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Superficial granulomatous pyoderma gangrenosum is a rare, superficial, vegetating form of pyoderma gangrenosum that tends to occur as a single lesion, most commonly on the trunk. Herein, we report a clinically confounding case of disseminated superficial granulomatous pyoderma gangrenosum in a patient with a 5-year history of painful and chronic ulcerations of the bilateral upper extremities and face in a sun exposed distribution. This was a diagnostically challenging case due to the treatment-refractory nature of our patient's skin lesions and the atypical clinical and histologic presentations encountered. We review our clinical decision process and acknowledge other entities that were considered during the clinical course of this case. Additionally, we discuss the lack of responsiveness to various treatment options with eventual successful clearance of this patient's active skin disease with initiation of adalimumab.

Nicholas L Bormann,1 Cindy J Stoppel,1 Stephan Arndt,2,3 Tyler S Oesterle1 1Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, USA; 2Department of Psychiatry, University of Iowa, Iowa City, Iowa, USA; 3Department of Biostatistics, University of Iowa, Iowa City, Iowa, USACorrespondence: Nicholas L Bormann, Department of Psychiatry, Mayo Clinic, 200 1 st Street SW, Rochester, MN, 55905, USA, Tel +1 507 284 2088, Fax +1 507 284 4158, Email bormann.nicholas@mayo.eduPurpose: Telehealth use has grown tremendously since the onset of the COVID-19 pandemic. While the benefits of virtual care delivery are numerous, little is known about patient experiences in group treatment settings when members join both virtually and in person with the counselor (a hybrid model). We sought to fill this gap by comparing patient survey data across care delivery models.Patients and Methods: Adult patients with a substance use disorder enrolled at one of seven intensive outpatient (IOP) programs in rural Minnesota voluntarily completed a questionnaire assessing patient satisfaction, perceived therapeutic alliance, group cohesion, and insight gained from treatment. Starting 7/1/2021, groups were either all virtual, all in-person, or a hybrid model. The survey began on 1/1/2022. Analysis of covariance (ANCOVA) tested for differences among treatment groups. Separate models were used for each survey question, where the dependent variable was the survey response, the test of interest being treatment group-type, with covariates of length of stay and age. Model estimates and model-based standard deviations were used to calculate the Cohen’s d effect size.Results: Survey results from a total of 1037 individuals were included, one survey per respondent. Data was deidentified upon receipt of the survey, preventing specific demographic comparisons. For the hybrid groups, no significant differences were noted with survey responses relative to in-person, with negligible to small effect sizes seen. When comparing virtual to in-person, virtual was rated as significantly worse than in-person on 6 of the 8 questions; effect size estimates exceeded the small effect size cut-off, and the 95% CI exceeded the moderate cut-off.Conclusion: Creating a group model where patients can attend both virtually and in-person together appears to improve perceived therapeutic alliance, group cohesion, and treatment insight, compared to virtual-only groups, which may have a negative effect relative to in-person.Keywords: addiction, telemedicine, group psychotherapy, survey, questionnaire

Abstract Neuroglia critically shape the brain´s response to ischemic stroke. However, their phenotypic heterogeneity impedes a holistic understanding of the cellular composition of the early ischemic lesion. Here we present a single cell resolution transcriptomics dataset of the brain´s acute response to infarction. Oligodendrocyte lineage cells and astrocytes range among the most transcriptionally perturbed populations and exhibit infarction- and subtype-specific molecular signatures. Specifically, we find infarction restricted proliferating oligodendrocyte precursor cells (OPCs), mature oligodendrocytes and reactive astrocytes, exhibiting transcriptional commonalities in response to ischemic injury. OPCs and reactive astrocytes are involved in a shared immuno-glial cross talk with stroke-specific myeloid cells. Within the perilesional zone, osteopontin positive myeloid cells accumulate in close proximity to CD44+ proliferating OPCs and reactive astrocytes. In vitro, osteopontin increases the migratory capacity of OPCs. Collectively, our study highlights molecular cross talk events which might govern the cellular composition of acutely infarcted brain tissue.

