Brain-phenotype models fail for individuals who defy sample stereotypes.

Individual differences in brain functional organization track a range of traits, symptoms and behaviours1-12. So far, work modelling linear brain-phenotype relationships has assumed that a single such relationship generalizes across all individuals, but models do not work equally well in all participants13,14. A better understanding of in whom models fail and why is crucial to revealing robust, useful and unbiased brain-phenotype relationships. To this end, here we related brain activity to phenotype using predictive models-trained and tested on independent data to ensure generalizability15-and examined model failure. We applied this data-driven approach to a range of neurocognitive measures in a new, clinically and demographically heterogeneous dataset, with the results replicated in two independent, publicly available datasets16,17. Across all three datasets, we find that models reflect not unitary cognitive constructs, but rather neurocognitive scores intertwined with sociodemographic and clinical covariates; that is, models reflect stereotypical profiles, and fail when applied to individuals who defy them. Model failure is reliable, phenotype specific and generalizable across datasets. Together, these results highlight the pitfalls of a one-size-fits-all modelling approach and the effect of biased phenotypic measures18-20 on the interpretation and utility of resulting brain-phenotype models. We present a framework to address these issues so that such models may reveal the neural circuits that underlie specific phenotypes and ultimately identify individualized neural targets for clinical intervention.

Predicting the future of neuroimaging predictive models in mental health.

Predictive modeling using neuroimaging data has the potential to improve our understanding of the neurobiology underlying psychiatric disorders and putatively information interventions. Accordingly, there is a plethora of literature reviewing published studies, the mathematics underlying machine learning, and the best practices for using these approaches. As our knowledge of mental health and machine learning continue to evolve, we instead aim to look forward and "predict" topics that we believe will be important in current and future studies. Some of the most discussed topics in machine learning, such as bias and fairness, the handling of dirty data, and interpretable models, may be less familiar to the broader community using neuroimaging-based predictive modeling in psychiatry. In a similar vein, transdiagnostic research and targeting brain-based features for psychiatric intervention are modern topics in psychiatry that predictive models are well-suited to tackle. In this work, we target an audience who is a researcher familiar with the fundamental procedures of machine learning and who wishes to increase their knowledge of ongoing topics in the field. We aim to accelerate the utility and applications of neuroimaging-based predictive models for psychiatric research by highlighting and considering these topics. Furthermore, though not a focus, these ideas generalize to neuroimaging-based predictive modeling in other clinical neurosciences and predictive modeling with different data types (e.g., digital health data).

(Un)common space in infant neuroimaging studies: A systematic review of infant templates.

In neuroimaging, spatial normalization is an important step that maps an individual's brain onto a template brain permitting downstream statistical analyses. Yet, in infant neuroimaging, there remain several technical challenges that have prevented the establishment of a standardized template for spatial normalization. Thus, many different approaches are used in the literature. To quantify the popularity and variability of these approaches in infant neuroimaging studies, we performed a systematic review of infant magnetic resonance imaging (MRI) studies from 2000 to 2020. Here, we present results from 834 studies meeting inclusion criteria. Studies were classified into (a) processing data in single subject space, (b) using an off the shelf, or "off the shelf," template, (c) creating a study specific template, or (d) using a hybrid of these methods. We found that across the studies in the systematic review, single subject space was the most used (no common space). This was the most used common space for diffusion-weighted imaging and structural MRI studies while functional MRI studies preferred off the shelf atlases. We found a pattern such that more recently published studies are more commonly using off the shelf atlases. When considering special populations, preterm studies most used single subject space while, when no special populations were being analyzed, an off the shelf template was most common. The most used off the shelf templates were the UNC Infant Atlases (24%). Using a systematic review of infant neuroimaging studies, we highlight a lack of an established "standard" template brain in these studies.

Perioperative Management of Gastric Cancer Patients Treated With (Sub)Total Gastrectomy, Cytoreductive Surgery, and Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Lessons Learned.

