The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.

A rotationally-driven dynamic solid phase sodium bisulfite conversion disc for forensic epigenetic sample preparation.

The approaches to forensic human identification (HID) are largely comparative in nature, relying upon the comparison of short tandem repeat profiles to known reference materials and/or database profiles. However, many profiles are generated from evidence materials that either do not have a reference material for comparison or do not produce a database hit. As an alternative to individualizing analysis for HID, researchers of forensic DNA have demonstrated that the human epigenome can provide a wealth of information. However, epigenetic analysis requires sodium b̲is̲ulfite c̲onversion (BSC), a sample preparation method that is time-consuming, labor-intensive, prone to contamination, and characterized by DNA loss and fragmentation. To provide an alternative method for BSC that is more amenable to integration with the forensic DNA workflow, we describe a rotationally-driven, microfluidic method for dynamic solid phase-BSC (dSP-BSC) that streamlines the sample preparation process in an automated format, capable of preparing up to four samples in parallel. The method permitted decreased incubation intervals by ∼36% and was assessed for relative DNA recovery and conversion efficiency and compared to gold-standard and enzymatic approaches.

Nuclear Equation of State for Arbitrary Proton Fraction and Temperature Based on Chiral Effective Field Theory and a Gaussian Process Emulator.

We calculate the equation of state of asymmetric nuclear matter at finite temperature based on chiral effective field theory interactions to next-to-next-to-next-to-leading order. Our results assess the theoretical uncertainties from the many-body calculation and the chiral expansion. Using a Gaussian process emulator for the free energy, we derive the thermodynamic properties of matter through consistent derivatives and use the Gaussian process to access arbitrary proton fraction and temperature. This enables a first nonparametric calculation of the equation of state in beta equilibrium, and of the speed of sound and the symmetry energy at finite temperature. Moreover, our results show that the thermal part of the pressure decreases with increasing densities.

Development and validation of a brief screener for posttraumatic stress disorder risk in emergency medical settings.

OBJECTIVE: Predicting risk of posttraumatic stress disorder (PTSD) in the acute care setting is challenging given the pace and acute care demands in the emergency department (ED) and the infeasibility of using time-consuming assessments. Currently, no accurate brief screening for long-term PTSD risk is routinely used in the ED. One instrument widely used in the ED is the 27-item Immediate Stress Reaction Checklist (ISRC). The aim of this study was to develop a short screener using a machine learning approach and to investigate whether accurate PTSD prediction in the ED can be achieved with substantially fewer items than the IRSC. METHOD: This prospective longitudinal cohort study examined the development and validation of a brief screening instrument in two independent samples, a model development sample (N = 253) and an external validation sample (N = 93). We used a feature selection algorithm to identify a minimal subset of features of the ISRC and tested this subset in a predictive model to investigate if we can accurately predict long-term PTSD outcomes. RESULTS: We were able to identify a reduced subset of 5 highly predictive features of the ISRC in the model development sample (AUC = 0.80), and we were able to validate those findings in the external validation sample (AUC = 0.84) to discriminate non-remitting vs. resilient trajectories. CONCLUSION: This study developed and validated a brief 5-item screener in the ED setting, which may help to improve the diagnostic process of PTSD in the acute care setting and help ED clinicians plan follow-up care when patients are still in contact with the healthcare system. This could reduce the burden on patients and decrease the risk of chronic PTSD.

Standard values of the upper body posture in healthy adults with special regard to age, sex and BMI.

