Abstract. Interest in quantifying linkage disequilibrium (LD, the nonrandom association of alleles at different loci) has skyrocketed in recent years as re

A cognitive bias is an umbrella term for systematic but flawed patterns of response to judgment and decision problems, and those patterns are predictably nonrandom rather than random mistakes. Biases exist largely because the brain relies on fast mental shortcuts, called heuristics, to cope with limited processing capacity, trading some accuracy for speed. Why Your Brain Takes Shortcuts Your mind has a finite ability to store and recall information, so it cannot weigh every relevant fact before each inference or decision.

In blood plasma, cfDNA molecules are typically short double-stranded fragments (mode of ~167 bp) generated by nonrandom chromatin cleavage, often exhibiting single-stranded overhangs at 5′ or 3′ termini (Fig. 1a)14,22,23. During the typical end repair of double-stranded DNA molecules being prepared for methylation libraries before adapter ligation, the 5′ overhangs are filled in through synthesis templated by the opposing strand, whereas 3′ overhangs are cleaved off to generate blunt ends (Fig. 1a and Extended Data Fig. 1a). During this process, unmethylated cytosines are incorporated into newly extended strands at the 3′ termini, irrespective of native cfDNA methylation (Fig. 1a and Extended Data Fig. 1a). Therefore, all cytosines, including CpGs, of newly synthesized strands become completely unmethylated at the 3′ ends, erasing the native methylation status of these regions upon repair and amplification. To quantify these distortions, we performed EM-seq cfDNA methylation profiling in three healthy adults, tracking individual double-stranded DNA duplexes using customized duplex adapters (Fig. 1b, Extended Data Fig. 1b and Supplementary Table 1). As expected, CpG methylation was substantially higher near the 5′ ends of cfDNA molecules (corresponding to R1) than near the 3′ ends (corresponding to R2), with the magnitude varying with the length of newly synthesized...

In blood plasma, cfDNA molecules are typically short double-stranded fragments (mode of ~167 bp) generated by nonrandom chromatin cleavage, often exhibiting single-stranded overhangs at 5′ or 3′ termini (Fig. 1a)14,22,23. During the typical end repair of double-stranded DNA molecules being prepared for methylation libraries before adapter ligation, the 5′ overhangs are filled in through synthesis templated by the opposing strand, whereas 3′ overhangs are cleaved off to generate blunt ends (Fig. 1a and Extended Data Fig. 1a). During this process, unmethylated cytosines are incorporated into newly extended strands at the 3′ termini, irrespective of native cfDNA methylation (Fig. 1a and Extended Data Fig. 1a). Therefore, all cytosines, including CpGs, of newly synthesized strands become completely unmethylated at the 3′ ends, erasing the native methylation status of these regions upon repair and amplification. To quantify these distortions, we performed EM-seq cfDNA methylation profiling in three healthy adults, tracking individual double-stranded DNA duplexes using customized duplex adapters (Fig. 1b, Extended Data Fig. 1b and Supplementary Table 1). As expected, CpG methylation was substantially higher near the 5′ ends of cfDNA molecules (corresponding to R1) than near the 3′ ends (corresponding to R2), with the magnitude varying with the length of newly synthesized...

A 19-year-old man died at the scene of a shooting Saturday morning at 625 N. Washington St. in Danville. Police said a 17-year-old male is in custody and described the shooting as nonrandom.

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Importance  Interleukin (IL)-17 inhibitors have emerged as effective therapies for moderate to severe hidradenitis suppurativa (HS), but concerns remain regarding their potential association with inflammatory bowel disease (IBD). It is known that there is an increased risk of IBD in HS populations, but it remains unclear whether IL-17 inhibition increases the IBD risk or unmasks underlying disease.Objective  To evaluate the incidence of IBD in patients with HS treated with IL-17 inhibitors and to compare IBD event rates between treatment and placebo groups.Data Sources  PubMed, Embase, and the Cochrane CENTRAL were searched from inception through November 2025.Study Selection  Randomized clinical trials (RCTs), nonrandomized studies, and case reports reporting IBD outcomes in patients with HS treated with IL-17 inhibitors were included. Of 1467 records identified, 24 studies met inclusion criteria (10 RCTs, 11 nonrandomized studies, and 3 case reports).Data Extraction and Synthesis  Extracted variables included study design, IL-17 inhibitor, study duration, dosing regimen, sample size, patient age, sex, baseline personal or family history of IBD, new-onset IBD, relapse of preexisting IBD, IBD subtype and clinical features, and time to IBD onset.Main Outcomes and Measures  Incidence of IBD event, defined as new-onset or worsening Crohn disease or ulcerative colitis during IL-17 inhibitor treatment in a patient with HS. For RCTs, pooled risk differences were calculated using a common effects Mantel-Haenszel model. For nonrandomized studies, a single group meta-analysis of proportions was performed to estimate pooled IBD incidence. Case reports were synthesized qualitatively.Results  Across 10 RCTs, new-onset IBD occurred in 6 of 2572 patients treated with IL-17 inhibitors (0.23%) and in 0 of 1066 patients treated with placebo through week 16. There was no significant difference between groups (risk difference, 0.002; 95% CI, −0.003 to 0.007). In nonrandomized studies, 7 new-onset IBD events occurred among 469 patients (crude incidence, 1.49%), with a pooled incidence of 3.90% (95% CI, 2.30%-6.50%). Across randomized trials, long-term extension studies, and nonrandomized studies, 17 new-onset cases and 4 IBD flares were reported.Conclusions  In this systematic review and meta-analysis, IBD events were rare. No significant increase in IBD risk was observed with IL-17 inhibitors, although low event rates and inconsistent reporting limited interpretation.