In addition to storm tides, inland flooding due to intense rainfall has become an increasing threat at coastal lowlands. In particular, the coincidence of both types of events poses great challenges to regional water boards since their technical drainage capacities are limited. In this study, we analysed historical data and scenario-based simulations for gauge Knock near Emden at the German North Sea coast. The evaluation of observed inland flood events shows that mainly moderate storm tide series in combination with large-scale, intense precipitation led to an overload of inland drainage systems, whereas the highest individual storm tides or precipitation events alone could be handled well. Proactive risk management requires climate projections for the future. Therefore, a hydrological and a hydrodynamic ocean model were set up and driven by the same climate simulations to estimate future drainage system overloads. The evaluation of the simulations for the control period of two climate models confirms that the models can reproduce the generation mechanism of the compound events. The coincidence of storm tides and precipitation leads to the highest drainage system overloads, while system overload is also caused by intense rainfall events alone rather than by storm tides without intense precipitation. Scenario projections based on two climate models and two emission scenarios suggest that the intensity of compound events of rainfall and storm tides will increase consistently against the background of mean sea level rise for all investigated climate projections, while simulated system overload is higher for the RCP8.5 scenario compared to the RCP2.6 scenario. Comparable to the past, future compound events will cause more potential damage compared to single extreme events. The model results indicate an increasing frequency and intensity of inland drainage system overloads along the North Sea coast if timely adaptation measures are not taken.

Machine learning algorithms are increasingly applied in hydrological studies with promising results. However, these algorithms generally lack the ability for easy interpretability of the results by users. In this study, we compare six different explainable artificial intelligence (XAI) algorithms that help understand the effect of input data on the simulation results. The methods are explored on two distinct approaches for streamflow modeling using a long short-term memory (LSTM) model: a single model approach using only meteorological forcing data and a regional approach including also static catchment attributes. To gain further insight into the internal dynamics of the LSTM models, the relationship between cell states and soil moisture is investigated. A strong correlation suggests that the LSTM models inherently capture the concept of soil moisture as a catchment-scale storage mechanism. The XAI methods are applied to derive a timestep of influence, revealing how many days of input data are relevant for the model output. All XAI methods result in similar seasonal patterns in the timestep of influence, suggesting that the methods are comparable. Setting soil moisture dynamics in context to seasonal development of the timestep of influence suggests resetting LSTM as soon as soil moisture saturation occurs. HIGHLIGHTS Two long short-term memory (LSTM) models were trained for streamflow modeling.; Internal cell states of LSTMs correspond well with ERA5-Land soil moisture dynamics.; Six explainable artificial intelligence algorithms show similar results.; LSTM resets as soon as soil moisture saturation is reached.;

Mobile phone applications (MPAs) for substance use disorder (SUD) treatment are increasingly used by patients. Although pilot studies have shown promising results, multiple previous systematic reviews noted insufficient evidence for MPA use in SUD treatment—many of the previously published reviews evaluated different trials. Subsequently, we aimed to conduct an umbrella review of previously published reviews investigating the efficacy of MPAs for SUD treatment, excluding nicotine/tobacco because umbrella reviews have been done in this population and the nicotine/tobacco MPA approach often differs from SUD-focused MPAs. No previous reviews have included a statistical meta-analysis of clinical trials to quantify an estimated overall effect. Seven reviews met inclusion criteria, and 17 unique studies with available data were taken from those reviews for the meta-analysis. Overall, reviews reported a lack of evidence for recommending MPAs for SUD treatment. However, MPA-delivered recovery support services, cognitive behavioral therapy, and contingency management were identified across multiple reviews as having promising evidence for SUD treatment. Hedges g effect size for an MPA reduction in substance use–related outcomes relative to the control arm was insignificant (0.137; 95% CI, −0.056 to 0.330; P=.16). In subgroup analysis, contingency management (1.29; 95% CI, 1.088-1.482; τ2=0; k=2) and cognitive behavioral therapy (0.02; 95% CI, 0.001-0.030; τ2=0; k=2) were significant. Although contingency management’s effect was large, both trials were small (samples of 40 and 30). This review includes an adapted framework for the American Psychiatric Association’s MPA guidelines that clinicians can implement to review MPAs critically with patients.

