[Federal Register Volume 86, Number 158 (Thursday, August 19, 2021)]
[Notices]
[Pages 46706-46707]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-17777]



[[Page 46706]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Office of the Secretary


Findings of Research Misconduct

AGENCY: Office of the Secretary, HHS.

ACTION: Notice.

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SUMMARY: Findings of research misconduct have been made against 
Viravuth Yin, Ph.D. (Respondent), former Associate Professor, Mount 
Desert Island Biological Laboratory (MDIBL). Respondent engaged in 
research misconduct in research supported by U.S. Public Health Service 
(PHS) funds, specifically National Institute of General Medical 
Sciences (NIGMS), National Institutes of Health (NIH), grants P20 
GM104318 and P20 GM103423. The administrative actions, including 
supervision for a period of two (2) years, were implemented beginning 
on August 2, 2021, and are detailed below.

FOR FURTHER INFORMATION CONTACT: Wanda K. Jones, Dr.P.H., Acting 
Director, Office of Research Integrity, 1101 Wootton Parkway, Suite 
240, Rockville, MD 20852, (240) 453-8200.

SUPPLEMENTARY INFORMATION: Notice is hereby given that the Office of 
Research Integrity (ORI) has taken final action in the following case:
    Viravuth Yin, Ph.D., Mount Desert Island Biological Laboratory: 
Based on the report of an investigation conducted by MDIBL and analysis 
conducted by ORI in its oversight review, ORI found that Dr. Viravuth 
Yin, former Associate Professor, MDIBL, engaged in research misconduct 
in research supported by PHS funds, specifically NIGMS, NIH, grants P20 
GM104318 and P20 GM103423.
    Respondent neither admits nor denies ORI's findings of research 
misconduct. The settlement is not an admission of liability on the part 
of the Respondent. The parties entered into a Voluntary Settlement 
Agreement to conclude this matter without further expenditure of time, 
finances, or other resources.
    ORI found that Respondent engaged in research misconduct by 
knowingly, intentionally, and/or recklessly falsifying and/or 
fabricating data included in the following three (3) published papers 
and two (2) submitted manuscripts:
    <bullet> Smith AM, Dykeman CA, King BL, Yin VP. Modulation of 
TNF[alpha] Activity by the microRNA Let-7 Coordinates Heart 
Regeneration. iScience 2019;15:1-15; doi: 10.1016/j.isci.2019.04.009 
(hereafter referred to as ``iScience 2019'').
    <bullet> Smith AM, Dykeman CA, King BL, Yin VP. Modulation of 
TNF[alpha] Activity by the microRNA Let-7 Coordinates Heart 
Regeneration. iScience 2019;17:225-29; doi: 10.1016/j.isci.2019.06.017 
(hereafter referred to as ``iScience Correction'').
    <bullet> Beauchemin M, Smith A, Yin VP. Dynamic microRNA-101a and 
Fosab expression controls zebrafish heart regeneration. Development 
2015;142:4026-37; doi: 10.1242/dev.126649 (hereafter referred to as 
``Development 2015'').
    <bullet> Smith AM, Dykeman CA, Yin VP. Modulation of epicardial 
TNF[alpha] Activity by the microRNA Let-7 Coordinates the Zebrafish 
Heart Regeneration. Manuscript submitted to iScience in 2018 (hereafter 
referred to as ``iScience 2018 draft'').
    <bullet> Smith AM, Dykeman CA, Yin VP. Modulation of epicardial 
TNF[alpha] Activity by the microRNA let-7 coordinates the zebrafish 
heart regeneration. Manuscript submitted to PNAS in 2018 (hereafter 
referred to as ``PNAS 2018 draft'').
    Specifically, Respondent intentionally, knowingly, and/or 
recklessly falsified and/or fabricated data by:
    <bullet> Reusing, relabeling, and reporting Phosphate Buffered 
Saline (PBS) controls as scrambled antisense Locked Nucleic Acids 
(LNAs) in the following experimental results:

