The Snippet: China cracks down on fake peer reviews

The Chinese government is going on the offensive against scientists who dupe journals by creating fraudulent reviews of submitted papers. A coalition of agencies led by the science ministry announced on 14 June that the government would suspend the grants of researchers involved in such fraud, which surfaced earlier this year when a cancer journal retracted 107 research papers from Chinese authors. And funding agencies in China promised to increase policing of the scientific community to prevent similar deceptions. The harsh penalties and stricter enforcement were decided earlier this month at a meeting of representatives of the science ministry, the health ministry, the National Natural Science Foundation of China (NSFC) and other agencies. The meeting was a response to retractions made in April by the journal Tumor Biology, after its publisher, Springer Nature, found that reviews submitted in support of 107 papers had been fabricated. Fraud in peer review is a global problem. It occurs when researchers — or companies acting on their behalf — suggest scientists as potential peer reviewers, but the e-mails supplied for the reviewers route back to the authors or the companies, who then write spurious reviews supporting publication. Online companies that orchestrate fake peer review are among the main targets of the crackdown. The coalition hopes to enlist the government’s Cyberspace Administration of China, the agency that censors the Internet in China. It could identify the culprits behind the companies, says Yang Wei, head of the NSFC. Surprisingly, only 17 of the 107 retracted papers were funded by the NSFC, even though the agency supports more than 60% of Chinese scientific research. The NSFC found that more than 30 of its pending grant applications were based on the retracted papers. Those applications have been canceled. The success of the government’s crackdown will depend on whether it can link strict implementation to a fairer system of evaluation for doctors and researchers, says Jiang.

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The Snippet: New cancer drug tested in mice may benefit certain leukemia patients

Almost 6,000 new cases of acute lymphoblastic leukemia, or ALL, are expected to be diagnosed this year in the United States. Up to 30 percent of adult acute lymphoblastic leukemia or ALL patients have Philadelphia chromosome, where two segments of chromosomes have aberrantly fused together. Adult ALL patients often see high relapse rates, and treatment-related deaths remain high. Researchers now report on a study that could provide better therapeutic options for patients. In the Leukemia study, HCI scientists learned how to inhibit and override the negative activity of this chromosome. The findings could possibly lead to future novel drug treatments. The Philadelphia chromosome promotes repair through numerous proteins. But putting together a cocktail of drugs to inhibit them all would likely be too toxic and affect normal cells. So, Srividya Bhaskara, HCI investigator and assistant professor of radiation oncology at the University of Utah, focused on two specific proteins she found directly involved in DNA repair, called histone deacetylases (HDAC) 1 and 2. She has now collaborated with a company to make a drug that inhibits HDAC1,2 activity. The HDAC1,2 inhibitor drug has been tested in patient samples and mice, showing encouraging results, either alone or in combination with a chemotherapy drug called doxorubicin.

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The Snippet: Gut bacteria can stop cancer drugs from working

In the quest for personalized therapies, most research has focused on how an individual’s genome controls their body’s responses to drugs. However, there is increasing evidence that a person’s unique microbiome — the population of bacteria and other microbes that live in their body — can be key to determining whether or not a drug works for their condition. Researchers now have evidence that healthy people metabolize some drugs in different ways depending on their microbial make-up. They presented their data on 4 June at the meeting of the American Society for Microbiology in New Orleans, Louisiana. Bacteria living in the human body will eat any nutrient that comes their way, whether it’s food from the host’s diet or a drug that the person is taking. But this dietary flexibility can become problematic if the microbes metabolize a drug into useless or toxic compounds. To see whether a person’s microbiome affected how they metabolized drugs, Guthrie and her colleagues collected faecal samples from 20 healthy people. When the researchers analysed the proteins produced in the faecal samples, they found that those from people with high bacterial metabolisms contained strains that made more β-glucuronidases. These people also had increased levels of proteins that transport sugar into cells, which suggests they would be more likely to absorb the toxic compound and develop gastrointestinal problems. It’s a nice step towards understanding how gut-bacterial enzymes interact with drugs, says Matthew Redinbo, a structural biologist at the University of North Carolina at Chapel Hill who also studies irinotecan. “Our biggest insight is to look at gut enzymes and think about them the same way as human” enzymes, he says.

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The Snippet: Bio-manufacturing with Spider Silk for pre-term babies

Researchers at Karolinska Institutet in Sweden have managed to synthesise lung surfactant, a drug used in the care of preterm babies, by mimicking the production of spider silk. Animal studies reveal it to be just as effective as the biological drugs currently in clinical use. Surfactant revolutionised the care of preterm babies by reducing the surface tension in their pulmonary alveoli and allowing them to be inflated at the moment of birth. Curosurf, the most globally widespread drug, was developed by scientists at Karolinska Institutet in the 1970s and 1980s. The drug is produced by the isolation of proteins from pig lungs, a process that is expensive, complicated and potentially risky. Researchers at Karolinska Institutet and their colleagues from the University of Riga amongst other institutions, have now developed a surfactant drug that can be produced much more simply and cheaply using spider protein. The researchers also compared their synthetic lung surfactant with the biological analogue currently on the market and found it equally effective at reducing the surface tension in an animal model of neonate respiratory disorders. This study was primarily financed by the Swedish Research Council and was performed in collaboration with the Italian pharmaceutical company Chiesi Farmaceutici.

