#experiments and lies

[reasoningdaily]

Science: Did a top NIH official manipulate Alzheimer's and Parkinson’s studies for decades?

In 2016, when the U.S. Congress unleashed a flood of new funding for Alzheimer’s disease research, the National Institute on Aging (NIA) tapped veteran brain researcher Eliezer Masliah as a key leader for the effort. He took the helm at the agency’s Division of Neuroscience, whose budget—$2.6 billion in the last fiscal year—dwarfs the rest of NIA combined.

As a leading federal ambassador to the research community and a chief adviser to NIA Director Richard Hodes, Masliah would gain tremendous influence over the study and treatment of neurological conditions in the United States and beyond. He saw the appointment as his career capstone. Masliah told the online discussion site Alzforum that “the golden era of Alzheimer’s research” was coming and he was eager to help NIA direct its bounty. “I am fully committed to this effort. It is a historical moment.”

Masliah appeared an ideal selection. The physician and neuropathologist conducted research at the University of California San Diego (UCSD) for decades, and his drive, curiosity, and productivity propelled him into the top ranks of scholars on Alzheimer’s and Parkinson’s disease. His roughly 800 research papers, many on how those conditions damage synapses, the junctions between neurons, have made him one of the most cited scientists in his field. His work on topics including alpha-synuclein—a protein linked to both diseases—continues to influence basic and clinical science.

But over the past 2 years questions have arisen about some of Masliah’s research. A Science investigation has now found that scores of his lab studies at UCSD and NIA are riddled with apparently falsified Western blots—images used to show the presence of proteins—and micrographs of brain tissue. Numerous images seem to have been inappropriately reused within and across papers, sometimes published years apart in different journals, describing divergent experimental conditions.

After Science brought initial concerns about Masliah’s work to their attention, a neuroscientist and forensic analysts specializing in scientific work who had previously worked with Science produced a 300-page dossier revealing a steady stream of suspect images between 1997 and 2023 in 132 of his published research papers. (Science did not pay them for their work.) “In our opinion, this pattern of anomalous data raises a credible concern for research misconduct and calls into question a remarkably large body of scientific work,” they concluded.

Neither Masliah nor the various drug companies, universities, or federal ­agencies that were provided the dossier have so far rejected or challenged any of its examples of possible misconduct despite being given the material more than 2 weeks ago. And today, the National Institutes of Health (NIH) released a statement saying that following an investigation, it had “made findings of research misconduct” against Masliah for “falsification and/or fabrication involving re-use and relabel of figure panels” in two publications. According to the statement, Masliah no longer serves as NIA’s neuroscience division director, but NIH declined to further clarify his employment status.

Masliah and Hodes, via a spokesperson, declined to reply to detailed questions, provide an interview, or comment on the dossier. NIH Director Monica Bertagnolli also declined to comment. And Masliah did not reply to Science’s requests for raw images and other data related to the examples in suspect papers, or to a new request for comment on the NIH misconduct finding.

The dossier challenges far more studies than the two cited in NIH’s statement, including many that underpin the development and testing of experimental drugs (see sidebar). Masliah’s work, for example, helped win a nod from the U.S. Food and Drug Administration (FDA) for clinical trials of an antibody called prasinezumab for Parkinson’s. Made by Prothena—a company backed by big money—the drug is intended to attack alpha-synuclein, whose build up in the brain has been linked to the condition’s debilitating physical and cognitive symptoms.

But in a trial of 316 Parkinson’s patients, reported in 2022 in The New England Journal of Medicine, prasinezumab showed no benefit compared with a placebo. And volunteers given infusions of the antibody suffered from far more side effects such as nausea and headaches than those in a placebo group who received sham infusions. Prothena is now collaborating in another trial of the drug candidate involving 586 Parkinson’s patients.

The creators of the dossier, who were unaware of NIH’s probe when they spoke with Science, emphasize that they are not themselves accusing Masliah or his colleagues of fraud or misconduct. They note that some of the identified image problems might have been simple errors, and that when images are prepared for publication, some can acquire innocent visual artifacts that resemble improper changes. Distinguishing the two sometimes requires comparison to raw, high-resolution images and other data, which the dossier’s authors did not have. But they say their findings merit formal investigations.

The enormity of apparent problems described in the Masliah dossier stunned 11 neuroscientists who agreed to review it for Science. “Breathtaking,” says neuroscientist Christian Haass of the Ludwig Maximilian University of Munich. “People will, of course, be shocked, as I was. … I was falling from a chair, basically.”

He and the other researchers didn’t personally verify every example of possible misconduct, but they agreed that most of the suspect work cannot reasonably be explained as careless errors or publishing anomalies. “I’m floored,” says Samuel Gandy, a prominent neurologist at the Mount Sinai Alzheimer’s Disease Research Center who was visibly shaken during a video interview. “Hundreds of images. There had to have been ongoing manipulation for years.”