--RT-qPCR data representing the knockdown of let7 expression in Figure 
2B of PNAS 2018 draft, iScience 2018 draft, and iScience 2019
--images of tcf21:Dsred expression in LNA-let-7 treated hearts at 3, 
14, and 21 days post- amputation (dpa) showing defects in wound closure 
in Figure 2C of PNAS 2018 draft, iScience 2018 draft, and iScience 2019
--quantification of tcf21:Dsred expression within the resection wound 
in LNA-let-7 treated hearts in Figure 2D of iScience 2019
--images exhibiting proliferating cardiac muscle (CM) in Figure 3A of 
PNAS 2018 draft, iScience 2018 draft, and iScience 2019
--suppression of CM proliferation indices in LNA-let-7 hearts at 3 and 
7 dpa in Figure 3B of PNAS 2018 draft, iScience 2018 draft, and 
iScience 2019
--severity of the injured heart phenotype in Figure 3C of PNAS 2018 
draft, iScience 2018 draft, and iScience 2019
--quantification of the severity of the injury heart phenotype in 
Figure 3D of iScience 2019
--electron microscopy images of remote and injury zones of resected 7-
dpa hearts in Figure 4A of PNAS 2018 draft, iScience 2018 draft, 
iScience 2019, and iScience Correction
--images of Tg(gata4:GFP) expression in the primordial heart muscle 
layer in Figure 4B of PNAS 2018 draft, iScience 2018 draft, iScience 
2019, and iScience Correction
--quantification of gata4:GFP expression in control and LNA-let-7 
treated hearts in Figure 4C of iScience 2019 and iScience Correction
--RNA transcripts identifying differentially upregulated TNF[alpha] 
transcripts in Figure 5A of PNAS 2018 draft, iScience 2018 draft, 
iScience 2019, and their resultant qPCR results, which identified 
increased TNF[alpha] expression in Figure 5C of PNAS 2018 draft, Figure 
5B of iScience 2018 draft, iScience 2019, and Table S1 of iScience 2019
--CM proliferation analyses results in Figures S4B and S4C of PNAS 2018 
draft and iScience 2018 draft, and Figures S5B and S5C of iScience 2019
--images representing the function of let-7 in Figure 2C of iScience 
Correction and reusing and relabeling images from an unrelated 
experiment, such that let-7 function is not represented in the image
--images reporting the function of let-7 in Figure 3A of iScience 
Correction
--images representing differences in the effects of miR-101a depletion 
on Met2 and PNA expression and the quantification of cardiomyocyte 
proliferation in uninjured control and Tg(hs:miR-101a-sp) heat exposed 
hearts (CM proliferation analysis) in Figures 2A, 2B, 2C, and 2D, and 
results in Figure 2E of Development 2015
--muscle, fibrin, and collagen staining images representing increased 
scar tissue presence in Tg(hs:miR-101a-sp) heat-treated hearts, as 
compared to wild type hearts in Figures 3A, 3B, 3C, 3D, 3E, and 3F of 
Development 2015
--scarring indices and the size of the injured area in wild type versus 
Tg(hs:miR-101a-sp) heat-treated hearts in Figures 3G and 3H of 
Development 2015
--differences in (1) the amount of scarring, as represented by AFOG 
staining in control and Tg (hs:miR-101-a-sp) ventricles from resected 
and heat-treated hearts in Figures 4B and 4C; (2) the amount of scar 
tissue in the presence of suppressed miR-101a expression in Tg(hs:miR-
101a-sp) hearts, compared to control hearts in Figures 4H and 4I; and 
(3) the quantification of the scarring indices

[[Page 46707]]

in control versus Tg(hs:miR-101a-sp) hearts in Figure 4J of Development 
2015
--differences in (1) the amount of scarring, as represented by 
comparing AFOG staining in control and Tg(hs:miR-101a-sp) and 
Tg(hs:miR-133a1-pre) hearts exposed to long term heat therapy in 
Figures 5A, 5B and 5C, or Tropomyosin staining in Figures 5D, 5E, and 
5F; and (2) the quantification of the scarring indices, tropomyosin 
expression, and injury area in Figures 5G, 5H, and 5I of Development 
2015
--increased Fosab expression in Tg(hs:miR-101a-sp) ventricles relative 
to controls in Figures 6A and 6B, RNA in situ hybridization studies in 
control and regenerating hearts detecting miR-101a expression in 
Figures 6C, 6D, 6E, and 6E', and Fosab expression in Figures 6F, 6G, 
6H, and 6H' of Development 2015
--images reporting significant differences in Dsred expression, 
cardiomyocyte proliferation, collagen and fibrin staining, and scar 
tissue removal in ventricles from zebrafish treated with lna-Let-7, as 
compared to scrambled control, to support the importance of miR-101a in 
scar tissue removal/ventricular regeneration in Figures 6H, 6I, 6J, 7C, 
7D, and 7E of Development 2015

    <bullet> reporting research methods and statistics that were not 
performed in the following experimental results:

