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In a range of settings, human operators make decisions with the assistance of automation, the reliability of which can vary depending upon context. Currently, the processes by which humans track the level of reliability of automation are unclear. In the current study, we test cognitive models of learning that could potentially explain how humans track automation reliability. We fitted several alternative cognitive models to a series of participants' judgements of automation reliability observed in a maritime classification task in which participants were provided with automated advice. We examined three experiments including eight between-subjects conditions and 240 participants in total. Our results favoured a two-kernel delta-rule model of learning, which specifies that humans learn by prediction error, and respond according to a learning rate that is sensitive to environmental volatility. However, we found substantial heterogeneity in learning processes across participants. These outcomes speak to the learning processes underlying how humans estimate automation reliability and thus have implications for practice.

Abstract Background This study demonstrates how formative process evaluation was used to assess implementation and improve dose and fidelity in the Together Everyone Achieves More Physical Activity (TEAM-PA) randomized controlled trial. TEAM-PA uses a randomized group cohort design to evaluate the efficacy of a group-based intervention for increasing physical activity among African American women. Methods Intervention groups met for 10 weeks and were co-led by female African American facilitators, with intervention sessions consisting of group feedback, a health curriculum, group-based physical activity games, and group-based goal-setting. Drawing from a multi-theoretical framework, the intervention targeted social affiliation using collaborative and competitive group strategies, including essential elements focused on group-based behavioral skills, peer-to-peer positive communication, collectivism, optimal challenge, social facilitation, and peer to peer challenges. Formative process evaluation was used to monitor reach, dose, and fidelity, and implement feedback and solutions. Results Across two cohorts, four groups (n = 54) were randomized to the TEAM-PA intervention. On average 84.8% of participants attended each week, which exceeded the a priori criteria. Results from the systematic observations indicated that on average 93% of the dose items were completed in each session and adequate levels of fidelity were achieved at both the facilitator and group-levels. Participants were compliant with wearing the FitBits (6.73 ± 0.42 days/week) and most participants successfully contributed to meeting the group-based goals. The use of open-ended items also revealed the need for additional modifications to the group-based PA games, including allowing for individuals to take breaks, incorporating a broader range of exercises, minimizing activities that required bending/reaching down without assistance, and providing facilitators with additional training for implementing the games. Initial evidence suggests that these changes were successful in increasing participants’ comprehension of the games from Cohort 1 (M = 1.83, SD = 0.71) to Cohort 2 (M = 3.33, SD = 0.69). Conclusion Findings from this study demonstrated high levels of reach, dose, and fidelity, while also highlighting strategies for implementing competitive group-based PA games that are accessible across physical fitness levels. Formative process evaluation, including open-ended items and collaborative brainstorming, holds tremendous potential for improving future interventions. Trial registration This study was registered on Clinicaltrials.gov (# NCT05519696) on August 22, 2022 prior to the enrollment of the first participant on September 12, 2022 ( https://clinicaltrials.gov/study/NCT05519696?term=NCT05519696&rank=1 ).

Erectile dysfunction (ED) poses a significant challenge in clinical practice, necessitating accurate diagnostic strategies to distinguish between organic and psychogenic causes. Current guidelines advocate a comprehensive approach involving medical history, physical examination and blood tests, with second-level analyses like the intracavernous injection of vasoactive drugs (ICI test) and penile duplex ultrasound (PDU) reserved for specific cases. A survey involving 24 urologists experienced in ED was conducted to assess their opinions on the appropriateness of the ICI test and PDU in six clinical scenarios. Results were analyzed using pie charts, revealing varied preferences among experts. The responses indicated diverse viewpoints, with preferences for the ICI test or PDU depending on the patient’s age, comorbidities, response to phosphodiesterase type 5 inhibitors (PDE5i) and concomitant Peyronie’s disease. In some cases, a significant proportion of experts opted for neither test. The study highlights the lack of consensus among experts regarding the routine use of PDU in ED management. Despite its diagnostic capabilities, the clinical utility of PDU remains unclear, and its role may be more justified in certain populations with anatomical abnormalities or specific conditions. The need for rigorous research to determine the impact of PDU on ED management decision-making is emphasized.

ABSTRACT Background Prostate cancer is the second leading cause of cancer deaths in men, second only to lung cancer. Despite this, diagnosis and prognosis methods remain limited, with effective treatments being few and far between. Traditionally, prostate cancer is initially tested for through a prostate serum antigen (PSA) test and a digital rectum examination (DRE), followed by confirmation through an invasive prostate biopsy. The DRE and biopsy are uncomfortable for the patient, so less invasive, accurate diagnostic tools are needed. Current diagnostic tools, along with genes that hold possible biomarker uses in diagnosis, prognosis and indications for personalised treatment plans, were reviewed in this article. Recent Findings Several genes from multiple families have been identified as possible biomarkers for disease, including those from the MYC and ETS families, as well as several tumour suppressor genes, Androgen Receptor signalling genes and DNA repair genes. There have also been advances in diagnostic tools, including MRI‐targeted and liquid biopsies. Several personalised treatments have been developed over the years, including those that target metabolism‐driven prostate cancer or those that target inflammation‐driven cancer. Conclusion Several advances have been made in prostate cancer diagnosis and treatment, but the disease still grows year by year, leading to more and more deaths annually. This calls for even more research into this disease, allowing for better diagnosis and treatment methods and a better chance of patient survival.

In recent years, there has been an increase in the adventive establishment and spread of parasitoid wasps outside of their native range. However, lack of taxonomic tools can hinder the efficient screening of field-collected samples to document the establishment and range expansion of parasitoids on continent-wide geographic scales. Here we report that Leptopilina japonica (Hymenoptera, Figitidae), a parasitoid of the globally invasive fruit pest Drosophila suzukii (Diptera, Drosophilidae), is now widespread in much of North America despite not having been intentionally introduced. Surveys in 2022 using a variety of methods detected L. japonica in 10 of 11 surveyed USA States and one Canadian Province where it was not previously known to occur. In most surveys, L. japonica was the most common species of D. suzukii parasitoid found. The surveys also resulted in the detection of Ganaspis cf. brasiliensis (Hymenoptera, Figitidae), the recently-released biological control agent of D. suzukii, in six USA States where it had not previously been found. These new detections are likely a result of intentional biological control introductions rather than spread of adventive populations. A species-specific multiplex PCR assay was developed as a rapid, accurate and cost-effective method to distinguish L. japonica, G. cf. brasiliensis, the closely-related cosmopolitan parasitoid Leptopilina heterotoma (Hymenoptera, Figitidae) and other native parasitoid species. This dataset and the associated molecular tools will facilitate future studies of the spread and ecological impacts of these introduced parasitoids on multiple continents.