Gandy was disturbed, for example, that Masliah and colleagues seem to have used the same image of a mitochondrion, a cellular energy-producing structure, in two articles on different topics published 2 years apart in different journals. “The bus driver could see that they are identical,” Gandy says.

MASLIAH IS THE SOLE common author on every paper in the dossier, usually taking the first or last position in multiauthor articles. Those positions imply he did the majority of the publication’s work or bears primary responsibility for it, although the others contributed.

Several of the neuroscientists who reviewed the dossier say it seems implausible that Masliah was duped by a colleague. “Given the extended time frame and huge number of differing collaborators and co-authors on these papers, [possible misconduct] by a rogue postdoc or a collaborating scientist doesn’t apply here,” says Tim Greenamyre, director of the University of Pittsburgh Institute for Neurodegenerative Diseases. “I have a hard time believing that he didn’t know, whether he changed the images himself or somebody else did so on his behalf.”

I’m floored ... Hundreds of images. There had to have been ongoing manipulation for years.

Samuel Gandy

Mount Sinai Alzheimer’s Disease Research Center

At a minimum, according to neuroscientists who spoke with Science, the large volume of doubtful images erodes trust in Masliah’s overall body of work. All 11 who reviewed the dossier agree that all his problem papers should be investigated by NIH, scholarly journals, funders, and UCSD. The university declined to comment, and NIH did not say whether it planned or was conducting a broad misconduct investigation into his research. Masliah this week, days after NIH said it concluded its probe, still appeared with Hodes, the NIA director, to give introductory remarks at the start of a national Alzheimer’s summit on the NIH campus.

As a division director, Masliah would hold sway over NIA’s neuroscience funding, according to Alan Leshner, who previously led two other NIH institutes and headed AAAS (publisher of Science) until 2015. In most cases, he says, institutes select grants based on scores awarded by peer-review “study sections.” But institute and division directors can fund preferred projects, such as studies of amyloid, the brain protein linked to Alzheimer’s disease, over better scoring competitors.

“There’s no question that in most cases, a division director … is viewed as someone who has the judgment to set priorities,” Leshner says. They can also alter the direction of a field. If a division director shows interest in a particular aspect of neuro-science related to aging, he adds, “you get [many] proposals in the next round in that area.”

There’s no evidence that Masliah has been a poor steward of NIA’s neuroscience budget or directed it down blind alleys underpinned by suspect data, but NIH’s statement today still leaves many crucial questions unaddressed.

“The volume of papers and resources involved are enormous—as is Dr. Masliah’s leadership and influence on the field, including drug development pipelines,” says Vanderbilt University neuroscientist Matthew Schrag, one of those who helped assemble the dossier. “That makes it a very influential example of possible misconduct.”

MASLIAH, 65, TRAINED in medicine and neuropathology at the National Autonomous University of Mexico (UNAM), earning his medical degree in 1982 and completing a residency in pathology in 1986. He married a U.S. resident who also studied medicine at UNAM. They relocated to San Diego after Masliah’s training.

Soon after, he landed a plum research fellowship in the lab of Robert Terry, a titan in neuropathology and Alzheimer’s research who reportedly received NIH’s first grant for the neurodegenerative condition in the 1960s. “I was incredibly lucky to meet Dr. Bob Terry,” he told a UCSD interviewer in 2016. In a 1990 photo of Terry’s lab staff, a dark-bearded, youthful Masliah stands proudly, arms folded and wearing his trademark large glasses, beside his famous mentor, who died in 2017. Terry and Masliah pioneered the use of an optical imaging method known as confocal microscopy to create high-resolution 3D images of brain cells.

Masliah went on the lead UCSD’s Experimental Neuropathology Laboratory, where he contributed to early work on alpha-synuclein and novel antibody and vaccine approaches to attack Alzheimer’s and ­Parkinson’s—some of which led to experimental drugs such as prasinezumab that have reached human trials. For Parkinson’s, he also explored antidepressants, and anti-inflammatory drugs or compounds. And for Alzheimer’s, he looked into compounds to decrease the production of amyloid, which builds up in the brain and forms deposits known as plaques outside neurons.

Neurologist Douglas Galasko, who formerly directed the UCSD Alzheimer’s Disease Research Center, where Masliah worked, praises his scholarship and character, calling him “highly collegial and very hardworking.” Galasko co-authored five papers in the dossier, making modest contributions unrelated to apparently doctored images. (He opted not to view the document.)

Galasko says he never heard concerns or doubts about Masliah, whom he describes as “very serious, yet warm and thoughtful, and engaging to have a conversation with.” Those qualities earned him long-term loyalty from investigators working in his lab, Galasko adds. “He’s a very effective spokesperson, organizer, and synthesizer of ideas.” Colleagues at UCSD, he notes, felt enormous pride when Masliah took the helm at NIA’s neuroscience division.

