Research integrity

ORI Fail

“Dr. Elgazzar is a brilliant researcher”

The Office of Research Integrity at the US Department of Health & Human Services (HHS-ORI) is United States’ highest public authority on, well, research integrity. The government-employed officials investigate research misconduct and mete out punishments in form of retraction verdicts, year-long funding bans and enforced supervision. HHS-ORI has the best experts on data integrity in America and their skills and professionalism are unmatched.

Except when they aren’t. Here is such a case.

HHS-ORI failed before, already at the time point of its inception around 30 years ago, by whitewashing the massive fraudsters Robert Gallo and Thereza Imanishi-Kari. Both were initially found guilty of research misconduct, but the decision were completely overruled in the higher instances by HHS-ORI itself. Read here:

It is not just lawyers and politicians who meddle and sabotage the work of academically-trained HHS-ORI experts. Quite recently, two former HHS-ORI senior executives, the men in charge of investigations of data manipulation, served as paid witnesses to defend a fraudster in his lawsuit against a publisher. The two greedy old men were John Dahlberg, former HHS-ORI Deputy Director in charge of Investigative Oversight, and his former Associate Director Alan Price. I personally don’t think the two left all their decency behind when they departed from HHS-ORI, rather that they never had any decency, which would explain why so many US fraudsters went unpunished on their watch. And these are not the only incompetents at that institution, it seems.

Reddy vs JBC

Pittsburgh associate professor Raju Reddy and a colleague sued JBC over a retraction. The case has been settled in January 2021, the baddies won and the precedent is set.

So what do we have now? This rather new paper, by the Egyptian-born critical care medicine professor Mohamed El Gazzar, or Elgazzar, as his East Tennessee State University (ETSU) in USA lists him. The paper has been already corrected, twice. First concern was raised in June 2020:

Isatou Bah , Ajinkya Kumbhare , Lam Nguyen , Charles E. McCall , Mohamed El Gazzar IL-10 induces an immune repressor pathway in sepsis by promoting S100A9 nuclear localization and MDSC development Cellular Immunology (2018) doi: 10.1016/j.cellimm.2018.07.003

Mesocyclops major: “Same western blot with slightly different exposure time duplicated in two separate experiments with a horizontal flip.”

A Corrigendum was issued soon after, in November 2020:

“The authors regret the incorrect publication of Fig. 7C in the original article. The right protein band (S100A9/cytosolic) in the top Western blot image in Fig. 7C was a duplicate of the right band (S100A9/cytosolic) of the top right image in Fig. 7B. This was due to a mistake in the cutting and alignment of the correct bands. The correct bands in Fig. 7C have been restored and are presented below. This correction does not influence the results or any parts of the paper.”

How does a horizontal flip and contrast adjustment happen by “mistake” though? But then, in April 2022, something else was found, and this is where HHS-ORI comes in.

The image integrity sleuth Cheshire asked El Gazzar to share the original western blot data for Figure 7b and 7D. El Gazzar refused, but commented on PubPeer:

I inspected an enlarged image in a power point slide we have. These two bands look very close but they are not the same.

Other PubPeer users insisted the bands were identical enough to count as a copy-paste. El Gazzar protested, and accused his critics back:

I cannot see the similarity with my naked eye, but the sensitive tool you use can reveal tiny similarities. You or your associates screened this paper two years ago and alerted me to an error in this same figure, which we corrected then (Fig. 7C), but there was no mention of band similarities in Fig. 7B & D. Why are you certain now these two bands are similar?

Not the first time US scientists accuse Cheshire of being maliciously delusional, here some recent cases:

So in May 2022 Cheshire wrote to HHS-ORI, about

NIH-funded research with possible image manipulation; original data may be unavailable. Authors seem to have have a number of papers with similar concerns.

Indeed, there is a dozen or so papers by El Gazzar being criticized on PubPeer, but we will get there. Wait a bit, we aren’t yet done with this one. This was the reply Cheshire received on 15 September from a Scientist Investigator at the Division of Investigative Oversight (whom I shall not name for now):

Thank you for your expression of concern, and bringing the discussion thread to the attention of ORI.  Forensic evaluation of the images in question supports that while the two blots are very similar, each blot has distinct differences in size and shape, such that they are not the same.

If you would like further clarification from the authors and/or institution, or have additional concerns in other publications, please contact the institution directly:  Dr. Nick Hagemeier, Interim Vice Provost for Research, ETSU at […]

As this allegation does not meet the definition of research misconduct, ORI considers this matter closed.