Abstract The cardiovascular system is strongly impacted by the hazards of spaceflight. Astronauts spending steadily increasing lengths of time in microgravity are subject to cardiovascular deconditioning resulting in loss of vascular tone, reduced total blood volume, and diminished cardiac output. Appreciating the mechanisms by which the cells of the vasculature are altered during spaceflight will be integral to understanding and combating these deleterious effects as the human presence in space advances. In this study, we performed RNA-Seq analysis coupled with review by QIAGEN Ingenuity Pathway Analysis software on human aortic smooth muscle cells (HASMCs) cultured for 3 days in microgravity and aboard the International Space Station to assess the transcriptomic changes that occur during spaceflight. The results of our RNA-Seq analysis show that SMCs undergo a wide range of transcriptional alteration while in space, significantly affecting 4422 genes. SMCs largely down-regulate markers of the contractile, synthetic, and osteogenic phenotypes including smooth muscle alpha actin (αSMA), matrix metalloproteinases (MMPs), and bone morphogenic proteins (BMPs). Additionally, components of several cellular signaling pathways were strongly impacted including the STAT3, NFκB, PI3K/AKT, HIF1α, and Endothelin pathways. This study highlights the significant changes in transcriptional behavior SMCs exhibit during spaceflight and puts these changes in context to better understand vascular function in space.

Globally, energy demands are massive, and environmental issues are rising against our sustainability. To maximize the use of renewable energy sources, development of efficient energy storage systems is mandatory. Lithium-ion batteries (LIBs) play an indispensable role in powering portable devices and electric vehicles, due to their high specific capacity and long cycle life. Manganese oxide (Mn3O4) is an environmentally friendly anode active material with high theoretical specific capacity of 936 mAh g−1 for applications in Li-ion cells.In the present work, Mn3O4-functionalized carbon nanotubes (FCNT) nanocomposite, coated on carbon cloth (CC) current collector and termed as Mn3O4-FCNT @CC, is used as the anode material. Li-ion coin cells based on this nanocomposite anode show discharge capacity of 1371mAhg−1 and charge capacity of 1141mAhg−1 at current density of 100 mA g−1 with initial Coulombic efficiency of 83%. After 70 cycles, the charge-discharge capacities of the cells are 953mAhg−1 and 958mAhg−1, respectively, with capacity retention of 91% at current rate of 100 mA g−1. These cells are found to deliver reversible charge capacity of 575mAhg−1 after 100 cycles at 1C (∼1 A g−1) and offer prospects of stable operation at high current rates.

Staphylococcus aureus is an important human and veterinary pathogen. The present study aimed to determine the prevalence of antibiotic resistance among S. aureus isolated from samples obtained from free-flying wild pigeons and houseflies from different locations surrounding a local hospital in the Greater Durban area in KwaZulu-Natal Province, South Africa. Environmental fecal samples were obtained from wild pigeons that inhabits the grounds of a local public hospital located on the South Beach area, Durban, South Africa. Housefly samples were collected from three different locations (Kenneth Stainbank Nature Reserve, Montclair/Clairwood, and Glenwood/Berea) in the greater Durban area, all within a close proximity to the hospital. Following enrichment, identification, and antimicrobial resistance profiling, S. aureus isolates were subjected to DNA extraction using the boiling method. It was found that 57 out of 252 samples (22.62%) were positive for S. aureus. The Kirby-Bauer disk diffusion method of antibiotic susceptibility testing was performed and revealed that antibiotic resistance rates to penicillin and rifampicin were the most common, with both returning 48 (84.2%) out of the 57 S. aureus isolates being resistant to penicillin and rifampicin. Antibiotic resistance rates to clindamycin, linezolid, erythromycin, tetracycline, cefoxitin, and ciprofloxacin were 82.5%, 78.9%, 73.7%, 63.2%, 33.3%, and 15.8% respectively. Antibiotic resistance genes were detected using primer-specific PCR and it was found that the prevalence rates of tetM, aac(6′)–aph(2″), mecA, tetK, ermc, and blaZ genes were 66.7%, 40.4%, 40.4%, 38.6%, 24.6%, and 3.51% respectively. Statistical analysis revealed significant (p

The current study aimed to determine virulence determinants among S. aureus isolated from wild pigeons and houseflies around hospital areas in the Greater Durban area, South Africa. Following enrichment and bacterial growth, DNA extraction using the boiling method was performed. Overall, 57 out of 252 samples (22.6%) were positive for S. aureus. Six known virulence genes were tested, where five known virulence determinants were positive and none of the S. aureus isolates were positive to coagulase (coa) gene. The highest prevalence rates were found in the genes encoding haemolysins, with the hla and hld genes having 8 (14%) and 9 (15.8%) positive isolates respectively. The sea, LukS/F-PV, and spa genes had 5 (8.8%), 4 (7%), and 2 (3.5%) positive isolates respectively. These results demonstrated the detection of pathogenic S. aureus from hospital environment in Durban, South Africa which may account for the emergence staphylococcal infections. The findings of the present study highlights the significant role of wild pigeons and houseflies as potenital infectious disease vectors in a One Health context.

Abstract Background Cancers exhibit complex transcriptomes with aberrant splicing that induces isoform-level differential expression compared to non-diseased tissues. Transcriptomic profiling using short-read sequencing has utility in providing a cost-effective approach for evaluating isoform expression, although short-read assembly displays limitations in the accurate inference of full-length transcripts. Long-read RNA sequencing (Iso-Seq), using the Pacific Biosciences (PacBio) platform, can overcome such limitations by providing full-length isoform sequence resolution which requires no read assembly and represents native expressed transcripts. A constraint of the Iso-Seq protocol is due to fewer reads output per instrument run, which, as an example, can consequently affect the detection of lowly expressed transcripts. To address these deficiencies, we developed a concatenation workflow, PacBio Full-Length Isoform Concatemer Sequencing (PB_FLIC-Seq), designed to increase the number of unique, sequenced PacBio long-reads thereby improving overall detection of unique isoforms. In addition, we anticipate that the increase in read depth will help improve the detection of moderate to low-level expressed isoforms. Results In sequencing a commercial reference (Spike-In RNA Variants; SIRV) with known isoform complexity we demonstrated a 3.4-fold increase in read output per run and improved SIRV recall when using the PB_FLIC-Seq method compared to the same samples processed with the Iso-Seq protocol. We applied this protocol to a translational cancer case, also demonstrating the utility of the PB_FLIC-Seq method for identifying differential full-length isoform expression in a pediatric diffuse midline glioma compared to its adjacent non-malignant tissue. Our data analysis revealed increased expression of extracellular matrix (ECM) genes within the tumor sample, including an isoform of the Secreted Protein Acidic and Cysteine Rich (SPARC) gene that was expressed 11,676-fold higher than in the adjacent non-malignant tissue. Finally, by using the PB_FLIC-Seq method, we detected several cancer-specific novel isoforms. Conclusion This work describes a concatenation-based methodology for increasing the number of sequenced full-length isoform reads on the PacBio platform, yielding improved discovery of expressed isoforms. We applied this workflow to profile the transcriptome of a pediatric diffuse midline glioma and adjacent non-malignant tissue. Our findings of cancer-specific novel isoform expression further highlight the importance of long-read sequencing for characterization of complex tumor transcriptomes.

