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In 2022, concurrent outbreaks of hepatitis A, invasive meningococcal disease (IMD), and mpox were identified in Florida, USA, primarily among men who have sex with men. The hepatitis A outbreak (153 cases) was associated with hepatitis A virus genotype IA. The IMD outbreak (44 cases) was associated with Neisseria meningitidis serogroup C, sequence type 11, clonal complex 11. The mpox outbreak in Florida (2,845 cases) was part of a global epidemic. The hepatitis A and IMD outbreaks were concentrated in Central Florida and peaked during March–­June, whereas mpox cases were more heavily concentrated in South Florida and had peak incidence in August. HIV infection was more common (52%) among mpox cases than among hepatitis A (21%) or IMD (34%) cases. Where feasible, vaccination against hepatitis A, meningococcal disease, and mpox should be encouraged among at-risk groups and offered along with program services that target those groups.

Abstract. This interview was conducted on August 21st, 2022 by Charles Buck and Ioannis Solos. Peter Deadman has worked in the field of health promotion for 50 years. He co-founded Infinity Foods (an organic and natural foods workers co-op) in 1971, followed by the Brighton Natural Health Centre—a charity dedicated to teaching ways to improve personal, community and planetary health and wellbeing. He qualified as an acupuncturist in 1978 and in Chinese herbal medicine in 1990. He founded The Journal of Chinese Medicine (UK) in 1979 (Fig. 1), and co-authored A Manual of Acupuncture (published in 1998). He is the author of Live Well Live Long: Teachings from the Chinese Nourishment of Life Tradition. He has taught Chinese medicine and health promotion internationally for decades and is a dedicated practitioner and teacher of Qi Gong (气功). Figure 1 Front cover of The Journal of Chinese Medicine, published in 1980 (source from: the authors).

Abstract. It has historically been very difficult to trace the history of the westward transmission of Chinese medicine through the accounts of its protagonists. Many of the early scholars such as Jack Worsley, Dick Van Buren, and Joe Goodman were reluctant to divulge information about the source of their knowledge, or their professional qualifications. Others, such as John Shen and Hong Yuan-bain were early 20th century immigrants who transmitted highly personalized versions of acupuncture and Chinese medicine to select disciples. Eventually, a new class of scholars appeared, including names such as Ted Kaptchuk, Peter Deadman, Nigel Wiseman, William Morris, Peter Eckman, John McDonald, Charles Buck, and the late Giovanni Maciocia who looked for answers back in China, developed translation methodologies and terminology, compiled the main textbooks currently in use at TCM colleges, overcame enormous scholastic adversity, developed courses and pursued the regulation and accreditation of TCM in various countries. This special issue synopsizes the path towards the global acculturation of TCM over the last 50 years, the main protagonists, the enormous accomplishments they have achieved for the profession, their philosophy, their clinical perspectives and visions for the future.

Abstract. The interview was conducted on November 20th, 2022 by Ioannis Solos and Charles Buck. Ted Kaptchuk (泰开阳) is a Professor of Medicine and a Professor of Global Health & Social Medicine at Harvard Medical School. In 1975, he graduated from the Macau Institute of Chinese Medicine, Macau, China. After returning to the West, Ted taught Chinese medicine throughout the States, Europe, Latin America, and Australia. Ted’s book, The Web that Has No Weaver: Understanding Chinese Medicine is a groundbreaking explanation of East Asian medicine that continues to shape the discourse of the Chinese medicine profession in the West and has been translated into 13 languages. In 1990, Ted was recruited in Harvard Medical School to help research Chinese medicine. After encountering high placebo responses in multiple acupuncture clinical trials, Ted decided to switch his career to primarily studying placebo. He has published over 300 peer-reviewed articles. He has been awarded the Lifetime Achievement Award from the Society of Acupuncture Research (2015), the Lifetime Achievement Award from the Society for Interdisciplinary Placebo Studies (2021), and the William Silen Lifetime Achievement Award in Mentoring from Harvard Medical School (2022).

Abstract. The interview was conducted on March 2nd, 2023 by Ioannis Solos and Charles Buck. William Morris has sustained practice since 1980. He has served on the California, Texas and Massachusetts Professional Associations, as well as the National Association. He has tendered 20 years of service to the field through academic medicine, earning a master’s degree in medical education to assist in developing Chinese medical doctoral programs and institutional review boards. He earned an OM.D. in 1988, a DAOM in 2002, and a Ph.D. focused on pulse diagnosis as clinical epistemology in 2009. He has published five books, including TCM Case Studies Dermatology, Li Shi-zhen Pulse Studies: An Illustrated Guide, Neoclassical Pulse Diagnosis, Cycles in Medical Astrology, and Transformation: Treating Trauma with Acupuncture and Herbs.

Abstract Substance use disorders (SUDs) are highly comorbid with HIV infection, necessitating an understanding of the interactive effects of drug exposure and HIV. The relationship between HIV infection and cocaine use disorder is likely bidirectional, with cocaine use directly impacting immune function while HIV infection alters addiction-related behavior. To better characterize the neurobehavioral and immune consequences of HIV infection and cocaine exposure, this study utilizes a humanized mouse model to investigate the outcomes of HIV-1 infection on cocaine-related behaviors in a conditioned place preference (CPP) model, and the interactive effects of cocaine and HIV infection on peripheral and central nervous system inflammation. HIV infection selectively impairs cocaine CPP extinction without effecting reinstatement or cocaine seeking under conflict. Behavioral alterations are accompanied by immune changes in HIV infected mice, including increased prefrontal cortex astrocyte immunoreactivity and brain-region specific effects on microglia number and reactivity. Peripheral immune system changes are observed in human cytokines, including HIV-induced reductions in human TNFα, and cocaine and HIV interactions on GM-CSF levels. Together these data provide new insights into the unique neurobehavioral outcomes of HIV infection and cocaine exposure and how they interact to effect immune responses.