So did Cheshire and others make a mistake? False alarm, as El Gazzar explained already months ago? Cheshire asked HHS-ORI for the details of their analysis, or the high-resolution image El Gazzar claimed to have at his disposal. But Cheshire was told by HHS-ORI to contact El Gazzar’s employer directly.

But wait, what is this second Corrigendum from 4 August 2022?

“The authors regret that the lower S100A9 bands in Fig. 7D are duplicate of the lower S100A9 bands in Fig. 7B and were misplaced during figure assembly. The correct bands in Fig. 7D have been restored. This correction does not influence the results or conclusions of this paper.”

Huh?

If the bands are not identical, as HHS-ORI educated Cheshire, why did El Gazzar declare those same bands as “duplicate” in his recent Corrigendum? Maybe he should retract the correction, what with the autorotative HHS-ORI findings?

Cheshire asked HHS-ORI to explain the existence of that Corrigendum, and informed El Gazzar’s employer ETSU as well. No reply so far. Maybe these cats are moping and need to be confused?

Maybe El Gazzar should ask HHS-ORI if it was premature to correct this paper also?

Jun Dai , Ajinkya Kumbhare , Dima Youssef , Zhi Q. Yao , Charles E. McCall author has email , Mohamed El Gazzar Expression of C/EBPβ in myeloid progenitors during sepsis promotes immunosuppression Molecular Immunology (2017) doi: 10.1016/j.molimm.2017.09.008

The Corrigendum from June 2022 stated: “The authors regret that the two β-actin bands in Fig. 7A are duplicate of the first two β-actin bands in Fig. 7B and were misplaced during figure assembly. The correct bands in Fig. 7A have been restored. This correction does not influence the results

Also the following study was swiftly corrected, in November 2020. The Corrigendum explained “due to a mistake in the cutting and alignment of the correct bands” and please be aware that “This correction does not influence the results or the study’s conclusions“:

Isatou Bah , Tuqa Alkhateeb , Ajinkya Kumbhare , Dima Youssef , Zhi Q. Yao , Gregory A. Hawkin , Charles E. McCall , Mohamed El Gazzar HuR promotes miRNA-mediated upregulation of NFI-A protein expression in MDSCs during murine sepsis Molecular Immunology (2020) doi: 10.1016/j.molimm.2020.04.014 

Or how about this paper, flagged on PubPeer in May 2020 and swiftly corrected, also in November 2020?

Tuqa Alkhateeb , Ajinkya Kumbhare , Isatou Bah , Dima Youssef , Zhi Q. Yao , Charles E. McCall, Mohamed El Gazzar S100A9 maintains myeloid-derived suppressor cells in chronic sepsis by inducing miR-21 and miR-181b Molecular Immunology (2019) doi: 10.1016/j.molimm.2019.04.019 

Oh wow, That looks quite fake. But not to El Gazzar, who was able to explain everything on PubPeer:

Mistakes were made. Some of the Western blottings were not performed properly. Samples from different experiments were resolved onto the same gel and, for some blots, the membranes were reprobed without being stripped properly, resulting in band overlapping and misidentification of the target protein bands.

Say what? The western blots faked themselves while being stained??? The Editor-in-Chief of the journal, whom El Gazzar announced to contact, obviously agreed, because we are now treated to this Corrigendum:

This correction does not influence the results or the study’s conclusions.”

All well now? Not quite, because the Corrigendum contained forged data also.

Actinopolyspora biskrensis: “Examining the corrected images, there may be some additional similarities.

El Gazzar was ready with new bullshit:

These bands come from non-specific/background binding to the IgG control antibody used in immunoprecipitation. So, I am not surprised that some of these bands look similar as the same cell lysate and antibody were used.

That was in April 2022, and since no further correction, or god beware, a retraction, arrived, we must assume the experts at the journal and Elsevier swallowed this explanation. Maybe even HHS-ORI has cast an approving glance also?

Also in April 2022, El Gazzar announced in another case to “contact the journal for how to address this error” and be “looking” for the original data of this paper:

Laura Brudecki , Donald A Ferguson , Charles E McCall, Mohamed El Gazzar MicroRNA‐146a and RBM4 form a negative feed‐forward loop that disrupts cytokine mRNA translation following TLR4 responses in human THP‐1 monocytes Immunology & Cell Biology (2013) doi: 10.1038/icb.2013.37

He probably gave up on both projects, or got distracted. Or maybe El Gazzar asked HHS-ORI for an expert opinion, you know.

