Saturday, October 24, 2020

Master of the Travelling Tumors

This post was earlier cross-posted at Leonid Schneider's site, hence the unfrivolous tone. The version there is improved by Leonid's editing, background details and frame-story.

We begin today's communiqué with the curious phenomenon of the Travelling Tumors. Not just the plot of a 1936 horror story! Over a dozen teams of Chinese medical clinicians published photographs of excised nude-mouse xenograft tumors to illustrate how different microRNA or long-non-coding-RNA treatments could reduce the malignancy of different carcinoma cell-lines. The tumors were all posed five at a time on the same blue distinctively-creased fabric pad or sheet, with the same plastic ruler for scale. In fact the same tumors featured repeatedly, though rearranged, and rolled to present their different flanks.

Curated by PubPeer commenter 'Campanula Pseudostenocodon'

It appears that this small cast of carcinomas went on tour across the breadth and width of China, with their retinue of ruler and creased fabric. Either that, or some unfortunate lab jockey was tasked with excising tumors from even less fortunate mice and shuffling them around on the bench-top in the course of an afternoon photoshoot, documenting each combination for later sale to papermill customers. A few decades ago when I worked in the field of 'vocational psychology', studying how people perceive the range of employment options, I had no idea that one day there would exist the niche of Mouse Malignancy Group Portraitist.

The venue for about half these images was Oncology Research, from Cognizant Communications. This is a small player in the cancer-research-results industry, with papers-per-year numbering in low hundreds rather than thousands. Cognizant identify tourism as a core publishing focus, but at some point in the past they must have seen an unfilled niche for cutting-edge oncology results.

I am not convinced by the suggestion that tumor-tourism is a natural cross-over field:

#2 Actinopolyspora Biskrensis 
Whatever the initial inspiration was for founding OR, it has become yet another of those journals that were hollowed out by papermills and turned into a conduit for their compositions, so the main need it satisfies now is that of Chinese clinicians, for research publications as part of their CVs. Occasional seemingly-genuine studies from actual researchers still blunder into the pages of OR by mistake, but they are a tiny minority, and many issues contain no papers that are not papermilled persiflage. As if in illustration, OR hosted 63 of the 520 papers linked (at time of writing) to the 'Tadpole papermill'.

The hollowing-out or takeover was probably facilitated by the journal's tripartite peer-review model, in which a triumvirate of regional Editors-in-Chief handle submissions from their separate geographical spheres of influence (Americas, Asia, Europe) and maintain their own region-specific panels of amenable peer-reviewers. There is no sign of any concern from the American or European Eds-in-C about the torrent of cookie-cutter products flooding across the desk of their Asian colleague or its contrast with the emptiness of their own in-trays, so I guess that they (and the publisher) have come to terms with the journal's new role.

Perhaps for legacy reasons, OR has the imprimatur of PubMed indexing so its contents show up in the hits when someone searches PubMed for a given micro-RNA (miR) in the course of establishing the importance and fundability of their own phony-baloney projects. Which is to say, its contents accrue citations. Which is not to say that the citers read the papers. Nor is there evidence that the editors or peer-review rubber-stampers read them, nor the nominal authors, and other than the anonymous studio scriveners who actually wrote them, the audience for most of OR's contents appears to be limited to me.

What commends this obscure, inconsequential journal to our attention is the opportunity it provides to watch the papermills perfecting their templates before exposing their compositions to less sheltered environments. Many of those 63 'tadpole' productions represent early stages in the evolution of that oeuvre. The studio had not yet realised that they could hand-stipple clouds of dots inspired by lutes and embryonic zebrafish and Death Stars shooting planet-buster energy bolts, and the peer-reviewers would just shrug and reach for their No Revision Required stamp, so they were still basing their cytometry scatterplots on real data.

Often the Transwell Assay images are the smoky, smudge-tool-dominated phenomena that first caught the eye of 'Indigofera Tanganyikensis' and started us down this rabbit-hole... while the Western Blots are practically WB-like, reminiscent of rows of toboggans, rather than the flapping tadpoles / zany sardines that later become that studio's trademark motif. Even so, there is enough continuity to justify classifying these early, aberrant images with the rest of the tadpole oeuvre.
The journal is also a chance for the connoisseur to admire the papermills' work in isolation, undiluted and undistracted by any admixture of authenticity. It is so much easier to characterise a distinct style in forgery when the examples are concentrated at one source rather than dispersed across the biomedical literature.
Different ruler photoshopped in
After all that, I can finally return to the travelling tumors. The fabrications they adorn are not confined to Oncology Research as their dumping ground - they have spread out from that first host, and examples can be found in Elsevier journals, and International Journal of Oncology and Onccology Letters and Oncology Reports from the stable of Diomedes Spandidos, and Bioscience Reports, and a RSC journal, and Frontiers in Bioscience (a hybrid journal, pay-to-read as well as pay-to-publish, not to be confused with the usual Frontiers empire). It goes without saying that I made a Google-document spreadsheet.

