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The burden of simultaneous acute code stroke activation (ACSA) is not known. We aim to assess the effect of simultaneous ACSA on workflow metrics and home time at 90 days in patients undergoing reperfusion therapies in the emergency department. Simultaneous ACSA was defined as code activation within 60 min of the arrival of any patient receiving intravenous thrombolysis, within 150 min of the arrival of any patient receiving endovascular thrombectomy, within 45 min of the arrival of any patient receiving no reperfusion therapies (based on mean local door-to-needle and door-to-puncture times). Simultaneous ACSA was further graded as 1, 2 and 3. We assessed workflow metrics as door-to-CT (DTC) time, in minutes, and functional outcome as home time at 90 days. A total of 2605 patients were assessed as ACSA at a mean ± SD activations of 130.8 ± 17.1/month and 859 (33%) were simultaneous. Among all ACSA, 545 (20.9%) underwent acute reperfusion therapy with a mean age of 70.6 ± 14.2 years, 45.9% (n = 254) were female with a median (IQR) NIHSS of 13 (8–18). A total of 220 (40.4%) patients underwent simultaneous treatments. The median DTC time, in minutes, was prolonged in grade 3 simultaneous ACSA (18 (13, 28)) compared to non-simultaneous ACSA (15 (11, 21) β = 0.23, p < 0.0001). There was no difference in the median home time at 90 days between the simultaneous (58, 0–84.5 days) and non-simultaneous (54, 0–85 days) patients. Simultaneous ACSA is frequent in patients receiving acute reperfusion therapies. An optimal workflow in high-volume centers may help mitigate the clinical and system burden associated with simultaneity.

Abstract Background Therapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking. Methods Trans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses. Discussion The SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research. Trial registration anzctr.org.au, ACTRN12621001444875, registered 21 October 2021.

Abstract In recent years, the diagnosis of gliomas has become increasingly complex. Analysis of glioma histopathology images using artificial intelligence (AI) offers new opportunities to support diagnosis and outcome prediction. To give an overview of the current state of research, this review examines 83 publicly available research studies that have proposed AI-based methods for whole-slide histopathology images of human gliomas, covering the diagnostic tasks of subtyping (23/83), grading (27/83), molecular marker prediction (20/83), and survival prediction (29/83). All studies were reviewed with regard to methodological aspects as well as clinical applicability. It was found that the focus of current research is the assessment of hematoxylin and eosin-stained tissue sections of adult-type diffuse gliomas. The majority of studies (52/83) are based on the publicly available glioblastoma and low-grade glioma datasets from The Cancer Genome Atlas (TCGA) and only a few studies employed other datasets in isolation (16/83) or in addition to the TCGA datasets (15/83). Current approaches mostly rely on convolutional neural networks (63/83) for analyzing tissue at 20x magnification (35/83). A new field of research is the integration of clinical data, omics data, or magnetic resonance imaging (29/83). So far, AI-based methods have achieved promising results, but are not yet used in real clinical settings. Future work should focus on the independent validation of methods on larger, multi-site datasets with high-quality and up-to-date clinical and molecular pathology annotations to demonstrate routine applicability.

Abstract The human microbiome plays a crucial role in human health. However, the influence of maternal factors on the neonatal microbiota remains obscure. Herein, our observations suggest that the neonatal microbiotas, particularly the buccal microbiota, change rapidly within 24–48 h of birth but begin to stabilize by 48–72 h after parturition. Network analysis clustered over 200 maternal factors into thirteen distinct groups, and most associated factors were in the same group. Multiple maternal factor groups were associated with the neonatal buccal, rectal, and stool microbiotas. Particularly, a higher maternal inflammatory state and a lower maternal socioeconomic position were associated with a higher alpha diversity of the neonatal buccal microbiota and beta diversity of the neonatal stool microbiota was influenced by maternal diet and cesarean section by 24–72 h postpartum. The risk of admission of a neonate to the newborn intensive care unit was associated with preterm birth as well as higher cytokine levels and probably higher alpha diversity of the maternal buccal microbiota.