Maybe you noticed what El Gazzar’s research focus is:

“His specific contributions and emphasis are on epigenetic and microRNA based regulation that generates reprogramming of genes linked to inflammation. His recent work indicates that microRNAs play a role in sepsis pathogenesis, including immunosuppression and chronic inflammation, a poorly understood and highly prevalent aspect of sepsis that increases rates of mortality to infection or injury.”

A big red flag. By now everyone working on miRNAs in diseases is suspicious, so much fraud has been committed in the field, that it has inspired the Chinese papermill industry. For example, Carlo Croce and George Calin established the field of miRNAs in cancer, and you can imagine how trustworthy their research is.

With El Gazzar’s papers, it’s not just fake western blots. Also flawed cytometry:

Melissa B. McPeak , Dima Youssef , Danielle A. Williams , Christopher Pritchett , Zhi Q. Yao , Charles E. McCall, Mohamed El Gazzar Myeloid Cell-Specific Knockout of NFI-A Improves Sepsis Survival Infection and Immunity (2017)  doi: 10.1128/iai.00066-17

Hoya camphorifolia: “Fig 5A, “Example of flow cytometry of bone marrow cells harvested at intervals after sepsis induction and gated by Gr1+ CD11b+ staining.” The four panels in Nfia cKO column have more points in common than one would expect. They seem to have come from a single data set, differently filtered or gated.

El Gazzar explained on PubPeer that because mice are genetical knock-outs, their blood cells emit exactly identical fluorescent signal in FACS when stained with antibodies:

For these knockout mice, they should look like naive/normal mice because in the absence of this Nfia (KO) these mice will generate the same numbers of Gr1 CD11b cells, although the cells were harvested at different time points. So, I would not be surprised that these mice have more points in common.

This bullshit explanation makes no sense, but maybe let’s ask HHS-ORI for an expert opinion before El Gazzar has to issue another “conclusions not affected” Corrigendum? We shall all defer to ORI’s expertise here.

A similar situation in this very recent study:

Dechao Cao , Sushant Khanal , Ling Wang , Zhengke Li , Juan Zhao , Lam Nhat Nguyen , Lam Ngoc Thao Nguyen , Xindi Dang , Madison Schank , Bal Krishna Chand Thakuri , Jinyu Zhang , Zeyuan Lu , Xiao Y. Wu , Zheng D. Morrison , Mohamed El Gazzar, Shunbin Ning , Jonathan P. Moorman , Zhi Q. Yao A Matter of Life or Death: Productively Infected and Bystander CD4 T Cells in Early HIV Infection Frontiers in Immunology (2021) doi: 10.3389/fimmu.2020.626431 

Actinopolyspora biskrensis: “Could the authors please provide high resolution images of the flow cytometry results in Figure 1B and 1D? There seem to be some unexpected similarities in the plots

This time, El Gazzar’s colleague at ETSU, the hepatology professor Zhi Q Yao replied:

After review the original data, we found that Fig.1B is correct, however, the representative dot plots for Fig.1D were selected wrongly (may be due to repeated copy/paste) by accident, but the summary graph is correct.”

It was not a copy/paste accident though, what happened was this: a sample measurement file wase plotted with different settings to make the two copies look dissimilar, supported by different quantification numbers. Nevertheless, the Frontiers Correction from July 2022 insisted:

“In the original article, there was a mistake in Figure 1D as published. The representative flow dot plots were misplaced. […] The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.”

Original image: ETSU/YouTube

Two years ago, Yao celebrated his colleague when El Gazzar received some faculty award:

““Dr. Elgazzar is a brilliant researcher,” said Dr. Zhi Q. Yao, professor in ETSU’s Division of Infectious Diseases and director of the Hepatitis (HCV/HIV) Program at the James H. Quillen VA Medical Center. “He has the ability to recognize and respond to fundamental gaps in our understanding of clinical immunology and inflammatory diseases.” […]

Promising scientists like Dr. Elgazzar are extremely important to ETSU and the College of Medicine’s research programs,” Yao said.”

All considered, it’s quite unlikely that El Gazzar became a hapless victim of a rogue lab member or a rogue colleague. Rather, someone else may have become a hapless (or in case of Yao, a willing) victim of El Gazzar’s rogue creativity. Or who else copy-pasted the blots on this author paper?

M. A. El Gazzar Thymoquinone suppressses in vitro production of IL-5 and IL-13 by mast cells in response to lipopolysaccharide stimulation Inflammation research (2007) doi: 10.1007/s00011-007-7051-0 

Back in April 2022, Cheshire suggested “Could the author please review Figure 1B. It appears that the bands used to represent IL-13 and IL-10 are the same.” The author was too busy. Or maybe he asked HHS-ORI to review that figure?

