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Vitamin D3 transporter (DBP) is a multifunctional protein. Site-specific deglycosylation results in its conversion to group-specific component protein-derived macrophage activating factor (GcMAF), which is capable of activating macrophages. It has been shown that depending on precursor conversion conditions, the resulting GcMAF activates mouse peritoneal macrophages towards synthesis of either pro- (IL-1β, TNF-α—M1 phenotype) or anti-inflammatory (TGF-β, IL-10—M2 phenotype) cytokines. The condition for the transition of the direction of the inflammatory response of macrophages when exposed to GcMAF is the initial glycosylated state of the population of DBP molecules and the associated effective deglycosylation of DBP by β-galactosidase. In vivo experiments with GcMAF exhibiting anti-inflammatory properties on models of induced arthritis in mice and cystitis in rats indicate a significant anti-inflammatory effect of the macrophage activator. The feasibility of unidirectional induction of anti-inflammatory properties of macrophages allows creation of combined therapeutic platforms where M2 macrophages are among the key therapeutic components.

Background. Small cell lung cancer (SCLC), predominantly due to smoking, is a highly differentiated, rapidly growing epithelial cell carcinoma of high malignancy originating from bronchial neuroendocrine cells. Almost 70% of SCLC patients have metastases at the time of diagnosis, which requires the use of drug therapies, including immunotherapy. Aim. To evaluate the efficacy and safety of immune checkpoint inhibitors in patients with small cell lung cancer. Materials and methods. One hundred and twenty one patients (90 men and 31 women) aged 44 to 84 years were included in the retrospective multicentre non-randomised study. The majority (90.9%) of patients were treated in the 1st line of therapy. IT were administered in the 2nd line and subsequent lines of treatment in 9.1% of patients. Weakened (ECOG 2–3) state at the time of treatment initiation was noted in 30 (24.8%) patients. Results. Progression-free survival in patients with SCLC receiving 1st-line treatment was 5.82 (95% CI 3.92–7.72) months, and 2nd-line and beyond was 6.21 (95% CI 0.76–11.66) months. Survival in patients with small-cell lung cancer receiving 1st-line IT was 8.0 (95% CI 6.18–9.81) months, and 2nd-line or longer was 11.3 months (95% CI 4.31–18.29) months (p=0.108). Objective response was achieved in 43 (35.5%) patients, of whom 38 (34.5%) were on first-line IT and 5 (45.5%) patients were on 2nd or more. iAEs grade 3–4 was observed in only 18 (14.9%) patients. Conclusion. Immunotherapy for SCLC allows achieving high rates of objective response and disease control. This method of treatment is characterized by insignificant number of grade 3–4 immune-mediated adverse events, which indicates an acceptable safety profile.

Abstract Despite widespread engagement in contemplative religious practices, comparatively little research has been conducted on their potential effects on well-being. Furthermore, few studies have focused on how an explicitly religious framing may impact the outcomes of such practices. In this online randomized controlled trial (N = 702), we tested the well-being effects of a contemplative prayer practice called Centering Prayer on self-identifying Christians. We compared 1) presenting the practice with an explicitly religious framing (experimental condition), 2) presenting the practice without an explicitly religious framing (active control), and 3) presenting simple instructions to reflect on the day, without any instructions regarding a meditation-like practice (passive control). After randomization into one of these three conditions, participants were asked to complete their assigned practice daily for 28 days. We hypothesized that the religious framing version of the practice would increase well-being over the active and passive control conditions. Well-being was assessed at three follow-up time points: one day, one week, and one month after the practice period. We found no group differences between the conditions on our primary outcome measure of well-being at one-week post-intervention. Each group increased in well-being from baseline to follow-up. We found significant group differences on acute measures of spiritual experience, the Mystical Experience Questionnaire (MEQ-30) and Daily Spiritual Experience Questionnaire (DSES). These results suggest that a religious framing may not enhance well-being effects but may alter spiritual outcomes related to contemplative practices.

The heterogeneity of the physical environment determines the cost of transport for animals, shaping their energy landscape. Animals respond to this energy landscape by adjusting their distribution and movement to maximize gains and reduce costs. Much of our knowledge about energy landscape dynamics focuses on factors external to the animal, particularly the spatio-temporal variations of the environment. However, an animal’s internal state can significantly impact its ability to perceive and utilize available energy, creating a distinction between the ‘fundamental’ and the ‘realized’ energy landscapes. Here, we show that the realized energy landscape varies along the ontogenetic axis. Locomotor and cognitive capabilities of individuals change over time, especially during the early life stages. We investigate the development of the realized energy landscape in the Central European Alpine population of the golden eagle Aquila chrysaetos, a large predator that requires negotiating the atmospheric environment to achieve energy-efficient soaring flight. We quantified weekly energy landscapes using environmental features for 55 juvenile golden eagles, demonstrating that energetic costs of traversing the landscape decreased with age. Consequently, the potentially flyable area within the Alpine region increased 2170-fold during their first three years of independence. Our work contributes to a predictive understanding of animal movement by presenting ontogeny as a mechanism shaping the realized energy landscape.

Abstract Background To translate and culturally adapt the Children’s Sleep Habits Questionnaire (CSHQ) to a Swedish version, CSHQ-SWE, and to assess its validity and reliability for use with children with attention deficit hyperactivity disorder (ADHD). Methods A total of 84 children with ADHD (51 boys and 33 girls; 6–12 years) and parents (7 men and 77 women; 28–51 years) were included in the study. CSHQ was translated and culturally adapted to Swedish, and assessed for concurrent validity with sleep actigraphy (analyzed by Kendall’s Tau) and for reliability by internal consistency (analyzed by McDonald’s Omega H). Face and content validity was evaluated by parents (n = 4) and healthcare professionals (n = 6) qualitatively (comprehensiveness, relevance, and comprehensibility assessed by interviews and analyzed by thematic analysis) and quantitatively (analyzed by content validity ratio and content validity index for 33 items and four non-scored inquiries). Results Parent-reported sleep problems (CSHQ-SWE total score) were moderately correlated with less “Sleep Efficiency” (Tau = −0.305; p 0.700). Comprehensiveness, relevance, and comprehensibility of CSHQ-SWE were satisfactory overall. Content validity ratio was 0.80 to 1.00 for six items, 0.00 to 0.60 for 22 items, and

Abstract Background The purinergic P2X7 receptor (P2X7R) plays an important role in the crosstalk between pancreatic stellate cells (PSCs) and cancer cells, thus promoting progression of pancreatic ductal adenocarcinoma (PDAC). Single nucleotide polymorphisms (SNPs) in the P2X7R have been reported for several cancers, but have not been explored in PDAC. Materials and methods Blood samples from PDAC patients and controls were genotyped for 11 non-synonymous SNPs in P2X7R and a risk analysis was performed. Relevant P2X7R-SNP GFP variants were expressed in PSCs and cancer cells and their function was assayed in the following tests. Responses in Ca2+ were studied with Fura-2 and dye uptake with YO-PRO-1. Cell migration was monitored by fluorescence microscopy. Released cytokines were measured with MSD assay. Results Risk analysis showed that two SNPs 474G>A and 853G>A (rs28360447, rs7958316), that lead to the Gly150Arg and Arg276His variants, had a significant but opposite risk association with PDAC development, protecting against and predisposing to the disease, respectively. In vitro experiments performed on cancer cells and PSCs expressing the Gly150Arg variant showed reduced intracellular Ca2+ response, fluorescent dye uptake, and cell migration, while the Arg276His variant reduced dye uptake but displayed WT-like Ca2+ responses. As predicted, P2X7R was involved in cytokine release (IL-6, IL-1β, IL-8, TNF-α), but the P2X7R inhibitors displayed varied effects. Conclusion In conclusion, we provide evidence for the P2X7R SNPs association with PDAC and propose that they could be considered as potential biomarkers.

