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Survival from pancreatic cancer is low worldwide. In the US, the 5-year relative survival has been slightly higher for women, whites and younger patients than for their counterparts, and differences in age and stage at diagnosis [Corrections added Nov 16, 2022, after first online publication: a new affiliation is added to Maja Nikšić] may contribute to this pattern. We aimed to examine trends in survival by race, stage, age and sex for adults (15-99 years) diagnosed with pancreatic cancer in the US.This population-based study included 399,427 adults registered with pancreatic cancer in 41 US state cancer registries during 2001-2014, with follow-up to December 31, 2014. We estimated age-specific and age-standardized net survival at 1 and 5 years.Overall, 12.3% of patients were blacks, and 84.2% were whites. About 9.5% of patients were diagnosed with localized disease, but 50.5% were diagnosed at an advanced stage; slightly more among blacks, mainly among men. No substantial changes were seen over time (2001-2003, 2004-2008, 2009-2014). In general, 1-year net survival was higher in whites than in blacks (26.1% vs. 22.1% during 2001-2003, 35.1% vs. 31.4% during 2009-2014). This difference was particularly evident among patients with localized disease (49.6% in whites vs. 44.6% in blacks during 2001-2003, 60.1% vs. 55.3% during 2009-2014). The survival gap between blacks and whites with localized disease was persistent at 5 years after diagnosis, and it widened over time (from 24.0% vs. 21.3% during 2001-2003 to 39.7% vs. 31.0% during 2009-2014). The survival gap was wider among men than among women.Gaps in 1- and 5-year survival between blacks and whites were persistent throughout 2001-2014, especially for patients diagnosed with a localized tumor, for which surgery is currently the only treatment modality with the potential for cure.

Background: In a 2018 descriptive study, cancer incidence in children (age 0–19) in diagnosis years 2003 to 2014 was reported as being highest in New Hampshire and in the Northeast region. Methods: Using the Cancer in North America (CiNA) analytic file, we tested the hypotheses that incidence rates in the Northeast were higher than those in other regions of the United States either overall or by race/ethnicity group, and that rates in New Hampshire were higher than the Northeast region as a whole. Results: In 2003 to 2014, pediatric cancer incidence was significantly higher in the Northeast than other regions of the United States overall and among non-Hispanic Whites and Blacks, but not among Hispanics and other racial minorities. However, there was no significant variability in incidence in the states within the Northeast overall or by race/ethnicity subgroup. Overall, statistically significantly higher incidence was seen in the Northeast for lymphomas [RR, 1.15; 99% confidence interval (CI), 1.10–1.19], central nervous system neoplasms (RR, 1.12; 99% CI, 1.07–1.16), and neuroblastoma (RR, 1.13; 99% CI, 1.05–1.21). Conclusions: Pediatric cancer incidence is statistically significantly higher in the Northeast than in the rest of the United States, but within the Northeast, states have comparable incidence. Differences in cancer subtypes by ethnicity merit further investigation. Impact: Our analyses clarify and extend previous reports by statistically confirming the hypothesis that the Northeast has the highest pediatric cancer rates in the country, by providing similar comparisons stratified by race/ethnicity, and by assessing variability within the Northeast.

Supplementary Figures 1-2 and Tables 1-7

In a randomized trial of folic acid supplementation for the prevention of colorectal adenomas, we previously found indications of increased risk during later treatment and follow-up. This could have been due to the unmetabolized folic acid (UFA) or natural reduced and methylated folates (mF) to which it is metabolized. In post hoc analyses, we measured mF (the sum of 5-methyl-tetrahydrofolate and 4-alfa-hydroxy-5-methyl-THF) and UFA concentrations in the serum of 924 participants. Using binomial regression models with a log link, we assessed the associations between plasma mF or UFA and adenoma occurrence. We found no association between plasma mF or UFA and overall adenoma risk. However, during later follow-up, the prespecified, composite endpoint of high-risk findings (advanced or multiple adenomas) was positively associated with plasma mF (Plinear trend = 0.009), with a 58% increased risk for participants in the upper versus lowest quartile. An irregular association was seen with plasma UFA, with suggestions of an inverse trend (Plinear trend=0.049). A modest, significant inverse association was also seen between mF and risk of serrated lesions, with a 39% lower risk for upper versus lower quartile participants (Plinear trend = 0.03). In conclusion, during the later follow-up period in which folic acid supplementation was previously seen to increase the risk of advanced and multiple adenomas, higher serum mF was associated with a higher risk of multiple and/or advanced adenomas, but no clear indication that UFA played a direct role. There were indications that higher mF was associated with reduced risk of serrated polyps. Cancer Prev Res; 10(8); 451–8. ©2017 AACR.