Abstract Purpose To report a case of Purpureocillium lilacinum endophthalmitis. Methods The case of a fungal endophthalmitis caused by Purpureocillium lilacinum documented in an immunocompetent patient with no apparent trigger. Results A 64-year-old male with a two-month history of panuveitis in his left eye was referred to our hospital. Initially misdiagnosed as sympathetic ophthalmia due to a previous surgery on his right eye 4 months before the onset of the left ocular picture, the patient received corticosteroid treatment, leading to a rapid deterioration of the left eye condition. An urgent exploratory vitrectomy was performed to identify the underlying cause, revealing endophthalmitis. Microbiological investigation yielded Purpureocillium lilacinum as the causative agent. Despite intensive treatment, including intravitreal antibiotics and antifungals, along with another surgical intervention, clinical evolution remained unfavourable, ultimately leading to the evisceration of the affected eye. Conclusions Purpureocillium lilacinum poses a rare yet sever threat as a causative agent of fungal endophthalmitis. Managing such cases is challenging due to the delayed identification, fungus’s resistance to common antifungals, and its association with prior corticosteroid misuse in most patients. This case underscores the crucial importance of heightened clinical suspicion, early diagnosis, and the exploration of alternative treatment strategies in addressing Purpureocillium lilacinum endophthalmitis. The challenges posed by this rare fungal pathogen emphasize the need for a multidisciplinary approach and continued research to improve outcomes in these complex cases.

Lithium-ion and sodium-ion batteries (LIBs and SIBs) are crucial in our shift toward sustainable technologies. In this work, the potential of layered boride materials (MoAlB and Mo2 AlB2 ) as novel, high-performance electrode materials for LIBs and SIBs, is explored. It is discovered that Mo2 AlB2 shows a higher specific capacity than MoAlB when used as an electrode material for LIBs, with a specific capacity of 593 mAh g-1 achieved after 500 cycles at 200 mA g-1 . It is also found that surface redox reactions are responsible for Li storage in Mo2 AlB2 , instead of intercalation or conversion. Moreover, the sodium hydroxide treatment of MoAlB leads to a porous morphology and higher specific capacities exceeding that of pristine MoAlB. When tested in SIBs, Mo2 AlB2 exhibits a specific capacity of 150 mAh g-1 at 20 mA g-1 . These findings suggest that layered borides have potential as electrode materials for both LIBs and SIBs, and highlight the importance of surface redox reactions in Li storage mechanisms.

BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.

The number of identified human polyomaviruses (HPyVs) has increased steadily over the last decade. Some of the novel HPyVs have been shown to cause disease in immunocompromised individuals. The Lyon-IARC polyomavirus (LIPyV) belonging to species Alphapolyomavirus quardecihominis was identified in 2017 in skin and saliva samples from healthy individuals. Since its initial discovery, LIPyV has rarely been detected in human clinical samples but has been detected in faeces from cats with diarrhoea. Serological studies show low LIPyV seroprevalence in human populations. To investigate the possibility that LIPyV is a feline rather than a human polyomavirus, we compared serum IgG responses against the VP1 major capsid protein of LIPyV and 13 other HPyVs among cats (n = 40), dogs (n = 38) and humans (n = 87) using an in-house immunoassay. Seropositivity among cats was very high (92.5%) compared to dogs (31.6%) and humans (2.3%). Furthermore, the median antibody titres against LIPyV were 100-10,000x higher in cats compared to dogs and humans. In conclusion, the high prevalence and intensity of measured seroresponses suggest LIPyV to be a feline rather than a human polyomavirus. Whether LIPyV infection induces diarrhoea or other symptoms in cats remains to be established.

The nuclear factor I/X (NFIX) gene encodes a ubiquitously expressed transcription factor whose mutations lead to two allelic disorders characterized by developmental, skeletal, and neural abnormalities, namely, Malan syndrome (MAL) and Marshall-Smith syndrome (MSS). NFIX mutations associated with MAL mainly cluster in exon 2 and are cleared by nonsense-mediated decay (NMD) leading to NFIX haploinsufficiency, whereas NFIX mutations associated with MSS are clustered in exons 6-10 and escape NMD and result in the production of dominant-negative mutant NFIX proteins. Thus, different NFIX mutations have distinct consequences on NFIX expression. To elucidate the in vivo effects of MSS-associated NFIX exon 7 mutations, we used CRISPR-Cas9 to generate mouse models with exon 7 deletions that comprised: a frameshift deletion of two nucleotides (Nfix Del2); in-frame deletion of 24 nucleotides (Nfix Del24); and deletion of 140 nucleotides (Nfix Del140). Nfix +/Del2, Nfix +/Del24, Nfix +/Del140, Nfix Del24/Del24, and Nfix Del140/Del140 mice were viable, normal, and fertile, with no skeletal abnormalities, but Nfix Del2/Del2 mice had significantly reduced viability (p