Major impact

Eliezer Masliah’s research on Parkinson’s and Alzheimer’s diseases has enjoyed global influence. His output, as well as the number of citations to his papers, place him among the world’s top 10 scientists in certain subfields (highlighted in red).

“NIA sets the agenda worldwide for age-related diseases,” says Scott Ayton, who directs a neuroscience center at the Florey research institute in Australia, echoing peers in the U.S. and Europe. He was among those who reviewed the dossier and considered the concerns highly credible.

University of Texas at San Antonio neuroscientist George Perry, chief editor of the Journal of Alzheimer’s Disease, describes Masliah’s research as influential and well-regarded, as do other experts in neurodegenerative diseases. In key topics related to Alzheimer’s and Parkinson’s, Masliah frequently ranks in the global top 10 researchers—and often first—by number of papers and citations to them, according to an analysis of data from Dimensions Analytics, a scholarly research data bank from the U.K. company Digital Science (see chart, above). For example, Masliah placed first for papers that use the terms “synuclein” and “synapse.”

His most influential work includes fundamental studies of synaptic damage in mice genetically engineered to mimic various neurodegenerative conditions. “People are very dependent on all of these descriptions,” says Perry, who also reviewed the dossier on Masliah’s research for Science. Many are among the 132 questioned papers, which have racked up more than 18,000 citations, often by leading scholars. “Now I think that work was probably fabricated, in part,” Perry adds, calling the influence of the questioned papers “very problematic.”

BEGINNING IN 2023, forensic image sleuths began to flag a few papers in which Masliah played a central role, posting to PubPeer, an online forum where research publications are discussed and allegations of misconduct often raised. In a few cases, Masliah or a co-author replied or made corrections. Soon after, Science spotted the posts, and because of Masliah’s position and standing decided to take a deeper look.

Schrag, Columbia University neurobiologist Mu Yang, and independent forensic image analyst Kevin Patrick agreed to examine a wider swath of Masliah’s output. (Patrick, a nonscientist who uses the moniker “Cheshire” on social media, had pseudonymously submitted several PubPeer posts on Masliah papers.) In 2023, after a similar request from Science, the same group had assessed work by University of Southern California (USC) Alzheimer’s and stroke expert Berislav Zlokovic. Their dossier of possible misconduct and a subsequent Science report prompted university and NIH investigations, which are apparently ongoing, and led NIH to pause a late-stage clinical trial of a stroke drug based in part on apparently manipulated studies.

For the new dossier, Schrag provided examples, technical context, and expertise on how the findings might affect the promise of prasinezumab and other drugs. Yang took the lead role in identifying and examining questionable images. She used Image- twin, a software program, to assist her own personal scrutiny. (The software, for example, initially spotted the reused mitochondrion image.) Schrag and Yang worked independently of their employers.

Microbiologist and research integrity expert Elisabeth Bik, who also worked on the Zlokovic dossier, contributed other Masliah examples and reviewed and concurred with almost all of the findings. All of the dossier authors worked as volunteers, poring over papers and images in their spare time. The group says it will post many of the examples from the Masliah dossier on PubPeer for others to review; Schrag provided the dossier to NIH, as did Science in the course of producing this story. (NIH’s statement says it had initiated its own investigation much earlier, in May 2023, after receiving allegations from the HHS Office of Research Integrity [ORI].)

In Yang’s analysis of multiple Masliah-authored papers, duplicated sections in some Western blots that had been “seamlessly blended” quickly floated into view, she says. “It tells me someone put a lot of thought and effort into the image … and usually indicates something is very wrong.”

Yang began to see patterns in the apparent image doctoring, which also included images that had been duplicated or seemingly altered by “cloning” portions of them. “I started feeling like a curator or art historian—when you look at a piece of art without the label, you know the artist by the style. Like a painting from Picasso’s blue period,” she adds, “it’s a signature style that I saw in many, many papers—the way they lay out the figures, even the color contrast.”

After finding hundreds of questionable images, the group had more than enough strong signs of misconduct and stopped looking, Yang says. But she suspects similar problems would emerge from a close examination of the hundreds of other Masliah papers.

Making a drug look better?

National Institute on Aging neuroscience chief Eliezer Masliah was senior author of a 2015 study of the Alzheimer’s disease treatment Cerebrolysin in BMC Neuroscience. Brain-tissue images from normal mice and mice engineered to overexpress a mutant form of the tau protein might have been doctored to suggest the drug reduces damage from the tau.

Overlapping copies

In the paper, normal (non-tg) mice show no tau damage. The mutant mice (3RTau) show tau damage unless treated with Cerebrolysin. But a merged image of the younger, normal mouse and the older, treated mutant appear unnaturally similar. Yellow sections are identical.

