Prehospital anesthesia in postcardiac arrest patients: a multicenter retrospective cohort study.

BACKGROUND: Currently, the data regarding the impact of prehospital postcardiac arrest anesthesia on target hemodynamic and ventilatory parameters of early postresuscitation care and recommendations on its implementation are rare. The present study examines the incidence and impact of prehospital postcardiac arrest anesthesia on hemodynamic and ventilatory target parameters of postresuscitation care. METHODS: In this multicentre observational study between 2019 and 2021 unconscious adult patients after out-of-hospital-cardiac arrest with the presence of a return-of-spontaneous circulation until hospital admission were included. Primary endpoint was the application of postarrest anesthesia. Secondary endpoints included the medication group used, predisposing factors to its implementation, and its influence on achieving target parameters of postresuscitation care (systolic blood pressure: ≥ 100 mmHg, etCO2:35-45 mmHg, SpO2: 94-98%) at hospital handover. RESULTS: During the study period 2,335 out-of-hospital resuscitations out of 391,305 prehospital emergency operations (incidence: 0.58%; 95% CI 0.54-0.63) were observed with a return of spontaneous circulation to hospital admission in 706 patients (30.7%; 95% CI 28.8-32.6; female: 34.3%; age:68.3 ± 14.2 years). Postcardiac arrest anesthesia was performed in 482 patients (68.3%; 95% CI 64.7-71.7) with application of hypnotics in 93.4% (n = 451), analgesics in 53.7% (n = 259) and relaxants in 45.6% (n = 220). Factors influencing postcardiac arrest sedation were emergency care by an anesthetist (odds ratio: 2.10; 95% CI 1.34-3.30; P < 0.001) and treatment-free interval ≤ 5 min (odds ratio: 1.59; 95% CI 1.01-2.49; P = 0.04). Although there was no evidence of the impact of performing postcardiac arrest anesthesia on achieving a systolic blood pressure ≥ 100 mmHg at the end of operation (odds ratio: 1.14; 95% CI 0.78-1.68; P = 0.48), patients with postcardiac arrest anesthesia were significantly more likely to achieve the recommended ventilation (odds ratio: 1.59; 95% CI 1.06-2.40; P = 0.02) and oxygenation (odds ratio:1.56; 95% CI 1.04-2.35; P = 0.03) targets. Comparing the substance groups, the use of hypnotics significantly more often enabled the target values for etCO2 to be reached alone (odds ratio:2.79; 95% CI 1.04-7.50; P = 0.04) as well as in combination with a systolic blood pressure ≥ 100 mmHg (odds ratio:4.42; 95% CI 1.03-19.01; P = 0.04). CONCLUSIONS: Postcardiac arrest anesthesia in out-of-hospital cardiac arrest is associated with early achievement of respiratory target parameters in prehospital postresuscitation care without evidence of more frequent hemodynamic complications.

Interface-modulated kinetic differentials in electron and hole transfer rates as a key design principle for redox photocatalysis by Sb2VO5/QD heterostructures.

The efficient conversion of solar energy to chemical energy represents a critical bottleneck to the energy transition. Photocatalytic splitting of water to generate solar fuels is a promising solution. Semiconductor quantum dots (QDs) are prime candidates for light-harvesting components of photocatalytic heterostructures, given their size-dependent photophysical properties and band-edge energies. A promising series of heterostructured photocatalysts interface QDs with transition-metal oxides which embed midgap electronic states derived from the stereochemically active electron lone pairs of p-block cations. Here, we examine the thermodynamic driving forces and dynamics of charge separation in Sb2VO5/CdSe QD heterostructures, wherein a high density of Sb 5s2-derived midgap states are prospective acceptors for photogenerated holes. Hard-x-ray valence band photoemission spectroscopy measurements of Sb2VO5/CdSe QD heterostructures were used to deduce thermodynamic driving forces for charge separation. Interfacial charge transfer dynamics in the heterostructures were examined as a function of the mode of interfacial connectivity, contrasting heterostructures with direct interfaces assembled by successive ion layer adsorption and reaction (SILAR) and interfaces comprising molecular bridges assembled by linker-assisted assembly (LAA). Transient absorption spectroscopy measurements indicate ultrafast (<2 ps) electron and hole transfer in SILAR-derived heterostructures, whereas LAA-derived heterostructures show orders of magnitude differentials in the kinetics of hole (<100 ps) and electron (∼1 ns) transfer. The interface-modulated kinetic differentials in electron and hole transfer rates underpin the more effective charge separation, reduced charge recombination, and greater photocatalytic efficiency observed for the LAA-derived Sb2VO5/CdSe QD heterostructures.