Supplementary Table 1

The oxysterol 27-hydroxycholesterol (27-OHC) is an endogenous selective estrogen receptor modulator implicated in breast cancer etiology. It is unknown whether circulating 27-OHC is associated with colorectal neoplasia risk. Circulating 27-OHC was measured using LC/MS in fasting plasma collected at baseline from participants of the Vitamin D/Calcium Polyp Prevention Study, a completed randomized clinical trial. Participants were between 45 and 75 years old, recently diagnosed with ≥1 colorectal adenoma, and followed for new colorectal polyps during colonoscopic surveillance. Adjusted risk ratios (RR) with 95% confidence intervals (CI) of new colorectal polyps were estimated for quartiles of circulating 27-OHC using log-linear regression for repeated outcomes. Polyp phenotypes included any adenomas, advanced adenomas, hyperplastic polyps, and sessile serrated adenomas/polyps. Circulating 27-OHC was measured at baseline for 1,246 participants. Compared with participants with circulating 27-OHC below the first quartile (Prevention Relevance:This study found that plasma concentration of 27-hydroxycholesterol, a metabolite of cholesterol that regulates lipid metabolism and acts as a selective estrogen receptor modulator, is associated with the risk of developing precursor lesions for colorectal cancer.

Additional analyses of folate and adenoma outcomes.

Vitamin D and calcium supplementation are postulated to have chemopreventive effects against colorectal neoplasia, yet in our previously reported randomized trial, there was no overall efficacy of calcium and/or vitamin D3 against colorectal adenoma recurrence. It is possible vitamin D3 and calcium chemopreventive effects are not detectable until beyond the 3- to 5-year follow-up captured in that trial. Accordingly, we explored possible vitamin D and calcium effects on posttreatment (observational) adenoma occurrence. In this secondary analysis of the observational follow-up phase of the Vitamin D/Calcium Polyp Prevention Study, participants who completed the treatment phase were invited to be followed for one additional surveillance colonoscopy cycle. We evaluated adenoma occurrence risk at surveillance colonoscopy, with a mean of 55 ± 15 months after treatment follow-up, according to randomized treatment with vitamin D versus no vitamin D, calcium versus no calcium, and calcium plus vitamin D versus calcium alone. Secondary outcomes included advanced and multiple adenomas. Among the 1,121 participants with observational follow-up, the relative risk (95% confidence interval, CI) of any adenoma was 1.04 (0.93–1.17) for vitamin D versus no vitamin D; 0.95 (0.84–1.08) for calcium versus no calcium; 1.07 (0.91–1.25) for calcium plus vitamin D versus calcium; and 0.96 (0.81–1.15) for calcium plus vitamin D versus neither. Risks of advanced or multiple adenomas also did not differ by treatment. Our results do not support an association between supplemental calcium and/or vitamin D3 for 3 to 5 years and risk of recurrent colorectal adenoma at an average of 4.6 years after treatment.