Introduction: The primary objective of this study was to assess the feasibility of a 6-week internet-delivered Mantram Repetition Program (MRP) for women recently treated for breast cancer. A secondary objective explored changes in perceived stress, psycho-spiritual measures, and cytokines in the treatment group compared to a waitlist. Methods: A feasibility study (ORBIT model Phase IIa) with a randomized controlled trial pilot was conducted. Eligible women recently treated for breast cancer were randomized to the treatment group ( n = 14) or a waitlist group ( n = 12) and participated for 12 weeks. During weeks 1-6, the treatment group received the MRP intervention while the waitlisted group was inactive. During weeks 7-12, the treatment group was inactive while the waitlisted group received the MRP intervention. The primary outcomes were feasibility and acceptability of the internet-delivered MRP intervention protocol. Participants completed pre and post-intervention psycho-spiritual health assessments. A subset of participants provided serum for cytokine analyses at enrollment and week 6, coinciding with the period in which the treatment group receiving the MRP intervention. Results: Overall study attrition was 19.2%. MRP adherence for both groups was 86% at post-intervention and 90% in the treatment group at 6-week follow-up. Pre-to-post-intervention analyses pooling both groups’ data demonstrated decreased perceived stress ( p = .045) and increased spiritual well-being ( p =.004). IFN-γ and IL-17A were increased in the waitlisted group and decreased in the treatment group ( p = 0.048). Conclusion: Feasibility of a 6-week, internet-delivered MRP intervention for breast cancer survivors was established. Psycho-spiritual variables and serum cytokines are suitable clinical outcome measures for future MRP studies with breast cancer survivors. Data suggest MRP may reduce perceived stress and support spiritual well-being in women with breast cancer; however, additional studies are needed.

This data note introduces an update to the widely-used Democratic Electoral Systems (DES) data that encompasses the period from 1919 to 1945. The data include 243 legislative lower house and presidential elections in 34 interwar democracies. Information on these elections falls into four categories: first and foremost, DES contains variables that capture the institutional rules that define how elections are organized. Second, the data captures the consequences of electoral rules in the form of summary statistics of electoral outcomes. Third, we include democracy classifications for four major democracy datasets so that users can choose their preferred democracy definition when working with the data. Finally, the DES dataset contains multiple identification variables that allow linking the DES data to a wide variety of other datasets. This update to the DES data is fully compatible with prior releases for the post-war period 1–3 .