Genes and pathways revealed by whole transcriptome analysis of milk derived bovine mammary epithelial cells after Escherichia coli challenge.

Mastitis, inflammation of the mammary gland, is the costliest disease in dairy cattle and a major animal welfare concern. Mastitis is usually caused by bacteria, of which staphylococci, streptococci and Escherichia coli are most frequently isolated from bovine mastitis. Bacteria activate the mammary immune system in variable ways, thereby influencing the severity of the disease. Escherichia coli is a common cause of mastitis in cattle causing both subclinical and clinical mastitis. Understanding of the molecular mechanisms that activate and regulate the host response would be central to effective prevention of mastitis and breeding of cows more resistant to mastitis. We used primary bovine mammary epithelial cell cultures extracted noninvasively from bovine milk samples to monitor the cellular responses to Escherichia coli challenge. Differences in gene expression between control and challenged cells were studied by total RNA-sequencing at two time points post-challenge. In total, 150 and 440 (Padj < 0.05) differentially expressed genes were identified at 3 h and 24 h post-challenge, respectively. The differentially expressed genes were mostly upregulated at 3 h (141/150) and 24 h (424/440) post-challenge. Our results are in line with known effects of E. coli infection, with a strong early inflammatory response mediated by pathogen receptor families. Among the most significantly enriched early KEGG pathways were the TNF signalling pathway, the cytokine-cytokine receptor interaction, and the NF-kappa B signalling pathway. At 24 h post-challenge, most significantly enriched were the Influenza A, the NOD-like receptor signalling, and the IL-17 signaling pathway.

Midazolam for Post-Arrest Sedation in Pre-Hospital Emergency Care­a Multicenter Propensity Score Analysis.

BACKGROUND: An out-of-hospital cardiac arrest (OHCA) with return of spontaneous circulation (ROSC) may need to be treated with airway management, emergency ventilation, invasive interventions, and post-arrest sedation. We investigated the influence of the use of midazolam for post-arrest sedation on achieving post-resuscitation care targets and the associated risk of hemodynamic complications. METHODS: All emergency rescue missions of the Dresden, Gütersloh, and Lippe medical rescue services in the years 2019-2021 were reviewed to identify adult patients who had OHCA, unconsciousness, and sustained ROSC with spontaneous circulation until arrival at the hospital; the findings were supplemented with data from the German Resuscitation Registry. Patients who received midazolam (alone or in combination with other anesthetic agents) for post-arrest sedation were compared with those who did not. The endpoints were the regaining of a systolic blood pressure ≥ 100 mmHg, end-tidal pCO2 35-45 mmHg, and oxygen saturation (SpO2) 94-98%. A propensity score analysis was used to adjust for age, sex, and variables potentially affecting hemodynamic status or the targets for oxygenation and ventilation. RESULTS: There were 2335 cases of OHCA among 391 305 emergency rescue missions. 571 patients had ROSC before arrival in the hospital (24.5%; female, 33.6%; age, 68 ± 14 years). Of the 395 among them (69.2%) who were treated with post-arrest sedation, 249 (63.0%) received midazolam. Patients who received midazolam reached the guideline-recommended targets for oxygenation, ventilation, and blood pressure more frequently than those who were not sedated: the respective odds ratios and 95% confidence intervals were 2.00 [1.20; 3.34], 1.57 [0.99; 2.48], and 1.41 [0.89; 2.21]. CONCLUSION: The pre-hospital administration of midazolam leads to more frequent pre-hospital attainment of the oxygenation and ventilation targets in post-resuscitation care, without any evidence of an elevated risk of hemodynamic complications.

Urinary comprehensive genomic profiling predicts urothelial carcinoma recurrence and identifies responders to intravesical therapy.

