paper mills Smut Clyde

Ticket to Tianjin

"So here is a novelty in the annals of fictional research: a nomadic digital caliper. It visited a series of laboratories, accompanied by a backing troupe of mouse-mined xenograft tumours for it to measure" - Smut Clyde

by smut.clyde
Comments 13

Smut Clyde has discovered the Tianjin Papermill and would like to tell you about it. This one specialises in cancer research papers, all dedicated to proteins of the kinesin family, and seems to be somehow connected to the University of Rochester bigwig cheater Chainsaw Chang.

Before I pass the metaphorical mike to Smut Clyde, let me tell you what the real problem with papermills actually is.

It is not the AI or the digital technologies which Asian fraudsters use to generate “research” papers out of thin air and which the publishing industry and the scientific community are so afraid of. Everything AI generates on text or images is inane rubbish, and proper experts easily detect it as such, here for example the case of a science fiction magazine which editor rejects AI-generated texts in the matter of seconds. The sci-fi magazine never once published an AI story by mistake. Because to a qualified human seeking originality, they all look the same kind of unoriginal boring machine-written trash.

The real problem with science papermills lies with the scholarly publishers and the scientific community themselves. Because nobody actually reads the manuscripts properly as they march through peer review towards approval.

Sure, sometimes the papermills manipulate peer review, often they are even invited to do so by the publishers, via the guest-edited special issue business model. But even where the peer review is “real”, it often fails. Because the reviewing scientists are too often incompetent, lazy or naive.

An attractive and “natural” target for fraudsters

“In the various excellent texts on paper mills the question is discussed why Naunyn-Schmiedebergs Archives of Pharmacology has become a target for fake papers. I oppose the assumption that we simply want to fill pages with pseudo-scientific content. We actually look for quality and good science.” – Prof Dr Roland Seifert, Editor-in-Chief

by Leonid Schneider

The academic editors and peer reviewers only check if the manuscript looks like a scientific paper. And how is a scientific paper supposed to look like? Decades of massive fraud and bullshittery in science have trained generations of readers, editors and peer reviewers on what a “good” paper must look like. It must have this kind of writing style, this kind of experimental data, in fact, even this kind of results. The sacred “novelty” aspect has very little to do with originality. Novelty in science means nothing else but interchangeable use of random gene or molecule names in random contexts decorated with random buzzwords.

This system operates for many years almost like the classic machine-learning algorithm, except it is not a computer which is being trained on patterns, but actual humans, all of them professors and doctors of science and medicine. The result of this evolution is a standard template which is ridiculously easy to emulate when your science is totally fake, but which is difficult to comply with if you were that stupid to describe actual honest research.

Quite possibly, manuscripts containing real research get rejected exactly because they don’t comply to the trashy standard which the broken academic system trained itself on. Oh the irony.

But papermills pass the peer review with flying colours. Even without AI. Like this hand-made papermill fraud from Tianjin.

Ticket to Tianjin (coincidentally, “Xenograft Choreography” is also the name of my favorite Black-Metal / Klezmer dance band)

By Smut Clyde

From “Forty five papers from Tianjin Medical University” (Bik 2020)

If the city of Tianjin is familiar, it could be because of this egregious account of whistle-blowing and professorial corruption. Or perhaps you recall the place from Elisabeth Bik’s discovery, that 45 papers from Dr. Hua Tang’s research group at Tianjin Life Science Research Center (at Tianjin Medical University) recycled the same images again and again.

Readers can be forgiven for not remembering the name of Yuanjie Niu, who only appears in the For Better Science annals in the context of Chawnshang “Chainsaw” Chang and Soo Ok Lee.

