Airborne DNA reveals predictable spatial and seasonal dynamics of fungi.

Fungi are among the most diverse and ecologically important kingdoms in life. However, the distributional ranges of fungi remain largely unknown as do the ecological mechanisms that shape their distributions1,2. To provide an integrated view of the spatial and seasonal dynamics of fungi, we implemented a globally distributed standardized aerial sampling of fungal spores3. The vast majority of operational taxonomic units were detected within only one climatic zone, and the spatiotemporal patterns of species richness and community composition were mostly explained by annual mean air temperature. Tropical regions hosted the highest fungal diversity except for lichenized, ericoid mycorrhizal and ectomycorrhizal fungi, which reached their peak diversity in temperate regions. The sensitivity in climatic responses was associated with phylogenetic relatedness, suggesting that large-scale distributions of some fungal groups are partially constrained by their ancestral niche. There was a strong phylogenetic signal in seasonal sensitivity, suggesting that some groups of fungi have retained their ancestral trait of sporulating for only a short period. Overall, our results show that the hyperdiverse kingdom of fungi follows globally highly predictable spatial and temporal dynamics, with seasonality in both species richness and community composition increasing with latitude. Our study reports patterns resembling those described for other major groups of organisms, thus making a major contribution to the long-standing debate on whether organisms with a microbial lifestyle follow the global biodiversity paradigms known for macroorganisms4,5.

EAES/SAGES evidence-based recommendations and expert consensus on optimization of perioperative care in older adults.

BACKGROUND: As the population ages, more older adults are presenting for surgery. Age-related declines in physiological reserve and functional capacity can result in frailty and poor outcomes after surgery. Hence, optimizing perioperative care in older patients is imperative. Enhanced Recovery After Surgery (ERAS) pathways and Minimally Invasive Surgery (MIS) may influence surgical outcomes, but current use and impact on older adults patients is unknown. The aim of this study was to provide evidence-based recommendations on perioperative care of older adults undergoing major abdominal surgery. METHODS: Expert consensus determined working definitions for key terms and metrics related to perioperative care. A systematic literature review and meta-analysis was performed using the PubMed, Embase, Cochrane Library, and Clinicaltrials.gov databases for 24 pre-defined key questions in the topic areas of prehabilitation, MIS, and ERAS in major abdominal surgery (colorectal, upper gastrointestinal (UGI), Hernia, and hepatopancreatic biliary (HPB)) to generate evidence-based recommendations following the GRADE methodology. RESULT: Older adults were defined as 65 years and older. Over 20,000 articles were initially retrieved from search parameters. Evidence synthesis was performed across the three topic areas from 172 studies, with meta-analyses conducted for MIS and ERAS topics. The use of MIS and ERAS was recommended for older adult patients particularly when undergoing colorectal surgery. Expert opinion recommended prehabilitation, cessation of smoking and alcohol, and correction of anemia in all colorectal, UGI, Hernia, and HPB procedures in older adults. All recommendations were conditional, with low to very low certainty of evidence, with the exception of ERAS program in colorectal surgery. CONCLUSIONS: MIS and ERAS are recommended in older adults undergoing major abdominal surgery, with evidence supporting use in colorectal surgery. Though expert opinion supported prehabilitation, there is insufficient evidence supporting use. This work has identified evidence gaps for further studies to optimize older adults undergoing major abdominal surgery.

Catalytic Differences between Flavohemoglobins of Giardia intestinalis and E. coli.