I write "recognising a distinct style in forgery" because the tumors are often accompanied by other forms of recycling, and those other forms co-occur often enough that they clearly come from the same authorship even in the absence of a tumor or two. Perhaps this is how art historians of the Northern Renaissance feel when they recognise the same stylistic quirks in several unsigned altarpiece paintings, and they coin some label like "Master of the Virgo inter Virgines" or "Master of the Day of Judgment" for the anonymous artist.

Western Blots drawn in the manner of processionary caterpillars are not an essential feature of the atelier but they are a frequent one. They were what first brought these instances together in my mind.
The four-quadrant flow-cytometry scatterplots are distinctive. They give every indication of being genuine, and the studio is recycling a limited archive, so if you stumble across one of them then there is a good chance that it will have already appeared elsewhere. Colored boxes added.

I choose to see some as portraits of Thidwick the Big-Hearted Moose, juxtaposed with porcupines.

Another limited resource for the Traveling Tumors atelier is the Invasion assay, requiring "illustrative scenes of cells proliferating on a transwell membrane". The available images have been repurposed so often that they could succumb to bit fatigue at any moment.

These scatterplots recur: duplicated and hexaplicated, purporting to show that various combinations of miRs and cell-signalling axes and tumor biomarkers are correlated, all with the level of precision that German car engineers can only dream of.
They have none of the nonlinearity and noise and clumping of data-points within subranges that one expects from biological processes; I think they came from the lab-book of a first-year physics student, making up the results of an experiment that was neglected in favour of partying. Was it really too much work to draw a new line for each customer and scatter some randomised points above and below it? It's not as if any special commitment to the cause of plausibility went into these constructions, to make them worth repeating.

It is tempting to set up a GoFundMe appeal to help these visually-impoverished dudes. If you have any cell-proliferation scenes or highly-correlated scatterplots, consider donating them to those in greater need. Also, with your financial donations we can buy them a new plastic ruler!

Friday, October 23, 2020

Our three weapons are Physiologic Nutraceuticals and Low Dose Cytokines and faecal transplantation and an almost fanatical devotion to the Pope

This post was earlier cross-posted at Leonid Schneider's site, hence the unfrivolous tone. The version there is improved by Leonid's editing, background details and frame-story.

To whet your appetite for what is to follow, I offer this Brief Communication from the Open Access Macedonian Journal of Medical Sciences:

"The Physiologic Nutraceuticals and the Low Dose Cytokines Medicine and faecal transplantation two of the most promising approaches for the treatment of skin diseases based on the rebalance of the immune response and the recovery of gut dysbiosis."
Despite the prominence of Nutraceuticals and f(a)ecal transplantation in the title, Abstract and Conclusions, they feature nowhere in the main body of the text, which is devoted exclusively to "low dose cytokines medicine". It is as if different groups of authors wrote the separate sections with relatively little inter-communication, which would also explain why the list of co-authors is so long.

Are there editors at the Open Access Macedonian Journal? Possibly not, as it has a history of contributing to the gaiety of nations by accepting brainfarts from one Alireza Sepehri, who was once an actual scientist in Iran before abandoning physics (along with coherence and the conventional meanings of words) in favour of an experimental program of decapitating chickens. Elisabeth Bik has more details, both on Twiddle and at at her website.
The story really begins with the "Russian Homeopathy" imbroglio which some months ago roiled the usually-tranquil routines of scholarly retraction. The staff of Materia Medica Holding - a Russian company within the Big Dilute industry -- had made up sets of results for their high-concept drug-free placebos, claiming that these worked in vitro and in vivo despite the absence of bioactive molecules; they had infiltrated these into various biomed journals by the clever expedient of never using the word "homeopathy". The idea, of course, was to have publications they could brandish as proof of efficacy in consumer-targeted advertising. Science-integrity enthusiasts questioned the editorial decisions to accept these stalking horses and the BATTLE WAS EPIC. The homeopathic not-a-drug for enhancing penis size (in rats) was especially noteworthy.