Chainsaw Chang and Soo Not Ok Lee

Smut Clyde celebrates here a highly successful US cancer research lab at University of Rochester. Its head is Chawnshang “Chainsaw” Chang, and his most productive scientist is Soo “Not” Ok Lee.

by Leonid Schneider

For Niu professes at Tianjin Medical University – more specifically in the Department of Urology at the Second Hospital attached to TMU. In fact he is President of that 2nd Hospital, a lofty pedestal from which he can rehearse the Party line about the importance of publications as well as clinical practice, and the need for respectful attendance to the teachings of one’s superiors. And about the importance of papermills for busy doctors:

“… a spirit of excellence in the hospital, so that the concept of “not only being a clinical worker, but also a clinical scientist” is deeply rooted in the hearts of the people.“

But he also boasts an affiliation to the George Whipple Laboratory for Cancer Research at the University of Rochester, reflecting his frequent collaborations with Chang. Not to forget his status as a professor in the Chawnsung Chang Sex Hormone Research Center at TMU… one of a series of eponymous centres, Chang having franchised his operation.

From “Targeting the Unique Methylation Pattern of Androgen Receptor (AR) Promoter in Prostate Stem/Progenitor Cells with 5-Aza-2′-deoxycytidine (5-AZA) Leads to Suppressed Prostate Tumorigenesis“ (Tian et al 2012)

The backstory is that Chawnshang Chang once patented a synthetic curcumin-based molecule ASC-J9 that promised to treat prostate cancer: endearing him and his colleagues to male gerontocracies such as university administration. The drug never worked outside of the narrow scope of faked papers, but Chang remains an apex predator within the University of Rochester ecosystem.

That is just a digression, for Niu’s presence within PubPeer threads extends beyond his Chang collaborations. A few threads were spawned by papers that seem to be products of what I am calling the Tianjin Papermill (after toying with ‘Promotion’ as a title for it).

Spreadsheet here

I hasten to add that this putative mill is not bound rigidly to TMU or any other Tianjin institution, in contrast to the in-house fraud factories set up at Jilin University and Central South University (to spare those faculties the expense and inconvenience of dealing with outside papermillers with their questionable ethics). It is not restricted to the publication requirements of exclusively Tianjin researchers… and conversely, the fire-hose torrent of fake biomedical papers streaming out of Tianjin comes from sources besides this one. But see later!

The papers are coming from inside the house!

“It feels like half the higher-echelon professors at Jilin University have built their careers on these fairy-tales, with successions of papers itemising the interactions of ADAM10 or GRIM-19. […] if only they had published instead about the Tooth-Fairy circ-RNA and how it targets the Easter-Bunny Pathway…”, – Smut Clyde

by smut.clyde

So here is a novelty in the annals of fictional research: a nomadic digital caliper. It visited a series of laboratories, accompanied by a backing troupe of mouse-mined xenograft tumours for it to measure, while a strip of sellotape that holds the battery in place (replacing a missing cover-flap) kept it recognisable. Four appearances are known so far, plus a fifth where only the tips of the caliper grippers are visible, and two more with the tumour troupe on their own.

[left] Fig 5A from “ASPM predicts poor prognosis and regulates cell proliferation in bladder cancer” (Gao et al 2020):
[right] Fig 5a from “KIF20B Promotes Cell Proliferation and May Be a Potential Therapeutic Target in Pancreatic Cancer” (Chen et al 2021)
[left] Fig 4a from “AK4 Promotes the Progression of HER2-Positive Breast Cancer by Facilitating Cell Proliferation and Invasion” (Zhang et al 2019).
[right] Fig 5A from “Kinesin Superfamily Member 18B (KIF18B) Promotes Cell Proliferation in Colon Adenocarcinoma” (Zhao et al 2020).
[left] Fig 5A from “KIF23 enhances cell proliferation in pancreatic ductal adenocarcinoma and is a potent therapeutic target” (Gao et al 2020)
[right] Fig 4a from “KIF5A Promotes Bladder Cancer Proliferation In Vitro and In Vivo” (Tian et al 2019).
Fig 5A from “High expression of RAB38 promotes malignant progression of pancreatic cancer” (Li et al 2019)
The Dance to the Music of Time is probably not a gavotte

In fact the same tumors remain present from one posed photo-opportunity to the next, though they roll around on the paper towel into new arrangements in the manner of Mexican jumping beans, swapping places as if performing a country dance. A sprightly gavotte perhaps, or a Roger de Coverley.1

Alternative title: You had one eye in the mirror, as you watched yourself gavotte

Tumor recycling happens a lot in this Tianjin corpus. A few examples will have to suffice, for I am impatient to move on to Transwell invasion assays.