With this article, we describe and analyze the experience of a scientist as she delineated the meaning of scientific inquiry and developed a new professional identity as a science teacher educator. Our inquiry adopted a self-study methodology with a variety of data sources, including sixteen-weeks of journal entries, critical friends' meetings and reflections, video and audio-taped lessons and students' artifacts. The self-study process captured her conflict between scientific inquiry in the classroom and her chemistry research. We captured three stages of her understanding of scientific inquiry. The idea of "authentic scientific novice research" finally resolved her conflicts. This study also revealed three factors that influenced the formation of her professional identity (i.e., competing identities, contextual influences, and personal struggles). This finding and resulting conclusions not only report the evolution of personal understanding, but also bring out the discussion of teacher educator development, especially for those transitioning to science education from natural sciences.

While the medical field in the United States is renowned for research and innovation, with large numbers of world-class healthcare facilities and cutting-edge technologies, inequities in overall health outcomes demonstrate pronounced disparities in accessing care. This article addresses increasing provider diversity and cultural humility as critical steps in ensuring advancements are made to equitable care under the current confines of the American healthcare system. Increasing diversity amongst medical providers starts before students begin applying to medical school. Critical strategies are needed at the K-12 level to ensure early exposure to Science, Technology, Engineering, and Mathematics (STEM). Research demonstrates that early exposure to STEM can positively impact children's interest, confidence, and pursuit of STEM careers, including medicine. Early exposure to STEM can increase engagement and motivation in STEM subjects particularly for girls and racially marginalized groups.

The term “offshore” with regards to aquaculture has hitherto encompassed various perspectives, including technology, geographic location, legal jurisdiction, and more. To resolve the ambiguity in this term and understand its implications for current and future aquaculture development, “offshore” should be resolved into two separate metrics: distance from shore and energy exposure. The United Nations Convention on the Law of the Sea (UNCLOS) distinguishes between internal waters, territorial sea, contiguous zone, exclusive economic zone (EEZ), and the high seas, but currently has no precise definition for “offshore” in its provisions, and therefore no applicable laws pertaining to “offshore” aquaculture. Regulating a multi-technology aquaculture sector may require integrating new spatial concepts into the law rather than merely adapting and extending current regulatory designs to include new production concepts. The metrics of distance from shore and exposure are seen as a range rather than a specific threshold, allowing for a continuum. Distance from shore is readily quantified as a distance from a baseline. To rigorously quantify the exposure, the influence and interactions of oceanic parameters (water depth, water current, and wave height and period) we utilized to generate six indices. These oceanic parameters are seen as the main contributions which influence the physical and some biological parameters required for site, species, and technology selection. Four shellfish, three seaweed, and three finfish sites along with 20 potential aquaculture sites were examined using the indices in association with the energy index to determine tolerances of the structures and their ability to cultivate their relevant species. Two indices, Specific Exposure Energy (SEE) and Exposure Velocity (EV), were selected for utilization in the analysis of sites based on their ease of use and applicability. The interaction between the energy indices and various aspects of farm operations and performance were explored. The indices developed and used in the case studies presented have been shown to be useful tools in the general assessment of the energy that will influence the species and equipment selection at potential aquaculture sites. The indices do not provide a definitive answer as to the potential financial success of a site as this requires other inputs relating to infrastructure costs, annual production, distance from port, sales strategy, etc. However, the Specific Exposure Energy index creates a useful tool to describe site energy and be comprehensible to a wide range of stakeholders. We recommend the SEE index be adopted as the predominant tool to communicate the exposure level of aquaculture sites.

