An Improved Assessment Method to Estimate (Poly)phenol Intake in Adults with Chronic Pancreatitis.

BACKGROUND: Insights into (poly)phenol exposure represent a modifiable factor that may modulate inflammation in chronic pancreatitis (CP), yet intake is poorly characterized and methods for assessment are underdeveloped. AIMS: The aims are to develop and test a method for estimating (poly)phenol intake from a 90-day food frequency questionnaire (FFQ) using the Phenol-Explorer database and determine associations with dietary patterns in CP patients versus controls via analysis of previously collected cross-sectional data. METHODS: Fifty-two CP patients and 48 controls were recruited from an ambulatory clinic at a large, academic institution. To assess the feasibility of the proposed methodology for estimating dietary (poly)phenol exposure, a retrospective analysis of FFQ data was completed. Mann-Whitney U tests were used to compare (poly)phenol intake by group; Spearman correlations and multivariable-adjusted log-linear associations were used to compare (poly)phenol intakes with dietary scores within the sample. RESULTS: Estimation of (poly)phenol intake from FFQs was feasible and produced estimates within a range of intake previously reported. Total (poly)phenol intake was significantly lower in CP vs controls (463 vs. 567mg/1000kcal; p = 0.041). In adjusted analyses, higher total (poly)phenol intake was associated with higher HEI-2015 (r = 0.34, p < 0.001), aMED (r = 0.22, p = 0.007), EDIH (r = 0.29, p < 0.001), and EDIP scores (r = 0.35, p < 0.001), representing higher overall diet quality and lower insulinemic and anti-inflammatory dietary potentials, respectively. CONCLUSIONS: Using enhanced methods to derive total (poly)phenol intake from an FFQ is feasible. Those with CP have lower total (poly)phenol intake and less favorable dietary pattern indices, thus supporting future tailored dietary intervention studies in this population.

Ovarian vein thrombus in a pediatric patient: A case study.

Acute abdominal pain is a very common chief complaint in the pediatric population, accounting for 5-10% of emergency department (ED) visits. Etiology differentiation is determined by complete history and physical examination, basic laboratory studies, and a variety of imaging study options. In this case report, we present an 8-year-old female with an unusual etiology of acute lower abdominal pain. She presented with tachycardia, hypertension, and bilateral lower quadrant abdominal tenderness without peritonitis. Laboratory studies were unremarkable and appendix ultrasound was indeterminate. CT with contrast revealed right ovarian vein thrombosis. Hematology evaluation did not reveal hypercoagulability. She was discharged on rivaroxaban, which was discontinued after a 3 month course and negative follow-up MRI. Ovarian vein thrombosis (OVT) most commonly develops in the peripartum time frame, with an estimated 20%-40% of cases not related to pregnancies. However, patients with nonpregnancy related OVT were determined to be significantly older than patients with pregnancy related OVT. This case report demonstrates the youngest documented case of OVT. This patient was not in the peripartum period and did not have any identifiable risk factors. Given this unprovoked OVT in a pediatric patient, in patients presenting with abdominal pain with unspecified etiology, advanced imaging studies may be helpful in establishing a diagnosis.

mini-MED: study protocol for a randomized, multi-intervention, semi-controlled feeding trial of a Mediterranean-amplified vs. habitual Western dietary pattern for the evaluation of food-specific compounds and cardiometabolic health.