The sole known heme enzyme of the parasitic protist Giardia intestinalis is a flavohemoglobin (gFlHb) that acts as a nitric oxide dioxygenase (NOD) and protects the organism from the free radical nitric oxide. To learn more about the properties of this enzyme, we measured its nitric oxide dioxygenase, NADH oxidase, and cytochrome c reductase activities and compared these to the activities of the E. coli flavohemoglobin (Hmp). The turnover number for the NOD activity of gFlHb (23 s-1) is about two-thirds of that of Hmp (34 s-1) at pH 6.5 and 37 °C. The two enzymes differ in their sensitivity towards molecules that act as heme ligands. For both gFlHb and Hmp, inhibition with miconazole, a large imidazole ligand, is adequately described by simple competitive inhibition, with KI = 10 µM and 0.27 µM for gFlHb and Hmp, respectively. Inhibition plots with the small ligand imidazole were biphasic, which is consistent with previous experiments with carbon monoxide as a probe that show that the active site of flavohemoglobins exists in two conformations. Interestingly, the largest difference is observed with nitrite, which, like imidazole, also shows a biphasic inhibition plot; however, nitrite inhibits gFlHb at sub-millimolar concentrations while Hmp is not significantly affected. NADH oxidase activity measured under aerobic conditions in the absence of nitric oxide for Hmp was more than twice the activity of gFlHb. The addition of 1 mM hydrogen peroxide in these assays stimulated the NADH oxidase activity of gFlHb but not Hmp. Both enzymes had nearly identical cytochrome c reductase activities but the extent of the contribution of indirect reduction by flavohemoglobin-generated superoxide was much lower with gFlHb (4% SOD-inhibited) than with Hmp (17% SOD-inhibited). Although the active sites of the two enzymes share the same highly conserved residues that are important for catalysis, differences in the distal ligand binding site may account for these differences in activity and sensitivity towards NOD inhibitors. The differences observed in the NADH oxidase and cytochrome c reductase assays suggest that gFlHb may have evolved to protect the protist, which lacks both superoxide dismutase and catalase, from the damaging effects of superoxide by minimizing its production and from peroxide by actively reducing it.

The Impact of a Digital Contraceptive Decision Aid on User Outcomes: Results of an Experimental, Clinical Trial.

BACKGROUND: Nearly 40% of unplanned pregnancies in the USA are the result of inconsistent or incorrect contraceptive use. Finding ways to increase women's comfort and satisfaction with contraceptive use is therefore critical to public health. One promising pathway for improving patient outcomes is through the use of digital decision aids that assist women and their physicians in choosing a contraceptive option that women are comfortable with. Testing the ability of these aids to improve patient outcomes is therefore a necessary first step toward incorporating this technology into traditional physician appointments. PURPOSE: To evaluate the effectiveness of a novel contraceptive decision aid at minimizing decisional conflict and increasing comfort with contraception among adult women. METHODS: In total, 310 adult women were assigned to use either the Tuune contraceptive decision aid or a control aid modeled after a leading online contraceptive prescriber's patient intake form. Participants then completed self-report measures of decisional conflict, contraceptive expectations, satisfaction, and contraceptive use intentions. Individual between-subjects analysis of variance (ANOVA) models were used to examine these outcomes. RESULTS: Women using the Tuune decision aid (vs. those using the control aid) reported lower decisional conflict, more positive contraceptive expectations, greater satisfaction with the decision aid and recommendation, and more positive contraceptive use intentions. CONCLUSIONS: Use of Tuune improved each of the predicted patient outcomes relative to a control decision aid. Online decision aids, particularly when used alongside physician consultations, may be an effective tool for increasing comfort with contraceptive use. CLINICAL TRIALS REGISTRATION #: NCT05177783, ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT05177783.

Digital decision aids that help women and their physicians choose contraceptive options that women are most comfortable with present one promising way to improve contraceptive use outcomes, such as avoiding unplanned pregnancies. However, current decision aids have been found to struggle in helping improve women's satisfaction with and confidence in their contraceptive choices. The aim of this study was to test the effectiveness of a new digital decision aid, named Tuune, at helping improve women's confidence and comfort with contraception. Three hundred and ten adult women were randomly assigned to use and then receive a contraceptive recommendation from either the Tuune decision aid or a control aid designed after leading traditional health intake forms. Women's confidence and satisfaction with the aids, as well as their contraceptive recommendation, were then compared between groups. We found good evidence to suggest that women using the Tuune contraceptive decision aid were more satisfied and positive about their contraceptive choices and reported greater intentions to use contraception with increased confidence compared to women who used the control decision aid. New online decision aids, like Tuune, may be an effective tool for increasing women's comfort and experiences using contraception.

Longitudinal associations between women's cycle characteristics and sexual motivation using Flo cycle tracking data.