BACKGROUND: The PERISCOPE I study was designed to assess the safety and feasibility of (sub)total gastrectomy, cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin and docetaxel for gastric cancer patients who have limited peritoneal dissemination. The current analysis investigated changes in perioperative management together with their impact on postoperative outcomes. METHODS: Patients with resectable gastric cancer and limited peritoneal dissemination were administered (sub)total gastrectomy, CRS, and HIPEC with oxaliplatin (460 mg/m2) and docetaxel (escalating scheme: 0, 50, 75 mg/m2). Of the 25 patients who completed the study protocol, 14 were treated in the dose-escalation cohort and 11 were treated in the expansion cohort (to optimize perioperative management). RESULTS: A significant proportion of the patients in the dose-escalation cohort (n = 7, 50%) had ileus-related complications. In this cohort, enteral nutrition was started immediately after surgery at 20 ml/h, which was increased on day 1 to meet nutritional needs. In the expansion cohort, enteral nutrition was administered at 10 ml/h until day 3, then restricted to 20 ml/h until day 6, supplemented with total parenteral nutrition to meet nutritional needs. Ileus-related complications occurred for two patients (18%) of the expansion cohort. The intensive care unit (ICU) readmission rate decreased from 50 (n = 7) to 9% (n = 1; p = 0.04). CONCLUSION: The implementation of a strict nutritional protocol during the PERISCOPE I study was associated with a decrease in postoperative complications. Based on these results, a perioperative care path was described for the gastric cancer HIPEC patients in the PERISCOPE II study.

Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomised, placebo-controlled, phase II crossover trial.

BACKGROUND: This multicentre, randomised, double-blinded, placebo-controlled, phase II/III trial aimed to evaluate an oral THC:CBD (tetrahydrocannabinol:cannabidiol) cannabis extract for prevention of refractory chemotherapy-induced nausea and vomiting (CINV). Here we report the phase II component results. PATIENTS AND METHODS: Eligible patients experienced CINV during moderate-to-high emetogenic intravenous chemotherapy despite guideline-consistent antiemetic prophylaxis. Study treatment consisted of one cycle of 1-4 self-titrated capsules of oral THC 2.5 mg/CBD 2.5 mg (TN-TC11M) three times daily, from days -1 to 5, and 1 cycle of matching placebo in a crossover design, then blinded patient preference for a third cycle. The primary end point was the proportion of participants with complete response during 0-120 h from chemotherapy. A total of 80 participants provided 80% power to detect a 20% absolute improvement with a two-sided P value of 0.1. RESULTS: A total of 81 participants were randomised; 72 completing two cycles were included in the efficacy analyses and 78 not withdrawing consent were included in safety analyses. Median age was 55 years (range 29-80 years); 78% were female. Complete response was improved with THC:CBD from 14% to 25% (relative risk 1.77, 90% confidence interval 1.12-2.79, P = 0.041), with similar effects on absence of emesis, use of rescue medications, absence of significant nausea, and summary scores for the Functional Living Index-Emesis (FLIE). Thirty-one percent experienced moderate or severe cannabinoid-related adverse events such as sedation, dizziness, or disorientation, but 83% of participants preferred cannabis to placebo. No serious adverse events were attributed to THC:CBD. CONCLUSION: The addition of oral THC:CBD to standard antiemetics was associated with less nausea and vomiting but additional side-effects. Most participants preferred THC:CBD to placebo. Based on these promising results, we plan to recruit an additional 170 participants to complete accrual for the definitive, phase III, parallel group analysis. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616001036404; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370473&isReview=true.

Genomic Characterization of Candidate Division LCP-89 Reveals an Atypical Cell Wall Structure, Microcompartment Production, and Dual Respiratory and Fermentative Capacities.