Background: Practice facilitators (PFs) oversee quality improvement (QI) initiatives aimed at enhancing patient outcomes and operational efficiencies. Little research has explored the amount of time PFs spend with practices on QI activities. This short report expands on previously published work which detailed a 12-month practice facilitation intervention focusing on improving hypertension control among people living in rural settings in the southeastern USA. This report analyzes data on the time PFs spent to guide 32 primary care practices in implementing QI activities to support enhanced outcomes in patients with high blood pressure. Methods: As part of the parent study, the Southeastern Collaboration to Improve Blood Pressure Control trial, four PFs documented time spent: 1) driving to support practices; 2) working on-site with staff and clinicians; and 3) communicating remotely (phone, email, or video conference) with practice members. We analyzed the data using descriptive statistics to help understand time devoted to individual and aggregated tasks. Additionally, we explored correlations between practice characteristics and time spent with PFs. Results: An average of 130 (SD 65) minutes was spent per visit driving to and from individual practices. The average time spent on-site per visit with practices was 87 (SD 37) minutes, while an average of 17 (SD 12) minutes was spent on individual remote communications. During the 12-month intervention, 1131 remote communications were conducted with practices. PFs spent most of their time with clinical staff members (n=886 instances) or with practice managers alone (n=670 instances) while relatively few on-site visits were conducted with primary care providers alone (n=15). In 19 practices, no communications were solely with providers. No significant correlations were found between time spent on PF activities and a practices’ percent of Medicaid and uninsured patients, staff-provider ratio, or FQHC status. Conclusions: PFs working with practices serving rural patients with hypertension devote substantial time to driving, highlighting the importance of optimizing a balance between time spent on-site vs. communicating remotely. Most time spent was with clinical staff, not providers. These findings may be useful to researchers and business leaders who design, test, and implement efficient facilitation services. Trial registration: NIH ClinicalTrials.gov. NCT number: NCT02866669. Registered 15 August 2016. https://clinicaltrials.gov/ct2/show/NCT02866669?term=NCT02866669&draw=2&rank=1. NHLBI AWARD number: PCS-1UH3HL130691.

Author(s): Sherman, Jeffrey; Rees, Heather; Fujita, Kentaro; Han, H Anna; Sklar, Asael Y | Abstract: Previous research has found that construal level—how abstractly or concretely people represent events—can impact implicit evaluations. Abstract high-level construal (vs. concrete low-level construal) promotes evaluative responses consistent with global (strongly held, long-term) rather than local (short-term, situational) goals. It remains unclear by what cognitive process(es) this occurs. In this paper, we examine two possibilities. High-level construal might enhance the unintended influence of activated evaluative associations or facilitate the detection and implementation of intentional responses. To examine these possibilities, the current study applies a multinomial processing tree model to data from Fujita and Han (2009). Results suggest that high-level construal facilitates goal-consistent evaluations by increasing both the unintentional influence of activated goal-consistent positive associations and the intentional detection of and implementation of accurate responding to goal-relevant stimuli. These findings extend our understanding of how construal level promotes goal consistent evaluations.

Prion diseases are fatal and infectious neurodegenerative diseases in humans and other mammals caused by templated misfolding of the endogenous prion protein (PrP). Although there is currently no vaccine or therapy against prion disease, several classes of small-molecule compounds have been shown to increase disease-free incubation time in prion-infected mice. An apparent obstacle to effective anti-prion therapy is the emergence of drug-resistant strains during static therapy with either single compounds or multi-drug combination regimens. Here, we treated scrapie-infected mice with dynamic regimens that alternate between different classes of anti-prion drugs. The results show that alternating regimens containing various combinations of Anle138b, IND24 and IND116135 reduce the incidence of combination drug resistance, but do not significantly increase long-term disease-free survival compared to monotherapy. Furthermore, the alternating regimens induced regional vacuolation profiles resembling those generated by a single component of the alternating regimen, suggesting the emergence of strain dominance.

This case study presents a 31-yr-old male weightlifter without known neuromuscular disease who presented with 5 wks of atraumatic, constant fasciculations of his right teres major muscle without recent injury. Electromyography identified fasciculation potentials within the teres major and pronator teres, suggesting an acute C6 radiculopathy, although a cervical magnetic resonance imaging demonstrated no significant neuroforaminal stenosis. Trigger point injections and multiple medications failed to stop the fasciculations. Under electromyography and ultrasound guidance, he was focally injected with botulinum toxin to the teres major 10 wks from initial onset with subsequent complete resolution of the symptoms and no side effects.

