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Laser-driven ion acceleration provides ultrashort, high-charge, low-emittance beams, which are desirable for a wide range of high-impact applications. Yet after decades of research, a significant increase in maximum ion energy is still needed. This paper introduces a quality-preserving staging concept for ultraintense ion bunches that is seamlessly applicable from the nonrelativistic plasma source to the relativistic regime. Full three-dimensional particle-in-cell simulations prove robustness and capture of a high-charge proton bunch, suitable for readily available and near-term laser facilities. Published by the American Physical Society 2024

It is widely accepted that the next lepton collider beyond a Higgs factory would require center-of-mass energy of the order of up to 15 TeV. Since, given reasonable space and cost restrictions, conventional accelerator technology reaches its limits near this energy, high-gradient advanced acceleration concepts are attractive. Advanced and novel accelerators (ANAs) are leading candidates due to their ability to produce acceleration gradients on the order of 1-100 GV/m, leading to compact acceleration facilities. However, intermediate energy facilities (IEF) are required to test the critical technology elements on the way towards multi-TeV-class collliders. Here a science case for a 20-100 GeV center-of-mass energy ANA-based lepton collider that can be a candidate for an intermediate energy facility is presented. The IEF can provide numerous opportunities for high energy physics studies including precision Quantum Chromodynamics and Beyond the Standard Model physics measurements, investigation of charged particle interactions with extreme electromagnetic fields, and exploring muon and proton beam acceleration. Possible applications of this collider include the studies of γγ and electron beam-fixed target/beamdump collider designs. Thus, the goal of the proposed IEF is to both carry out particle physics measurements in the 20-100 GeV ranges as well as to serve as an ANA demonstrator facility.

Layered double hydroxide (LDH) phases that form during cement hydration can incorporate a variety of interlayer anions in their interlayer positions. Here, a range of phases of general formula [MII(1−x)MIII(x)(OH)2][An−]x/n·zH2O were synthesized, where MII = Mg2+ (hydrotalcite) or Ca2+ (AFm), MIII = Al3+ such that [MII/Al] = 2 (Ca and Mg, atomic units) or 3 (Mg only), and A = Cl−, Br−, or I−. All the synthesized phases were characterized to assess their composition, density, and crystal structure. By approach from undersaturation, the solubility data of these compounds was measured at 5, 25, and 60°C. This thermochemical data was used to successfully model their formation using thermodynamic modeling and to infer the fields of stability of these compounds for conditions of relevance to cementitious systems. It is seen that halide-containing hydrotalcite phases strongly compete with hydroxide-containing hydrotalcite, with the latter prevailing at high pH. In contrast, halide-containing AFm compounds are more stable compared with hydroxide-containing AFm compositions.

Human milk (HM) contains macronutrients, micronutrients, and a multitude of other bioactive factors, which can have a long-term impact on infant growth and development. We systematically searched MEDLINE, EMBASE, Cochrane Library, Scopus, and Web of Science to synthesize evidence published between 1980 and 2022 on HM components and anthropometry through 2 y of age among term-born infants. From 9992 abstracts screened, 141 articles were included and categorized based on their reporting of HM micronutrients, macronutrients, or bioactive components. Bioactives including hormones, HM oligosaccharides (HMOs), and immunomodulatory components are reported here, based on 75 articles from 69 unique studies reporting observations from 9980 dyads. Research designs, milk collection strategies, sampling times, geographic and socioeconomic settings, reporting practices, and outcomes varied considerably. Meta-analyses were not possible because data collection times and reporting were inconsistent among the studies included. Few measured infant HM intake, adjusted for confounders, precisely captured breastfeeding exclusivity, or adequately described HM collection protocols. Only 5 studies (6%) had high overall quality scores. Hormones were the most extensively examined bioactive with 46 articles (n = 6773 dyads), compared with 13 (n = 2640 dyads) for HMOs and 12 (n = 1422 dyads) for immunomodulatory components. Two studies conducted untargeted metabolomics. Leptin and adiponectin demonstrated inverse associations with infant growth, although several studies found no associations. No consistent associations were found between individual HMOs and infant growth outcomes. Among immunomodulatory components in HM, IL-6 demonstrated inverse relationships with infant growth. Current research on HM bioactives is largely inconclusive and is insufficient to address the complex composition of HM. Future research should ideally capture HM intake, use biologically relevant anthropometrics, and integrate components across categories, embracing a systems biology approach to better understand how HM components work independently and synergistically to influence infant growth.