Recent experimental and bioinformatic advances enable the recovery of genomes belonging to yet-uncultured microbial lineages directly from environmental samples. Here, we report on the recovery and characterization of single amplified genomes (SAGs) and metagenome-assembled genomes (MAGs) representing candidate phylum LCP-89, previously defined based on 16S rRNA gene sequences. Analysis of LCP-89 genomes recovered from Zodletone Spring, an anoxic spring in Oklahoma, predicts slow-growing, rod-shaped organisms. LCP-89 genomes contain genes for cell wall lipopolysaccharide (LPS) production but lack the entire machinery for peptidoglycan biosynthesis, suggesting an atypical cell wall structure. The genomes, however, encode S-layer homology domain-containing proteins, as well as machinery for the biosynthesis of CMP-legionaminate, inferring the possession of an S-layer glycoprotein. A nearly complete chemotaxis machinery coupled to the absence of flagellar synthesis and assembly genes argues for the utilization of alternative types of motility. A strict anaerobic lifestyle is predicted, with dual respiratory (nitrite ammonification) and fermentative capacities. Predicted substrates include a wide range of sugars and sugar alcohols and a few amino acids. The capability of rhamnose metabolism is confirmed by the identification of bacterial microcompartment genes to sequester the toxic intermediates generated. Comparative genomic analysis identified differences in oxygen sensitivities, respiratory capabilities, substrate utilization preferences, and fermentation end products between LCP-89 genomes and those belonging to its four sister phyla (Calditrichota, SM32-31, AABM5-125-24, and KSB1) within the broader FCB (Fibrobacteres-Chlorobi-Bacteroidetes) superphylum. Our results provide a detailed characterization of members of the candidate division LCP-89 and highlight the importance of reconciling 16S rRNA-based and genome-based phylogenies.IMPORTANCE Our understanding of the metabolic capacities, physiological preferences, and ecological roles of yet-uncultured microbial phyla is expanding rapidly. Two distinct approaches are currently being utilized for characterizing microbial communities in nature: amplicon-based 16S rRNA gene surveys for community characterization and metagenomics/single-cell genomics for detailed metabolic reconstruction. The occurrence of multiple yet-uncultured bacterial phyla has been documented using 16S rRNA surveys, and obtaining genome representatives of these yet-uncultured lineages is critical to our understanding of the role of yet-uncultured organisms in nature. This study provides a genomics-based analysis highlighting the structural features and metabolic capacities of a yet-uncultured bacterial phylum (LCP-89) previously identified in 16S rRNA surveys for which no prior genomes have been described. Our analysis identifies several interesting structural features for members of this phylum, e.g., lack of peptidoglycan biosynthetic machinery and the ability to form bacterial microcompartments. Predicted metabolic capabilities include degradation of a wide range of sugars, anaerobic respiratory capacity, and fermentative capacities. In addition to the detailed structural and metabolic analysis provided for candidate division LCP-89, this effort represents an additional step toward a unified scheme for microbial taxonomy by reconciling 16S rRNA gene-based and genomics-based taxonomic outlines.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy versus palliative systemic chemotherapy in stomach cancer patients with peritoneal dissemination, the study protocol of a multicentre randomised controlled trial (PERISCOPE II).