Now a key component of the classical Homeopathic ritual, as it hatched fully-fledged from Samuel Hahnemann's over-stuffed Teutonic head in 1810, is "succussion", in which the process of successive dilution is punctuated by striking the phial or mixing vessel with a leather-bound bible. This agitates the little whirling atoms of both bible and vessel, causing atoms of bibleness to migrate into the vessel during the moment of contact and contrariwise in accordance with the Mollycule Theory, until after sufficient repetitions the vessel is increasingly biblical while the bible becomes 50% vessel NO WAIT that's a plot device from "The Third Policeman". The agitation causes active molecules from the original preparation to impart their therapeutic properties to the solvent or dilutant, so that their elimination through sufficient dilution is nuncupatory.

But to modern sensibilities "succussion" is connotative of mumbo-jumbo and magical-thinking absurdity, so a Milan-based member of Big Dilute (GUNA S.p.a.) rebranded it as SKA, Sequential Kinetic Activation, which sounds more scientifical. Like the Russian team, GUNA commissioned a series of studies to show the efficacy of their products, and used tame researchers as stovepipes to insert paper-shaped advertisements for their SKA product range into academic journals. The Laboratories & Research page on the company website shows that they are result-driven empiricists and not shameless mountebanks.
Further down the human centipede, the list of commissioned studies emerged as the References Sections of a whole secondary literature.

Here the parallel with the Russian papers breaks down, and I am not sanguine about the prospect of persuading the editors of these secondary journals to reverse their acceptance decisions and retract the papers. For "iMedPub", the conduit for Medical Case Reports, is simply a polyp of OMICS, a pioneer and perhaps the best-known practitioner of parasitical publishing. OMICS extruded a series of these polyps as their reputation for fraudulence developed, or bought existing publishers and turned them into Potemkin Presses, so that researchers could go on using their fake-scholarly services without the OMICS stink rubbing off on them to reveal their desperation.

As for the Journal of Pigmentary Disorders, in 2015 that was an OMICS spigot. And who was the Editor-in-Chief to whom one might appeal? That would be Professor Torello Lotti, founder and recurring co-author. At some subsequent point the OMICS scampire evicted him from that role and renamed his journal as Dermatology & Dermatologic Diseases in the hope of broadening its income stream, though they kept the old JPD logo, judging it as too classy to lose. Later still they devolved DDD to Hilaris, one of their subsidiaries polyps skinpuppets.

Now some OMICS staffers have repented of careers spent spamming scientists around this interconnected world in the hope of defrauding a few to maintain Srinubabu Gedela's lifestyle, and realising that they could be spamming scientists to defraud a few to make themselves wealthy, they set up OAText, another parasitical publisher in Hyderabad. OAText comes into the story as the publishers of Global Dermatology. One could appeal to the Editor-in-Chief of that cloaca to de-publish "Low Dose Cytokine", but that was the author, Torello Lotti again.

OAText subsequently replaced Lotti in that role some time between April and June 2018. GD is now in abeyance, with no new issues since the end of 2018, though they are still spamming for submissions and accepting "payment charges" from gullible eedjits while the manuscripts pile up in an "in press" section.

Anyway, we are now in the territory of Professor Lotti, whose oeuvre is the main topic of this post. I first encountered the Professor in his role as Secretary-General and sometimes President of Dermatology of the World Health Academy. Supposedly this is the "directing and coordinating organization" for the entire global medical field, a world-spanning network of eminent medical professionals with a board of Nobel Laureates, advising governments and pooling their expertise to further causes of public health.

In this reality the WHA consists of Lotti, and a New Jersey cosmetic dermatologist whose vanity was insufficiently assuaged by his self-penned W*k*pedia entry. The WHA's own self-penned W*k*pedia entry is adapted from its website (a trichobezoar of grandiosity where one could wander entranced for hours) and both would benefit from the fact-checking attentions of some more neutral Wikipedians.

What concerns us here is the International Journal of Medicine, official journal of the WHA,
an international open-access, peer-reviewed general medical journal, currently in development. a publication of the highest academic profile that will bring new and important information to the medical, scientific, and policymaking community worldwide. Its editorial board consist of Nobel Prize laureates, Lasker Award winners, and other distinguished persons. The WHA's devotion to international health guarantees that research and analysis from all regions of the world will be vastly covered.
Despite that distinguished editorial board, and despite a payment fee of only $500, and despite six years of existence, the IJM has yet to acquire a single article. Fortunately back-ups exist, and the JPD and GD were also designated as the Official Organ of the WHA, at least while they existed under Prof. Lotti's control.

