Search

Summary: The vast amount of publicly available genomic data requires analysis and visualization tools. Here, we present figeno, an application for generating publication-quality FIgures for GENOmics. Figeno particularly focuses on multi-region views across genomic breakpoints and on long reads with base modifications. In addition, we support epigenomic data including ATAC-seq, ChIP-seq or HiC, as well as whole genome sequencing data with copy numbers and structural variants., Availability and Implementation: Figeno is available as a python package with both a command line and graphical user interface. It can be installed via PyPI and the source code is available at https://github.com/CompEpigen/figeno., (© The Author(s) 2024. Published by Oxford University Press.)

Not available.

Statement of Problem: Additive manufacturing procedures for fabricating interim restorations include rinsing postprocessing procedures. However, the impact of different rinsing solutions and times on flexural strength is unknown., Purpose: The purpose of this in vitro study was to assess the influence of the rinsing solutions and duration, as well as accelerated aging (thermocycling) procedures, on the flexural strength and Weibull characteristics of an additively manufactured interim dental material., Material and Methods: A bar design (25×2×2 mm) file was used to fabricate all the specimens with 3D printing and an interim material (Nextdent C&B MFH). Five groups were created based on the rinsing solution used during the postprocessing procedures: 91% isopropyl alcohol (IPA) (control or IPA-91), 99% IPA (IPA-99 group), bio-ethyl alcohol 100% (BE group), tripropylene glycol monomethyl ether (TPM) 100% (TPM group), and water miscible formula (Resinaway) (RA group). Each group was divided into 4 subgroups depending on the total rinsing time: 5, 6, 7, and 8 minutes (5, 6, 7, and 8 subgroups). Additionally, each subgroup was distributed between nonaged and aged thermocycling procedures (n=10). Flexural strength measurements were made by using a universal testing machine. Two-parameter Weibull distribution values, including the Weibull modulus, scale (m), and shape (0), were calculated. Three-way ANOVA and pairwise multiple comparison Tukey tests were used to analyze the data (α=.05)., Results: Three-way ANOVA showed that the rinsing solution (P<.001), rinsing time (P=.004), and thermocycling procedures (P<.001) were significant predictors of the flexural strength values obtained. The IPA-91 and IPA-99 groups obtained the highest flexural strength, while the RA, TPM, and BE groups obtained the lowest flexural strength. The 7- and 8-minute subgroups obtained the highest flexural strength, while the 5-minute subgroup obtained the lowest flexural strength. The nonaged specimens obtained significantly higher mean flexural strength values than the aged specimens., Conclusions: The vat-polymerized additively manufactured interim dental material tested with differing rinsing solutions and times demonstrated significant differences in the flexural strength values measured. Accelerated artificial aging procedures significantly decreased the flexural strength of the vat-polymerized interim dental material tested., (Copyright © 2022 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Fatty liver disease or the accumulation of fat in the liver, has been reported to affect the global population. This comes with an increased risk for the development of fibrosis, cirrhosis, and hepatocellular carcinoma. Yet, little is known about the effects of a diet containing high fat and alcohol towards epigenetic aging, with respect to changes in transcriptional and epigenomic profiles. In this study, we took up a multi-omics approach and integrated gene expression, methylation signals, and chromatin signals to study the epigenomic effects of a high-fat and alcohol-containing diet on mouse hepatocytes. We identified four relevant gene network clusters that were associated with relevant pathways that promote steatosis. Using a machine learning approach, we predict specific transcription factors that might be responsible to modulate the functionally relevant clusters. Finally, we discover four additional CpG loci and validate aging-related differential CpG methylation. Differential CpG methylation linked to aging showed minimal overlap with altered methylation in steatosis., (© 2023. The Author(s).)

Inter-patient variability and the similarity of healthy and leukemic stem cells (LSCs) have impeded the characterization of LSCs in acute myeloid leukemia (AML) and their differentiation landscape. Here, we introduce CloneTracer, a novel method that adds clonal resolution to single-cell RNA-seq datasets. Applied to samples from 19 AML patients, CloneTracer revealed routes of leukemic differentiation. Although residual healthy and preleukemic cells dominated the dormant stem cell compartment, active LSCs resembled their healthy counterpart and retained erythroid capacity. By contrast, downstream myeloid progenitors constituted a highly aberrant, disease-defining compartment: their gene expression and differentiation state affected both the chemotherapy response and leukemia's ability to differentiate into transcriptomically normal monocytes. Finally, we demonstrated the potential of CloneTracer to identify surface markers misregulated specifically in leukemic cells. Taken together, CloneTracer reveals a differentiation landscape that mimics its healthy counterpart and may determine biology and therapy response in AML., Competing Interests: Declaration of interests The Department of Medicine V (Director C.M.-T.) receives research funding from multiple pharmaceutical and biotech companies especially for clinical trials but also for translational research., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: Osteoporotic thoracolumbar fractures are of increasing importance. To identify the optimal treatment strategy this multicentre prospective cohort study was performed., Purpose: Patients suffering from osteoporotic thoracolumbar fractures were included. Excluded were tumour diseases, infections and limb fractures. Age, sex, trauma mechanism, OF classification, OF-score, treatment strategy, pain condition and mobilization were analysed., Methods: A total of 518 patients' aged 75 ± 10 (41-97) years were included in 17 centre. A total of 174 patients were treated conservatively, and 344 were treated surgically, of whom 310 (90%) received minimally invasive treatment. An increase in the OF classification was associated with an increase in both the likelihood of surgery and the surgical invasiveness., Results: Five (3%) complications occurred during conservative treatment, and 46 (13%) occurred in the surgically treated patients. 4 surgical site infections and 2 mechanical failures requested revision surgery. At discharge pain improved significantly from a visual analogue scale score of 7.7 (surgical) and 6.0 (conservative) to a score of 4 in both groups (p < 0.001). Over the course of treatment, mobility improved significantly (p = 0.001), with a significantly stronger (p = 0.007) improvement in the surgically treated patients., Conclusion: Fracture severity according to the OF classification is significantly correlated with higher surgery rates and higher invasiveness of surgery. The most commonly used surgical strategy was minimally invasive short-segmental hybrid stabilization followed by kyphoplasty/vertebroplasty. Despite the worse clinical conditions of the surgically treated patients both conservative and surgical treatment led to an improved pain situation and mobility during the inpatient stay to nearly the same level for both treatments., (© 2023. The Author(s).)