Tyler S Oesterle,1,&ast; Nicholas L Bormann,1,&ast; Domenic A Ochal,2 Stephan Arndt,3,4 Scott A Breitinger1 1Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA; 2Mayo Clinic Alix School of Medicine, Rochester, MN, USA; 3Department of Psychiatry, University of Iowa, Iowa City, IA, USA; 4Department of Biostatistics, University of Iowa, Iowa City, IA, USA&ast;These authors contributed equally to this workCorrespondence: Nicholas L Bormann, Department of Psychiatry and Psychology, Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA, Tel +1 507 284 2088, Fax +1 507 284 4158, Email bormann.nicholas@mayo.eduPurpose: Telehealth is associated with a myriad of benefits; however, little is known regarding substance use disorder (SUD) treatment outcomes when participants join group therapy sessions in a combination in-person and virtual setting (hybrid model). We sought to determine if treatment completion rates differed.Patients and Methods: Policy changes caused by the COVID-19 pandemic created a naturalistic, observational cohort study at seven intensive outpatient (IOP) programs in rural Minnesota. Virtual-only delivery occurred 6/1/2020-6/30/2021, while hybrid groups occurred 7/1/2021-7/31/2022. Data was evaluated retrospectively for participants who initiated and discharged treatment during the study period. Participants were IOP group members 18 years and older who had a SUD diagnosis that both entered and discharged treatment during the 26-month period. A consecutive sample of 1502 participants (181– 255 per site) was available, with 644 removed: 576 discharged after the study conclusion, 49 were missing either enrollment or discharge data, 14 transferred sites during treatment, and 5 initiated treatment before the study initiation. Helmert contrasts evaluated the impact of hybrid group exposure.Results: A total of 858 individuals were included. Data was not from the medical chart and was deidentified preventing specific demographics; however, the overall IOP sample for 2020– 2022, from which the sample was derived, was 29.8% female, and 64.1% were 18– 40 years of age. For completed treatment, hybrid group exposure relative to virtual-only had a univariate odds ratio of 1.88 (95% CI: 1.50– 2.41, p < 0.001). No significant difference was seen across IOP sites.Conclusion: These results describe a novel hybrid group approach to virtual care for SUDs with outcome data not previously documented in the literature. While virtual treatment delivery can increase access, these results suggest a benefit is derived from including an in-person option. Further research is needed to identify how an in-person component may change dynamics and if it can be replicated in virtual-only models.Keywords: substance-related disorders, telemedicine, group psychotherapy, comparative study, outcome assessment, health care

Andrea Nicole Weber,1 Joshua Trebach,2 Marielle A Brenner,2 Mary Margaret Thomas,3 Nicholas L Bormann4 1Department of Psychiatry, University of Iowa, Iowa City, IA, USA; 2Department of Emergency Medicine, University of Iowa, Iowa City, IA, USA; 3Hardin Library for the Health Sciences, University of Iowa, Iowa City, IA, USA; 4Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USACorrespondence: Andrea Nicole Weber, Department of Psychiatry, University of Iowa, 500 Newton Road, 1-308 MEB, Iowa City, IA, 52242, USA, Tel +1-319-335-6980, Fax +1-319-384-7467, Email andrea-n-weber@uiowa.eduAbstract: Illicitly manufactured fentanyl (IMF) is a significant contributor to the increasing rates of overdose-related deaths. Its high potency and lipophilicity can complicate opioid withdrawal syndromes (OWS) and the subsequent management of opioid use disorder (OUD). This scoping review aimed to collate the current OWS management of study populations seeking treatment for OWS and/or OUD directly from an unregulated opioid supply, such as IMF. Therefore, the focus was on therapeutic interventions published between January 2010 and November 2023, overlapping with the period of increasing IMF exposure. A health science librarian conducted a systematic search on November 13, 2023. A total of 426 studies were screened, and 173 studies were reviewed at the full-text level. Forty-nine studies met the inclusion criteria. Buprenorphine and naltrexone were included in most studies with the goal of transitioning to a long-acting injectable version. Various augmenting agents were tested (buspirone, memantine, suvorexant, gabapentin, and pregabalin); however, the liberal use of adjunctive medication and shortened timelines to initiation had the most consistently positive results. Outside of FDA-approved medications for OUD, lofexidine, gabapentin, and suvorexant have limited evidence for augmenting opioid agonist initiation. Trials often have low retention rates, particularly when opioid agonist washout is required. Neurostimulation strategies were promising; however, they were developed and studied early. Precipitated withdrawal is a concern; however, the rates were low and adequately mitigated or managed with low- or high-dose buprenorphine induction. Maintenance treatment continues to be superior to detoxification without continued management. Shorter induction protocols allow patients to initiate evidence-based treatment more quickly, reducing the use of illicit or non-prescribed substances.Keywords: synthetic opioids, treatment, diagnosis, prevention, addiction medicine