And if the franchising of WHA Official Journals is not sufficiently confusing, there is Dermatologic Therapy (published by Wiley), which seems to have acquired the WHA "Official Journal" status and logo in 2010. It also acquired Prof Lotti as Associate Editor. He later ascended to Editor-in-Chief, although Wiley were recently advertising for a new Editor-in-Chief so they may have rethought that part. In addition, "Global Dermatology" is evidently not so much a journal and more a state of mind; any journal can become Global Dermatology (and a WHA Official Organ) if it is graced with T. Lotti as Guest Editor and enough T. Lotti co-authorships, like Henry VIII and his peripatetic court.. Two cases in point: the Journal of Biological Regulators and Homeostatic Agents, a.k.a. J.Brouhaha; and the Open Access Macedonian Journal with which we began.

Not actually indexed in the J.Brouhaha website

With this serial journal-founding and the stream of grandiose though irreal institution in which Prof. Lotti invariably fills a central role, one could take him to be a confabulating fantasist in the mold of Walter Mitty or the Space Dentist. But the WWW is a fertile environment for this turn of personality, and the internet economy is a realm where anyone who builds castles in the sky can rent them out and charge other people real money to live there. The Space Dentist has convinced enough suckers to share his belief in illusory organisations and fooled enough of them with his third-tier mockademic scamferences that he continues to announce them. Likewise, Dermatologic Therapy has a real publisher and real subscribers (most may be librarians, obliged to accept the subscription as part of a bundled package, not because they value the Lotti-centric Special Issues so highly).

This all leads me to this list of Professor Lotti's corporate entanglements, as of 2014, grabbed from a presentation.

No formal tie to GUNA S.p.a. is listed there, though clearly there is an informal link: a convergence of interests or a pragmatic alliance. Resulting in co-authorship of a foundational document...

...And in seminar collaborations like this, where for only £90
you can hear an extended advertisement for homeopathic dogwash. If prior form is any guide there will be Worship-Word invocations of Quantum Physics, and recitation of "Psycho-Neuro-Endocrine-immunology" sung to the tune of the Oompa-Loompa song... though disappointingly, Lotti and Perra do not walk in Deepak Chopra's footsteps and there will be no mock-mystical Transcendental Derp. It is not too late to buy tickets! Nor is it too late to contact the Royal Institute of Medicine to change their minds about renting out their venue to this kind of charlatan charivari.

Not to forget the Vitiligo Clinic in Bulgaria, another of Lotti's operations (in partnership with Prof. Dr. M. Kadurina), It would be harsh to call them "pimps for GUNA homeopathy", and not the whole truth, for they also pimp antioxidant food supplements, and laser partial skin ablation, and maybe snake-oil-based liniment.

Going back to that sprawling corpus of publications, I hasten to add that it is not all apologia for rebranded homeopathy. The Special Issues are rife with case studies from practitioners' diaries: tricky diagnoses and unusual comorbidities and interestingly invasive surgeries and reconstructions. There are exercises in market research, rating consumer satisfaction after being implanted with Biofibre polyamide hair strands (for people who desire the plastic coiffure of Barbie dolls). A coterie of co-authors recurs in frequent collaboration, more inbred than the Hapsburg dynasty, and I gain a sense of a kind of mutual-support cartel (or if you like, a mind-melded collective intelligence) where any one of the circle includes co-authorship for everyone else by default on everything they publish. It may also be that as Editor, Lotti is granted co-authorship on every Special Issue contribution out of courtesy.
    The content page lists 39 papers. Of these:
  1. 37 list Torello Lotti as an author
  2. 37 list Aleksandra Vojvodic;
  3. 36 list Uwe Wollina;
  4. 19 list Petar Vojvodi;
  5. 19 list Michael Tirant;
  6. 18 list Massimo Fioranelli;
  7. 14 list Van Thuong Nguyen;
  8. 8 list Maria Grazia Rocci;
  9. 7 list Alireza Sepehri
Some familiar names

This was all very well until someone recruited Alireza Sepehri into the mind-meld. Now all the names of the authorship cartel are credited with every one of the omicron-fritillary-fishbucket exercises in Ionescu absurdism that emerge from his short-circuited misfiring synapses. About the black hole in Earth's core that communicates with human DNA though a 4+N-dimensional manifold. Or how radio waves in the frequency band used by 5G protocol interact with human DNA to cause COVID-19 virions to arise spontaneously out of the quantum vacuum. Or how to regenerate the brains and hearts of decapitated chickens... and much more besides. All of these would be improved by the current trend for full-disclosure authorship statements (detailing what each author contributed to a manuscript), for I would dearly like to know who provides Sepehri's psilocybin supply.