Left to right: Fig 5A from “CENPF promotes papillary thyroid cancer progression by mediating cell proliferation and apoptosis” (Han et al 2021).
Fig 5A from Kinesin family member 23 (KIF23) contributes to the progression of bladder cancer cells in vitro and in vivo (Yao et al 2021).
Fig 5A from “Upregulation of CENPF is linked to aggressive features of osteosarcoma” (Zou et al 2021).
[left]  Fig 5A from “SMYD3 promotes colon adenocarcinoma (COAD) progression by mediating cell proliferation and apoptosis” (Yue et al 2020).
[right] Fig 3A from “KIF4A promotes the development of bladder cancer by transcriptionally activating the expression of CDCA3” (Sheng et al 2021).

So here are some comparisons among Transwell images. A colour code across the corpus is required to keep track of their various cameo roles, although the basic-colour markers of red and green and brown and so on are soon exhausted so we progress to the specialty palette of cyan, flamingo or fuchsia, puce and taupe.

[left] Fig 3d from “APLNR promotes the progression of osteosarcoma by stimulating cell proliferation and invasion” (Cui et al 2019).
[right]] Fig 3d from “Identification of Kinesin Family Member 2A (KIF2A) as a Promising Therapeutic Target for Osteosarcoma” (Wang et al 2020a).
[left] Fig 3D from “Kinesin Family Member 18A (KIF18A) Contributes to the Proliferation, Migration, and Invasion of Lung Adenocarcinoma Cells In Vitro and In Vivo” (Chen & Zhong 2019).
[right] Fig 3B from “Identification of Lysosome-Associated Protein Transmembrane-4 as a Novel Therapeutic Target for Osteosarcoma Treatment” (Wang et al 2020b).

Colour codes were also needed to identify the Immunohistochemistry panels consistently across the entire corpus.

Sixty papers was a good point to stop looking (there are bound to be more). Not bad for a newcomer on the scene. Favourite targets are Spandidos and Hindawi journals (of course) – the millers are not ambitious. Notably, “Disease Markers”. Some later papers in this corpus found their homes in the dreaded Guest-Edited Special Issues of Hindawi journals and bear no apparent connection to the nominal theme of the SI, but most predate Wiley‘s purchase of Hindawi and the subsequent debauch of editorial / reviewing standards.

The millers were thus relieved of any pressure to vary the template, and most papers in the corpus cleave closely to a pattern. Typically they begin with a four-well proliferation / colony-formation assay (cut down from six-well originals). Yes, there are overlaps and duplications.

Clockwise from upper left: Fig 4A from “KIF20B promotes the progression of clear cell renal cell carcinoma by stimulating cell proliferation” (Li et al 2019).
Fig 3a from “Nesfatin-1/Nucleobindin-2 Is a Potent Prognostic Marker and Enhances Cell Proliferation, Migration, and Invasion in Bladder Cancer” (Liu et al 2018).
Fig 4a from “KIF20B Promotes Cell Proliferation and May Be a Potential Therapeutic Target in Pancreatic Cancer (Chen et al 2021).
Fig 3A from “KIF3B Promotes the Proliferation of Pancreatic Cancer” (Liu et al 2019).
[left] Fig 3A from “Abnormal spindle-like microcephaly-associated protein (ASPM) contributes to the progression of Lung Squamous Cell Carcinoma (LSCC) by regulating CDK4” (Yuan et al 2020).
[right] Fig 4A from “Upregulation of CENPF is linked to aggressive features of osteosarcoma” (Zou et al 2021).
[left] Fig 4a from “KIF4A Regulates the Progression of Pancreatic Ductal Adenocarcinoma through Proliferation and Invasion” (Chen et al 2021).
[right] Fig 3a from “FK506-binding protein 5 promotes the progression of papillary thyroid carcinoma” (Gao et al 2021).
Left to right: Fig 3a from “AK4 Promotes the Progression of HER2-Positive Breast Cancer by Facilitating Cell Proliferation and Invasion” (Zhang et al 2019).
Fig 4A from “ASPM predicts poor prognosis and regulates cell proliferation in bladder cancer” (Gao et al 2020).
Fig 4A from “KIF4A Promotes Clear Cell Renal Cell Carcinoma (ccRCC) Proliferation in vitro and in vivo” (Yang et al 2020).