The Arctic is seasonally exposed to long periods of low temperatures and complete darkness. Consequently, perennial primary producers have to apply strategies to maximize energy efficiency. Global warming is occurring in the Arctic faster than the rest of the globe. The highest amplitude of temperature rise occurs during Polar Night. To determine the stress resistance of the ecosystem-engineering kelp Laminaria digitata against Arctic winter warming, non-meristematic discs of adult sporophytes from Porsangerfjorden (Finnmark, Norway) were kept in total darkness at 0°C and 5°C over a period of three months. Physiological variables, namely maximum quantum yield of photosynthesis (Fv/Fm) and dry weight, as well as underlying biochemical variables including pigments, storage carbohydrates, total carbon and total nitrogen were monitored throughout the experiment. Although all samples remained in generally good condition with Fv/Fm values above 0.6, L. digitata performed better at 0°C than at 5°C. Depletion of metabolic products resulted in a constant decrease of dry weight over time. A strong decrease in mannitol and laminarin was observed, with greater reductions at 5°C than at 0°C. However, the total carbon content did not change, indicating that the sporophytes were not suffering from “starvation stress” during the long period of darkness. A decline was also observed in the accessory pigments and the pool of xanthophyll cycle pigments, particularly at 5°C. Our results indicate that L. digitata has a more active metabolism, but a lower physiological and biochemical performance at higher temperatures in the Arctic winter. Obviously, L. digitata is well adapted to Arctic Polar Night conditions, regardless of having its distributional center at lower latitudes. Despite a reduced vitality at higher temperatures, a serious decline in Arctic populations of L. digitata due to winter warming is not expected for the near future.

The next generation of central receivers is expected to reach high outlet temperatures of 800 °C and above, maintain stable operation and react to a varying incoming flux magnitude caused by hourly and seasonal variations, endure high-temperature operation, and remain cost-effective. Particle-based central receivers are being considered due to their high-temperature durability and favorable thermal properties of particle materials such as bauxite particles. This paper describes a new particle-based central receiver concept and provides an initial exploration of its performance in comparison with the existing CentRec® technology. Discrete Element Method (DEM) simulations demonstrated that a stable falling and sliding particle film can be achieved inside the SlideRec. The residence time of particle flow within the SlideRec is estimated to be higher than a falling particle receiver and similar to that of an obstructed-flow receiver. The results of the thermal model (incorporating reflective, radiative, convective and conductive heat losses) indicate that the SlideRec demonstrates a higher thermal efficiency than the CentRec® under an incoming aperture flux of between 0.1 MW/m2 and 1.7 MW/m2. The concept therefore is promising and is recommended for further experimental exploration.

In the free-living nematode Caenorhabditis elegans, the transmembrane protein SID-2 imports double-stranded RNA into intestinal cells to trigger systemic RNA interference (RNAi), allowing organisms to sense and respond to environmental cues such as the presence of pathogens. This process, known as environmental RNAi, has not been observed in the most closely related parasites that are also within clade V. Previous sequence-based searches failed to identify sid-2 orthologues in available clade V parasite genomes. In this study, we identified sid-2 orthologues in these parasites using genome synteny and protein structure-based comparison, following identification of a SID-2 orthologue in extracellular vesicles from the murine intestinal parasitic nematode Heligmosomoides bakeri. Expression of GFP-tagged H. bakeri SID-2 in C. elegans showed similar localization to the intestinal apical membrane as seen for GFP-tagged C. elegans SID-2, and further showed mobility in intestinal cells in vesicle-like structures. We tested the capacity of H. bakeri SID-2 to functionally complement environmental RNAi in a C. elegans SID-2 null mutant and show that H. bakeri SID-2 does not rescue the phenotype in this context. Our work identifies SID-2 as a highly abundant EV protein whose ancestral function may be unrelated to environmental RNAi, and rather highlights an association with extracellular vesicles in nematodes.

ABSTRACT Chickpea has recently gained prominence in agriculture, being an excellent option for crop rotation in areas cultivated with soybean or corn. Seeds must have good physiological quality, mainly during storage, to ensure crop success. Seeds undergo metabolic reactions that impair their performance when stored improperly. In this context, a study was carried out to evaluate the physiological variables of the chickpea cultivar BRS Aleppo in different types of packaging and storage environments. The analyses were performed with seeds evaluating water content, germination, first count, and accelerated aging, according to established standards. Therefore, the physiological quality of chickpea seeds can be preserved through controlled storage in hermetic packaging, thus ensuring their viability and vigor over time.

By Kachina Yeager, Shelley Buck, and Sage Yeager. Mni Wičoni. Water is life. For many of us, water truly is synonymous with life—and not only because human life as we understand it necessitates water for survival. For me, as a Dakota person who also happens to be a poet, I think of water as a type of lineage. I can use waterways as a map that transcends borders of nationhood, of spatial and temporal constraint. In this way, water is a map of not only my life, but all those lives interwoven into the same cycle of water.