Human milk (HM) provides a plethora of nutritional and non-nutritional compounds that support infant development. For many compounds, concentrations vary substantially among mothers and across lactation, and their impact on infant growth is poorly understood. We systematically searched MEDLINE, Embase, the Cochrane Library, Scopus, and Web of Science to synthesize evidence published between 1980 and 2022 on HM components and anthropometry through 2 y of age among term-born infants. Outcomes included weight-for-length, length-for-age, weight-for-age, body mass index (in kg/m2)-for-age, and growth velocity. From 9992 abstracts screened, 144 articles were included and categorized based on their reporting of HM micronutrients, macronutrients, or bioactive components. Micronutrients (vitamins and minerals) are reported here, based on 28 articles involving 2526 mother-infant dyads. Studies varied markedly in their designs, sampling times, geographic and socioeconomic settings, reporting practices, and the HM analytes and infant anthropometrics measured. Meta-analysis was not possible because data were sparse for most micronutrients. The most-studied minerals were zinc (15 articles, 1423 dyads) and calcium (7 articles, 714 dyads). HM iodine, manganese, calcium, and zinc concentrations were positively associated with several outcomes (each in ≥2 studies), whereas magnesium (in a single study) was negatively associated with linear growth during early lactation. However, few studies measured HM intake, adjusted for confounders, provided adequate information about complementary and formula feeding, or adequately described HM collection protocols. Only 4 studies (17%) had high overall quality scores. The biological functions of individual HM micronutrients are likely influenced by other HM components; yet, only 1 study analyzed data from multiple micronutrients simultaneously, and few addressed other HM components. Thus, available evidence on this topic is largely inconclusive and fails to address the complex composition of HM. High-quality research employing chronobiology and systems biology approaches is required to understand how HM components work independently and together to influence infant growth and to identify new avenues for future maternal, newborn, or infant nutritional interventions.

Among exclusively breastfed infants, human milk (HM) provides complete nutrition in the first mo of life and remains an important energy source as long as breastfeeding continues. Consisting of digestible carbohydrates, proteins, and amino acids, as well as fats and fatty acids, macronutrients in human milk have been well studied; however, many aspects related to their relationship to growth in early life are still not well understood. We systematically searched Medline, EMBASE, the Cochrane Library, Scopus, and Web of Science to synthesize evidence published between 1980 and 2022 on HM components and anthropometry through 2 y of age among term-born healthy infants. From 9992 abstracts screened, 57 articles reporting observations from 5979 dyads were included and categorized based on their reporting of HM macronutrients and infant growth. There was substantial heterogeneity in anthropometric outcome measurement, milk collection timelines, and HM sampling strategies; thus, meta-analysis was not possible. In general, digestible carbohydrates were positively associated with infant weight outcomes. Protein was positively associated with infant length, but no associations were reported for infant weight. Finally, HM fat was not consistently associated with any infant growth metrics, though various associations were reported in single studies. Fatty acid intakes were generally positively associated with head circumference, except for docosahexaenoic acid. Our synthesis of the literature was limited by differences in milk collection strategies, heterogeneity in anthropometric outcomes and analytical methodologies, and by insufficient reporting of results. Moving forward, HM researchers should accurately record and account for breastfeeding exclusivity, use consistent sampling protocols that account for the temporal variation in HM macronutrients, and use reliable, sensitive, and accurate techniques for HM macronutrient analysis.