BackgroundVeterans with post-traumatic stress disorder (PTSD) are more likely to report chronic pain than veterans without PTSD. Yoga has been shown to reduce both chronic pain and PTSD symptoms in clinical trials. The goal of our study was to assess the feasibility and acceptability of conducting a randomized controlled trial (RCT) that combined yoga and mantram repetition (Yoga + MR) into one program for military veterans with both chronic pain and PTSD.MethodsIn this feasibility RCT, 27 veterans were randomized to either Yoga + MR or a relaxation intervention. Due to the COVID-19 pandemic, in-person recruitment, assessments, and intervention attendance were re-evaluated. Although remote delivery of aspects of the study were utilized, interventions were delivered in-person. Feasibility benchmarks met included full recruitment in 12 months or less, 75%+ retention at initial follow-up assessment, 50%+ attendance rate, and 75%+ of participants satisfied with the interventions.ResultsThe sample was racially and ethnically diverse, and 15% of participants were women. Participant recruitment lasted approximately 11 months. Out of 32 participants initially randomized, two participants asked to be dropped from the study and three did not meet PTSD symptom criteria. For the remaining 27 participants, retention rates were 85% at 12 weeks and 81% at 18 weeks. Participants attended 66% of in-person yoga and 55% of in-person relaxation sessions. Satisfaction was high, with 100% of yoga participants and 75%/88% of relaxation participants agreeing or strongly agreeing they were satisfied with the intervention/instructors. After 12 weeks (end of intervention), Yoga + MR participants reported reduced back-pain related disability (primary outcome), reduced alcohol use, reduced fatigue, and increased quality of life, while relaxation group participants reported reductions in pain severity, PTSD symptoms, and fatigue.ConclusionsAmidst many research challenges during the pandemic, recruitment, retention, and efficacy results from this feasibility trial support advancement to a larger RCT to study Yoga + MR for chronic pain and PTSD.

Summary: Background: Household transmission studies seek to understand the transmission dynamics of a pathogen by estimating the risk of infection from household contacts and community exposures. We estimated within/extra-household SARS-CoV-2 infection risk and associated factors in a household cohort study in one of the most vulnerable neighbourhoods in Rio de Janeiro city. Methods: Individuals ≥1 years-old with suspected or confirmed COVID-19 in the past 30 days (index cases) and household members aged ≥1 year were enrolled and followed at 14 and 28 days (study period November/2020–December/2021). RT-PCR testing, COVID-19 symptoms, and SARS-CoV-2 serologies were ascertained in all visits. Chain binomial household transmission models were fitted using data from 2024 individuals (593 households). Findings: Extra-household infection risk was 74.2% (95% credible interval [CrI] 70.3–77.8), while within-household infection risk was 11.4% (95% CrI 5.7–17.2). Participants reporting having received two doses of a COVID-19 vaccine had lower extra-household (68.9%, 95% CrI 57.3–77.6) and within-household (4.1%, 95% CrI 0.4–16.6) infection risk. Within-household infection risk was higher among participants aged 10–19 years, from overcrowded households, and with low family income. Contrastingly, extra-household infection risk was higher among participants aged 20–29 years, unemployed, and public transportation users. Interpretation: Our study provides important insights into COVID-19 household/community transmission in a vulnerable population that resided in overcrowded households and who struggled to adhere to lockdown policies and social distancing measures. The high extra-household infection risk highlights the extreme social vulnerability of this population. Prioritising vaccination of the most socially vulnerable could protect these individuals and reduce widespread community transmission. Funding: Fundação Oswaldo Cruz, CNPq, FAPERJ, Royal Society, Instituto Serrapilheira, FAPESP.