In the current research, we used data from a sample of 16,327 menstrual cycle tracking app users to examine the association between menstrual cycle characteristics and sexual motivation tracked over 10 months of app use. Guided by past work that finds links between menstrual cycle characteristics related to conception risk and sexual motivation, we found that (a) between-women, shorter (r = - 0.04, p = 0.007), more regular cycles predicted small increases in sexual motivation (r = - 0.04, p = 0.001); (b) within-women, shorter cycles predicted greater sexual motivation that month (r = - 0.04, p < 0.001) and (c) the next month (ßs: - 0.10 to - 0.06, ps < 0.001), but (d) changes in sexual motivation did not reliably precede changes in cycle length (ßs: - 0.01 to 0.02, ps > 0.15). Within-woman analyses also revealed that (e) shorter cycles were followed by more frequent reports of fatigue (ß = - 0.06, p < 0.001), insomnia (ß = - 0.03, p < 0.001), and food cravings (ß = - 0.04, p < 0.001). Together, results suggest that menstrual cycles characteristics and sexual motivation may covary together in ways that reflect changing investments in reproduction. Small effect sizes and lack of experimental control warrant cautious interpretations of results.

Reducing time to differentiated service delivery for newly-diagnosed people living with HIV in Kigali, Rwanda: a pilot, unblinded, randomized controlled trial.

BACKGROUND: Differentiated service delivery (DSD) programs for people living with HIV (PWH) limit eligibility to patients established on antiretroviral therapy (ART), yet uncertainty exists regarding the duration on ART necessary for newly-diagnosed PWH to be considered established. We aimed to determine the feasibility, acceptability, and preliminary impact of entry into DSD at six months after ART initiation for newly-diagnosed PWH. METHODS: We conducted a pilot randomized controlled trial in three health facilities in Rwanda. Participants were randomized to: (1) entry into DSD at six months after ART initiation after one suppressed viral load (DSD-1VL); (2) entry into DSD at six months after ART initiation after two consecutive suppressed viral loads (DSD-2VL); (3) treatment as usual (TAU). We examined feasibility by examining the proportion of participants assigned to intervention arms who entered DSD, assessed acceptability through patient surveys and by examining instances when clinical staff overrode the study assignment, and evaluated preliminary effectiveness by comparing study arms with respect to 12-month viral suppression. RESULTS: Among 90 participants, 31 were randomized to DSD-1VL, 31 to DSD-2VL, and 28 to TAU. Among 62 participants randomized to DSD-1VL or DSD-2VL, 37 (60%) entered DSD at 6 months while 21 (34%) did not enter DSD because they were not virally suppressed. Patient-level acceptability was high for both clinical (mean score: 3.8 out of 5) and non-clinical (mean score: 4.1) elements of care and did not differ significantly across study arms. Viral suppression at 12 months was 81%, 81% and 68% in DSD-1VL, DSD-2VL, and TAU, respectively (p = 0.41). CONCLUSIONS: The majority of participants randomized to intervention arms entered DSD and had similar rates of viral suppression compared to TAU. Results suggest that early DSD at six months after ART initiation is feasible for newly-diagnosed PWH, and support current WHO guidelines on DSD. TRIAL REGISTRATION: Clinicaltrials.gov NCT04567693; first registered on September 28, 2020.

Higher HIV-1 evolutionary rate is associated with cytotoxic T lymphocyte escape mutations in infants.

Escape from cytotoxic T lymphocyte (CTL) responses toward HIV-1 Gag and Nef has been associated with reduced control of HIV-1 replication in adults. However, less is known about CTL-driven immune selection in infants as longitudinal studies of infants are limited. Here, 1,210 gag and 1,264 nef sequences longitudinally collected within 15 months after birth from 14 HIV-1 perinatally infected infants and their mothers were analyzed. The number of transmitted founder (T/F) viruses and associations between virus evolution, selection, CTL escape, and disease progression were determined. The analyses indicated that a paraphyletic-monophyletic relationship between the mother-infant sequences was common (80%), and that the HIV-1 infection was established by a single T/F virus in 10 of the 12 analyzed infants (83%). Furthermore, most HIV-1 CTL escape mutations among infants were transmitted from the mothers and did not revert during the first year of infection. Still, immune-driven selection was observed at approximately 3 months after HIV-1 infection in infants. Moreover, virus populations with CTL escape mutations in gag evolved faster than those without, independently of disease progression rate. These findings expand the current knowledge of HIV-1 transmission, evolution, and CTL escape in infant HIV-1 infection and are relevant for the development of immune-directed interventions in infants.IMPORTANCEDespite increased coverage in antiretroviral therapy for the prevention of perinatal transmission, paediatric HIV-1 infection remains a significant public health concern, especially in areas of high HIV-1 prevalence. Understanding HIV-1 transmission and the subsequent virus adaptation from the mother to the infant's host environment, as well as the viral factors that affect disease outcome, is important for the development of early immune-directed interventions for infants. This study advances our understanding of vertical HIV-1 transmission, and how infant immune selection pressure is shaping the intra-host evolutionary dynamics of HIV-1.