Clinical observations of three patients aged 26, 43 and 37 years with severe psoriasis and psoriatic arthritis are presented. Clinical examples show the experience of effective treatment of patients with psoriasis and psoriatic arthritis using anti-cytokine therapy with an interleukin-17 inhibitor, initiated when the disease progresses. The clinical picture of the presented observations was characterized by an aggressive course of the skin and articular process, torpidity to basic therapy, despite the young age of the patients. It has been shown that the early termination of the progression of the inflammatory process in psoriasis with the use of genetically engineered biological therapy with secukinumab leads to a decrease in symptoms, both on the part of the skin and manifestations of the disease on the part of the musculoskeletal system. The high efficacy and safety of the drug allow complete control of the disease and improve the quality of life in patients suffering from severe forms of dermatosis.

ABSTRACT The limited temporal completeness and taxonomic accuracy of species lists, made available in a traditional manner in scientific publications, has always represented a problem. These lists are invariably limited to a few taxonomic groups and do not represent up-to-date knowledge of all species and classifications. In this context, the Brazilian megadiverse fauna is no exception, and the Catálogo Taxonômico da Fauna do Brasil (CTFB) (http://fauna.jbrj.gov.br/), made public in 2015, represents a database on biodiversity anchored on a list of valid and expertly recognized scientific names of animals in Brazil. The CTFB is updated in near real time by a team of more than 800 specialists. By January 1, 2024, the CTFB compiled 133,691 nominal species, with 125,138 that were considered valid. Most of the valid species were arthropods (82.3%, with more than 102,000 species) and chordates (7.69%, with over 11,000 species). These taxa were followed by a cluster composed of Mollusca (3,567 species), Platyhelminthes (2,292 species), Annelida (1,833 species), and Nematoda (1,447 species). All remaining groups had less than 1,000 species reported in Brazil, with Cnidaria (831 species), Porifera (628 species), Rotifera (606 species), and Bryozoa (520 species) representing those with more than 500 species. Analysis of the CTFB database can facilitate and direct efforts towards the discovery of new species in Brazil, but it is also fundamental in providing the best available list of valid nominal species to users, including those in science, health, conservation efforts, and any initiative involving animals. The importance of the CTFB is evidenced by the elevated number of citations in the scientific literature in diverse areas of biology, law, anthropology, education, forensic science, and veterinary science, among others.

African golden-spotted lappet moths from the genera Haplopacha Aurivillius, 1905 and Dasychirinula Hering, 1926 are reviewed. Antennae, heads and legs are investigated in addition to the traditional comparison of habitus, genitalia, and distribution areas. Two new genera are established and four new species are described as a result: Eudoumbia gen. n. with the type-species Eudoumbia thorogood sp. n. from Angola, Namibia, and Botswana; Auripluvia gen. n. with the type species Auripluvia sophia sp. n. from Ethiopia; Haplopacha mason sp. n. from Tanzania; and Dasychirinula julia sp. n. from Ethiopia. One species is reattributed to the new genus as Eudoumbia ndoumoi (Dupont, Simonsen & Zilli, 2016) stat. n. One new synonymy is established for two Tanzanian species: Dasychirinula chrysogramma Hering, 1926 = Haplopacha lunata Dupont, Simonsen & Zilli, 2016 syn. n.; and one potential synonymy is remarked between Haplopacha tangani Dupont, Simonsen & Zilli, 2016 from Tanzania and Malawi and Haplopacha riftensis Dupont, Simonsen & Zilli, 2016 from Malawi. Photos of the related material stored in the main collections of Ditsong National Museum of Natural History (Pretoria, RSA) and Natural History Museum of Zimbabwe (Bulawayo, Zimbabwe) are showed.

Abstract Purpose The aim of the present study is to define the minimal clinically important difference (MCID) for International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS) for patients undergoing tibial tubercle osteotomy (TTO) for either (1) patellofemoral pain or (2) patellar instability. Methods Patients undergoing TTO for either patellofemoral pain or patellar instability by one of two sports medicine fellowship‐trained surgeons at a single institution between September 2014 and May 2023 were included in the study. IKDC and KOOS scores were collected preoperatively and minimum 1 year postoperatively. Distribution‐based methods were used to calculate the MCID. Results Seventy‐seven patients (82 knees) were included, with a median age of 29.3 years (interquartile range [IQR]: 22.2−36.3 years) and a median BMI of 24.5 kg/m2 [IQR: 22.3−28.3 kg/m2]. Fifty‐seven patients (74%) were female, and there were 40 right knees (49%). The median time to IKDC and KOOS score was 1.8 and 1.7 years, respectively. Forty‐five patients (46 knees) underwent TTO for patellofemoral instability, and 32 patients (36 knees) underwent TTO for patellofemoral pain. The MCID was 11.5 for IKDC, 10.2 for KOOS pain, 10.1 for KOOS symptoms, 9.9 for KOOS ADL, 14.2 for KOOS sport and 14.2 for KOOS QoL for patients undergoing TTO for patellofemoral pain. The MCID was 11.2 for IKDC, 10.1 for KOOS pain, 10.6 for KOOS symptoms, 10.2 for KOOS ADL, 16.0 for KOOS sport and 13.2 for KOOS QoL for patients undergoing TTO for patellar instability. Conclusion We define the MCIDs for commonly used patient‐reported outcome measures for patients undergoing TTO for either patellofemoral pain or patellar instability. Level of Evidence Level II.

Background: Chronic mental illnesses such as schizophrenia affect patients’ functioning, making caregiving necessary although burdensome. Aim: This study aimed to determine caregiver burden and its sociodemographic determinants in family caregivers of patients with schizophrenia attending a Psychiatric Outpatient Department (POD). Setting: Tertiary hospital in Northern Pretoria, South Africa. Methods: In this cross-sectional study conducted over 3 months, 300 consecutive family caregivers who attended the POD were administered a 22-item Zarit Burden Interview (ZBI-22), which has a score of 0–88, with higher values indicating more burden. Their sociodemographic characteristics were ascertained. Linear and ordinal logistic regression analyses were performed to identify determinants or predictors of total and severe burdens, respectively. Results: Most caregivers were aged 46.0 ± 14 years, females (62%), parents (39%), of low-income status (93.7%), had secondary education (70%), resided with the patient (87%), and helped with all troublesome activities (95.3%). The median ZBI-22 score was 19.0 (interquartile range: 13.0–30.5). The determinants of both total and severe burdens were: caregiver age ≥ 50 years adjusted odds ratio (aOR): 2.55, confidence interval (CI): 1.49–4.36; residential area farther away from the hospital aOR: 1.76, CI: 1.3–2.99; increasing months of caregiving aOR: 1.0, CI: 1.001–1.009, p = 0.006; and not having another family member that needs care aOR: 0.43, CI: 0.24–0.78. Conclusion: Having mental healthcare facilities close to residential areas and assisting caregivers aged ≥ 50 years who have multiple family members who need care may alleviate the burden. Contribution: Predicting total and severe caregiver burdens contemporaneously is effective for identifying potential burden interventions.

Aim. To study overall drug resistance genes (resistome) in the human gut microbiome and the changes in these genes during COVID-19 in-hospital therapy. Materials and methods. A single-center retrospective cohort study was conducted. Only cases with laboratory-confirmed SARS-CoV-2 RNA using polymerase chain reaction in oro-/nasopharyngeal swab samples were subject to analysis. The patients with a documented history of or current comorbidities of the hepatobiliary system, malignant neoplasms of any localization, systemic and autoimmune diseases, as well as pregnant women were excluded. Feces were collected from all study subjects for subsequent metagenomic sequencing. The final cohort was divided into two groups depending on the disease severity: mild (group 1) and severe (group 2). Within group 2, five subgroups were formed, depending on the use of antibacterial drugs (ABD): group 2A (receiving ABD), group 2AC (receiving ABD before hospitalization), group 2AD (receiving ABD during hospitalization), group 2AE (receiving ABD during and before hospitalization), group 2B (not receiving ABD). Results. The median number of antibiotic resistance (ABR) genes (cumulative at all time points) was significantly higher in the group of patients treated with ABD: 81.0 (95% CI 73.8–84.5) vs. 51.0 (95% CI 31.1–68.4). In the group of patients treated with ABD (2A), the average number of multidrug resistance genes (efflux systems) was significantly higher than in controls (group 2B): 47.0 (95% CI 46.0–51.2) vs. 21.5 (95% CI 7.0–43.9). Patients with severe coronavirus infection tended to have a higher median number of ABR genes but without statistical significance. Patients in the severe COVID-19 group who did not receive ABD before and during hospitalization also had more resistance genes than the patients in the comparison group. Conclusion. This study demonstrated that fewer ABR genes were identified in the group with a milder disease than in the group with a more severe disease associated with more ABR genes, with the following five being the most common: SULI, MSRC, ACRE, EFMA, SAT.