Idiopathic subglottic stenosis (ISGS) is a rare fibrotic disease of the upper trachea with an unknown pathomechanism. It typically affects adult Caucasian female patients, leading to severe airway constrictions caused by progressive scar formation and inflammation with clinical symptoms of dyspnoea, stridor and potential changes to the voice. Endoscopic treatment frequently leads to recurrence, whereas surgical resection and reconstruction provides excellent long-term functional outcome. This study aimed to identify so far unrecognized pathologic aspects of ISGS using single cell RNA sequencing. Our scRNAseq analysis uncovered the cellular composition of the subglottic scar tissue, including the presence of a pathologic, profibrotic fibroblast subtype and the presence of Schwann cells in a profibrotic state. In addition, a pathology-associated increase of plasma cells was identified. Using extended bioinformatics analyses, we decoded pathology-associated changes of factors of the extracellular matrix. Our data identified ongoing fibrotic processes in ISGS and provide novel insights on the contribution of fibroblasts, Schwann cells and plasma cells to the pathogenesis of ISGS. This knowledge could impact the development of novel approaches for diagnosis and therapy of ISGS.

ObjectiveTo determine whether endometrial thickness (EMT) differs between i) clomiphene citrate (CC) and gonadotropin (Gn) utilizing patients as their own controls, and ii) patients who conceived with CC and those who did not. Furthermore, to investigate the association between late-follicular EMT and pregnancy outcomes, in CC and Gn cycles.MethodsRetrospective study. Three sets of analyses were conducted separately for the purpose of this study. In analysis 1, we included all cycles from women who initially underwent CC/IUI (CC1, n=1252), followed by Gn/IUI (Gn1, n=1307), to compare EMT differences between CC/IUI and Gn/IUI, utilizing women as their own controls. In analysis 2, we included all CC/IUI cycles (CC2, n=686) from women who eventually conceived with CC during the same study period, to evaluate EMT differences between patients who conceived with CC (CC2) and those who did not (CC1). In analysis 3, pregnancy outcomes among different EMT quartiles were evaluated in CC/IUI and Gn/IUI cycles, separately, to investigate the potential association between EMT and pregnancy outcomes.ResultsIn analysis 1, when CC1 was compared to Gn1 cycles, EMT was noted to be significantly thinner [Median (IQR): 6.8 (5.5–8.0) vs. 8.3 (7.0–10.0) mm, p

The Karlsruhe Tritium Neutrino (KATRIN) experiment is designed to measure a high-precision integral spectrum of the endpoint region of T2 β decay, with the primary goal of probing the absolute mass scale of the neutrino. After a first tritium commissioning campaign in 2018, the experiment has been regularly running since 2019, and in its first two measurement campaigns has already achieved a sub-eV sensitivity. After 1000 days of data-taking, KATRIN’s design sensitivity is 0.2 eV at the 90% confidence level. In this white paper we describe the current status of KATRIN; explore prospects for measuring the neutrino mass and other physics observables, including sterile neutrinos and other beyond-Standard-Model hypotheses; and discuss research-and-development projects that may further improve the KATRIN sensitivity.

PurposeThis research examined the expression of cortical auditory evoked potentials in a cohort of children who received cochlear implants (CIs) for treatment of congenital deafness (n = 28) and typically hearing controls (n = 28).MethodWe make use of a novel electroencephalography paradigm that permits the assessment of auditory responses to ambiently presented speech and evaluates the contributions of concurrent visual stimulation on this activity.ResultsOur findings show group differences in the expression of auditory sensory and perceptual event-related potential components occurring in 80- to 200-ms and 200- to 300-ms time windows, with reductions in amplitude and a greater latency difference for CI-using children. Relative to typically hearing children, current source density analysis showed muted responses to concurrent visual stimulation in CI-using children, suggesting less cortical specialization and/or reduced responsiveness to auditory information that limits the detection of the interaction between sensory systems.ConclusionThese findings indicate that even in the face of early interventions, CI-using children may exhibit disruptions in the development of auditory and multisensory processing.