Best practices for data management and sharing in experimental biomedical research.

Effective data management is crucial for scientific integrity and reproducibility, a cornerstone of scientific progress. Well-organized and well-documented data enable validation and building on results. Data management encompasses activities including organization, documentation, storage, sharing, and preservation. Robust data management establishes credibility, fostering trust within the scientific community and benefiting researchers' careers. In experimental biomedicine, comprehensive data management is vital due to the typically intricate protocols, extensive metadata, and large datasets. Low-throughput experiments, in particular, require careful management to address variations and errors in protocols and raw data quality. Transparent and accountable research practices rely on accurate documentation of procedures, data collection, and analysis methods. Proper data management ensures long-term preservation and accessibility of valuable datasets. Well-managed data can be revisited, contributing to cumulative knowledge and potential new discoveries. Publicly funded research has an added responsibility for transparency, resource allocation, and avoiding redundancy. Meeting funding agency expectations increasingly requires rigorous methodologies, adherence to standards, comprehensive documentation, and widespread sharing of data, code, and other auxiliary resources. This review provides critical insights into raw and processed data, metadata, high-throughput versus low-throughput datasets, a common language for documentation, experimental and reporting guidelines, efficient data management systems, sharing practices, and relevant repositories. We systematically present available resources and optimal practices for wide use by experimental biomedical researchers.

Trials and tribulations of statistical significance in biochemistry and omics.

Over recent years many statisticians and researchers have highlighted that statistical inference would benefit from a better use and understanding of hypothesis testing, p-values, and statistical significance. We highlight three recommendations in the context of biochemical sciences. First recommendation: to improve the biological interpretation of biochemical data, do not use p-values (or similar test statistics) as thresholded values to select biomolecules. Second recommendation: to improve comparison among studies and to achieve robust knowledge, perform complete reporting of data. Third recommendation: statistical analyses should be reported completely with exact numbers (not as asterisks or inequalities). Owing to the high number of variables, a better use of statistics is of special importance in omic studies.

Are self-reported fertility preferences biased? Evidence from indirect elicitation methods.

Desired fertility measures are routinely collected and used by researchers and policy makers, but their self-reported nature raises the possibility of reporting bias. In this paper, we test for the presence of such bias by comparing responses to direct survey questions with indirect questions offering a varying, randomized, degree of confidentiality to respondents in a socioeconomically diverse sample of Nigerian women ([Formula: see text]). We find that women report higher fertility preferences when asked indirectly, but only when their responses afford them complete confidentiality, not when their responses are simply blind to the enumerator. Our results suggest that there may be fewer unintended pregnancies than currently thought and that the effectiveness of family planning policy targeting may be weakened by the bias we uncover. We conclude with suggestions for future work on how to mitigate reporting bias.

Turn-on RNA Mango Beacons for trans-acting fluorogenic nucleic acid detection.

The Mango I and II RNA aptamers have been widely used in vivo and in vitro as genetically encodable fluorogenic markers that undergo large increases in fluorescence upon binding to their ligand, TO1-Biotin. However, while studying nucleic acid sequences, it is often desirable to have trans-acting probes that induce fluorescence upon binding to a target sequence. Here, we rationally design three types of light-up RNA Mango Beacons based on a minimized Mango core that induces fluorescence upon binding to a target RNA strand. Our first design is bimolecular in nature and uses a DNA inhibition strand to prevent folding of the Mango aptamer core until binding to a target RNA. Our second design is unimolecular in nature, and features hybridization arms flanking the core that inhibit G-quadruplex folding until refolding is triggered by binding to a target RNA strand. Our third design builds upon this structure, and incorporates a self-inhibiting domain into one of the flanking arms that deliberately binds to, and precludes folding of, the aptamer core until a target is bound. This design separates G-quadruplex folding inhibition and RNA target hybridization into separate modules, enabling a more universal unimolecular beacon design. All three Mango Beacons feature high contrasts and low costs when compared to conventional molecular beacons, with excellent potential for in vitro and in vivo applications.

ReProMSig: an integrative platform for development and application of reproducible multivariable models for cancer prognosis supporting guideline-based transparent reporting.