Abstract Porphyromonas gingivalis, a Gram-negative anaerobic bacterium commonly found in human subgingival plaque, is a major etiologic agent for periodontitis and has been associated with multiple systemic pathologies. Many P. gingivalis strains have been identified and different strains possess different virulence factors. Current oral microbiome approaches (16S or shotgun) have been unable to differentiate P. gingivalis strains. This study presents a new approach that aims to improve the accuracy of strain identification, using a detection method based on sequencing of the intergenic spacer region (ISR) which is variable between P. gingivalis strains. Our approach uses two-step PCR to amplify only the P. gingivalis ISR region. Samples are then sequenced with an Illumina sequencer and mapped to specific strains. Our approach was validated by examining subgingival plaque from 153 participants with and without periodontal disease. We identified the avirulent strain ATCC33277/381 as the most abundant strain across all sample types. The W83/W50 strain was significantly enriched in periodontitis, with 13% of participants harboring that strain. Overall, this approach can have significant implications not only for the diagnosis and treatment of periodontal disease but also for other diseases where P. gingivalis or its toxins have been implicated, such as Alzheimer's disease.

Abstract One of the major hurdles that has hindered the success of chimeric antigen receptor (CAR) T cell therapies against solid tumors is on-target off-tumor (OTOT) toxicity due to sharing of the same epitopes on normal tissues. To elevate the safety profile of CAR-T cells, an affinity/avidity fine-tuned CAR was designed enabling CAR-T cell activation only in the presence of a highly expressed tumor associated antigen (TAA) but not when recognizing the same antigen at a physiological level on healthy cells. Using direct stochastic optical reconstruction microscopy (dSTORM) which provides single-molecule resolution, and flow cytometry, we identified high carbonic anhydrase IX (CAIX) density on clear cell renal cell carcinoma (ccRCC) patient samples and low-density expression on healthy bile duct tissues. A Tet-On doxycycline-inducible CAIX expressing cell line was established to mimic various CAIX densities, providing coverage from CAIX-high skrc-59 tumor cells to CAIX-low MMNK-1 cholangiocytes. Assessing the killing of CAR-T cells, we demonstrated that low-affinity/high-avidity fine-tuned G9 CAR-T has a wider therapeutic window compared to high-affinity/high-avidity G250 that was used in the first anti-CAIX CAR-T clinical trial but displayed serious OTOT effects. To assess the therapeutic effect of G9 on patient samples, we generated ccRCC patient derived organotypic tumor spheroid (PDOTS) ex vivo cultures and demonstrated that G9 CAR-T cells exhibited superior efficacy, migration and cytokine release in these miniature tumors. Moreover, in an RCC orthotopic mouse model, G9 CAR-T cells showed enhanced tumor control compared to G250. In summary, G9 has successfully mitigated OTOT side effects and in doing so has made CAIX a druggable immunotherapeutic target.

Abstract Introduction Healthcare services face significant challenges due to the aging population, increasing complexity of health issues, and a global shortage of health professionals. Health professions education needs to adapt and develop with healthcare services’ needs. Interprofessional education and patient partnership are two trends that are increasingly being reinforced. Health professions students worldwide are expected to acquire competencies in interprofessional collaboration through undergraduate and postgraduate studies. Developing interprofessional collaborative skills in clinical placements is crucial. This study aims to explore two patients’ meetings with an interprofessional student team and better understand how the patient can participate actively in the students´ learning processes. Methods This is a small single-case study. Two patients participated. Data was generated through participant observation and qualitative interviews. A practical iterative framework for qualitative data analysis inspired the analysis. Results The patients observed and reflected on the interprofessional students’ learning process and felt responsible for contributing to their learning. The patients contributed to students’ learning by making themselves available for practicing and sometimes giving feedback. They considered it a win-win situation to be involved in the interprofessional learning activity as they perceived being taken seriously by the students when addressing their problems and experienced positive outcomes for their situation, such as better physical functioning and adjustments to assistive devices. Patients emphasized the importance of learning collaboration between health professionals and how this could contribute to them feeling safer as patients. Discussion This study highlights the importance of including patients in interprofessional students’ learning processes. Patients’ active participation in interprofessional clinical placements can empower them, improve their self-efficacy, and potentially shift the power dynamic between patients and healthcare professionals. The study emphasizes the importance of the patient perspective in future research on interprofessional education in clinical settings. The study also highlights the need for clinical supervisors to facilitate patient involvement in interprofessional clinical placements and reinforce patients’ feedback for the student team. Concluding comments Overall, this study contributes to the growing body of research on interprofessional education and patient partnership and emphasizes the importance of including patients in health professions education.

The ongoing panzootic of highly pathogenic H5 clade 2.3.4.4b avian influenza (HPAI) spread to North America in late 2021, with detections of HPAI viruses in Alaska beginning in April 2022. HPAI viruses have since spread across the state, affecting many species of wild birds as well as domestic poultry and wild mammals. To better understand the dissemination of HPAI viruses spatiotemporally and among hosts in Alaska and adjacent regions, we compared the genomes of 177 confirmed HPAI viruses detected in Alaska during April–December 2022. Results suggest multiple viral introductions into Alaska between November 2021 and August or September 2022, as well as dissemination to areas within and outside of the state. Viral genotypes differed in their spatiotemporal spread, likely influenced by timing of introductions relative to population immunity. We found evidence for dissemination of HPAI viruses between wild bird species, wild birds and domestic poultry, as well as wild birds and wild mammals. Continued monitoring for and genomic characterization of HPAI viruses in Alaska can improve our understanding of the evolution and dispersal of these economically costly and ecologically relevant pathogens.