We describe the pathology of natural infection with highly pathogenic avian influenza A(H5N1) virus of Eurasian lineage Goose/Guangdong clade 2.3.4.4b in 67 wild terrestrial mammals throughout the United States during April 1‒July 21, 2022. Affected mammals include 50 red foxes (Vulpes vulpes), 6 striped skunks (Mephitis mephitis), 4 raccoons (Procyon lotor), 2 bobcats (Lynx rufus), 2 Virginia opossums (Didelphis virginiana), 1 coyote (Canis latrans), 1 fisher (Pekania pennanti), and 1 gray fox (Urocyon cinereoargenteus). Infected mammals showed primarily neurologic signs. Necrotizing meningoencephalitis, interstitial pneumonia, and myocardial necrosis were the most common lesions; however, species variations in lesion distribution were observed. Genotype analysis of sequences from 48 animals indicates that these cases represent spillover infections from wild birds.

IntroductionWe conducted mental model interviews in Aotearoa NZ to understand perspectives of uncertainty associated with natural hazards science. Such science contains many layers of interacting uncertainties, and varied understandings about what these are and where they come from creates communication challenges, impacting the trust in, and use of, science. To improve effective communication, it is thus crucial to understand the many diverse perspectives of scientific uncertainty.MethodsParticipants included hazard scientists (n = 11, e.g., geophysical, social, and other sciences), professionals with some scientific training (n = 10, e.g., planners, policy analysts, emergency managers), and lay public participants with no advanced training in science (n = 10, e.g., journalism, history, administration, art, or other domains). We present a comparative analysis of the mental model maps produced by participants, considering individuals’ levels of training and expertise in, and experience of, science.ResultsA qualitative comparison identified increasing map organization with science literacy, suggesting greater science training in, experience with, or expertise in, science results in a more organized and structured mental model of uncertainty. There were also language differences, with lay public participants focused more on perceptions of control and safety, while scientists focused on formal models of risk and likelihood.DiscussionThese findings are presented to enhance hazard, risk, and science communication. It is important to also identify ways to understand the tacit knowledge individuals already hold which may influence their interpretation of a message. The interview methodology we present here could also be adapted to understand different perspectives in participatory and co-development research.

Background: As the use of all-suture anchors continues to increase, limited biomechanical data on the use of these anchors in various configurations for tenodesis of the long head biceps tendon (LHBT) exists. The aim of this study was to compare the biomechanical properties of a 2-anchor luggage tag suprapectoral biceps tenodesis (Sup-BT) vs. a single-anchor whipstitch subpectoral biceps tenodesis (Sub-BT) using all-suture anchors. The hypothesis was that the Sub-BT will have a higher ultimate load to failure and less creep relative to the Sup-BT construct. Methods: Eighteen fresh frozen cadaveric humeri were used. The specimens were randomly divided into 2 groups of 9; i) The Sup-BT were performed with 2 1.8 mm knotless all-suture anchors using a luggage-tag fixation configuration, ii) The Sub-BT were performed using a single 1.9 mm all-suture anchor and a whipstitch suture configuration with a tied knot. The humeri were tested on a hydraulic MTS machine where the specimens were preloaded at 5 N for 2 minutes and then cyclically loaded from 5 to 50 N for 1000 cycles at 1 Hz while maximum displacement was recorded with a motion system and markers attached to the bone and bicep tendon. The tendon was then tensioned at a rate of 1 mm/s to obtain the ultimate load to failure. CT scans of the specimens were used to calculate the bone mineral density at the site of the anchor/bone interface and video recordings were captured during load to failure to document all modes of failure. Results: There was no significant difference in the average load to failure of the Sup-BT and Sub-BT groups (197 N ± 45 N (SD), 164 N ± 68 N (SD) respectively; P = .122) or creep under fatigue between the Sup-BT vs. Sub-BT specimens (3.1 mm, SD = 1.5 vs. 2.2 mm, SD = 0.9; P = .162). The bone mineral density was statistically different between the 2 groups (P

Abstract Background Collagens are the major components of the extracellular matrix (ECM) and are known to contribute to tumor progression and metastasis. There are 28 different types of collagens each with unique functions in maintaining tissue structure and function. Type XVII collagen (BP180) is a type II transmembrane protein that provides stable adhesion between epithelial cells and the underlying basement membrane. Aberrant expression and ectodomain shedding of type XVII collagen have been associated with epithelial damage, tumor invasiveness, and metastasis in multiple tumor types and may consequently be used as a potential (non-invasive) biomarker in cancer and treatment target. Method An ELISA targeting the type XVII collagen ectodomain (PRO-C17) was developed for use in serum. PRO-C17 was measured in a cohort of patients with 11 different cancer types (n = 214) and compared to healthy controls (n = 23) (cohort 1). Based on the findings from cohort 1, PRO-C17 and its association with survival was explored in patients with metastatic colorectal cancer (mCRC) treated with bevacizumab in combination with chemotherapy (n = 212) (cohort 2). Results PRO-C17 was robust and specific towards the ectodomain of type XVII collagen. In cohort 1, PRO-C17 levels were elevated (p

Abstract Background Congenital heart defects (CHDs) affect approximately half of individuals with Down syndrome (DS), but the molecular reasons for incomplete penetrance are unknown. Previous studies have largely focused on identifying genetic risk factors associated with CHDs in individuals with DS, but comprehensive studies of the contribution of epigenetic marks are lacking. We aimed to identify and characterize DNA methylation differences from newborn dried blood spots (NDBS) of DS individuals with major CHDs compared to DS individuals without CHDs. Methods We used the Illumina EPIC array and whole-genome bisulfite sequencing (WGBS) to quantitate DNA methylation for 86 NDBS samples from the California Biobank Program: (1) 45 DS-CHD (27 female, 18 male) and (2) 41 DS non-CHD (27 female, 14 male). We analyzed global CpG methylation and identified differentially methylated regions (DMRs) in DS-CHD versus DS non-CHD comparisons (both sex-combined and sex-stratified) corrected for sex, age of blood collection, and cell-type proportions. CHD DMRs were analyzed for enrichment in CpG and genic contexts, chromatin states, and histone modifications by genomic coordinates and for gene ontology enrichment by gene mapping. DMRs were also tested in a replication dataset and compared to methylation levels in DS versus typical development (TD) WGBS NDBS samples. Results We found global CpG hypomethylation in DS-CHD males compared to DS non-CHD males, which was attributable to elevated levels of nucleated red blood cells and not seen in females. At a regional level, we identified 58, 341, and 3938 CHD-associated DMRs in the Sex Combined, Females Only, and Males Only groups, respectively, and used machine learning algorithms to select 19 Males Only loci that could distinguish CHD from non-CHD. DMRs in all comparisons were enriched for gene exons, CpG islands, and bivalent chromatin and mapped to genes enriched for terms related to cardiac and immune functions. Lastly, a greater percentage of CHD-associated DMRs than background regions were differentially methylated in DS versus TD samples. Conclusions A sex-specific signature of DNA methylation was detected in NDBS of DS-CHD compared to DS non-CHD individuals. This supports the hypothesis that epigenetics can reflect the variability of phenotypes in DS, particularly CHDs.