Background: The dense stroma of pancreatic ductal adenocarcinoma (PDAC) is thought to impede tumour drug delivery. LSTA1, a novel cyclic tumour-penetrating peptide internalising arginylglycylaspartic acid, promotes tumour-specific drug delivery. In the phase Ib setting, LSTA1 3.2 mg/kg with gemcitabine and nab-paclitaxel showed a 92% disease control rate at 16 weeks and was well tolerated. Methods/design: This is a multicentre, phase II, double-blinded, placebo-controlled, randomised trial evaluating the activity and safety of LSTA1 in combination with gemcitabine and nab-paclitaxel in untreated advanced PDAC. Initially, participants were randomised 2 : 1 to receive gemcitabine 1000 mg/m2, nab-paclitaxel 125 mg/m2 and LSTA1 3.2 mg/kg or placebo. The trial design was updated in a protocol amendment (v4.0) to include a second placebo-controlled cohort which receives a second dose of LSTA1/placebo 4 h following chemotherapy. Treatment is administered on days 1, 8, and 15 of each 28-day cycle until progression (progressive disease). The sample size is 155 based on a clinically worthwhile increase in 6-month progression-free survival (PFS) of 16%-63% with 80% power and 95% confidence to exclude the null hypothesis. The recruitment period is 22 months and follow-up 18 months. Study endpoints are: (1) PFS; (2) objective response rate (RECIST 1.1), safety (Common Terminology Criteria for Adverse Events v5.0), overall survival, participant-reported outcomes; (3) predictive/prognostic biomarkers via archival tissue, and to assess whether a second dose of LSTA1 warrants further evaluation.

Due to global population declines, there is a pressing need for data on the life history traits of many elasmobranch species to support the development of species-specific management plans. A lack of information on the reproductive cycle of the Critically Endangered flapper skate Dipturus intermedius was recently identified as a hindrance to its conservation. To address this data gap, we combined non-lethal ultrasound and hormone analysis to investigate the size at maturity and reproductive cycle of the flapper skate in the Loch Sunart to the Sound of Jura Marine Protected Area off the west coast of Scotland. In-field ultrasound imagery revealed encapsulated eggs in utero and was used to determine the presence and size of ovarian follicles. Combining these images with levels of plasma testosterone, progesterone and oestradiol provided valuable insights into the timing of the reproductive cycle and maturity state of the flapper skate. This preliminary study suggests that male skate start to mature at 165 cm and females at 203 cm total length. Oestradiol appears to be the primary hormone controlling the female reproductive cycle and, along with ultrasound images, indicates that females lay pairs of eggs throughout a winter egg-laying season. Our study further highlights how non-lethal methods can be used to investigate the life history of oviparous elasmobranchs in the field. This information will support the identification of important life history groups and their associated habitats and contribute to the development of management strategies for these species.

Abstract Sustainably managing fisheries requires regular and reliable evaluation of stock status. However, most multispecies reef fisheries around the globe tend to lack research and monitoring capacity, preventing the estimation of sustainable reference points against which stocks can be assessed. Here, combining fish biomass data for >2000 coral reefs, we estimate site-specific sustainable reference points for coral reef fisheries and use these and available catch estimates to assess the status of global coral reef fish stocks. We reveal that >50% of sites and jurisdictions with available information have stocks of conservation concern, having failed at least one fisheries sustainability benchmark. We quantify the trade-offs between biodiversity, fish length, and ecosystem functions relative to key benchmarks and highlight the ecological benefits of increasing sustainability. Our approach yields multispecies sustainable reference points for coral reef fisheries using environmental conditions, a promising means for enhancing the sustainability of the world’s coral reef fisheries.

The generation and evolution of entanglement in many-body systems is an active area of research that spans multiple fields, from quantum information science to the simulation of quantum many-body systems encountered in condensed matter, subatomic physics, and quantum chemistry. Motivated by recent experiments exploring quantum information processing systems with electrons trapped above the surface of cryogenic noble gas substrates, we theoretically investigate the generation of motional entanglement between two electrons via their unscreened Coulomb interaction. The model system consists of two electrons confined in separate electrostatic traps that establish microwave-frequency quantized states of their motion. We compute the motional energy spectra of the electrons, as well as their entanglement, by diagonalizing the model Hamiltonian with respect to a single-particle Hartree product basis. We also compare our results with the predictions of an effective Hamiltonian. The computational procedure outlined here can be employed for device design and guidance of experimental implementations. In particular, the theoretical tools developed here can be used for fine-tuning and optimization of control parameters in future experiments with electrons trapped above the surface of superfluid helium or solid neon.

Abstract Background In this article, I utilize the concept of the Plantationocene as an analytical framework to generate a holistic and historical understanding of the present-day struggles of a mostly Haitian migrant workforce on sugar plantations in the Dominican Republic. Methods Inspired by Paul Farmer’s methodology, I combine political economy, history, and ethnography approaches to interpret the experiences of sugarcane cutters across historical and contemporary iterations of colonial, post-colonial, and neo-colonial practices over the course of five centuries. Results My findings elucidate the enduring power of capitalism, implicating corporate and state elites, as the structural scaffolding for acts of racialized violence that condition the life-and-death circumstances of Black laborers on Caribbean plantations to this day. Although today’s sugarcane cutters may suffer differently than their enslaved or wage labor ancestors on the plantation, I argue that an unfettered racialized pattern of lethal exploitation is sustained through the structural violence of neoliberalism that links present conditions with the colonial past. Conclusions Ultimately, this paper contributes understandings of the plantationocene’s enduring effects in the global south by demonstrating how imperialist arrangements of capitalism are not a distant memory from the colonial past but instead are present yet hidden and obscured while relocated and reanimated overseas to countries like the Dominican Republic, where American capitalists still exploit Black bodies for profit and power.

Abstract Background The complex systemic responses of tree species to fight pathogen infection necessitate attention due to the potential for yield protection in forestry. Results In this paper, both the localized and systemic responses of model plants, such as Arabidopsis and tobacco, are reviewed. These responses were compared to information available that investigates similar responses in woody plant species and their key differences were highlighted. In addition, tree-specific responses that have been documented were summarised, with the critical responses still relying on certain systemic acquired resistance pathways. Importantly, coniferous species have been shown to utilise phenolic compounds in their immune responses. Here we also highlight the lack of focus on systemic induced susceptibility in trees, which can be important to forest health. Conclusions This review highlights the possible mechanisms of systemic response to infection in woody plant species, their potential applications, and where research may be best focused in future.

Knowledge of the distribution and abundance of resident parasitoid species of Drosophila flies constitutes an important base for developing and implementing a biological control program for Drosophila suzukii (Matsumura) (Diptera: Drosophilidae), an invasive pest that attacks ripening thin-skinned wild and cultivated berries and stone fruits. For this purpose, a field survey was conducted to identify the parasitoid community associated with D. suzukii infested sites in tart cherry orchards and woodlots in west, northwest, and central Michigan. Sentinel traps baited with D. suzukii larvae and pupae in banana slices were deployed in the center of tart cherry orchards, in woodlots adjacent to tart cherry orchards, and in woodlots isolated from any known commercial host of D. suzukii. Traps were placed from the beginning of July to the end of October 2021. Three parasitoid species that are known to use drosophilids as hosts were recovered from these traps. Pachycrepoideus vindemiae (Rondani) (Hymenoptera: Pteromalidae) and Leptopilina boulardi Barbotin, Carton & Keiner-Pillault (Hymenoptera: Figitidae) emerged from the infested bananas. Leptopilina heterotoma (Thomson) was collected as an adult in a sentinel trap. Among these wasps, only P. vindemiae successfully parasitized D. suzukii pupae in the laboratory. This pupal parasitoid was abundant and widely distributed in both cherry orchards and woodlots. The highest number of P. vindemiae was collected from orchards, followed by woodlots adjacent to orchards, with woodlots without nearby cultivated fruit having the lowest detections. These findings suggest that future release of augmentative or classical biological control agents for D. suzukii could be successful in orchards post-harvest to control late-season populations of this pest.