Intravesical therapy (IVT) is the standard of care to decrease risk of recurrence and progression for high-grade nonmuscle-invasive bladder cancer. However, post-IVT recurrence remains common and the ability to risk-stratify patients before or after IVT is limited. In this prospectively designed and accrued cohort study, we examine the utility of urinary comprehensive genomic profiling (uCGP) for predicting recurrence risk following transurethral resection of bladder tumor (TURBT) and evaluating longitudinal IVT response. Urine was collected before and after IVT instillation and uCGP testing was done using the UroAmp™ platform. Baseline uCGP following TURBT identified patients with high (61%) and low (39%) recurrence risk. At 24 months, recurrence-free survival (RFS) was 100% for low-risk and 45% for high-risk patients with a hazard ratio (HR) of 9.3. Longitudinal uCGP classified patients as minimal residual disease (MRD) Negative, IVT Responder, or IVT Refractory with 24-month RFS of 100%, 50%, and 32%, respectively. Compared with MRD Negative patients, IVT Refractory patients had a HR of 10.5. Collectively, uCGP enables noninvasive risk assessment of patients following TURBT and induction IVT. uCGP could inform surveillance cystoscopy schedules and identify high-risk patients in need of additional therapy.

Liver failure after treatment with inotuzumab and polychemotherapy including PEG-asparaginase in a patient with relapsed Philadelphia chromosome-negative acute lymphoblastic leukemia.

We present the case of a 58-year-old female patient who presented with an extramedullary B-ALL relapse after prior allogenic HSCT and blinatumomab therapy. The patient died from complications of a drug-induced acute liver failure after a salvage therapy combining inotuzumab ozogamicin (InO)-based induction followed by consolidation with high dose MTX and pegaspargase based on the GMALL protocol for older ALL patients. After a diagnosis of the extramedullary relapse in the form of a retro vesical chloroma, the patient received an individualized multi-agent chemotherapy based on induction chemotherapy for older patients in combination with InO. After four administrations of InO, in combination with vincristine, dexamethasone, cytarabine, and cyclophosphamide, CT-imaging showed a reduction in volume of the chloroma and response to therapy. Consolidation with high-dose methotrexate and pegaspargase was administered. The patient developed toxic liver damage manifested by hyperbilirubinemia and progressive hepatic encephalopathy. The diagnostic criteria for VOD were met, and therapy with defibrotide was initiated. Liver biopsy revealed no histological signs of VOD but instead steatohepatitis indicative of drug-induced toxicity. The patient ultimately died of hemorrhagic shock through postinterventional hemorrhage after liver biopsy. In conclusion, although InO shows promising results in the therapy of r/r ALL with and without additional chemotherapy, the combination with MTX and pegaspargase in an intensively pretreated patient with relapse after HCST may impart an increased risk for liver-related toxicity. Special caution is required when assessing fitness for further liver toxic regimens. A key takeaway is also the reminder that InO can cause liver damage not only in the form of VOD but also through direct hepatocellular toxicity.

Genomic selection for survival under naturally occurring Saprolegnia oomycete infection in farmed European whitefish Coregonus lavaretus.

Saprolegnia oomycete infection causes serious economic losses and reduces fish health in aquaculture. Genomic selection based on thousands of DNA markers is a powerful tool to improve fish traits in selective breeding programs. Our goal was to develop a single nucleotide polymorphism (SNP) marker panel and to test its use in genomic selection for improved survival against Saprolegnia infection in European whitefish Coregonus lavaretus, the second most important farmed fish species in Finland. We used a double digest restriction site associated DNA (ddRAD) genotyping by sequencing method to produce a SNP panel, and we tested it analyzing data from a cohort of 1,335 fish, which were measured at different times for mortality to Saprolegnia oomycete infection and weight traits. We calculated the genetic relationship matrix (GRM) from the genome-wide genetic data, integrating it in multivariate mixed models used for the estimation of variance components and genomic breeding values (GEBVs), and to carry out Genome-Wide Association Studies for the presence of quantitative trait loci (QTL) affecting the phenotypes in analysis. We identified one major QTL on chromosome 6 affecting mortality to Saprolegnia infection, explaining 7.7% to 51.3% of genetic variance, and a QTL for weight on chromosome 4, explaining 1.8% to 5.4% of genetic variance. Heritability for mortality was 0.20 to 0.43 on the liability scale, and heritability for weight was 0.44 to 0.53. The QTL for mortality showed an additive allelic effect. We tested whether integrating the QTL for mortality as a fixed factor, together with a new GRM calculated excluding the QTL from the genetic data, would improve the accuracy estimation of GEBVs. This test was done through a cross-validation approach, which indicated that the inclusion of the QTL increased the mean accuracy of the GEBVs by 0.28 points, from 0.33 to 0.61, relative to the use of full GRM only. The area under the curve of the receiver-operator curve for mortality increased from 0.58 to 0.67 when the QTL was included in the model. The inclusion of the QTL as a fixed effect in the model increased the correlation between the GEBVs of early mortality with the late mortality, compared to a model that did not include the QTL. These results validate the usability of the produced SNP panel for genomic selection in European whitefish and highlight the opportunity for modeling QTLs in genomic evaluation of mortality due to Saprolegnia infection.

