Clustered mutations in yeast and in human cancers can arise from damaged long single-strand DNA regions.

Mutations are typically perceived as random, independent events. We describe here nonrandom clustered mutations in yeast and in human cancers. Genome sequencing of yeast grown under chronic alkylation damage identified mutation clusters that extend up to 200 kb. A predominance of "strand-coordinated" changes of either cytosines or guanines in the same strand, mutation patterns, and genetic controls indicated that simultaneous mutations were generated by base alkylation in abnormally long single-strand DNA (ssDNA) formed at double-strand breaks (DSBs) and replication forks. Significantly, we found mutation clusters with analogous features in sequenced human cancers. Strand-coordinated clusters of mutated cytosines or guanines often resided near chromosome rearrangement breakpoints and were highly enriched with a motif targeted by APOBEC family cytosine-deaminases, which strongly prefer ssDNA. These data indicate that hypermutation via multiple simultaneous changes in randomly formed ssDNA is a general phenomenon that may be an important mechanism producing rapid genetic variation.

Description and outcomes of a buprenorphine maintenance treatment program integrated within Prevention Point Philadelphia, an urban syringe exchange program.

BACKGROUND: Syringe exchange programs are uniquely positioned to offer treatment services to interested clients. Prevention Point Philadelphia recently expanded to offer buprenorphine maintenance treatment through its Stabilization, Treatment, and Engagement Program (STEP). OBJECTIVE: To describe the STEP model of care and report treatment outcomes. METHODS: Retrospective chart review of patients enrolled in STEP (October 2011-August 2014). Our main outcome measure was time retained in treatment, defined as time from treatment initiation to treatment failure. Secondary outcome measures were buprenorphine and opiate use, from urine toxicology screens. We analyzed retention in treatment using Kaplan-Meier survival estimates; patients who remained in treatment at the end of the study period were censored on that day. For buprenorphine and opiate use, we calculated the percentage of patients who were positive for buprenorphine and opiates in each month of treatment. RESULTS: Of the 124 patients enrolled in STEP, the median age was 41 (range 21 to 63) and 80% reported injection heroin use. Comorbidities were common: 33% had HIV infection, most reported anxiety (78%) or depression (71%), and 20% were homeless. The most common program outcomes were unplanned self-discharge (n = 29; 23%), incarceration (n = 20; 16%), and administrative discharge (n = 19; 15%). The percentage of patients retained in treatment at 3, 6, 9, and 12 months was 77%, 65%, 59%, and 56%, respectively. Among those retained, the percentage with a positive buprenorphine screen at 3, 6, 9, and 12 months was 88%, 100%, 96%, and 95%, respectively. The percentage with a positive opiates screen was 19%, 13%, 17%, and 16%, respectively. CONCLUSIONS: With a program that blended organizational and community resources, retention in buprenorphine maintenance treatment was comparable to retention rates reported from other settings. Further research should directly compare treatment outcomes in syringe exchange program-based settings versus primary care and specialty settings.

Informed consent for biobanking: consensus-based guidelines for adequate comprehension.

PURPOSE: Federal regulations and best practice guidelines identify categories of information that should be communicated to prospective biobank participants during the informed consent process. However, uncertainty remains about which of this information participants must understand to provide valid consent. METHODS: We conducted a Delphi process to define "adequate comprehension" in the context of biobanking consent. The process involved an iterative series of three online surveys of a diverse panel of 51 experts, including genome scientists, biobank managers, ethics and policy experts, and community and participant representatives. We sought consensus (>70% agreement) concerning what specific details participants should know about 16 biobank consent topics. RESULTS: Consensus was achieved for 15 of the 16 consent topics. The exception was the comprehension needed regarding the Genetic Information Nondiscrimination Act. CONCLUSION: Our Delphi process was successful in identifying a concise set of key points that prospective participants must grasp to provide valid consent for biobanking. Specifying the level of knowledge sufficient for individuals to make an informed choice provides a basis for improving consent forms and processes, as well as an absolute metric for assessing the effectiveness of other interventions to improve comprehension.Genet Med 17 3, 226-233.

Imaging findings of gastric glomus tumors.

Sparse literature describes the imaging findings of gastric glomus tumors (GGT), focusing on benign tumors. We are not aware of prior radiology reports on malignant GGT. The aim of the study was to determine whether it is possible to differentiate between benign and malignant GGT on CT or MR. Institutional radiology and pathology databases were queried for the diagnosis of GGT between January 2010 to December 2023. Of 22 identified subjects, five were excluded due to non-availability of preoperative CT or MR images and three due to lack of pathological confirmation in our institution. The study cohort comprised of 14 patients (males = 6) with median age of 65 years (range 31 to 79 years). Two abdominal radiologists in consensus reviewed all relevant CT and MR images. There were 10 benign and 4 malignant GGT. Benign tumors were smaller than malignant GGT (median size of 2.0 cm vs. 5.3 cm, p = 0.03), more likely to exhibit homogeneous hyperenhancement (9/10 vs. 0/4, p < 0.01), and demonstrated intramural rather than exophytic growth. There was no substantial difference in T2 signal or diffusion restriction between benign and malignant GGT. On follow up, benign GGT were essentially stable in size, while malignant GGT grew. A biopsy proven GGT larger than 5 cm or showing necrosis is likely to be malignant. This is important since preoperative endoscopic ultrasound-guided fine needle aspiration may be indeterminate for malignancy.