Abstract Downregulation of endothelial Sirtuin1 (Sirt1) in insulin resistant states contributes to vascular dysfunction. Furthermore, Sirt1 deficiency in skeletal myocytes promotes insulin resistance. Here, we show that deletion of endothelial Sirt1, while impairing endothelial function, paradoxically improves skeletal muscle insulin sensitivity. Compared to wild-type mice, male mice lacking endothelial Sirt1 (E-Sirt1-KO) preferentially utilize glucose over fat, and have higher insulin sensitivity, glucose uptake, and Akt signaling in fast-twitch skeletal muscle. Enhanced insulin sensitivity of E-Sirt1-KO mice is transferrable to wild-type mice via the systemic circulation. Endothelial Sirt1 deficiency, by inhibiting autophagy and activating nuclear factor-kappa B signaling, augments expression and secretion of thymosin beta-4 (Tβ4) that promotes insulin signaling in skeletal myotubes. Thus, unlike in skeletal myocytes, Sirt1 deficiency in the endothelium promotes glucose homeostasis by stimulating skeletal muscle insulin sensitivity through a blood-borne mechanism, and augmented secretion of Tβ4 by Sirt1-deficient endothelial cells boosts insulin signaling in skeletal muscle cells.

A new phlebovirus variant was isolated from an acute febrile patient in Chanchamayo, Peru. Genome characterization and p-distance analyses based on complete open reading frames revealed that the virus is probably a natural reassortant of the Echarate virus (large and small segments) with a yet-unidentified phlebovirus (M segment).

The American white ibis (Eudocimus albus), a common bird species in Florida, has become increasingly urban, with many populations relying heavily on urban and suburban habitats, which may alter parasite transmission. Parasites of ibis, especially haemosporidians, are understudied. Avian haemosporidia can have a wide range of impacts on birds, including decreased reproductive success or increased mortality. Because southern Florida is subtropical and has a high diversity of potential vectors for haemosporidia, we hypothesized that there will be a high prevalence and genetic diversity of haemosporidia in white ibis. A total of 636 ibis from South Florida were sampled from 2010 to 2022, and blood samples were tested for haemosporidia by examination of Giemsa-stained thin blood smears and/or nested PCRs targeting the cytochrome b gene. A total of 400 (62.9%, 95% CI 59–66.7%) ibis were positive for parasites that were morphologically identified as Haemoproteus plataleae. Sequences of 302 positives revealed a single haplotype of Haemoproteus (EUDRUB01), which was previously reported from white ibis in South Florida and captive scarlet ibis (E. ruber) in Brazil. No Plasmodium or Leucocytozoon infections were detected. Parasitemias of the 400 positive birds were very low (average 0.084%, range 0.001%-2.16% [although only 2 birds had parasitemias >1%]). Prevalence and parasitemias were similar for males and females (68% vs. 61.6% and 0.081% vs. 0.071%, respectively). Prevalence in juveniles was lower compared with adults (52% vs. 67.4%) but parasitemias were higher in juveniles (0.117% vs. 0.065%). This data shows that H. plataleae is common in ibis in South Florida. Although parasitemias were generally low, additional research is needed to determine if this parasite has subclinical effects on ibis, if additional haplotypes or parasite species infect ibis in other regions of their range, or if H. plataleae is pathogenic for other sympatric avian species.

Abstract Fatty acid isomers are responsible for an under-reported lipidome diversity across all kingdoms of life. Isomers of unsaturated fatty acids are often masked in contemporary analysis by incomplete separation and the absence of sufficiently diagnostic methods for structure elucidation. Here, we introduce a comprehensive workflow, to discover unsaturated fatty acids through coupling liquid chromatography and mass spectrometry with gas-phase ozonolysis of double bonds. The workflow encompasses semi-automated data analysis and enables de novo identification in complex media including human plasma, cancer cell lines and vernix caseosa. The targeted analysis including ozonolysis enables structural assignment over a dynamic range of five orders of magnitude, even in instances of incomplete chromatographic separation. Thereby we expand the number of identified plasma fatty acids two-fold, including non-methylene-interrupted fatty acids. Detection, without prior knowledge, allows discovery of non-canonical double bond positions. Changes in relative isomer abundances reflect underlying perturbations in lipid metabolism.

Extractive text summarization selects asmall subset of sentences from a document, which gives good “coverage” of a document. When given a set of term weights indicating the importance of the terms, the concept of coverage may be formalized into a combinatorial optimization problem known as the budgeted maximum coverage problem. Extractive methods in this class are known to beamong the best of classic extractive summarization systems. This paper gives a synopsis of thesoftware package occams, which is a multilingual extractive single and multi-document summarization package based on an algorithm giving an optimal approximation to the budgeted maximum coverage problem. The occams package is written in Python and provides an easy-to-use modular interface, allowing it to work in conjunction with popular Python NLP packages, such as nltk, stanza or spacy.

Abstract Background Pain is common in children and its associations with various biopsychosocial factors is complex. Comprehensive pain assessments could contribute to a better understanding of pediatric pain, but these assessments are scarce in literature. The aim of this study was to examine differences in pain prevalence and pain patterns in 10-year-old boys and girls from a Swedish birth cohort and to study associations between pain, health-related quality of life and various lifestyle factors stratified by sex. Methods 866 children (426 boys and 440 girls) and their parents from the “Halland Health and Growth Study” participated in this cross-sectional study. Children were categorized into two pain groups, “infrequent pain” (never–monthly pain) or “frequent pain” (weekly–almost daily pain), based on a pain mannequin. Univariate logistic regression analyses, stratified by sex, were performed to study associations between frequent pain and children’s self-reports of disease and disability and health-related quality of life (Kidscreen-27, five domains), and parents’ reports of their child’s sleep (quality and duration), physical activity time, sedentary time, and participation in organized physical activities. Results The prevalence of frequent pain was 36.5% with no difference between boys and girls (p = 0.442). Boys with a longstanding disease or disability had higher odds of being in the frequent pain group (OR 2.167, 95% CI 1.168–4.020). Higher scores on health-related quality of life in all five domains for girls, and in two domains for boys, was associated with lower odds of being categorized into the frequent pain group. Frequent pain was associated with poor sleep quality (boys OR 2.533, 95% CI 1.243–5.162; girls OR 2.803, 95% CI 1.276–6.158) and more sedentary time (boys weekends OR 1.131, 95% CI 1.022–1.253; girls weekdays OR 1.137, 95% CI 1.032–1.253), but not with physical activity. Conclusions The high prevalence of frequent pain needs to be acknowledged and treated by school health-care services and the healthcare sector in order to prevent pain from influencing health and lifestyle factors negatively in children.

Background: Mycobacterium cosmeticum is an emerging rapidly growing mycobacteria (RGM) species that has been rarely reported to cause human disease. RGM catheter-related bloodstream infections (CRBSI) are often challenging to treat given the need for line removal, variable species-dependent antimicrobial susceptibility, combination antimicrobial treatment, and historically longer courses of antibiotics. Case presentation: We present a case of an immunocompetent pediatric patient with severe hemophilia B and M. cosmeticum CRBSI. While the patient’s hemophilia B precluded a standard line holiday, he successfully cleared his infection with two line exchanges followed by two weeks of antibiotics. Conclusions: RGM, including emerging species M. cosmeticum, may be considered in patients with an indolent presentation of CRBSI. Our case suggests source control with shorter courses of antimicrobials can be successful.