Background. Healthline is one of the 39 free telehealth services that Whakarongorau Aotearoa/New Zealand Telehealth Services provides to New Zealanders. In early 2021, an image upload system for viewing service user-uploaded images was implemented into the Healthline service. Aims. The aim of this research was to understand the utilisation of Healthline’s image upload system by clinicians and service users in New Zealand. Methods. This is a retrospective observational study analysing Healthline image upload data over a two-year period: March 2021 through to December 2022. A total of 40,045 images were analysed, including demographics of the service users who uploaded an image: ethnicity, age group, and area of residence. The outcome or recommendation of the Healthline call was also assessed based on whether an image was included. Results. Images uploaded accounted for 6.0% of total Healthline calls (n=671,564). This research found that more service users were advised to go to an Emergency Department if they did not upload an image compared to service users who used the tool (13.5% vs. 7.7%), whereas a higher proportion of service users were given a lower acuity outcome if they included an image, including visiting an Urgent Care (24.0% vs. 16.9%) and GP (36.7% vs. 24.3%). Conclusion. Service users who did not upload an image had a higher proportion of Emergency Department outcomes than service users who did use the tool. This image upload tool has shown the potential to decrease stress on Emergency Departments around Aotearoa, New Zealand, through increased lower acuity outcomes.

Background: Leigh syndrome is a rare, genetic, and severe mitochondrial disorder characterized by neuromuscular issues (ataxia, seizure, hypotonia, developmental delay, dystonia) and ocular abnormalities (nystagmus, atrophy, strabismus, ptosis). It is caused by pathogenic variants in either mitochondrial or nuclear DNA genes, with an estimated incidence rate of 1 per 40,000 live births.Case presentation: Herein, we present an infant male with nystagmus, hypotonia, and developmental delay who carried a clinical diagnosis of Leigh-like syndrome. Cerebral magnetic resonance imaging changes further supported the clinical evidence of an underlying mitochondrial disorder, but extensive diagnostic testing was negative. Trio exome sequencing under a research protocol uncovered compound-heterozygous missense variants in the HTRA2 gene (MIM: #606441): NM_013247.5:c.1037A>T:(p.Glu346Val) (maternal) and NM_013247.5:c.1172T>A:(p.Val391Glu) (paternal). Both variants are absent from public databases, making them extremely rare in the population. The maternal variant is adjacent to an exon-intron boundary and predicted to disrupt splicing, while the paternal variant alters a highly conserved amino acid and is predicted to be damaging by nearly all in silico tools. Biallelic variants in HTRA2 cause 3-methylglutaconic aciduria, type VIII (MGCA8), an extremely rare autosomal recessive disorder with fewer than ten families reported to date. Variant interpretation is challenging given the paucity of known disease-causing variants, and indeed we assess both paternal and maternal variants as Variants of Uncertain Significance under current American College of Medical Genetics guidelines. However, based on the inheritance pattern, suggestive evidence of pathogenicity, and significant clinical correlation with other reported MGCA8 patients, the clinical care team considers this a diagnostic result.Conclusion: Our findings ended the diagnostic odyssey for this family and provide further insights into the genetic and clinical spectrum of this critically under-studied disorder.

ABSTRACT While the asexual cycle of Toxoplasma gondii can occur in any warm-blooded animal, the sexual cycle is restricted to the feline intestine. We previously determined that because cats lack delta-6-desaturase activity in their intestines, they build up excess linoleic acid, which signals T. gondii to undergo sexual development. We hypothesized that T. gondii oxygenates linoleic acid to signal sexual development, so we examined the T. gondii genome for lipoxygenases-like enzymes (TgLOXL) enzymes. We identified seven TgLOXLs that were at least 100-fold more abundant in the cat intestinal versus the tissue culture tachyzoite stage. Parasites deleted in TgLOXL1 (TgΔLOXL1) had no significant growth differences in tissue culture fibroblast cells. Because the sexual development assay begins with brain cysts, we infected mice with TgΔLOXL1 and were surprised to find that TgΔLOXL1 had reduced virulence. The TgΔLOXL1 parasitemia was reduced by 3 d post-infection and largely cleared by 7 d post-infection. At 3 d post-infection, the cytokines interferon gamma (IFN-γ), IL-6, MCP-1, and TNF-α were significantly reduced in TgΔLOXL1-infected mice, which prompted us to examine TgΔLOXL1 in IFN-γ KO mice. We found that IFN-γ KO mice infected with TgΔLOXL1 succumbed to acute infection with the same kinetics as the parental and complemented strains, suggesting that TgLOXL1 plays a role in the IFN-γ signaling cascade. In tissue culture fibroblasts, TgLOXL1 was localized within the parasite, but in leukocytes from infected mice and activated macrophages, TgLOXL1 was localized within the host cytoplasm. These results suggest that TgLOXL1 changes localization in response to host immune activation. IMPORTANCE Lipoxygenases (LOXs) are enzymes that catalyze the deoxygenation of polyunsaturated fatty acids such as linoleic and arachidonic acid. These modifications create signaling molecules that are best characterized for modulating the immune response. Deletion of the first lipoxygenase-like enzyme characterized for Toxoplasma gondii (TgLOXL1) generated a less virulent strain, and infected mice showed a decreased immune response. This virulence defect was dependent on the mouse cytokine interferon gamma IFNγ. TgLOXL1 changes location from inside the parasite in tissue culture conditions to vesicular structures within the host immune cells during mouse infection. These results suggest that TgLOXL1 plays a role in the modification of the host immune response in mice.

Spiky hedgehog particles are reported to access a photocatalytic pathway for alkane oxidation directly to industrially relevant epoxides in one step, providing a lower cost and less energy-intensive pathway as compared to common alkene feedstocks.

Wilson-Aggarwal et al. use electronic medical records and door access logs from a London teaching hospital during the COVID-19 pandemic to calculate health care worker mobility and patient contacts. Significant fluctuations are seen, particularly on floors with more COVID-19 patients.

Background. Accidental intraoperative hypothermia is a common and avoidable adverse event of the perioperative period and is associated with detrimental effects on multiple organ systems and postoperative patient outcomes. In a resource-limited environment, prevention of intraoperative hypothermia is often challenging. Resourceful clinicians overcome these challenges through creative devices and frugal innovations. Objective. To investigate the thermal performance of two Baragwanath Rewarming Appliances (BaRA) against that of the Hotline device to describe an optimal setup for these devices. Methods. This was a quasi-experimental laboratory study that measured the thermal performance of two BaRA devices and the Hotline device under a number of scenarios. Independent variables including fluid type, flow rate, warming temperature and warming transit distance were sequentially altered and temperatures measured along the fluid stream. Change in temperature (ΔT) was calculated as the difference between entry and exit temperature for each combination of variables for each warming device. Results. A total of 219 experiments were performed. At a temperature of 43.0°C and a transit distance of 200 cm, the BaRA A configuration either matched or exceeded the ΔT of the Hotline over all fluid type and flowrate combinations. The BaRA B configuration does not provide comparable thermal performance to the Hotline. Measured flowrates were noticeably slower than manufacturer-quoted values for all intravenous (IV) cannulae used. Conclusion. A warm-water bath at 43.0°C with 200 cm of submerged IV tubing provides thermal performance comparable to the Hotline device, with all fluid type and flowrate combinations.