BACKGROUND: Diet is among the most influential lifestyle factors impacting chronic disease risk. Nutrimetabolomics, the application of metabolomics to nutrition research, allows for the detection of food-specific compounds (FSCs) that can be used to connect dietary patterns, such as a Mediterranean-style (MED) diet, to health. This validation study is based upon analyses from a controlled feeding MED intervention, where our team identified FSCs from eight foods that can be detected in biospecimens after consumption and may therefore serve as food intake biomarkers. METHODS: Individuals with overweight/obesity who do not habitually consume a MED dietary pattern will complete a 16-week randomized, multi-intervention, semi-controlled feeding study of isocaloric dietary interventions: (1) MED-amplified dietary pattern, containing 500 kcal/day from eight MED target foods: avocado, basil, cherry, chickpea, oat, red bell pepper, walnut, and a protein source (alternating between salmon or unprocessed, lean beef), and (2) habitual/Western dietary pattern, containing 500 kcal/day from six non-MED target foods: cheesecake, chocolate frozen yogurt, refined grain bread, sour cream, white potato, and unprocessed, lean beef. After a 2-week washout, participants complete four, 4-week intervention periods, with biospecimen sampling and outcome assessments at baseline and at intervention weeks 4, 8, 12, and 16. The primary outcome is change in the relative abundance of FSCs from the eight MED target foods in participant biospecimens from baseline to the end of each intervention period. Secondary outcomes include mean change in cardiometabolic health indicators, inflammatory markers, and adipokines. Exploratory outcomes include change in diversity and community composition of the gut microbiota. DISCUSSION: Our stepwise strategy, beginning with identification of FSCs in whole diets and biospecimens, followed by relating these to health indicators will lead to improved methodology for assessment of dietary patterns and a better understanding of the relationship between food and health. This study will serve as a first step toward validating candidate food intake biomarkers and allow for assessment of relationships with cardiometabolic health. The identification of food intake biomarkers is critical to future research and has implications spanning health promotion and disease prevention for many chronic conditions. TRIAL REGISTRATION: Registered at ClinicalTrials.gov: NCT05500976 ; Date of registration: August 15, 2022.

Longitudinal Outcomes of Malignant Ureteral Obstruction Secondary to Ovarian Cancer: Predictors of Resolution and the Role of Surgical Management.

OBJECTIVE: To review the management of ovarian cancer (OCa) associated hydronephrosis (HN). Specifically, we aim to identify optimal management of HN in the acute setting, predictors of HN resolution, and the role of surgery (tumor debulking/(+/-)ureterolysis/hysterectomy). MATERIALS/METHODS: The study cohort included OCa patients managed at our institution from 2004-2019 that developed OCa-associated HN. Initial HN management was recorded as none, retrograde ureteral stent (RUS) or percutaneous nephrostomy tube (PCN). Primary outcomes included (1) HN management failure, (2) HN management complications, and (3) HN resolution. Patient, cancer, and treatment predictors of outcomes were assessed using logistic regression and fine-Gray competing risk models. RESULTS: Of 2580 OCa patients, 190 (7.4%) developed HN. HN was treated in 121; 90 (74.4%) with RUS, 31 (25.6%) with PCN. Complication rates were similar between PCN and RUS (83% vs 85.1%; P = .79; all Clavian Grade I/II). Initial HN treatment failure occurred in 28 patients, predicted by renal atrophy (hazard ratios (HR) 3.27, P <.01). HN resolution occurred in only 52 (27%) patients and was predicted by lower International Federation of Gynecology and Obstetrics (FIGO) stage (FIGO III/IV HR 0.42, P <.01) and surgical tumor debulking/ureterolysis (HR 2.83, P = .02). CONCLUSION: Resolution of HN associated with malignant obstruction from OCa is rare and is most closely associated with tumor debulking and International Federation of Gynecology and Obstetrics (FIGO) stage. Initial endoscopic treatment modality was not significantly associated with complications or resolution, though RUS failures were slightly more common. Ureteral reconstruction at time of debulking/ureterolysis is potentially underutilized.

Salmon Food-Specific Compounds and Their Metabolites Increase in Human Plasma and Are Associated with Cardiometabolic Health Indicators Following a Mediterranean-Style Diet Intervention.