Study Design: Subgroup analysis of a multicenter prospective cohort study., Objective: To analyse surgical strategies applied to osteoporotic thoracolumbar osteoporotic fracture (OF) 5 injuries with anterior or posterior tension band failure and to assess related complications and clinical outcome., Methods: A multicenter prospective cohort study (EOFTT) was conducted at 17 spine centers including 518 consecutive patients who were treated for an osteoporotic vertebral fracture (OVF). For the present study, only patients with OF 5 fractures were analysed. Outcome parameters were complications, Visual Analogue Scale (VAS), Oswestry Disability Questionnaire (ODI), Timed Up & Go test (TUG), EQ-5D 5L, and Barthel Index., Results: In total, 19 patients (78 ± 7 years, 13 female) were analysed. Operative treatment consisted of long-segment posterior instrumentation in 9 cases and short-segment posterior instrumentation in 10 cases. Pedicle screws were augmented in 68 %, augmentation of the fractured vertebra was performed in 42%, and additional anterior reconstruction was done in 21 %. Two patients (11 %) received short-segment posterior instrumentation without either anterior reconstruction or cement-augmentation of the fractured vertebra. No surgical or major complications occurred, but general postoperative complications were observed in 45%. At a follow-up of mean 20 ± 10 weeks (range, 12 to 48 weeks), patients showed significant improvements in all functional outcome parameters., Conclusions: In this analysis of patients with type OF 5 fractures, surgical stabilization was the treatment of choice and lead to significant short-term improvement in terms of functional outcome and quality of life despite a high general complication rate.

Purpose: To measure the flexural strength and Weibull characteristics of aged and nonaged printed interim dental material fabricated with different layer thickness., Material and Methods: Bars (25×2×2 mm) were additively fabricated by using a polymer printer (Asiga Max) and an interim resin (Nexdent C&B MFH). Specimens were fabricated with the same printing parameters and postprocessing procedures, but with 7 different layer thickness: 50 (control or 50-G group), 10 (10-G group), 25 (25-G group), 75 (75-G group), 100 (100-G group), 125 (125-G group), and 150 μm (150-G group). Two subgroups were created: nonaged and aged subgroups (n = 10). A universal testing machine was selected to measure flexural strength. Two-parameter Weibull distribution values were computed. Two-way ANOVA and Tukey tests were selected for statistical evaluation of the data (α = 0.05)., Results: Artificial aging methods (p < 0.001) were a significant predictor of the flexural strength computed. Aged specimens acquired less flexural strength than nonaged specimens. The Weibull distribution obtained the highest shape for nonaged 50-G and 75-G group specimens compared with those of other nonaged groups, while the Weibull distribution showed the highest shape for aged 125-G specimens., Conclusions: The flexural strength of the additively fabricated interim material examined was not influenced by the layer thickness at which the specimens were fabricated; however, artificial aging techniques reduced its flexural strength. Aged specimens presented lower Weibull distribution values compared with nonaged specimens, except for the 125-G specimens., (© 2022 by the American College of Prosthodontists.)

Study Design: Multicenter prospective cohort study., Objective: The study aims to validate the recently developed OF score for treatment decisions in patients with osteoporotic vertebral compression fractures (OVCF)., Methods: This is a prospective multicenter cohort study (EOFTT) in 17 spine centers. All consecutive patients with OVCF were included. The decision for conservative or surgical therapy was made by the treating physician independent of the OF score recommendation. Final decisions were compared to the recommendations given by the OF score. Outcome parameters were complications, Visual Analogue Scale, Oswestry Disability Questionnaire, Timed Up & Go test, EQ-5D 5 L, and Barthel Index., Results: In total, 518 patients (75.3% female, age 75 ± 10) years were included. 344 (66%) patients received surgical treatment. 71% of patients were treated following the score recommendations. For an OF score cut-off value of 6.5, the sensitivity and specificity to predict actual treatment were 60% and 68% (AUC .684, P < .001). During hospitalization overall 76 (14.7%) complications occurred. The mean follow-up rate and time were 92% and 5 ± 3.5 months, respectively. While all patients in the study cohort improved in clinical outcome parameters, the effect size was significantly less in the patients not treated in line with the OF score's recommendation. Eight (3%) patients needed revision surgery., Conclusions: Patients treated according to the OF score's recommendations showed favorable short-term clinical results. Noncompliance with the score resulted in more pain and impaired functional outcome and quality of life. The OF score is a reliable and save tool to aid treatment decision in OVCF.

Study Design: Multicenter prospective cohort study., Objective: To analyse therapeutical strategies applied to osteoporotic thoracolumbar OF 4 injuries, to assess related complications and clinical outcome., Methods: A multicenter prospective cohort study (EOFTT) including 518 consecutive patients who were treated for an Osteoporotic vertebral compression fracture (OVCF). For the present study, only patients with OF 4 fractures were analysed. Outcome parameters were complications, Visual Analogue Scale, Oswestry Disability Questionnaire, Timed Up & Go test, EQ-5D 5L, and Barthel Index after a minimum follow-up of 6 weeks., Results: A total of 152 (29%) patients presented with OF 4 fractures with a mean age of 76 years (range 41-97). The most common treatment was short-segment posterior stabilization (51%; hybrid stabilization in 36%). Mean follow up was 208 days (±131 days), mean ODI was 30 ± 21. Dorsoventral stabilized patients were younger compared to the other groups ( P < .001) and had significant better TuG compared to hybrid stabilization ( P = .049). The other clinical outcomes did not differ in the therapy strategies (VAS pain: P = 1.000, ODI: P > .602, Barthel: P > .252, EQ-5D 5L index value: P > .610, VAS-EQ-5D 5L: P = 1.000). The inpatient complication rate was 8% after conservative and 16% after surgical treatment. During follow-up period 14% of conservatively treated patients and 3% of surgical treated patients experienced neurological deficits., Conclusions: Conservative therapy of OF 4 injuries seems to be viable option in patients with only moderate symptoms. Hybrid stabilization was the dominant treatment strategy leading to promising clinical short-term results. Stand-alone cement augmentation seems to be a valid alternative in selected cases.

Mental health services are experiencing unprecedented levels of demand from clients during COVID resulting in longer wait lists and therapist burnout. As Nemoyer et al. (2019) point out, minorities experience a higher burden of mental illness while having less access and lower quality treatments. COVID has increased demands for mental health services even further, creating bottlenecks of care, therapist burnout, and leading to ever longer wait lists. This article will argue that inefficient supply of services is created by mental health providers being incentivized toward individual therapy. Group therapy offers a solution because it is a "triple E treatment"-efficient, effective, and equivalent to individual therapy in terms of outcomes (Burlingame & Strauss, 2021). Group interventions also address systemic racism and the needs of minorities who have been marginalized and cope with minority stress. This article will utilize a labor and financial impact analysis to demonstrate how increasing group therapy by 10% nationally, particularly in private practice and primary care integration settings, would increase treatment access for over 3.5 million people while reducing the need for 34,473 additional new therapists and simultaneously saving over $5.6 billion. It will discuss how incentivizing groups while holding therapists accountable for training, competency when working with people from diverse backgrounds, and outcomes can result in improved efficiency. This will allow therapists greater freedom to collaboratively select the most effective treatments for those from underserved and minority backgrounds and create easier access to quality treatments. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A perfluorocarbon (PFC) investigated for treatment of traumatic brain injury (TBI) delivers oxygen to support brain function, but causes transient thrombocytopenia. TBI can cause acute inflammation with resulting thrombocytopenia; an interaction between the PFC effects and TBI inflammation might exacerbate thrombocytopenia. Therefore, PFC effects on platelet (PLT) function and hemostasis in a lipopolysaccharide (LPS) model of inflammation in the baboon were studied. Animals were randomized to receive saline ±LPS, and ± one of two doses of PFC. PLT count, transmission electron microscopy, and microparticle populations were quantified at baseline (BL) and at 2, 24, 48, 72, and 96 hours; hemostatic parameters for aggregometry and for blood clotting were measured at baseline (BL) and days 3 and 4. Injection of vehicle and LPS caused thrombocytopenia within hours; PFCs caused delayed thrombocytopenia beginning 48 hours post-infusion. LPS+PFC produced a more prolonged PLT decline and decreased clot strength. LPS+PFC increased ADP-stimulated aggregation, but PFC alone did not. Microparticle abundance was greatest in the LPS+PFC groups. LPS+PFC caused diffuse microvascular hemorrhage and death in 2 of 5 baboons in the low dose LPS-PFC group and 2 of 2 in the high dose LPS-PFC group. Necropsy and histology suggested death was caused by shock associated with hemorrhage in multiple organs. Abnormal morphology of platelets and red blood cells were notable for PFC inclusions. In summary, PFC infusion caused clinically significant thrombocytopenia and exacerbated LPS-induced platelet activation. The interaction between these effects resulted in decreased hemostatic capacity, diffuse bleeding, shock and death., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Digital technology has tremendously impacted implant dentistry and particularly the production of full-arch reconstructions. The use of digital methods to fabricate removable and fixed complete dental prostheses with implants offers many benefits, yet for some clinicians a hybrid method that combines analog and digital techniques for full-arch restorations may be beneficial. This article describes a combination analog-digital method that utilizes the patient's existing removable prosthesis to guide fabrication of a fixed full-arch restoration using a novel stud-style abutment system with a contemporary housing and insert combination.

