RELEASE DATE:  October 31, 2003
RFA Number:  RFA-DE-05-001

Department of Health and Human Services (DHHS)

National Institutes of Health (NIH)
National Institute of Dental and Craniofacial Research (NIDCR) 

No. 93.121, Oral Diseases and Disorders Research

o Purpose of This RFA
o Research Objectives
o Mechanism(s) of Support 
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements 
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations


The purpose of this initiative is to stimulate research that will 
improve our understanding of the biological basis of development and 
progression of AIDS-related oral cancers and tumors, and to encourage 
research identifying novel targets for treatment, and biomarkers for 
early diagnosis and monitoring of disease progression. The role of 
chronic latent viruses of the oral cavity and their interaction with 
one another or with environmental factors in the context of HIV 
infection leading to the development of tumors or lesions with 
oncogenic potential is especially sought.

HIV infection is a major public health problem throughout the world. 
The hallmark of this infection is a gradual depletion of CD 4+ T cells 
which eventually leads to a state of immunosuppression. This 
immunosuppression predisposes the patients to warts, preneoplastic oral 
lesions and oral cancers. Some of these neoplasms are aggressive, hard 
to treat and can affect the quality of life of the patients. Oral 
malignancies and tumors affect up to 25% of patients with AIDS. The 
most frequent oral malignancies are Kaposi’s sarcoma (KS) and non-
Hodgkin’s lymphoma. Oral warts and oral hairy leukoplakia (OHL), a 
benign epithelial hyperplasia of the lingual squamous epithelium, have 
also been shown to increase among patients with HIV infection. 

The incidence of some of these conditions has changed following the 
introduction of highly active antiretroviral therapy (HAART). For 
example, the incidence of KS has significantly decreased, while 
plasmablastic lymphoma has increased. The latter is a diffuse large B-
cell lymphoma with a unique immunophenotype and appears to be 
associated with Epstein Barr virus (EBV). EBV is also associated with 
OHL and nasopharyngeal carcinoma. Human papillomavirus (HPV), another 
DNA virus, has been associated with the development of oral warts. The 
incidence of these warts appears to be increasing in the HAART era. 
Occasionally the oral warts in HIV infected patients show marked 
epithelial dysplasia. Recently the presence of HPV 16 and 18 in oral 
warts of some AIDS patients has been reported. HPV 16 has previously 
been implicated in invasive squamous cell carcinoma of the head and 
neck. However, until the patients are followed for an extended period 
of time, the risk for development of squamous cell carcinomas from oral 
dysplastic warts will remain unknown. 

The biological basis for AIDS-related oral lesions is not yet clear. 
There appears to be an emerging role for various concurrent viral 
infections in the HIV-infected host that are likely implicated in the 
pathogenesis of these ailments. For the purpose of this RFA the oral 
lesions of interest are the ones associated with concomitant infection 
with viruses that frequently confer latency, such as EBV, human 
herpesvirus 8 and HPV. In each case, the infection by each concomitant 
virus appears to be necessary, but not sufficient, for subsequent tumor 
Interestingly, the genomes of some of the viruses that are associated 
with the oral complications of HIV infection have sequence homology 
with some human cytokines and/or chemokines. For example, 
cytomegalovirus encodes vIL10 and CXC1&2, EBV encodes vIL10 and HHV-8 
encodes vIL6. The role of this mimicry to cellular cytokines in disease 
pathogenesis is not known. IL10 and IL6 are known to mediate Th2 cell 
responses and to inhibit Th1 immune responses. IL6 is also known to 
stimulate lymphocyte proliferation. 

Patients with HIV-related salivary gland disease present with signs and 
symptoms similar to those of patients with Sjögren’s syndrome. The 
condition is characterized by lymphocytic infiltration of the salivary 
glands and lymphoepithelial cysts of the major salivary glands and is 
part of diffuse interstitial lymphocytosis syndrome. Occasionally, 
lymphomas may develop within the salivary glands. The search for an 
etiology for this disease has so far been inconclusive. The incidence 
of salivary gland disease among HIV infected patients appear to has 
increased following the introduction of HAART. The cause of this 
increase is not known at the present time.


