Miracle-dz/UniFAR-FTUs huggingface dataset:
Factors Affecting Genetic Consultation in Adolescent and Young Adult Patients With Sarcoma.

BACKGROUND Given a link between sarcomas and hereditary cancer predisposition syndromes, including Li-Fraumeni syndrome, the consideration for genetic counseling is recommended for all adolescent and young adult (AYA) patients diagnosed with sarcoma. The aim of this study was to evaluate factors influencing genetic consultations in AYA patients with sarcoma at the University of Wisconsin (UW). METHODS A retrospective chart review was performed on AYA patients diagnosed with sarcoma between the ages of 15 and 39 years who were seen at least once between 2015 to 2019 at UW. Our chart review identified discussions regarding genetics, referrals to genetics, genetic consultations, and results of genetic testing. Variables hypothesized to affect patient referrals for genetic consultation were identified a priori. Descriptive statistical methods and a univariate analysis were used to identify patient characteristics associated with genetic counseling referral. RESULTS We identified 87 AYA patients with sarcoma. Only 19 (22%) of these patients had documentation of a discussion about genetics, 15 (17%) of whom were subsequently referred for genetic consultation. Of these 15 patients, 9 (60%) were seen in consultation. All 9 patients seen by genetics underwent genetic testing, with 4 (44%) of these patients having identified heritable cancer predisposition syndromes. Likelihood for genetics referral was linked most strongly to documented genetics discussion with an oncology provider (P<.001). CONCLUSIONS Despite the recommendation for consideration for genetic counseling in AYA patients with sarcoma, <25% of such patients in our study had a documented discussion about genetics. Supporting this need, all referred patients met criteria for genetic testing, and 44% of tested patients were found to have a heritable cancer predisposition syndrome. These data support the initial conversation by a provider as critical to genetic referral and suggest the need for more specific national recommendations for the genetic evaluation of all AYA patients with sarcoma.
Differences in Prostate Cancer Genomes by Self-reported Race: Contributions of Genetic Ancestry, Modifiable Cancer Risk Factors, and Clinical Factors

Purpose: Black men die from prostate cancer twice as often as White men, a disparity likely due to inherited genetics, modifiable cancer risk factors, and healthcare access. It is incompletely understood how and why tumor genomes differ by self-reported race and genetic ancestry. Experimental Design: Among 2,069 men with prostate cancer (1,841 self-reported White, 63 Asian, 165 Black) with access to clinical-grade sequencing at the same cancer center, prevalence of tumor and germline alterations was assessed in cancer driver genes reported to have different alteration prevalence by race. Results: Clinical characteristics such as prostate-specific antigen and age at diagnosis as well as cancer stage at sample procurement differed by self-reported race. However, most genomic differences persisted when adjusting for clinical characteristics. Tumors from Black men harbored fewer PTEN mutations and more AR alterations than those from White men. Tumors from Asian men had more FOXA1 mutations and more ZFHX3 alterations than White men. Despite fewer TP53 mutations, tumors from Black men had more aneuploidy, particularly chromosome arm 8q gains, an adverse prognostic factor. Genetic ancestry was associated with similar tumor alterations as self-reported race, but also with modifiable cancer risk factors. Community-level average income was associated with chr8q gains after adjusting for race and ancestry. Conclusions: Tumor genomics differed by race even after accounting for clinical characteristics. Equalizing access to care may not fully eliminate such differences. Therapies for alterations more common in racial minorities are needed. Tumor genomic differences should not be assumed to be entirely due to germline genetics.
Changes in Sewage Sludge Chemical Signatures During a COVID‐19 Community Lockdown, Part 1: Traffic, Drugs, Mental Health, and Disinfectants