Statement of Problem: The influence of postpolymerization methods and artificial aging procedures on the fracture resistance and flexural strength of additively manufactured interim polymers remains unclear., Purpose: The purpose of this in vitro study was to evaluate the effect of the conditions (dry and water- and glycerin-submerged) and time (25, 30, 35, 40, and 45 minutes) of postpolymerization methods with and without artificial aging procedures on the fracture resistance and flexural strength of an additively manufactured interim material., Material and Methods: Bar specimens (25×2×2 mm) were manufactured from an interim resin (NexDent C&B MFH N1) with a 3-dimensional printer (NexDent 5100) as per the manufacturer's recommendations. Three groups were created based on the postpolymerization condition: dry (D group) and submerged in a container with water (W group) or glycerin (G group) inside the ultraviolet polymerization machine (LC-3DPrint Box). Each group was divided into 5 subgroups (D1 to D5, W1 to W5, and G1 to G5) depending on the polymerizing time (25, 30, 35, 40, and 45 minutes) (n=20). Each subgroup was divided into nonaged and aged subgroups. The aged groups were treated in a mastication simulator. Fracture strength was measured on a universal testing machine. The flexural strength was calculated as per International Organization for Standardization (ISO) 10477-2018. The Kolmogorov-Smirnov test demonstrated that data were normally distributed. The 3-way ANOVA test was used to analyze the data (α=.05)., Results: A significant main effect was found on the fracture strength analysis for each of the 3 factors: postpolymerization condition (F[2, 449]=81.00, P<.001), treatment duration (F[4, 449]=2.84, P=.024), and aging procedure (F [1, 449] =7.62, P=.006). The only significant 2-way interaction was between postpolymerization condition and treatment duration (F[8, 449]=3.12, P=.002). Furthermore, a significant main effect was found on the flexural strength for each of the 3 factors including postpolymerization condition (F[2, 449]=82.55, P<.001), treatment duration (F[4, 449]=2.85, P=.024), and artificial aging procedure (F[1, 449]=6.72, P=.010). The only significant 2-way interaction was between postpolymerization condition and treatment duration (F[8, 449]=3.33, P=.001). Dry postconditions at 25 minutes and nonaged procedures obtained the significantly highest fracture resistance and flexural strength values., Conclusions: Postpolymerization conditions and duration time affected the fracture resistance and flexural strength of the additively manufactured interim material assessed. Artificial aging procedures significantly decreased the fracture resistance and flexural strength of the additively manufactured interim dental material., (Copyright © 2021 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Single-cell DNA methylation profiling currently suffers from excessive noise and/or limited cellular throughput. We developed scTAM-seq, a targeted bisulfite-free method for profiling up to 650 CpGs in up to 10,000 cells per experiment, with a dropout rate as low as 7%. We demonstrate that scTAM-seq can resolve DNA methylation dynamics across B-cell differentiation in blood and bone marrow, identifying intermediate differentiation states that were previously masked. scTAM-seq additionally queries surface-protein expression, thus enabling integration of single-cell DNA methylation information with cell atlas data. In summary, scTAM-seq is a high-throughput, high-confidence method for analyzing DNA methylation at single-CpG resolution across thousands of single cells., (© 2022. The Author(s).)

Background and Aims: Treatment with tumor necrosis factor α (TNFα) antagonists in IBD patients suffers from primary non-response rates of up to 40%. Biomarkers for early prediction of therapy success are missing. We investigated the dynamics of gene expression and DNA methylation in blood samples of IBD patients treated with the TNF antagonist infliximab and analyzed the predictive potential regarding therapy outcome., Methods: We performed a longitudinal, blood-based multi-omics study in two prospective IBD patient cohorts receiving first-time infliximab therapy (discovery: 14 patients, replication: 23 patients). Samples were collected at up to 7 time points (from baseline to 14 weeks after therapy induction). RNA-sequencing and genome-wide DNA methylation data were analyzed and correlated with clinical remission at week 14 as a primary endpoint., Results: We found no consistent ex ante predictive signature across the two cohorts. Longitudinally upregulated transcripts in the non-remitter group comprised TH2- and eosinophil-related genes including ALOX15, FCER1A, and OLIG2. Network construction identified transcript modules that were coherently expressed at baseline and in non-remitting patients but were disrupted at early time points in remitting patients. These modules reflected processes such as interferon signaling, erythropoiesis, and platelet aggregation. DNA methylation analysis identified remission-specific temporal changes, which partially overlapped with transcriptomic signals. Machine learning approaches identified features from differentially expressed genes cis-linked to DNA methylation changes at week 2 as a robust predictor of therapy outcome at week 14, which was validated in a publicly available dataset of 20 infliximab-treated CD patients., Conclusions: Integrative multi-omics analysis reveals early shifts of gene expression and DNA methylation as predictors for efficient response to anti-TNF treatment. Lack of such signatures might be used to identify patients with IBD unlikely to benefit from TNF antagonists at an early time point., (© 2022. The Author(s).)