The objective of this RFA is to encourage research on the mechanisms 
and factors involved in the initiation and progression of AIDS–related 
oral malignancies, their detection and management. Multidisciplinary 
approaches and collaborations are encouraged. Examples of research 
responsive to this RFA are listed below but are by no means inclusive: 

o Studies to characterize the host genetic susceptibility to AIDS- 
related oral malignancies and tumors in patients with HIV infection.
o Studies to determine the pathogenic mechanisms involved in EBV, HHV-
8, and HPV mediated tumor initiation and promotion of malignancies of 
the oral cavity. For example, the interaction of viral gene products 
with cellular factors involved in the regulation of the cell cycle.
o Studies to determine the cellular proteome and transcriptome of 
virally-induced tumors of the oral cavity in the context of HIV 
o Studies to determine the mode of entry, latency, reactivation and 
transformation of oncogenic viruses of mucosal cells of the oral 
o Studies to determine the interactions of HIV structural and non- 
structural proteins with oncogenic viruses and their role in 
potentiation of transformation. 
o Studies to identify novel molecular targets for therapeutic 
interventions for oral KS and non-Hodgkin’s lymphoma.
o Studies to determine the immunological mechanisms that are involved 
in EBV, HPV and HHV-8 driven oral malignancies and tumors, in the 
context of HIV infection.
o Studies to determine the effect of prolonged moderate 
immunosuppression or incomplete or failed responses to HAART on the 
development of oral malignancies and tumors.
o Studies to determine the effect of the concomitant prolonged exposure 
of HIV infected patients to antiretroviral therapy and viruses with 
oncogenic potential on the development of AIDS-related oral 
malignancies and pre-neoplastic lesions.
o Studies to determine the molecular epidemiology of the viral strains 
that are implicated in the promotion of AIDS-related malignant 
transformations of the oral cavity.  
o Development of animal and cell based models for AIDS-related oral 
o Studies to determine the similarities and differences between AIDS-
related tumors of the oral mucosa and other anatomical mucosal 
surfaces, e.g. vaginal and gastrointestinal.
o Studies that are geared towards identifying reliable diagnostic and 
prognostic biomarkers, useful for detection of AIDS-related oral 
malignancies and their progression. 


This RFA will use NIH individual research project grant (R01) and the 
exploratory/development research grant (R21) award mechanisms.  As an 
applicant you will be solely responsible for planning, directing, and 
executing the proposed project.  This RFA is a one-time solicitation.  
Future unsolicited, competing-continuation applications based on this 
project will compete with all investigator-initiated applications and 
will be reviewed according to the customary peer review procedures. 

This RFA uses just-in-time concepts.  It also uses the modular as well 
as the non-modular budgeting formats (see  
Specifically, if you are submitting an application with direct costs in 
each year of $250,000 or less, use the modular format.  Otherwise 
follow the instructions for non-modular research grant applications.  
This program does not require cost sharing as defined in the current 
NIH Grants Policy Statement at  

The NIDCR intends to commit approximately $2,000,000 total cost in FY 
2005 to fund 6 to 8 new and/or competitive continuation grants in 
response to this RFA. An R01 applicant may request a project period of 
up to 4 years and a budget for direct costs of up to $499,999 per year. 
An R21 applicant may request a project period of up to two years with a 
combined budget for direct costs of up to $275,000 for the two year 
period.  For example, the applicant may request $100,000 in the first 
year and $175,000 in the second year.  The request should be tailored 
to the needs of the project. Normally, no more than $200,000 may be 
requested in any single year. This R21 cap may be exceeded by $25,000, 
direct costs per year to accommodate the facilities and administrative 
(indirect) costs associated with collaborative research at another 
institution. Because the nature and scope of the proposed research will 
vary from application to application, it is anticipated that the size 
and duration of each award will also vary. Although the financial plans 
of the NIDCR provide support for this program, awards pursuant to this 
RFA are contingent upon the availability of funds and the receipt of a 
sufficient number of meritorious applications.  
You may submit an application(s) if your institution has any of the 
following characteristics: 
o For-profit or non-profit organizations 
o Public or private institutions, such as universities, colleges, 
hospitals, and laboratories 
o Units of State and local governments
o Eligible agencies of the Federal government  
o Domestic or foreign institutions/organizations

Any individual with the skills, knowledge, and resources necessary to 
carry out the proposed research is invited to work with their 
institution to develop an application for support.  Individuals from 
underrepresented racial and ethnic groups as well as individuals with 
disabilities are always encouraged to apply for NIH programs.   