In order to classify and analyze the parameters of upper body posture in clinical or physiotherapeutic settings, a baseline in the form of standard values with special regard to age, sex and BMI is required. Thus, subjectively healthy men and women aged 21-60 years were measured in this project. The postural parameters of 800 symptom-free male (n = 397) and female (n = 407) volunteers aged 21-60 years (Ø♀: 39.7 ± 11.6, Ø â™‚: 40.7 ± 11.5 y) were studied. The mean height of the men was 1.8 ± 0.07 m, with a mean body weight of 84.8 ± 13.1 kg and an average BMI of 26.0 ± 3.534 kg/m2. In contrast, the mean height of the women was 1.67 ± 0.06 m, with a mean body weight of 66.5 ± 12.7 kg and an average BMI of 23.9 ± 4.6 kg/m2. By means of video rasterstereography, a 3-dimensional scan of the upper back surface was measured when in a habitual standing position. The means or medians, confidence intervals, tolerance ranges, the minimum, 2.5, 25, 50, 75, 97.5 percentiles and the maximum, plus the kurtosis and skewness of the distribution, were calculated for all parameters. Additionally, ANOVA and a factor analyses (sex, BMI, age) were conducted. In both sexes across all age groups, balanced, symmetrical upper body statics were evident. Most strikingly, the females showed greater thoracic kyphosis and lumbar lordosis angles (kyphosis: Ø â™€ 56°, Ø♂ 51°; lordosis: Ø â™€ 49°, Ø♂ 32°) and lumbar bending angles (Ø â™€ 14°, Ø♂ 11°) than the males. The distance between the scapulae was more pronounced in men. These parameters also show an increase with age and BMI, respectively. Pelvic parameters were independent of age and sex. The upper body postures of women and men between the ages of 21 and 60 years were found to be almost symmetrical and axis-conforming with a positive correlation for BMI or age. Consequently, the present body posture parameters allow for comparisons with other studies, as well as for the evaluation of clinical (interim) diagnostics and applications.

Prior differences in previous trauma exposure primarily drive the observed racial/ethnic differences in posttrauma depression and anxiety following a recent trauma.

BACKGROUND: Racial and ethnic groups in the USA differ in the prevalence of posttraumatic stress disorder (PTSD). Recent research however has not observed consistent racial/ethnic differences in posttraumatic stress in the early aftermath of trauma, suggesting that such differences in chronic PTSD rates may be related to differences in recovery over time. METHODS: As part of the multisite, longitudinal AURORA study, we investigated racial/ethnic differences in PTSD and related outcomes within 3 months after trauma. Participants (n = 930) were recruited from emergency departments across the USA and provided periodic (2 weeks, 8 weeks, and 3 months after trauma) self-report assessments of PTSD, depression, dissociation, anxiety, and resilience. Linear models were completed to investigate racial/ethnic differences in posttraumatic dysfunction with subsequent follow-up models assessing potential effects of prior life stressors. RESULTS: Racial/ethnic groups did not differ in symptoms over time; however, Black participants showed reduced posttraumatic depression and anxiety symptoms overall compared to Hispanic participants and White participants. Racial/ethnic differences were not attenuated after accounting for differences in sociodemographic factors. However, racial/ethnic differences in depression and anxiety were no longer significant after accounting for greater prior trauma exposure and childhood emotional abuse in White participants. CONCLUSIONS: The present findings suggest prior differences in previous trauma exposure partially mediate the observed racial/ethnic differences in posttraumatic depression and anxiety symptoms following a recent trauma. Our findings further demonstrate that racial/ethnic groups show similar rates of symptom recovery over time. Future work utilizing longer time-scale data is needed to elucidate potential racial/ethnic differences in long-term symptom trajectories.

Conversion of unresponsiveness to immune checkpoint inhibition by fecal microbiota transplantation in patients with metastatic melanoma: study protocol for a randomized phase Ib/IIa trial.

BACKGROUND: The gut microbiome plays an important role in immune modulation. Specifically, presence or absence of certain gut bacterial taxa has been associated with better antitumor immune responses. Furthermore, in trials using fecal microbiota transplantation (FMT) to treat melanoma patients unresponsive to immune checkpoint inhibitors (ICI), complete responses (CR), partial responses (PR), and durable stable disease (SD) have been observed. However, the underlying mechanism determining which patients will or will not respond and what the optimal FMT composition is, has not been fully elucidated, and a discrepancy in microbial taxa associated with clinical response has been observed between studies. Furthermore, it is unknown whether a change in the microbiome itself, irrespective of its origin, or FMT from ICI responding donors, is required for reversion of ICI-unresponsiveness. To address this, we will transfer microbiota of either ICI responder or nonresponder metastatic melanoma patients via FMT. METHODS: In this randomized, double-blinded phase Ib/IIa trial, 24 anti-PD1-refractory patients with advanced stage cutaneous melanoma will receive an FMT from either an ICI responding or nonresponding donor, while continuing anti-PD-1 treatment. Donors will be selected from patients with metastatic melanoma treated with anti-PD-1 therapy. Two patients with a good response (≥ 30% decrease according to RECIST 1.1 within the past 24 months) and two patients with progression (≥ 20% increase according to RECIST 1.1 within the past 3 months) will be selected as ICI responding or nonresponding donors, respectively. The primary endpoint is clinical benefit (SD, PR or CR) at 12 weeks, confirmed on a CT scan at 16 weeks. The secondary endpoint is safety, defined as the occurrence of grade ≥ 3 toxicity. Exploratory endpoints are progression-free survival and changes in the gut microbiome, metabolome, and immune cells. DISCUSSION: Transplanting fecal microbiota to restore the patients' perturbed microbiome has proven successful in several indications. However, less is known about the potential role of FMT to improve antitumor immune response. In this trial, we aim to investigate whether administration of FMT can reverse resistance to anti-PD-1 treatment in patients with advanced stage melanoma, and whether the ICI-responsiveness of the feces donor is associated with its effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05251389 (registered 22-Feb-2022). Protocol V4.0 (08-02-2022).