BACKGROUND: Nutrimetabolomics allows for the comprehensive analysis of foods and human biospecimens to identify biomarkers of intake and begin to probe their associations with health. Salmon contains hundreds of compounds that may provide cardiometabolic benefits. OBJECTIVES: We used untargeted metabolomics to identify salmon food-specific compounds (FSCs) and their predicted metabolites that were found in plasma after a salmon-containing Mediterranean-style (MED) diet intervention. Associations between changes in salmon FSCs and changes in cardiometabolic health indicators (CHIs) were also explored. METHODS: For this secondary analysis of a randomized, crossover, controlled feeding trial, 41 participants consumed MED diets with 2 servings of salmon per week for 2 5-wk periods. CHIs were assessed, and fasting plasma was collected pre- and postintervention. Plasma, salmon, and 99 MED foods were analyzed using liquid chromatography-mass spectrometry-based metabolomics. Compounds were characterized as salmon FSCs if detected in all salmon replicates but none of the other foods. Metabolites of salmon FSCs were predicted using machine learning. For salmon FSCs and metabolites found in plasma, linear mixed-effect models were used to assess change from pre- to postintervention and associations with changes in CHIs. RESULTS: Relative to the other 99 MED foods, there were 508 salmon FSCs with 237 unique metabolites. A total of 143 salmon FSCs and 106 metabolites were detected in plasma. Forty-eight salmon FSCs and 30 metabolites increased after the intervention (false discovery rate <0.05). Increases in 2 annotated salmon FSCs and 2 metabolites were associated with improvements in CHIs, including total cholesterol, low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B. CONCLUSIONS: A data-driven nutrimetabolomics strategy identified salmon FSCs and their predicted metabolites that were detectable in plasma and changed after consumption of a salmon-containing MED diet. Findings support this approach for the discovery of compounds in foods that may serve, upon further validation, as biomarkers or act as bioactive components influential to health. The trials supporting this work were registered at NCT02573129 (Mediterranean-style diet intervention) and NCT05500976 (ongoing clinical trial).

Ectopic transcription due to inappropriately inherited histone methylation may interfere with the ongoing function of terminally differentiated cells.

Many human neurodevelopmental disorders are caused by de novo mutations in histone modifying enzymes. These patients have craniofacial defects, developmental delay, intellectual disability and behavioral abnormalities, but it remains unclear how the mutations lead to such developmental defects. Here we take advantage of the invariant C. elegans lineage along with a unique double mutant in the H3K4me1/2 demethylase SPR-5/LSD1/KDM1A and the H3K9 methyltransferase MET-2/SETDB1 to address this question. We demonstrate that spr-5; met-2 double mutant worms have a severe chemotaxis defect that is dependent upon the ectopic expression of germline genes in somatic tissues. In addition, by performing single-cell RNAseq, we find that germline genes begin to be ectopically expression widely in spr-5; met-2 embryos. However, surprisingly we found that spr-5; met-2 mutants have no somatic lineage defects prior to the 200-cell stage of embryogenesis. This suggests that the altered chemotaxis behavior may be due to ongoing defect in terminally differentiated cells rather than a defect in development. To test this directly, we used RNAi to shut off the ectopic expression of germline genes in L2 spr-5; met-2 larvae, which have a fully formed nervous system. Remarkably, we find that shutting off the ectopic germline expression rescues normal chemotaxis behavior in the same adult worms that previously had a chemotaxis defect at the L2 stage. This suggests that ongoing ectopic transcription can block normal behavior in a fully intact nervous system. These data raise the possibility that intellectual disability and altered behavior in neurodevelopmental syndromes, caused by mutations in histone modifying enzymes, could be due to ongoing ectopic transcription and may be reversible.

History of obstructive sleep apnea associated with incident cognitive impairment in white but not black individuals in a US national cohort study.

BACKGROUND: We sought to determine if risk for obstructive sleep apnea (OSA), a history of OSA, and/or treatment of OSA has a different association with incident cognitive impairment or cognitive decline in Black individuals and White individuals. METHODS: To determine whether the risk for OSA, a history of OSA, and/or treatment of OSA has a different association with incident cognitive impairment or cognitive decline in Black individuals and White individuals; data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) was used. Participants that completed the sleep questionnaire module, had baseline cognitive assessment, and at least one cognitive assessment during follow-up were included. Risk of OSA was determined based on Berlin Sleep Questionnaire. History of sleep apnea was determined based on structured interview questions. Optimally treated OSA was defined as treated sleep apnea as at least 4 h of continuous positive airway pressure use per night for ≥5 nights per week. RESULTS: In 19,017 participants stratified by race, White participants with history of OSA were 1.62 times more likely to have incident cognitive impairment compared to White participants without history of OSA after adjusting for demographic characteristics, history, and lifestyle factors (OR = 1.62, 95% CI = 1.05-2.50, p-value = 0.03). This relationship was not seen in Black participants (OR = 0.92, 95% CI = 0.60-1.43, p-value = 0.72). DISCUSSION: A previous diagnosis of OSA is associated with incident cognitive impairment in White Americans but not Black Americans. Further investigations are required to determine the mechanism for this difference.

Changes in Running Kinematics and Kinetics Following a 10 km Run.