Efficacy of the Flo App in Improving Health Literacy, Menstrual and General Health, and Well-Being in Women: Pilot Randomized Controlled Trial.

BACKGROUND: Reproductive health literacy and menstrual health awareness play a crucial role in ensuring the health and well-being of women and people who menstruate. Further, awareness of one's own menstrual cycle patterns and associated symptoms can help individuals identify and manage conditions of the menstrual cycle such as premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). Digital health products, and specifically menstrual health apps, have the potential to effect positive change due to their scalability and ease of access. OBJECTIVE: The primary aim of this study was to measure the efficacy of a menstrual and reproductive health app, Flo, in improving health literacy and health and well-being outcomes in menstruating individuals with and without PMS and PMDD. Further, we explored the possibility that the use of the Flo app could positively influence feelings around reproductive health management and communication about health, menstrual cycle stigma, unplanned pregnancies, quality of life, work productivity, absenteeism, and body image. METHODS: We conducted 2 pilot, 3-month, unblinded, 2-armed, remote randomized controlled trials on the effects of using the Flo app in a sample of US-based (1) individuals who track their cycles (n=321) or (2) individuals who track their cycles and are affected by PMS or PMDD (n=117). RESULTS: The findings revealed significant improvements at the end of the study period compared to baseline for our primary outcomes of health literacy (cycle tracking: D̄=1.11; t311=5.73, P<.001; PMS or PMDD: D̄=1.20; t115=3.76, P<.001) and menstrual health awareness (D̄=3.97; t311=7.71, P<.001), health and well-being (D̄=3.44; t311=5.94, P<.001), and PMS or PMDD symptoms burden (D̄=-7.08; t115=-5.44, P<.001). Improvements were also observed for our secondary outcomes of feelings of control and management over health (D̄=1.01; t311=5.08, P<.001), communication about health (D̄=0.93; t311=2.41, P=.002), menstrual cycle stigma (D̄=-0.61; t311=-2.73, P=.007), and fear of unplanned pregnancies (D̄=-0.22; t311=-2.11, P=.04) for those who track their cycles, as well as absenteeism from work and education due to PMS or PMDD (D̄=-1.67; t144=-2.49, P=.01). CONCLUSIONS: These pilot randomized controlled trials demonstrate that the use of the Flo app improves menstrual health literacy and awareness, general health and well-being, and PMS or PMDD symptom burden. Considering the widespread use and affordability of the Flo app, these findings show promise for filling important gaps in current health care provisioning such as improving menstrual knowledge and health. TRIAL REGISTRATION: OSF Registries osf.io/pcgw7; https://osf.io/pcgw7 ; OSF Registries osf.io/ry8vq; https://osf.io/ry8vq.

Global Spore Sampling Project: A global, standardized dataset of airborne fungal DNA.

Novel methods for sampling and characterizing biodiversity hold great promise for re-evaluating patterns of life across the planet. The sampling of airborne spores with a cyclone sampler, and the sequencing of their DNA, have been suggested as an efficient and well-calibrated tool for surveying fungal diversity across various environments. Here we present data originating from the Global Spore Sampling Project, comprising 2,768 samples collected during two years at 47 outdoor locations across the world. Each sample represents fungal DNA extracted from 24 m3 of air. We applied a conservative bioinformatics pipeline that filtered out sequences that did not show strong evidence of representing a fungal species. The pipeline yielded 27,954 species-level operational taxonomic units (OTUs). Each OTU is accompanied by a probabilistic taxonomic classification, validated through comparison with expert evaluations. To examine the potential of the data for ecological analyses, we partitioned the variation in species distributions into spatial and seasonal components, showing a strong effect of the annual mean temperature on community composition.

Sialyl-Tn serves as a potential therapeutic target for ovarian cancer.