Prenatal exposure to endocrine disrupting chemicals can interfere with development, and has been associated with social-cognitive functioning and adverse health outcomes later in life. Exposure-associated changes of DNA methylation (DNAm) patterns have been suggested as a possible mediator of this relationship. This study investigated whether prenatal low-dose exposure to polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) is associated with altered DNAm patterns across the genome in a Western urban-industrial population. In 142 mother-infant pairs from the Duisburg Birth Cohort Study, PCBs and PCDD/Fs levels were quantified from maternal blood during late pregnancy and associated with DNAm levels in cord blood using the Illumina EPIC beadchip. The epigenome-wide association studies (EWAS) identified 32 significantly differentially methylated positions (DMPs) and eight differentially methylated regions (DMRs) associated with six congeners of PCB and PCDD in females or males (FDRs < 0.05). DMPs and DMRs mapped to genes involved in neurodevelopment, gene regulation, and immune functioning. Weighted gene correlation network analysis (WGCNA) showed 31 co-methylated modules (FDRs < 0.05) associated with one congener of PCDF levels in females. Results of both analytical strategies indicate that prenatal exposure to PCBs and PCDD/Fs is associated with altered DNAm of genes involved in neurodevelopment, gene expression and immune functioning. DNAm and gene expression levels of several of these genes were previously associated with EDC exposure in rodent models. Follow-up studies will clarify whether these epigenetic changes might contribute to the origin for adverse mental and health outcomes.

Objective: A common intervention to prevent alcohol-impaired driving are alcohol ignition interlock devices (IIDs), which prevent drivers with a blood alcohol concentration greater than .025% from starting the car. These devices force drivers to adapt their drinking to accommodate the device. Prior studies indicated a transfer of risk as some drivers with an IID may increase cannabis use as they decrease alcohol use. This study examines whether this increase in cannabis use persists after IID removal when alcohol use reverts to pre-IID levels., Method: The data are from the Managing Heavy Drinking (MHD) study of drivers in New York State. The MHD is a comprehensive three-wave study of drivers convicted of driving under the influence from 2015 to 2020. Participants ( N = 189) completed all waves, and provided oral fluid/blood and hair samples to measure cannabis and alcohol use, respectively. Mixed between-within analysis of variance was conducted to assess cannabis use at IID installation (Time 1), removal (Time 2), and at 6-month follow-up (Time 3)., Results: In aggregate, participants increased their cannabis use over the course of the study. Drivers who decreased their alcohol use while the IID was installed on their car significantly increased their cannabis use while the IID was in place and further increased cannabis use after the device's removal., Conclusions: IIDs are efficacious in preventing alcohol-impaired driving. However, in some cases, they may have the unintended effect of increasing other substance use. The current study outlines the need for supplemental treatment interventions while on IID to prevent a transfer of risk to other substances, or polysubstance use after the device is removed., Competing Interests: The authors have no conflicts of interest.

For millennia, ceramics have been densified via sintering in a furnace, a time-consuming and energy-intensive process. The need to minimize environmental impact calls for new physical concepts beyond large kilns relying on thermal radiation and insulation. Here, we realize ultrarapid heating with intense blue and UV-light. Thermal management is quantified in experiment and finite element modelling and features a balance between absorbed and radiated energy. With photon energy above the band gap to optimize absorption, bulk ceramics are sintered within seconds and with outstanding efficiency (≈2 kWh kg -1 ) independent of batch size. Sintering on-the-spot with blacklight as a versatile and widely applicable power source is demonstrated on ceramics needed for energy storage and conversion and in electronic and structural applications foreshadowing economic scalability.

This study examined co-occurring psychosocial problems among 120 women living with HIV (WLWH) in Washington, DC, USA. Participants completed a demographic survey, PHQ-9 (depressive symptoms), the Life Stressor Checklist (stressful events) and the PCL-C (PTSD symptoms in civilian populations). We calculated descriptive statistics and chi-square solutions for participant demographics. Classes of trauma history were established using latent class analysis (LCA). Latent indicators were extracted from participant self-reported traumatic histories on the LSC-R. Traumatic events have been found to be predictive of both depression. Latent class solution selection was guided by utility in evaluating and discriminating between classes as predictors of scales measuring depression or trauma exposure. Three distinct classes of trauma histories were identified: a high trauma (HT) class, an abuse/neglect (AN) class and a childhood trauma (CT) class. Binary logistic regression analyses determined whether trauma profiles predicted depression or PTSD after controlling for age, marital status, race and education. Participants in both the AN and CT class were over five times more likely than those in the HT class to endorse depressive symptoms. Classes differed significantly on whether they endorse depressive symptoms ( p  = .008) and marital status ( p  = .009), while PTSD appeared to trend toward significance ( p  = .085).

The present case report describes a technique to convert an interim mandibular complete dental prosthesis into a digitally designed and additively manufactured implant overdenture prosthesis. A patient had two dental implants placed, an interim complete denture, and a soft reline procedure completed. After implant osseointegration, existing healing abutments were removed, a functionally generated reline impression with polyvinyl siloxane impression material was made. Using an intraoral scanner, a 360-degree optical scan was obtained of the relined interim prosthesis. A new prosthesis was digitally designed using the optical scan, additively manufactured, and housings picked-up intraorally to create an implant-retained overdenture., (© 2021 by the American College of Prosthodontists.)

Background: Promoter methylation of the DNA repair gene O 6 -methylguanine-DNA methyltransferase (MGMT) is an acknowledged predictive epigenetic marker in glioblastoma multiforme and anaplastic astrocytoma. Patients with methylated CpGs in the MGMT promoter benefit from treatment with alkylating agents, such as temozolomide, and show an improved overall survival and progression-free interval. A precise determination of MGMT promoter methylation is of importance for diagnostic decisions. We experienced that different methods show partially divergent results in a daily routine. For an integrated neuropathological diagnosis of malignant gliomas, we therefore currently apply a combination of methylation-specific PCR assays and pyrosequencing., Results: To better rationalize the variation across assays, we compared these standard techniques and assays to deep bisulfite sequencing results in a cohort of 80 malignant astrocytomas. Our deep analysis covers 49 CpG sites of the expanded MGMT promoter, including exon 1, parts of intron 1 and a region upstream of the transcription start site (TSS). We observed that deep sequencing data are in general in agreement with CpG-specific pyrosequencing, while the most widely used MSP assays published by Esteller et al. (N Engl J Med 343(19):1350-1354, 2000. https://doi.org/10.1056/NEJM200011093431901 ) and Felsberg et al. (Clin Cancer Res 15(21):6683-6693, 2009. https://doi.org/10.1158/1078-0432.CCR-08-2801 ) resulted in partially discordant results in 22 tumors (27.5%). Local deep bisulfite sequencing (LDBS) revealed that CpGs located in exon 1 are suited best to discriminate methylated from unmethylated samples. Based on LDBS data, we propose an optimized MSP primer pair with 83% and 85% concordance to pyrosequencing and LDBS data. A hitherto neglected region upstream of the TSS, with an overall higher methylation compared to exon 1 and intron 1 of MGMT, is also able to discriminate the methylation status., Conclusion: Our integrated analysis allows to evaluate and redefine co-methylation domains within the MGMT promoter and to rationalize the practical impact on assays used in daily routine diagnostics., (© 2022. The Author(s).)