Tissue slides follow, immunohistochemistry-stained to expose the distribution of some protein of interest. Then there are Western Blots, two lanes at a time.

[above] Fig 2B from “High expression of RAB38 promotes malignant progression of pancreatic cancer” (Li et al 2019).
[below] Fig 3c from “KIF23 Promotes Gastric Cancer by Stimulating Cell Proliferation” (Li et al 2019).

And of course the tightly-choreographed performances of the dancing xenografts. I am open to the possibility that they were excised from waltzing mice.

Atypically for a papermill, the titles of the products are not dominated by cell-signalling proteins and pathways, nor by non-coding RNAs; not even by curative phytochemicals. Instead, the kinesin superfamily of cell-transport proteins show up a lot. These are apparently central not only for shuttling shipments of this and that among a cell’s compartments in intracellular supply chains, but also for centrosome formation and chromosome separation during mitosis, and for cell movement when they collaborate with microtubules to form amoeba-like pseudopods. It becomes plausible, then, to accuse them of involvement in cancer-cell aneuploidy and metastasis.

One could surmise that Tianjin researchers secured funding to study kinesins, obliging them to fabricate papers as proof that the money was well-spent. Or it might just be that kinesins are the area of expertise of the workers in this bogus-paper atelier, so they can spin Introduction and Discussion paragraphs without breaking a sweat (though of course they are willing to fake results on any other topic if the client insists). The operators could be moonlighting members of a group where actual research also goes on, or full-time professionals, who knows?

The only responses so far to all the PubPeer harassment came from Jing Ren of the Precision Medicine Center at TMU General Hospital.2 Ren claimed ownership of images published in

  1. Zhe-Xiang Wang , Shao-Chun Ren , Zi-Song Chang , Jing Ren Identification of Kinesin Family Member 2A (KIF2A) as a Promising Therapeutic Target for Osteosarcoma BioMed Research International (2020) doi: 10.1155/2020/7102757 
  2. Zhe-Xiang Wang , Shao-Chun Ren , Jing Ren Phosphotyrosine picked threonine kinase stimulates proliferation of human osteosarcoma cells in vitro and in vivo Archives of Medical Science (2021) doi: 10.5114/aoms/115135

and was puzzled how anyone else could have acquired copies of those illustrations.

Left to right: Fig 4A from “Identification of kinesin family member 3B (KIF3B) as a molecular target for gastric cancer” (Yao & King 2020); and Fig 6a from “KIF11 Is a Promising Therapeutic Target for Thyroid Cancer Treatment” (Han &c 2022).
Fig 4A from Wang et al (2021).
Fig 4a from “The role of fibroblast activation protein in progression and development of osteosarcoma cells” (Zhang et al 2020).

The Tianjin corpus contains a third entry from Jing Ren, but it is still waiting for a reply. Maybe Ren thought that another copy of the same comment would be redundant.

Now it is certainly conceivable that minions in Ren’s team had smuggled images of tumours, Transwell assays, and what-have-you out of the laboratory and sold them to the postulated papermill, explaining why other authors managed to published them first. Ren just wants us to know that if this was the case, it was not for lack of mentoring, as minions had been briefed about the ethics and responsibilities of the research vocation.

Even so, I feel compelled to point out that two rungs of the ladder that Ren climbed to his present status were obtained from the ‘Contractor’ papermill, during its “Ransom note” period of fictitious Western Blots:

[left] Fig 4a from Deng et al (2018). Enough colored boxes to put under a $mas tree.

So this papermill caters to established research specialists in need of regular publications, as well as to clinicians who only need a single paper as a prerequisite for promotion. To make the point, here are three entries from a group around Jing Chen and Cui-Cui Zhao at [draws breath] Tianjin Medical University Cancer Institute and Hospital; Key Laboratory of Breast Cancer Prevention and Therapy; and National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy.