Adequate reporting is essential for evaluating the performance and clinical utility of a prognostic prediction model. Previous studies indicated a prevalence of incomplete or suboptimal reporting in translational and clinical studies involving development of multivariable prediction models for prognosis, which limited the potential applications of these models. While reporting templates introduced by the established guidelines provide an invaluable framework for reporting prognostic studies uniformly, there is a widespread lack of qualified adherence, which may be due to miscellaneous challenges in manual reporting of extensive model details, especially in the era of precision medicine. Here, we present ReProMSig (Reproducible Prognosis Molecular Signature), a web-based integrative platform providing the analysis framework for development, validation and application of a multivariable prediction model for cancer prognosis, using clinicopathological features and/or molecular profiles. ReProMSig platform supports transparent reporting by presenting both methodology details and analysis results in a strictly structured reporting file, following the guideline checklist with minimal manual input needed. The generated reporting file can be published together with a developed prediction model, to allow thorough interrogation and external validation, as well as online application for prospective cases. We demonstrated the utilities of ReProMSig by development of prognostic molecular signatures for stage II and III colorectal cancer respectively, in comparison with a published signature reproduced by ReProMSig. Together, ReProMSig provides an integrated framework for development, evaluation and application of prognostic/predictive biomarkers for cancer in a more transparent and reproducible way, which would be a useful resource for health care professionals and biomedical researchers.

Sex reporting of cells used in cancer research: A systematic review.

Sex and gender disparities in biomedical research have been emphasized to improve scientific knowledge applied for the health of both men and women. Despite sex differences in cancer incidence, prognosis, and responses to therapeutic agents, mechanistic explanations at molecular levels are far from enough. Recent studies suggested that cell sex is an important biological variable due to differences in sex chromosome gene expression and differences in events associated with developmental biology. The objective of this study was to analyze the reporting of sex of cells used in cancer research using articles published in Cancer Cell, Molecular Cancer, Journal of Hematology & Oncology, Journal for ImmunoTherapy of Cancer, and Cancer Research in 2020, and to examine whether there exists any sex bias. We found that the percentage of cells with sex notation in the article was 36.5%. Primary cells exhibited higher sex notation compared to cell lines. A higher percentage of female cells were used in cell cultures with sex notation. Also, sex-common cells omitted sex description more often compared to sex-specific cells. None of the cells isolated from embryo and esophagus reported the cell sex in the article. Our results indicate cell sex report in cancer research is limited to a small proportion of cells used in the study. These results call for acknowledging the sex of cells to increase the applicability of biomedical research discoveries.

Association between immune checkpoint inhibitor and cytomegalovirus infection: A pharmacovigilance study based on the adverse event reporting system.

Immune checkpoint inhibitor (ICI)-induced adverse events due to excessive immune stimulation are problematic in immunotherapy. The activation of viral infection triggered by ICI-induced dysregulated immunity has been proposed; however, this association remains inconsistent. This study investigated the association between ICI administration and cytomegalovirus (CMV) infections, a pathogen linked to immune abnormalities and reactivation, using the Food and Drug Administration Adverse Event Reporting System. We used the crude data set and immunocompromise-free data set from the fourth quarter of 2012 to 2023. The disproportionality between CMV infection and ICI was analyzed using reporting odds ratio (ROR) and information component (IC) methodologies. Disproportionality between ipilimumab and nivolumab combination case and CMV infection was observed in the crude (ROR: 2.83, 95% confidence interval [CI]: 2.32-3.47; IC: 1.48, 95% CI: 1.14-1.73) and immunocompromise-free data set (ROR: 1.76, 95% CI: 1.33-2.33; IC: 0.80, 95% CI: 0.33-1.14), whereas disproportionality between other ICI and CMV infection was not observed in the immunocompromise-free data set. Multiple sensitivity analyses and time-scan analysis also revealed the consistent disproportionality between ipilimumab and nivolumab combination cases and CMV infection, regardless of the host's immune status. While further research is warranted to validate our findings, these results highlight new insights into ICI-induced viral infections and suggest the importance of considering the possibility of CMV infections during ipilimumab and nivolumab combination therapy, regardless of the host's immune status.

Assessing the Quality of Cause-of-Death Reporting Before and During the COVID-19 Pandemic.

This study assessed the quality of cause-of-death reporting in the US before and during the COVID-19 pandemic. We used the selection rate and the adjusted odds ratio (aOR) to analyze each cause identified by the National Center for Health Statistics as unsuitable for the underlying cause of death (UCOD). The selection rate was defined as the proportion of deaths with mention of a particular unsuitable UCOD on the death certificate where that cause was ultimately selected as the UCOD. Out of 36 unsuitable UCODs, 33 exhibited a significant decline in selection rates from 2019 to 2021. However, when deaths with mention of COVID-19 on the death certificate were excluded, only 19 causes revealed a significant decline. In analyses that controlled for the age of decedents, aORs in 2021 were significantly lower compared with 2019 for 26 causes, and this number decreased to 17 causes in analyses that excluded COVID-19-related deaths. In conclusion, the overall quality of COD reporting improved during the COVID-19 pandemic, attributable mainly to the fact that over one-tenth of the deaths were related to COVID-19. Yet, for deaths that did not involve COVID-19, improvements in the quality of COD reporting were less prominent for certain causes.