BACKGROUNDThe presence and reactivation of chronic viral infections, such as EBV, CMV, and HIV, have been proposed as potential contributors to long COVID (LC), but studies in well-characterized postacute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited.METHODSIn a cohort of 280 adults with prior SARS-CoV-2 infection, we assessed the presence and types of LC symptoms and prior medical history (including COVID-19 history and HIV status) and performed serological testing for EBV and CMV using a commercial laboratory. We used covariate-adjusted binary logistic regression models to identify independent associations between variables and LC symptoms.RESULTSWe observed that LC symptoms, such as fatigue and neurocognitive dysfunction, at a median of 4 months following initial diagnosis were independently associated with serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) or high nuclear antigen (EBNA) IgG levels but not with ongoing EBV viremia. Serological evidence suggesting recent EBV reactivation (early antigen-diffuse IgG positivity) was most strongly associated with fatigue (OR = 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR = 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR = 0.52).CONCLUSIONOverall, these findings suggest differential effects of chronic viral coinfections on the likelihood of developing LC and association with distinct syndromic patterns. Further assessment during the acute phase of COVID-19 is warranted.TRIAL REGISTRATIONLong-term Impact of Infection with Novel Coronavirus; ClinicalTrials.gov NCT04362150.FUNDINGThis work was supported by NIH/National Institute of Allergy and Infectious Diseases grants (3R01AI141003-03S1, R01AI158013, and K24AI145806); the Zuckerberg San Francisco General Hospital Department of Medicine and Division of HIV, Infectious Diseases, and Global Medicine; and the UCSF-Bay Area Center for AIDS Research (P30-AI027763).

ImportanceThe practice of using medical writers to communicate scientific information has gained popularity, but it may affect how and what information is communicated.ObjectiveTo assess characteristics of oncology trials that use medical writers and whether there is an association between the use of medical writers and trial success or the primary outcome evaluated.Design, setting, and participantsThis cross-sectional study included oncology trials testing a tumor-targeting intervention that were published in The Lancet, The Lancet Oncology, JAMA, JAMA Oncology, Journal of Clinical Oncology, and The New England Journal of Medicine between May 1, 2021, and May 1, 2022.ExposuresAssistance of medical writers or no assistance.Main outcomes and measuresThe main outcomes were the percentage of studies with medical writers, the percentage of trial successes reported with medical writers, the association between trial success and medical writer use, and the association between a primary end point and medical writer use.ResultsAmong 270 studies, 141 (52.2%) included a medical writer and 129 (47.8%) did not include a medical writer. Of the studies that included a medical writer, 83 (58.9%) were successful. Of the studies that did not include a medical writer, 64 (49.6%) were successful (P = .16 for difference). Studies with medical writers were less likely than studies without medical writers to have the end point of overall survival (15 [10.6%] vs 17 [13.2%]) and disease-free or event-free survival (16 [11.3%] vs 29 [22.5%]), whereas studies with a medical writer were more likely to have the end point of progression-free survival (32 [22.7%] vs 17 [13.2%]). Use of medical writer was associated with the conclusions being presented favorably in all studies (113 [80.1%] vs 89 [69.0%]; odds ratio [OR], 1.81 [95% CI, 1.04-3.19]), but when adjusted for other variables, there was no association (OR, 1.84 [95% CI, 0.92-3.72]).Conclusions and relevanceIn this cross-sectional study, trials using medical writers were more likely to report surrogate end points, such as progression-free survival, and favorable conclusions, but when adjusted for trial phase, randomization, and study funding, there was no association with favorable conclusions. These findings suggest that journals need heightened scrutiny for studies with medical writers and that authorship should be properly acknowledged.

INTRODUCTION: during the second wave of the COVID-19 pandemic in Mozambique, there was a surge in pediatric hospitalizations at a time when there was relatively little evidence, but significant concern about clinical outcomes in African children, particularly in higher-risk infants requiring, and health system capacity to respond. METHODS: a retrospective cohort study was conducted for patients 1-12 months of age admitted to the Breastfeeding ward at Hospital Central de Maputo from January-February 2021. All had routine SARS-CoV-2 PCR testing performed. For patients with positive results, hospital charts were retrospectively reviewed. Descriptive analyses were performed. RESULTS: of 209 patients that had SARS-CoV-2 PCR testing performed, 102 (48.8%) received results, of which 37 (36.3%) were positive. Positive results were received prior to discharge for 14 patients (37.8%). Median duration of hospitalization was 3 days. There were two deaths in COVID-positive patients (5.4%), both with complex comorbidities. For the 35 COVID-19 positive patients whose charts were located, the principal admission diagnosis was respiratory for 22 (62.9%), and 14 (40.0%) had oxygen saturation 12.0 x 103cells/mL in 10 patients (28.6%) and the most common abnormal finding on chest radiograph was peribronchial thickening (38.5% of patients with results). Oxygen therapy was needed for 20 patients (57.1%). CONCLUSION: the majority of infants with COVID-19 had a mild, short-duration respiratory illness that did not exceed ward capacity for care, including oxygen treatment. Laboratory capacity for PCR testing was overwhelmed, delaying the return of results and complicating inpatient infection control measures.