Abstract Rasmussen encephalitis (RE) is a rare childhood neurological disease characterized by progressive unilateral loss of function, hemispheric atrophy and drug-resistant epilepsy. Affected brain tissue shows signs of infiltrating cytotoxic T-cells, microglial activation, and neuronal death, implicating an inflammatory disease process. Recent studies have identified molecular correlates of inflammation in RE, but cell-type-specific mechanisms remain unclear. We used single-nucleus RNA-sequencing (snRNA-seq) to assess gene expression across multiple cell types in brain tissue resected from two children with RE. We found transcriptionally distinct microglial populations enriched in RE compared to two age-matched individuals with unaffected brain tissue and two individuals with Type I focal cortical dysplasia (FCD). Specifically, microglia in RE tissues demonstrated increased expression of genes associated with cytokine signaling, interferon-mediated pathways, and T-cell activation. We extended these findings using spatial proteomic analysis of tissue from four surgical resections to examine expression profiles of microglia within their pathological context. Microglia that were spatially aggregated into nodules had increased expression of dynamic immune regulatory markers (PD-L1, CD14, CD11c), T-cell activation markers (CD40, CD80) and were physically located near distinct CD4+ and CD8+ lymphocyte populations. These findings help elucidate the complex immune microenvironment of RE.

Abstract CUPID will be a next generation experiment searching for the neutrinoless double $$\beta $$ β decay, whose discovery would establish the Majorana nature of the neutrino. Based on the experience achieved with the CUORE experiment, presently taking data at LNGS, CUPID aims to reach a background free environment by means of scintillating Li $$_{2}$$ 2 $$^{100}$$ 100 MoO $$_4$$ 4 crystals coupled to light detectors. Indeed, the simultaneous heat and light detection allows us to reject the dominant background of $$\alpha $$ α particles, as proven by the CUPID-0 and CUPID-Mo demonstrators. In this work we present the results of the first test of the CUPID baseline module. In particular, we propose a new optimized detector structure and light sensors design to enhance the engineering and the light collection, respectively. We characterized the heat detectors, achieving an energy resolution of (5.9 ± 0.2) keV FWHM at the Q-value of $$^{100}$$ 100 Mo (about 3034 keV). We studied the light collection of the baseline CUPID design with respect to an alternative configuration which features gravity-assisted light detectors’ mounting. In both cases we obtained an improvement in the light collection with respect to past measures and we validated the particle identification capability of the detector, which ensures an $$\alpha $$ α particle rejection higher than 99.9%, fully satisfying the requirements for CUPID.

The molecular heterogeneity of KMT2A-rearranged infant acute lymphoblastic leukemia (ALL) remains poorly characterised. Here, the authors perform multi-omics analysis for 84 ALL patients and suggest 5 distinct subgroups for risk stratification and personalised treatment.’

BackgroundWeb-based tailored interventions offer rich opportunities for improved access to and personalization of behavioral interventions. However, despite the promise of this approach, the engagement and underrepresentation of minority groups remain major issues. ObjectiveThis study evaluated whether engagement (log-in status and log-in duration) with different types of tailored behavioral content from the Families Improving Together for weight loss web-based intervention was associated with changes in moderate to vigorous physical activity (MVPA) among African American families with overweight or obesity. MethodsParent-adolescent dyads were randomized to a web-based tailored intervention or web-based health education comparison program. The web-based intervention (N=119) was completed by parents and targeted 6 weight-related behaviors to support their adolescent children’s weight loss goals (session contents included energy balance, fast food, fruits and vegetables, physical activity [PA], sedentary behavior, and sweetened beverages). MVPA was measured using accelerometers at baseline and after the intervention. ResultsUsing a hierarchical approach, the log-in status and duration for each web-based session were used to evaluate the additive effects of engagement with different types of tailored behavioral content on MVPA after the web-based intervention. Among parents, logging in to the PA session was not associated with greater MVPA (B=−12.561, 95% CI −18.759 to −6.367), but MVPA increased with greater log-in duration for the PA (B=0.008, 95% CI 0.004-0.012) and sedentary behavior (B= 0.008, 95% CI 0.004-0.012) sessions. These results suggest that parents who logged in to the PA session had lower MVPA, but MVPA increased with greater log-in duration for the PA and sedentary behavior sessions. These associations remained even after accounting for engagement with other content sessions. However, these engagement effects did not translate to the adolescents. ConclusionsThe results of this study highlight the need to disentangle the impact of engagement with different tailored content to improve the efficacy of tailored web-based interventions, especially for promoting PA in African American families. Trial RegistrationClinicalTrials.gov NCT01796067; https://clinicaltrials.gov/ct2/show/NCT01796067

Atomic charge and its distribution across molecules provide important insight into chemical behavior. Though there are many studies on various routes for the determination of atomic charge, there are few studies that examine the broader impact of basis set and quantum method used over many types of population analysis methods across the periodic table. Largely, such a study of population analysis has focused on main-group species. In this work, atomic charges were calculated using several population analysis methods including orbital-based methods (Mulliken, Löwdin, and Natural Population Analysis), volume-based methods (Atoms-in-Molecules (AIM) and Hirshfeld), and potential derived charges (CHELP, CHELPG, and Merz-Kollman). The impact of basis set and quantum mechanical method choices upon population analysis has been considered. The basis sets utilized include Pople (6-21G**, 6-31G**, 6-311G**) and Dunning (cc-pVnZ, aug-cc-pVnZ; n = D, T, Q, 5) basis sets for main group molecules. For the transition metal and heavy element species examined, relativistic forms of the correlation consistent basis sets were used. This is the first time the cc-pVnZ-DK3 and cc-pwCVnZ-DK3 basis sets have been examined with respect to their behavior across all levels of basis sets for atomic charges for an actinide. The quantum methods chosen include two density functional (PBE0 and B3LYP), Hartree-Fock, and second-order Møller-Plesset perturbation theory (MP2) approaches.

Abstract Background AGITG DOCTOR was a randomised phase 2 trial of pre-operative cisplatin, 5 fluorouracil (CF) followed by docetaxel (D) with or without radiotherapy (RT) based on poor early response to CF, detected via PET, for resectable oesophageal adenocarcinoma. This study describes PROs over 2 years. Methods Participants (N = 116) completed the EORTC QLQ-C30 and oesophageal module (QLQ-OES18) before chemotherapy (baseline), before surgery, six and 12 weeks post-surgery and three-monthly until 2 years. We plotted PROs over time and calculated the percentage of participants per treatment group whose post-surgery score was within 10 points (threshold for clinically relevant change) of their baseline score, for each PRO scale. We examined the relationship between Grade 3+ adverse events (AEs) and PROs. This analysis included four groups: CF responders, non-responders randomised to DCF, non-responders randomised to DCF + RT, and “others” who were not randomised. Results Global QOL was clinically similar between groups from 6 weeks post-surgery. All groups had poorer functional and higher symptom scores during active treatment and shortly after surgery, particularly the DCF and DCF + RT groups. DCF + RT reported a clinically significant difference (−13points) in mean overall health/QOL between baseline and pre-surgery. Similar proportions of patients across groups scored +/− 10 points of baseline scores within 2 years for most PRO domains. Instance of grade 3+ AEs were not related to PROs at baseline or 2 years. Conclusions By 2 years, similar proportions of patients scored within 10 points of baseline for most PRO domains, with the exception of pain and insomnia for the DCF + RT group. Non-responders randomised to DCF or DCF + RT experienced additional short-term burden compared to CF responders, reflecting the longer duration of neoadjuvant treatment and additional toxicity. This should be weighed against clinical benefits reported in AGITG DOCTOR. This data will inform communication of the trajectory of treatment options for early CF non-responders. Trial registration Australia New Zealand Clinical Trials Registry (ANZCTR), ACTRN12609000665235 . Registered 31 July 2009.