I leave it to readers to decide how much the credibility of "Homeopathy works!!" research reports from (say) Victoria Barygina is enhanced by the presence in her CV of Sepehri's dream-time crystallisations.

Understandably enough, many of the case-studies in these Global Dermatologies are illustrated with photos of the patients' faces and genitalia -- often recognisable. As the punchline has it in the joke about the skinny-dipping dons, people recognise you by what of you they see most often. Elisabeth Bik has blogged about this, and whether patients' consent should be required for this use of their likenesses; and if so, whether ethical journals would expect authors to provide a statement about patient consent. It may be that arrivals to these authors' clinics and practices waive any right to privacy when they sign the small print in the admission forms, as is apparently the case in psychiatry (at least in the "Dr. Laza Lazarevic" Clinic for Psychiatric Disorders, Belgrade).

After learning that my prospective therapist believes that the Earth's core contains black holes and extra-dimensional neural-network DNA, I would be tempted to refuse to sign and forfeit the therapy. The knowledge in itself would provide a sufficient sense of happiness and relative sanity.

A second issue of ethics involves Conflicts of Interest. One school of thought has it that the minds of senior academics are so refined as to rise above the sway of pecuniary appeal, so there is no point in them disclosing any commercial commitments in their publications; as with lawyers, concepts like 'conflict of interest' simply do not apply to them. Prof. Lotti appears to espouse this position.

In a 2019 paper, he and his regular entourage plus a group of Vietnamese dermatologists reported significant clinical improvement in Vietnamese victims of vitiligo, treated with Vitilinex herbal emollients, with or without UV irradiation from BioSkin equipment. As noted above, Lotti is Chief Medical Officer for the BioSkin company, and one might think that he had some personal interest in its prosperity or failure; but apparently not, as we are assured that no commercial interests exist. The same question arose in a 2015 report published by J.Brouhaha (where in the context of that strange journal, "published" means "made unobtainable"), in which treatment was a combination of BioSkin treatment and GUNA products.

Those Vitilinex products are distributed through 'Vitiligo.Clinic' which is a collaboration of Lotti, Davinder Parsad and Michael Tirant a.k.a. 'MT Dermaceuticals' who manufactures Vitilinex products. They appear to be the same as the own-branded 'Vitiligo.Clinic' range of a few years earlier, in fresh packaging.

Did the authors purchase the creams from the company, or acquire them as free samples? Is there a competing or conflicting interest? Evidently not. Let us skip over the other unanswered question of whether the beneficiaries of the herbal-extract / UV treatments waived their privacy rights for the before-and-after photographs of sometimes-intimate areas of skin that illustrate this advertisement.

Given the philanthropic ideals of the WHA, it was inevitable that Lotti would direct his dermatological insights to the problem of preventing or even curing COVID-19. We have already seen his research into the 5G aetiology (now retracted), while a March-June "Dermatologic Therapy COVID-19" Special Issue at Dermatologic Therapy features Lotti's name on 21 of the contributions. Notably, Goren et al pursued the idea that testosterone is a risk factor for COVID-19 (as it is for so much else) because mumble mumble angiotensin‐converting enzyme 2 (ACE2) mumble mumble mumble.
So cast your eyes up-screen to the screen-capture of Lotti's competing conflicting commercial interests, and note his role as Chief Medical Officer of Applied Biology. This being a biomed start-up venture "Founded by industry luminaries Prof. Andy Goren and Prof Torello Lotti in collaboration with world renowned dermatologists Dr. Jerry Shapiro, Dr. Jana Hercogova, and Dr. Robert Schwartz". When last I checked in on Applied Biology in 2018 the company was promising trial results by 2017 for its six experimental products, all in the pipeline to oblivion.

But biotech start-ups continue for as long as venture investors keep paying rent to dwell in airy castles. The company is still around, having retargeted AB-101 as an experimental treatment "for restoring nipple sensitivity" in breast-cancer survivors ("AB-101" is simply bog-standard phenylephrine), while new products AB-103, AB-105 and AB-106 for different facets of hair loss have taken the place of now-abandoned drugs and tests.

It is a logical step from the company's previous emphasis on androgens as a risk factor for hair-loss to androgens as a risk-factor for COVID-19. Hospitalised subjects are sought for trials on androgen sensitivity as a prognostic test, and chemical castration as a treatment. Totally not shameless opportunism.

Over at Oca Sapiens, the extent of the hilarity has obliged Sylvie Coyaud to create separate tags for Torello Lotti and Alireza Sepehri and Massimo Fioranelli and Victoria Barygina.