mm-wave Rydberg-Rydberg transitions gauge intermolecular coupling in a molecular ultracold plasma.

Out-of-equilibrium, strong correlation in a many-body system can trigger emergent properties that act to constrain the natural dissipation of energy and matter. Signs of such self-organization appear in the avalanche, bifurcation, and quench of a state-selected Rydberg gas of nitric oxide to form an ultracold, strongly correlated ultracold plasma. Work reported here focuses on the initial stages of avalanche and quench and uses the mm-wave spectroscopy of an embedded quantum probe to characterize the intermolecular interaction dynamics associated with the evolution to plasma. Double-resonance excitation prepares a Rydberg gas of nitric oxide composed of a single selected state of principal quantum number, n0. Penning ionization, followed by an avalanche of electron-Rydberg collisions, forms a plasma of NO+ ions and weakly bound electrons, in which a residual population of n0 Rydberg molecules evolves to a state of high orbital angular momentum, ℓ. Predissociation depletes the plasma of low-ℓ molecules. Relaxation ceases and n0ℓ(2) molecules with ℓ ≥ 4 persist for very long times. At short times, varying excitation spectra of mm-wave Rydberg-Rydberg transitions mark the rate of electron-collisional ℓ-mixing. Deep depletion resonances that persist for long times signal energy redistribution in the basis of central-field Rydberg states. The widths and asymmetries of Fano line shapes witness the degree to which coupling in the arrested bath (i) broadens the allowed transition and (ii) mixes the local network of levels in the ensemble.

Prevalence and whole genome-based phylogenetic, virulence and antibiotic -resistance characteristics of nasal -Staphylococcus aureus in healthy Swiss horses.

INTRODUCTION: A total of 100 nasal swabs were collected from healthy horses in Switzerland between January 2020 and August 2020. The samples were taken from horses at 40 different stables in 12 different cantons and screened for both methicillin-resistant (MRSA) and methicillin-susceptible S. aureus (MSSA) using selective agar plates. S. aureus were tested for antibiotic susceptibility by measurement of the minimal inhibitory concentration (MIC) and for virulence factors, antibiotic resistance genes and phylogenetic characteristics using whole genome sequence analysis. Ten horses were found to be positive (10 %, CI: 95 %, 0,0552 - 0,1744) for S. aureus, and four of them harboured MRSA (4 %, CI: 95 %, CI: 1,5 % - 9 %). The MRSA were detected in horses from three different stables in the same region of one canton and MSSA were detected in horses from five different cantons. All the MRSA isolates were genetically related (ST398-t011-IVa), while the MSSA were diverse (ST1-t127/t398/t1508, ST816-t1294, ST133-t1403, ST30-t012). MRSA showed resistance to penicillin (blaZ), cefoxitin (mecA), trimethoprim (dfrK), gentamicin, kanamycin (aac(6')-Ie - aph(2'')-Ia), and tetracycline (tet(M)). MSSA were resistant to either none or one of the antibiotics tested like penicillin (blaZ) and erythromycin (erm(T)). Virulence genes were more abundant in MSSA than in MRSA. This study provides first insight into the prevalence and type of S. aureus in healthy Swiss horses and reveals a source of strains, which may cause infections in both horses and humans.