Grantees will meet annually at or near NIH, Bethesda, MD, to share 
results, to ensure that the NIDCR has a coherent view of the advances 
in the field, and to have an opportunity for collective problem solving 
among investigators.  Applicants should budget for travel in their 
requested budget for the principal investigator and one additional 
young investigator to attend this annual meeting. 


We encourage inquiries concerning this RFA and welcome the opportunity 
to answer questions from potential applicants.  Inquiries may fall into 
three areas:  scientific/research, peer review, and financial or grants 
management issues:

o Direct your questions about scientific/research issues to:

Mostafa Nokta, MD, PhD.
Division of Basic and Translational Sciences
National Institute of Dental and Craniofacial research
Building 45, Room 4AN-18H
45 Center Drive
Bethesda MD, 20892-6402
Telephone: (301) 594-7985
Fax (301) 480-8319
o Direct your questions about peer review issues to:

H. George Hausch, Ph.D.
Division of Extramural Activities
National Institute of Dental and Craniofacial Research
Building 45, Room 4AN-44F
45 Center Drive
Bethesda, MD  20892-6402
Telephone:  (301) 594-2904
Fax:  (301) 480-8303

o Direct your questions about financial or grants management matters 

Mary Daley
Grants Management Branch  
Division of Extramural Activities
National Institute of Dental and Craniofacial Research
45 Center Drive MSC 6402
Building 45, Room 4AN-44B
45 Center Drive
Bethesda, MD  20892-6402
Telephone: (301)-594-4808
Fax: (301)-480-3562

Prospective applicants are asked to submit a letter of intent that 
includes the following information:

o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel 
o Participating institutions
o Number and title of this RFA 

Although a letter of intent is not required, is not binding, and does 
not enter into the review of a subsequent application, the information 
that it contains allows NIDCR staff to estimate the potential review 
workload and plan the review.
The letter of intent is to be sent by the date listed at the beginning 
of this document.  The letter of intent should be sent to Dr. Hausch at 
the address listed above.


Applications must be prepared using the PHS 398 research grant 
application instructions and forms (rev. 5/2001). Applications must 
have a DUN and Bradstreet (D&B) Data Universal Numbering System (DUNS) 
number as the Universal Identifier when applying for Federal grants or 
cooperative agreements. The DUNS number can be obtained by calling 
(866) 705-5711 or through the web site at The DUNS number should be entered on 
line 11 of the face page of the PHS 398 form. The PHS 398 document is 
available at in 
an interactive format.  For further assistance contact GrantsInfo, 
Telephone (301) 710-0267, Email:


All application instructions outlined in the PHS 398 application kit 
are to be followed with the following modifications for R21 

1. FACE PAGE, Item 6:  Up to a total of two years of support may be 
requested.  Total direct costs for the two years may not exceed 

2. RESEARCH PLAN:  Items a-d may not exceed fifteen (15) pages, 
including tables and figures.  The following information should be 
taken into account for items a, b and c:  

o Item a, SPECIFIC AIMS--The instructions for this section suggest that 
the applicant state "the hypotheses to be tested".  Since some 
applications submitted in response to this RFA may also be design- or 
problem-driven (e.g., development of novel technologies), or need-
driven (initial research to develop a body of data upon which future 
research will build), hypothesis testing per se may not be the driving 
force in developing such a proposal and, therefore, may not be 
applicable.  The application should state the hypotheses, design, 
problem and/or need which will drive the proposed research.

o Item b, BACKGROUND AND SIGNIFICANCE--In this section, it is       
important to identify clearly how the application addresses the      
specific objectives of this RFA and the purpose of the R21            

o Item c, PRELIMINARY STUDIES/PROGRESS REPORT—No preliminary data are 
required for an R21 application.  