BackgroundImportant insights into the early pathogenesis of Alzheimer's disease can be provided by studies of autosomal dominant Alzheimer's disease and Down syndrome. However, it is unclear whether the timing and spatial distribution of amyloid accumulation differs between people with autosomal dominant Alzheimer's disease and those with Down syndrome. We aimed to directly compare amyloid changes between these two groups of people.MethodsIn this cross-sectional study, we included participants (aged ≥25 years) with Down syndrome and sibling controls who had MRI and amyloid PET scans in the first data release (January, 2020) of the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) study. We also included carriers of autosomal dominant Alzheimer's disease genetic mutations and non-carrier familial controls who were within a similar age range to ABC-DS participants (25-73 years) and had MRI and amyloid PET scans at the time of a data freeze (December, 2020) of the Dominantly Inherited Alzheimer Network (DIAN) study. Controls from the two studies were combined into a single group. All DIAN study participants had genetic testing to determine PSEN1, PSEN2, or APP mutation status. APOE genotype was determined from blood samples. CSF samples were collected in a subset of ABC-DS and DIAN participants and the ratio of amyloid β42 (Aβ42) to Aβ40 (Aβ42/40) was measured to evaluate its Spearman's correlation with amyloid PET. Global PET amyloid burden was compared with regards to cognitive status, APOE ɛ4 status, sex, age, and estimated years to symptom onset. We further analysed amyloid PET deposition by autosomal dominant mutation type. We also assessed regional patterns of amyloid accumulation by estimated number of years to symptom onset. Within a subset of participants the relationship between amyloid PET and CSF Aβ42/40 was evaluated.Findings192 individuals with Down syndrome and 33 sibling controls from the ABC-DS study and 265 carriers of autosomal dominant Alzheimer's disease mutations and 169 non-carrier familial controls from the DIAN study were included in our analyses. PET amyloid centiloid and CSF Aβ42/40 were negatively correlated in carriers of autosomal dominant Alzheimer's disease mutations (n=216; r=-0·565; p

Mercury (Hg) methylation genes (hgcAB) mediate the formation of the toxic methylmercury and have been identified from diverse environments, including freshwater and marine ecosystems, Arctic permafrost, forest and paddy soils, coal-ash amended sediments, chlor-alkali plants discharges and geothermal springs. Here we present the first attempt at a standardized protocol for the detection, identification and quantification of hgc genes from metagenomes. Our Hg-cycling microorganisms in aquatic and terrestrial ecosystems (Hg-MATE) database, a catalogue of hgc genes, provides the most accurate information to date on the taxonomic identity and functional/metabolic attributes of microorganisms responsible for Hg methylation in the environment. Furthermore, we introduce marky-coco, a ready-to-use bioinformatic pipeline based on de novo single-metagenome assembly, for easy and accurate characterization of hgc genes from environmental samples. We compared the recovery of hgc genes from environmental metagenomes using the marky-coco pipeline with an approach based on coassembly of multiple metagenomes. Our data show similar efficiency in both approaches for most environments except those with high diversity (i.e., paddy soils) for which a coassembly approach was preferred. Finally, we discuss the definition of true hgc genes and methods to normalize hgc gene counts from metagenomes.

BackgroundPneumonia is the primary cause of death among HIV-infected children in Africa, with mortality rates as high as 35-40% in infants hospitalized with severe pneumonia. Bacterial pathogens and Pneumocystis jirovecii are well known causes of pneumonia-related death, but other important causes such as cytomegalovirus (CMV) and tuberculosis (TB) remain under-recognized and undertreated. The immune response elicited by CMV may be associated with the risk of developing TB and TB disease progression, and CMV may accelerate disease caused both by HIV and TB. Minimally invasive autopsies confirm that CMV and TB are unrecognized causes of death in children with HIV. CMV and TB may also co-infect the same child. The aim of this study is to compare the impact on 15-day and 1-year mortality of empirical treatment against TB and CMV plus standard of care (SoC) versus SoC in HIV-infected infants with severe pneumonia.MethodsThis is a Phase II-III, open-label randomized factorial (2 × 2) clinical trial, conducted in six African countries. The trial has four arms. Infants from 28 to 365 days of age HIV-infected and hospitalized with severe pneumonia will be randomized (1:1:1:1) to (i) SoC, (ii) valganciclovir, (iii) TB-T, and (iv) TB-T plus valganciclovir. The primary endpoint of the study is all-cause mortality, focusing on the short-term (up to 15 days) and long-term (up to 1 year) mortality. Secondary endpoints include repeat hospitalization, duration of oxygen therapy during initial admission, severe and notable adverse events, adverse reactions, CMV and TB prevalence at enrolment, TB incidence, CMV viral load reduction, and evaluation of diagnostic tests such as GeneXpert Ultra on fecal and nasopharyngeal aspirate samples and urine TB-LAM.DiscussionGiven the challenges in diagnosing CMV and TB in children and results from previous autopsy studies that show high rates of poly-infection in HIV-infected infants with respiratory disease, this study aims to evaluate a new approach including empirical treatment of CMV and TB for this patient population. The potential downsides of empirical treatment of these conditions include toxicity and medication interactions, which will be evaluated with pharmacokinetics sub-studies.Trial registrationClinicalTrials.gov , NCT03915366, Universal Trial Number U111-1231-4736, Pan African Clinical Trial Registry PACTR201994797961340.