The International Multicenter Registry for Hyperbaric Oxygen Therapy (International Report Registered Identifier DERR1-10.2196/18857) was established in 2011 to capture outcomes and complications data for both Undersea and Hyperbaric Medical Society (UHMS) approved and selected unapproved hyperbaric oxygen (HBO2) therapy indications.A Research Electronic Data Capture (REDCap) template was designed and distributed to all participating centers for prospective data collection. Centers contributed de-identified demographic, treatment, complications, and outcome data. This report provides summary data on sites and enrollment, as well as pre- and post-treatment data on quality of life (EQ-5D-5L questionnaire), head and neck radiationoutcomes, non-healing wounds (Strauss score), and idiopathic sudden sensorineural hearing loss. Data were analyzed mainly using the Wilcoxon signed-rank test.Twenty-two centers contributed data for 2,880 patients. The most common UHMS-approved indication was delayed radiation injury, followed by enhancement of wound healing, and carbon monoxide poisoning. One hundred and twenty-five patients were treated for non-UHMS approved indications. Quality of life, head and neck radiation symptoms, Strauss wound scores, and hearing were significantly improved after HBO2. Complication rates were low and comparable to previous reports. The registry also offered the ability to analyze factors that affect outcomes, such as smoking and severity of hearing loss.The registry accrues prospective data on defined outcomes from multiple centers and allows for analysis of factors affecting outcomes. This registry does not have a control group, which is a limitation. Nevertheless, the registry provides a unique, comprehensive dataset on HBO2 outcomes from multiple centers internationally.

Background: A 2017 meta-analysis of data from 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infections (ARIs) revealed a protective effect of this intervention. We aimed to examine the link between vitamin D supplementation and prevention of ARIs in an updated meta-analysis. Methods: For this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry for studies listed from database inception to May 1, 2020. Double-blind RCTs of vitamin D3, vitamin D2, or 25-hydroxyvitamin D (25[OH]D) supplementation for any duration, with a placebo or low-dose vitamin D control, were eligible if they had been approved by a research ethics committee, and if ARI incidence was collected prospectively and prespecified as an efficacy outcome. Studies reporting results of long-term follow-up of primary RCTs were excluded. Aggregated study-level data, stratified by baseline 25(OH)D concentration and age, were obtained from study authors. Using the proportion of participants in each trial who had one or more ARIs, we did a random-effects meta-analysis to obtain pooled odds ratios (ORs) and 95% CIs to estimate the effect of vitamin D supplementation on the risk of having one or more ARIs (primary outcome) compared with placebo. Subgroup analyses were done to estimate whether the effects of vitamin D supplementation on the risk of ARI varied according to baseline 25(OH)D concentration (vs 25·0–49·9 nmol/L vs 50·0–74·9 nmol/L vs >75·0 nmol/L), vitamin D dose (daily equivalent of vs 400–1000 IU vs 1001–2000 IU vs >2000 IU), dosing frequency (daily vs weekly vs once per month to once every 3 months), trial duration (≤12 months vs >12 months), age at enrolment (vs 1·00–15·99 years vs 16·00–64·99 years vs ≥65·00 years), and presence versus absence of airway disease (ie, asthma only, COPD only, or unrestricted). Risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool. The study was registered with PROSPERO, CRD42020190633. Findings: We identified 1528 articles, of which 46 RCTs (75 541 participants) were eligible. Data for the primary outcome were obtained for 48 488 (98·1%) of 49 419 participants (aged 0–95 years) in 43 studies. A significantly lower proportion of participants in the vitamin D supplementation group had one or more ARIs (14 332 [61·3%] of 23 364 participants) than in the placebo group (14 217 [62·3%] of 22 802 participants), with an OR of 0·92 (95% CI 0·86–0·99; 37 studies; I2=35·6%, pheterogeneity=0·018). No significant effect of vitamin D supplementation on the risk of having one or more ARIs was observed for any of the subgroups defined by baseline 25(OH)D concentration. However, protective effects of supplementation were observed in trials in which vitamin D was given in a daily dosing regimen (OR 0·78 [95% CI 0·65–0·94]; 19 studies; I2=53·5%, pheterogeneity=0·003), at daily dose equivalents of 400–1000 IU (0·70 [0·55–0·89]; ten studies; I2=31·2%, pheterogeneity=0·16), for a duration of 12 months or less (0·82 [0·72–0·93]; 29 studies; I2=38·1%, pheterogeneity=0·021), and to participants aged 1·00–15·99 years at enrolment (0·71 [0·57–0·90]; 15 studies; I2=46·0%, pheterogeneity=0·027). No significant interaction between allocation to the vitamin D supplementation group versus the placebo group and dose, dose frequency, study duration, or age was observed. In addition, no significant difference in the proportion of participants who had at least one serious adverse event in the vitamin supplementation group compared with the placebo group was observed (0·97 [0·86–1·07]; 36 studies; I2=0·0%, pheterogeneity=0·99). Risk of bias within individual studies was assessed as being low for all but three trials. Interpretation: Despite evidence of significant heterogeneity across trials, vitamin D supplementation was safe and overall reduced the risk of ARI compared with placebo, although the risk reduction was small. Protection was associated with administration of daily doses of 400–1000 IU for up to 12 months, and age at enrolment of 1·00–15·99 years. The relevance of these findings to COVID-19 is not known and requires further investigation. Funding: None.