BACKGROUND: At present, palliative systemic chemotherapy is the standard treatment in the Netherlands for gastric cancer patients with peritoneal dissemination. In contrast to lymphatic and haematogenous dissemination, peritoneal dissemination may be regarded as locoregional spread of disease. Administering cytotoxic drugs directly into the peritoneal cavity has an advantage over systemic chemotherapy since high concentrations can be delivered directly into the peritoneal cavity with limited systemic toxicity. The combination of a radical gastrectomy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results in patients with gastric cancer in Asia. However, the results obtained in Asian patients cannot be extrapolated to Western patients. The aim of this study is to compare the overall survival between patients with gastric cancer with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with palliative systemic chemotherapy, and those treated with gastrectomy, CRS and HIPEC after neoadjuvant systemic chemotherapy. METHODS: In this multicentre randomised controlled two-armed phase III trial, 106 patients will be randomised (1:1) between palliative systemic chemotherapy only (standard treatment) and gastrectomy, CRS and HIPEC (experimental treatment) after 3-4 cycles of systemic chemotherapy.Patients with gastric cancer are eligible for inclusion if (1) the primary cT3-cT4 gastric tumour including regional lymph nodes is considered to be resectable, (2) limited peritoneal dissemination (Peritoneal Cancer Index < 7) and/or tumour positive peritoneal cytology are confirmed by laparoscopy or laparotomy, and (3) systemic chemotherapy was given (prior to inclusion) without disease progression. DISCUSSION: The PERISCOPE II study will determine whether gastric cancer patients with limited peritoneal dissemination and/or tumour positive peritoneal cytology treated with systemic chemotherapy, gastrectomy, CRS and HIPEC have a survival benefit over patients treated with palliative systemic chemotherapy only. TRIAL REGISTRATION: clinicaltrials.gov NCT03348150 ; registration date November 2017; first enrolment November 2017; expected end date December 2022; trial status: Ongoing.

Tidal changes in PaO2 and their relationship to cyclical lung recruitment/derecruitment in a porcine lung injury model.

BACKGROUND: Tidal recruitment/derecruitment (R/D) of collapsed regions in lung injury has been presumed to cause respiratory oscillations in the partial pressure of arterial oxygen (PaO2). These phenomena have not yet been studied simultaneously. We examined the relationship between R/D and PaO2 oscillations by contemporaneous measurement of lung-density changes and PaO2. METHODS: Five anaesthetised pigs were studied after surfactant depletion via a saline-lavage model of R/D. The animals were ventilated with a mean fraction of inspired O2 (FiO2) of 0.7 and a tidal volume of 10 ml kg-1. Protocolised changes in pressure- and volume-controlled modes, inspiratory:expiratory ratio (I:E), and three types of breath-hold manoeuvres were undertaken. Lung collapse and PaO2 were recorded using dynamic computed tomography (dCT) and a rapid PaO2 sensor. RESULTS: During tidal ventilation, the expiratory lung collapse increased when I:E <1 [mean (standard deviation) lung collapse=15.7 (8.7)%; P<0.05], but the amplitude of respiratory PaO2 oscillations [2.2 (0.8) kPa] did not change during the respiratory cycle. The expected relationship between respiratory PaO2 oscillation amplitude and R/D was therefore not clear. Lung collapse increased during breath-hold manoeuvres at end-expiration and end-inspiration (14% vs 0.9-2.1%; P<0.0001). The mean change in PaO2 from beginning to end of breath-hold manoeuvres was significantly different with each type of breath-hold manoeuvre (P<0.0001). CONCLUSIONS: This study in a porcine model of collapse-prone lungs did not demonstrate the expected association between PaO2 oscillation amplitude and the degree of recruitment/derecruitment. The results suggest that changes in pulmonary ventilation are not the sole determinant of changes in PaO2 during mechanical ventilation in lung injury.

Tumours in white suckers from Lake Michigan tributaries: pathology and prevalence.

The prevalence and histopathology of neoplastic lesions were assessed in white sucker Catostomus commersonii captured at two Lake Michigan Areas of Concern (AOCs), the Sheboygan River and Milwaukee Estuary. Findings were compared to those observed at two non-AOC sites, the Root and Kewaunee rivers. At each site, approximately 200 adult suckers were collected during their spawning migration. Raised skin lesions were observed at all sites and included discrete white spots, mucoid plaques on the body surface and fins and large papillomatous lesions on lips and body. Microscopically, hyperplasia, papilloma and squamous cell carcinoma were documented. Liver neoplasms were also observed at all sites and included both hepatocellular and biliary tumours. Based on land use, the Kewaunee River was the site least impacted by human activities previously associated with fish tumours and had significantly fewer liver neoplasms when compared to the other sites. The proportion of white suckers with liver tumours followed the same patterns as the proportion of urban land use in the watershed: the Milwaukee Estuary had the highest prevalence, followed by the Root, Sheboygan and Kewaunee rivers. The overall skin neoplasm (papilloma and carcinoma) prevalence did not follow the same pattern, although the percentage of white suckers with squamous cell carcinoma exhibited a similar relationship to land use. Testicular tumours (seminoma) were observed at both AOC sites but not at the non-AOC sites. Both skin and liver tumours were significantly and positively associated with age but not sex.