IntroductionBovine mastitis caused by Escherichia coli compromises animal health and inflicts substantial product losses in dairy farming. It may manifest as subclinical through severe acute disease and can be transient or persistent in nature. Little is known about bacterial factors that impact clinical outcomes or allow some strains to outcompete others in the mammary gland (MG) environment. Mastitis-associated E. coli (MAEC) may have distinctive characteristics which may contribute to the varied nature of the disease. Given their high levels of intraspecies genetic variability, virulence factors of commonly used MAEC model strains may not be relevant to all members of this group.MethodsIn this study, we sequenced the genomes of 96 MAEC strains isolated from cattle with clinical mastitis (CM). We utilized clinical severity data to perform genome-wide association studies to identify accessory genes associated with strains isolated from mild or severe CM, or with high or low competitive fitness during in vivo competition assays. Genes associated with mastitis pathogens or commensal strains isolated from bovine sources were also identified.ResultsA type-2 secretion system (T2SS) and a chitinase (ChiA) exported by this system were strongly associated with pathogenic isolates compared with commensal strains. Deletion of chiA from MAEC isolates decreased their adherence to cultured bovine mammary epithelial cells.DiscussionThe increased fitness associated with strains possessing this gene may be due to better attachment in the MG. Overall, these results provide a much richer understanding of MAEC and suggest bacterial processes that may underlie the clinical diversity associated with mastitis and their adaptation to this unique environment.

When moving from a very sheltered aquaculture site to a very exposed oceanic aquaculture site, the energy increases proportionally in a continuum. Lojek et al. (in review) considered the primary influential parameters (water current, wave height, wave period, wavelength and water depth) which influence the species, structure, technology, methods, and operational aspects of any aquaculture endeavour and investigated six possible indices which cover these variables. Added to advanced computer modelling, assisted by detailed and constant environmental monitoring, it may be possible to refine site selection, structure selection and design, species selection, equipment and logistic requirements and health and safety requirements. This manuscript has selected two indicative indices: Specific Exposure Energy (SEE) index and Exposure Velocity (EV) index from the potential equations provided by Lojek et al. (in review) and compared them with known operational aquaculture sites highlighting present structural capability and limitations. The two indices are also utilized to reflect on their suitability for assessing sample sites with respect to biological, technological, operational or maintenance aspects of aquaculture activities. The indices have shown themselves to be useful tools in the general assessment of the energy that will influence the species and structure selection at potential aquaculture sites. This information can help prospective fish farmers characterize their sites concisely and accurately to consultants, regulators, equipment vendors, and insurance brokers.

ABSTRACT In the wild, C. elegans are emersed in environments teeming with a veritable menagerie of microorganisms. The C. elegans cuticular surface serves as a barrier and first point of contact with their microbial environments. In this study, we identify microbes from C. elegans natural habitats that associate with its cuticle, constituting a simple “skin microbiome.” We rear our animals on a modified CeMbio, mCeMbio, a consortium of ecologically relevant microbes. We first combine standard microbiological methods with an adapted micro skin-swabbing tool to describe the skin-resident bacteria on the C. elegans surface. Furthermore, we conduct 16S rRNA gene sequencing studies to identify relative shifts in the proportion of mCeMbio bacteria upon surface-sterilization, implying distinct skin- and gut-microbiomes. We find that some strains of bacteria, including Enterobacter sp. JUb101, are primarily found on the nematode skin, while others like Stenotrophomonas indicatrix JUb19 and Ochrobactrum vermis MYb71 are predominantly found in the animal’s gut. Finally, we show that this skin microbiome promotes host cuticle integrity in harsh environments. Together, we identify a skin microbiome for the well-studied nematode model and propose its value in conferring host fitness advantages in naturalized contexts.IMPORTANCEThe genetic model organism C. elegans has recently emerged as a tool for understanding host–microbiome interactions. Nearly all of these studies either focus on pathogenic or gut-resident microbes. Little is known about the existence of native, nonpathogenic skin microbes or their function. We demonstrate that members of a modified C. elegans model microbiome, mCeMbio, can adhere to the animal's cuticle and confer protection from noxious environments. We combine a novel micro-swab tool, the first 16S microbial sequencing data from relatively unperturbed C. elegans, and physiological assays to demonstrate microbially mediated protection of the skin. This work serves as a foundation to explore wild C. elegans skin microbiomes and use C. elegans as a model for skin research.

Diverse and complex microbiomes are found in virtually every environment on Earth. Bacteria and fungi often co-dominate environmental microbiomes, and there is growing recognition that bacterial-fungal interactions (BFI) have significant impacts on the functioning of their associated microbiomes, environments, and hosts. Investigating BFI in vitro remains a challenge, particularly when attempting to examine interactions at multiple scales of system complexity. Fabricated devices can provide control over both biotic composition and abiotic factors within an experiment to enable the characterization of diverse BFI phenotypes such as modulation of growth rate, production of biomolecules, and alterations to physical movements. Engineered devices ranging from microfluidic chips to simulated rhizosphere systems have been and will continue to be invaluable to BFI research, and it is anticipated that such devices will continue to be developed for diverse applications in the field. This will allow researchers to address specific questions regarding the nature of BFI and how they impact larger microbiome and environmental processes such as biogeochemical cycles, plant productivity, and overall ecosystem resilience. Devices that are currently used for experimental investigations of bacteria, fungi, and BFI are discussed herein along with some of the associated challenges and several recommendations for future device design and applications.

Study region:: The Ohio River in the northeast United States (US). Study focus:: Low streamflows are critical for urban water security, agricultural irrigation, water quality regulatory thresholds, navigation passage, and ecological well-being. However, there is insufficient understanding of the natural low flow conditions in rivers containing dams and artificial reservoirs, in part because we have inadequate records of natural flows prior to the introduction of the water control infrastructure. We demonstrate an improved technique for estimation of human impact on low flow, and describe the analytical innovations necessary to apply the technique. The primary innovation necessary was the development of a parsimonious streamflow routing algorithm to aggregate naturalized flow from reservoirs operated by the US Army Corps of Engineers (USACE) to locations of concern along the Ohio River mainstem. New hydrological insights for the region:: This study shows that, in dry years, releases from USACE reservoirs during autumn months account for up to approximately half of the mainstem flow, and the influence of USACE water control infrastructure is more pronounced on many of the Ohio River’s tributaries. The Flow Duration Curves also show significant differences in low flow throughout the mainstem. This has implications for dry season river functionality in all the categories listed above; if the infrastructure were to fail, or lose effectiveness due to climate change, these river functions would be threatened.