INTRODUCTION: Au total, 100 écouvillons nasaux ont été prélevés sur des chevaux sains en Suisse entre janvier 2020 et août 2020. Les échantillons ont été prélevés sur des chevaux de 40 écuries différentes dans 12 cantons différents et ont été soumis à un dépistage de S. aureus résistant à la méthicilline (MRSA) et de S. aureus sensible à la méthicilline (MSSA) à l'aide de plaques de gélose sélectives. Les S. aureus ont été testés pour leur sensibilité aux antibiotiques en mesurant la concentration minimale inhibitrice (CMI) et pour les facteurs de virulence, les gènes de résistance aux antibiotiques et les caractéristiques phylogénétiques en analysant la séquence du génome entier. Dix chevaux se sont révélés positifs (10 %, IC: 95 %, 0,0552 ­ 0,1744) pour S. aureus, et quatre d'entre eux étaient porteurs de MRSA (4 %, IC: 95 %, IC: 1,5 % ­ 9 %). Les MRSA ont été détectés chez des chevaux provenant de trois écuries différentes de la même région d'un canton et les MSSA ont été détectés chez des chevaux provenant de cinq cantons différents. Tous les isolats de MRSA étaient génétiquement apparentés (ST398-t011-IVa), tandis que les MSSA étaient divers (ST1-t127/t398/t1508, ST816-t1294, ST133-t1403, ST30-t012). Les MRSA étaient résistants à la pénicilline (blaZ), à la céfoxitine (mecA), au triméthoprime (dfrK), à la gentamicine, à la kanamycine (aac(6')-Ie ­ aph(2")-Ia) et à la tétracycline (tet(M)). Les MSSA étaient résistants à aucun ou à un des antibiotiques testés soit à la pénicilline (blaZ) ou à l'érythromycine (erm(T)). Les gènes de virulence étaient plus abondants chez les MSSA que chez les MRSA. Cette étude donne, pour la première fois, un aperçu de la prévalence et du type de S. aureus chez les chevaux suisses en bonne santé et révèle la présence de souches susceptibles de provoquer des infections chez les chevaux et les humains.

Novel KEL allele associated with loss of Kpb identified in a white blood donor.

The importance of identifying variant alleles among blood donors is significant to the safety of transfusion for recipients. Molecular methods have become more prominent in the routine process of antigen typing donor units. Some variant antigens cannot be detected using only serologic methods. Molecular testing allows the determination of nucleotide sequences that are used to predict a phenotype. Antigens of the Kell blood group system are known for being highly immunogenic and causing adverse reactions upon antibody formation. A female white blood donor who typed Kp(b-) using serologic methods on multiple donations since 2005 was the subject of a typing discrepancy investigation. Routine genotyping using a commercial genotyping kit (HemoID DQS Panel; Agena Bioscience, San Diego, CA) predicted the donor to type Kp(a+b+). Investigation of the discrepancy between these two results identified a rare single nucleotide variant in the KEL gene at nucleotide position c.948G>T that alters amino acid residue 316 from tryptophan (Trp) to cysteine (Cys). After discovery of the novel allele, adsorption and elution studies were performed to see if there was weakened Kpb expression. The elution studies yielded negative results, which indicated that Kpb is not expressed. The KEL transcripts expressed by the donor were determined using cDNA analysis, and the predicted amino acid sequence of the novel allele was modeled to investigate the impact of the amino acid sequence on the structure of the KEL polypeptide. Both SWISS-MODEL and Robetta software were used to evaluate the impact of the p.Trp316Cys on the three-dimensional protein structure. There was no conformational change noted with SWISS-MODEL, whereas the Robetta software showed a significant conformational change compared with the normal Kp(b+) reference sequence. Because the donor is homozygous for variants associated with k and Jsb expression, it was not possible to determine whether the novel allele is associated with loss of Kpb only or loss of all Kell antigens.

Differences in observed and self-reported compliance with 'Five Moments for Hand Hygiene' as a function of the empathy of healthcare workers.