BackgroundChronic neuropsychological sequelae following SARS-CoV-2 infection, including depression, anxiety, fatigue, and general cognitive difficulties, are a major public health concern. Given the potential impact of long-term neuropsychological impairment, it is important to characterize the frequency and predictors of this post-infection phenotype.MethodsThe Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (EPICC) study is a longitudinal study assessing the impact of SARS-CoV-2 infection in U.S. Military Healthcare System (MHS) beneficiaries, i.e. those eligible for care in the MHS including active duty servicemembers, dependents, and retirees. Four broad areas of neuropsychological symptoms were assessed cross-sectionally among subjects 1-6 months post-infection/enrollment, including: depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), fatigue (PROMIS® Fatigue 7a), and cognitive function (PROMIS® Cognitive Function 8a and PROMIS® Cognitive Function abilities 8a). Multivariable Poisson regression models compared participants with and without SARS-CoV-2 infection history on these measures, adjusting for sex, ethnicity, active-duty status, age, and months post-first positive or enrollment of questionnaire completion (MPFP/E); models for fatigue and cognitive function were also adjusted for depression and anxiety scores.ResultsThe study population included 2383 participants who completed all five instruments within six MPFP/E, of whom 687 (28.8%) had at least one positive SARS-CoV-2 test. Compared to those who had never tested positive for SARS-CoV-2, the positive group was more likely to meet instrument-based criteria for depression (15.4% vs 10.3%, pConclusionsParticipants with a history of SARS-CoV-2 infection were up to twice as likely to report cognitive impairment and fatigue as the group without prior SARS-CoV-2 infection. These findings underscore the continued importance of preventing SARS-CoV-2 infection and while time since infection/enrollment was not significant through 6 months of follow-up, this highlights the need for additional research into the long-term impacts of COVID-19 to mitigate and reverse these neuropsychological outcomes.

Abstract Purpose Prognostic factors have been well described for osteosarcoma, but analyses evaluating the further course of long‐term survivors are lacking. We used the large database of the Cooperative Osteosarcoma Study Group (COSS) to perform such an analysis. Patients and Methods The COSS database 1980‐04/2019 was searched for 5‐year survivors of primary high‐grade central osteosarcoma of the extremities or trunk. Identified patients were analyzed for their further survival outcomes, assessing potentially prognostic and predictive factors already evident at initial disease presentation and treatment as well as their disease course during the first 5 years of follow‐up. Results Two thousand and nine former eligible patients were identified (median age at initial diagnosis 15.1 (2.5–63.0) years; male vs. female 1149 (57.2%) vs. 860 (42.8%); extremities vs. trunk 1927 (95.9%) vs. 82 (4.1%); extremity primaries

How can emergency management teams communicate to potentially impacted communities what a major event causing infrastructure outages might mean for them, and what they can do to prepare? In this paper we describe the process of creating a webtool for end users to visualise infrastructure outages that the Wellington region of New Zealand would face following a rupture of the Wellington fault. This webtool creates insight for three key groups: critical infrastructure owners, communities, and the emergency management sector itself. Critical infrastructure entities can use the tool to understand where they might consider infrastructure upgrades to mitigate gaps of delivery following a fault rupture, and to consider their emergency response plans for delivery in an emergency (leading to their consideration of ‘planning emergency levels of service’). Communities can use the tool to understand what infrastructure outages will mean at the household level in an emergency, including the considerable distances that some community members will have to walk to access services such as food and water and prepare for prolonged outages. Finally, with a greater knowledge of the gaps in delivery and of those community members that might need assistance with food and water collection, the emergency management sector can be better prepared. The methodology for creating the webtool is described, along with the insights that the completed webtool provides for emergency planning.

The increasing use of onshore wind energy is leading to an increased deployment of wind turbines in structurally rich habitats such as forests. Forest-affiliated bats, in turn, are at risk of colliding with the rotor blades. Due to the legal protection of bats in Europe, it is imperative to restrict the operation of wind turbines to periods of low bat activity to avoid collisions. However, bats have also been observed to avoid wind turbines over several hundred meters distance, indicating a displacement that cannot solely be explained by modifications to the habitat. This avoidance suggests a displacement of bats by indirect factors related to wind turbine operation, e.g., wake turbulences and noise emissions. Therefore, we investigated whether the activity of forest-affiliated bats is influenced by operation mode (on/off) under variable wind conditions along transects from 80 to 450 m distance to wind turbines. We divided recordings by foraging guild, i.e., either narrow-space (Myotis, Plecotus), edge-space (Pipistrellus, Barbastella), or open-space foraging bats (Nyctalus, Eptesicus, Vespertilio), and analyzed the effects of wind turbine operation and wind speed on the recorded bat guild activity with mixed effects models. The acoustic activity of narrow-space foraging bats decreased by 77% with increasing wind speed when wind turbines were operating, while bat activity remained unaffected by wind speed when turbines were not operating. This was neither observed for open-space foraging bats nor for edge-space foraging bats, and neither wind turbine operation nor wind speed (ranging between 0 – 4 m/s at 10 m height above ground) were found to affect bat activity when considered alone. Wind turbine noise emissions are known to increase with rotor speed and consequently, wind speed, thus presenting a likely explanation for the interactive negative effect of turbine operation and wind speed specifically on noise-sensitive narrow-space foraging bats. To understand potential ecological long-term consequences for bat populations in forest areas with wind turbines and to design effective conservation measures, future research should focus on disentangling the effects of different disturbances related to turbine operation.

Substance use disorders (SUDs) have an enormous impact on public health. With classic psychedelic-assisted therapies showing initial promise in treating multiple SUDs, it is possible that these treatments will become legally available options for patients with SUDs in the future. This article highlights how classic psychedelic-assisted therapies might be integrated into current clinical practice. We first describe contemporary evidence-based treatments for SUDs and highlight how classic psychedelic-assisted therapies might fit within each treatment. We suggest that classic psychedelic-assisted therapies can be integrated into most mainstream evidence-based SUD treatments that are currently used in clinical settings, indicating broad compatibility of classic psychedelics with contemporary SUD treatment paradigms.

ABSTRACT Allogeneic hematopoietic stem-cell transplant (allo-HSCT) is potentially curative for several hematological disorders. Before stem-cell infusion, recipients undergo a conditioning regimen with chemo/radiotherapy and immunosuppressants, requiring the use of antibiotics to treat and prevent infections. This regimen promotes drastic alterations in the recipient’s microbiota, including the oral microbiota, which have been associated with allo-HSCT complications and poor outcomes. However, long-term longitudinal studies on the oral microbiota of allo-HSCT recipients are scarce and disregard the existence of distinct microbiota within the oral cavity. Here, we used 16S rRNA gene sequencing to characterize the longitudinal microbiota dynamics in a prospective cohort of 31 allo-HSCT recipients at three oral sites (gingival crevicular fluid, oral mucosa, and supragingival biofilm). We found declines in bacterial diversity and major shifts in microbiota composition in all oral sites during allo-HSCT, including blooms of potentially pathogenic genera. These blooms in some cases preceded respiratory infections caused by the blooming bacteria. We also noticed that differences in microbiota composition between oral sites were lost during allo-HSCT. Overall, after allo-HSCT, the distinct oral microbiota returned to their preconditioning state, although at variable levels of competence per patient. After stratifying patients based on recovery levels, we found that recoverers of the oral mucosa microbiota composition had earlier reconstitution of normal blood leukocyte counts. Most notably, oral mucosa microbiota recovery was an independent biomarker of better allo-HSCT outcomes. This study highlights the potential clinical impact of the oral microbiota in the allo-HSCT setting and the clinical value of tracking oral microbiota changes during allo-HSCT. IMPORTANCE The oral cavity is the ultimate doorway for microbes entering the human body. We analyzed oral microbiota dynamics in allogeneic hematopoietic stem-cell transplant recipients and showed that microbiota injury and recovery patterns were highly informative on transplant complications and outcomes. Our results highlight the importance of tracking the recipient’s microbiota changes during allogeneic hematopoietic stem-cell transplant to improve our understanding of its biology, safety, and efficacy.