A series of clones

Dissimilar (red or green) areas within the merged image seem to be caused by efforts to obscure the duplication. Small “cloned” areas within each image are indicated by same-color boxes. The journal’s publisher said it would review the concerns.

YANG AND THE OTHER authors say the ongoing human trials of prasinezumab add to the urgency of their findings. According to Prothena, the drug blocks the spread of toxic alpha-synuclein and might slow the progression of Parkinson’s movement disorders and dementia. Prasinezumab’s documented side effects have not been dangerous. But if it is based on suspect scientific foundations and, as the first clinical results suggest, ineffective, further clinical testing could raise false hopes and divert patients from trials of other experimental drugs.

The concept for prasinezumab emerged from Masliah’s ties to the late Dale Schenk, a UCSD-trained neuroscientist whose research helped pioneer the idea of treating Alzheimer’s and Parkinson’s with vaccines designed to block the buildup of harmful amyloid and synuclein. Masliah, Schenk, and others proposed that immunizing people with benign parts of each protein could spur the immune system to produce antibodies that might block the full, toxic form. Infusing labmade antibodies might have the same effect. Either approach, they hypothesized, could offer a “disease modifying” attack on a condition’s root cause, rather than merely alleviating symptoms.

In a 2016 post on Alzforum, Masliah recalled an early discussion with Schenk on the idea. “Dale and I sat at a coffee shop (his favorite place) next to the Pacific Ocean and drew, on a napkin, the concept of how a potential synuclein vaccine might work,” he said. “People strongly doubted the potential use of a vaccine approach in Alzheimer’s and even more so in Parkinson’s. Dale was one of the few who listened and believed in the idea.”

To pursue that vision Schenk co-founded and served as chief executive of Prothena, spun off in 2012 from the former biopharma company Elan. Masliah worked extensively with Schenk until his death from pancreatic cancer at age 59 in 2016. Four of their joint studies, published between 2005 and 2017, proved foundational for prasinezumab, according to Prothena’s promotional material. Schenk was senior author on two of the papers, Masliah on two. All four used apparently doctored images, according to the dossier, as did other Masliah papers cited in clinical trial reports as important to prasinezumab’s development. Some of the papers suggested Parkinson’s symptoms could be generated in mice engineered to produce alpha-synuclein, and that those symptoms could be reduced by injecting antibodies akin to prasinezumab into the animals.

Greenamyre, a Parkinson’s specialist, says the papers showed an “astonishing level” of apparent image manipulation. But he notes that the image anomalies and the drug’s lack of success so far don’t necessarily mean “that synuclein is a bad target or that targeting it with antibodies is never going to work.” The clinical trial team testing the antibody reported earlier this year in Nature Medicine that a small subgroup of its patients showed hints that prasinezumab slows the worsening of movement symptoms—although the group acknowledged that the finding emerged in a “posthoc analysis,” a secondary review unrelated to the trial’s hypothesis.

Manipulations in key experiment?

Five images in a 2005 paper in Neuron from Masliah and Prothena founder Dale Schenk appear to have been doctored in ways that could influence paper's findings. It is among several papers cited as key to the experimental drug prasinezumab that show apparent falsifications.

Still, “The discovery that key papers supporting this approach contained manipulated figures certainly muddies the waters,” Greenamyre says. He’s now hoping independent studies will determine whether “the rationale for clinical development remains on firm ground—or if it is now a little shaky.”

“We do not interpret these claims as specifically relevant to the current prasinezumab clinical program,” Prothena told Science in a brief statement responding to questions about the image anomalies related to the drug.

Swiss pharma giant Hoffmann-La Roche, which partnered with Prothena to develop prasinezumab in 2013, also supplied a statement in response to Science’s questions, saying it would continue clinical development of the drug. “The evidence supporting targeting alpha-synuclein aggregates as a mechanism of action in [Parkinson’s] is based on a wide range of sources,” it stated. In the interest of scientific integrity, Roche added, “We are working to further understand the details of this matter.”

Roche has agreed to pay Prothena up to $620 million if its drug candidate passes a series of performance goals. So far, Roche has paid $135 million.

Schenk and Masliah shared inventor credit in patents in the U.S. and Europe related to synuclein, amyloids, and related science, and they and their co-inventors assigned the rights to Prothena, UCSD, or both. Numerous other Prothena patents refer to suspect work cited in the dossier. Prothena and NIH did not respond to questions about whether Masliah has received or was promised royalties.

The dossier also questions some of Masliah’s earliest work on alpha-synuclein, raising further doubts about the foundations of Prothena’s drug. A seminal 2000 Masliah article in Science, for example, suggested alpha-synuclein might kill certain brain cells and speed the development of brain deposits called Lewy bodies that are hallmarks of Parkinson’s and are often seen in Alzheimer’s patients. But the paper contains an apparently doctored image and another image the dossier authors deemed questionable.