Image quality comparison of 1.5T and 3T prostate MRIs of the same post-hip arthroplasty patients: multi-rater assessments including PI-QUAL version 2.

OBJECTIVES: To compare the image quality of 1.5T and 3T prostate MRIs of the same post-hip arthroplasty patients, with a specific focus on the degree of susceptibility artifacts. METHODS: This single-center retrospective study included post-hip arthroplasty patients who underwent 1.5T prostate MRIs between 2021 and 2023, as well as comparative 3T prostate MRIs. Three blinded abdominal radiologists retrospectively reviewed their diffusion-weighted imaging (DWI, 50 s/mm2), T2-weighted imaging (T2WI), and dynamic contrast-enhanced imaging (DCE) to evaluate the image quality. The degree of susceptibility artifacts was categorized using a three-point scale, with 3 indicating the least artifact and 1 indicating the most. Image quality was also evaluated using Prostate Imaging Quality (PI-QUAL) version 2. The median of the three raters' scores was compared between 1.5T and 3T prostate MRIs using the Wilcoxon signed-rank test. The inter-rater agreement was evaluated using the multi-rater generalized kappa. RESULTS: Twenty pairs of 1.5T and 3T prostate MRI examinations from 20 unique patients were included. The DWI susceptibility artifact score at 1.5T was significantly higher than at 3T (mean score ± standard deviation, 2.80 ± 0.41 vs. 2.35 ± 0.93, p = 0.014). In contrast, no significant differences were observed in the susceptibility artifact scores in T2WI and DCE, or in the PI-QUAL score. The inter-reader agreement in the susceptibility artifact score was moderate (multi-rater generalized kappa: 0.60) in DWI, perfect in T2WI (not applicable), and substantial (0.65) in DCE. The inter-reader agreement was fair (0.27) in the PI-QUAL score. CONCLUSION: Using 1.5T scanners may be preferable to reduce susceptibility artifacts from hip prostheses in DWI.

Use of percutaneous imaging-guided biopsy for Liver Imaging and Reporting Data System (LI-RADS) observations: A retrospective study from two liver transplant centers.

Since the adoption of guidelines for the non-invasive imaging diagnosis of hepatocellular carcinoma (HCC), the need for sampling of a lesion in cirrhosis has decreased. We aimed to retrospectively investigate the use of percutaneous imaging-guided biopsy for LI-RADS observations in cirrhosis in two large liver transplant centers. A review of the pathology database in the two Institutions (Institution A, Institution B) was conducted to identify patients that underwent percutaneous imaging-guided biopsy for a liver lesion in the interval time 01/01/2015-12/312020. Liver observations on pre-procedure contrast-enhanced CT or MRI were classified according to LI-RADS v2018. Among the 728 patients who underwent imaging guided biopsy of a liver lesion in Institution A, and among the 749 patients who underwent imaging guided biopsy of a liver lesion in Institution B, respectively 50 (6.8 %) and 16 (2.1 %) were cirrhotic with available pre-procedural contrast-enhanced CT or MRI. A total of 67 lesions were biopsied. 30/67 (45 %) biopsied observations were classified as LR-M. 55/67 (82 %) biopsies were positive for malignancy at histopathology and among them 33 (60 %) were HCC. In conclusion, a small percentage of percutaneous, imaging-guided biopsies for liver lesions are performed in cirrhosis, and more frequently for LR-M observations.

The Effectiveness of Spaced Learning, Interleaving, and Retrieval Practice in Radiology Education: A Systematic Review.

PURPOSE: Radiology is a highly complex field that requires mastery over an ever-expanding body of knowledge. Spaced learning, interleaving, and retrieval practice are evidence-based learning strategies that enhance long-term retention of information. The aim of this systematic review is to assess the effectiveness of these interventions in the setting of radiology education. METHODS: The authors searched MEDLINE, Embase, PsycInfo, ERIC, and forward and backward citations for studies published between database inception and February 19, 2023. Eligibility criteria for included studies were randomized and quasi-randomized controlled trials that investigated the impact of spaced, interleaved, or retrieval practice on knowledge retention of medical trainees after education related to medical imaging as assessed by postinterventional examination scores. RESULTS: Of 1,316 records reviewed, 8 studies met eligibility criteria. Two studies investigated spaced learning, two studies interleaving, and six studies retrieval practice, including two trials that evaluated interventions incorporating both spaced learning and retrieval practice. Five of eight studies reported statistically significant differences between interventional and control groups on either immediate or delayed postinterventional examinations. CONCLUSIONS: Despite extensive evidence in support of spaced, interleaved, and retrieval practice within the broader literature, few studies have examined the effectiveness of these strategies in radiology education. Additional trials are required to evaluate the usefulness of incorporating these techniques into educational programs related to medical imaging.