Saprolegnia infection causes serious economic losses and reduces fish health in aquaculture. We created a novel set of genetic markers to use in the selective breeding of European whitefish to reduce mortality due to the fungus. Using genetic markers, we estimated how much different fish traits are determined by genetic variation, and thus what potential traits have to be selected. We observed that resistance to infection was controlled by both a genetic variant with a major effect on mortality and by many other variants with a small effect distributed across the genome. We tested whether we could increase the precision of genomic breeding values used in the selective breeding by explicitly adding the major genetic variant to the analysis, and we observed an increase in precision in our results. We conclude that directly including information about the major genetic variant increases the precision of our predictions, rather than assuming that all genetic variants each explain a small amount of the genetic variation.

Effect of Stereochemically Active Electron Lone Pairs on Magnetic Ordering in Trivanadates.

Stereoactive electron lone pairs derived from filled 5/6s2 states of p-block cations are an intriguing electronic and geometric structure motif that have been exploited for diverse applications such as thermoelectrics, thermochromics, photocatalysis, and nonlinear optics. Layered trivanadates are dynamic intercalation hosts, where the insertion of cations can be used to tune electron correlation, charge localization, and magnetic ordering. However, the interaction of 5/6s2 stereoactive electron lone pairs with layered trivanadates remains unexplored. In this study, we contrast s- and p-block trivanadates and map off-centering in the coordination environment and reduction in symmetry arising from the stereochemical activity of lone pair cations to the emergence of filled antibonding lone-pair 6s2-O 2p hybridized states. The former is studied by high-resolution single-crystal X-ray diffraction studies of TlV3O8 and isostructural RbV3O8 to probe distinct differences in Tl and Rb coordination environments and the resulting modulation of V-V interactions in V3O8 slabs. The latter has been probed by variable-energy hard X-ray photoelectron spectroscopy (HAXPES) measurements, which manifest orbital-specific contributions from bonding and antibonding interactions of stereoactive Tl 6s2 electron lone pairs in TlV3O8. The spectroscopic assignment of valence band states to stereoactive lone pairs is further corroborated by first-principles electronic structure calculations, crystal orbital Hamilton population analyses, and electron localization function maps. The presence of the Tl 6s2 electron lone pair in TlV3O8 brings about the off-centering of Tl+ cations, which leads to anisotropy in Tl-O bonds. The off-centering of Tl ions weakens V-O bonds in one direction, which subsequently strengthens directional V-V coupling. Magnetic measurements reveal ferromagnetic signatures for both RbV3O8 and TlV3O8. However, the differences in V···V interactions significantly affect the energy balance of the superexchange interactions, resulting in an ordering temperature of 140 K for TlV3O8 as compared to 125 K for RbV3O8. The results demonstrate the distinctive effects of stereochemically active lone pairs in modifying electronic structure near the Fermi level and for mediating superexchange interactions.

Development and Multicenter Case-Control Validation of Urinary Comprehensive Genomic Profiling for Urothelial Carcinoma Diagnosis, Surveillance, and Risk-Prediction.