Src kinase as a mediator of convergent molecular abnormalities leading to NMDAR hypoactivity in schizophrenia.

Numerous investigations support decreased glutamatergic signaling as a pathogenic mechanism of schizophrenia, yet the molecular underpinnings for such dysregulation are largely unknown. In the post-mortem dorsolateral prefrontal cortex (DLPFC), we found striking decreases in tyrosine phosphorylation of N-methyl-D aspartate (NMDA) receptor subunit 2 (GluN2) that is critical for neuroplasticity. The decreased GluN2 activity in schizophrenia may not be because of downregulation of NMDA receptors as MK-801 binding and NMDA receptor complexes in postsynaptic density (PSD) were in fact increased in schizophrenia cases. At the postreceptor level, however, we found striking reductions in the protein kinase C, Pyk 2 and Src kinase activity that in tandem can decrease GluN2 activation. Given that Src serves as a hub of various signaling mechanisms affecting GluN2 phosphorylation, we postulated that Src hypoactivity may result from convergent alterations of various schizophrenia susceptibility pathways and thus mediate their effects on NMDA receptor signaling. Indeed, the DLPFC of schizophrenia cases exhibit increased PSD-95 and erbB4 and decreased receptor-type tyrosine-protein phosphatase-α (RPTPα) and dysbindin-1, each of which reduces Src activity via protein interaction with Src. To test genomic underpinnings for Src hypoactivity, we examined genome-wide association study results, incorporating 13 394 cases and 34 676 controls. We found no significant association of individual variants of Src and its direct regulators with schizophrenia. However, a protein-protein interaction-based network centered on Src showed significant enrichment of gene-level associations with schizophrenia compared with other psychiatric illnesses. Our results together demonstrate striking decreases in NMDA receptor signaling at the postreceptor level and propose Src as a nodal point of convergent dysregulations affecting NMDA receptor pathway via protein-protein associations.

Evidence of estrogenic endocrine disruption in smallmouth and largemouth bass inhabiting Northeast U.S. national wildlife refuge waters: A reconnaissance study.

Intersex as the manifestation of testicular oocytes (TO) in male gonochoristic fishes has been used as an indicator of estrogenic exposure. Here we evaluated largemouth bass (Micropterus salmoides) or smallmouth bass (Micropterus dolomieu) form 19 National Wildlife Refuges (NWRs) in the Northeast U.S. inhabiting waters on or near NWR lands for evidence of estrogenic endocrine disruption. Waterbodies sampled included rivers, lakes, impoundments, ponds, and reservoirs. Here we focus on evidence of endocrine disruption in male bass evidenced by gonad histopathology including intersex or abnormal plasma vitellogenin (Vtg) concentrations. During the fall seasons of 2008-2010, we collected male smallmouth bass (n=118) from 12 sites and largemouth bass (n=173) from 27 sites. Intersex in male smallmouth bass was observed at all sites and ranged from 60% to 100%; in male largemouth bass the range was 0-100%. Estrogenicity, as measured using a bioluminescent yeast reporter, was detected above the probable no effects concentration (0.73ng/L) in ambient water samples from 79% of the NWR sites. Additionally, the presence of androgen receptor and glucocorticoid receptor ligands were noted as measured via novel nuclear receptor translocation assays. Mean plasma Vtg was elevated (>0.2mg/ml) in male smallmouth bass at four sites and in male largemouth bass at one site. This is the first reconnaissance survey of this scope conducted on US National Wildlife Refuges. The baseline data collected here provide a necessary benchmark for future monitoring and justify more comprehensive NWR-specific studies.