A major challenge in mass spectrometry-based phosphoproteomics lies in identifying the substrates of kinases, as currently only a small fraction of substrates identified can be confidently linked with a known kinase. Machine learning techniques are promising approaches for leveraging large-scale phosphoproteomics data to computationally predict substrates of kinases. However, the small number of experimentally validated kinase substrates (true positive) and the high data noise in many phosphoproteomics datasets together limit their applicability and utility. Here, we aim to develop advanced kinase-substrate prediction methods to address these challenges. Using a collection of seven large phosphoproteomics datasets, and both traditional and deep learning models, we first demonstrate that a pseudo-positive learning strategy for alleviating small sample size is effective at improving model predictive performance. We next show that a data resampling-based ensemble learning strategy is useful for improving model stability while further enhancing prediction. Lastly, we introduce an ensemble deep learning model (SnapKin) by incorporating the above two learning strategies into a snapshot ensemble learning algorithm. We propose SnapKin, an ensemble deep learning method, for predicting substrates of kinases from large-scale phosphoproteomics data. We demonstrate that SnapKin consistently outperforms existing methods in kinase-substrate prediction. SnapKin is freely available at https://github.com/PYangLab/SnapKin.

Defect engineering is foundational to classical electronic device development and for emerging quantum devices. Here, we report on defect engineering of silicon with ion pulses from a laser accelerator in the laser intensity range of 1019 W cm−2 and ion flux levels of up to 1022 ions cm−2 s−1, about five orders of magnitude higher than conventional ion implanters. Low energy ions from plasma expansion of the laser-foil target are implanted near the surface and then diffuse into silicon samples locally pre-heated by high energy ions from the same laser-ion pulse. Silicon crystals exfoliate in the areas of highest energy deposition. Color centers, predominantly W and G-centers, form directly in response to ion pulses without a subsequent annealing step. We find that the linewidth of G-centers increases with high ion flux faster than the linewidth of W-centers, consistent with density functional theory calculations of their electronic structure. Intense ion pulses from a laser-accelerator drive materials far from equilibrium and enable direct local defect engineering and high flux doping of semiconductors.

Abstract Background Involving the public in evidence synthesis research is challenging due to the highly analytic nature of the projects, so it is important that involvement processes are documented, reflected upon, and shared to devise best practices. There is a literature gap on the involvement of the public in individual participant data meta-analyses, particularly in public health projects. We aimed to document and reflect on our collective experiences of involving and being involved as public stakeholders at all stages of a systematic review and individual participant data meta-analysis project. Methods We formed a stakeholder group made of four members of the public at the beginning of our evidence synthesis project comprising a systematic review, an aggregate data meta-analysis, and an individual participant data meta-analysis of mindfulness-based programmes for mental health promotion in non-clinical adults. Following each group meeting, members and participating researchers completed written reflections; one group member collected and collated these. At the end of the project, a reflective writing workshop was held before all members completed their final reflections. Everyone completed an adapted, open-ended questionnaire which asked about what did and did not work well, the overall experience, what could be improved, and the felt impact the stakeholder group had on the research. Results Overall, the stakeholders and researchers reported a positive experience of working together. Positives from the stakeholders’ point of view included learning new skills, experiencing research, and making new friends. For the researchers, stakeholders helped them focus on what matters to the public and were reinvigorating research partners. The challenges stakeholders experienced included having long gaps between meetings and feeling overwhelmed. The researchers found it challenging to strike the balance between asking stakeholders to be involved and for them to learn research-related skills without overburdening them and making sure that the learning was engaging. When looking back at their experience, stakeholders described seeing their impact on the project in hindsight but that this was not felt while the project was being carried out. Conclusion Successfully involving the public in complex evidence synthesis projects is possible and valuable from the points of view of the researchers and the stakeholders. However, it requires a significant time, skill, and resource investment that needs to be factored in from project inception. Further guidance and stakeholder training materials would be helpful. Specific suggestions are provided.