The early months of the COVID‐19 pandemic and the associated shutdowns disrupted many aspects of daily life and thus caused changes in the use and disposal of many types of chemicals. While records of sales, prescriptions, drug overdoses, and so forth provide data about specific chemical uses during this time, wastewater and sewage sludge analysis can provide a more comprehensive overview of chemical changes within a region. We analyzed primary sludge from a wastewater‐treatment plant in Connecticut, USA, collected March 19 to June 30, 2020. This time period encompassed the first wave of the pandemic, the initial statewide stay at home order, and the first phase of reopening. We used liquid chromatography–high‐resolution mass spectrometry and targeted and suspect screening strategies to identify 78 chemicals of interest, which included pharmaceuticals, illicit drugs, disinfectants, ultraviolet (UV) filters, and others. We analyzed trends over time for the identified chemicals using linear trend analyses and multivariate comparisons (p < 0.05). We found trends related directly to the pandemic (e.g., hydroxychloroquine, a drug publicized for its potential to treat COVID‐19, had elevated concentrations in the week following the implementation of the US Emergency Use Authorization), as well as evidence for seasonal changes in chemical use (e.g., increases for three UV‐filter compounds). Though wastewater surveillance during the pandemic has largely focused on measuring severe acute respiratory syndrome–coronavirus‐2 RNA concentrations, chemical analysis can also show trends that are important for revealing the public and environmental health effects of the pandemic. Environ Toxicol Chem 2022;41:1179–1192. © 2021 SETAC
Do research participants share genomic screening results with family members?

The public health impact of genomic screening can be enhanced by cascade testing. However, cascade testing depends on communication of results to family members. While the barriers and facilitators of family communication have been researched following clinical genetic testing, the factors impacting the dissemination of genomic screening results are unknown. Using the pragmatic Electronic Medical Records and Genomics Network‐3 (eMERGE‐3) study, we explored the reported sharing practices of participants who underwent genomic screening across the United States. Six eMERGE‐3 sites returned genomic screening results for mostly dominant medically actionable disorders and surveyed adult participants regarding communication of results with first‐degree relatives. Across the sites, 279 participants completed a 1‐month and/or 6‐month post‐results survey. By 6 months, only 34% of the 156 respondents shared their results with all first‐degree relatives and 4% did not share with any. Over a third (39%) first‐degree relatives were not notified of the results. Half (53%) of participants who received their results from a genetics provider shared them with all first‐degree relatives compared with 11% of participants who received their results from a non‐genetics provider. The most frequent reasons for sharing were a feeling of obligation (72%) and that the information could help family members make medical decisions (72%). The most common reasons indicated for not sharing were that the family members were too young (38%), or they were not in contact (25%) or not close to them (25%). These data indicate that the professional returning the results may impact sharing patterns, suggesting that there is a need to continue to educate healthcare providers regarding approaches to facilitate sharing of genetic results within families. Finally, these data suggest that interventions to increase sharing may be universally effective regardless of the origin of the genetic result.
CODEHOP-Mediated PCR Improves HIV-1 Genotyping and Detection of Variants by MinION Sequencing