PURPOSE: Urinary comprehensive genomic profiling (uCGP) uses next-generation sequencing to identify mutations associated with urothelial carcinoma and has the potential to improve patient outcomes by noninvasively diagnosing disease, predicting grade and stage, and estimating recurrence risk. EXPERIMENTAL DESIGN: This is a multicenter case-control study using banked urine specimens collected from patients undergoing initial diagnosis/hematuria workup or urothelial carcinoma surveillance. A total of 581 samples were analyzed by uCGP: 333 for disease classification and grading algorithm development, and 248 for blinded validation. uCGP testing was done using the UroAmp platform, which identifies five classes of mutation: single-nucleotide variants, copy-number variants, small insertion-deletions, copy-neutral loss of heterozygosity, and aneuploidy. UroAmp algorithms predicting urothelial carcinoma tumor presence, grade, and recurrence risk were compared with cytology, cystoscopy, and pathology. RESULTS: uCGP algorithms had a validation sensitivity/specificity of 95%/90% for initial cancer diagnosis in patients with hematuria and demonstrated a negative predictive value (NPV) of 99%. A positive diagnostic likelihood ratio (DLR) of 9.2 and a negative DLR of 0.05 demonstrate the ability to risk-stratify patients presenting with hematuria. In surveillance patients, binary urothelial carcinoma classification demonstrated an NPV of 91%. uCGP recurrence-risk prediction significantly prognosticated future recurrence (hazard ratio, 6.2), whereas clinical risk factors did not. uCGP demonstrated positive predictive value (PPV) comparable with cytology (45% vs. 42%) with much higher sensitivity (79% vs. 25%). Finally, molecular grade predictions had a PPV of 88% and a specificity of 95%. CONCLUSIONS: uCGP enables noninvasive, accurate urothelial carcinoma diagnosis and risk stratification in both hematuria and urothelial carcinoma surveillance patients.

Rumen Microbiota Predicts Feed Efficiency of Primiparous Nordic Red Dairy Cows.

Efficient feed utilization in dairy cows is crucial for economic and environmental reasons. The rumen microbiota plays a significant role in feed efficiency, but studies utilizing microbial data to predict host phenotype are limited. In this study, 87 primiparous Nordic Red dairy cows were ranked for feed efficiency during their early lactation based on residual energy intake, and the rumen liquid microbial ecosystem was subsequently evaluated using 16S rRNA amplicon and metagenome sequencing. The study used amplicon data to build an extreme gradient boosting model, demonstrating that taxonomic microbial variation can predict efficiency (rtest = 0.55). Prediction interpreters and microbial network revealed that predictions were based on microbial consortia and the efficient animals had more of the highly interacting microbes and consortia. Rumen metagenome data was used to evaluate carbohydrate-active enzymes and metabolic pathway differences between efficiency phenotypes. The study showed that an efficient rumen had a higher abundance of glycoside hydrolases, while an inefficient rumen had more glycosyl transferases. Enrichment of metabolic pathways was observed in the inefficient group, while efficient animals emphasized bacterial environmental sensing and motility over microbial growth. The results suggest that inter-kingdom interactions should be further analyzed to understand their association with the feed efficiency of animals.

Safety of an Initial Insulin Bolus in the Treatment of Diabetic Ketoacidosis.

Background Insulin is a mainstay of treatment in diabetic ketoacidosis (DKA) however controversy remains over the optimal dose and administration. An initial bolus dose of insulin prior to a continuous infusion is utilized despite a lack of data showing clinical benefit and potential for complications. Objective This study was designed to evaluate the safety and efficacy of an initial insulin bolus in the treatment of DKA. Methods A retrospective chart review of patients with DKA was conducted. Fifty-nine patients met inclusion for the bolus group and 108 in the no-bolus group. The primary outcome was a composite of interruption of insulin infusion, hypoglycemia (BG <70 mg/dL), or hypokalemia (K+ <3.4 mEq/L) occurring within eight hours of starting insulin. Secondary outcomes included time to discontinuation of insulin infusion, as well as time to discharge from the ICU and the hospital. Results Baseline characteristics were similar between groups. The majority of patients were classified as having mild DKA. The primary outcome occurred significantly more frequently in the bolus group (45.8% vs 25%, P = .003) which was primarily driven by incidence of hypokalemia. Time to anion gap closure (6:39 vs 9:00, P = .063) was shorter with a bolus, although not significantly so. This finding carried forward to non-significant differences in time to stopping insulin infusion as well as ICU and hospital discharge. Conclusion An insulin bolus prior to initiation of an insulin infusion was associated with significantly more adverse effects early in therapy without a corresponding benefit in time to resolution of DKA.