Abstract Background Australian Rural Resident Medical Officer Cadetships are awarded to medical students interested in a rural medical career. The Rural Residential Medical Officer Cadetship Program (Cadetship Program) is administered by the Rural Doctors Network on behalf of the NSW Ministry of Health. This study aimed to assess the overall experience of medical students and key factors that contributed to their satisfaction with the Cadetship Program. Methods A quantitative cross-sectional study was conducted among 107 former cadets who had completed the Cadetship Program. Data on medical students’ experience with the Cadetship Program (outcome variable) and potential explanatory variables were collected using a structured self-administered questionnaire. Explanatory variables included gender, geographical location, rural health club membership, rural clinical school attendance, financial support, mentorship benefits, networking opportunities, influence on career decisions, opportunity for preferential placements, and relocation. Both bivariate (Pearson’s chi-squared test) and multiple logistic regression analysis were employed to identify the factors associated with medical students’ overall experience with the Cadetship Program. The non-linear analysis was weighted to represent the rural/remote health workforce, in Stata/SE 14.1. Results Our results indicate that 91% of medical students were satisfied with the Cadetship Program. The logistic regression model identified two significant predictors of a positive experience with the Cadetship Program. Medical students who perceived financial support as beneficial were significantly more likely to report a satisfactory program experience (aOR = 6.22, 95% CI: 1.36–28.44, p = 0.019) than those who perceived financial support as not beneficial. Similarly, those who valued networking opportunities were more likely to have a positive view of their cadetship experience (aOR = 10.06, 95% CI: 1.11–91.06, p = 0.040) than their counterparts. Conclusion Our study found that students who valued financial support and networking opportunities had the most positive views of the Cadetship Program. These findings demonstrate that the Cadetship Program may be most helpful for those who need financial support and for students who seek networking opportunities. These findings increase our knowledge about the characteristics of medical students who have the most positive experiences with the Cadetship Program. They help us to understand the mechanisms of influence of such programs on individuals’ decisions to be part of the future rural health workforce.

Abstract Background Plasma total magnesium concentration (tMg) is a prognostic indicator in cats with chronic kidney disease (CKD), shorter survival time being associated with hypomagnesemia. Whether this risk factor is modifiable with dietary magnesium supplementation remains unexplored. Objectives Evaluate effects of a magnesium‐enriched phosphate‐restricted diet (PRD) on CKD–mineral bone disorder (CKD‐MBD) variables. Animals Sixty euthyroid client‐owned cats with azotemic CKD, with 27 and 33 allocated to magnesium‐enriched PRD or control PRD, respectively. Methods Prospective double‐blind, parallel‐group randomized trial. Cats with CKD, stabilized on a PRD, without hypermagnesemia (tMg >2.43 mg/dL) or hypercalcemia (plasma ionized calcium concentration, (iCa) >6 mg/dL), were recruited. Both intention‐to‐treat and per‐protocol (eating ≥50% of study diet) analyses were performed; effects of dietary magnesium supplementation on clinicopathological variables were evaluated using linear mixed effects models. Results In the per‐protocol analysis, tMg increased in cats consuming a magnesium‐enriched PRD (β, 0.25 ± .07 mg/dL/month; P 2.92 mg/dL, but none experienced adverse effects. Rate of change in iCa differed between groups (P = .01), with decreasing and increasing trends observed in cats fed magnesium‐enriched PRD and control PRD, respectively. Four control cats developed ionized hypercalcemia versus none in the magnesium supplemented group. Log‐transformed plasma fibroblast growth factor‐23 concentration (FGF23) increased significantly in controls (β, 0.14 ± .05 pg/mL/month; P = .01), but remained stable in the magnesium supplemented group (β, 0.05±.06 pg/mL/month; P =.37). Conclusions and Clinical Importance Magnesium‐enriched PRD is a novel therapeutic strategy for managing feline CKD‐MBD in cats, further stabilizing plasma FGF23 and preventing hypercalcemia.