Aquaculture in exposed and/or distant ocean sites is an emerging industry and field of study that addresses the need to improve food security along with the challenges posed by expansion of urban and coastal stakeholders into nearshore and sheltered marine waters. This move necessitates innovative solutions for this industry to thrive in high-energy environments. Some innovative research has increased understanding of the physics, hydrodynamics, and structural requirements enabling the development of appropriate systems. The blue mussel (Mytilus edulis), the New Zealand green shell or green lipped mussel (Perna canaliculus), and the Pacific Oyster (Magallana gigas), are the primary targets for commercial exposed bivalve aquaculture. Researchers and industry members are actively advancing existing structures and developing new structures and methodologies for these and alternative high-value species suitable for such conditions. For macroalgae (seaweed) cultivation, such as sugar kelp (Saccharina latissimi), oar weed (Laminaria digitata), or kelp sp. (Ecklonia sp.), longline systems are commonly used, but further development is needed to withstand fully exposed environments and improve productivity and efficiency. In marine finfish aquaculture, three primary design categories for open ocean net pens are identified: flexible gravity pens, rigid megastructures, closed pens, and submersible pens. As aquaculture ventures into more demanding environments, a concerted focus on operational efficiency is imperative. This publication considers the commercial and research progress relating to the requirements of aquaculture’s expansion into exposed seas, with a particular focus on the cultivation of bivalves, macroalgae, and marine finfish cultivation technologies and structural developments.

Paediatric patients often present with symptoms of respiratory illnesses in the weeks leading up to surgery. Current or recent illness can increase the risk of experiencing perioperative respiratory complications. Ideally, children with recent illnesses should be identified before coming to the hospital to determine the safest course of action. We recognised that our system lacked a standardised process for documenting preoperative respiratory illness during the preoperative phone call. The global aim of this quality improvement initiative was to decrease paediatric perioperative respiratory adverse events. The SMART Aim (Specific, Measurable, Achievable, Relevant and Time-bound) was to increase the percentage of patients with standardised documentation of preoperative respiratory illness from 0% to 90% by 1 March 2023. Implementation of a standardised preoperative illness questionnaire increased standardised illness documentation from 0% to 95%. Nurses quickly adopted this intervention and easily integrated it into their routine workflow. Clinical leaders elected to implement the intervention electronically across all three operating room (OR) locations (main OR, satellite location and procedure centre). Future implementation of additional standardised preoperative processes will be needed to improve the global aim of decreasing perioperative respiratory complications.

This work attempts to define metrics for hydrodynamic exposure, using known oceanographic variables to provide a universal site assessment method for mariculture structures. Understanding environmental conditions driving open-ocean mariculture siting is crucial in establishing consistent ocean governance, minimizing adverse environmental impacts, and facilitating economically sustainable farm operations. To provide a metric of oceanic conditions and associated requirements for structural design and operation of aquaculture systems, six Exposure Indices (EI) are proposed that consider physical energy levels related to hydrodynamic forces at a site. Four of the proposed indices consider only environmental conditions, while the other two also consider the dimensions of the gear that is exposed to the external loads. These indices are: Exposure Velocity (EV), Exposure Velocity at Reference Depth (EVRD), Specific Exposure Energy (SEE), Depth-integrated Energy Flux (DEF), Structure-centered Depth-integrated Energy (SDE), and a Structure-centered Drag-to-Buoyancy Ratio (SDBR). While these indices are derived with a focus on aquaculture structures, they may also have applications for estimating biological stressors and operational challenges. The proposed exposure indices were evaluated for a range of known aquaculture sites around the world. A sensitivity analysis was conducted that quantified the relationship between the exposure indices and storm event return period. At a regional scale, hindcast numerical data for the German Bight combined with calculations of 50-year extreme values were used to calculate and map each proposed index spatially. Resulting maps showed that exposure is not simply a function of distance from shore. The six indices show plausible performance regarding the objective assessment of aquaculture sites. The authors herein present the indices to the aquaculture and ocean engineering communities for discussion, application, and potential adoption of one or more of the proposed indices.