Measurement(s) Fish swimming speed • Fish morphology Technology Type(s) Swimming flume • Image analysis Factor Type(s) location • region • date Sample Characteristic - Organism Actinopteri Sample Characteristic - Environment marine water body Sample Characteristic - Location Great Barrier Reef • Caribbean Region • Morea • Taiwan Island Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.16988074

Inuit have lived along the shoreline of the frozen Arctic Ocean for centuries. Our wellbeing, culture, and identity are closely tied to safe and dependable ice access. As the ice becomes more unpredictable with a changing climate, Elders and experienced ice users recognize that their accumulated wisdom and experience of safe ice travel—their Inuit Qaujimajatuqangit (IQ; a term used to describe Inuit knowledge and values) of sea-ice—must be shared and applied in new ways for the benefit of younger generations. Here we illustrate one such application that enables young Inuit scientists to learn and apply the tools and skills they need to create operational community-scale sea-ice maps (Sikumik Qaujimajjuti, or “tool to know how the ice is”). Our cross-cultural partnership approach—called the Sikumiut-SmartICE model—focuses on developing the skills of young Inuit to create the maps, while non-Indigenous partners provide mentorship, tools, and training. Our novel maps incorporate culturally relevant ice terminology, on-ice monitoring data and observations, and IQ-grounded interpretations of ice features and travel conditions from near-real time optical and radar satellite imagery. The layers of data are integrated into a local GIS, enabling the creation of maps that reflect local and seasonal travel patterns and meet our information needs in information content, extent and frequency. The maps are posted and shared through social media platforms preferred by the community. The maps are a trusted source of travel information because they are made by one of our own, using local language, experience, and IQ. The Sikumik Qaujimajjuti program illustrates the incredible potential of Indigenous self-determination in cryospheric science when the scientific merit of IQ is fully recognized, when Indigenous researchers are able to access technologies and training to apply their IQ, and when non-Indigenous partners mentor and support young Indigenous scientists.

The COVID-19 pandemic has emphasised the need to rapidly assess infection risks for healthcare workers within the hospital environment. Using data from the first year of the pandemic, we investigated whether an individual's COVID-19 test result was associated with behavioural markers derived from routinely collected hospital data two weeks prior to a test. The temporal and spatial context of behaviours were important, with the highest risks of infection during the first wave, for staff in contact with a greater number of patients and those with greater levels of activity on floors handling the majority of COVID-19 patients. Infection risks were higher for BAME staff and individuals working more shifts. Night shifts presented higher risks of infection between waves of COVID-19 patients. Our results demonstrate the epidemiological relevance of deriving markers of staff behaviour from electronic records, which extend beyond COVID-19 with applications for other communicable diseases and in supporting pandemic preparedness.

Abstract Background Pediatric cancers typically have a distinct genomic landscape when compared to adult cancers and frequently carry somatic gene fusion events that alter gene expression and drive tumorigenesis. Sensitive and specific detection of gene fusions through the analysis of next-generation-based RNA sequencing (RNA-Seq) data is computationally challenging and may be confounded by low tumor cellularity or underlying genomic complexity. Furthermore, numerous computational tools are available to identify fusions from supporting RNA-Seq reads, yet each algorithm demonstrates unique variability in sensitivity and precision, and no clearly superior approach currently exists. To overcome these challenges, we have developed an ensemble fusion calling approach to increase the accuracy of identifying fusions. Results Our Ensemble Fusion (EnFusion) approach utilizes seven fusion calling algorithms: Arriba, CICERO, FusionMap, FusionCatcher, JAFFA, MapSplice, and STAR-Fusion, which are packaged as a fully automated pipeline using Docker and Amazon Web Services (AWS) serverless technology. This method uses paired end RNA-Seq sequence reads as input, and the output from each algorithm is examined to identify fusions detected by a consensus of at least three algorithms. These consensus fusion results are filtered by comparison to an internal database to remove likely artifactual fusions occurring at high frequencies in our internal cohort, while a “known fusion list” prevents failure to report known pathogenic events. We have employed the EnFusion pipeline on RNA-Seq data from 229 patients with pediatric cancer or blood disorders studied under an IRB-approved protocol. The samples consist of 138 central nervous system tumors, 73 solid tumors, and 18 hematologic malignancies or disorders. The combination of an ensemble fusion-calling pipeline and a knowledge-based filtering strategy identified 67 clinically relevant fusions among our cohort (diagnostic yield of 29.3%), including RBPMS-MET, BCAN-NTRK1, and TRIM22-BRAF fusions. Following clinical confirmation and reporting in the patient’s medical record, both known and novel fusions provided medically meaningful information. Conclusions The EnFusion pipeline offers a streamlined approach to discover fusions in cancer, at higher levels of sensitivity and accuracy than single algorithm methods. Furthermore, this method accurately identifies driver fusions in pediatric cancer, providing clinical impact by contributing evidence to diagnosis and, when appropriate, indicating targeted therapies.

Abstract Primary spinal cord tumors contribute to ≤ 10% of central nervous system tumors in individuals of pediatric or adolescent age. Among intramedullary tumors, spinal ependymomas make up ~ 30% of this rare tumor population. A twelve-year-old male presented with an intradural, extramedullary mass occupying the dorsal spinal canal from C6 through T2. Gross total resection and histopathology revealed a World Health Organization (WHO) grade 2 ependymoma. He recurred eleven months later with extension from C2 through T1-T2. Subtotal resection was achieved followed by focal proton beam irradiation and chemotherapy. Histopathology was consistent with WHO grade 3 ependymoma. Molecular profiling of the primary and recurrent tumors revealed a novel amplification of the MYC (8q24) gene, which was confirmed by fluorescence in situ hybridization studies. Although MYC amplification in spinal ependymoma is exceedingly rare, a newly described classification of spinal ependymoma harboring MYCN (2p24) amplification (SP-MYCN) has been defined by DNA methylation-array based profiling. These individuals typically present with a malignant progression and dismal outcomes, contrary to the universally excellent survival outcomes seen in other spinal ependymomas. DNA methylation array-based classification confidently classified this tumor as SP-MYCN ependymoma. Notably, among the cohort of 52 tumors comprising the SP-MYCN methylation class, none harbor MYC amplification, highlighting the rarity of this genomic amplification in spinal ependymoma. A literature review comparing our individual to reported SP-MYCN tumors (n = 26) revealed similarities in clinical, histopathologic, and molecular features. Thus, we provide evidence from a single case to support the inclusion of MYC amplified spinal ependymoma within the molecular subgroup of SP-MYCN.