[above] Fig 4B from Zhao et al (2021).
[below] Fig 4D from “KIF23 enhances cell proliferation in pancreatic ductal adenocarcinoma and is a potent therapeutic target” (Gao et al 2020).

Singly or in collaboration, Baoyu Li, Bin Liu and Zhenya Gao – of TMU’s Second Hospital – provided nine entries to the spreadsheet.

Left to right:  Fig 5A from (Jia et al 2021a).
Fig 5A from “KIF22 promotes bladder cancer progression by activating the expression of CDCA3” (Li et al 2021).
Fig 4A from Jia et al (2021b).
[left] Fig 4a from “APLNR promotes the progression of osteosarcoma by stimulating cell proliferation and invasion” (Cui et al 2019).
[right] Fig 5a from Gao et al (2021a).

Were these the same Bin Liu and Baoyu Li who helped fill the pages of J.BUOn with faked flow-cytometry results? Apparently so!

Victims as perpetrators

Smut Clyde as Detective Columbo investigates: The victims of a paper mill are actually in cahoots with the perpetrators! Stealth corrections happen faster than one can catch them!

by smut.clyde

Oh, I nearly forgot one last Jing Ren paper. No concerns have been raised about “Early Stage Biomarkers Screening of Prostate Cancer Based on Weighted Gene Coexpression Network Analysis” (Meng et al 2019) but the last author was Chawnshang Chang. There, the Taiwanese American sports a second affiliation with the urology department of The Second Hospital of Tianjin Medical University, a position he was awarded in 2010 (thanks to Yuanjie Niu of course) as “”Cheung Kong Scholar” Distinguished Chair Professor”, there was even a ceremony . It seems, Chainsaw is everywhere and has mentored everyone!

We might also look at Zheng Zhang (Niu’s Ph.D student), who has accrued an impressive PubPeer record, including several papers that fit the template of the present mill. But bored now.3

I didn’t want to interrupt the narrative by mentioning “MiR-154 inhibits the growth of laryngeal squamous cell carcinoma by targeting GALNT7” (Niu et al 2018) [retracted], for Yuanjie Niu bought it from a different papermill, less prolific and unrelated to the one of interest here.

Clockwise from upper left: Fig 6G from Niu et al (2018).
Fig 6B,F from “Circ_0002770, acting as a competitive endogenous RNA, promotes proliferation and invasion by targeting miR-331-3p in melanoma” (Qian et al 2020).
Fig 3g from “Growth-induced stress enhances epithelial-mesenchymal transition induced by IL-6 in clear cell renal cell carcinoma via the Akt/GSK-3β/β-catenin signaling pathway” (Chen et al 2017).
Fig 5A from “MicroRNA-23a promotes pancreatic cancer metastasis by targeting epithelial splicing regulator protein 1” (Wu et al 2017).

However, we do learn from this paper that these millers had access to a set of colony plates that were previously the property of the Jilin papermill.

 [left] Fig 6C from Niu et al (2018).
[right] Fig 5D from “MicroRNA-363 inhibits ovarian cancer progression by inhibiting NOB1” (Lin et al 2017)

If the ghost-authors of Niu et al (2018) were in contact with the Jilin fraud factory, is it possible that Yuanjie Niu also knew about the advantages of having one’s own institutional studio producing manuscripts for one’s students and department? It would be irresponsible not to speculate.

On the basis of his prestigious series of publications Niu was nominated in 2022 for the China Medical Science and Technology Awards run by the Chinese Medical Association, and in 2023 received a 3rd prize (worth RMB 20,000).

Thanks to Huanzi for suggestions and explanations.

tianjin-sheet1Download

1. Bonus Roger de Coverley from Locus Solus, because Surrealism.

2. I tell a lie. Yi Liu also responded, with that time-tested old favorite: “The uncredited outside laboratory did it”.

[left] Fig 4a from “Suppression of KIF22 Inhibits Cell Proliferation and Xenograft Tumor Growth in Tongue Squamous Cell Carcinoma” (Liu et al 2020).
[right] Fig 5a from “Nesfatin-1/Nucleobindin-2 Is a Potent Prognostic Marker and Enhances Cell Proliferation, Migration, and Invasion in Bladder Cancer” (Liu et al 2018).