Other researchers have yet to validate aspects of that study, according to Ayton and neurologist Michael Okun of the University of Florida.

“A single nonreplicable finding is in itself not worrisome,” Okun says. But it raises greater concern in light of “convincing evidence of spliced and cloned images which appeared frequently in the decades following.” He calls it “deeply troubling” that FDA greenlighted human trials of prasinezumab based largely on suspect papers from Masliah’s lab.

People will, of course, be shocked, as I was. ... I was falling from a chair, basically.

Christian Haass

Ludwig Maximilians University Munich

FDA declined to comment on the prasinezumab findings challenged within the dossier. Holden Thorp, editor-in-chief of the Science family of journals, says the journal will “contact the authors [of the 2000 paper] to hear their response to these concerns. If any adjustments are required, we will certainly make them.” (Science’s News department is editorially independent of the journal.)

The new phase 2 trial of prasinezumab is examining whether it might slow the progression of certain movement difficulties caused by Parkinson’s, as the posthoc analysis suggested it might. Roche and Prothena expect to announce preliminary results later this year. The companies would likely decide in 2025 or 2026 on whether to move on to phase 3 trials—larger efficacy experiments needed for possible FDA approval.

The findings in the dossier cast a shadow on the other drug development efforts that rely on Masiah’s challenged work. And they raise questions about the roles and responsibilities of the many prominent scientists as well as more junior researchers who collaborated on some of his suspect experiments.

UCSD neuroscientist Edward Rockenstein, who worked under Masliah for years, co-authored 91 papers that contain questioned images, including 11 as first author. He died in 2022 at age 57. And neuroscientist Robert Rissman worked on 16 of the papers highlighted in the dossier, seven as senior author. He managed biomarkers and brain tissue samples for UCSD’s Alzheimer’s Disease Research Center prior to moving recently to USC, where he occupies a similar role and manages programs that try to move basic research into treatments for patients. Rissman did not reply to requests for comment. USC says it will conduct a confidential review of Rissman’s involvement with Masliah’s work.  

Haass questions whether Masliah’s closest collaborators could have remained unaware of the steady stream of apparent image manipulation, even if they were not personally culpable. “I mean, come on,” he says. “They must know.”

Other neuroscientists who spoke to Science urged caution in placing blame. “We should be careful … not to rush to judgment on the generation of researchers who may have been innocent members of this laboratory over the span of 20-plus years,” Okun says. “It is entirely possible that many were unaware of improprieties.”

In its statement today, NIH provided few details about the agency’s own investigation into Masliah’s work, including whether it had examined more than two of his publications. The agency says it has notified ORI of its findings and that the NIA deputy director, Amy Kelley, is also now acting head of the neuroscience division.

Given the NIH misconduct determination and the questions raised by the dossier about more than 100 other papers, many scientists—and perhaps congressional appropriators and the public—might question NIH’s vetting process for key roles and how Masliah retained stewardship of NIA’s billions of neuroscience dollars for so long. “For so important a job, you want somebody who is beyond reproach. You want somebody to be an exemplar of what you aspire to be,” Greenamyre says.

By the time NIA hired Masliah in 2016, image manipulation in scientific papers had already become a general concern. Prominent researchers increasingly faced accusations of image manipulation, plagiarism, or other misconduct—which often proved credible. But a former NIA official who would only speak if granted anonymity says he assumes the agency did not assess Masliah’s work for possible misconduct or data doctoring before he was hired.

Indeed, NIH told Science it does not routinely conduct such reviews, because of the difficulty of the process. “There is no evidence that such proactive screening would improve, or is necessary to improve, the research integrity environment at NIH,” the agency added.

Gandy disagrees. “It has to be part of the process now,” he says.

Greenamyre notes a concern about the episode also voiced by Haass and others who viewed the dossier: “I worry about it giving science a further black eye, just as the public’s confidence in science and scientists is sinking to new depths.” But, Greenamyre says, “In the interest of transparency and scientific integrity, this sad story has to come out.”

Questionable papers underpin other drugs

By Charles Piller

The possibility that neuroscientist Eliezer Masliah doctored images in scientific writings for decades is likely to provoke anxiety among multiple drug companies. The concerns documented by whistleblowers most directly challenge an experimental Parkinson’s therapy developed by Prothena (see main story). But 238 active patents concerning neurological conditions also cite suspect work noted in the dossier, according to data from Dimensions Analytics. And the corporate holders of those patents include dozens of firms at work on treatments.

The Austria-based biopharma company Ever Pharma relied heavily on Masliah’s questioned work in developing Cerebrolysin, a mixture of peptides—short chains of amino acids—derived from pig brains. Eight studies conducted at Masliah’s former lab at the University of California San Diego, funded in part by Ever Pharma, indicated the mixture suppresses brain inflammation, promotes growth of new brain cells, and has other benefits that could help dementia patients.