Background: Little is known about changes in kinetics or kinematics following a 10 km training run. This information has implications on risk of running-related injury. Purpose: The purpose of this study was to examine the effect of a 10 km run on running kinematics and kinetics in a sample of experienced runners. Study Design: Cross-Sectional Study. Subjects: Nineteen runners ages 18-48 (7 female, 12 male) consented to participate including eight (3 female, 5 male) ultra-runners, and 11 (4 female, 7 male) recreational runners. Methods: Following collection of demographic data and completion of a short running survey, participants did a 6-minute run at their self-selected running speed to acclimate to the instrumented treadmill. Reflective markers were placed over designated anatomical landmarks on both sides of the pelvis as well as the left lower extremity and marked with a skin pen. Subjects then ran on the treadmill and 30 seconds of video data were recorded at 240 frames/sec using a high-speed camera for the sagittal plane and the frontal plane. Simultaneously, ground reaction forces (GRFs) were recorded at 1200 Hz through the treadmill's embedded force plates. Each runner then ran 10 km on a paved trail at their self-selected pace. Immediately following the run, reflective markers were reattached, guided by markings placed before the run, and a 30-second post-run trial of the video and GRF data were recorded. Video data were analyzed using Kinovea software to measure the kinematic variables of interest. Paired t-tests with Bonferroni corrections were used to find if significant differences existed between pre- and post-run data for all kinematic and kinetic variables. Results: No significant or clinically relevant differences existed between the pre- and post-run measurements for the kinematic or kinetic variables. The only significant difference noted between the ultra-runners and recreational runners was that the ultra-runners had significantly higher cadence (p=0.045). Conclusions: A 10 km run at a self-selected pace did not result in change in the mean kinematic or kinetic variables in this group of experienced runners. Ultra-runners employ higher cadence than recreational runners, but their kinematics and kinetics are similar. Level of Evidence: Level 3.

Meta-analysis of skill-based and therapeutic interventions to address math anxiety.

The purpose of this meta-analysis was to examine the impact of school-based therapeutic and math skill interventions on math anxiety symptoms and math achievement among K-12 students. Potential moderators included treatment type and study quality. A systematic search yielded 17 included studies representing 1786 primary and secondary students. The results suggested that therapeutic interventions reduced math anxiety symptoms (gav = -0.51) better than math skill interventions (gav = -0.32) and math skill interventions improved math achievement (gav = 0.76) more than therapeutic interventions (gav = 0.12). Moderator analysis indicated that when accounting for study quality, the differences between intervention type were not significant for either of the outcome measures (i.e., achievement and math anxiety). Theoretical and practical implications of these findings are discussed.

The Microbiome, Epigenome, and Diet in Adults with Obesity during Behavioral Weight Loss.

Obesity has been linked to the gut microbiome, epigenome, and diet, yet these factors have not been studied together during obesity treatment. Our objective was to evaluate associations among gut microbiota (MB), DNA methylation (DNAme), and diet prior to and during a behavioral weight loss intervention. Adults (n = 47, age 40.9 ± 9.7 years, body mass index (BMI) 33.5 ± 4.5 kg/m2, 77% female) with data collected at baseline (BL) and 3 months (3 m) were included. Fecal MB was assessed via 16S sequencing and whole blood DNAme via the Infinium EPIC array. Food group and nutrient intakes and Healthy Eating Index (HEI) scores were calculated from 7-day diet records. Linear models were used to test for the effect of taxa relative abundance on DNAme and diet cross-sectionally at each time point, adjusting for confounders and a false discovery rate of 5%. Mean weight loss was 6.2 ± 3.9% at 3 m. At BL, one MB taxon, Ruminiclostridium, was associated with DNAme of the genes COL20A1 (r = 0.651, p = 0.029), COL18A1 (r = 0.578, p = 0.044), and NT5E (r = 0.365, p = 0.043). At 3 m, there were 14 unique MB:DNAme associations, such as Akkermansia with DNAme of GUSB (r = -0.585, p = 0.003), CRYL1 (r = -0.419, p = 0.007), C9 (r = -0.439, p = 0.019), and GMDS (r = -0.559, p = 0.046). Among taxa associated with DNAme, no significant relationships were seen with dietary intakes of relevant nutrients, food groups, or HEI scores. Our findings indicate that microbes linked to mucin degradation, short-chain fatty acid production, and body weight are associated with DNAme of phenotypically relevant genes. These relationships offer an initial understanding of the possible routes by which alterations in gut MB may influence metabolism during weight loss.