HIV-1 drug resistance is the main cause of treatment failure. Regular surveillance of resistance-associated mutations in HIV-1 genomes is essential for the optimal management of HIV-1 infections. ABSTRACT HIV-1 is genetically heterogeneous, having different subtypes and circulating recombinant forms (CRFs). HIV-1 genotyping is used to determine drug resistance profiles and is based on the use of a mixture of consensus and degenerate primers targeting the pol gene. However, the use of this type of primers is associated with either PCR bias or PCR failure. Consensus-degenerate hybrid oligonucleotide primers (CODEHOPs) can detect and identify unknown and distantly related gene sequences by PCR. CODEHOPs designed using different HIV-1 subtypes and CRFs were evaluated for HIV-1 genotyping by Sanger and MinION sequencing. A total of 321 plasma samples were used for the validation of CODEHOP-mediated HIV-1 genotyping. CODEHOP-mediated PCR showed 100% sensitivity and specificity, with limits of detection and genotyping below 200 copies/ml. The head-to-head evaluation of CODEHOP-mediated PCR and standard PCR showed 97 to 98% and 82 to 84% PCR success rates, respectively. There was 100% agreement between the CODEHOP and the reference method in the drug resistance profiles determined by Sanger-based sequencing. Using MinION sequencing, the CODEHOP-mediated PCR scheme resulted in better depth of genome coverage and detection of more drug resistance variants in the protease and reverse transcriptase genes than the standard amplification scheme. The overall prevalences of drug resistance mutations were 17.1% in treatment-experienced patients and 1.2% in treatment-naive patients. They were mainly associated with resistance to reverse transcriptase inhibitors and were linked to virological failure and the patient’s treatment history. Findings from this study suggest that the performance of HIV-1 genotyping is improved by using CODEHOP-mediated PCR. IMPORTANCE HIV-1 drug resistance is the main cause of treatment failure. Regular surveillance of resistance-associated mutations in HIV-1 genomes is essential for the optimal management of HIV-1 infections. Due to HIV-1’s genetic diversity, different HIV-1 genotypes are circulating worldwide. Standard primers used in the amplification of HIV-1 RNA have not been designed to cover all HIV-1 genotypes and are the main cause of amplification and drug resistance test failure. In this study, new sets of PCR primers targeting the protease, reverse transcriptase, and integrase genes were designed using the CODEHOP approach. They were compared to primers recommended in part by WHO for drug resistance testing using in-house PCR. Unsuccessful HIV-1 RNA amplification was less likely to occur with CODEHOP primers, leading to fewer test failures and lower cost. Furthermore, CODEHOP primers were more effective than standard primers for the detection of minority resistant variants by MinION sequencing.
Helpful or Harmful? The Role of Personality Traits in Student Experiences of the COVID-19 Crisis and School Closure

Little is known about the individual differences in student experiences and expectations of the COVID-19 crisis and the resulting school closures. Yet, as the crisis may have uniquely impacted students, knowledge about their personalities is highly relevant. In a sample of 347 Flemish students, this study explored the association between personality traits and differences in responses to the crisis. The Big Five personality traits of students were assessed in January 2020, prior to the COVID-19 outbreak. Students were reassessed in June 2020 with a set of items related to well-being, remote learning, and family and social life. The results suggested that more conscientious students (showing a better perception of remote learning) and more open students (considering the period as an opportunity to learn new skills) adjusted well to the changes induced by the crisis. On the contrary, students high in neuroticism (showing higher stress levels) were harmed.
Robust Weighted-Average Continuous-Time Consensus With Communication Time Delay

Achieving consensus behavior robust to time delay in multiagent systems has attracted much attention. This work is concerned with optimizing the convergence rate of the consensus algorithm in such systems with time delays. Previous approaches optimize either the robustness to time delay or the convergence rate separately, while imposing a limit on the other. Eigenratio optimization is another method, which does not necessarily result in a unique set of weights. Here, the problem is treated in its general form as a multiobjective optimization problem. It is shown that the corresponding Pareto frontier depends solely on the optimal condition number of the Laplacian, and it includes the optimal answer of previously adopted approaches as special cases. A notion of optimal consensusability is then defined, which allows a particular point on the Pareto Frontier with special properties to be identified. The resulting optimization problem is shown to be convex, as is solved by reformulating it as a standard semidefinite programming problem. The optimal weights for individual topologies, clique lifted graphs, and different types of subgraphs are provided, where for the latter, the optimal weights have shown to be independent of the rest of topology. Through numerical simulations, the tradeoff between robustness and convergence rate is demonstrated.
Qualitative Descriptive Study of Illegal Behaviors among Those with Gambling Disorder in South Korea: Their Efforts for Recovery and Role of Mental Health Care Providers