Small clinical trials of Cerebrolysin have suggested modest cognitive benefits in Alzheimer’s disease and vascular dementia, and Ever Pharma now distributes the drug in dozens of nations to treat dementia and stroke. But no large trials have demonstrated it helps dementia patients, and the Food and Drug Administration has not approved Cerebrolysin for use in the United States. And the eight lab studies used suspect images, according to the dossier.

For example, an article by Masliah and colleagues, in BMC Neuroscience in 2014, described the purported benefits of Cerebrolysin for symptoms of neurodegeneration in mice, including reducing mitochondrial damage. Another, published in Neurotoxicity Research in 2016, concerned mice infected with HIV. It republished what appears to be the same image of a mitochondrion.

A spokesperson for Springer Nature, publisher of Neurotoxicity Research, says the concerns will be examined, and responded to if warranted. Stefan Winter, who heads R&D for Ever Pharma’s neurological division, said in a written statement to Science that none of the challenged work in the dossier “played a crucial role in the clinical development of Cerebrolysin.” But, he added, “We take [the allegations] seriously. We will therefore review Prof. Masliah’s work based on the information you provided and refrain from using data from the mentioned publications until this matter is clarified.”

Another company, Neuropore Therapies, cites seven other papers in the Masliah dossier—all with apparently doctored images—as important to the company’s potential drugs for Parkinson’s. Masliah co-founded Neuropore in 2008 but no longer has any apparent affiliation. The most prominent drug candidate his work helped develop, minzasolmin, is in early clinical trials and targets the protein alpha-synuclein for Parkinson’s.

Masliah also provided imaging services for a 2023 paper in NPJ Parkinson’s Disease. The images, which purportedly show enhanced benefits in mice from minzasolmin, appear to be altered, according to the dossier. The concerns will be examined and responded to if warranted, says the journal’s publisher, Springer Nature. “We stand by our data related to clinical development programs,” said Mark Yung, executive chairman of Neuropore, in a brief written reply to detailed questions.

Minzasolmin has Big Pharma backing. In 2015, Neuropore licensed rights to develop and commercialize it and other molecules to the Brussels-based pharma company UCB for $63 million, plus possible future payments. In turn, the Swiss pharma titan Novartis paid UCB $150 million of a possible $1.5 billion for codevelopment rights for minzasolmin and another experimental drug.

“UCB will investigate the preclinical publication on minzasolmin” described in the Masliah dossier and will respond should “evidence of impropriety emerge,” said company spokesperson Laurent Schots in a written statement. But UCB knows of no “facts or circumstances that raise concerns on the quality, validity, and safety of the ongoing clinical development program for minzasolmin,” which is supported by evidence beyond the suspect Masliah work, Schots added.

Preliminary results for the drug’s efficacy from a clinical trial of 496 people in the U.S., Canada, and Europe could be announced later this year.

[revelisms]

lachryma mv got me feeling some type of way

[humanjarvis]

i only really tolerate being touched by certain people and i’m projecting onto zayne and thinking he’s the same way.

too-friendly patients clasp his hand as they thank him, and he’s bristling so much he barely processes their gratitude. he takes a step back, gentle but firm, and sends them on their way, trying to look past the confusion on their faces.

the only intern who doesn’t fear him aces an assessment one day. but when she bounds up to him and asks for a high-five, he can only spare her a curt nod. her dejected flush replays in his mind when she shrinks away from him in the hallway.

he questions his personhood when he retreats from the pediatric patients’ eager touches, their tiny hands reaching up to grab at his stethoscope. shouldn’t he like this? shouldn’t he chuckle and beckon them forward? shouldn’t his heart fill with warmth? that’s how he hears greyson describe it. that’s how he sees the nurses act. so why can’t he do the same?

it’s only when you touch him—when you hold his face, kiss his nose, or wrap your arms around his waist—that his worries fade away. your touch is good. safe. familiar. he craves it, he seeks it, he leans into it instead of shying away. in your arms, he doesn’t bristle. doesn’t wonder if he was meant to be a recluse, never to be touched by another hand. in your arms, he feels a little more human.

[reality-detective]

If you need a reason as to "Why you should drink Jack Daniels," this 👆 is it. 🤔

[rhiangalaxy]

The transmigrators meeting (Li Yu, Shen Yuan, Shang Qinghua). Oh, the chaos it would be when SY and SQH find out Li Yu transmigrated into a fish.

Li Yu's experience was not universal 😔Thanks for the request!!