Human Adult Astrocyte Extracellular Vesicle Transcriptomics Study Identifies Specific RNAs Which Are Preferentially Secreted as EV Luminal Cargo.

Astrocytes are central nervous system (CNS)-restricted glial cells involved in synaptic function and CNS blood flow regulation. Astrocyte extracellular vesicles (EVs) participate in neuronal regulation. EVs carry RNAs, either surface-bound or luminal, which can be transferred to recipient cells. We characterized the secreted EVs and RNA cargo of human astrocytes derived from an adult brain. EVs were isolated by serial centrifugation and characterized with nanoparticle tracking analysis (NTA), Exoview, and immuno-transmission electron microscopy (TEM). RNA from cells, EVs, and proteinase K/RNase-treated EVs was analyzed by miRNA-seq. Human adult astrocyte EVs ranged in sizes from 50 to 200 nm, with CD81 as the main tetraspanin marker and larger EVs positive for integrin ß1. Comparison of the RNA between the cells and EVs identified RNA preferentially secreted in the EVs. In the case of miRNAs, enrichment analysis of their mRNA targets indicates that they are good candidates for mediating EV effects on recipient cells. The most abundant cellular miRNAs were also abundant in EVs, and the majority of their mRNA targets were found to be downregulated in mRNA-seq data, but the enrichment analysis lacked neuronal specificity. Proteinase K/RNase treatment of EV-enriched preparations identified RNAs secreted independently of EVs. Comparing the distribution of cellular and secreted RNA identifies the RNAs involved in intercellular communication via EVs.

Improving the mental health and well-being of healthcare providers using the transcendental meditation technique during the COVID-19 pandemic: A parallel population study.

INTRODUCTION: Frontline Healthcare provider (HCP) burnout has dramatically increased due to the COVID 19 pandemic. Hospitals are supporting wellness programs and techniques to reduce burnout including the Transcendental Meditation (TM) technique. This study evaluated the use of TM on HCP symptoms of stress, burnout and wellness. METHODS: A total of 65 HCPs at three South Florida hospitals were recruited and instructed in the TM technique which they practiced at home for 20 minutes twice a day. A parallel lifestyle as usual control group was enrolled. Validated measurement scales (Brief Symptom Inventory 18 (BSI-18), Insomnia Severity Index (ISI), Maslach Burnout Inventory-Human Services Survey [MBI-HSS (MP)] and the Warwick Edinburgh Mental Well Being Scale (WEMWBS) were administered at baseline, 2 weeks, one and three months. RESULTS: No significant demographic differences were seen between the 2 groups; however, some baseline scales were higher in the TM group. TM average weekly session completion rate was very high at 83%. After 2-weeks, symptoms of somatization, depression, and anxiety in the TM group had all shown near 45% reductions, while insomnia, emotional exhaustion, and well-being had improved by 33%, 16%, and 11% respectively (P = 0.02 for somatization and < .001 for all others); no significant change was noted in the LAU group. At 3-months, in the TM group, the improvement in symptoms showed a mean reduction of in anxiety, 62%, somatization, 58%, depression, 50%, insomnia, 44%, emotional exhaustion 40%, depersonalization, 42%, and improvement of well-being 18% (for all p<0.004). P-values for between-group differences in change from baseline, based upon repeated measures ANCOVA covarying for baseline measurements, showed significance for all scales at 3-months. CONCLUSION: The study confirmed the reported significant and rapid benefits of the practice of TM and demonstrated its positive psychological impact on healthcare workers in a high stress setting.

Entertain Me Well: An Entertaining, Tailorable, Online Platform Delivering CBT for Depression.