Abstract The prevalence of Gambling Disorder among Koreans suggests that it is relatively higher than other countries. This study explored gambling-related crimes and related mental health care needs of those with Gambling Disorder on a case-by-case basis. Participants (n = 6) included men attending Gamblers Anonymous in South Korea with gambling debts and histories of illegal acts. Thematic analysis of qualitative interviews identified themes: (1) Meaning of Gambling Disorder in life, (2) Initiation of illegal acts stemming from Gambling Disorder, and (3) Life after addiction, efforts for recovery, and mental health care needs. Gambling Disorder destroyed lives and created criminal victims thereby threatening familial and community health.
Can We Eliminate Opioids After Anterior Cruciate Ligament Reconstruction? A Prospective, Randomized Controlled Trial

Background: Multimodal pain protocols have been effective for postsurgical pain control; however, no published protocol has been effective in eliminating opioid consumption. Purpose: To compare a multimodal nonopioid pain protocol versus traditional opioid medication for postoperative pain control in patients undergoing anterior cruciate ligament reconstruction (ACLR). Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 90 patients undergoing primary ACLR were assessed for participation. We performed a prospective, randomized controlled trial in accordance with the CONSORT (Consolidated Standards of Reporting Trials) 2010 statement. The study arms were a multimodal nonopioid analgesic protocol (acetaminophen, ketorolac, diazepam, gabapentin, and meloxicam) and a standard opioid regimen (hydrocodone-acetaminophen), and the primary outcome was postoperative visual analog scale (VAS) pain scores for 10 days. Secondary outcomes included patient-reported outcomes, complications, and satisfaction. The observers were blinded, and the patients were not blinded to the intervention. Results: A total of 9 patients did not meet inclusion criteria, and 19 patients declined participation. Thus, 62 patients were analyzed, with 28 patients randomized to the opioid group and 34 to the multimodal nonopioid group. Patients receiving the multimodal nonopioid pain regimen demonstrated significantly lower VAS scores compared with patients who received opioid pain medication (P < .05). Patients were administered the Patient-Reported Outcomes Measurement and Information System Pain Interference Short Form, and no significant difference was found in patients’ preoperative scores (opioid group, 58.6 ± 7.9; multimodal nonopioid group, 57.5 ± 7.4; P = .385) and 1-week postoperative scores (opioid group, 66.3 ± 8.2; multimodal nonopioid group, 61.4 ± 8.8; P = .147). When we adjusted for possible confounders (age, sex, body mass index, graft type), no significant differences in pain control were found between the 2 groups. The most common adverse effects for both groups were drowsiness and constipation, with no difference between the groups. All patients in the multimodal nonopioid group reported satisfactory pain management. Conclusions: A multimodal nonopioid pain protocol provided at least equivalent pain control compared with traditional opioid analgesics in patients undergoing ACLR. Minimal side effects, which did not differ between groups, were noted, and all patients reported satisfaction with their pain management.
Proportion of conflict, contingency learning, and recency effects in a Stroop task

Recent research on the relation between learning and cognitive control has assumed that conflict modulates learning, either by increasing arousal and hence improving learning in high-conflict situations, or by inducing control, and hence inhibiting the processing of distracters and their eventual association with the imperative responses. We analyse whether the amount of conflict, manipulated through the proportion of congruency in a set of Stroop inducer trials, affects learning of contingencies established on diagnostic trials composed by neutral words associated with colour responses. The results reproduced the list-wide proportion of congruency effect on the inducer trials, and showed evidence of contingency learning on the diagnostic trials, but provided no indication that this learning was modulated by the level of conflict. Specific analyses conducted to control for the impact of episodic effects on the expression of learning indicated that contingency effects were not driven by the incremental processes that could be expected by associative learning, but rather they were due to the impact of the most recent trial involving the same distracter. Accordingly, these effects disappeared when tested selectively on trials that required a non-matching response with respect to the previous occurrence of the distracter. We interpret this result in the context of the debate on how learning and memory interact with the processes of cognitive control.
Left Atrial Appendage Occlusion for Stroke Prevention in Nonvalvular Atrial Fibrillation