Patients who require transitioning from natural teeth to dental implants present a unique challenge to clinicians. When evaluating decisionmaking processes, clinicians must determine the best restorative treatment options for the patient. Fixed and removable treatment options may both become ideal possibilities for a patient, depending on the patient's clinical presentation. Patients who are interested in fixed options but may not have the financial resources to be able to afford this more expensive alternative often may choose removable overdenture solutions. This article discusses ideal treatment planning strategies for patients interested in dual-arch overdenture restorations and reviews a clinical case describing this treatment.

Objective: Self-medication using alcohol is a common coping response among individuals dealing with trauma as is driving under the influence of alcohol (DUI). A common intervention for drivers convicted of DUI, is an alcohol ignition interlock device (IID)-which requires breath samples before starting the car. If the sample is above a predetermined limit (.025), the car will not start, thus preventing impaired driving. IIDs are an effective intervention to reduce rates of drinking and driving among high risk populations; however, limited research has examined how traumatic experiences may impact performance on IIDs., Methods: This study is an archival analysis of the Managing Heavy Drinking (MHD) study of drivers in New York state. The MHD is a comprehensive study of drivers convicted of a DUI from 2015-2020. Participants (N = 121) completed questionnaires and provided consent to retrieve information from interlock providers. Outcome variable included high BAC lockout ratios (number of high BAC lockouts [BAC>.08]/number of clean blows [BAC ≤ .025]). Other variables included demographic variables, alcohol treatment history, trauma experiences, and prior DUI history. Variables were entered into a structural equation model., Results: In the final structural model, pathways that demonstrated a p -value of greater than .10 were dropped from the model. This produced acceptable overall model fit statistics (χ2 = 27.059(10), p =.003; CFI = .900; NFI = .898; RMSEA = .063). A significant pathway was found from the trauma measure to alcohol use ( β = .132), and from alcohol use to interlock performance ( β = .636). However, no significant relationship was found between trauma and interlock performance other than through alcohol use., Conclusions: The current study provides a useful framework upon which to understand the role traumatic experiences have on alcohol IID performance. Traumatic experiences are in of themselves insufficient to impact IID performance directly, but it may indirectly impact IID performance through increasing alcohol use.

Recently, the twist angle between adjacent sheets of stacked van der Waals materials emerged as a new knob to engineer correlated states of matter in two-dimensional heterostructures in a controlled manner, giving rise to emergent phenomena such as superconductivity or correlated insulating states. Here, we use an ab initio based approach to characterize the electronic properties of twisted bilayer MoS 2 . We report that, in marked contrast to twisted bilayer graphene, slightly hole-doped MoS 2 realizes a strongly asymmetric p x -p y Hubbard model on the honeycomb lattice, with two almost entirely dispersionless bands emerging due to destructive interference. The origin of these dispersionless bands, is similar to that of the flat bands in the prototypical Lieb or Kagome lattices and co-exists with the general band flattening at small twist angle due to the moiré interference. We study the collective behavior of twisted bilayer MoS 2 in the presence of interactions, and characterize an array of different magnetic and orbitally-ordered correlated phases, which may be susceptible to quantum fluctuations giving rise to exotic, purely quantum, states of matter., (© 2021. The Author(s).)

Background: Understanding the influence of genetic variants on DNA methylation is fundamental for the interpretation of epigenomic data in the context of disease. There is a need for systematic approaches not only for determining methylation quantitative trait loci (methQTL), but also for discriminating general from cell type-specific effects., Results: Here, we present a two-step computational framework MAGAR ( https://bioconductor.org/packages/MAGAR ), which fully supports the identification of methQTLs from matched genotyping and DNA methylation data, and additionally allows for illuminating cell type-specific methQTL effects. In a pilot analysis, we apply MAGAR on data in four tissues (ileum, rectum, T cells, B cells) from healthy individuals and demonstrate the discrimination of common from cell type-specific methQTLs. We experimentally validate both types of methQTLs in an independent data set comprising additional cell types and tissues. Finally, we validate selected methQTLs located in the PON1, ZNF155, and NRG2 genes by ultra-deep local sequencing. In line with previous reports, we find cell type-specific methQTLs to be preferentially located in enhancer elements., Conclusions: Our analysis demonstrates that a systematic analysis of methQTLs provides important new insights on the influences of genetic variants to cell type-specific epigenomic variation., (© 2021. The Author(s).)

Domain wall motion in ferroics, similar to dislocation motion in metals, can be tuned by well-concepted microstructural elements. In demanding high-power applications of piezoelectric materials, the domain wall motion is considered as a lossy hysteretic mechanism that should be restricted. Current applications for so-called hard piezoelectrics are abundant and hinge on the use of an acceptor-doping scheme. However, this mechanism features severe limitations due to enhanced mobility of oxygen vacancies at moderate temperatures. By analogy with metal technology, the authors present here a new solution for electroceramics, where precipitates are utilized to pin domain walls and improve piezoelectric properties. Through a sequence of sintering, nucleation, and precipitate growth, intragranular precipitates leading to a fine domain structure are developed as shown by transmission electron microscopy, piezoresponse force microscopy, and phase-field simulation. This structure impedes the domain wall motion as elucidated by electromechanical characterization. As a result, the mechanical quality factor is increased by ≈50% and the hysteresis in electrostrain is suppressed considerably. This is even achieved with slightly increased piezoelectric coefficient and electromechanical coupling factor. This novel process can be smoothly implemented in industrial production processes and is accessible to simple laboratory experimentation for microstructure optimization and implementation in various ferroelectric systems., (© 2021 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Introduction: Literature notes the efficacious use of alcohol ignition interlock devices (IID) in reducing rates of drinking and driving while installed on the vehicle. Some drivers who are convicted of driving while intoxicated (DWI) elect to have their license suspended/revoked instead of installing the device. These individuals represent a high-risk subsample of drivers, yet limited literature has addressed this concern. The current study seeks to fill this gap using qualitative interviews addressing: (i) why do non-installers make the choice to not install a mandated IID; and (ii) how are non-installers managing without the IID?, Methods: The study utilises the Managing Heavy Drinkers study of drivers in Erie County, New York, USA. Participants were purposively sampled from a group of non-installers (n = 6; four females, two males) who completed semi-structured interviews. Constructed grounded theory was used to develop a theoretical understanding of participant's experiences., Results: To understand why participants elect not to install the IID, thematic analysis revealed: alleviating constraints, predominantly the financial burdens associated with an IID, and institutional mistrust. Additionally, data revealed that participants are managing without the IID by mitigating apprehension. This included driving cautiously to avoid detection and utilising alternative transportation., Discussion and Conclusions: This study furthers understanding of why drivers convicted of a DWI elect not to install an IID. Future research should seek to identify barriers to IID installation. This work provides evidence for establishing institutional protocols that ensure drivers convicted of a DWI receive consistent and correct information about the IID process., (© 2021 Australasian Professional Society on Alcohol and other Drugs.)