ABSTRACT The Gardnerella genus, comprising at least 13 species, is associated with the polymicrobial disorder bacterial vaginosis (BV). However, the details of BV pathogenesis are poorly defined, and the contributions made by individual species, including Gardnerella spp., are largely unknown. We report here that colony phenotypes characterized by size (large and small) and opacity (opaque and translucent) are phase variable and are conserved among all tested Gardnerella strains, representing at least 10 different species. With the hypothesis that these different variants could be an important missing piece to the enigma of how BV develops in vivo, we characterized their phenotypic, proteomic, and genomic differences. Beyond increased colony size, large colony variants showed reduced vaginolysin secretion and faster growth rate relative to small colony variants. The ability to inhibit the growth of Neisseria gonorrhoeae and commensal Lactobacillus species varied by strain and, in some instances, differed between variants. Proteomics analyses indicated that 127–173 proteins were differentially expressed between variants. Proteins with increased expression in large variants of both strains were associated with amino acid and protein synthesis and protein folding, whereas those increased in small variants were related to nucleotide synthesis, phosphate transport, ABC transport, and glycogen breakdown. Furthermore, whole genome sequencing analyses revealed an abundance of genes associated with variable homopolymer tracts, implicating slipped strand mispairing in Gardnerella phase variation and illuminating the potential for previously unrecognized heterogeneity within clonal populations. Collectively, these results suggest that phase variants may be primed to serve different roles in BV pathogenesis.IMPORTANCEBacterial vaginosis is the most common gynecological disorder in women of childbearing age. Gardnerella species are crucial to the development of this dysbiosis, but the mechanisms involved in the infection are not understood. We discovered that Gardnerella species vary between two different forms, reflected in bacterial colony size. A slow-growing form makes large amounts of the toxin vaginolysin and is better able to survive in human cervix tissue. A fast-growing form is likely the one that proliferates to high numbers just prior to symptom onset and forms the biofilm that serves as a scaffold for multiple BV-associated anaerobic bacteria. Identification of the proteins that vary between different forms of the bacteria as well as those that vary randomly provides insight into the factors important for Gardnerella infection and immune avoidance.

IntroductionThis study examined the efficacy of a five-module cognitive behavioral therapy for nightmares in children (CBT-NC) and improving sleep.Materials and methodsForty-six youth aged 6–17 years with sleep problems and at least weekly chronic and distressing nightmares were randomized to treatment (n = 23) or waiting list (n = 23) using a block four randomized design. Among participants, 65% (n = 30) were White, 4% (n = 2) were Black/African American, 2% (n = 1) were Asian American, 13% (n = 6) were Native American or Pacific Islander, and 15% (n = 7) were multiracial. Fifty percent of participants (n = 23) were cisgender girls, 35% were cisgender boys (n = 16), 7% were transgender boys (n = 3), and 9% were gender non-binary (n = 4). The baseline nightmare persistence ranged from 6 months to 13.5 years. The treatment adapted exposure, relaxation, and rescription therapy for trauma-related nightmares in adults and added elements of cognitive behavioral therapy for insomnia in children. Psychoeducation included topics of sleep and nightmares, relaxation, anxiety management, and sleep hygiene; the youth were guided through nightmare exposure and rescription.ResultsThere was a statistically significant improvement in the number of nights with awakening (Cohen's d = 1.08), the number of weekly nightmares (Cohen's d = 0.82), and nightmare distress (Cohen's d = 1.05) for the treatment group compared to the wait-list group. Parent-reported youth sleep improved for the entire group from pretreatment to posttreatment (p < 0.001) but did not reach statistical significance for between-subjects analyses of the treatment group compared to the wait-list group (p = 0.05). Between-subjects analyses saw improvement for the treatment group compared to the wait-list group on internalizing and externalizing problems and suicidal thoughts and behaviors.DiscussionThis study supports the efficacy of CBT-NC for improving sleep maintenance, nightmare frequency and distress, and other mental health difficulties in youth. Preliminary evidence of possibly improving suicidal thinking and behavior is also presented.Clinical trial registrationhttps://clinicaltrials.gov/study/NCT05588739, identifier: NCT05588739.

The terms “offshore” and “open ocean” have been used to describe aquaculture sites that are further from the coast or in higher energy environments. Neither term has been clearly defined in the scientific literature nor in a legal context, and the terms are often used interchangeably. These and other related terms (for example “exposed”, “high-energy”) variously refer to aspects of a site such as the geographic distance from shore or infrastructure, the level of exposure to large waves and strong currents, the geographic fetch, the water depth, or some combination of these parameters. The ICES Working Group (ICES, 2024) on Open Ocean Aquaculture (WGOOA) therefore identified a need to define the terminology to reduce ambiguity for these types of aquaculture sites or more precisely, to: (1) promote a common understanding and avoid misuse for different classifications; (2) enable regulators to identify the characteristics of a marine site; (3) allow farmers to be able to assess or quantitatively compare sites for development; (4) equip developers and producers to identify operational parameters in which the equipment and vessels will need to operate; (5) provide insurers and investors with the terminology to consistently assess risk and premiums; and (6) circumvent the emergence of narratives that root in different cognitive interpretations of the terminology in public discourse. This paper describes the evolution of the use of the term “offshore aquaculture” and define the most relevant parameters to shift to a more definitive and robust term “exposed aquaculture” that can inherently relay clearer information. Adoption of this more definitive definition of “exposed” will allow the user to define a site with more than just distance from shore. Key differences and the importance of these terms are discussed that affect various interest groups. Follow-up articles in this compilation from scientific members of the WGOOA as well as other scientists outside ICES are incorporated that develop a set of definitions and a rigorous exposure index.