It is unclear why some melanomas aggressively metastasize while others remain indolent. Available studies employing multi-omic profiling of melanomas are based on large primary or metastatic tumors. We examine the genomic landscape of early-stage melanomas diagnosed prior to the modern era of immunological treatments. Untreated cases with Stage II/III cutaneous melanoma were identified from institutions throughout the United States, Australia and Spain. FFPE tumor sections were profiled for mutation, methylation and microRNAs. Preliminary results from mutation profiling and clinical pathologic correlates show the distribution of four driver mutation sub-types: 31% BRAF; 18% NRAS; 21% NF1; 26% Triple Wild Type. BRAF mutant tumors had younger age at diagnosis, more associated nevi, more tumor infiltrating lymphocytes, and fewer thick tumors although at generally more advanced stage. NF1 mutant tumors were frequent on the head/neck in older patients with severe solar elastosis, thicker tumors but in earlier stages. Triple Wild Type tumors were predominantly male, frequently on the leg, with more perineural invasion. Mutations in TERT, TP53, CDKN2A and ARID2 were observed often, with TP53 mutations occurring particularly frequently in the NF1 sub-type. The InterMEL study will provide the most extensive multi-omic profiling of early-stage melanoma to date. Initial results demonstrate a nuanced understanding of the mutational and clinicopathological landscape of these early-stage tumors.

People often form impressions of others in contexts where both relatively static demographic cues (e.g., age, race, gender) and situationally flexible, dynamic cues (e.g., emotion expressions) are available. We examined whether and how attending to gender (male, female) versus emotion expression (neutral, smiling) affects threat-based person impressions. In three experiments, we heightened the salience of either gender categories or emotion categories in a sequential priming task. Category salience consistently moderated the use of both categories in threat impressions. The effect of gender (emotion) categories was stronger when attention was directed to gender (emotion) than when attention was directed to emotion (gender); however, category salience did not eliminate the use of either category. Implications for models of person construal and bias in person impressions are discussed.

IntroductionWe are conducting a multicenter study to identify classifiers predictive of disease-specific survival in patients with primary melanomas. Here we delineate the unique aspects, challenges, and best practices for optimizing a study of generally small-sized pigmented tumor samples including primary melanomas of at least 1.05mm from AJTCC TNM stage IIA-IIID patients. This ongoing study will target 1,000 melanomas within the international InterMEL consortium. We also evaluated tissue-derived predictors of extracted nucleic acids’ quality and success in downstream testing.MethodsFollowing a pre-established protocol, participating centers ship formalin-fixed paraffin embedded (FFPE) tissue sections to Memorial Sloan Kettering Cancer Center for the centralized handling, dermatopathology review and histology-guided coextraction of RNA and DNA. Samples are distributed for evaluation of somatic mutations using next gen sequencing (NGS) with the MSK-IMPACT™ assay, methylation-profiling (array), and miRNA expression (Nanostring nCounter).ResultsSufficient material was obtained for screening of miRNA expression in 683/685 (99%) eligible melanomas, methylation in 467 (68%), and somatic mutations in 560 (82%). In 446/685 (65%) cases, aliquots of RNA/DNA were sufficient for testing with all three platforms. Among samples evaluated by the time of this analysis, the mean NGS coverage was 249x, 59 (18.6%) samples had coverage below 100x, and 41/414 (10%) failed methylation QC due to low intensity probes or insufficient Meta-Mixed Interquartile (BMIQ)- and single sample (ss)- Noob normalizations. Six of 683 RNAs (1%) failed Nanostring QC due to the low proportion of probes above the minimum threshold. Age of the FFPE tissue blocks (pConclusionOur experience with many archival tissues demonstrates that with careful management of tissue processing and quality control it is possible to conduct multi-omic studies in a complex multi-institutional setting for investigations involving minute quantities of FFPE tumors, as in studies of early-stage melanoma.