BACKGROUND: Ovarian cancer remains the deadliest of the gynecologic cancers in the United States. There have been limited advances in treatment strategies that have seen marked increases in overall survival. Thus, it is essential to continue developing and validating new treatment strategies and markers to identify patients who would benefit from the new strategy. In this report, we sought to further validate applications for a novel humanized anti-Sialyl Tn antibody-drug conjugate (anti-STn-ADC) in ovarian cancer. METHODS: We aimed to further test a humanized anti-STn-ADC in sialyl-Tn (STn) positive and negative ovarian cancer cell line, patient-derived organoid (PDO), and patient-derived xenograft (PDX) models. Furthermore, we sought to determine whether serum STn levels would reflect STn positivity in the tumor samples enabling us to identify patients that an anti-STn-ADC strategy would best serve. We developed a custom ELISA with high specificity and sensitivity, that was used to assess whether circulating STn levels would correlate with stage, progression-free survival, overall survival, and its value in augmenting CA-125 as a diagnostic. Lastly, we assessed whether the serum levels reflected what was observed via immunohistochemical analysis in a subset of tumor samples. RESULTS: Our in vitro experiments further define the specificity of the anti-STn-ADC. The ovarian cancer PDO, and PDX models provide additional support for an anti-STn-ADC-based strategy for targeting ovarian cancer. The custom serum ELISA was informative in potential triaging of patients with elevated levels of STn. However, it was not sensitive enough to add value to existing CA-125 levels for a diagnostic. While the ELISA identified non-serous ovarian tumors with low CA-125 levels, the sample numbers were too small to provide any confidence the STn ELISA would meaningfully add to CA-125 for diagnosis. CONCLUSIONS: Our preclinical data support the concept that an anti-STn-ADC may be a viable option for treating patients with elevated STn levels. Moreover, our STn-based ELISA could complement IHC in identifying patients with whom an anti-STn-based strategy might be more effective.

Determination of the Nanoscale Silica Mass Fraction by AF4/ICP-MS with Isotope Dilution Analysis Using 29Si-Enriched Silica Nanoparticles.

A methodology based on the use of asymmetrical flow field-flow fractionation (AF4) coupled to ICP-MS with size fraction-targeted isotope dilution analysis (IDA) has been developed, validated, and applied for the first time to determine the mass fraction of nanoscale silica (SiO2). For this purpose, 29Si-enriched SiO2 nanoparticles, to be used as an IDA spike/internal standard, were synthesized and characterized in-house. Double IDA was used to quantify an aqueous suspension of Stöber silica particles of similar characteristics to those of the 29SiO2 nanoparticle (NP) spike using a representative test material of natural Si isotopic composition as the calibrant. For fumed SiO2 NP in a highly complex food matrix, a methodology based on single IDA with AF4/ICP-MS using the same 29SiO2 NP spike was developed and validated. Relative expanded measurement uncertainties (k = 2) of 4% (double IDA) and 8% (single IDA) were achieved for nanoscale silica mass fractions of 5143 and 107 mg kg-1 in water suspension and food matrix, respectively. To assess the accuracy of AF4/ICP-IDMS for the characterization of SiO2 NP in a food matrix, standard addition measurements on samples spiked with Aerosil AF200, also in-house characterized for Si mass fraction, were undertaken, with an average recovery of 95.6 ± 4.1% (RSD, n = 3) obtained. The particle-specific IDA data obtained for both SiO2 NP-containing samples were also compared with that of post-AF4 channel external calibration using inorganic Si standards. The mass fractions obtained by IDA agreed well with those obtained by external calibration within their associated measurement uncertainties.

Germline and Somatic Fumarate Hydratase Testing in Atypical Uterine Leiomyomata.

Women with germline pathogenic variants (PV) in the fumarate hydratase (FH) gene develop cutaneous and uterine leiomyomata and have an increased risk of developing aggressive renal cell carcinomas. Many of these women are unaware of their cancer predisposition until an atypical uterine leiomyoma is diagnosed during a myomectomy or hysterectomy, making a streamlined genetic counseling process after a pathology-based atypical uterine leiomyoma diagnosis critical. However, the prevalence of germline pathogenic/likely PVs in FH among atypical uterine leiomyomata cases is unknown. To better understand FH germline PV prevalence and current patterns of genetic counseling and germline genetic testing, we undertook a retrospective review of atypical uterine leiomyomata cases at a single large center. We compared clinical characteristics between the FH PV, FH wild-type (WT), and unknown genetic testing cohorts. Of the 144 cases with atypical uterine leiomyomata with evaluable clinical data, only 49 (34%) had documented genetic test results, and 12 (8.3%) had a germline FH PV. There were 48 IHC-defined FH-deficient cases, of which 41 (85%) had FH testing and nine had a germline FH PV, representing 22% of the tested cohort and 18.8% of the FH-deficient cohort. Germline FH PVs were present in 8.3% of evaluable patients, representing 24.5% of the cohort that completed genetic testing. These data highlight the disconnect between pathology and genetic counseling, and help to refine risk estimates that can be used when counseling patients with atypical uterine leiomyomata. PREVENTION RELEVANCE: Women diagnosed with fumarate hydratase (FH)-deficient uterine leiomyomata are at increased risk of renal cancer. This work suggests a more standardized pathology-genetic counseling referral pathway for these patients, and that research on underlying causes of FH-deficient uterine leiomyomata in the absence of germline FH pathogenic/likely pathogenic variants is needed.