Identification of ligand-receptor pairs that drive human astrocyte development.

Extrinsic signaling between diverse cell types is crucial for nervous system development. Ligand binding is a key driver of developmental processes. Nevertheless, it remains a significant challenge to disentangle which and how extrinsic signals act cooperatively to affect changes in recipient cells. In the developing human brain, cortical progenitors transition from neurogenesis to gliogenesis in a stereotyped sequence that is in part influenced by extrinsic ligands. Here we used published transcriptomic data to identify and functionally test five ligand-receptor pairs that synergistically drive human astrogenesis. We validate the synergistic contributions of TGFß2, NLGN1, TSLP, DKK1 and BMP4 ligands on astrocyte development in both hCOs and primary fetal tissue. We confirm that the cooperative capabilities of these five ligands are greater than their individual capacities. Additionally, we discovered that their combinatorial effects converge in part on the mTORC1 signaling pathway, resulting in transcriptomic and morphological features of astrocyte development. Our data-driven framework can leverage single-cell and bulk genomic data to generate and test functional hypotheses surrounding cell-cell communication regulating neurodevelopmental processes.

Parkinson's disease diagnosis codes are insufficiently accurate for electronic health record research and differ by race.

BACKGROUND: There are no evidence-based guidelines for data cleaning of electronic health record (EHR) databases in Parkinson's disease (PD). Previous filtering criteria have primarily used the 9th International Statistical Classification of Diseases and Related Health Problems (ICD) with variable accuracy for true PD cases. Prior studies have not excluded atypical or drug-induced parkinsonism, and little is known about differences in accuracy by race. OBJECTIVE: To determine if excluding parkinsonism diagnoses improves accuracy of ICD-9 and -10 PD diagnosis codes. METHODS: We included ≥2 instances of an ICD-9 and/or -10 code for PD. We removed any records with at least one code indicating atypical or drug-induced parkinsonism first in all races, and then in Non-Hispanic White and Black patients. We manually reviewed 100 randomly selected charts per group before and after filtering, and performed a test of proportion (null hypothesis 0.5) for confirmed PD. RESULTS: 5633 records had ≥2 instances of a PD code. 2833 remained after filtering. The rate of true PD cases was low before and after filtering to remove parkinsonism codes (0.55 vs. 0.51, p = 0.84). Accuracy was lowest in Black patients before filtering (0.48, p = 0.69), but filtering had a greater (though modest) impact on accuracy (0.68, p < 0.001). CONCLUSIONS: There was inadequate accuracy of PD diagnosis codes in the largest study of ICD-9 and -10 codes. Accuracy was lowest in Black patients but improved the most with removing other parkinsonism codes. This highlights the limitations of using current real-world EHR data in PD research and need for further study.

Bottle mix-up: Ethanol intoxication in an infant.

Alcohol intoxication is a common ingestion in pediatrics with close to 10,000 reports to poison control centers annually. Hypoglycemia, neurological depression (ataxia, coma, nystagmus, etc.) and unstable vitals (hypothermia, hypotension, bradycardia, and respiratory depression) are common presentations. The patient is a 3 month old female who was brought into the Emergency Department (ED) for one day of decreased oral intake and inconsolability. Vital signs were reassuring. Physical exam revealed gaze preference to the right with inability to look left, dysconjugate gaze, and hypotonia. Work-up including CT of the head, and urinalysis was unremarkable. Urine drug screen was found to be positive for ethanol with follow up serum ethanol at 162 mg/dL. With conservative management the patient returned to her baseline. On follow-up with her pediatrician, it was elicited that the mother inadvertently used a water bottle of vodka to mix the patient's formula. This case adds to the paucity of literature of abnormal presentations of alcohol intoxication in an infant.

Differences in Adherence to American Heart Association's Life's Essential 8, Diet Quality, and Weight Loss Strategies Between Those With and Without Recent Clinically Significant Weight Loss in a Nationally Representative Sample of US Adults.