This study presents an updated and homogenised ozone time series covering 34 years (1987–2020) of ozonesonde measurements at Lauder, New Zealand, and attributes vertically resolved ozone trends using a multiple linear regression (MLR) analysis and a chemistry–climate model (CCM). Homogenisation of the time series leads to a marked difference in ozone values before 1997, in which the ozone trends are predominantly negative from the surface to ∼ 30 km, ranging from ∼ −2 % per decade to −13 % per decade, maximising at around 12–13 km, in contrast to the uncorrected time series which shows no clear trends for this period. For the post-2000 period, ozone at Lauder shows negative trends in the stratosphere, maximising just below 20 km (∼ −5 % per decade) despite the fact that stratospheric chlorine and bromine from ozone-depleting substances (ODSs) have both been declining since 1997. However, the ozone trends change from negative for 1987–1999 to positive in the post-2000 period in the free troposphere. The post-2000 ozone trends calculated from the ozonesonde measurements compare well with those derived from the co-located low-vertical-resolution Fourier-transform infrared spectroscopy (FTIR) ozone time series. The MLR analysis identifies that the increasing tropopause height, associated with CO2-driven dynamical changes, is the leading factor driving the continuous negative trend in lower-stratospheric ozone at Lauder over the whole observational period, whilst the ozone-depleting substances (ODSs) only contribute to the negative ozone trend in the lower stratosphere over the pre-1999 period. Meanwhile, stratospheric temperature changes contribute significantly to the negative ozone trend above 20 km over the post-2000 period. Furthermore, the chemistry–climate model (CCM) simulations that separate the effects of individual forcings show that the predominantly negative modelled trend in ozone for the 1987–1999 period is driven not only by ODSs but also by increases in greenhouse gases (GHGs), with large but opposing impacts from methane (positive) and CO2 (negative), respectively. Over the 2000–2020 period, the model results show that the CO2 increase is the dominant driver for the negative trend in the lower stratosphere, in agreement with the MLR analysis. Although the model underestimates the observed negative ozone trend in the lower stratosphere for both periods, it clearly shows that CO2-driven dynamical changes have played an increasingly important role in driving the lower-stratospheric ozone trends in the vicinity of Lauder.

Abstract Background Women who live with disadvantages such as socioeconomic deprivation, substance misuse, poor mental health, or domestic abuse face inequalities in health before, during, and after pregnancy and for their infants through to childhood. Women do not experience these factors alone; they accumulate and interact. Therefore, there is a need for an overview of interventions that work across health and social care and target women at risk of inequalities in maternal or child health. Methods Systematic review methodology will be used to identify systematic reviews from high-income countries that describe interventions aiming to reduce inequalities for women who experience social disadvantage during pregnancy. We will describe the range of interventions and their effectiveness in reducing inequalities in maternal or child health. Any individual, hospital, or community-level activity specific to women during the pre-conception, antenatal, or postpartum period up to 1 year after birth will be included, regardless of the setting in which they are delivered. We will search eight electronic databases with the pre-determined search strategy and supplement them with extensive grey literature searches. We will present a narrative synthesis, taking into account the quality assessment and coverage of included studies. Discussion Inequalities in maternal and child health are a key priority area for national policymakers. Understanding the range and effectiveness of interventions across the perinatal period will inform policy and practice. Identifying gaps in the evidence will inform future research. Systematic review registration PROSPERO CRD42023455502.