The Cigarette Mob of Palermo

On the gate of Constantinople was written, in a steel plate, the order of the Sultan:
“All the males of the Gjomarkaj, generation after generation, from the cradle to the grave, will carry the title of Kapidan”

Here, my “favourite” kind of fraud, fake science about the dangers of smoking, what can cigarette industry wish for more? Flagged by Cheshire in April 2022:

Christopher Railwah , Alnardo Lora , Kanza Zahid , Hannah Goldenberg , Michael Campos , Anne Wyman , Bakr Jundi , Magdalena Ploszaj , Melissa Rivas , Abdoulaye Dabo , Susan M. Majka , Robert Foronjy , Mohamed El Gazzar , Patrick Geraghty Cigarette smoke induction of S100A9 contributes to chronic obstructive pulmonary disease American journal of physiology. Lung cellular and molecular physiology (2020) doi: 10.1152/ajplung.00207.2020 

Two images in Figure 3C appear to overlap but are described differently. Although the scale bars are the same, the images seem to be a slightly different scale.
Two bands in Figure 6D appear to be the same, after horizontal flip and adjustment to contrast. Not clear how those transformations could occur merely as an error during figure assembly.
An image in Figure 2B and Figure 3C appear to overlap, but I believe they may be described differently.

Here, El Gazzar was unavailable for discussion. Maybe he went out for a smoke.

Here also refused a discussion here, on a paper from his postdoc period at Wake Forest, also flagged by Cheshire in April 2022:

Tie Fu Liu , Barbara K. Yoza , Mohamed El Gazzar , Vidula T. Vachharajani , Charles E. McCall NAD+-dependent SIRT1 deacetylase participates in epigenetic reprogramming during endotoxin tolerance The Journal of biological chemistry (2011) doi: 10.1074/jbc.m110.196790

A band seems to appear in both Figure 4A and Figure 5B (stretched) where they seem to be described differently. Could the authors please check? 5B shown here with increased brightness. Arrows indicate some common background features.”
Seems to be a similarly recycled band (after horizontal stretching) used in both Figure 5B and Figure 6A. Some common background features indicated with arrows.

An older one, from El Gazzar’s PhD period at Kumamoto University School of Medicine in Japan:

Rabab El Mezayen , Mohamed El Gazzar, Mark R. Nicolls, John C. Marecki , Stephen C. Dreskin, Hisayuki Nomiyama Effect of thymoquinone on cyclooxygenase expression and prostaglandin production in a mouse model of allergic airway inflammation Immunology Letters (2006) doi: 10.1016/j.imlet.2006.04.012 

El Gazzar: “With close inspection and by looking at the color contrast, these bands look very close but are not similar.”

Eventually, El Gazzar kind of admitted there was a problem:

“We no longer have access to the original data. Are you 100% certain these bands are similar? Even with your sensitive tool that can reveal tiny similarities, I still see some differences. Acknowledging mistakes and taking steps to correct them should be encouraged, not seen as inherent carelessness.”

And now what? Nothing?

One can’t expect much from El Gazzar. But one could have expected a bit more from HHS-ORI. It’s not like they were ignorant of this professor’s PubPeer record. And still they did not bother to look properly. And they seem unwilling to admit being wrong and reopen the case.


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10 comments on “ORI Fail

  1. Another sincere thank you. As a hobbyist, I am not as diligent as you-all scientist types, so I don’t keep careful track of the connections between some of these papers, authors, and journals. Your ability to tie these things into a narrative is probably a valuable service to science, but who am I to say?

    Like

    • Klaas van Dijk

      hi Leonid,

      Thanks, great posting about some activities of ORI.

      The posting reminded me to a recent verdict by LOWI at https://lowi.nl/besluit-2022-06/ This verdict reveals that LOWI will refuse to process appeals (= throw them away) when the complainer (a journalist?) has published the complaint on a public part of a / his own website.

      The verdict reveals as well that LOWI supports earlier punishments of this complainer by the Committee of Research Integrity of Tilburg University:

      (1): no hearing (mandatory according to all Regulations).
      (2): a refusal to send the complainer a copy of the response of the complainant (only allow the complainer to see with his own eyes this response from the complainant).

      Source: “Dat de CWI ervoor heeft gekozen om het verweerschrift van Betrokkene niet aan Verzoeker toe te sturen, maar hem slechts de mogelijkheid te bieden het verweerschrift in te zien, en dat de CWI de schending van de geheimhouding mee heeft laten wegen bij de beslissing om geen hoorzitting te houden, is naar het oordeel van het LOWI niet onzorgvuldig.”