Intra-breath arterial oxygen oscillations detected by a fast oxygen sensor in an animal model of acute respiratory distress syndrome.

BACKGROUND: There is considerable interest in oxygen partial pressure (Po2) monitoring in physiology, and in tracking Po2 changes dynamically when it varies rapidly. For example, arterial Po2 ([Formula: see text]) can vary within the respiratory cycle in cyclical atelectasis (CA), where [Formula: see text] is thought to increase and decrease during inspiration and expiration, respectively. A sensor that detects these [Formula: see text] oscillations could become a useful diagnostic tool of CA during acute respiratory distress syndrome (ARDS). METHODS: We developed a fibreoptic Po2 sensor (<200 µm diameter), suitable for human use, that has a fast response time, and can measure Po2 continuously in blood. By altering the inspired fraction of oxygen ([Formula: see text]) from 21 to 100% in four healthy animal models, we determined the linearity of the sensor's signal over a wide range of [Formula: see text] values in vivo. We also hypothesized that the sensor could measure rapid intra-breath [Formula: see text] oscillations in a large animal model of ARDS. RESULTS: In the healthy animal models, [Formula: see text] responses to changes in [Formula: see text] were in agreement with conventional intermittent blood-gas analysis (n=39) for a wide range of [Formula: see text] values, from 10 to 73 kPa. In the animal lavage model of CA, the sensor detected [Formula: see text] oscillations, also at clinically relevant [Formula: see text] levels close to 9 kPa. CONCLUSIONS: We conclude that these fibreoptic [Formula: see text] sensors have the potential to become a diagnostic tool for CA in ARDS.

Sirolimus conversion after heart transplant: risk factors for acute rejection and predictors of renal function response.

In a randomized, comparative study of cardiac transplant patients with mild-to-moderate renal insufficiency, conversion from calcineurin inhibitors (CNIs) to sirolimus improved renal function at 1 year versus continuing CNIs, with an attendant risk of biopsy-confirmed acute rejection (BCAR). Post hoc analyses were conducted to identify predictors of BCAR and GFR improvement associated with conversion. Patients with proteinuria >500 mg/day were excluded. Univariate and multivariate regression analyses tested 13 parameters for BCAR and six for GFR improvement. In 57 sirolimus-treated patients, mean daily mycophenolate mofetil (MMF) dose was lower in those with versus without BCAR (1000 vs. 1420 mg; p = 0.014). Receiver operating characteristic analysis identified MMF dose ≤1000 mg/day as the optimal cutoff to predict BCAR. Multivariate analysis confirmed low MMF dose (odds ratio: 9.94; p = 0.007) and non-white race (odds ratio: 15.3; p = 0.06) were independently associated with BCAR. GFR improvement was evaluated in intent-to-treat patients (n = 116). Significant interaction was detected between treatment effect and preexisting diabetes status (univariate p = 0.077; multivariate p = 0.022), indicating greater beneficial effect of sirolimus in those without preexisting diabetes. These findings suggest that sirolimus is more effective in improving GFR in patients without preexisting diabetes, and adequate MMF doses are needed for sirolimus conversion.

Full control of the spin-wave damping in a magnetic insulator using spin-orbit torque.

It is demonstrated that the threshold current for damping compensation can be reached in a 5 µm diameter YIG(20 nm)|Pt(7 nm) disk. The demonstration rests upon the measurement of the ferromagnetic resonance linewidth as a function of I(dc) using a magnetic resonance force microscope (MRFM). It is shown that the magnetic losses of spin-wave modes existing in the magnetic insulator can be reduced or enhanced by at least a factor of 5 depending on the polarity and intensity of an in-plane dc current I(dc) flowing through the adjacent normal metal with strong spin-orbit interaction. Complete compensation of the damping of the fundamental mode by spin-orbit torque is reached for a current density of ∼3×10(11) A·m(-2), in agreement with theoretical predictions. At this critical threshold the MRFM detects a small change of static magnetization, a behavior consistent with the onset of an auto-oscillation regime.