3.  APPENDIX.  Up to five articles may be submitted as appendix 

requesting up to $250,000 per year in direct costs must be submitted in 
a modular grant format.  The modular grant format simplifies the 
preparation of the budget in these applications by limiting the level 
of budgetary detail.  Applicants request direct costs in $25,000 
modules.  Section C of the research grant application instructions for 
the PHS 398 (rev. 5/2001) at includes step-
by-step guidance for preparing modular grants.  Additional information 
on modular grants is available at

USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 
5/2001) application form must be affixed to the bottom of the face page 
of the application.  Type the RFA number on the label.  Failure to use 
this label could result in delayed processing of the application such 
that it may not reach the review committee in time for review.  In 
addition, the RFA title and number must be typed on line 2 of the face 
page of the application form and the YES box must be marked. The RFA 
label is also available at:
SENDING AN APPLICATION TO THE NIH: Submit a signed, original copy of 
the application, including the Checklist, and three signed, 
photocopies, in one package to:
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD  20892-7710
Bethesda, MD  20817 (for express/courier service)
At the time of submission, send two additional copies of the 
application and all copies of the appendix material to:

H. George Hausch, Ph.D.
Division of Extramural Activities
National Institute of Dental and Craniofacial Research
Building 45, Room 4AN-44F
45 Center Drive
Bethesda, MD  20892-6402
Telephone:  (301) 594-2904
FAX:  (301) 480-8303
APPLICATION PROCESSING: Applications must be received on or before June 
16, 2004.  If an application is received after that date, it will be 
returned to the applicant without review. 

Although there is no immediate acknowledgement of the receipt of an 
application, applicants are generally notified of the review and 
funding assignment within 8 weeks.
The Center for Scientific Review (CSR) will not accept any application 
in response to this RFA that is essentially the same as one currently 
pending initial review, unless the applicant withdraws the pending 
application.  However, when a previously unfunded application, 
originally submitted as an investigator-initiated application, is to be 
submitted in response to an RFA, it is to be prepared as a NEW 
application.  That is, the application for the RFA must not include an 
Introduction describing the changes and improvements made, and the text 
must not be marked to indicate the changes from the previous unfunded 
version of the application.  

Upon receipt, applications will be reviewed for completeness by the CSR 
and responsiveness by the NIDCR. Incomplete and/or non-responsive 
applications will be returned to the applicant without further 
consideration. Applications that are complete and responsive to the RFA 
will be evaluated for scientific and technical merit by an appropriate 
peer review group convened by the NIDCR in accordance with the review 
criteria stated below.  As part of the initial merit review, all 
applications will:

o Undergo a process in which only those applications deemed to have the 
highest scientific merit, generally the top half of the applications 
under review, will be discussed and assigned a priority score 
o Receive a written critique
o Receive a second level review by the NIDCR National Advisory Council. 

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  
In the written comments, reviewers will be asked to discuss the 
following aspects of the application in order to judge the likelihood 
that the proposed research will have a substantial impact on the 
pursuit of these goals. The scientific review group will address and 
consider each of these criteria in assigning the application’s overall 
score, weighting them as appropriate for each application.  

o Significance 
o Approach 
o Innovation
o Investigator
o Environment

The application does not need to be strong in all categories to be 
judged likely to have major scientific impact and thus deserve a high 
priority score.  For example, an investigator may propose to carry out 
important work that by its nature is not innovative but is essential to 
move a field forward.

SIGNIFICANCE: Does this study address an important problem? If the aims 
of the application are achieved, how will scientific knowledge be 
advanced? What will be the effect of these studies on the concepts or 
methods that drive this field?

APPROACH: Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of 
the project? Does the applicant acknowledge potential problem areas and 
consider alternative tactics?