Abstract Background Identification of nephrocalcinosis in cats with chronic kidney disease (CKD) is of clinical interest but the ability of ultrasonography to detect nephrocalcinosis is uncertain. Objectives To compare ultrasonography, micro‐computed tomography (μCT) and histopathology for identification of nephrocalcinosis. Animals Twelve kidneys from 7 euthyroid client‐owned cats with CKD. Methods Descriptive study. Renal ultrasonography was performed ante‐mortem for nephrocalcinosis detection. Kidneys were grouped based on nephrocalcinosis: present, suspected, or absent. When cats died, necropsy was performed. Renal tissue was evaluated using μCT for macroscopic nephrocalcinosis, and nephrocalcinosis volume‐to‐kidney tissue ratio (macro‐VN:KT) and sagittal nephrocalcinosis area‐to‐kidney tissue ratio (macro‐AN:KT) were calculated. Each kidney subsequently was bisected longitudinally, formalin‐fixed, and paraffin‐embedded for microscopic nephrocalcinosis assessment using von Kossa and Alizarin red staining with AN:KT (VK‐micro‐AN:KT and AR‐micro‐AN:KT) quantified using ImageJ. Data are presented as median (range). Relationships between macroscopic and microscopic AN:KT were assessed using Spearman's correlation. Results Nephrocalcinosis by ultrasonography was considered to be absent in 3, suspected in 3, and present in 5 kidneys; 1 kidney had nephrolithiasis with nephrocalcinosis. The macro‐VN:KT was 0.001%, 0.001%, and 0.019%, and the macro‐AN:KT was 0.08%, 0.30%, and 1.47%, respectively. Histologically, VK‐micro‐AN:KT was 0.21%, 2.85%, and 4.56%, and AR‐micro‐AN:KT was 1.73%, 5.82%, and 8.90% for kidneys where ultrasonographic macro‐nephrocalcinosis was absent, suspected, or present, respectively. A strong correlation was identified between macroscopic (macro‐AN:KT) and microscopic (VK‐micro‐AN:KT) nephrocalcinosis (rs = 0.76; P = .01). Conclusions and Clinical Importance Ultrasonographically diagnosed nephrocalcinosis correlates well with macroscopic and microscopic nephrocalcinosis at necropsy despite their separation in time.

Abstract Background Microscopic nephrocalcinosis is a common pathological feature of chronic kidney disease (CKD) in cats. Detection of macroscopic nephrocalcinosis using ultrasonography and its implications remain unexplored. Objectives Identify risk factors associated with ultrasound‐diagnosed nephrocalcinosis and evaluate the influence of nephrocalcinosis on CKD progression. Animals Thirty‐six euthyroid client‐owned cats with CKD. Methods Prospective cohort study. Cats with CKD with and without ionized hypercalcemia were enrolled for renal ultrasonography. Cats were categorized according to the presence or absence of ultrasound‐diagnosed nephrocalcinosis. Binary logistic regression was performed to identify nephrocalcinosis risk factors. The influence of nephrocalcinosis on CKD progression was assessed using linear mixed models. Results Ultrasound‐diagnosed nephrocalcinosis was evident in 61% of CKD cats overall, with increased prevalence (81%) in those with hypercalcemia. At enrollment, higher blood ionized calcium concentration (odds ratio [OR], 1.27 per 0.1 mg/dL; P = .01), plasma phosphate concentration (OR, 1.16 per 0.1 mg/dL; P = .05), plasma creatinine concentration (OR, 1.29 per 0.1 mg/dL; P = .02) and alanine aminotransferase activity (OR, 2.08 per 10 U/L; P = .04) were independent nephrocalcinosis risk factors. The rate of change in log‐transformed fibroblast growth factor‐23 differed significantly between groups (P = .04). Cats with CKD and nephrocalcinosis had increasing plasma creatinine concentrations (.03 ± .01 mg/dL/month; P = .04) and phosphate concentrations (.06 ± .02 mg/dL/month; P

We demonstrate ultra-broadband spectral combining of ultrashort pulses from Yb-doped fiber amplifiers, with coherently spectrally synthesized pulse shaping, to achieve tens-of-fs pulses. This method can fully compensate for gain narrowing and high order dispersion over broad bandwidth. We produce 42fs pulses by spectrally synthesizing three chirped-pulse fiber amplifiers and two programmable pulse shapers across an 80nm overall bandwidth. To the best of our knowledge, this is the shortest pulse duration achieved from a spectrally combined fiber system at one-micron wavelength. This work provides a path toward high-energy, tens-of-fs fiber chirped-pulse amplification systems.

