted to evaluate the PK of brigatinib (90 mg) in patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m
MeSH term(s)	Aged ; Anaplastic Lymphoma Kinase/antagonists & inhibitors ; Area Under Curve ; Female ; Glomerular Filtration Rate ; Half-Life ; Humans ; Male ; Metabolic Clearance Rate ; Middle Aged ; Organophosphorus Compounds/blood ; Organophosphorus Compounds/pharmacokinetics ; Organophosphorus Compounds/urine ; Patient Acuity ; Protein Binding/physiology ; Pyrimidines/blood ; Pyrimidines/pharmacokinetics ; Pyrimidines/urine ; Renal Insufficiency/metabolism
Chemical Substances	Organophosphorus Compounds ; Pyrimidines ; Anaplastic Lymphoma Kinase (EC 2.7.10.1) ; brigatinib (HYW8DB273J)
Language	English
Publishing date	2021-03-20
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604895-x
ISSN	1573-0646 ; 0167-6997
ISSN (online)	1573-0646
ISSN	0167-6997
DOI	10.1007/s10637-021-01095-5
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Article ; Online: Herding cats and other epic challenges: Creating meaningful stakeholder engagement in community mental health research.

Pandi-Perumal, Seithikurippu R / Zeller, John L / Parthasarathy, Sairam / Edward Freeman, R / Narasimhan, Meera

Asian journal of psychiatry

2019 Volume 42, Page(s) 19–21

Abstract: Stakeholder-centered approaches, that restrict patient barriers to clinical community mental health research, affect outcomes. It is suggested that a restructuring of clinical research organizational behavior and attitudes may overcome this problem. It ... ...

Abstract	Stakeholder-centered approaches, that restrict patient barriers to clinical community mental health research, affect outcomes. It is suggested that a restructuring of clinical research organizational behavior and attitudes may overcome this problem. It is further advocated that consultation with an engagement of study patient stakeholders encourages their interest in the study, and is essential for successful research. This editorial considers the concept of stakeholder participation and management in the clinical research environment. It further offers practical suggestions for fostering meaningful stakeholder engagement.
MeSH term(s)	Community-Based Participatory Research ; Humans ; Mental Health ; Patient Participation ; Stakeholder Participation
Language	English
Publishing date	2019-03-26
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2456678-0
ISSN	1876-2026 ; 1876-2018
ISSN (online)	1876-2026
ISSN	1876-2018
DOI	10.1016/j.ajp.2019.03.019
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Article ; Online: Factors Contributing to Adolescents' and Young Adults' Participation in Web-Based Challenges: Survey Study.

Khasawneh, Amro / Chalil Madathil, Kapil / Zinzow, Heidi / Rosopa, Patrick / Natarajan, Gitanjali / Achuthan, Krishnashree / Narasimhan, Meera

JMIR pediatrics and parenting

2021 Volume 4, Issue 1, Page(s) e24988

Abstract: Background: Web-based challenges, phenomena that are familiar to adolescents and young adults who spend large amounts of time on social media, range from minimally harmful behaviors intended to support philanthropic endeavors to significantly harmful ... ...

Abstract	Background: Web-based challenges, phenomena that are familiar to adolescents and young adults who spend large amounts of time on social media, range from minimally harmful behaviors intended to support philanthropic endeavors to significantly harmful behaviors that may culminate in injury or death. Objective: This study aims to investigate the beliefs that lead adolescents and young adults to participate in these activities by analyzing the amyotrophic lateral sclerosis (ALS) ice bucket challenge, representing nonharmful behaviors associated with web-based challenges, and the cinnamon challenge, representing web-based challenges that lead to harmful behaviors. Methods: A retrospective quantitative study was conducted with a total of 471 participants aged between 13 and 35 years who either had participated in the ALS ice bucket challenge or the cinnamon challenge, or had never participated in any web-based challenge. Binomial logistic regression models were used to classify those who participated in the ALS ice bucket challenge or cinnamon challenge versus those who did not engage in either challenge using the integrated behavioral model's beliefs as predictors. Results: The findings showed that participants of both the cinnamon challenge and the ALS ice bucket challenge had significantly greater expectations from the public to participate in the challenge they completed in comparison with individuals who never participated in any challenge (P=.01 for the cinnamon challenge and P=.003 for the ALS ice bucket challenge). Cinnamon challenge participants had greater value for the outcomes of the challenge (P<.001) and perceived positive public opinion about the challenge (P<.001), in comparison with individuals who never participated in any challenge. In contrast, ALS ice bucket challenge participants had significantly greater positive emotional responses than individuals who never participated in any challenge (P<.001). Conclusions: The constructs that contribute to the spread of web-based challenges vary based on the level of self-harm involved in the challenge and its purpose. Intervention efforts could be tailored to address the beliefs associated with different types of web-based challenges.
Language	English
Publishing date	2021-02-17
Publishing country	Canada
Document type	Journal Article
ISSN	2561-6722
ISSN (online)	2561-6722
DOI	10.2196/24988
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