Abstract The CUORE experiment is a large bolometric array searching for the lepton number violating neutrino-less double beta decay ( $$0\nu \beta \beta $$ 0 ν β β ) in the isotope $$\mathrm {^{130}Te}$$ 130 Te . In this work we present the latest results on two searches for the double beta decay (DBD) of $$\mathrm {^{130}Te}$$ 130 Te to the first $$0^{+}_2$$ 0 2 + excited state of $$\mathrm {^{130}Xe}$$ 130 Xe : the $$0\nu \beta \beta $$ 0 ν β β decay and the Standard Model-allowed two-neutrinos double beta decay ( $$2\nu \beta \beta $$ 2 ν β β ). Both searches are based on a 372.5 kg $$\times $$ × yr TeO $$_2$$ 2 exposure. The de-excitation gamma rays emitted by the excited Xe nucleus in the final state yield a unique signature, which can be searched for with low background by studying coincident events in two or more bolometers. The closely packed arrangement of the CUORE crystals constitutes a significant advantage in this regard. The median limit setting sensitivities at 90% Credible Interval (C.I.) of the given searches were estimated as $$\mathrm {S^{0\nu }_{1/2} = 5.6 \times 10^{24} \, \mathrm {yr}}$$ S 1 / 2 0 ν = 5.6 × 10 24 yr for the $${0\nu \beta \beta }$$ 0 ν β β decay and $$\mathrm {S^{2\nu }_{1/2} = 2.1 \times 10^{24} \, \mathrm {yr}}$$ S 1 / 2 2 ν = 2.1 × 10 24 yr for the $${2\nu \beta \beta }$$ 2 ν β β decay. No significant evidence for either of the decay modes was observed and a Bayesian lower bound at $$90\%$$ 90 % C.I. on the decay half lives is obtained as: $$\mathrm {(T_{1/2})^{0\nu }_{0^+_2} > 5.9 \times 10^{24} \, \mathrm {yr}}$$ ( T 1 / 2 ) 0 2 + 0 ν > 5.9 × 10 24 yr for the $$0\nu \beta \beta $$ 0 ν β β mode and $$\mathrm {(T_{1/2})^{2\nu }_{0^+_2} > 1.3 \times 10^{24} \, \mathrm {yr}}$$ ( T 1 / 2 ) 0 2 + 2 ν > 1.3 × 10 24 yr for the $$2\nu \beta \beta $$ 2 ν β β mode. These represent the most stringent limits on the DBD of $$^{130}$$ 130 Te to excited states and improve by a factor $$\sim 5$$ ∼ 5 the previous results on this process.

Abstract Background Health promotion efforts among African American men have been met with significant challenges and have produced limited results. Interventions that do not align with the values, perspectives, and preferences of African American men often produce less effective results. Research among African American men has provided compelling evidence that these men prefer informal networks of health support. Recent successful health promotion efforts among these men have benefited from peer-to-peer models of implementation. To date, no known scoping or systematic review of peer-to-peer health promotion interventions among African American men has been conducted. The goal of this scoping review is to understand the extent of, design, implementation, and use of peer-to-peer interventions to promote health, improve quality of life, and prevent disease among African American men. Methods A review of the literature will be performed in PubMED, EMBASE, PsycInfo, CINAHL, and Web of Science. The development of this protocol was guided by the work of Arksey and O’Malley and the PICOS statement. Reporting will be guided by the PRISMA-ScR checklist. Eligible studies include those testing the effects of a peer-to-peer health promotion intervention targeting African American men. A comparison group will not be required. For the purposes of the current review, “peers” will be limited to other African American men. An initial screening of the titles and abstracts of potentially eligible studies will be completed by two independent reviewers. The full text of records that appear to meet the eligibility criteria will be accessed and further screened. Data will then be extracted and collected using a custom Microsoft Excel spreadsheet. Extracted data will include authors’ name and publication year, target health issue(s), design of the intervention, components of the intervention, peer-led components of the intervention, peer role, length and type of training for peer leaders, intervention duration, frequency of the intervention, study design and number of participants, and main outcomes. Finally, results will be presented in table format and summarized in text format. Discussion Results will have implications for the design, implementation, and evaluation of health promotion interventions among African American men. Systematic review registration PROSPERO CRD42020198664

Rhabdoid tumors (RTs) of the brain (atypical teratoid/rhabdoid tumor; AT/RT) and extracranial sites (most often the kidney; RTK) are malignant tumors predominantly occurring in children, frequently those with SMARCB1 germline alterations. Here we present data from seven RTs from three pediatric patients who all had multi-organ involvement. The tumors were analyzed using a multimodal molecular approach, which included exome sequencing of tumor and germline comparator and RNA sequencing and DNA array-based methylation profiling of tumors. SMARCB1 germline alterations were identified in all patients and in all tumors. We observed a second hit in SMARCB1 via chr22 loss of heterozygosity. By methylation profiling, all tumors were classified as rhabdoid tumors with a corresponding subclassification within the MYC, TYR, or SHH AT/RT subgroups. Using RNA-seq gene expression clustering, we recapitulated the classification of known AT/RT subgroups. Synchronous brain and kidney tumors from the same patient showed different patterns of either copy number variants, single-nucleotide variants, and/or genome-wide DNA methylation, suggestive of non-clonal origin. Furthermore, we demonstrated that a lung and abdominal metastasis from two patients shared overlapping molecular features with the patient’s primary kidney tumor, indicating the likely origin of the metastasis. In addition to the SMARCB1 events, we identified other whole-chromosome events and single-nucleotide variants in tumors, but none were found to be prognostic, diagnostic, or offer therapeutic potential for rhabdoid tumors. While our findings are of biological interest, there may also be clinical value in comprehensive molecular profiling in patients with multiple rhabdoid tumors, particularly given the potential prognostic and therapeutic implications for different rhabdoid tumor subgroups demonstrated in recent clinical trials and other large cohort studies.

Abstract Retinoblastoma is a childhood cancer of the retina involving germline or somatic alterations of the RB Transcriptional Corepressor 1 gene, RB1. Rare cases of sellar-suprasellar region retinoblastoma without evidence of ocular or pineal tumors have been described. A nine-month-old male presented with a sellar-suprasellar region mass. Histopathology showed an embryonal tumor with focal Flexner-Wintersteiner-like rosettes and loss of retinoblastoma protein (RB1) expression by immunohistochemistry. DNA array-based methylation profiling confidently classified the tumor as pineoblastoma group A/intracranial retinoblastoma. The patient was subsequently enrolled on an institutional translational cancer research protocol and underwent comprehensive molecular profiling, including paired tumor/normal exome and genome sequencing and RNA-sequencing of the tumor. Additionally, Pacific Biosciences (PacBio) Single Molecule Real Time (SMRT) sequencing was performed from comparator normal and disease-involved tissue to resolve complex structural variations. RNA-sequencing revealed multiple fusions clustered within 13q14.1-q21.3, including a novel in-frame fusion of RB1-SIAH3 predicted to prematurely truncate the RB1 protein. SMRT sequencing revealed a complex structural rearrangement spanning 13q14.11-q31.3, including two somatic structural variants within intron 17 of RB1. These events corresponded to the RB1-SIAH3 fusion and a novel RB1 rearrangement expected to correlate with the complete absence of RB1 protein expression. Comprehensive molecular analysis, including DNA array-based methylation profiling and sequencing-based methodologies, were critical for classification and understanding the complex mechanism of RB1 inactivation in this diagnostically challenging tumor.

