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Interleukin-22 (IL-22) plays a role in epithelial barrier function and repair, and may provide benefits in conditions like inflammatory bowel disease. However, limited human data are available to assess the clinical effect of IL-22 administration. This study used a human intestinal cell line to identify an IL-22-dependent gene signature that could serve as a pharmacodynamic biomarker for IL-22 therapy. The response to IL-22Fc (UTTR1147A, an Fc-stabilized version of IL-22) was assessed in HT-29 cells by microarray, and the selected responsive genes were confirmed by qPCR. HT-29 cells demonstrated dose-dependent increases in STAT3 phosphorylation and multiple gene expression changes in response to UTTR1147A. Genes were selected that were upregulated by UTTR1147A, but to a lesser extent by IL-6, which also signals via STAT3. IL-1R1 was highly upregulated by UTTR1147A, and differential gene expression patterns were observed in response to IL-22Fc in the presence of IL-1β. An IL-22-dependent gene signature was identified that could serve as a pharmacodynamic biomarker in intestinal biopsies to support the clinical development of an IL-22 therapeutic. The differential gene expression pattern in the presence of IL-1β suggests that an inflammatory cytokine milieu in the disease setting could influence the clinical responses to IL-22.

Recent data‐sharing initiatives of clinical and preclinical Alzheimer's disease (AD) have led to a growing number of non‐clinical researchers analyzing these datasets using modern data‐driven computational methods. Cognitive tests are key components of such datasets, representing the principal clinical tool to establish phenotypes and monitor symptomatic progression. Despite the potential of computational analyses in complementing the clinical understanding of AD, the characteristics and multifactorial nature of cognitive tests are often unfamiliar to computational researchers and other non‐specialist audiences. This perspective paper outlines core features, idiosyncrasies, and applications of cognitive test data. We report tests commonly featured in data‐sharing initiatives, highlight key considerations in their selection and analysis, and provide suggestions to avoid risks of misinterpretation. Ultimately, the greater transparency of cognitive measures will maximize insights offered in AD, particularly regarding understanding the extent and basis of AD phenotypic heterogeneity.

Background To establish which major disorders are susceptible to increased mortality following acute admissions on weekends, compared with week days, and how this may be explained. Methods Cohorts based on national administrative inpatient and mortality data for 14,168,443 hospitalised patients in England and 913,068 in Wales who were admitted for 66 disorders that were associated with at least 200 deaths within 30 days of acute admission. The main outcome measure was the weekend mortality effect (defined as the conventional mortality odds ratio for admissions on weekends compared with week days). Results There were large, statistically significant weekend mortality effects (> 20%) in England for 22 of the 66 conditions and in both countries for 14. These 14 were 4 of 13 cancers (oesophageal, colorectal, lung and lymphomas); 4 of 13 circulatory disorders (angina, abdominal aortic aneurysm, peripheral vascular disease and arterial embolism & thrombosis); one of 8 respiratory disorders (pleural effusion); 2 of 12 gastrointestinal disorders (alcoholic and other liver disease); 2 of 3 ageing-related disorders (Alzheimer’s disease and dementia); none of 7 trauma conditions; and one of 10 other disorders (acute renal failure). Across the disorders, 64% of the variation in weekend mortality effects in England and Wales was explained by reductions in admission rates at weekends and the medical disease category. Conclusions The effect of weekend admission on 30 day mortality is seen mainly for cancers, some circulatory disorders, liver disease and a few other conditions which are mainly ageing- or cancer-related. Most of the increased mortality is associated with reduced admission rates at weekends and the medical disease category.

Shifts in pollination may drive adaptive diversification of reproductive systems within plant lineages. The monophyletic genus Schiedea is a Hawaiian lineage of 32 extant species, with spectacular diversity in reproductive systems. Biotic pollination is the presumed ancestral condition, but this key element of the life history and its role in shaping reproductive systems has remained undocumented. We observed floral visitors to two species of Schiedea and conducted field experiments to test pollinator effectiveness. We used choice tests to compare attraction of pollinators to species hypothesized to be biotically vs wind-pollinated. Pseudoschrankia brevipalpis (Erebidae), a recently described moth species known only from O‘ahu, visited hermaphroditic Schiedea kaalae and S. hookeri and removed nectar from their unique tubular nectary extensions. Pseudoschrankia brevipalpis effectively pollinates S. kaalae; single visits to emasculated flowers resulted in pollen transfer. In choice tests, P. brevipalpis strongly preferred these hermaphroditic species over two subdioecious species capable of wind pollination. A shift from biotic to abiotic pollination is clearly implicated in the diversification of reproductive systems within Schiedea. Abundant pollination by a previously unknown native moth in experimental and restored populations suggests the potential for restoration to re-establish native plant–pollinator interactions critical for production of outcrossed individuals with high fitness.