BackgroundLight microscopy remains a standard method for the detection of malaria parasites in clinical cases but training of staff to a WHO level 2 or higher requires considerable time. Moreover, excessive workflow can rapidly lead to fatigue and impact performance, even for a highly skilled technician. An automated microscopy tool that can perform consistent, accurate diagnoses could be an effective aid in clinics with limited access to highly skilled microscopists, where the daily number of cases are excessively high for the number of available technicians or in multi-site studies where consistency between sites is essential. The EasyScan GO is an automated scanning microscope combined with machine learning software designed to detect malaria parasites in field-prepared Giemsa-stained blood films. This study evaluates the performance of the EasyScan GO to determine its ability to detect, quantify and identify the species of parasite present in Giemsa-stained blood films compared with expert light microscopy.MethodsTravelers returning to the UK and testing positive for malaria parasite infection were screened for eligibility and enrolled into the study. Surplus blood samples from enrolled patients were subsequently used to make Giemsa-stained thick and thin slide smears that were assessed by expert light microscopy and the EasyScan GO to determine parasite density and species. Blood samples were also assessed by real time PCR and nested PCR (Snounou) to confirm parasite density and species present and to resolve any discrepancy between manual microscopy and the EasyScan GO.ResultsWhen compared to light microscopy, the EasyScan GO exhibited a sensitivity of 90% (95% CI: 82–95%) and a specificity of 89% (95% CI: 86–90%). Of the 95 samples labelled positive by both light microscopy and the EasyScan GO, manual microscopy identified 83 as Plasmodium falciparum (P. falciparum) and 12 as non-P. falciparum. The EasyScan GO correctly reported P. falciparum for 82 out of the 83 P. falciparum samples and non-P. falciparum for 11 out of 12 non-P. falciparum samples. However, it failed to distinguish between non-P. falciparum species, reporting all non-P. falciparum samples as P. vivax. EasyScan GO calculated parasite densities were within +/-25% of the light microscopy densities for 33% of samples between 200 and 2000 p/µL, falling short of WHO level 1 (expert) manual microscopy competency (50% of samples should be within +/-25% of the true parasitaemia).ConclusionsThis study shows that the EasyScan GO can be proficient in detecting malaria parasites in Giemsa-stained blood films relative to expert manual light microscopy and can accurately distinguish between P. falciparum and non-P. falciparum species. Performance of the device at low parasite densities, distinguishing between non-P. falciparum species and accurate quantitation of parasitaemias require further development and evaluation. Nonetheless, the data shown here suggests that the EasyScan GO could provide assistance as a tool for malaria diagnosis in settings where work load is frequently higher than manageable or where access to expert microscopy is difficult.

Does information about how other people feel about COVID-19 vaccination affect immunization intentions? We conducted preregistered survey experiments in Great Britain (5,456 respondents across 3 survey waves from September 2020 to February 2021), Canada (1,315 respondents in February 2021), and the state of New Hampshire in the United States (1,315 respondents in January 2021). The experiments examine the effects of providing accurate public opinion information to people about either public support for COVID-19 vaccination (an injunctive norm) or public beliefs that the issue is contentious. Across all 3 countries, exposure to this information had minimal effects on vaccination intentions even among people who previously held inaccurate beliefs about support for COVID-19 vaccination or its perceived contentiousness. These results suggest that providing information on public opinion about COVID vaccination has limited additional effect on people’s behavioral intentions when public discussion of vaccine uptake and intentions is highly salient.

The oxysterol 27-hydroxycholesterol (27-OHC) is an endogenous selective estrogen receptor modulator implicated in breast cancer etiology. It is unknown whether circulating 27-OHC is associated with colorectal neoplasia risk. Circulating 27-OHC was measured using LC/MS in fasting plasma collected at baseline from participants of the Vitamin D/Calcium Polyp Prevention Study, a completed randomized clinical trial. Participants were between 45 and 75 years old, recently diagnosed with ≥1 colorectal adenoma, and followed for new colorectal polyps during colonoscopic surveillance. Adjusted risk ratios (RR) with 95% confidence intervals (CI) of new colorectal polyps were estimated for quartiles of circulating 27-OHC using log-linear regression for repeated outcomes. Polyp phenotypes included any adenomas, advanced adenomas, hyperplastic polyps, and sessile serrated adenomas/polyps. Circulating 27-OHC was measured at baseline for 1,246 participants. Compared with participants with circulating 27-OHC below the first quartile ( Prevention Relevance: This study found that plasma concentration of 27-hydroxycholesterol, a metabolite of cholesterol that regulates lipid metabolism and acts as a selective estrogen receptor modulator, is associated with the risk of developing precursor lesions for colorectal cancer.