ABSTRACT Conventional Mycoplasma spp. diagnostics involve culture, often considered the gold standard in diagnostic test evaluation. However, culture protocols lack empirical derivation and primarily adhere to National Mastitis Council recommendations, tracing back to initial cultivation of Mycoplasma bovis. Despite a wide range of carbon dioxide (CO2) supplementation reported in literature, specific impacts of CO2 on Mycoplasma spp. growth remain unexplored. Our objective was to assess the effect of CO2 concentration on growth detection rates of 24 Mycoplasma spp. isolates from dairy cows. These isolates, mainly M. bovis, were incubated at 37°C in triplicate and three dilution ranges under three CO2 conditions: ambient air or 5% CO2 or 10% CO2. Bacterial growth was evaluated on incubation days 3, 5, 7, and 10. When cultured using ambient air, log10 cfu/mL was lower on days 3, 5, and 7 of incubation compared with isolates incubated in the recommended 5% or 10% CO2, with less variation observed in ambient air compared with 5% or 10% CO2. However, by 10 days of incubation, no differences in the detection of observable growth were noted among isolates incubated in ambient air, 5% CO2, or 10% CO2. Consequently, Mycoplasma spp. isolated from dairy cattle demonstrated growth after the recommended 7–10 days of culture, even in the absence of supplemental CO2. Given the expected concentration of M. bovis in (sub)clinical samples had similar concentrations to those used in our study, with the majority of isolates being M. bovis, we recommend expanding CO2 concentration ranges in M. bovis culture from 10% CO2 to ambient air when incubating for 10 days. However, the turnaround time could be shortened when incubating with supplemental CO2.IMPORTANCECurrent Mycoplasma spp. culture protocols lack empirical derivation concerning carbon dioxide (CO2) supplementation and are primarily based on the initial cultivation of Mycoplasma bovis. This study indicates that the suitable range for CO2 supplementation is broader than what is currently recommended by the National Mastitis Council for culturing within the specified 7–10 days. No differences in bacterial growth detection rates were observed among ambient air, 5% CO2, or 10% CO2 supplementation during the 7- and 10-day incubation intervals. These new insights provide evidence supporting the possibility of culturing Mycoplasma spp. under ambient air conditions in a laboratory setting.

The Ebola Data Platform (EDP) was developed to strengthen knowledge and capacity across health, research, and humanitarian communities to reduce the impact of Ebola through responsible data use. This collaborative initiative was established by West African governments, NGOs, academic organisations, and intra-governmental health organisations directly involved in the 2013–2016 West African Ebola outbreak. The platform was established to provide a centralised, standardised dataset of individual patient data collected during the outbreak for the purpose of research to improve Ebola treatment and control, and includes over 13,600 patient records of individuals infected and treated from 22 different Ebola treatment centres across Guinea, Sierra Leone, Liberia, and Nigeria. Patient data are available from treatment centre triage and admission, inpatient clinical observations, and outcomes, with outpatient follow-up available for some datasets. Data include signs and symptoms, pre-existing comorbidities, vital signs, laboratory testing, treatments, complications, dates of admission and discharge, mortality, viral strains, and other data. This publication describes characteristics of the EDP dataset, its architecture, methods for data access and tools for utilising the dataset.

As in the transport sector, it is also necessary to investigate alternatives to fossil diesel fuel in the agricultural sector. In addition to technical feasibility, ecological viability and social acceptance, economic viability is ultimately decisive in determining whether an alternative energy source is competitive. Against this background, in this paper, a cost calculation model is described to analyze the competitiveness of different future technologies and applied on the case of future electrical energy supply concepts. The model is applied to compare a continuous energy supply system via a wide-span system (WSS) with a discontinuous battery swapping system (BSS) on the example of tillage. The results show that on area sizes of more than 100 ha, a continuous energy supply for agricultural machinery with a WSS is competitive to a discontinuous BSS.

Synthetic genetic circuits have revolutionised our capacity to control cell viability by conferring microorganisms with programmable functionalities to limit survival to specific environmental conditions. Here, we present the GenoMine safeguard, a CRISPR-Cas9-based kill switch for the biotechnological workhorse Pseudomonas putida that employs repetitive genomic elements as cleavage targets to unleash a highly genotoxic response. To regulate the system’s activation, we tested various circuit-based mechanisms including the digitalised version of an inducible expression system that operates at the transcriptional level and different options of post-transcriptional riboregulators. All of them were applied not only to directly control Cas9 and its lethal effects, but also to modulate the expression of two of its inhibitors: the AcrIIA4 anti-CRISPR protein and the transcriptional repressor TetR. Either upon direct induction of the endonuclease or under non-induced conditions of its inhibitors, the presence of Cas9 suppressed cell survival which could be exploited beyond biocontainment in situations where further CRISPR genome editing is undesirable.

We report the generation of a gene-edited human induced pluripotent stem cell (iPSC) line from an Alzheimer’s disease patient-derived iPSC line harbouring the PSEN1 H163R mutation. This line demonstrates pluripotent stem cell morphology, expression of pluripotency markers, and maintains a normal karyotype.