--PCR data in the graph represented in Figure 2B of PNAS 2018 draft, 
iScience 2018 draft, and iScience 2019, by representing the data from 
two (2) remote PCR experiments as being from the same experiment
--PCR data in the graph represented in Figure 2B of iScience Correction 
by reusing and relabeling a graph containing data that were the result 
of different experimental conditions (exposure to heat shock), to 
include scrambled control data
--control data and statistical differences between control and 
experimental data represented in PNAS 2018 draft, iScience 2018 draft, 
iScience 2019, and iScience Correction, by falsely reporting the use of 
both antisense scrambled and LNA oligonucleotides that were designed 
and administered to adult animals via intraperitoneal injection at 
10ug/g body weight
--representing the ``n'' of one biological replicate or one experiment 
as being multiple independent samples or experiments in iScience 2019 
and iScience Correction
--control data and statistical differences between control and 
experimental data and the reported methods in Development 2015, 
concluding that miR-101a controls both CM proliferation and scar tissue 
removal, by falsely reporting the use of LNA oligonucleotides to 
modulate miR-101 activity in vivo to elucidate its contributions during 
adult heart regeneration

    Dr. Yin entered into a Voluntary Settlement Agreement (Agreement) 
and voluntarily agreed to the following:
    (1) Respondent agreed to have his research supervised for a period 
of two (2) years beginning on August 2, 2021. Respondent agreed that 
prior to submission of an application for PHS support for a research 
project on which Respondent's participation is proposed and prior to 
Respondent's participation in any capacity on PHS-supported research, 
Respondent shall ensure that a plan for supervision of Respondent's 
duties is submitted to ORI for approval. The supervision plan must be 
designed to ensure the scientific integrity of Respondent's research 
contribution. Respondent agreed that he shall not participate in any 
PHS-supported research until such a supervision plan is submitted to 
and approved by ORI. Respondent agreed to maintain responsibility for 
compliance with the agreed upon supervision plan.
    (2) The requirements for Respondent's supervision plan are as 
follows:
    i. A committee of 2-3 senior faculty members at the institution who 
are familiar with Respondent's field of research, but not including 
Respondent's supervisor or collaborators, will provide oversight and 
guidance for a period of two (2) years from the effective date of the 
Agreement. The committee will review primary data from Respondent's 
laboratory on a quarterly basis and submit a report to ORI at six (6) 
month intervals setting forth the committee meeting dates and 
Respondent's compliance with appropriate research standards and 
confirming the integrity of Respondent's research.
    ii. The committee will conduct an advance review of any PHS grant 
applications (including supplements, resubmissions, etc.), manuscripts 
reporting PHS-funded research submitted for publication, and abstracts. 
The review will include a discussion with Respondent of the primary 
data represented in those documents and will include a certification to 
ORI that the data presented in the proposed application/publication is 
supported by the research record.
    (3) Respondent agreed that for a period of two (2) years beginning 
on August 2, 2021, any institution employing him shall submit, in 
conjunction with each application of PHS funds, or report, manuscript, 
or abstract involving PHS-supported research in which Respondent is 
involved, a certification to ORI that the data provided by Respondent 
are based on actual experiments or are otherwise legitimately derived 
and that the data, procedures, and methodology are accurately reported 
in the application, report, manuscript or abstract.
    (4) If no supervisory plan is provided to ORI, Respondent agreed to 
provide certification to ORI at the conclusion of the supervision 
period that he has not engaged in, applied for, or had his name 
included on any application, proposal, or other request for PHS funds 
without prior notification to ORI.
    (5) Respondent agreed to exclude himself voluntarily from serving 
in any advisory capacity to PHS including, but not limited to, service 
on any PHS advisory committee, board, and/or peer review committee, or 
as a consultant for a period of two (2) years, beginning on August 2, 
2021.
    (6) As a condition of the Agreement, Respondent will request that 
the following papers be retracted in accordance with 42 CFR 
93.407(a)(1) and Sec.  93.411(b):

<bullet> Development 2015 Dec 1;142(23):4026-37
<bullet> iScience 2019 May 31;15:1-15
<bullet> iScience 2019 Jul 26;17:225-29

    Respondent will copy ORI and the Research Integrity Officer at 
MDIBL on the correspondence.

    Dated: August 16, 2021.
Wanda K. Jones,
Acting Director, Office of Research Integrity, Office of the Assistant 
Secretary for Health.
[FR Doc. 2021-17777 Filed 8-18-21; 8:45 am]
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