First-Year Radiology Residents Teaching Anatomy to First-Year Medical Students: A Symbiotic Relationship.

OBJECTIVES: Our institution has developed an educational program in which first-year radiology residents teach first-year medical students during gross anatomy laboratory sessions. The purpose of this study is to assess the impact of this program on medical student knowledge and perceptions of radiology, and on resident attitudes toward teaching. MATERIALS AND METHODS: First-year resident pairs taught small groups of medical students during weekly 15-minute interactive sessions, and were evaluated on teaching skills by senior residents. A survey about attitudes toward radiology and a knowledge quiz were sent to the medical students, and a survey about attitudes toward teaching was sent to the first-year radiology residents, both pre-course and post-course. RESULTS: Students' radiology knowledge significantly increased between the pre-course and post-course survey across all categories tested (P < 0.001). Additionally, there were significant improvements in terms of students' confidence in radiologic anatomy skills, perceived importance of radiology for medical training, familiarity with the field of radiology, and perception that radiologists are friendly (P < 0.001). Radiology residents felt more confident in their teaching proficiency (P < 0.001) by the conclusion of the course. CONCLUSIONS: Resident-led small-group teaching sessions during anatomy laboratory are mutually beneficial for medical students and radiology residents. The program also allows radiology residents to be exposed early on in residency to teaching and academic medicine.

Brain morphology of the threespine stickleback (Gasterosteus aculeatus) varies inconsistently with respect to habitat complexity: A test of the Clever Foraging Hypothesis.

The Clever Foraging Hypothesis asserts that organisms living in a more spatially complex environment will have a greater neurological capacity for cognitive processes related to spatial memory, navigation, and foraging. Because the telencephalon is often associated with spatial memory and navigation tasks, this hypothesis predicts a positive association between telencephalon size and environmental complexity. The association between habitat complexity and brain size has been supported by comparative studies across multiple species but has not been widely studied at the within-species level. We tested for covariation between environmental complexity and neuroanatomy of threespine stickleback (Gasterosteus aculeatus) collected from 15 pairs of lakes and their parapatric streams on Vancouver Island. In most pairs, neuroanatomy differed between the adjoining lake and stream populations. However, the magnitude and direction of this difference were inconsistent between watersheds and did not covary strongly with measures of within-site environmental heterogeneity. Overall, we find weak support for the Clever Foraging Hypothesis in our study.

Many-to-one form-to-function mapping weakens parallel morphological evolution.

Evolutionary ecologists aim to explain and predict evolutionary change under different selective regimes. Theory suggests that such evolutionary prediction should be more difficult for biomechanical systems in which different trait combinations generate the same functional output: "many-to-one mapping." Many-to-one mapping of phenotype to function enables multiple morphological solutions to meet the same adaptive challenges. Therefore, many-to-one mapping should undermine parallel morphological evolution, and hence evolutionary predictability, even when selection pressures are shared among populations. Studying 16 replicate pairs of lake- and stream-adapted threespine stickleback (Gasterosteus aculeatus), we quantified three parts of the teleost feeding apparatus and used biomechanical models to calculate their expected functional outputs. The three feeding structures differed in their form-to-function relationship from one-to-one (lower jaw lever ratio) to increasingly many-to-one (buccal suction index, opercular 4-bar linkage). We tested for (1) weaker linear correlations between phenotype and calculated function, and (2) less parallel evolution across lake-stream pairs, in the many-to-one systems relative to the one-to-one system. We confirm both predictions, thus supporting the theoretical expectation that increasing many-to-one mapping undermines parallel evolution. Therefore, sole consideration of morphological variation within and among populations might not serve as a proxy for functional variation when multiple adaptive trait combinations exist.

Contrasting effects of environment and genetics generate a continuum of parallel evolution.

Parallel evolution of similar traits by independent populations in similar environments is considered strong evidence for adaptation by natural selection. Often, however, replicate populations in similar environments do not all evolve in the same way, thus deviating from any single, predominant outcome of evolution. This variation might arise from non-adaptive, population-specific effects of genetic drift, gene flow or limited genetic variation. Alternatively, these deviations from parallel evolution might also reflect predictable adaptation to cryptic environmental heterogeneity within discrete habitat categories. Here, we show that deviations from parallel evolution are the consequence of environmental variation within habitats combined with variation in gene flow. Threespine stickleback (Gasterosteus aculeatus) in adjoining lake and stream habitats (a lake-stream 'pair') diverge phenotypically, yet the direction and magnitude of this divergence is not always fully parallel among 16 replicate pairs. We found that the multivariate direction of lake-stream morphological divergence was less parallel between pairs whose environmental differences were less parallel. Thus, environmental heterogeneity among lake-stream pairs contributes to deviations from parallel evolution. Additionally, likely genomic targets of selection were more parallel between environmentally more similar pairs. In contrast, variation in the magnitude of lake-stream divergence (independent of direction) was better explained by differences in lake-stream gene flow; pairs with greater lake-stream gene flow were less morphologically diverged. Thus, both adaptive and non-adaptive processes work concurrently to generate a continuum of parallel evolution across lake-stream stickleback population pairs.