BACKGROUND: Hand hygiene at critical time-points (as established by the World Health Organization's model 'Five Moments for Hand Hygiene') remains the leading measure for minimizing the risk of healthcare-associated infections. While many interventions have been tested to improve hand hygiene compliance (HHC) of healthcare workers (HCWs), little is known about the relationship between HHC and empathy of HCWs. AIM: To investigate the relationship between moment-specific HHC rates and empathy of HCWs at both individual and ward levels. METHODS: HHC data were collected via observation and self-report, and empathy levels were measured using an established questionnaire. The survey was conducted on 38 wards of three tertiary care hospitals in Germany. Observation data were obtained via in-house observations conducted ≤8 months before or after the survey. FINDINGS: Evidence for the expected correlation between empathy of HCWs and moment-specific HHC was found for both observed HHC (Moment 1: r=0.483, P=0.031; Moment 2: r=588, P=0.006) and self-reported HHC (Moment 1: r=0.093, P=0.092; Moment 2: r=0.145, P=0.008). In analyses of variance, the critical interaction effect between empathy (i.e. lower vs higher empathy) and designated time-point of hand hygiene (i.e. before vs after reference task) was also significant. CONCLUSION: Empathy of HCWs should be considered as an important factor in explaining differences between moment-specific HHC rates. In consequence, empathy comes into focus not only as a crucial factor for high-quality patient care, but also as an important contributor to improving HHC.

Prevalence and characterization of -methicillin-resistant Macrococcus spp. in food producing animals and meat in Switzerland in 2019.

INTRODUCTION: The prevalence of methicillin-resistant Macrococcus spp. in calves and pigs at slaughterhouses and in retail beef and pork meat was determined using samples taken in 2019 within the framework of the national monitoring of methicillin-resistant Staphylococcus aureus in food producing animals in Switzerland. The isolates were submitted to antimicrobial susceptibility testing of 19 antibiotics and to molecular techniques (e.g. PCR, microarray, WGS) for the identification of resistance genes, elements containing the methicillin resistance genes mec and sequence type (ST). Methicillin-resistant Macrococcus spp. (M. caseolyticus (n=38), M. bohemicus (n=4) and Macrococcus spp. (n=2)) were isolated in 40 of 299 nasal swabs from calves representing a prevalence of 13,38 % (95 % CI, 9,98 % - 17,70 %), and in four of 303 nasal swabs from pigs [1,32 % (95 % CI, 0,36 % - 3,35 %)]. One of 311 samples of Swiss pork meat contained a Macrococcus sp. [0,32 % (95 % CI, 0,01 % - 1,78 %)], and four of 309 beef meat samples (260 domestic and 49 imported) contained M. caseolyticus [1,29 % (95 % CI, 0,35 % - 3,28 %)]. The M. caseolyticus strains belonged to diverse STs, with ST21 being the most common in both pigs and calves. The mecD gene was located on Macrococcus resistance island mecD (McRImecD) in 42 strains and on staphylococcal cassette chromosome mec (SCCmecD) in three strains, while mecB was found on plasmids in four strains. In addition to resistance to ß-lactams, the strains also exhibited resistance to tetracycline (n=17; tet(L), tet(K), tet(M)), streptomycin (n=13; str, ant(6)-Ia, rpsL mutation [K56R in ribosomal protein S12]), kanamycin (n=10; aac(6')-Ie - aph(2'')-Ia, aph(2')-Ib, aph(2')-Ic, ant(4')-Ia), clindamycin (n=9; erm(B), erm(45)), erythromycin (n=9; erm(B), msr(G), erm(45)), fusidic acid (n=9; fusC) and gentamicin (n=1; aac(6')-Ie - aph(2'')-Ia). This study represents the first national prevalence study of methicillin-resistant Macrococcus spp. in pigs, calves, pork and beef meat in Switzerland and revealed a reservoir of genetically diverse strains carrying several resistance traits.