Background: International guidelines recommend a side-lying recovery position for unresponsive individuals with normal breathing who do not require cardiopulmonary resuscitation. However, high-certainty evidence about an optimal recovery position is lacking. Recent guidelines recommend a position with the arm extended rather than bent, hypothesizing that venous drainage in the dependent lower arm might be compromised. This cross-over randomized controlled trial aims to evaluate the effect of recovery positions with bent or extended arm on perfusion of the lower forearm and comfort. Methods: Eight healthy volunteers were placed in each of the recovery positions for 15 min, in random order, with an interval of 15 min in supine position. Various perfusion indices of the dependent arm were assessed by radial artery tonometry, ulnar artery echo doppler, and venous congestion plethysmography, as well as participant discomfort, pain and skin discoloration. Differences in outcomes were analyzed with linear mixed models. Results: Our study found no statistically significant difference in systolic peripheral arterial pressure in the radial artery, peripheral venous pressure at the back of the hand, oxygen saturation, heart rate, subjective pain and discomfort, when comparing both postures. Participants slightly experienced more skin discoloration in the position with extended arm. Conclusions: We conclude that, since perfusion of the dependent arm was shown to be similar in both positions, both recovery positions can be used. These conclusions fill a gap in evidence and can further support the treatment recommendations regarding the recovery position in first aid settings.

BackgroundAlthough super-boosted lopinavir/ritonavir (LPV/r; ratio 4:4 instead of 4:1) is recommended for infants living with HIV and receiving concomitant rifampicin, in clinical practice, many different LPV/r dosing strategies are applied due to poor availability of pediatric separate ritonavir formulations needed to superboost. We evaluated LPV pharmacokinetics in infants with HIV receiving LPV/r dosed according to local guidelines in various sub-Saharan African countries with or without rifampicin-based tuberculosis (TB) treatment.MethodsThis was a 2-arm pharmacokinetic substudy nested within the EMPIRICAL trial (#NCT03915366). Infants aged 1-12 months recruited into the main study were administered LPV/r according to local guidelines and drug availability either with or without rifampicin-based TB treatment; during rifampicin cotreatment, they received double-dosed (ratio 8:2) or semisuperboosted LPV/r (adding a ritonavir 100 mg crushed tablet to the evening LPV/r dose). Six blood samples were taken over 12 hours after intake of LPV/r.ResultsIn total, 14/16 included infants had evaluable pharmacokinetic curves; 9/14 had rifampicin cotreatment (5 received double-dosed and 4 semisuperboosted LPV/r). The median (IQR) age was 6.4 months (5.4-9.8), weight 6.0 kg (5.2-6.8), and 10/14 were male. Of those receiving rifampicin, 6/9 infants (67%) had LPV Ctrough

A small percentage of bladder cancers in the general population have been found to harbor DNA viruses. In contrast, up to 25% of tumors of solid organ transplant recipients, who are at an increased risk of developing bladder cancer and have an overall poorer outcomes, harbor BK polyomavirus (BKPyV). To better understand the biology of the tumors and the mechanisms of carcinogenesis from potential oncoviruses, we performed whole genome and transcriptome sequencing on bladder cancer specimens from 43 transplant patients. Nearly half of the tumors from this patient population contained viral sequences. The most common were from BKPyV (N=9, 21%), JC polyomavirus (N=7, 16%), carcinogenic human papillomaviruses (N=3, 7%), and torque teno viruses (N=5, 12%). Immunohistochemistry revealed variable Large T antigen expression in BKPyV-positive tumors ranging from 100% positive staining of tumor tissue to less than 1%. In most cases of BKPyV-positive tumors, the viral genome appeared to be clonally integrated into the host chromosome consistent with microhomology-mediated end joining and coincided with focal amplifications of the tumor genome similar to other virus-mediated cancers. Significant changes in host gene expression consistent with the functions of BKPyV Large T antigen were also observed in these tumors. Lastly, we identified four mutation signatures in our cases, with those attributable to APOBEC3 and SBS5 being the most abundant. Mutation signatures associated with an antiviral drug, ganciclovir, and aristolochic acid, a nephrotoxic compound found in some herbal medicines, were also observed. The results suggest multiple pathways to carcinogenesis in solid organ transplant recipients with a large fraction being virus-associated.