TNF-α is essential for induction and maintenance of inflammatory responses and its dysregulation is associated with susceptibility to various pathogens that infect the central nervous system. Activation of both microglia and astrocytes leads to TNF-α production, which in turn triggers further activation of these cells. Astrocytes have been implicated in the pathophysiology of a wide range of neurodegenerative diseases with either harmful or protective roles, as these cells are capable of secreting several inflammatory factors and also promote synapse elimination and remodeling. These responses are possible because they sense their surroundings via several receptors, including the metabotropic glutamate receptor 5 (mGluR5). Under neuroinflammatory conditions, mGluR5 activation in astrocytes can be neuroprotective or have the opposite effect. In the current study, we investigated the role of mGluR5 in hiPSC-derived astrocytes subjected to pro-inflammatory stimulation by recombinant TNF-α (rTNF-α). Our results show that mGluR5 blockade by CTEP decreases the secreted levels of pro-inflammatory cytokines (IL-6 and IL-8) following short rTNF-α stimulation, although this effect subsides with time. Additionally, CTEP enhances synaptoneurosome phagocytosis by astrocytes in both non-stimulated and rTNF-α-stimulated conditions, indicating that mGluR5 blockade alone is enough to drive synaptic material engulfment. Finally, mGluR5 antagonism as well as rTNF-α stimulation augment the expression of the reactivity marker SERPINA3 and reduces the expression of synaptogenic molecules. Altogether, these data suggest a complex role for mGluR5 in human astrocytes, since its blockade may have beneficial and detrimental effects under inflammatory conditions.

The emergence of ophidiomycosis (or snake fungal disease) in snakes has prompted increased awareness of the potential effects of fungal infections on wild reptile populations. Yet, aside from Ophidiomyces ophidiicola, little is known about other mycoses affecting wild reptiles. The closely related genus Paranannizziopsis has been associated with dermatomycosis in snakes and tuataras in captive collections, and P. australasiensis was recently identified as the cause of skin infections in non-native wild panther chameleons (Furcifer pardalis) in Florida, USA. Here we describe five cases of Paranannizziopsis spp. associated with skin lesions in wild snakes in North America and one additional case from a captive snake from Connecticut, USA. In addition to demonstrating that wild Nearctic snakes can serve as a host for these fungi, we also provide evidence that the genus Paranannizziopsis is widespread in wild snakes, with cases being identified in Louisiana (USA), Minnesota (USA), Virginia (USA), and British Columbia (Canada). Phylogenetic analyses conducted on multiple loci of the fungal strains we isolated identified P. australasiensis in Louisiana and Virginia; the remaining strains from Minnesota and British Columbia did not cluster with any of the described species of Paranannizziopsis, although the strains from British Columbia appear to represent a single lineage. Finally, we designed a pan-Paranannizziopsis real-time PCR assay targeting the internal transcribed spacer region 2. This assay successfully detected DNA of all described species of Paranannizziopsis and the two potentially novel taxa isolated in this study and did not cross-react with closely related fungi or other fungi commonly found on the skin of snakes. The assay was 100% sensitive and specific when screening clinical (skin tissue or skin swab) samples, although full determination of the assay’s performance will require additional follow up due to the small number of clinical samples (n = 14 from 11 snakes) available for testing in our study. Nonetheless, the PCR assay can provide an important tool in further investigating the prevalence, distribution, and host range of Paranannizziopsis spp. and facilitate more rapid diagnosis of Paranannizziopsis spp. infections that are otherwise difficult to differentiate from other dermatomycoses.

Objectives First, to map the prevalence of symptoms of positive mental health, anxiety, depression and sleep difficulties, along with the coexistence of these symptoms, among players in the Swedish Women’s Hockey League (SDHL). Second, to investigate relationships between these mental health symptoms and demographic variables (ie, age, injuries, dual careers), social support and psychological flexibility.Methods Players from nine teams in SDHL (n=182; mean age 22.3±SD 4.8, range 16–35) participated in this cross-sectional study. An online survey, including validated self-assessment questionnaires, conducted data collection. The questionnaires were distributed just before the play-offs started in the 2022–2023 season. Mental health variables were presented as descriptive statistics, and associations were investigated through multivariate binary logistic regression analyses.Results The response rate was 91%. Moderate or severe symptoms were reported among 29.7% for sleep difficulties, 20.9% for anxiety and 18.1% for depression. Nineteen per cent reported comorbidities. Sixty percent reported flourishing mental health. Lower psychological flexibility was associated with lower odds of flourishing mental health and higher odds of symptoms of anxiety, depression and sleep difficulties. Social support was associated with higher odds of flourishing mental health and lower odds of sleep difficulties.Conclusion 6 of every 10 players reported not reaching the ideal state of mental health (ie, flourishing mental health without mental illness). Mental health symptoms were statistically significantly associated with psychological flexibility and social support, suggesting that these factors will be beneficial to consider when preventing mental illness and promoting mental health in this population.

Weight loss interventions seldom include individuals with neurologic disease. The aims of the present study were to: 1) develop and assess the prefeasibility of a 6-month telehealth behavioral weight loss program for people with multiple sclerosis (MS) and obesity and 2) examine changes in weight loss (primary outcome), physical activity, and fruit/vegetable consumption at follow-up. Participants with obesity and MS engaged in a 24-week weight loss program. Participants followed established diet, exercise, and self-monitoring guidelines and attended weekly online group meetings. Median percentage weight loss was 10.54 % (SD = 7.19). Participants who adhered more closely to the self-monitoring guidelines (r = 0.81, p =.02), and who averaged higher weekly active minutes (r = 0.91, p =.002) achieved greater percentage weight loss. Six of the eight pilot participants achieved clinically meaningful weight loss (>5%) after 6-months.

Background. Exocrine pancreatic insufficiency (EPI) is a critical host factor in determining the composition of the gut microbiota. Diseases that cause exocrine insufficiency can affect the gut microbiome, which can potentiate disease progression and complications. To date, the relationship of exocrine insufficiency in various pancreatic (PA) pathologies, in chronic pancreatitis (CP), with dysbiotic changes in the intestinal microbiota (IM) has not been reliably studied. The available data are heterogeneous and contradictory, which determines the need for further research. Aim. To conduct a comparative analysis of the taxonomic composition of the intestinal microbiota in patients with CP of various etiologies, without or with the presence of EPI of varying severity, as well as patients with severe EPI with a history of surgical intervention (SI) on the pancreas. Materials and methods. A total of 85 patients were included in the study. Patients were divided into groups according to the severity of EPI: Group 1 (n=16) patients with CP without EPI; Group 2 (n=11) patients with CP and mild EPI; Group 3 (n=17) patients with severe CP and EPI; Group 4 (n=41) severe EPI in persons with a history of SI on the pancreas. Verification of CP was carried out according to clinical, anamnestic and instrumental data. The degree of EPI was determined by the level of pancreatic elastase-1 (PE-1) feces. Informed consent for the study was obtained for each patient, an anamnesis was collected, physical and laboratory examinations were performed, and a stool sample was obtained. DNA was extracted from each stool sample, the taxonomic composition of BM was determined by sequencing the bacterial 16S rRNA genes, followed by bioinformatic analysis. Results. We followed the changes in the gut microbiota from a group of patients with CP without EPI to a group with severe EPI, in those who underwent SI. At the level of the phylum, the IM of all groups showed the dominance of Firmicutes, with the lowest representation in the severe EPI group, both with SI and CP, and the growth of the Actinobacteria, Verrucomicrobiota and Fusobacteria types. The differential representation of childbirth varied: in patients with severe EPI and CP, compared with mild, statistically significant genera Akkermansia, Ruminococcus gauvreauii group and Holdemanella; compared with CP without exocrine insufficiency, Prevotella, Ruminococcus gauvreauii group, Peptostreptococcus and Blautia dominated. The CP group with mild EPI was dominated by the following genera: Lachnospiraceae_ND 2004 group, Faecalitalea, Fusobacterium, Catenibacterium, Roseburia, Atopobium, Cloacibacillus, Clostridium innococum group, Ruminococcus torques group. All groups showed a low diversity of taxa with a predominance of opportunistic flora, including participants in oncogenesis. Conclusion. The results of the study show that patients with CP of various etiologies and patients with severe EPI who underwent specific intervention on the pancreas have intestinal microbiota dysbiosis, the severity of which is significantly influenced by the degree of EPI.