INTRODUCTION: La prévalence des macrococques résistants à la méthicilline chez les veaux et les porcs à l'abattoir et dans la viande de bœuf et de porc au détail a été déterminée à partir d'échantillons prélevés en 2019 dans le cadre du monitoring national des Staphylococcus aureus résistants à la méthicilline chez les animaux de rente en Suisse. Les isolats ont été soumis à des tests de sensibilité à 19 antibiotiques et à des techniques moléculaires (par exemple PCR, microarray, WGS) pour l'identification des gènes de résistance, des éléments contenant les gènes mec responsible de la résistance à la méthicilline, ainsi que du type de séquence (ST). Des macocoques résistants à la méthicilline (M. caseolyticus (n=38), M. bohemicus (n=4) et Macrococcus spp. (n=2)) ont été isolés dans 40 des 299 écouvillons nasaux de veaux, ce qui représente une prévalence de 13,38 % (IC 95 %, 9,98 % ­ 17,70 %), et dans quatre des 303 écouvillons nasaux de porcs [1,32 % (IC 95 %, 0,36 % ­ 3,35 %)]. Un des 311 échantillons de viande de porc suisse contenait un Macrococcus sp. [0,32 % (IC 95 %, 0,01 % ­ 1,78 %)], et quatre des 309 échantillons de viande de bœuf (260 domestiques et 49 importés) contenaient M. caseolyticus [1,29 % (IC 95 %, 0,35 % ­ 3,28 %)]. Les souches de M. caseolyticus appartenaient à divers ST, le ST21 étant le plus fréquent chez les porcs et les veaux. Le gène mecD a été localisé sur des éléments du chromosome McRImecD dans 42 souches et SCCmecD dans trois souches, tandis que le gène mecB se trouvait sur des plasmides dans quatre souches. En plus de la résistance aux ß-lactamines, les souches étaient également résistantes à la tétracycline (n=17 ; tet(L), tet(K), tet(M)), à la streptomycine (n=13 ; str, ant(6)-Ia, mutation rpsL [K56R dans la protéine ribosomale S12]), à la kanamycine (n=10 ; aac(6')-Ie ­ aph(2'')-Ia, aph(2')-Ib, aph(2')-Ic, ant(4')-Ia), clindamycine (n=9 ; erm(B), erm(45)), érythromycine (n=9 ; erm(B), msr(G), erm(45)), acide fusidique (n=9 ; fusC) et gentamicine (n=1 ; aac(6')-Ie ­ aph(2'')-Ia). Cette étude est la première à déterminer prévalence des Macrococcus spp. résistants à la méthicilline chez les porcs, les veaux, la viande de porc et de bœuf en Suisse et a révélé un réservoir de souches génétiquement diverses et portant plusieurs traits de résistance.

Hygiene-Eliciting Brood Semiochemicals as a Tool for Assaying Honey Bee (Hymenoptera: Apidae) Colony Resistance to Varroa (Mesostigmata: Varroidae).

Despite numerous interventions, the ectoparasitic mite Varroa (Varroa destructor Anderson and Trueman [Mesostigmata: Varroidae]) and the pathogens it vectors remain a primary threat to honey bee (Apis mellifera Linnaeus [Hymenoptera: Apidae]) health. Hygienic behavior, the ability to detect, uncap, and remove unhealthy brood from the colony, has been bred for selectively for over two decades and continues to be a promising avenue for improved Varroa management. Although hygienic behavior is expressed more in Varroa-resistant colonies, hygiene does not always confer resistance to Varroa. Additionally, existing Varroa resistance selection methods trade efficacy for efficiency, because those achieving the highest levels of Varroa resistance can be time-consuming, and thus expensive and impractical for apicultural use. Here, we tested the hypothesis that hygienic response to a mixture of semiochemicals associated with Varroa-infested honey bee brood can serve as an improved tool for predicting colony-level Varroa resistance. In support of our hypothesis, we demonstrated that a mixture of the compounds (Z)-10-tritriacontene, (Z)-8-hentriacontene, (Z)-8-heptadecene, and (Z)-6-pentadecene triggers hygienic behavior in a two-hour assay, and that high-performing colonies (hygienic response to ≥60% of treated cells) have significantly lower Varroa infestations, remove significantly more introduced Varroa, and are significantly more likely to survive the winter compared to low-performing colonies (hygienic response to <60% of treated cells). We discuss the relative efficacy and efficiency of this assay for facilitating apiary management decisions and selection of Varroa-resistant honey bees, as well as the relevance of these findings to honey bee health, pollination services, and social insect communication.

Spotted Lanternfly (Hemiptera: Fulgoridae) Nymphal Dispersion Patterns and Their Influence on Field Experiments.