Depression prevalence is high, impacting approximately 20% of Americans during their lifetime, and on the rise due to stress and loss associated with the COVID-19 pandemic. Despite the high prevalence of depression, unacceptable treatment access disparities persist. When depression goes untreated, it leads to substantial negative impacts in multiple life domains. Cognitive behavioral therapy (CBT), the gold-standard psychosocial treatment for depression, remains largely unavailable to individuals living with depression, particularly individuals who are members of underrepresented groups in our society. Digital mental health interventions (DMHI) have led to important advances in extending the reach of CBT for depression; however, they are underutilized and treatment engagement remains low. We sought to address some of the current gaps in DMHI by developing an online platform for delivering CBT for depression that is entertaining, simple and straightforward, and tailorable. First, this article introduces our online platform, Entertain Me Well (EMW) and its key innovations, including the use of an engaging, character-driven storyline presented as "episodes" within each session, as well as customizable content that allows for tailoring of text, images, and examples to create content most relevant to the target client population, context, or setting. Next, we describe two EMW depression treatment programs that have been tailored: one for delivery in the rural church setting, called Raising Our Spirits Together, and one tailored for delivery in dialysis centers, called Doing Better on Dialysis. Finally, we discuss future directions for the EMW platform, including the ability to create programs for other common mental health and health conditions, the development of additional character-driven storylines with greater treatment personalization, translation of content in multiple languages, and the use of additional technological innovation, such as artificial intelligence like natural language processing, to enhance platform interactivity.

The Effectiveness of Metacognitive Therapy Compared to Behavioral Activation for Severely Depressed Outpatients: A Single-Center Randomized Trial.

INTRODUCTION: Major depressive disorder (MDD) is a highly prevalent and disabling disorder. This study examines two psychotherapy methods for MDD, behavioral activation (BA), and metacognitive therapy (MCT), when applied as outpatient treatments to severely affected patients. METHODS: The study was conducted in a tertiary outpatient treatment center. Patients with a primary diagnosis of MDD (N = 122) were included in the intention-to-treat sample (55.7% female, mean age 41.9 years). Participants received one individual and one group session weekly for 6 months (M). Assessments took place at baseline, pretreatment, mid-treatment (3 M), post-treatment (6 M), and follow-up (12 M). The primary outcome was depressive symptomatology assessed by the Hamilton Rating Scale for Depression at 12 M follow-up. Secondary outcomes included general symptom severity, psychosocial functioning, and quality of life. RESULTS: Linear mixed models indicated a change in depressive symptoms (F(2, 83.495) = 12.253, p < 0.001) but no between-group effect (F(1, 97.352) = 0.183, p = 0.670). Within-group effect sizes were medium for MCT (post-treatment: d = 0.610; follow-up: d = 0.692) and small to medium for BA (post-treatment: d = 0.636, follow-up: d = 0.326). In secondary outcomes, there were improvements (p ≤ 0.040) with medium to large within-group effect sizes (d ≥ 0.501) but no between-group effects (p ≥ 0.304). Response and remission rates did not differ between conditions at follow-up (response MCT: 12.9%, BA: 13.3%, remission MCT: 9.7%, BA: 10.0%). The deterioration rate was lower in MCT than in BA (χ21 = 5.466, p = 0.019, NTT = 7.4). DISCUSSION: Both MCT and BA showed symptom reductions. Remission and response rates were lower than in previous studies, highlighting the need for further improvements in adapting/implementing treatments for severely affected patients with MDD.

Toggling Stereochemical Activity through Interstitial Positioning of Cations between 2D V2O5 Double Layers.