Abstract Background and methods Inflammation is a hallmark of cancer and its progression. Plasma levels of C‐reactive protein (CRP), interleukin‐6 (IL‐6) and YKL‐40 reflect inflammation, and are elevated in patients with cancer. This study investigated whether plasma CRP, IL‐6 and YKL‐40 had diagnostic value in 753 patients referred with nonspecific signs and symptoms of cancer to a diagnostic outpatient clinic. Results In total, 111 patients were diagnosed with cancer within 3 months and 30 after 3 months. CRP, IL‐6 and YKL‐40 were elevated in 44%, 60% and 45% of the cancer patients, and in 15%, 33% and 25% of the patients without cancer. Elevated levels of all three markers were associated with risk of cancer within 3 months: CRP (odds ratio (OR) 4.41, 95% confidence interval (CI) 2.86–6.81), IL‐6 (OR = 2.89, 1.91–4.37) and YKL‐40 (OR = 2.42, 1.59–3.66). Multivariate explorative analyses showed that increasing values were associated with the risk of getting a cancer diagnosis (continuous scale: CRP (OR = 1.28, 1.12–1.47), carcinoembryonic antigen (CEA) (OR = 1.61, 1.41–1.98), CA19‐9 (OR = 1.15, 1.03–1.29), age (OR = 1.29, 1.02–1.63); dichotomized values: CRP (OR = 2.54, 1.39–4.66), CEA (OR = 4.22, 2.13–8.34), age (OR = 1.42, 1.13–1.80)). CRP had the highest diagnostic value (area under the curve = 0.69). Combined high CRP, IL‐6 and YKL‐40 was associated with short overall survival (HR = 3.8, 95% CI 2.5–5.9, p

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has significantly impacted global healthcare, underscoring the importance of exploring the virus’s effects on infected individuals beyond treatments and vaccines. Notably, recent findings suggest that SARS-CoV-2 can infect the gut, thereby altering the gut microbiota. This study aimed to analyze the gut microbiota composition differences between COVID-19 patients experiencing mild and severe symptoms. We conducted 16S rRNA metagenomic sequencing on fecal samples from 49 mild and 43 severe COVID-19 cases upon hospital admission. Our analysis identified a differential abundance of specific bacterial species associated with the severity of the disease. Severely affected patients showed an association with Enterococcus faecium, Akkermansia muciniphila, and others, while milder cases were linked to Faecalibacterium prausnitzii, Alistipes putredinis, Blautia faecis, and additional species. Furthermore, a network analysis using SPIEC-EASI indicated keystone taxa and highlighted structural differences in bacterial connectivity, with a notable disruption in the severe group. Our study highlights the diverse impacts of SARS-CoV-2 on the gut microbiome among both mild and severe COVID-19 patients, showcasing a spectrum of microbial responses to the virus. Importantly, these findings align, to some extent, with observations from other studies on COVID-19 gut microbiomes, despite variations in methodologies. The findings from this study, based on retrospective data, establish a foundation for future prospective research to confirm the role of the gut microbiome as a predictive biomarker for the severity of COVID-19.

The involvement of the second pair of chlorophylls, termed A-1A and A-1B, in light-induced electron transfer in photosystem I (PSI) is currently debated. Asparagines at PsaA600 and PsaB582 are involved in coordinating the A-1B and A-1A pigments, respectively. Here we have mutated these asparagine residues to methionine in two single mutants and a double mutant in PSI from Synechocystis sp. PCC 6803, which we term NA600M, NB582M, and NA600M/NB582M mutants. (P700+–P700) FTIR difference spectra (DS) at 293 K were obtained for the wild-type and the three mutant PSI samples. The wild-type and mutant FTIR DS differ considerably. This difference indicates that the observed changes in the (P700+–P700) FTIR DS cannot be due to only the PA and PB pigments of P700. Comparison of the wild-type and mutant FTIR DS allows the assignment of different features to both A-1 pigments in the FTIR DS for wild-type PSI and assesses how these features shift upon cation formation and upon mutation. While the exact role the A-1 pigments play in the species we call P700 is unclear, we demonstrate that the vibrational modes of the A-1A and A-1B pigments are modified upon P700+ formation. Previously, we showed that the A-1 pigments contribute to P700 in green algae. In this manuscript, we demonstrate that this is also the case in cyanobacterial PSI. The nature of the mutation-induced changes in algal and cyanobacterial PSI is similar and can be considered within the same framework, suggesting a universality in the nature of P700 in different photosynthetic organisms.

OBJECTIVES/GOALS: to investigate the potential impact of grandparental factors and multigenerational epigenetic inheritance on the development of ASD METHODS/STUDY POPULATION: Our study recruited participants from the CHARGE (Child Autism Risks from Genetics and the Environment) study, including grandparents, parents, and children. A questionnaire was used to gather information about the participants’ exposure to environmental factors. Saliva samples werecollected from 349 participants. Newborn dried blood spotsfrom probands and parents are still being collected from the California New born Registry. DNA was extracted from 349 saliva samples from 85 families and subjected to whole genome bisulfite sequencing (WGBS) to analyze DNA methylation. Sequence alignments and bioinformatic analyses will be performed using R packages called DMRichR and Comethyl. RESULTS/ANTICIPATED RESULTS: Sequence alignments and bioinformatic analyses are ongoing, utilizing DMRichR to identify individual genomic loci associated with ASD in each of the three generations and Comethyl to compare correlation patterns between methylation marks and selected variables, including grand parental exposures. New born blood spot collections of parents and probands are ongoing and will be used to identify potential ASD epigenomic signatures that are tissue and life-stage independent. DISCUSSION/SIGNIFICANCE: This research will provide new insights into the increased prevalence and underlying etiology of ASD that should pave the way for future research in the field. DNA Methylation signatures can help create molecular biomarkers which can be used together with behavioral clinical tests for diagnosis of ASD.

IntroductionThe perception of phonemes is guided by both low-level acoustic cues and high-level linguistic context. However, differentiating between these two types of processing can be challenging. In this study, we explore the utility of pupillometry as a tool to investigate both low- and high-level processing of phonological stimuli, with a particular focus on its ability to capture novelty detection and cognitive processing during speech perception.MethodsPupillometric traces were recorded from a sample of 22 Danish-speaking adults, with self-reported normal hearing, while performing two phonological-contrast perception tasks: a nonword discrimination task, which included minimal-pair combinations specific to the Danish language, and a nonword detection task involving the detection of phonologically modified words within sentences. The study explored the perception of contrasts in both unprocessed speech and degraded speech input, processed with a vocoder.ResultsNo difference in peak pupil dilation was observed when the contrast occurred between two isolated nonwords in the nonword discrimination task. For unprocessed speech, higher peak pupil dilations were measured when phonologically modified words were detected within a sentence compared to sentences without the nonwords. For vocoded speech, higher peak pupil dilation was observed for sentence stimuli, but not for the isolated nonwords, although performance decreased similarly for both tasks.ConclusionOur findings demonstrate the complexity of pupil dynamics in the presence of acoustic and phonological manipulation. Pupil responses seemed to reflect higher-level cognitive and lexical processing related to phonological perception rather than low-level perception of acoustic cues. However, the incorporation of multiple talkers in the stimuli, coupled with the relatively low task complexity, may have affected the pupil dilation.