The general concept of radiation therapy used in conventional cancer treatment is to increase the therapeutic index by creating a physical dose differential between tumors and normal tissues through precision dose targeting, image guidance, and radiation beams that deliver a radiation dose with high conformality, e.g., protons and ions. However, the treatment and cure are still limited by normal tissue radiation toxicity, with the corresponding side effects. A fundamentally different paradigm for increasing the therapeutic index of radiation therapy has emerged recently, supported by preclinical research, and based on the FLASH radiation effect. FLASH radiation therapy (FLASH-RT) is an ultra-high-dose-rate delivery of a therapeutic radiation dose within a fraction of a second. Experimental studies have shown that normal tissues seem to be universally spared at these high dose rates, whereas tumors are not. While dose delivery conditions to achieve a FLASH effect are not yet fully characterized, it is currently estimated that doses delivered in less than 200 ms produce normal-tissue-sparing effects, yet effectively kill tumor cells. Despite a great opportunity, there are many technical challenges for the accelerator community to create the required dose rates with novel compact accelerators to ensure the safe delivery of FLASH radiation beams.

Some plant species retain mature seeds in plant canopies aboveground which are released later during opportune windows for germination and establishment. This process, known as serotiny, can lead to aerial seedbanks that exist simultaneously with soil seedbanks. However, little is known about how serotiny affects the persistence of weed seeds in the aerial seedbank. A randomized-stratified survey of 117 sites in southern Alberta, Canada, was conducted in 2022 to determine whether the summer-annual tumbleweed Russian thistle (Salsola tragus L.) exhibits seed serotiny. The observational study confirmed that Russian thistle plants exhibit serotiny and that the seeds can exist simultaneously in aerial and soil seedbanks. On average, the plants sampled retained 332 ± 62 viable seeds plant-1 seven to eight months after senescence. This time frame followed winter and emergence of the subsequent generation of plants from the soil seedbank. Russian thistle plants that were attached to the soil retained about double (P = 0.0274) the number of seeds (549 ± 133 viable seeds plant-1) than those detached from the soil (270 ± 71 viable seeds plant-1), likely due to seeds dislodging during movement of the tumbleweeds with prevailing winds. Seeds persisting in aerial seedbanks could evade decay, predation, or lethal germination leading to seed mortality in the soil seedbank, and increase the likelihood of seed persistence and successful establishment of new plants in stressful environments.