INNOVATION: Does the project employ novel concepts, approaches or 
methods? Are the aims original and innovative? Does the project 
challenge existing paradigms or develop new methodologies or 

INVESTIGATOR: Is the investigator appropriately trained and well suited 
to carry out this work? Is the work proposed appropriate to the 
experience level of the principal investigator and other researchers 
(if any)?

ENVIRONMENT: Does the scientific environment in which the work will be 
done contribute to the probability of success? Do the proposed 
experiments take advantage of unique features of the scientific 
environment or employ useful collaborative arrangements? Is there 
evidence of institutional support?  

ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the 
following items will be considered in the determination of scientific 
merit and the priority score:

human subjects and protections from research risk relating to their 
participation in the proposed research will be assessed. (See criteria 
included in the section on Federal Citations, below).
of plans to include subjects from both genders, all racial and ethnic 
groups (and subgroups), and children as appropriate for the scientific 
goals of the research.  Plans for the recruitment and retention of 
subjects will also be evaluated. (See Inclusion Criteria in the 
sections on Federal Citations, below).

are to be used in the project, the five items described under Section f 
of the PHS 398 research grant application instructions (rev. 5/2001) 
will be assessed.  


BUDGET:  The reasonableness of the proposed budget and the requested 
period of support in relation to the proposed research.

R21 APPLICATIONS:  The potential for ground-breaking, precedent-
setting research, with particular emphasis on novel and innovative 
approaches; and the potential to stimulate new concepts or approaches 
regarding important biomedical/behavioral problems, or provide a 
technique/system of wide applicability.


Letter of Intent Receipt Date: May 18, 2004
Application Receipt Date: June 16, 2004
Peer Review Date: August 2004
Council Review: September/October 2004
Earliest Anticipated Start Date: December 1, 2004


Award criteria that will be used to make award decisions include:

o Scientific merit (as determined by peer review)
o Availability of funds
o Programmatic priorities.

HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that 
applications and proposals involving human subjects must be evaluated 
with reference to the risks to the subjects, the adequacy of protection 
against these risks, the potential benefits of the research to the 
subjects and others, and the importance of the knowledge gained or to 
be gained. 

DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required 
for all types of clinical trials, including physiologic, toxicity, and 
dose-finding studies (phase I); efficacy studies (phase II); efficacy, 
effectiveness and comparative trials (phase III). The establishment of 
data and safety monitoring boards (DSMBs) is required for multi-site 
clinical trials involving interventions that entail potential risk to 
the participants. (NIH Policy for Data and Safety Monitoring, NIH Guide 
for Grants and Contracts, June 12, 1998:
of the NIH that women and members of minority groups and their sub-
populations must be included in all NIH-supported clinical research 
projects unless a clear and compelling justification is provided 
indicating that inclusion is inappropriate with respect to the health of 
the subjects or the purpose of the research. This policy results from 
the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43).

All investigators proposing clinical research should read the "NIH 
Guidelines for Inclusion of Women and Minorities as Subjects in 
Clinical Research - Amended, October, 2001," published in the NIH Guide 
for Grants and Contracts on October 9, 2001 
a complete copy of the updated Guidelines are available at   
The amended policy incorporates: the use of an NIH definition 
of clinical research; updated racial and ethnic categories in 
compliance with the new OMB standards; clarification of language 
governing NIH-defined Phase III clinical trials consistent with the new 
PHS Form 398; and updated roles and responsibilities of NIH staff and 
the extramural community.  The policy continues to require for all NIH-
defined Phase III clinical trials that: a) all applications or 
proposals and/or protocols must provide a description of plans to 
conduct analyses, as appropriate, to address differences by sex/gender 
and/or racial/ethnic groups, including subgroups if applicable; and b) 
investigators must report annual accrual and progress in conducting 
analyses, as appropriate, by sex/gender and/or racial/ethnic group 

SUBJECTS: The NIH maintains a policy that children (i.e., individuals 
under the age of 21) must be included in all human subjects research, 
conducted or supported by the NIH, unless there are scientific and 
ethical reasons not to include them. This policy applies to all initial 
(Type 1) applications submitted for receipt dates after October 1, 