[ID: A Scum Villain and DTBPF Crossover doodle. The top part has Shen Qingqiu looking off to the side with the lower part of his face covered by his fan saying "I transmigrated into the villain..." Shang Qinghua, to the right of SQQ, with a closed eye exasperated expression whilst pointing up to himself says "I transmigrated as a traitor." It then cuts to Li Yu would is holding up one hand to his own cheek with a nervous smile and goes "Yeesh... I just transmigrated into a fish..." The bottom has SQQ and SQH on either side of LY looking at him with expressions of concern and surprise responding "WHAT?!" As LY is continuing to smile nervously with a flushed face in the middle. End ID]

[llemon-soda]

joy and whimsy

[cosmoszyn]

We've always talked about Zayne having recurring nightmares and waking up in the middle of the night because of it, but what if you experience the same?

Experiencing such traumatic events in your life—it's apparent that it's affected your sleeping pattern.

But unlike Zayne, who wakes up gasping and in a cold sweat, you, on the other hand, stir awake because tears are trickling down your face in your sleep. It's not often that nightmares come haunting you in your dreams; it was more of a seasonal thing. Most of the time, those nightmares weren't even inherently frightening but rather extremely mournful.

And the first time it plagued you during your relationship with Zayne, it reminded you of the sanctity of his love for you.

You don't remember what the bad dream was all about. You were sure it was something about a deceased loved one visiting you on a warm sunny day with tea in hand. You only realize you were having those night terrors when your heart sinks, and you can physically feel it clench tightly across your chest. Fluttering your eyelids open, clusters of salty tears litter your lash line and dribble down your cheeks. With a heavy gulp, you carefully attempt to untangle yourself from Zayne's snug embrace.

Unfortunately for you, that never seems to work out, especially since your lover is a very light sleeper. The moment you shift and remove your hand from his chest, he stirs awake.

"My love?" He groggily calls, peering into you. "What's the matter?"

You take the opportunity to lift his arm away from his hold, shuffling to the edge of the bed, "'S nothing," you snivel, the scratch in your throat betraying you, "Just need water."

You get stopped by the edge of the bed by Zayne's soft grip on your arm, and with no words exchanged, you find him already padding through the small space of your apartment. In a few seconds, he hands you the glass of water, patiently waiting for you to guzzle down the drink. You sniffle as you place the empty cup on the bedside table, darting your gaze elsewhere.

The grief lingers in your ribcage, sharp needles pricking your heart as you breathe. You pathetically wipe away your tears with the back of your hand, staring into the open space of the shared room. Just as you are about to plop to the cushion and screw your eyes shut, you feel the mattress dip beside you and two strong arms carefully engulfing you.

With uncertainty, you turn your body to Zayne's direction, eyes focusing on the wrinkles of the duvet under your hands. You expect Zayne to speak up and have you explain what happened. Or invite you back to doze, foregoing the conversation until the following morning.

And yet, his fingers delicately brush your tear-stained cheeks, tucking stray strands of hair behind your ear. His actions surprise you, allowing you to glance upwards—only to meet his gentle irises and lips slightly parted. Your breathing hitches, feeling the tears welling up again. Before a drop could even streak down, Zayne reaches out and envelopes you in a solacing hug.

You choke back the tears, shakily accepting his tight grasp. He nuzzles into the crook of your neck, inhaling your scent while drawing soothing circles on your back. With a tender push from your side, he guides you back to the cushions, pulling back the blanket to encase you two without escaping from his hold. Zayne soothingly shushes your hiccups, stroking your skin, and whispers sweet nothings into your ear.

You barely notice Zayne's firmer embrace and his glassy eyes, too engrossed with the way he consoles you despite not having an idea why. And within beats of his lullabies and devotion, he cradles you back into slumber.

And while Zayne didn't have an idea why you suddenly sobbed in the dusk, perhaps he understood the feeling too well. The least thing he could do at the moment is provide you a secure hug, letting you know that he's with you—no matter what.

a/n: a short drabble dedicated to my people who have trouble sleeping :)

[benevolenterrancy]

Finally got Fish Book 3 out from the library (and 4 on its way!), at last I will be experiencing Real Pregnant Li Yu for myself! After being there for your experience of it finally it's my turn xD You said a bit back you like getting drawing prompts, could I suggest flustered just-realized-his-fish-is-a-cute-boy Prince Jing? He gained confidence quickly but that period where he was embarrassed about things like petting his fish because if his fish is a person petting his tail is like touching his butt was very funny and very cute 💖 He's such a dork <3

hey, prince jing, what exactly are you touching there? 🤨

[amarriageoftrueminds]

thing I've realised which alters how I see the howling commandos:

if the actors' ages reflect the characters’ ages, then all of the Howlies are considerably older than Steve.

The youngest Howlie (after Bucky & Steve) would be eight years older than Steve (that's Monty). The oldest is eighteen years older.

So they're a bunch of guys in their 30s and 40s who voluntarily put themselves under the command of a clueless 25 year old whippersnapper who's never even been in the field before. 