Objectives: Attitude of health care workers (HCW), namely registered nurses, towards SARS-CoV-2 vaccination and compulsory vaccination., Method: In a structured anonymous scientific survey from January 29 to April 26, 2021 a questionnaire was sent to 72 heads of orthopedic and trauma departments. The doctors were asked to distribute and recollect the questionnaire after obtaining informed consent from the hospital administration, the nursing management and the works council. Descriptive statistics were used to explain the results., Results: 355 answers from 5 departments were evaluated. In 65 out of 72 hospitals the top managers of either hospital or nursing administration or the works council declined participation, 2 heads of department were not interested. 50,7% of HCW were already vaccinated or had a scheduled appointment for vaccination, 14,9% had not yet made up their mind and 34,4% refuse vaccination. The majority of HCW vote against compulsory vaccination (47,6%), less than a quarter approves it (23,4%)., Conclusion: The willingness to vaccinate was extremely low in this survey. The main reason for refusal to vaccinate is fear of side effects, so an information campaign should primarily focus on this topic., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Therapies based on targeting immune checkpoints have revolutionized the treatment of metastatic melanoma in recent years. Still, biomarkers predicting long-term therapy responses are lacking., Methods: A novel approach of reference-free deconvolution of large-scale DNA methylation data enabled us to develop a machine learning classifier based on CpG sites, specific for latent methylation components (LMC), that allowed for patient allocation to prognostic clusters. DNA methylation data were processed using reference-free analyses (MeDeCom) and reference-based computational tumor deconvolution (MethylCIBERSORT, LUMP)., Results: We provide evidence that DNA methylation signatures of tumor tissue from cutaneous metastases are predictive for therapy response to immune checkpoint inhibition in patients with stage IV metastatic melanoma., Conclusions: These results demonstrate that LMC-based segregation of large-scale DNA methylation data is a promising tool for classifier development and treatment response estimation in cancer patients under targeted immunotherapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Before the COVID-19 pandemic, very little was known about the impact of social isolation on individuals' alcohol use and misuse. This study examines how socially isolated individuals with a history of heavy drinking used alcohol during the pandemic., Methods: Data for this study came from an add-on to the Managing Heavy Drinking (MHD) longitudinal study of drivers convicted of DWI that was conducted in Erie County, New York. Pre-COVID information (October 2019-March 2020) was augmented with a COVID-19 questionnaire collected between July and August 2020. A total of 92 participants completed the COVID-19 survey., Results: The sample of problem drinkers showed a significant increase after the pandemic outbreak in the average number of drinking days from 1.99 to 2.49 per week (p = 0.047), but a significant decrease in the average number of drinks per drinking day, from 3.74 to 2.74 (p = 0.003). The proportion of individuals who drank more frequently was greater among those who, before the outbreak had an Alcohol Use Disorders Identification Test (AUDIT) score <8 (26% increase) compared with those with an AUDIT score of >8 (13%). Alcohol treatment was also associated with the frequency of drinking, with individuals who were not in alcohol treatment showing a 16% increase in frequency compared with a 10% increase among those in treatment. Further, individuals who, after the outbreak worried about their health (30%) or finances (37%) reported greater increases in the frequency of drinking than those who did not worry about their health (17%) or finances (10%)., Conclusions: Overall, the individuals in our sample showed small changes in the frequency andheaviness of drinking after the outbreak of COVID-19, effects that opposite in direction from one another and thus resulted in no overall change in drinks consumed. Nonetheless, we identified factors that influenced the effects of the pandemic on drinking behavior among individuals convicted of DWI, which emphasizes the need to individualize these individuals' treatment, particularly in the context of dramatic environmental change., (© 2021 by the Research Society on Alcoholism.)

Background: Half of the offenders convicted of impaired driving in the United States are sentenced to install alcohol ignition interlock devices (IIDs), which prevent them from starting their vehicles if they have been drinking. No research has yet explored offenders' patterns of alcohol consumption and driving under the influence of alcohol (DUI) from the time before the arrest to the time period after the IID is installed. This study aims to fill that gap in knowledge., Methods: Using the Timeline Follow-back interview procedure, we assessed the daily drinking of 153 convicted DUI offenders' self-reported total alcohol consumption and rates of self-reported driving after drinking over 4 phases: before DUI arrest, between arrest and IID installation, during the phase on the interlock, and after the interlock is removed. Because information about behaviors in each period was not available for every participant, comparisons were made using paired-sample contrasts., Results: Compared with before the arrest, total alcohol use decreased by 50% in the 4-month phase following arrest and before IID installation, though it did not change much afterward. The frequency of drinking and driving decreased sharply after the arrest (-82%), with further decrease upon installation of the interlock (-58%, p = 0.05). The frequency of drinking and driving after the IID was removed returned to preinstallation drinking and driving status (+58%, p = 0.01)., Conclusions: Participants made significant adjustments to their drinking behavior by adhering to the traditional DUI driving restrictions in the postarrest phase. Although installation of an IID was not associated with a significant change in drinking, it further reduced the frequency of drinking and driving. Evaluations of the IID experience should take into account information on an individual's drinking and DUI behaviors not only before the IID was installed, but before the individual was arrested., (© 2021 by the Research Society on Alcoholism.)

Epigenetics studies inheritable and reversible modifications of DNA that allow cells to control gene expression throughout their development and in response to environmental conditions. In computational epigenomics, machine learning is applied to study various epigenetic mechanisms genome wide. Its aim is to expand our understanding of cell differentiation, that is their specialization, in health and disease. Thus far, most efforts focus on understanding the functional encoding of the genome and on unraveling cell-type heterogeneity. Here, we provide an overview of state-of-the-art computational methods and their underlying statistical concepts, which range from matrix factorization and regularized linear regression to deep learning methods. We further show how the rise of single-cell technology leads to new computational challenges and creates opportunities to further our understanding of epigenetic regulation., (© 2021. Springer Nature America, Inc. part of Springer Nature.)

The hard- and soft-tissue replacement materials in the traditional workflow for an implant fixed complete denture are acrylic resin and conventional resin denture teeth supported by a rigid substructure. A novel technique is described combining a modified digital complete denture workflow with analog components and systems, allowing the use of multicolored zirconia and 3D-printed resin. In combination with an appropriate metal substructure, a high-quality prosthesis can be fabricated with reduced effort and cost., (Copyright © 2020 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Wound healing is a complex process, and disturbance of even a single mechanism can result in chronic ulcers developing after exposure to the alkylating agent sulfur mustard (SM). A possible contributor may be SM-induced chronic senescent mesenchymal stem cells (MSCs), unable to fulfil their regenerative role, by persisting over long time periods and creating a proinflammatory microenvironment. Here we show that senescence induction in human bone marrow derived MSCs was time- and concentration-dependent, and chronic senescence could be verified 3 weeks after exposure to between 10 and 40 µM SM. Morphological changes, reduced clonogenic and migration potential, longer scratch closure times, differences in senescence, motility and DNA damage response associated genes as well as increased levels of proinflammatory cytokines were revealed. Selective removal of these cells by senolytic drugs, in which ABT-263 showed initial potential in vitro, opens the possibility for an innovative treatment strategy for chronic wounds, but also tumors and age-related diseases.