Bovine mastitis is predominantly caused by intramammary infections with various Gram-positive and Gram-negative bacteria, requiring accurate pathogen identification for effective treatment and antimicrobial resistance prevention. Here, a novel diagnostic method was developed to detect mastitis pathogens in milk samples by combining loop-mediated isothermal amplification with a split enzyme biosensor whereby trehalase fragments were fused with a DNA-binding protein, SpoIIID. Three primer sets, LAMPstaph, LAMPstrep, and LAMPneg, harboring SpoIIID recognition sequences targeted Staphylococcus, Streptococcus, and Gram-negative pathogens, respectively. Limits of detection were determined for DNA extracted from bacterial culture and bacteria-spiked milk. The combined method detected as low as 2, 24, and 10 copies of genomic DNA of staphylococci, streptococci and Escherichia coli and 11 CFU/ml for milk spiked with Escherichia coli. Higher detection limits were observed for Gram-positive bacteria in spiked milk. When testing genomic DNA of 10 mastitis isolates at concentrations of 106 and 103 copies per reaction, no cross-reactivity was detected for LAMPstaph nor LAMPstrep, whereas the LAMPneg assay cross-reacted only with Corynebacterium sp. at the highest concentration. This combined method demonstrated the potential to distinguish mastitis pathogenic Gram types for a rapid decision of antimicrobial treatment without culturing.

This paper reports on a two-year project to form teaching development groups in engineering departments. The goal of each group was to discuss and implement interactive teaching strategies (e.g., in-class problem solving). The research design used meetings notes, feedback from group leaders and a case study of one participant to describe how the groups can be designed to support teaching development. This research was grounded in the following questions: What are the design principles underlying a successful, ongoing, small-group model for faculty teaching development? What logistical and structural features are important for ongoing faculty teaching development in a small-group format? This paper presents the five principles identified in the study and provides a case study of an engineering faculty member's teaching innovations over the several years during and after his participation in the faculty development group.

The "School Pantry: Mystery Food Box Cook-Off " is a program designed to increase awareness of food insecurity among youth and teach strategies to prepare healthy foods on a budget. A pre-and-post survey showed a statistically significant difference in participants' overall knowledge, skills, and confidence level after the program compared to before the program. Findings revealed a hands-on nutrition education strategy via cook-off could educate youth on food insecurity and increase their knowledge and confidence to make healthy and affordable meals at home. Other Extension educators seeking to address food insecurity and food preparation skills among youth can replicate this program.

Incorporating counterarguments can be challenging for many student-writers, including those for whom English is a second or other language. In this study, we present findings that may lead to improvements in students' understanding of the benefits of integrating counterarguments. In our study, expert readers were presented with excerpts of student academic writing in order to assess the degree to which counterarguments could be identified through student deployment of metadiscoursal features. The results suggest that student-writers deploy metadiscoursal features with insufficient frequency and consistency. The results further suggest that when metadiscoursal features are used in counterarguments, their deployment is largely restricted to the sentence-initial position. The study also considers the pedagogical and technological issues associated with the findings.

BackgroundKnown risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort.MethodsSingle nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test. We performed enrichment analysis of CNVs at known EOC risk loci and functional biofeatures in ovarian cancer-related cell types.ResultsWe identified statistically significant risk associations with CNVs at known EOC risk genes; BRCA1 (PEOC = 1.60E-21; OREOC = 8.24), RAD51C (Phigh-grade serous ovarian cancer [HGSOC] = 5.5E-4; odds ratio [OR]HGSOC = 5.74 del), and BRCA2 (PHGSOC = 7.0E-4; ORHGSOC = 3.31 deletion). Four suggestive associations (P

Multiomics approaches need to be applied in the central Arctic Ocean to benchmark biodiversity change and to identify novel species and their genes. As part of MOSAiC, EcoOmics will therefore be essential for conservation and sustainable bioprospecting in one of the least explored ecosystems on Earth.

Environmental contamination is widespread and can negatively impact wildlife health. Some contaminants, including heavy metals, have immunosuppressive effects, but prior studies have rarely measured contamination and disease simultaneously, which limits our understanding of how contaminants and pathogens interact to influence wildlife health. Here, we measured mercury concentrations, influenza infection, influenza antibodies and body condition in 749 individuals from 11 species of wild ducks overwintering in California. We found that the odds of prior influenza infection increased more than fivefold across the observed range of blood mercury concentrations, while accounting for species, age, sex and date. Influenza infection prevalence was also higher in species with higher average mercury concentrations. We detected no relationship between influenza infection and body fat content. This positive relationship between influenza prevalence and mercury concentrations in migratory waterfowl suggests that immunotoxic effects of mercury contamination could promote the spread of avian influenza along migratory flyways, especially if influenza has minimal effects on bird health and mobility. More generally, these results show that the effects of environmental contamination could extend beyond the geographical area of contamination itself by altering the prevalence of infectious diseases in highly mobile hosts.