Or, another way to put it: 

Bucky was asked to pick a team to put under Steve's command and he chose a bunch of much older, seasoned soldiers, because clearly a bunch of kids in their twenties couldn't be trusted to cope with this idiot.

[humanjarvis]

it's nice to have a friend

big glasses and a bowl cut. 

for the bulk of his short life, that was all anyone saw when they looked at zayne.

no one knew much about him, other than how annoying it was when the teachers praised his intelligence. more than a classmate, he was a goalpost. a standard they couldn’t meet. 

more often than not, his head was buried in a book. he found it much more worthwhile to study people than to speak to them. so he hid in the shade, away from the constant chatter and blistering heat of recess.

that day in september, he’d been too busy absorbing neatly stacked paragraphs to process the muffled voice above him—until you lightly shook his shoulder. 

you’d asked him if he wanted to play. they’d said it was his birthday, after all. but after a long pause and bewildered blush, zayne said no. 

the first three times you asked him, zayne said no.

his answer changed when the leaves did. 

in the brisk november air, pushed forward by a gust of wind, he bumped into a rowdy group of older kids. apparently, his murmured apology hadn’t been good enough. 

first, they threatened to snap his glasses. shatter the lenses so he couldn’t read anymore.

the wicked sneers and guesses that he was special came after. 

through it all, zayne hadn't said a word—he didn't have to. 

because before he could decide whether to tell a teacher or walk away, you were blocking him from view as best you could with your shorter frame, glaring at the boys with molten hatred in your heart. 

and when their leader snorted and took a step toward you both, you unclenched your fist and scratched him right across the face. 

zayne had never been one for violence. his parents told him it never solved anything, and he’d always seen more value in helping people than hurting them. 

but the next time you asked him to play, he nodded his head yes.

he was surprisingly good at make-believe—the doctor to your nurse. and when you invited him back the next day, and the next day, and the day after that, zayne felt he’d made his first friend. 

adult zayne still gets teased, sometimes. 

for the way he speaks like a nonfiction narrator. for the way he retreats from interactions and rejects invitations. for the way he’s hard to read unless you’re fluent in the language of him.

but with you by his side, he’s learned to pay it no mind. 

you like his cadence and his reticence and his rigid kind of softness. you tell him all of it, so he doesn’t have to wonder.

and when the crueler slights wear down the barrier you’ve helped him build, you repeat yourself. 

day after day, you save him. just like you did on the playground. 

so when zayne finds himself in linkon’s finest jewelry store, browsing through shimmering stones he never thought he’d have a need for, he knows one thing for certain: his first friend is his best. 

[reality-detective]

To all the Supermarkets and BIG commercial stores that operate 'Self Check-outs'... You are heading towards being almost exclusively self-checkout now. Today I went shopping at one such store and the lady checking receipts at the exit was stopping everyone.

I didn't choose to participate in that nonsense, I had already filled my cart, emptied my cart and scanned the items, refilled my cart so I just skipped the exit line and left.

I heard her saying "Umm - Excuse me“ as I kept walking and raised the receipt above my head and left the store.

You can either trust me to do self-checkout, or you can put your cashiers back in place like it used to be.

• I'm not interested in proving that I did your job for you.

• If you want me to be a cashier with no training then that's your problem not mine.

• Keep employing young people and give them job opportunities.

YOU DON'T PAY ME TO SCAN MY OWN SHOPPING.

YOU DON’T GIVE ME STAFF DISCOUNTS FOR WORKING FOR YOU.

Signed... All of us

People we need to share this statement, its all about PROFIT to the stores AND putting People out of a JOB!!! 🤔

[thatswhatsushesaid]

i'm finally doing it, i'm watching mysterious lotus casebook

congratulations on your new appointed-by-the-narrative husband, li lianhua, i think you're going to be very happy together

[slime-crafters]

There is nothing more humiliating than being stumped by a skyrim puzzle. It's like if a toddler KO'd Mike Tyson

[hana-bobo-finch]

new headcanon. zasp touched a bug zapper as a child because he was a little prick and hasn’t been the same since

[princepinkart]

From a matter most dark, a blade pierces through the night.

Process under the cut!

At first, it was only supposed to be a quick doodle to get his design down. ↓

Then innocently, I decided "why not clean it?" ↓

Of course, the next logical step would be to add shading. ↓

I continued to add shadows until the areas I wanted focus on were clear. ↓

At the end I realised I did not like how his mask and shoulder pad turned out, so I changed them with a much more prominent shadow. ↓

I added some simple gradients, and voilà! ↓

What a fun drawing it was!!!!

[macksartblock]

your dndads s2 art makes me so sad I love it so much I need those weird teens to be happy for once they deserve a break </3

i need them to go on a weekend-long field trip it's the only thing that will bring me peace