ABSTRACT The increasing prevalence of invasive fungal pathogens is dramatically changing the clinical landscape of infectious diseases, posing an imminent threat to public health. Specifically, Cryptococcus neoformans, the human opportunistic pathogen, expresses elaborate virulence mechanisms and is equipped with sophisticated adaptation strategies to survive in harsh host environments. This study extensively characterizes Wos2, an Hsp90 co-chaperone homolog, featuring bilateral functioning for both cryptococcal adaptation and the resulting virulence response. In this study, we evaluated the proteome and secretome signatures associated with wos2 deletion in enriched and infection-mimicking conditions to reveal Wos2-dependent regulation of the oxidative stress response through global translational reprogramming. The wos2Δ strain demonstrates defective intracellular and extracellular antioxidant protection systems, measurable through a decreased abundance of critical antioxidant enzymes and reduced growth in the presence of peroxide stress. Additional Wos2-associated stress phenotypes were observed upon fungal challenge with heat shock, osmotic stress, and cell membrane stressors. We demonstrate the importance of Wos2 for intracellular lifestyle of C. neoformans during in vitro macrophage infection and provide evidence for reduced phagosomal replication levels associated with wos2Δ. Accordingly, wos2Δ featured significantly reduced virulence within impacting fungal burden in a murine model of cryptococcosis. Our study highlights a vulnerable point in the fungal chaperone network that offers a therapeutic opportunity to interfere with both fungal virulence and fitness.IMPORTANCEThe global impact of fungal pathogens, both emerging and emerged, is undeniable, and the alarming increase in antifungal resistance rates hampers our ability to protect the global population from deadly infections. For cryptococcal infections, a limited arsenal of antifungals and increasing rates of resistance demand alternative therapeutic strategies, including an anti-virulence approach, which disarms the pathogen of critical virulence factors, empowering the host to remove the pathogens and clear the infection. To this end, we apply state-of-the-art mass spectrometry-based proteomics to evaluate the impact of a recently defined novel co-chaperone, Wos2, toward cryptococcal virulence using in vitro and in vivo models of infection. We explore global proteome and secretome remodeling driven by the protein and uncover the novel role in modulating the fungal oxidative stress response. Complementation of proteome findings with in vitro infectivity assays demonstrated the protective role of Wos2 within the macrophage phagosome, influencing fungal replication and survival. These results underscore differential cryptococcal survivability and weakened patterns of dissemination in the absence of wos2. Overall, our study establishes Wos2 as an important contributor to fungal pathogenesis and warrants further research into critical proteins within global stress response networks as potential druggable targets to reduce fungal virulence and clear infection.

The emphasis on artificial intelligence (AI) is rapidly increasing across many diverse aspects of society. This manuscript discusses some of the key topics related to the expansion of AI. These include a comparison of the unique cognitive capabilities of human intelligence with AI, and the potential risks of using AI in clinical medicine. The general public attitudes towards AI are also discussed, including patient perspectives. As the promotion of AI in high-risk situations such as clinical medicine expands, the limitations, risks and benefits of AI need to be better understood.

Nanostructured surfaces enhance ion yields in matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS). The spike protein complex, S1, is one fingerprint signature of Sars-CoV-2 with a mass of 75 kDa. Here, we show that MALDI-MS yields of Sars-CoV-2 spike protein ions in the 100 kDa range are enhanced 50-fold when the matrix-analyte solution is placed on substrates that are coated with a dense forest of multi-walled carbon nanotubes, compared to yields from uncoated substrates. Nanostructured substrates can support the development of mass spectrometry techniques for sensitive pathogen detection and environmental monitoring.

We would like to correct an error affecting the horizontal scale of panels (c) and (d) of Fig. 4 in Ref. 1. A scale factor of kp was neglected when generating the plots. The correct figure is shown below. The authors would like to thank Yujian Zhao for pointing out this issue. We would also like to correct a typo introduced during the preparation of the proofs and affecting Eq. (25); the correct equation reads. (Formula presented).

A novel ultraviolet spectrometer has been developed and tested over 10 years at Lauder, New Zealand. The system, UV2, makes alternating measurements of the global and direct UV irradiance and can therefore be used to measure ozone and aerosol optical depth. After an analysis of the stability of UV2, these measurements, along with UV irradiance, are compared to relevant observations made by an additional UV spectrometer (UV4), a Dobson spectrophotometer (no. 072), and two radiometers measuring aerosol optical depth – a Prede sky radiometer and a Middleton Solar radiometer (SP02). UV2 irradiance is shown to be lower than UV4 by between 2.5 % and 3.5 %, with a standard deviation of a similar magnitude. Total column ozone values are shown to agree with Dobson spectrophotometer values with a mean bias of 2.57 Dobson units (DU) and standard deviation of 1.15 DU when using the direct sun measurements. Aerosol optical depth at 400–412 and 500 nm agrees to within 0.015 and is comparable to the difference between the reference radiometers. Further work is needed, particularly in the radiometric calibration at longer wavelengths, in order to determine if this instrument can supersede or enhance measurements made by the Dobson spectrophotometer or the aerosol radiometers.