Background The American Heart Association defines ideal cardiovascular health based on 8 risk factors (Life's Essential 8 [LE8]); a high LE8 score (range 0-100) reflects greater adherence to their recommendations. Weight status influences cardiovascular health, yet individuals may use detrimental diet and weight loss strategies to improve weight status. We assessed differences in LE8 adherence, diet quality, and weight loss strategies between those with and without a recent history of clinically significant weight loss (CSWL). Methods and Results Data from 2007 to 2016 National Health and Nutrition Examination Survey questionnaires, clinical measures, and 24-hour dietary recalls were assessed to determine LE8 adherence, diet quality (Healthy Eating Index), and weight loss strategies between adults with: (1) intentional CSWL ≥5%; and (2) non-CSWL <5%, weight maintenance, or weight gain over the past 12 months using ANCOVA and chi-square tests. Those with CSWL demonstrated higher scores for diet quality (P=0.014), physical activity (P<0.001), and blood lipids (P<0.001). Those without CSWL reported lower BMI (P<0.001). There were no differences in total LE8 cardiovascular health scores between those with and without CSWL. More individuals with CSWL reported weight loss strategies of exercising (P=0.016); those without CSWL reported skipping meals (P=0.002) and using prescription diet pills (P<0.001). Conclusions Greater adherence to the LE8 recommendations was observed among individuals with CSWL, although overall LE8 scores were low. Future research should address the implementation of evidence-based strategies that improve diet quality while promoting optimal cardiovascular health among those with intent to lose weight.

Tau in cerebrospinal fluid induces neuronal hyperexcitability and alters hippocampal theta oscillations.

Alzheimer's disease (AD) and other tauopathies are characterized by the aggregation of tau into soluble and insoluble forms (including tangles and neuropil threads). In humans, a fraction of both phosphorylated and non-phosphorylated N-terminal to mid-domain tau species, are secreted into cerebrospinal fluid (CSF). Some of these CSF tau species can be measured as diagnostic and prognostic biomarkers, starting from early stages of disease. While in animal models of AD pathology, soluble tau aggregates have been shown to disrupt neuronal function, it is unclear whether the tau species present in CSF will modulate neural activity. Here, we have developed and applied a novel approach to examine the electrophysiological effects of CSF from patients with a tau-positive biomarker profile. The method involves incubation of acutely-isolated wild-type mouse hippocampal brain slices with small volumes of diluted human CSF, followed by a suite of electrophysiological recording methods to evaluate their effects on neuronal function, from single cells through to the network level. Comparison of the toxicity profiles of the same CSF samples, with and without immuno-depletion for tau, has enabled a pioneering demonstration that CSF-tau potently modulates neuronal function. We demonstrate that CSF-tau mediates an increase in neuronal excitability in single cells. We then observed, at the network level, increased input-output responses and enhanced paired-pulse facilitation as well as an increase in long-term potentiation. Finally, we show that CSF-tau modifies the generation and maintenance of hippocampal theta oscillations, which have important roles in learning and memory and are known to be altered in AD patients. Together, we describe a novel method for screening human CSF-tau to understand functional effects on neuron and network activity, which could have far-reaching benefits in understanding tau pathology, thus allowing for the development of better targeted treatments for tauopathies in the future.

B.Y.O. Bees: Managing wild bee biodiversity in urban greenspaces.

As cities become more populated and the density of urban development increases, local biodiversity is threatened. Urban greenspaces have the capacity to preserve pollinator biodiversity, but the quality of support they provide depends on greenspace landscape attributes, including the availability of pollinator habitat and foraging resources. Wild native bees provide important pollination services to urban ecosystems, yet relatively little is known about how urban landscape management influences pollinator community composition and diversity. Our study explores how wild bee communities are affected by greenspace and landscape-level features like pollinator management practices, in urban greenspaces in and around Appleton Wisconsin: a mid-sized urban community spanning more than 100 sq. km. We sampled and identified native bees periodically between late-May 2017 and mid-September of 2018 using standardized arrays of pan traps at 15 sites around the city. We classified greenspaces based on their level of development (urban or suburban) and whether they were managed or unmanaged for increasing wild pollinator diversity. We quantified floral species diversity, floral color diversity, tree species diversity, and proximity of sites to open water for each site and used remotely sensed satellite data from both the USGS National Land Cover Database (NLCD) and the Normalized Difference Vegetation Index (NDVI). All variables were tested as potential correlates of wild bee abundance and species richness. Active pollinator management sites supported higher levels of bee abundance and richness. Notably, active greenspace management (e.g. planting native wildflowers) was a stronger correlate of bee abundance and richness than greenspace size and other landscape-level attributes. Within-greenspace attributes such as floral diversity, tree diversity, and proximity to open water contributed positively to both bee abundance and richness. Based on these findings, we suggest that urban greenspaces may be managed more efficiently and cost-effectively by focusing resources on active management by planting wildflowers, removing invasive species, creating nesting habitat, and providing water resources, rather than simply expanding in area.

Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer.

BACKGROUND: Standard first-line chemotherapy for endometrial cancer is paclitaxel plus carboplatin. The benefit of adding pembrolizumab to chemotherapy remains unclear. METHODS: In this double-blind, placebo-controlled, randomized, phase 3 trial, we assigned 816 patients with measurable disease (stage III or IVA) or stage IVB or recurrent endometrial cancer in a 1:1 ratio to receive pembrolizumab or placebo along with combination therapy with paclitaxel plus carboplatin. The administration of pembrolizumab or placebo was planned in 6 cycles every 3 weeks, followed by up to 14 maintenance cycles every 6 weeks. The patients were stratified into two cohorts according to whether they had mismatch repair-deficient (dMMR) or mismatch repair-proficient (pMMR) disease. Previous adjuvant chemotherapy was permitted if the treatment-free interval was at least 12 months. The primary outcome was progression-free survival in the two cohorts. Interim analyses were scheduled to be triggered after the occurrence of at least 84 events of death or progression in the dMMR cohort and at least 196 events in the pMMR cohort. RESULTS: In the 12-month analysis, Kaplan-Meier estimates of progression-free survival in the dMMR cohort were 74% in the pembrolizumab group and 38% in the placebo group (hazard ratio for progression or death, 0.30; 95% confidence interval [CI], 0.19 to 0.48; P<0.001), a 70% difference in relative risk. In the pMMR cohort, median progression-free survival was 13.1 months with pembrolizumab and 8.7 months with placebo (hazard ratio, 0.54; 95% CI, 0.41 to 0.71; P<0.001). Adverse events were as expected for pembrolizumab and combination chemotherapy. CONCLUSIONS: In patients with advanced or recurrent endometrial cancer, the addition of pembrolizumab to standard chemotherapy resulted in significantly longer progression-free survival than with chemotherapy alone. (Funded by the National Cancer Institute and others; NRG-GY018 ClinicalTrials.gov number, NCT03914612.).

Attribution of Blame in an Intimate Partner Violence Situation: The Effect of Victim Sexuality and Observer Sex.

Intimate partner violence (IPV) is an extensive public health concern, largely affecting women aged 20 to 24 years. Research suggests that bisexual women are more likely than heterosexual and homosexual women to be victims of IPV. Bisexual women are also more likely to be blamed for their abuse experiences after disclosing, a phenomenon known as victim blame attribution (VBA). However, very little VBA research recognizes bisexuality as a separate category. Therefore, the main aim of this quasi-experimental study was to investigate the role of female victim sexuality (bisexuality, homosexuality, and heterosexuality) and observer sex in the attribution of blame to the victim and perpetrator of IPV. Participants (N = 232; aged 18-24 years, M = 21.05, SD = 1.73) were randomly assigned into one of four conditions (heterosexual victim, bisexual victim with same-sex partner, bisexual victim with different-sex partner, homosexual victim), each containing a vignette portraying IPV within a relationship. Randomization checks were performed to ensure that participants in the four conditions did not differ significantly on underlying attitudes (institutional heterosexism (IH), aversive heterosexism (AH), heterosexual privilege (HP), sexist attitudes, just world beliefs) that may have affected their responses on outcome measures. Main analyses demonstrated that bisexual victims with a same-sex partner received the highest attribution of blame, whereas perpetrators in this condition received the lowest blame attribution. Male participants attributed significantly higher blame to victims than did female participants, regardless of victim sexuality. These findings substantiate the role of victim sexuality and observer sex in IPV blame attribution patterns. This research aimed to promote equality and rightful treatment to all victims of IPV regardless of their sexuality.