Abstract The majority of embolic strokes in patients with nonvalvular atrial fibrillation are caused by thrombi in the left atrial appendage. It is projected that strokes related to atrial fibrillation will markedly increase in the future unless effective mitigation strategies are implemented. Systemic anticoagulation has been known to be highly effective in reducing stroke risk in patients with atrial fibrillation. However, bleeding complications and nonadherence are barriers to effective anticoagulation therapy. Surgical and percutaneous left atrial appendage occlusion devices are nonpharmacologic strategies to mitigate the challenges of drug therapy. We present a contemporary review of left atrial appendage occlusion for stroke prevention in nonvalvular atrial fibrillation. A thorough review of the history of surgical and percutaneous left atrial appendage occlusion devices, recent trials, and US Food and Drug Administration milestones of current left atrial appendage occlusion devices are discussed.
Evaluation of aortic biomechanics in patients with aortic disease via imaging: A review

As a bridge between the heart and the arteries, the aorta plays an important role in the cardiovascular system. The morbidity and mortality of aortic disease are extremely high, which is a serious threat to human life. The biomechanical abnormality of the aorta is an important factor of a series of pathological changes in the aortic wall. At present, there are many imaging methods to evaluate the biomechanics of the aorta, which will benefit to the early diagnosis and treatment of aortic disease. In this review, we describe the application of various imaging methods and parameters in aortic disease.
So happy together … Examining the association between relationship happiness, socio-economic status, and family transitions in the UK

The increases in cohabitation and in childbearing within cohabitation raise questions about who marries. Most studies have found that childbearing within cohabitation is associated with disadvantage; here, we examine the role of relationship happiness and whether it helps to explain this association. Using the UK Household Longitudinal Study (2009–17), our competing risk hazard models follow respondents as they transition: (1) from cohabitation into marriage or childbearing; and (2) from marriage or cohabitation into childbearing. We find that marriage risks are highest among individuals who are happiest with their relationship. On average, the association between relationship quality and childbearing operates through marriage: the happiest individuals marry, and those who marry have children. While higher socio-economic status is weakly associated with marriage, conception, and separation, the associations do not differ by relationship happiness. The findings indicate that overall, relationship happiness appears to be most salient for transitions into marriage.
Experiment level curation of transcriptional regulatory interactions in neurodevelopment

To facilitate the development of large-scale transcriptional regulatory networks (TRNs) that may enable in-silico analyses of disease mechanisms, a reliable catalogue of experimentally verified direct transcriptional regulatory interactions (DTRIs) is needed for training and validation. There has been a long history of using low-throughput experiments to validate single DTRIs. Therefore, we reason that a reliable set of DTRIs could be produced by curating the published literature for such evidence. In our survey of previous curation efforts, we identified the lack of details about the quantity and the types of experimental evidence to be a major gap, despite the theoretical importance of such details for the identification of bona fide DTRIs. We developed a curation protocol to inspect the published literature for support of DTRIs at the experiment level, focusing on genes important to the development of the mammalian nervous system. We sought to record three types of low-throughput experiments: Transcription factor (TF) perturbation, TF-DNA binding, and TF-reporter assays. Using this protocol, we examined a total of 1,310 papers to assemble a collection of 1,499 unique DTRIs, involving 251 TFs and 825 target genes, many of which were not reported in any other DTRI resource. The majority of DTRIs (965; 64%) were supported by two or more types of experimental evidence and 27% were supported by all three. Of the DTRIs with all three types of evidence, 170 had been tested using primary tissues or cells and 44 had been tested directly in the central nervous system. We used our resource to document research biases among reports towards a small number of well-studied TFs. To demonstrate a use case for this resource, we compared our curation to a previously published high-throughput perturbation screen and found significant enrichment of the curated targets among genes differentially expressed in the developing brain in response to Pax6 deletion. This study demonstrates a proof-of-concept for the assembly of a high resolution DTRI resource to support the development of large-scale TRNs.