Health of white sucker within the St. Louis River area of concern associated with habitat usage as assessed using stable isotopes.

In Spring 2011, 200 adult white sucker were collected in four areas of the St. Louis River area of concern (AOC), located in Minnesota and Wisconsin, USA. The areas included the upper AOC as a reference area, the upper estuary, St. Louis Bay and Superior Bay. Grossly visible abnormalities were documented and preserved for microscopic analyses, as were five to eight representative pieces of liver tissue. A piece of dorsal muscle was preserved for stable isotope analyses and otoliths removed for age determination. The incidence of raised skin lesions (mucoid plaques) was high (31 %), however, microscopically only 4.5 % of the white suckers had neoplasia (papillomas). The remaining lesions were epidermal hyperplasia. Superior Bay had the lowest percentage of skin/lip lesions (10 %), while St. Louis Bay had the highest (44 %). St. Louis Bay also had the highest incidence of skin neoplasms (12 %). No hepatocellular neoplasms were documented, however bile duct tumors were observed in 4.5 % of the suckers. Foci of cellular alteration were observed in fish from all sites except the upper AOC. Stable isotope data indicated that most of the suckers relied on the St. Louis River AOC for the majority (>75 %) of their diet, indicating they were resident within the AOC and not in Lake Superior. The amount of diet obtained from the upper estuary was a significant predictor of skin lesion incidence. Hence, habitat use within the AOC appears to be an important risk factor for skin and possibly, liver lesions.

Metagenomic sequencing of a Patescibacteria-containing enrichment from Zodletone spring in Oklahoma, USA.

An enrichment of sulfidic sediments from Zodletone spring was sequenced as a metagenome. Draft genomes representing Cloacimonadota, Deltabacterota, Firmicutes, and Patescibacteria were binned and annotated and will aid functional genomics and cultivation efforts.

Investigating brain dynamics and their association with cognitive control in opioid use disorder using naturalistic and drug cue paradigms.

Objectives: Opioid use disorder (OUD) impacts millions of people worldwide. The prevalence and debilitating effects of OUD present a pressing need to understand its neural mechanisms to provide more targeted interventions. Prior studies have linked altered functioning in large-scale brain networks with clinical symptoms and outcomes in OUD. However, these investigations often do not consider how brain responses change over time. Time-varying brain network engagement can convey clinically relevant information not captured by static brain measures. Methods: We investigated brain dynamic alterations in individuals with OUD by applying a new multivariate computational framework to movie-watching (i.e., naturalistic; N=76) and task-based (N=70) fMRI. We further probed the associations between cognitive control and brain dynamics during a separate drug cue paradigm in individuals with OUD. Results: Compared to healthy controls (N=97), individuals with OUD showed decreased variability in the engagement of recurring brain states during movie-watching. We also found that worse cognitive control was linked to decreased variability during the rest period when no opioid-related stimuli were present. Conclusions: These findings suggest that individuals with OUD may experience greater difficulty in effectively engaging brain networks in response to evolving internal or external demands. Such inflexibility may contribute to aberrant response inhibition and biased attention toward opioid-related stimuli, two hallmark characteristics of OUD. By incorporating temporal information, the current study introduces novel information about how brain dynamics are altered in individuals with OUD and their behavioral implications.

Detection of microwave spin pumping using the inverse spin Hall effect.

We report on the electrical detection of the dynamical part of the spin-pumping current emitted during ferromagnetic resonance using inverse spin Hall effect methods. The experiment is performed on a YIG|Pt bilayer. The choice of yttrium iron garnet (YIG), a magnetic insulator, ensures that no charge current flows between the two layers and only the pure spin current produced by the magnetization dynamics is transferred into the adjacent strong spin-orbit Pt layer via spin pumping. To avoid measuring the parasitic eddy currents induced at the frequency of the microwave source, a resonance at half the frequency is induced using parametric excitation in the parallel geometry. Triggering this nonlinear effect allows us to directly detect on a spectrum analyzer the microwave component of the inverse spin Hall effect voltage. Signals as large as 30 µV are measured for precession angles of a couple of degrees. This direct detection provides a novel efficient means to study magnetization dynamics on a very wide frequency range with great sensitivity.