3. TigerBB8 read Zheng Zhang’s PhD dissertation so we don’t have to, and found shenanigans in the flow-cytometry apoptosis assays. The same data-set had been replotted with different gate settings, then presented as the results of separate experiments on cells cultured under different conditions. Naughty naughty naughty!

From Fig 4 (page 28) and Fig 5 (p.30).
Fig 7 (p. 66) and Fig 6 (p. 39)
Fig 8M, “Tumor” and Fig 8G (“Spleen”) (p.56). The task of turning them into colored overlays to dramatise the number of points shared in common is left as an exercise for the reader.

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13 comments on “Ticket to Tianjin”

  1. Aneurus
    April 24, 2023

    I’m impressed how nicely the papermillers managed to fake the values onto the display of the nomadic digital caliper.

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  2. Zebedee
    April 24, 2023

    https://www.nature.com/nature-index/supplements/nature-index-2022-science-cities/tables/overall

    Tianjin is one of the top 20 cities in the world by scientific research outputs as tracked by the Nature Index,[15] and home to multiple notable institutes of higher education in Northern China, including ….

    More of the same?

    How clever Nature is!

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    Reply
  3. tv
    April 24, 2023

    I think you are missing the main reason why peer-review often doesn’t recognise fraudulent research: reviewers are normally working under the assumption that a manuscript is legitimate. The review process is concerned with the question if the conclusions of a paper are supported by the data, models, etc. presented. This presupposes that the data itself is what it seems to be. If a picture has been obviously tinkered with, a reviewer might detect this. However, any more sophisticated fraud is likely not going to be detected during peer review. The review process is build on the assumption that submitted manuscripts are honest attempts at real scientific research. Trying to use peer-review to detect frauds will never work, no matter how well intentioned reviewers are, as that is not what the review system is intended to do.

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    • Zebeee
      April 24, 2023

      “reviewers are normally working under the assumption that a manuscript is legitimate.”

      In 2010 you might have claimed that, but now is 2023.

      Reviewers need to let go of that assumption.

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    • alfricabos
      April 26, 2023

      To paraphrase Richard Smith, a manuscript to be fraudulent until proven otherwise.

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      Reply
  4. Hunter
    April 24, 2023

    Maybe there should be at least one reviewer that is recruited to work under the opposite assumption: that the data are not legit. One of the tenets of science is (should be) falsifiability. Yet, this hardly ever features in high level discussions when it comes to life sciences….

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  5. Scotus
    April 25, 2023

    Yet another tour de force from Smut Clyde. Bravo!

    At least having a tumor collection you can roll out for photoshoots eliminates the mouse torturing.

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  6. smut.clyde
    April 26, 2023

    Who could have guessed that Hong Liu, corresponding author of “Lamin B2 promotes the progression of triple negative breast cancer via mediating cell proliferation and apoptosis”, would also be corresponding author on a Coordination-Polymer papermill product, “Cu(II) and Co(II) coordination polymers: Magnetic properties, regulating the YAP signaling pathway activation and exerting anticancer activity against breast cancer combined with Sevoflurane”?

    https://pubpeer.com/publications/1D52F2FC71A08627836FD54801EB72

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    • Leonid Schneider
      April 26, 2023

      “In investigating concerns brought up regarding the authenticity of the article, the editors reached out to the corresponding author for an explanation.
      Despite several attempts in requesting clarification on the concerns, the authors have not replied to the editors’ requests. The editors therefore feel that the findings of the manuscript cannot be relied upon and that the article needs to be retracted.”

      What a crappy service this papermill provides. Just dead-box email addresses. Now, why not offering a 2 year customer service and warranty against retraction, for a small additional fee?

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  7. smut.clyde
    April 26, 2023

    Ah, a collaboration that included Feng-xia Xue (three-times Tianjin Papermill customer) and Anil K. Sood. What could go wrong?
    “MIIP remodels Rac1-mediated cytoskeleton structure in suppression of endometrial cancer metastasis”
    https://pubpeer.com/publications/6FEEE500CAAF869B3CEB720EA61A5F

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