Previous studies of serum 25-hydroxyvitamin D (25(OH)D) in relation to melanoma have shown conflicting results. We conducted a nested case–control study of 708 cases and 708 controls, using prediagnostically collected serum, to study 25(OH)D and melanoma risk in the population-based Janus Serum Bank Cohort. Stratified Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for ultraviolet radiation (UVR) indicators and stratified by ambient UVB of residence and body mass index (BMI). Non-linear associations were studied by restricted cubic splines. Missing data were handled with multiple imputation by chained equations. We found an HR of melanoma risk of 1.01 (95% CI: 0.99, 1.04) and an HRimputed of 1.02 (95% CI: 1.00, 1.04) per 5-nmol/L increase. The spline model showed exposure-risk curves with significantly reduced melanoma risk between 60 and 85 nmol/L 25(OH)D (reference 50 nmol/L). Non-significant J-shaped curves were found in sub-analyses of subjects with high ambient UVB of residence and of subjects with BMI 2. Our data did not yield persuasive evidence for an association between 25(OH)D and melanoma risk overall. Serum levels within the medium range might be associated with reduced risk, an association possibly mediated by BMI.

A major challenge in the study of high-impact, low-frequency procedures in trauma is the lack of accurate data for time-sensitive processes of care. Trauma video review offers a possible solution, allowing investigators to collect extremely granular time-stamped data. Using resuscitative thoracotomy as a model, we compared data collected using review of audiovisual recordings to data prospectively collected in real time with the hypothesis that data collected using video review would be subject to less missingness and bias.We conducted a prospective cohort study of patients undergoing resuscitative thoracotomy at a single urban academic level 1 trauma center. Key data on the timing and completion of procedural milestones of resuscitative thoracotomy were collected using video review and prospective collection. We used McNemar's test to compare proportions of missing data between the 2 methods and calculated bias in time measurements for prospective collection with respect to video review. Statistical analyses were performed using Stata v. 15.0 (College Station, TX).We included 51 subjects (88% Black, 82% male, 90% injured by gunshot wounds) over the study period. Missingness in resuscitative thoracotomy procedural milestone time measurements ranged from 34% to 63% for prospective collection and 0 to 8% for video review and was less missing for video review for all key variables (Plt; .001). When not missing, bias in data collected by prospective collection was 10% to 43% compared with data collected by video review.The data collected using video review have less missingness and bias than prospective collection data collected by trained research assistants. Audiovisual recording should be the gold standard for data collection for the study of time-sensitive processes of care in resuscitation.

Evaluating metagenomic software is key for optimizing metagenome interpretation and focus of the Initiative for the Critical Assessment of Metagenome Interpretation (CAMI). The CAMI II challenge engaged the community to assess methods on realistic and complex datasets with long- and short-read sequences, created computationally from around 1,700 new and known genomes, as well as 600 new plasmids and viruses. Here we analyze 5,002 results by 76 program versions. Substantial improvements were seen in assembly, some due to long-read data. Related strains still were challenging for assembly and genome recovery through binning, as was assembly quality for the latter. Profilers markedly matured, with taxon profilers and binners excelling at higher bacterial ranks, but underperforming for viruses and Archaea. Clinical pathogen detection results revealed a need to improve reproducibility. Runtime and memory usage analyses identified efficient programs, including top performers with other metrics. The results identify challenges and guide researchers in selecting methods for analyses., Nature Methods, 19 (8), ISSN:1548-7105, ISSN:1548-7091