Combination of prostate volume and apparent diffusion coefficient can stratify patients with a PI-RADS score of 3 to reduce unnecessary prostate biopsies.

BACKGROUND: Nowadays, there are many patients who undergo unnecessary prostate biopsies after receiving a prostate imaging reporting and data system (PI-RADS) score of 3. Our purpose is to identify cutoff values of the prostate volume (PV) and minimum apparent diffusion coefficient (ADCmin) to stratify those patients to reduce unnecessary prostate biopsies. METHODS: Data from 224 qualified patients who received prostate biopsies from January 2019 to June 2023 were collected. The Mann-Whitney U test was used to compare non-normal distributed continuous variables, which were recorded as median (interquartile ranges). The correlation coefficients were calculated using Spearman's rank correlation analysis. Categorical variables are recorded by numbers (percentages) and compared by χ2 test. Both univariate and multivariate logistic regression analysis were used to determine the independent predictors. The receiver-operating characteristic curve and the area under the curve (AUC) were used to evaluate the diagnostic performance of clinical variables. RESULTS: Out of a total of 224 patients, 36 patients (16.07%) were diagnosed with clinically significant prostate cancer (csPCa), whereas 72 patients (32.14%) were diagnosed with any grade prostate cancer. The result of multivariate analysis demonstrated that the PV (p < 0.001, odds ratio [OR]: 0.952, 95% confidence interval [95% CI]: 0.927-0.978) and ADCmin (p < 0.01, OR: 0.993, 95% CI: 0.989-0.998) were the independent factors for predicting csPCa. The AUC values of the PV and ADCmin were 0.779 (95% CI: 0.718-0.831) and 0.799 (95% CI: 0.740-0.849), respectively, for diagnosing csPCa. After stratifying patients by PV and ADCmin, 24 patients (47.06%) with "PV < 55 mL and ADCmin < 685 µm2/s" were diagnosed with csPCa. However, only one patient (1.25%) with PV ≥ 55 mL and ADCmin ≥ 685 µm2/s were diagnosed with csPCa. CONCLUSIONS: In this study, we found the combination of PV and ADCmin can stratify patients with a PI-RADS score of 3 to reduce unnecessary prostate biopsies. These patients with "PV ≥ 55 mL and ADCmin ≥ 685 µm2/s" may safely avoid prostate biopsies.

Outcome reporting in studies on pregnant women with cardiac disease: a systematic review: Outcomes in studies on pregnancy and heart disease.

BACKGROUND: Although considerable variation in the reporting and definition of outcomes in cardio-obstetric studies is known, the extent of this variation has not been documented. The primary objective of this systematic review was to highlight this variation and inform the development of a Core Outcome Set for studies on Cardiac disease in Pregnancy (COSCarP). METHODS: Medline, Embase, Web of Science and Cochrane Central databases were searched from 1980 to 2018 to identify all English-language publications on pregnancy and heart disease. Title/abstract screening and data extraction which included details on the study, patient population, and all reported outcomes, was performed in duplicate by two reviewers. As the aim of the review was to identify variation in outcome reporting, risk-of-bias assessment was not performed. The study protocol was registered on PROSPERO (CRD42016038218). RESULTS: The final analysis included 422 cardio-obstetric studies. Maternal mortality or survival were reported in 232/422 studies, with inconsistency in terms of cause of death [all-cause (n=65), cardiac (n=55) or obstetric (n=10)] or timeframe (ranging from in-hospital mortality (n=11) to mortality 5 years following pregnancy). In 95/232 studies (41%), the cause and timeframe were not specified. Similar inconsistencies in reporting and definitions were noted for outcomes such as heart failure (n=298), perinatal loss (n=296), fetal growth (n=221), bleeding (n=205), arrhythmias (n=202), preterm birth (n=191), thromboembolism (n=153) and hypertensive disorders (n=122). Functioning / life-impact and adverse effects of treatment were sparingly reported in cardio-obstetric studies. CONCLUSIONS: This systematic review hopes to create awareness among cardio-obstetric teams about the inconsistencies in reporting and defining outcomes which makes it difficult to compare studies and perform meta-analyses. COSCarP which is being developed through international consensus between patients and care-providers will provide cardio-obstetrics teams with a minimal set of outcomes to be reported in future cardio-obstetric studies.