Feeding difficulties in children with food allergies: An EAACI Task Force Report.

The term "feeding difficulties" refers to a spectrum of phenotypes characterized by suboptimal intake of food and/or lack of age-appropriate eating habits. While it is evident that feeding difficulties are prevalent within healthy children, no consensus has been reached for those with food allergies. The aim of this study was to systematically review all the available literature reporting the prevalence of feeding difficulties within food allergic children. We searched eight international electronic databases for all published studies until June 2022. International experts in the field were also contacted for unpublished and ongoing studies. All publications were screened against pre-defined eligibility criteria and critically appraised by established instruments. The substantial heterogeneity of included studies precluded meta-analyses, so narrative synthesis of quantitative data was performed. A total of 2059 abstracts were assessed, out of which 21 underwent full-text screening and 10 studies met the study criteria. In these, 12 different terms to define feeding difficulties and 11 diagnostic tools were used. Five papers included data of feeding difficulty prevalence in children with food allergies, ranging from 13.6% to 40%. Higher prevalence was associated with multiple food allergies. The current literature suggests that feeding difficulties are prevalent within food allergic children, particularly those with multiple food allergies. However, the heterogeneity of terminologies and diagnostic tools makes drawing conclusions challenging. Consensus guidelines for the diagnosis and management of feeding difficulties within food allergic children and further research on the development and perpetuation of feeding difficulties are needed to appropriately manage such patients.

Longitudinal changes in sexual desire and attraction among women who started using the Natural Cycles app.

Many women experience sexual side effects, such as decreased libido, when taking hormonal contraceptives (HCs). However, little is known about the extent to which libido recovers after discontinuing HCs, nor about the timeframe in which recovery is expected to occur. Given that HCs suppress the activities of multiple endogenous hormones that regulate both the ovulatory cycle and women's sexual function, resumption of cycles should predict libido recovery. Here, using a combination of repeated and retrospective measures, we examined changes in sexual desire and partner attraction (among partnered women) across a three-month period in a sample of Natural Cycles users (Survey 1: n = 1596; Survey 2: n = 550) who recently discontinued HCs. We also tested whether changes in these outcomes coincided with resumption of the ovulatory cycle and whether they were associated with additional factors related to HC use (e.g., duration of HC use) or relationship characteristics (e.g., relationship length). Results revealed that both sexual desire and partner attraction, on average, increased across three months after beginning to use Natural Cycles. While the prediction that changes in sexual desire would co-occur with cycle resumption was supported, there was also evidence that libido continued to increase even after cycles resumed. Together, these results offer new insights into relationships between HC discontinuation and women's sexual psychology and lay the groundwork for future research exploring the mechanisms underlying these effects.

A Methodological Study to Compare Alternative Modes of Administration With Value EQ-5D Using Preference-Elicitation Techniques.

OBJECTIVES: Time trade-off (TTO) and discrete choice experiment (DCE) preference-elicitation techniques can be administered using face-to-face interviews (F2F), unassisted online (UO) surveys, or remote-assisted (RA) interviews. The objective of this study was to explore how the mode of administration affects the quality and reliability of preference-elicitation data. METHODS: EQ-5D-5L health states were valued using composite TTO (cTTO) and DCE approaches by the UK general population. Participants were allocated to 1 of 2 study groups. Group A completed both F2F and UO surveys (n = 271), and group B completed both RA and UO surveys (n = 223). The feasibility of survey completion and the reliability and face-validity of data collected were compared across all modes of administration. RESULTS: Fewer participants reported receiving sufficient guidance on the cTTO tasks during the UO survey compared with the 2 assisted modes. Participants across all modes typically reported receiving sufficient guidance on the DCE tasks. cTTO data were less reliable from the UO survey compared with both assisted modes, but there were no differences in DCE data reliability. cTTO data from all modes demonstrated face-validity; however, the UO survey produced higher utilities for moderate and severe health states than both assisted modes. Both F2F and RA modes provided comparably reliable data. CONCLUSIONS: The reliability of DCE data is not affected by the mode of administration. Interviewer-assisted modes of administration (F2F or RA) yield more reliable cTTO data than unassisted surveys. Both F2F and RA surveys produced similar-quality data.