Abstract Background Suicide, especially by firearm, remains a leading cause of death in military populations in the USA. Reducing access to firearms, especially during high risk times, may help prevent suicide and other forms of violence. The purpose of this study was to adapt a promising existing lethal means safety intervention (Project Safe Guard, PSG) for cross-cutting violence prevention and peer support in active-duty service communities using community engagement methods. Methods A two-pronged community-engaged research approach was employed, including the Community Translation (CT) process that engaged 15 Service Members from one installation to help adapt PSG successfully. In addition, qualitative data was collected from 40 active-duty service members and military violence prevention specialists through in-depth interviews and focus group discussions. Results Qualitative data and CT feedback led to site-specific PSG adaptations. Participants emphasized the importance of peer-to-peer discussions and highlighted resource allocation, leadership support, and stigma on firearm ownership as potential implementation challenges. Conclusions Findings demonstrate the feasibility of community-engaged research to adapt lethal means safety interventions within military populations. PSG implementation should consider resource allocation, leadership support, and addressing stigma. This study has implications for future policies and standards for performing research on sensitive topics, particularly among military populations.

Abstract Prevention of intestinal fibrosis remains an unresolved problem in the treatment of Crohn’s disease (CD), as specific antifibrotic therapies are not yet available. Appropriate analysis of fibrosis severity is essential for assessing the therapeutic efficacy of potential antifibrotic drugs. The aim of this study was to develop an observer-independent method to quantify intestinal fibrosis in surgical specimens from patients with CD using structural analysis of the extracellular matrix (ECM). We performed fractal analysis in fibrotic and control histological sections of patients with surgery for CD (n = 28). To specifically assess the structure of the collagen matrix, polarized light microscopy was used. A score to quantify collagen fiber alignment and the color of the polarized light was established. Fractal dimension as a measure for the structural complexity correlated significantly with the histological fibrosis score whereas lacunarity as a measure for the compactness of the ECM showed a negative correlation. Polarized light microscopy to visualize the collagen network underlined the structural changes in the ECM network in advanced fibrosis. In conclusion, observer-independent quantification of the structural complexity of the ECM by fractal analysis is a suitable method to quantify the degree of intestinal fibrosis in histological samples from patients with CD.

Abstract Point-contact p-type high-purity germanium detectors (PPC HPGe) are particularly suited for detection of sub-keV nuclear recoils from coherent elastic scattering of neutrinos or light dark matter particles. While these particles are expected to interact homogeneously in the entire detector volume, specific classes of external background radiation preferably deposit their energy close to the semi-active detector surface, in which diffusion processes dominate that subsequently lead to slower rising pulses compared to the ones from the fully active bulk volume. Dedicated studies of their shape are therefore highly beneficial for the understanding and the rejection of these unwanted events. This article reports about the development of a data-driven pulse shape discrimination (PSD) method for the four 1 kg size PPC HPGe detectors of the Conus experiment in the keV and sub-keV regime down to 210 eV $$_{ee}.$$ ee . The impact of the electronic noise at such low energies is carefully examined. It is shown that for an acceptance of 90% of the faster signal-like pulses from the bulk volume, approx. 50% of the surface events can be rejected at the energy threshold and that their contribution is fully suppressed above 800 eV $$_{ee}.$$ ee . Applied to the Conus background data, such a PSD rejection cut allows to achieve an overall $$(15{-}25)\%$$ ( 15 - 25 ) % reduction of the total background budget. The new method allows to improve the sensitivity of future Conus analyses and to refine the corresponding background model in the sub-keV energy region.

A re-examination of the original collection of Plagiothecium novae-seelandiae described by Brotherus in 1916 indicated that this material is not homogeneous. Re-examination of the diagnosis of this species and morphological analysis supports that two separate taxa should be distinguished – Plagiothecium novae-seelandiae var. novae-seelandiae and P. novae-seelandiae var. brotheri var. nov. Also, comparisons with the original collection of Hypnum lamprostachys (= P. lamprostachys) showed differences, which supported their treatment as separate taxa. Revision of the genus Plagiothecium from Australasia (CANB, CHR, HO, MEL, WELT) and types of other species described from this part of the world (P. funale and P. lucidum) supported by the study of their diagnoses, qualitative and quantitative characteristics as well as mathematical analyses (PCA, HCA) allowed the division of the examined material into six separate groups – six separate taxa. Thereby, three distinct taxa are proposed – P. cordatum sp. nov., P. semimortuum sp. nov., and P. semimortuum var. macquariense var. nov. All taxa mentioned above are described in detail, their current known distribution and ecological preferences are also included. In addition, images illustrating their most important taxonomic features, as well as an original key to distinguish individual taxa are presented.

Interferers with a high bearing rate challenge the ability of the minimum variance distortionless response (MVDR) beamformer to place accurate notches in the direction of the interferer. Consequently, the MVDR notch location always slightly lags the interferer’s actual location, degrading the MVDR’s ability to suppress moving interferers. Creating a flatter and broader notch is a more effective approach to dealing with the interferer’s motion. This paper proposes a hybrid double zero (HDZ) MVDR beamformer that generalizes the double zero (DZ) MVDR beamformer proposed by Tuladhar and Buck in 2015. The DZ MVDR beamformer constraints the array polynomial to be the square of a lower-order polynomial so that all beampattern notches are second-order roots of the array polynomial. However, constraining every notch to be a second-order notch reduces the degrees of freedom (DoF) available for background white noise attenuation. In contrast to the DZ beamformer, the HDZ beamformer factors the beampattern into adaptive and fixed components. The adaptive component has wide notches to suppress moving interferers, while the fixed component improves the white noise gain (WNG) and ensures the array weight vector length matches the array size. The HDZ beamformer spends fewer DoFs on adaptive nulling than the original DZ beamformer, freeing more DoFs for WNG. Simulations and microphone array experiment results show that the HDZ beamformer outperforms the competing beamformers in terms of array output power and WNG.