The 5/6s2 lone-pair electrons of p-block cations in their lower oxidation states are a versatile electronic and geometric structure motif that can underpin lattice anharmonicity and often engender electronic and structural instabilities that underpin the function of active elements in nonlinear optics, thermochromics, thermoelectrics, neuromorphic computing, and photocatalysis. In contrast to periodic solids where lone-pair-bearing cations are part of the structural framework, installing lone-pair-bearing cations in the interstitial sites of intercalation hosts provides a means of a systematically modulating electronic structure through the choice of the group and the period of the inserted cation while preserving the overall framework connectivity. The extent of stereochemical activity and the energy positioning of lone-pair-derived mid-gap states depend on the cation identity, stoichiometry, and strength of anion hybridization. V2O5 polymorphs are versatile insertion hosts that can accommodate a broad range of s-, p-, and d-block cations. However, the insertion of lone-pair-bearing cations remains largely underexplored. In this article, we examine the implications of varying the 6s2 cations situated in interlayer sites between condensed [V4O10]n double layers. Systematic modulations of lattice distortions, electronic structure, and magnetic ordering are observed with increasing strength of stereochemical activity from group 12 to group 14 cations. We compare and contrast p-block-layered MxV2O5 (M = Hg, Tl, and Pb) compounds and map the significance of local off-centering arising from the stereochemical activity of lone-pair cations to the emergence of filled antibonding lone-pair 6s2-O 2p-hybridized mid-gap states mediated by second-order Jahn-Teller distortions. Crystallographic studies of cation coordination environments and the resulting modulation of V-V interactions have been used in conjunction with variable-energy hard X-ray photoelectron spectroscopy measurements, first-principles electronic structure calculations, and crystal orbital Hamilton population analyses to decipher the origins of stereochemical activity. Magnetic susceptibility measurements reveal antiferromagnetic signatures for all the three compounds. However, the differences in V-V interactions significantly affect the energy balance of the superexchange interactions, resulting in an ordering temperature of 160 and 260 K for Hg0.5V2O5 and δ-Tl0.5V2O5, respectively, as compared to 7 K for δ-Pb0.5V2O5. In δ-Pb0.5V2O5, the strong stereochemical activity of electron lone pairs and the resulting electrostatic repulsions enforce superlattice ordering, which strongly modifies the electronic localization patterns along the [V4O10] slabs, resulting in disrupted magnetic ordering and an anomalously low ordering temperature. The results demonstrate a versatile strategy for toggling the stereochemical activity of electron lone pairs to modify the electronic structure near the Fermi level and to mediate superexchange interactions.

Urinary Comprehensive Genomic Profiling Correlates Urothelial Carcinoma Mutations with Clinical Risk and Efficacy of Intervention.

The clinical standard of care for urothelial carcinoma (UC) relies on invasive procedures with suboptimal performance. To enhance UC treatment, we developed a urinary comprehensive genomic profiling (uCGP) test, UroAmplitude, that measures mutations from tumor DNA present in urine. In this study, we performed a blinded, prospective validation of technical sensitivity and positive predictive value (PPV) using reference standards, and found at 1% allele frequency, mutation detection performs at 97.4% sensitivity and 80.4% PPV. We then prospectively compared the mutation profiles of urine-extracted DNA to those of matched tumor tissue to validate clinical performance. Here, we found tumor single-nucleotide variants were observed in the urine with a median concordance of 91.7% and uCGP revealed distinct patterns of genomic lesions enriched in low- and high-grade disease. Finally, we retrospectively explored longitudinal case studies to quantify residual disease following bladder-sparing treatments, and found uCGP detected residual disease in patients receiving bladder-sparing treatment and predicted recurrence and disease progression. These findings demonstrate the potential of the UroAmplitude platform to reliably identify and track mutations associated with UC at each stage of disease: diagnosis, treatment, and surveillance. Multiple case studies demonstrate utility for patient risk classification to guide both surgical and therapeutic interventions.

Evidence that gecko setae are coated with an ordered nanometre-thin lipid film.

The fascinating adhesion of gecko to virtually any material has been related to surface interactions of myriads of spatula at the tips of gecko feet. Surprisingly, the molecular details of the surface chemistry of gecko adhesion are still largely unknown. Lipids have been identified within gecko adhesive pads. However, the location of the lipids, the extent to which spatula are coated with lipids, and how the lipids are structured are still open questions. Lipids can modulate adhesion properties and surface hydrophobicity and may play an important role in adhesion. We have therefore studied the molecular structure of lipids at spatula surfaces using near-edge X-ray absorption fine structure imaging. We provide evidence that a nanometre-thin layer of lipids is present at the spatula surfaces of the tokay gecko (Gekko gecko) and that the lipids form ordered, densely packed layers. Such dense, thin lipid layers can effectively protect the spatula proteins from dehydration by forming a barrier against water evaporation. Lipids can also render surfaces hydrophobic and thereby support the gecko adhesive system by enhancement of hydrophobic-hydrophobic interactions with surfaces.