Transcriptome profiling of UPF3B/NMD-deficient lymphoblastoid cells from patients with various forms of intellectual disability.

The nonsense-mediated mRNA decay (NMD) pathway was originally discovered by virtue of its ability to rapidly degrade aberrant mRNAs with premature termination codons. More recently, it was shown that NMD also directly regulates subsets of normal transcripts, suggesting that NMD has roles in normal biological processes. Indeed, several NMD factors have been shown to regulate neurological events (for example, neurogenesis and synaptic plasticity) in numerous vertebrate species. In man, mutations in the NMD factor gene UPF3B, which disrupts a branch of the NMD pathway, cause various forms of intellectual disability (ID). Using Epstein Barr virus-immortalized B cells, also known as lymphoblastoid cell lines (LCLs), from ID patients that have loss-of-function mutations in UPF3B, we investigated the genome-wide consequences of compromised NMD and the role of NMD in neuronal development and function. We found that ~5% of the human transcriptome is impacted in UPF3B patients. The UPF3B paralog, UPF3A, is stabilized in all UPF3B patients, and partially compensates for the loss of UPF3B function. Interestingly, UPF3A protein, but not mRNA, was stabilised in a quantitative manner that inversely correlated with the severity of patients' phenotype. This suggested that the ability to stabilize the UPF3A protein is a crucial modifier of the neurological symptoms due to loss of UPF3B. We also identified ARHGAP24, which encodes a GTPase-activating protein, as a canonical target of NMD, and we provide evidence that deregulation of this gene inhibits axon and dendrite outgrowth and branching. Our results demonstrate that the UPF3B-dependent NMD pathway is a major regulator of the transcriptome and that its targets have important roles in neuronal cells.

Tolerability and effects on quality of life of liposomal nasal spray treatment compared to nasal ointment containing dexpanthenol or isotonic NaCl spray in patients with rhinitis sicca.

This study aimed to investigate symptom reduction via the liposomal nasal spray LipoNasal (LN) in patients with rhinitis sicca. Tolerability and the impact on quality of life were also examined. The same parameters were established in parallel for treatment approaches with Bepanthen (BP) nasal ointment containing dexpanthenol and the Rhinomer (RH) nasal spray containing NaCl. This prospective, controlled, open-label observation study was a multicenter trial. 92 patients with rhinitis sicca were allocated to three arms according to their symptoms: LN: n = 33; BP: n = 32 and RH: n = 27. The study comprised three visits at an interval of 14 days. Efficacy was examined by the Rhinitis Sicca Symptom Score (RSSS) documented daily and at the visits based on an endoscopic evaluation. The nasal spray sensory scale was used to investigate the tolerability. Quality of life (QoL) was measured by means of the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and the "Short Form 12" of the "Impact on Health-Related Quality of Life (HRQL)" questionnaire on general quality of life. Nasal symptoms improved significantly (p = 0.001) under all three treatment approaches, reflected by the reduction in the RSSS and the Endoscopy Sum Score. A comparison of the three groups showed that no therapy was significantly superior to any of the others (p = 0.410). The tolerability of all treatments was good. Concerning the nasal moisturization, LipoNasal was evaluated better than Bepanthen and Rhinomer. Quality of life improved in all groups, but not significantly. The results show good efficacy and tolerability of the liposomal nasal spray compared to generally recognized treatments of rhinitis sicca with dexpanthenol nasal ointment and NaCl nasal spray. LipoNasal therefore constitutes a good treatment for patients suffering from dry nose.