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In the scientific literature, spin refers to reporting practices that distort the interpretation of results and mislead readers so that results are viewed in a more favourable light. The presence of spin in biomedical research can negatively impact the development of further studies, clinical practice, and health policies. This systematic review aims to explore the nature and prevalence of spin in the biomedical literature. We searched MEDLINE, PreMEDLINE, Embase, Scopus, and hand searched reference lists for all reports that included the measurement of spin in the biomedical literature for at least 1 outcome. Two independent coders extracted data on the characteristics of reports and their included studies and all spin-related outcomes. Results were grouped inductively into themes by spin-related outcome and are presented as a narrative synthesis. We used meta-analyses to analyse the association of spin with industry sponsorship of research. We included 35 reports, which investigated spin in clinical trials, observational studies, diagnostic accuracy studies, systematic reviews, and meta-analyses. The nature of spin varied according to study design. The highest (but also greatest) variability in the prevalence of spin was present in trials. Some of the common practices used to spin results included detracting from statistically nonsignificant results and inappropriately using causal language. Source of funding was hypothesised by a few authors to be a factor associated with spin; however, results were inconclusive, possibly due to the heterogeneity of the included papers. Further research is needed to assess the impact of spin on readers’ decision-making. Editors and peer reviewers should be familiar with the prevalence and manifestations of spin in their area of research in order to ensure accurate interpretation and dissemination of research. [ABSTRACT FROM AUTHOR]

Recurrent tumors originate from cancer stem cells (CSCs) that survive conventional treatments. CSCs consist of heterogeneous subpopulations that display distinct sensitivity to anticancer drugs. Such a heterogeneity presents a significant challenge in preventing tumor recurrence. In the current study, we observed that quiescent CUB-domain–containing protein 1 (CDCP1)+ CSCs are enriched after chemotherapy in mutant Kirsten rat sarcoma viral oncogene homolog (Kras) colorectal carcinomas (CRCs) and serve as a reservoir for recurrence. Mechanistically, glucose catabolism in CDCP1+ CSCs is routed to the oxidative pentose phosphate pathway (PPP); multiple cycling of carbon backbones in the oxidative PPP potentially maximizes NADPH reduction to counteract chemotherapy-induced reactive oxygen species (ROS) formation, thereby allowing CDCP1+ CSCs to survive chemotherapeutic attack. This is dependent on silent mating type information regulation 2 homolog 5 (Sirt5)-mediated inhibition of the glycolytic enzyme triosephosphate isomerase (TPI) through demalonylation of Lys56. Blocking demalonylation of TPI at Lys56 increases chemosensitivity of CDCP1+ CSCSs and delays recurrence of mutant Kras CRCs in vivo. These findings pinpoint a new therapeutic approach for combating mutant Kras CRCs. [ABSTRACT FROM AUTHOR]

Hypervariable T cell receptors (TCRs) play a key role in adaptive immunity, recognizing a vast diversity of pathogen-derived antigens. Our ability to extract clinically relevant information from large high-throughput sequencing of TCR repertoires (RepSeq) data is limited, because little is known about TCR–disease associations. We present Antigen-specific Lymphocyte Identification by Clustering of Expanded sequences (ALICE), a statistical approach that identifies TCR sequences actively involved in current immune responses from a single RepSeq sample and apply it to repertoires of patients with a variety of disorders—patients with autoimmune disease (ankylosing spondylitis [AS]), under cancer immunotherapy, or subject to an acute infection (live yellow fever [YF] vaccine). We validate the method with independent assays. ALICE requires no longitudinal data collection nor large cohorts, and it is directly applicable to most RepSeq datasets. Its results facilitate the identification of TCR variants associated with diseases and conditions, which can be used for diagnostics and rational vaccine design. [ABSTRACT FROM AUTHOR]

Curiosity about the sex life of a wasp led to a new way of thinking and a powerful demonstration that evolutionary science could be predictive. That same approach could help find ways to slow or prevent treatment failures in cancer and infectious diseases. [ABSTRACT FROM AUTHOR]

Failure in cancer drug development exacts heavy burdens on patients and research systems. To investigate inefficiencies and burdens in targeted drug development in cancer, we conducted a systematic review of all prelicensure trials for the anticancer drug, sorafenib (Bayer/Onyx Pharmaceuticals). We searched Embase and MEDLINE databases on October 14, 2014, for prelicensure clinical trials testing sorafenib against cancers. We measured risk by serious adverse event rates, benefit by objective response rates and survival, and trial success by prespecified primary endpoint attainment with acceptable toxicity. The first two clinically useful applications of sorafenib were discovered in the first 2 efficacy trials, after five drug-related deaths (4.6% of 108 total) and 93 total patient-years of involvement (2.4% of 3,928 total). Thereafter, sorafenib was tested in 26 indications and 67 drug combinations, leading to one additional licensure. Drug developers tested 5 indications in over 5 trials each, comprising 56 drug-related deaths (51.8% of 108 total) and 1,155 patient-years (29.4% of 3,928 total) of burden in unsuccessful attempts to discover utility against these malignancies. Overall, 32 Phase II trials (26% of Phase II activity) were duplicative, lacked appropriate follow-up, or were uninformative because of accrual failure, constituting 1,773 patients (15.6% of 11,355 total) participating in prelicensure sorafenib trials. The clinical utility of sorafenib was established early in development, with low burden on patients and resources. However, these early successes were followed by rapid and exhaustive testing against various malignancies and combination regimens, leading to excess patient burden. Our evaluation of sorafenib development suggests many opportunities for reducing costs and unnecessary patient burden in cancer drug development. [ABSTRACT FROM AUTHOR]