Abstract Background The stable fly, Stomoxys calcitrans, is a major blood-feeding pest of livestock that has near worldwide distribution, causing an annual cost of over $2 billion for control and product loss in the USA alone. Control of these flies has been limited to increased sanitary management practices and insecticide application for suppressing larval stages. Few genetic and molecular resources are available to help in developing novel methods for controlling stable flies. Results This study examines stable fly biology by utilizing a combination of high-quality genome sequencing and RNA-Seq analyses targeting multiple developmental stages and tissues. In conjunction, 1600 genes were manually curated to characterize genetic features related to stable fly reproduction, vector host interactions, host-microbe dynamics, and putative targets for control. Most notable was characterization of genes associated with reproduction and identification of expanded gene families with functional associations to vision, chemosensation, immunity, and metabolic detoxification pathways. Conclusions The combined sequencing, assembly, and curation of the male stable fly genome followed by RNA-Seq and downstream analyses provide insights necessary to understand the biology of this important pest. These resources and new data will provide the groundwork for expanding the tools available to control stable fly infestations. The close relationship of Stomoxys to other blood-feeding (horn flies and Glossina) and non-blood-feeding flies (house flies, medflies, Drosophila) will facilitate understanding of the evolutionary processes associated with development of blood feeding among the Cyclorrhapha.

Abstract Background Women may need or seek male partner approval to safely and consistently use oral antiretroviral pre-exposure prophylaxis (PrEP) or vaginal microbicides. We developed CHARISMA, a counseling intervention to support women’s relationships and their ability to consistently use HIV prevention products. Methods In a pilot study with 95 female participants in Johannesburg, South Africa, lay counselors implemented CHARISMA, assessing participants’ relationship(s) with their male partner(s) and barriers or facilitators to HIV prevention method use, and then providing tailored, interactive counseling. We conducted study participant surveys and clinic staff interviews to evaluate CHARISMA’s feasibility and acceptability. Results The CHARISMA pilot study indicates that a two-session relationship counseling intervention with 6-month follow-up to support women’s ability to safely and effectively use vaginal microbicides was generally acceptable and feasible. Most participants thought CHARISMA was relevant, helpful, and about the right length, and that it had a positive impact on their relationships with their partners and their product use. Staff estimated that the intervention took 1.5–2 h to implement at enrollment and 45 min to an hour for the month 1 visit. They thought that overall CHARISMA was generally feasible to implement. Conclusions Findings from this study suggest several lessons learned that may be relevant to others developing interventions supporting women’s use of oral PrEP or vaginal microbicides. The use of lay counselors instead of nurses to deliver counseling appeared to be successful, but the counselors experienced significant stress from hearing about participants’ traumatic experiences and required emotional support to avoid burnout. Although staff and participants felt that having multiple intervention sessions over time was valuable, a similar level of intensity may not be feasible in other settings. Further research is needed to determine an intervention delivery mode and follow-up period that optimally balances participant needs and clinic resources. Male engagement was a challenge, as it has been in previous studies of vaginal microbicides. Alternative strategies to reach men that do not require them to come to the clinic or rely on their female partners may be more effective.

Abstract The CUPID Collaboration is designing a tonne-scale, background-free detector to search for double beta decay with sufficient sensitivity to fully explore the parameter space corresponding to the inverted neutrino mass hierarchy scenario. One of the CUPID demonstrators, CUPID-Mo, has proved the potential of enriched Li $$_{2}$$ 2 $$^{100}$$ 100 MoO $$_4$$ 4 crystals as suitable detectors for neutrinoless double beta decay search. In this work, we characterised cubic crystals that, compared to the cylindrical crystals used by CUPID-Mo, are more appealing for the construction of tightly packed arrays. We measured an average energy resolution of ( $$6.7\pm 0.6$$ 6.7 ± 0.6 ) keV FWHM in the region of interest, approaching the CUPID target of 5 keV FWHM. We assessed the identification of $$\alpha $$ α particles with and without a reflecting foil that enhances the scintillation light collection efficiency, proving that the baseline design of CUPID already ensures a complete suppression of this $$\alpha $$ α -induced background contribution. We also used the collected data to validate a Monte Carlo simulation modelling the light collection efficiency, which will enable further optimisations of the detector.

Abstract Background Manual microscopy remains a widely-used tool for malaria diagnosis and clinical studies, but it has inconsistent quality in the field due to variability in training and field practices. Automated diagnostic systems based on machine learning hold promise to improve quality and reproducibility of field microscopy. The World Health Organization (WHO) has designed a 55-slide set (WHO 55) for their External Competence Assessment of Malaria Microscopists (ECAMM) programme, which can also serve as a valuable benchmark for automated systems. The performance of a fully-automated malaria diagnostic system, EasyScan GO, on a WHO 55 slide set was evaluated. Methods The WHO 55 slide set is designed to evaluate microscopist competence in three areas of malaria diagnosis using Giemsa-stained blood films, focused on crucial field needs: malaria parasite detection, malaria parasite species identification (ID), and malaria parasite quantitation. The EasyScan GO is a fully-automated system that combines scanning of Giemsa-stained blood films with assessment algorithms to deliver malaria diagnoses. This system was tested on a WHO 55 slide set. Results The EasyScan GO achieved 94.3 % detection accuracy, 82.9 % species ID accuracy, and 50 % quantitation accuracy, corresponding to WHO microscopy competence Levels 1, 2, and 1, respectively. This is, to our knowledge, the best performance of a fully-automated system on a WHO 55 set. Conclusions EasyScan GO’s expert ratings in detection and quantitation on the WHO 55 slide set point towards its potential value in drug efficacy use-cases, as well as in some case management situations with less stringent species ID needs. Improved runtime may enable use in general case management settings.

DNA templating is a useful strategy to control the positioning and aggregation of molecular dyes on a sub-nanometer scale, but sub-angstrom control is desirable for the precise tailoring of excitonic properties. Here, the authors show that templating squaraine dyes functionalized with rotaxane rings promotes an elusive oblique packing arrangement and extended excited-state lifetimes.

Abstract Background Infection after the penile prosthesis can be devastating to both the patient and surgeon with various complications and consequences. After introduction of antibiotic-coated implants, the rate of infection has dramatically decreased, but still we see uncommon organisms causing infection. We present a first case report of penile prosthesis infection by brucellosis due to raw milk ingestion. To our knowledge, this is the first reported case of brucellosis penile prosthesis infection. Case presentation We present a first case report of penile prosthesis infection by brucellosis due to raw milk ingestion. A 75-year-old, diabetic male patient presented with penile prosthesis infection 5 months post-penile exchange surgery due to mechanical malfunctioning of 2-piece penile prosthesis which was inserted 11 years ago. The initial treatment with broad spectrum antibiotics did not subside the infection. After diagnosis of brucellosis, the antibiotic was changed to anti-brucellosis (Rifampicin + Tetracycline). The patient improved dramatically and was discharged home with smooth follow-up course. Conclusion Brucellosis can cause infection of penile prosthesis and can be treated with anti-brucellosis antibiotics without necessitating surgical intervention and removal of prosthesis.