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The Snippet: FDA grants accelerated approval to pembrolizumab

The U.S. Food and Drug Administration granted accelerated approval to pembrolizumab (KEYTRUDA, Merck & Co.) for adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options or with MSI-H or dMMR colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This is the FDA’s first tissue/site-agnostic approval. The approval was based on data from 149 patients with MSI-H or dMMR cancers enrolled across five uncontrolled, multi-cohort, multi-center, single-arm clinical trials. The major efficacy outcome measures were objective response rate (ORR) assessed by blinded independent central radiologists’ review according to RECIST 1.1, and response duration. ORR was 39.6% (95% CI: 31.7, 47.9). Responses lasted six months or more for 78% percent of those who responded to pembrolizumab. There were 11 complete responses and 48 partial responses. ORR was similar irrespective of whether patients were diagnosed with CRC (36%) or a different cancer type (46% across the 14 other cancer types). The recommended pembrolizumab dose for this indication is 200 mg for adults or 2 mg/kg (up to a maximum of 200 mg) for children, administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

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The Snippet: Geneticists enlist engineered virus and CRISPR to battle citrus disease

Fruit farmers in the United States have long feared the arrival of harmful citrus tristeza virus to their fields. But now, this devastating pathogen could be their best hope as they battle a much worse disease that is laying waste to citrus crops across the south of the country. The agricultural company Southern Gardens Citrus in Clewiston, Florida, applied to the US Department of Agriculture (USDA) in February for permission to use an engineered version of the citrus tristeza virus (CTV) to attack the bacterium behind citrus greening. This disease has slashed US orange production in half over the past decade, and threatens to destroy the US$3.3-billion industry entirely. The required public comment period on the application ended last week, and the USDA will now assess the possible environmental effects of the engineered virus. Field trials of engineered CTV are already under way. If the request is approved, it would be the first time this approach has been used commercially. It could also provide an opportunity to sidestep the regulations and public stigma attached to genetically engineered crops.

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The Snippet: Scientists relieved by Emmanuel Macron’s French election victory

French scientists say they’re relieved and happy that their country’s next president will be Emmanuel Macron, a 39-year-old former civil servant and economy minister who swept to victory in elections on 7 May. Macron intends to make cuts to public spending but has said he will ring-fence the budgets for research and higher education, areas that he wants to make the central plank of a program to boost innovation and cut unemployment. He has also pledged to invest in environmental and clean-energy measures. But his ability to implement these policies will depend heavily on the results of legislative elections in June. If he doesn’t have enough support in France’s parliament, the new president will find it hard to propose and pass new laws. French research bodies rarely take overt positions on elections, but this one was different. France’s academy of science, the heads of nine national research agencies and many prominent scientists had all made public appeals against Le Pen’s party ahead of Sunday’s head-to-head vote, arguing that the Front National’s illiberal and anti-immigrant views threatened the tolerant, open and democratic environment in which science and evidence-based policy thrives.

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The Snippet: Science wins reprieve in US budget deal

Funding for US science agencies will stay flat or even increase over the next several months, under a US$1-trillion spending deal announced on 30 April. The plan devised by Congress, which covers the remainder of the 2017 budget year, avoids the sharp cuts to science proposed by US President Donald Trump. The biggest winner is the National Institutes of Health (NIH), whose budget would rise by $2 billion compared with the 2016 level, for a total of $34 billion. The National Science Foundation would remain steady at just under $7.5 billion, and NASA’s budget would rise by about 2%, to $19.7 billion. And the Environmental Protection Agency, which Trump wants to cut by 31% in the fiscal year 2018, would receive roughly $8.1 billion, a decrease of about 1% from 2016. But that does not mean that scientists can breathe easily just yet: the largely positive 2017 deal does not necessarily indicate how Congress will handle funding for 2018, says Michael Lubell, a physicist at City College of New York in New York City. Lawmakers “have a year to fall in line [with the president] if they want to”, he says.

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The Snippet: Cord Blood makes brains of elderly mice young again

A protein found in umbilical cord blood may help restore its youthful vigor. Researchers have previously found that blood from human teenagers can rejuvenate memory and cognition in elderly mice, probably due to factors present in the plasma – the liquid portion of the blood. Now, blood harvested from babies’ umbilical cords has been found to have even stronger anti-ageing effects. Joseph Castellano at Stanford University in California and his colleagues discovered this by collecting blood from people at three different life stages – babies, young people around the age of 22, and older people around the age of 66 – and injecting the plasma component into mice that were the equivalent of around 50 years old in human years. The most dramatic effects occurred when these mice received babies’ cord plasma. They became faster learners and were better at remembering their way through a maze. This corresponded with enhanced activity in their hippocampi – the brain regions responsible for learning and memory.

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The Snippet: Targeting metabolism in Renal Cell Carcinoma

Loss of VHL and elevated expression of HIF transcription factors leads to reprogramming of tumour cell metabolism, enabling renal cell carcinoma (RCC) cells to use carbons from glutamine-derived aspartate to drive pyrimidine biosynthesis. Now, researchers show that inhibition of glutamine availability decreases aspartate availability, leading to growth inhibition of RCC cells. Moreover, glutaminase 1 (GLS1) inhibition increases oxidative stress, leading to DNA replication stress and growth arrest. “These findings led us to combine a GLS1 inhibitor with an inhibitor of DNA repair enzymes — in this case, a poly(ADPribose) polymerase (PARP) inhibitor — to achieve therapeutic synergism,” explains Othon Iliopoulos. “In other words, we discovered how targeting a metabolic pathway renders VHL-deficient cancer cells sensitive to DNA repair mechanisms.” Iliopoulos hopes to take their findings directly to a clinical trial. “We now plan to treat patients with renal and other HIF-expressing cancers with this novel combination of GLS1 and PARP inhibitors,” he explains.

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