Background Patients’ smoking status is routinely collected by General Practitioners (GP) in UK primary health care. There is an abundance of Read codes pertaining to smoking, including those relating to smoking cessation therapy, prescription, and administration codes, in addition to the more regularly employed smoking status codes. Large databases of primary care data are increasingly used for epidemiological analysis; smoking status is an important covariate in many such analyses. However, the variable definition is rarely documented in the literature. Methods The Secure Anonymised Information Linkage (SAIL) databank is a repository for a national collection of person-based anonymised health and socio-economic administrative data in Wales, UK. An exploration of GP smoking status data from the SAIL databank was carried out to explore the range of codes available and how they could be used in the identification of different categories of smokers, ex-smokers and never smokers. An algorithm was developed which addresses inconsistencies and changes in smoking status recording across the life course and compared with recorded smoking status as recorded in the Welsh Health Survey (WHS), 2013 and 2014 at individual level. However, the WHS could not be regarded as a “gold standard” for validation. Results There were 6836 individuals in the linked dataset. Missing data were more common in GP records (6%) than in WHS (1.1%). Our algorithm assigns ex-smoker status to 34% of never-smokers, and detects 30% more smokers than are declared in the WHS data. When distinguishing between current smokers and non-smokers, the similarity between the WHS and GP data using the nearest date of comparison was κ = 0.78. When temporal conflicts had been accounted for, the similarity was κ = 0.64, showing the importance of addressing conflicts. Conclusions We present an algorithm for the identification of a patient’s smoking status using GP self-reported data. We have included sufficient details to allow others to replicate this work, thus increasing the standards of documentation within this research area and assessment of smoking status in routine data.

Despite advances in diagnosis, treatment, and management of brain tumors, a brain tumor (BT) can significantly disrupt a person's life and create stress. To design effective stress reduction interventions, it is essential to have an understanding of the beliefs, past experiences, and preferences concerning stress reduction techniques and programs among patients with BTs. Using a convenience sample, 60 adult patients with primary BTs completed the study questionnaire. Demographic information and patient preferences were collected using self-reported measures, medical information was collected via medical chart review, and stress was assessed using Perceived Stress Scale. Sixty-three percent of the population sampled experienced elevated levels of stress. Eighty-six percent wanted to learn about techniques to reduce stress and 78% believed stress reduction techniques can help reduce stress. However, only 56% indicated they would be able to participate in a stress reduction program twice a week and only 40% of the sample wanted to participate in the various stress reduction programs presented to them in this study. Furthermore, only 26% of the sample actually wanted to receive information about stress reduction programs and only 25% would participate in programs using the various modes presented. The results of this study clearly indicate that patients with BTs experience stress. Furthermore, the data is encouraging in regard to the patients' desire to learn about stress reduction techniques. However, the lack of interest in actually receiving information and the inability to envision themselves participating in programs present a major challenge.

Caregivers of patients with brain tumors (BT) experience elevated levels of stress. Using pilot data, we sought to determine which caregivers are at risk for experiencing elevated levels of stress based on caregiver-demographic and patient-medical information. Using a convenience sample of 60 caregivers, participants were asked to complete the Perceived Stress Scale and to provide demographic information. The Perceived Stress Scale is a 10-item scale designed to measure the degree to which situations in life are perceived as stressful. Demographic information was collected using self-reported measures. Medical data concerning tumor grade of patient were obtained from most recent medical note. Data for study were standardized using z-scores and analyzed using SPSS software. Seventy-two percent (n=43) of caregivers reported experiencing elevated levels of stress within the last 30 days. Thirty-five percent (n=21) of the sample scored at least one standard deviation above the mean. A statistical trend [F(1, 57)=3.12, p=0.08] exists between caregiver stress and tumor grade of patients for which they are providing care. Caregivers of patients with BT experience significant stress. Furthermore, this data provide an indication of the profound levels of stress these caregivers experience. Caregivers of patients with grade I/II tumors are at increased risk for experiencing stress. Younger caregiver age and higher levels of education were also found to correlate to higher levels of stress.

The CDC releases guidelines for fully-vaccinated Americans on what they can and can't do. The House is set to vote on the Senate-passed COVID Relief Package tomorrow. A bipartisan group of lawmakers is getting their first briefing from the Capitol Security Review Task Force about security recommendations following the January 6th attack on Capitol Hill. Democratic senators on more Senate Democrats backing elimination of the filibuster. Jury selection delayed as Minnesota appeals court opened the door for third degree murder charge against Derek Chauvin. New York's governor facing growing calls to resign over harassment claims. The Duchess of Sussex claimed there were conversations expressing concerns about her son Archie's skin color before he was born. GUESTS: Megan Ranney, Tina Smith

Breaking silence for the first time since the tragedy in Newtown, the NRA speaks out as momentum now grows across the country to do something about guns. In Newtown, four days after this tragedy at the elementary school, the rest of the town schools reopened and kids returned to class, even as others were being laid to rest. In Dunblane Scotland, the people there, more than most, know what Newtown is going through and what may lie ahead for them. NBC's Richard Engel and his crew set free after being kidnapped for five days inside Syria, and tonight, we'll hear from Richard about what happened and how they made it out. A deal that so-called fiscal cliff may hinge on how both sides define \"rich.\" It started as a simple idea, just being kind, and tonight, Ann Curry reports on the overwhelming response now being felt around the world that is \"Making a Difference.\"