Summary: Background: Depression is three to four times more prevalent in patients with neurological and inflammatory disorders than in the general population. For example, in patients with multiple sclerosis, the 12-month prevalence of major depressive disorder is around 25% and it is associated with a lower quality of life, faster disease progression, and higher morbidity and mortality. Despite its clinical relevance, there are few treatment options for depression associated with multiple sclerosis and confirmatory trials are scarce. We aimed to evaluate the safety and efficacy of a multiple sclerosis-specific, internet-based cognitive behavioural therapy (iCBT) programme for the treatment of depressive symptoms associated with the disease. Methods: This parallel-group, randomised, controlled, phase 3 trial of an iCBT programme to reduce depressive symptoms in patients with multiple sclerosis was carried out at five academic centres with large outpatient care units in Germany and the USA. Patients with a neurologist-confirmed diagnosis of multiple sclerosis and depressive symptoms were randomly assigned (1:1:1; automated assignment, concealed allocation, no stratification, no blocking) to receive treatment as usual plus one of two versions of the iCBT programme Amiria (stand-alone or therapist-guided) or to a control condition, in which participants received treatment as usual and were offered access to the iCBT programme after 6 months. Masking of participants to group assignment between active treatment and control was not possible, although raters were masked to group assignment. The predefined primary endpoint, which was analysed in the intention-to-treat population, was severity of depressive symptoms as measured by the Beck Depression Inventory-II (BDI-II) at week 12 after randomisation. This trial is registered at ClinicalTrials.gov, NCT02740361, and is complete. Findings: Between May 3, 2017, and Nov 4, 2020, we screened 485 patients for eligibility. 279 participants were enrolled, of whom 101 were allocated to receive stand-alone iCBT, 85 to receive guided iCBT, and 93 to the control condition. The dropout rate at week 12 was 18% (50 participants). Both versions of the iCBT programme significantly reduced depressive symptoms compared with the control group (BDI-II between-group mean differences: control vs stand-alone iCBT 6·32 points [95% CI 3·37–9·27], p

The purpose of this guide is to provide a resource for archery leaders that includes reflection, application and evaluation with the activities. Written by Julia S. Kelly, and published by the Florida 4-H Youth Development Program, UF/IFAS Extension, June 2023.

The 2023 annual meeting of the British Society for Haemostasis and Thrombosis (BSHT) was held in Birmingham, United Kingdom. The theme of this year's meeting was novel therapeutics and emerging technology. Here, the exciting research presented at the meeting is discussed.

The detrimental effects of loneliness and social isolation on health and well-being outcomes are well documented. In response, governments, corporations, and community-based organizations have begun leveraging tools to create interventions and policies aimed at reducing loneliness and social isolation at scale. However, these efforts are frequently hampered by a key knowledge gap: when attempting to improve specific health and well-being outcomes, decision-makers are often unsure whether to target loneliness, social isolation, or both. Filling this knowledge gap will inform the development and refinement of effective interventions. Using data from the Health and Retirement Study (13,752 participants (59% women and 41% men, mean [SD] age = 67 [10] years)), we examined how changes in loneliness and social isolation over a 4-year follow-up period (from t0:2008/2010 to t1:2012/2014) were associated with 32 indicators of physical-, behavioral-, and psychosocial-health outcomes 4-years later (t2:2016/2018). We used multiple logistic-, linear-, and generalized-linear regression models, and adjusted for sociodemographic, personality traits, pre-baseline levels of both exposures (loneliness and social isolation), and all outcomes (t0:2008/2010). We incorporated data from all participants into the overall estimate, regardless of whether their levels of loneliness and social isolation changed from the pre-baseline to baseline waves. After adjusting for a wide range of covariates, we observed that both loneliness and social isolation were associated with several physical health outcomes and health behaviors. However, social isolation was more predictive of mortality risk and loneliness was a stronger predictor of psychological outcomes. Loneliness and social isolation have independent effects on various health and well-being outcomes and thus constitute distinct targets for interventions aimed at improving population health and well-being.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death. Less than 20% of patients are diagnosed with resectable disease. Identifying truly resectable disease is challenging because 20%–40% of the patients subjected to resection are found to have advanced disease during surgery. The aim of our study was to identify panels of circulating proteins that could be used to distinguish patients with unresectable PDAC from patients with resectable PDAC and to identify prognostic signatures for both groups. Methods We measured 92 circulating immuno‐oncology‐related proteins using the proximity extension assay from Olink Proteomics in 273 patients eligible for surgery for PDAC. Two bioinformaticians worked independently of one another on the same data. LASSO and Ridge regression were used in the statistical analyses. Results One protein index for determining resectability had an AUC value of 0.66. Several indices for prognosis had AUC values between 0.50 and 0.75 and were therefore not better than existing prognostic markers. Discussion Our study did not reveal any new high‐performing protein panels that could be used to identify patients with inoperable PDAC before surgery. The panel of 92 proteins investigated has previously been found to be applicable for diagnostic use in patients with PDAC, but it does not seem to warrant further investigation regarding resectability in the subgroup of patients with PDAC referred to surgery.

Abstract The purpose of this study is to present baseline data from a longitudinal study assessing behavioral factors in three groups of boys in Israel with varying myopia prevalence. Ultra-Orthodox (N = 57), religious (N = 67), and secular (N = 44) Jewish boys (age 8.6 ± 1.4 years) underwent cycloplegic autorefraction and axial-length measurement. Time-outdoors and physical-activity were assessed objectively using an Actiwatch. Ocular history, educational factors, and near-work were assessed with a questionnaire. Group effects were tested and mixed effects logistic and linear regression were used to evaluate behaviors and their relationship to myopia. The prevalence of myopia (≤ − 0.50D) varied by group (ultra-Orthodox: 46%, religious: 25%, secular: 20%, P

Abstract Children born with congenital heart disease (CHD) have seen a dramatic decrease in mortality thanks to surgical innovations. However, there are numerous risk factors associated with CHD that can disrupt neurodevelopment. Recent studies have found that psychological deficits and structural brain abnormalities persist into adulthood. The goal of the current study was to investigate white matter connectivity in early school-age children (6–11 years), born with complex cyanotic CHD (single ventricle physiology), who have undergone Fontan palliation, compared to a group of heart-healthy, typically developing controls (TPC). Additionally, we investigated associations between white matter tract connectivity and measures on a comprehensive neuropsychological battery within each group. Our results suggest CHD patients exhibit widespread decreases in white matter connectivity, and the extent of these decreases is related to performance in several cognitive domains. Analysis of network topology showed that hub distribution was more extensive and bilateral in the TPC group. Our results are consistent with previous studies suggesting perinatal ischemia leads to white matter lesions and delayed maturation.

Measurement(s) plant trait Technology Type(s) various Factor Type(s) none Sample Characteristic - Organism Tracheophyta Sample Characteristic - Environment natural environment Sample Characteristic - Location global

Abstract Oral mucositis (OM) is a complex acute cytotoxicity of antineoplastic treatment that affects 40–85% of patients undergoing hematopoietic stem-cell transplantation. OM is associated with prolonged hospitalization, increased extensive pharmacotherapy, need for parenteral nutrition, and elevated treatment costs. As OM onset relates to the mucosal microenvironment status, with a particular role for microbiota-driven inflammation, we aimed to investigate whether the oral mucosa microbiota was associated with the clinical course of OM in patients undergoing allogeneic hematopoietic stem-cell transplantation. We collected oral mucosa samples from 30 patients and analyzed the oral mucosa microbiota by 16S rRNA sequencing. A total of 13 patients (43%) developed ulcerative OM. We observed that specific taxa were associated with oral mucositis grade and time to oral mucositis healing. Porphyromonas relative abundance at preconditioning was positively correlated with ulcerative OM grade (Spearman ρ = 0.61, P = 0.028) and higher Lactobacillus relative abundance at ulcerative OM onset was associated with shortened ulcerative OM duration (P = 0.032). Additionally, we generated a machine-learning-based bacterial signature that uses pre-treatment microbial profiles to predict whether a patient will develop OM during treatment. Our findings suggest that further research should focus on host-microbiome interactions to better prevent and treat OM.

To increase inclusivity, diversity, equity and accessibility in Antarctic science, we must build more positive and inclusive Antarctic field work environments. The International Thwaites Glacier Collaboration (ITGC) has engaged in efforts to contribute to that goal through a variety of activities since 2018, including creating an open-access ‘Field and Ship Best Practices’ guide, engaging in pre-field season team dynamics meetings, and surveying post-field season reflections and experiences. We report specific actions taken by ITGC and their outcomes. We found that strong and supported early career researchers brought new and important perspectives regarding strategies for transforming culture. We discovered that engaged and involved senior leadership was also critical for expanding participation and securing funding to support efforts. Pre-field discussions involving all field team members were particularly helpful for setting expectations, improving sense of belonging, describing field work best practices, and co-creating a positive work culture.