Background: Antibiotics may increase colorectal neoplasia risk by modifying the gut microbiome. It is unknown whether use is associated with the risk of new colorectal adenomas among individuals with prior adenomas. Methods: We performed a secondary analysis of four randomized clinical trials for the chemoprevention of colorectal adenomas. Participants self-reported all currently used prescription drugs shortly after an initial colorectal adenoma diagnosis and two or three times a year thereafter over 3 to 5 years of follow-up. We estimated adjusted risk ratios (RR) with 95% confidence intervals (CI) for incident adenomas, analyzing the four trials together. Results: Cumulatively, the four trials enrolled 5,174 participants (3,491 men and 1,683 women), of whom 4,769 (92%) completed ≥1 follow-up colonoscopy. A total of 763 (15%) participants reported using oral antibiotics on ≥2 occasions. Overall, 39% of those using oral antibiotics at least twice developed new colorectal adenomas compared with 40% of those with no use or a single report of use (RR, 0.99; 95% CI, 0.90–1.10). No statistically significant associations were found in study-specific analyses, and results were similar for high- and low-risk adenoma findings, antibiotic class, anatomic location of adenomas, and analyses excluding those with interim colorectal exams. Conclusions: Oral antibiotic use during colonoscopic surveillance after an initial adenoma diagnosis was not associated with risk of these polyps. Impact: Any changes to the gut microbiome as a consequence of oral antibiotic use during surveillance may not affect the development of metachronous colorectal adenomas.

Earliness and ripening behavior are important attributes of fruits on and off the vine, and affect quality and preference of both growers and consumers. Fruit ripening is a complex physiological process that involves metabolic shifts affecting fruit color, firmness, and aroma production. Melon is a promising model crop for the study of fruit ripening, as the full spectrum of climacteric behavior is represented across the natural variation. Using Recombinant Inbred Lines (RILs) population derived from the parental lines “Dulce” (reticulatus, climacteric) and “Tam Dew” (inodorus, non-climacteric) that vary in earliness and ripening traits, we mapped QTLs for ethylene emission, fruit firmness and days to flowering and maturity. To further annotate the main QTL intervals and identify candidate genes, we used Oxford Nanopore long-read sequencing in combination with Illumina short-read resequencing, to assemble the parental genomes de-novo. In addition to 2.5 million genome-wide SNPs and short InDels detected between the parents, we also highlight here the structural variation between these lines and the reference melon genome. Through systematic multi-layered prioritization process, we identified 18 potential polymorphisms in candidate genes within multi-trait QTLs. The associations of selected SNPs with earliness and ripening traits were further validated across a panel of 177 diverse melon accessions and across a diallel population of 190 F1 hybrids derived from a core subset of 20 diverse parents. The combination of advanced genomic tools with diverse germplasm and targeted mapping populations is demonstrated as a way to leverage forward genetics strategies to dissect complex horticulturally important traits.

Background: In 2019, ranitidine was withdrawn due to high levels of N-nitrosodimethylamine, a probable human carcinogen. The risk of bladder and kidney cancer in ranitidine users, however, remains unclear. Methods: In a Danish nationwide cohort study, we included adults (18 years or older) without previous cancer, who between 1996 and 2008 redeemed at least two prescriptions for ranitidine and, as two separate comparison cohorts, patients with at least two prescriptions for other H2-receptor antagonists (H2-blockers), or proton pump inhibitors (PPI). Follow-up for bladder or kidney cancer started at date of the second prescription and continued to date of cancer, death, emigration, or December 31, 2018, whichever occurred first. We used propensity scores for ranitidine use to compute stabilized inverse probability of treatment (sIPT) weights and used Cox regression to compute crude and weighted HRs. Results: We identified 31,393 initiators of ranitidine, 65,384 initiating other H2-blockers, and 509,849 initiating PPI. Compared with other H2-blockers, the crude HR for bladder cancer was 1.33 [95% confidence interval (CI): 1.15–1.55], but sIPT weighting attenuated this to 1.11 (95% CI: 0.95–1.29). Compared with PPI initiators, the weighted HR was 1.24 (95% CI: 1.04–1.48). For kidney cancer, the weighted HR was 0.89 (95% CI: 0.72–1.10) compared with users of H2-blockers and 0.87 (95% CI: 0.67–1.13) compared with users of PPI. Conclusions: Our findings did not suggest a substantial increase in bladder or kidney cancer occurrence in ranitidine users. Impact: These findings are reassuring for previous ranitidine users.