All investigators proposing research involving human subjects should 
read the "NIH Policy and Guidelines" on the inclusion of children as 
participants in research involving human subjects that is available at

NIH policy requires education on the protection of human subject 
participants for all investigators submitting NIH proposals for 
research involving human subjects.  You will find this policy 
announcement in the NIH Guide for Grants and Contracts Announcement, 
dated June 5, 2000, at

HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of 
research on hESCs can be found at and at  
Only research using hESC lines that are registered in the NIH Human 
Embryonic Stem Cell Registry will be eligible for Federal funding (see   It is the responsibility of the applicant to 
provide, in the project description and elsewhere in the application as 
appropriate, the official NIH identifier(s)for the hESC line(s)to be 
used in the proposed research.  Applications that do not provide this 
information will be returned without review. 

The Office of Management and Budget (OMB) Circular A-110 has been 
revised to provide public access to research data through the Freedom of 
Information Act (FOIA) under some circumstances.  Data that are (1) 
first produced in a project that is supported in whole or in part with 
Federal funds and (2) cited publicly and officially by a Federal agency 
in support of an action that has the force and effect of law (i.e., a 
regulation) may be accessed through FOIA.  It is important for 
applicants to understand the basic scope of this amendment.  NIH has 
provided guidance at

Applicants may wish to place data collected under this PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application 
should include a description of the archiving plan in the study design 
and include information about this in the budget justification section 
of the application. In addition, applicants should think about how to 
structure informed consent statements and other human subjects 
procedures given the potential for wider use of data collected under 
this award.

The Department of Health and Human Services (DHHS) issued final 
modification to the “Standards for Privacy of Individually Identifiable 
Health Information”, the “Privacy Rule,” on August 14, 2002.  The 
Privacy Rule is a federal regulation under the Health Insurance 
Portability and Accountability Act (HIPAA) of 1996 that governs the 
protection of individually identifiable health information, and is 
administered and enforced by the DHHS Office for Civil Rights (OCR). 
Those who must comply with the Privacy Rule (classified under the Rule 
as “covered entities”) must do so by April 14, 2003  (with the 
exception of small health plans which have an extra year to comply).  

Decisions about applicability and implementation of the Privacy Rule 
reside with the researcher and his/her institution. The OCR website 
( provides information on the Privacy Rule, 
including a complete Regulation Text and a set of decision tools on “Am 
I a covered entity?”  Information on the impact of the HIPAA Privacy 
Rule on NIH processes involving the review, funding, and progress 
monitoring of grants, cooperative agreements, and research contracts 
can be found at

proposals for NIH funding must be self-contained within specified page 
limitations. Unless otherwise specified in an NIH solicitation, Internet 
addresses (URLs) should not be used to provide information necessary to 
the review because reviewers are under no obligation to view the 
Internet sites.   Furthermore, we caution reviewers that their anonymity 
may be compromised when they directly access an Internet site.

HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to 
achieving the health promotion and disease prevention objectives of 
"Healthy People 2010," a PHS-led national activity for setting priority 
areas. This RFA is related to one or more of the priority areas. 
Potential applicants may obtain a copy of "Healthy People 2010" at

AUTHORITY AND REGULATIONS: This program is described in the Catalog of 
Federal Domestic Assistance at and is not subject 
to the intergovernmental review requirements of Executive Order 12372 
or Health Systems Agency review.  Awards are made under the 
authorization of Sections 301 and 405 of the Public Health Service Act 
as amended (42 USC 241 and 284)and under Federal Regulations 42 CFR 52 
and 45 CFR Parts 74 and 92. All awards are subject to the terms and 
conditions, cost principles, and other considerations described in the 
NIH Grants Policy Statement.  The NIH Grants Policy Statement can be 
found at 

The PHS strongly encourages all grant recipients to provide a smoke-
free workplace and discourage the use of all tobacco products.  In 
addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits 
smoking in certain facilities (or in some cases, any portion of a 
facility) in which regular or routine education, library, day care, 
health care, or early childhood development services are provided to 
children.  This is consistent with the PHS mission to protect and 
advance the physical and mental health of the American people.

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