      The verdict of LOWI provides the arguments for this punishment to dismiss the processing of this appeal:

      “Een vroegtijdig in de openbaarheid gebrachte beschuldiging van schending van de wetenschappelijke integriteit kan aan wetenschappers veel schade toebrengen en een zorgvuldige behandeling van de klacht in de weg staan.”

      So LOWI argues that there might be (severe) issues with ‘a careful processing of the complaint’ when there is already a public debate about (severe) allegations of research misconduct.

      LOWI does not provide references for this point of view.

      Do you happen to have some good examples that ‘a careful processing of the complaint’ was indeed (severy) hampered because there was already a public debate about (severe) allegations of research misconduct?

      LOWI also argues that a public debate about (severe) allegations of research misconduct can severely damage the reputation of the researcher in question, and that it is therefore mandatory that the complaint is strictly mandatory. LOWI does not list references that this is indeed the case in The Netherlands.

      LOWI does as well not explain why in The Netherlands complaints about serious mistakes by medical doctors can be discussed in public and why such complaints are public, including public hearings see
      https://www.tuchtcollege-gezondheidszorg.nl/pers for some backgrounds.

      This verdict was sighed by Eric Daalder, chair of LOWI. See
      https://www.raadvanstate.nl/overrvs/organisatie/leden-staatsraden/cv-s-leden-en/mr-eric-daalder/ for some backgrounds about Daalder.

      I fail to understand how this acting by LOWI is in line with something like ‘fair trial’.

      Like

  2. Unfortunately, many scientific dogmas which have consequences in global health are far from being right and accurate. This includes the definition of exosomes, miRNA technology, the definition of viruses, mammography screening among other human health tragedies.

    Like

  3. The ORI is sending a clear message: serial images recycling is not fraud.

    Like

  4. I did correspond with the author in April and asked him several questions. His reply:

    Here are my answers to your questions:

    1- A number of papers seem to have concerns about Western blots. Which of the labs involved has been responsible for generating most of those?
    My lab is responsible for generating four of these papers.

    2- Do you know if the original files for the Western blots are still available?
    I am still looking for the original images. It is just hard to track down people who worked in the lab long ago and many have left.

    3- There seem to be several papers which were partially funded by the NIH. Do you know if they are aware of the concerns?
    I have just received an email from our Vice Provost for Research (Dr. Nicholas Hagemeier) inquiring about this (see attachment 1). I replied that I am aware of and looking into these concern, and that I would let him know the outcome (see attachment 2).
    Our institution has procedures and policies in place on how to communicate with the NIH regarding these issue. I do not know when they will contact the NIH, but I believe this will depend on how my investigations and communications with the journals go and when they will be concluded.

    Thank you.

    Sincerely,

    Mohamed Elgazzar, Ph.D.

    Like

  5. Dr Elgazzar works in a Department of Veterans Affairs facility and appears to have research funding from the VA. They have their own policies and procedures for investigations of research misconduct. Someone needs to inform the VA office of research oversight about this.

    Like

  6. https://www.va.gov/oro/

    Specific allegations related to fabrication, falsification, or plagiarism (“research misconduct”) should be presented to the Research Integrity Officer (RIO) at the VA Medical Center conducting the research. When direct contact with the Medical Center is not desired, research misconduct allegations may be directed to ORO Central Office. Click here for more information on research misconduct.

    ORO does its best to honor the confidentiality of persons who file concerns about VA research.

    Persons who do not wish to identify themselves and would rather remain anonymous may call ORO’s toll-free RESEARCH concern line at 1-833-986-1323. Please provide as much information as possible when calling the RESEARCH concern line. ORO may not be able to follow-up effectively without sufficient information.

    Owen D Murnane, PhD
    Role: ACOS
    Title: R&D ACOS
    James H. Quillen VA Medical Center
    Sidney & Lamont St.
    Mountain Home, TN (621)
    423-926-1171 x7632
    Joseph Wilkerson
    Role: AO
    Title: R&D AO
    Mountain Home VA Medical Center James H. Quillen VA Medical Center, Mountain Home, TN
    Sidney & Lamont St.
    Mountain Home, TN (621)
    423-979-2859

    Like

  7. “The two greedy old men were John Dahlberg, former HHS-ORI Deputy Director in charge of Investigative Oversight, and his former Associate Director Alan Price.”

    Happy to oblige the rich and corrupted.

    “My sense was, Carlo Croce’s too big to make findings of misconduct on,” Dr. Dahlberg said in an interview. “It just wasn’t going to happen.”

    The fat cat bankers, and other fraudsters, would like excuse too.
    Come on down, Dahlberg!

    Like

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