A time trade-off study to determine health-state utilities of transplant recipients with refractory cytomegalovirus infection with or without resistance.

BACKGROUND: Health-state utility values (HSUVs) for post-transplant refractory cytomegalovirus (CMV) infection (with or without resistance [R/R]) were determined using a time trade-off (TTO) survey completed by 1,020 members of the UK general public. METHODS: Existing literature and qualitative interviews with clinicians experienced in treating R/R CMV were used to develop initial draft vignettes of health states. The vignettes were refined to describe three clinical states of R/R CMV: clinically significant and symptomatic (CS-symptomatic CMV); clinically significant and asymptomatic (CS-asymptomatic CMV); and non-clinically significant (non-CS CMV). Each clinical state was valued independently and combined with three events of interest: graft-versus-host disease; kidney graft loss; and lung graft loss to generate twelve vignettes. The final vignettes were evaluated by a sample of the UK general public using an online TTO survey. Exclusion criteria were applied to the final data to ensure that responses included in the analysis met pre-defined quality control criteria. RESULTS: Overall, 738 participants met the inclusion criteria and were included in the analysis. The sample was representative of the UK general population in terms of age and sex. Non-CS CMV had the highest mean HSUV (95% confidence interval) (0.815 [0.791, 0.839]), followed by CS-asymptomatic CMV (0.635 [0.602, 0.669]), and CS-symptomatic CMV (0.443 [0.404, 0.482]). CS-symptomatic CMV with lung graft loss had the lowest mean HSUV (0.289), with none of the health states considered on average worse than dead. CONCLUSIONS: Post transplant R/R CMV has substantial impact on the health-related quality of life of patients. The utility values obtained in this study may be used to support economic evaluations of therapies for R/R CMV infection.

Targeting Galectin 3 illuminates its contributions to the pathology of uterine serous carcinoma.

BACKGROUND: Uterine serous cancer (USC) comprises around 10% of all uterine cancers. However, USC accounts for approximately 40% of uterine cancer deaths, which is attributed to tumor aggressiveness and limited effective treatment. Galectin 3 (Gal3) has been implicated in promoting aggressive features in some malignancies. However, Gal3's role in promoting USC pathology is lacking. METHODS: We explored the relationship between LGALS3 levels and prognosis in USC patients using TCGA database, and examined the association between Gal3 levels in primary USC tumors and clinical-pathological features. CRISPR/Cas9-mediated Gal3-knockout (KO) and GB1107, inhibitor of Gal3, were employed to evaluate Gal3's impact on cell function. RESULTS: TCGA analysis revealed a worse prognosis for USC patients with high LGALS3. Patients with no-to-low Gal3 expression in primary tumors exhibited reduced clinical-pathological tumor progression. Gal3-KO and GB1107 reduced cell proliferation, stemness, adhesion, migration, and or invasion properties of USC lines. Furthermore, Gal3-positive conditioned media (CM) stimulated vascular tubal formation and branching and transition of fibroblast to cancer-associated fibroblast compared to Gal3-negative CM. Xenograft models emphasized the significance of Gal3 loss with fewer and smaller tumors compared to controls. Moreover, GB1107 impeded the growth of USC patient-derived organoids. CONCLUSION: These findings suggest inhibiting Gal3 may benefit USC patients.

Characterization of the genomic sequence of a circo-like virus and of three chaphamaparvoviruses detected in mute swan (Cygnus olor).

We report the complete genomes of four ssDNA viruses: a circular replication-associated protein-encoding single-stranded DNA virus belonging to a clade previously detected only in mammals, and three chaphamaparvoviruses, which were detected by viromic surveillance of mute swan (Cygnus olor) fecal samples from the United Kingdom.