The spotted lanternfly, Lycorma delicatula (Hemiptera: Fulgoridae) (White, 1845), is an invasive pest in the Mid-Atlantic region of the United States. Understanding this pest's dispersion patterns is fundamental for development of management and surveillance programs. To address this knowledge gap, we quantified spotted lanternfly nymph dispersion patterns by instar for rural and urban/suburban habitats, and we compared the number of sample units required for sticky traps and in situ visual counts to estimate population densities at several precisions. In addition, we assessed the ability of two experimental designs (completely random and randomized complete block) to detect management practices' impacts in the field. All instars typically followed an aggregated dispersion pattern. Sample size and time requirements for checking and replacing sticky traps and for conducting in situ counts were similar, but in situ counts do not require purchasing traps, installation time, or delays before treatment, and do not remove insects. Although the cost for using in situ counts is likely less than for sticky traps, early instar spotted lanternfly nymph populations are harder to visually detect than later instars because of their small size, which may negate any cost advantage when treatments are applied early. In general, using a randomized complete block design resulted in higher statistical power than a completely random design, allowing detection of proportional population reductions of 10-20% less with equal replication. Studies aiming to evaluate treatments that reduce spotted lanternfly numbers by less than 60% will require researchers to evaluate the feasibility of using the required large sample sizes.

Genomic data from NSCLC tumors reveals correlation between SHP-2 activity and PD-L1 expression and suggests synergy in combining SHP-2 and PD-1/PD-L1 inhibitors.

The identification of novel therapies, new strategies for combination of therapies, and repurposing of drugs approved for other indications are all important for continued progress in the fight against lung cancers. Antibodies that target immune checkpoints can unmask an immunologically hot tumor from the immune system of a patient. However, despite accounts of significant tumor regression resulting from these medications, most patients do not respond. In this study, we sought to use protein expression and RNA sequencing data from The Cancer Genome Atlas and two smaller studies deposited onto the Gene Expression Omnibus (GEO) to advance our hypothesis that inhibition of SHP-2, a tyrosine phosphatase, will improve the activity of immune checkpoint inhibitors (ICI) that target PD-1 or PD-L1 in lung cancers. We first collected protein expression data from The Cancer Proteome Atlas (TCPA) to study the association of SHP-2 and PD-L1 expression in lung adenocarcinomas. RNA sequencing data was collected from the same subjects through the NCI Genetic Data Commons and evaluated for expression of the PTPN11 (SHP-2) and CD274 (PD-L1) genes. We then analyzed RNA sequencing data from a series of melanoma patients who were either treatment naïve or resistant to ICI therapy. PTPN11 and CD274 expression was compared between groups. Finally, we analyzed gene expression and drug response data collected from 21 non-small cell lung cancer (NSCLC) patients for PTPN11 and CD274 expression. From the three studies, we hypothesize that the activity of SHP-2, rather than the expression, likely controls the expression of PD-L1 as only a weak relationship between PTPN11 and CD274 expression in either lung adenocarcinomas or melanomas was observed. Lastly, the expression of CD274, not PTPN11, correlates with response to ICI in NSCLC.

Influence of pregnancy and non-fasting conditions on the plasma metabolome in a rat prenatal toxicity study.

The current parameters for determining maternal toxicity (e.g. clinical signs, food consumption, body weight development) lack specificity and may underestimate the extent of effects of test compounds on the dams. Previous reports have highlighted the use of plasma metabolomics for an improved and mechanism-based identification of maternal toxicity. To establish metabolite profiles of healthy pregnancies and evaluate the influence of food consumption as a confounding factor, metabolite profiling of rat plasma was performed by gas- and liquid-chromatography-tandem mass spectrometry techniques. Metabolite changes in response to pregnancy, food consumption prior to blood sampling (non-fasting) as well as the interaction of both conditions were studied. In dams, both conditions, non-fasting and pregnancy, had a marked influence on the plasma metabolome and resulted in distinct individual patterns of changed metabolites. Non-fasting was characterized by increased plasma concentrations of amino acids and diet related compounds and lower levels of ketone bodies. The metabolic profile of pregnant rats was characterized by lower amino acids and glucose levels and higher concentrations of plasma fatty acids, triglycerides and hormones, capturing the normal biochemical changes undergone during pregnancy. The establishment of metabolic profiles of pregnant non-fasted rats serves as a baseline to create metabolic fingerprints for prenatal and maternal toxicity studies.