Introduction: Alcohol ignition interlock devices (IID) reduce rates of drinking and driving. The interlock offers an opportune time for tailoring targeted interventions to develop habits to separate drinking from driving among this high-risk population. This study identified different types of IID users upon whom targeted interventions could be developed., Methods: Participants (N = 114) were assessed at IID installation and again six months later. Latent class analysis (LCA) was conducted using drinking environment, drinking motivation, social support, drug use, and problem drinking behaviors as indicators. Multivariate regression analyses were conducted comparing latent class assignment with impaired driving attempts., Results: LCA supported a 4-class model where 14.8% of participants fell into the low use/high awareness class; 30.6% fell into the heavy use/high awareness class; 30.6% fell into the mixed use/high awareness class; and 24.0% fell into the moderate use/low awareness class. Drivers in the moderate use/low awareness condition had increased early morning BAC lockouts., Conclusions: These typologies demonstrate important differences within high risk drivers. Indeed, drivers who fell into the moderate use/low awareness class may not have considered their alcohol-related behaviors problematic. This information could lend itself to the development of targeted interventions to address subgroups of drinking drivers.

Objective: Alcohol-impaired driving results in thousands of deaths annually. Alcohol ignition interlocks require a negative breath test to start a vehicle's engine, and 44 states have mandated some form of interlock law for drivers convicted of driving while intoxicated (DWI). The objective of this study was to estimate the association between interlock laws and fatal impaired-driving crashes., Methods: Differences in three interlock laws were evaluated by comparing alcohol-impaired passenger vehicle drivers involved in fatal crashes between 2001 and 2019 in the United States across state and time. State/time differences unrelated to interlock laws were controlled for by fitting a Poisson model. The exposure measure was the number of passenger vehicle drivers in fatal crashes that did not involve impaired drivers. Laws requiring interlocks for drivers convicted of DWI covered: repeat offenders, repeat offenders and high-BAC offenders, all offenders, or none., Results: The number of states with all-offender interlock laws during the study period went from three in 2001 to 29 in 2019, and the number of states with any of the three laws increased from 16 to 44. All-offender laws were associated with 26% fewer drivers with 0.08+ BAC involved in fatal crashes, compared with no law. Repeat-offender laws were associated with a 9% reduction in impaired drivers, compared with no law. Repeat and high-BAC laws were associated with a 20% reduction in impaired drivers in fatal crashes, compared with no law., Conclusion: Laws mandating alcohol ignition interlocks, especially those covering all offenders, are an effective impaired-driving countermeasure that reduces the number of impaired drivers in fatal crashes.

Background: Alcohol ignition interlock devices (IIDs) reduce rates of drinking and driving when installed on the vehicles of offenders. While the IID is installed on their vehicle, some drivers adapt their drinking behaviors, while others cannot. Heavy alcohol use and mental health concerns reduce treatment adherence in clinical settings, but it has not yet known how they pertain to behavioral adaptation to IIDs., Objectives: This study focuses on identifying driver typologies as predictors of performance while on alcohol IIDs., Methods: The study utilizes the Managing Heavy Drinking study of drivers in New York state. Participants (N = 101; 59 males, 42 females) completed questionnaires assessing demographic information, drinking behaviors, driving history and mental health measures. All participants had been convicted of a DUI, and installed an IID. Latent class analysis was used to establish typologies and predict lockout ratios., Results: Four typologies emerged and drivers with elevations in mental health concerns had significantly worse lockout ratios than those in other classes., Conclusions: The current study may provide support for interventions designed to identify drivers with comorbid mental health concerns and tailor appropriate interventions to administer while the IID is installed with the aim of improving behavioral adaptation to the device.

DNA methylation profiling offers unique insights into human development and diseases. Often the analysis of complex tissues and cell mixtures is the only feasible option to study methylation changes across large patient cohorts. Since DNA methylomes are highly cell type specific, deconvolution methods can be used to recover cell type-specific information in the form of latent methylation components (LMCs) from such 'bulk' samples. Reference-free deconvolution methods retrieve these components without the need for DNA methylation profiles of purified cell types. Currently no integrated and guided procedure is available for data preparation and subsequent interpretation of deconvolution results. Here, we describe a three-stage protocol for reference-free deconvolution of DNA methylation data comprising: (i) data preprocessing, confounder adjustment using independent component analysis (ICA) and feature selection using DecompPipeline, (ii) deconvolution with multiple parameters using MeDeCom, RefFreeCellMix or EDec and (iii) guided biological inference and validation of deconvolution results with the R/Shiny graphical user interface FactorViz. Our protocol simplifies the analysis and guides the initial interpretation of DNA methylation data derived from complex samples. The harmonized approach is particularly useful to dissect and evaluate cell heterogeneity in complex systems such as tumors. We apply the protocol to lung cancer methylomes from The Cancer Genome Atlas (TCGA) and show that our approach identifies the proportions of stromal cells and tumor-infiltrating immune cells, as well as associations of the detected components with clinical parameters. The protocol takes slightly >3 d to complete and requires basic R skills.

DNA methylation is an epigenetic mark with important regulatory roles in cellular identity and can be quantified at base resolution using bisulfite sequencing. Most studies are limited to the average DNA methylation levels of individual CpGs and thus neglect heterogeneity within the profiled cell populations. To assess this within-sample heterogeneity (WSH) several window-based scores that quantify variability in DNA methylation in sequencing reads have been proposed. We performed the first systematic comparison of four published WSH scores based on simulated and publicly available datasets. Moreover, we propose two new scores and provide guidelines for selecting appropriate scores to address cell-type heterogeneity, cellular contamination and allele-specific methylation. Most of the measures were sensitive in detecting DNA methylation heterogeneity in these scenarios, while we detected differences in susceptibility to technical bias. Using recently published DNA methylation profiles of Ewing sarcoma samples, we show that DNA methylation heterogeneity provides information complementary to the DNA methylation level. WSH scores are powerful tools for estimating variance in DNA methylation patterns and have the potential for detecting novel disease-associated genomic loci not captured by established statistics. We provide an R-package implementing the WSH scores for integration into analysis workflows., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

On Mar 11th, 2020, the World Health Organization (WHO) stated in its Situation Report - 51 Coronavirus disease 2019 (COVID-19) as a pandemic. In early April 2020, a teaching hospital underwent shutdown and quarantine due to an outbreak of infection in accordance with Section 6 of the Infection Protection Act (index patient and 5 infected nursing staff). The complete staff (physicians, nurses and nonmedical personnel [NMP]) underwent COVID-19 testing within two phases: (1) between Apr 3rd and 5th, 2020 [n=1170], followed by (2) between Apr 8th and 9th, 2020 [n=953] with COVID-19 silent carrier positivity rates in accordance to testing phases of (1) n=19 (1.6%) and (2) n=25 (2.6%). The cumulative infection rate for NMP (1.6%), doctors (3.8%) and nurses (9.7%) was connected to type and extent of COVID-19 patient contact. Despite COVID-19 positivity of 34.8% (46 of 132 beds), a risk-free management of hospital operation is possible to a certain extent if hygiene regulations and strict patient selection are followed. However, a COVID-19-free clinic cannot be expected due to silent carriers.

Background: Cell-type heterogeneity of tumors is a key factor in tumor progression and response to chemotherapy. Tumor cell-type heterogeneity, defined as the proportion of the various cell-types in a tumor, can be inferred from DNA methylation of surgical specimens. However, confounding factors known to associate with methylation values, such as age and sex, complicate accurate inference of cell-type proportions. While reference-free algorithms have been developed to infer cell-type proportions from DNA methylation, a comparative evaluation of the performance of these methods is still lacking., Results: Here we use simulations to evaluate several computational pipelines based on the software packages MeDeCom, EDec, and RefFreeEWAS. We identify that accounting for confounders, feature selection, and the choice of the number of estimated cell types are critical steps for inferring cell-type proportions. We find that removal of methylation probes which are correlated with confounder variables reduces the error of inference by 30-35%, and that selection of cell-type informative probes has similar effect. We show that Cattell's rule based on the scree plot is a powerful tool to determine the number of cell-types. Once the pre-processing steps are achieved, the three deconvolution methods provide comparable results. We observe that all the algorithms' performance improves when inter-sample variation of cell-type proportions is large or when the number of available samples is large. We find that under specific circumstances the methods are sensitive to the initialization method, suggesting that averaging different solutions or optimizing initialization is an avenue for future research., Conclusion: Based on the lessons learned, to facilitate pipeline validation and catalyze further pipeline improvement by the community, we develop a benchmark pipeline for inference of cell-type proportions and implement it in the R package medepir.

Background: Some alcohol interventions have been found to have the adverse outcome of increasing non-alcohol-related substance use. It is unknown, however, how changes in alcohol use over the course of alcohol ignition interlocks - a common DUI intervention - may impact other substance use., Methods: Alcohol and cannabis use were measured using hair ethylglucuronide and Delta-9-Tetrahydrocannabinol concentrations in blood, respectively. Participants (N = 69) were measured at the interlock installation period and again 6-months later while the interlock was installed. A mixed ANOVA was conducted to examine changes in levels of ethanol and THC over time., Results: On measures of marijuana use, there was a significant interaction effect between the group that increased alcohol use and time F (2, 66) = 7.863, p =.001; partial η 2 =.192; as well as a main effect for time F (2, 66) = 21.106, p <.001; partial η 2 =.242., Conclusions: Installing interlocks may inadvertently increase cannabis use among those who decrease alcohol use. Crash risk associated with cannabis use is notably less than that of alcohol use, however, continued cannabis use may be problematic when the device is removed and alcohol use is expected to return to the higher pre-interlock levels.

Objectives: The purpose of this investigation was to compare the drinking patterns and experiences (both positive and negative) among DUI offenders who had installed an ignition interlock. The association between those experiences and interlock performance as measured by the number of times they had a lockout, was also assessed., Methods: Over 300 DUI offenders who installed an interlock in the State of Florida were recruited and completed an on-line survey at the beginning and end of their interlock restriction. A record of the interlock performance data from each was downloaded and used to determine how many lockouts they experienced during their interlock restriction period. Offenders were defined into two groups; successful cases (having 0 or 1 lockout) or poor performers (have 2 or more lockouts). Chi-square and binary regressions were used to assess differences between groups., Results: Poor performers reported significantly more drinking and were more likely to drink in a context of emotional comfort, yet they were more likely to report positive experiences with the interlock, especially as to its ability to remind them to avoid another DUI by reducing their drinking and driving. No difference was found between these two groups for the interlock's ability to reduce drinking., Conclusions: People with a more serious drinking pattern and who may be most at risk for recidivating may be more inclined to recognize the potential benefits of the interlock as a DUI preventive countermeasure. More research is needed to identify and influence high risk DUI offenders while on the interlock to increase its effectiveness once the interlock is removed.

Motivation: Predictive models are a powerful tool for solving complex problems in computational biology. They are typically designed to predict or classify data coming from the same unknown distribution as the training data. In many real-world settings, however, uncontrolled biological or technical factors can lead to a distribution mismatch between datasets acquired at different times, causing model performance to deteriorate on new data. A common additional obstacle in computational biology is scarce data with many more features than samples. To address these problems, we propose a method for unsupervised domain adaptation that is based on a weighted elastic net. The key idea of our approach is to compare dependencies between inputs in training and test data and to increase the cost of differently behaving features in the elastic net regularization term. In doing so, we encourage the model to assign a higher importance to features that are robust and behave similarly across domains., Results: We evaluate our method both on simulated data with varying degrees of distribution mismatch and on real data, considering the problem of age prediction based on DNA methylation data across multiple tissues. Compared with a non-adaptive standard model, our approach substantially reduces errors on samples with a mismatched distribution. On real data, we achieve far lower errors on cerebellum samples, a tissue which is not part of the training data and poorly predicted by standard models. Our results demonstrate that unsupervised domain adaptation is possible for applications in computational biology, even with many more features than samples., Availability and Implementation: Source code is available at https://github.com/PfeiferLabTue/wenda., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2019. Published by Oxford University Press.)

A straightforward method for simultaneous determination of 58 aromatic amines (AAs) in clothing textiles is described. Of the tested amines, 22 are known carcinogens and regulated under European law. Further unregulated amines, which are suspected to be carcinogenic or mutagenic, are also expected to occur in textiles. The focus of this study was to obtain a multimethod with regulated and unregulated AAs and to separate different positional isomers of specific amines. To achieve this goal, the HPLC parameters such as column phase chemistry and mobile phase pH were optimized. All other amines were separated with the same conditions evaluated for the positional isomers. The sample preparation was reduced to a minimum in accordance to DIN EN 14362-1. After reductive cleavage and dilution of the extracts, the samples were prepared for LC-MS/MS analysis. Further cleanup of the samples with diatomaceous earth was no longer required with this modified sample preparation. The method was validated by spiking the extracts of blank textiles with the chosen amines. Lower Limits of Quantification (LLOQs) ranged from 1 to 10 mg kg -1 . Excellent linearity from 10 to 500 μg L -1 was obtained with coefficients (r) higher than 0.99 allowing a one-point calibration (300 μg L -1 corresponding to 60 mg kg -1 in textiles) forced through zero for the samples. Recovery ranged from 88 to 116% with intra- and inter-day precision values of 1.8-12.1%. The accuracy of this method was tested by a certified reference material (iis18A03, Institute for laboratory Studies, the Netherlands) and showed excellent recoveries higher than 95%. Finally, the described method was successfully applied on 150 real samples with different textile fibres and colours. Positive results were confirmed by means of the spectral library and with the ion ratios., (Copyright © 2019 Elsevier B.V. All rights reserved.)

DNA methylation is a widely investigated epigenetic mark with important roles in development and disease. High-throughput assays enable genome-scale DNA methylation analysis in large numbers of samples. Here, we describe a new version of our RnBeads software - an R/Bioconductor package that implements start-to-finish analysis workflows for Infinium microarrays and various types of bisulfite sequencing. RnBeads 2.0 ( https://rnbeads.org/ ) provides additional data types and analysis methods, new functionality for interpreting DNA methylation differences, improved usability with a novel graphical user interface, and better use of computational resources. We demonstrate RnBeads 2.0 in four re-runnable use cases focusing on cell differentiation and cancer.