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Improving photosynthesis, the fundamental process by which plants convert light energy into chemical energy, is a key area of research with great potential for enhancing sustainable agricultural productivity and addressing global food security challenges. This perspective delves into the latest advancements and approaches aimed at optimizing photosynthetic efficiency. Our discussion encompasses the entire process, beginning with light harvesting and its regulation and progressing through the bottleneck of electron transfer. We then delve into the carbon reactions of photosynthesis, focusing on strategies targeting the enzymes of the Calvin-Benson-Bassham (CBB) cycle. Additionally, we explore methods to increase carbon dioxide (CO2) concentration near the Rubisco, the enzyme responsible for the first step of CBB cycle, drawing inspiration from various photosynthetic organisms, and conclude this section by examining ways to enhance CO2 delivery into leaves. Moving beyond individual processes, we discuss two approaches to identifying key targets for photosynthesis improvement: systems modeling and the study of natural variation. Finally, we revisit some of the strategies mentioned above to provide a holistic view of the improvements, analyzing their impact on nitrogen use efficiency and on canopy photosynthesis.

H5 influenza is considered a potential pandemic threat. Recently, H5 viruses belonging to clade 2.3.4.4b have caused large outbreaks in avian and multiple nonhuman mammalian species. Previous studies have identified molecular phenotypes of the viral hemagglutinin (HA) protein that contribute to pandemic potential in humans, including cell entry, receptor preference, HA stability, and reduced neutralization by polyclonal sera. However, prior experimental work has only measured how these phenotypes are affected by a handful of the >10,000 different possible amino-acid mutations to HA. Here, we use pseudovirus deep mutational scanning to measure how all mutations to a 2.3.4.4b H5 HA affect each phenotype. We identify mutations that allow HA to better bind α2-6-linked sialic acids and show that some viruses already carry mutations that stabilize HA. We also measure how all HA mutations affect neutralization by sera from mice and ferrets vaccinated against or infected with 2.3.4.4b H5 viruses. These antigenic maps enable rapid assessment of when new viral strains have acquired mutations that may create mismatches with candidate vaccine virus, and we show that a mutation present in some recent H5 HAs causes a large antigenic change. Overall, the systematic nature of deep mutational scanning combined with the safety of pseudoviruses enables comprehensive measurements of the phenotypic effects of mutations that can inform real-time interpretation of viral variation observed during surveillance of H5 influenza.

IntroductionOpen reduction and fixation are the standard of care for treating mandibular fractures and usually lead to successful healing. However, complications such as delayed healing, non-union, and infection can compromise patient outcomes and increase healthcare costs. The initial inflammatory response, particularly the response involving specific CD8+ T cell subpopulations, is thought to play a critical role in healing long bone fractures. In this study, we investigated the role of these immune cell profiles in patients with impaired healing of mandibular fractures.Materials and methodsIn this prospective study, we included patients with mandibular fractures surgically treated at Charité – Universitätsmedizin Berlin, Germany, between September 2020 and December 2022. We used follow-up imaging and clinical assessment to evaluate bone healing. In addition, we analyzed immune cell profiles using flow cytometry and quantified cytokine levels using electrochemiluminescence-based multiplex immunoassays in preoperative blood samples.ResultsOut of the 55 patients enrolled, 38 met the inclusion criteria (30 men and 8 women; mean age 32.18 years). Radiographic evaluation revealed 31 cases of normal healing and 7 cases of incomplete consolidation, including 1 case of non-union. Patients with impaired healing exhibited increased levels of terminally differentiated effector memory CD8+ T cells (TEMRA) and a higher TEMRA to regulatory T cell (Treg) ratio, compared with those with normal healing.ConclusionsOur analysis of mandibular fracture cases confirms our initial hypothesis derived from long bone fracture healing: monitoring the TEMRA to Treg ratio in preoperative blood can be an early indicator of patients at risk of impaired bone healing. Radiologic follow-up enabled us to detect healing complications that might not be detected by clinical assessment only. This study highlights the potential of individual immune profiles to predict successful healing and may form the basis for future strategies to manage healing complications.

INTRODUCTION: A major site of secondhand smoke exposure for children and adults is the home. Few studies have evaluated the impact of e-cigarette or hookah use on home air quality, despite evidence finding toxic chemicals in secondhand e-cigarette aerosols and hookah smoke. We assessed the effect of e-cigarette and hookah use on home air quality and compared it with air quality in homes where cigarettes were smoked and where no smoking or e-cigarette use occurred. METHODS: Non-smoking homes and homes where e-cigarettes, hookah or cigarettes were used were recruited in the New York City area (n=57) from 2015 to 2019. Particulate matter with diameter less than 2.5 µm (PM2.5), black carbon and carbon monoxide (CO) were measured during a smoking or vaping session, both in a primary smoking room and in an adjacent secondary room where no smoking or vaping occurred. Log transformed data were compared with postanalysis of variance Tukey simultaneous tests. RESULTS: Use of hookah significantly increased PM2.5 levels compared with non-smoking homes, in both the primary and secondary rooms, while use of e-cigarettes increased PM2.5 levels only in primary rooms. Additionally, in-home use of hookah resulted in greater CO concentrations than the use of cigarettes in primary rooms. CONCLUSIONS: Use of e-cigarettes or hookah increases air pollution in homes. For hookah, increases in PM2.5 penetrated even into rooms adjacent to where smoking occurs. Extending smoke-free rules inside homes to include e-cigarette and hookah products is needed to protect household members and visitors from passive exposure to harmful aerosols and gases.

Here, we report on the development of a new quantum cascade laser infrared absorption spectroscopy (QLAS) instrument, the Airborne Tropospheric Tracer In-situ Laser Absorption spectrometer (ATTILA), for atmospheric trace-gas measurements on board of the German High-Altitude Long-range Observatory (HALO) aircraft. Its small and light design makes it suitable for airborne measurements up to approximately 150 hPa of ambient pressure (13–14 km). The dual laser instrument can measure several trace gases simultaneously in two 36.4 m path astigmatic Herriott cells with a data acquisition frequency of 1 Hz. We describe the measurement method and the data acquisition of ATTILA and its in-flight performance by focusing on potential sources of influences on the signal, which we investigated with a dedicated test flight during which the instrument sampled from a constant source. We show that linear critical influences associated with challenging movement patterns can be corrected afterwards, while nonlinear limitations can be minimized by appropriate calibration frequencies and integrated time intervals. During the recent aircraft campaign CAFE Brazil (Chemistry of the Atmosphere Field Experiment in Brazil) from December 2022 to January 2023, carbon monoxide (CO) measurements from ATTILA show a good agreement of a R2 of 0.89 with simultaneous CO measurements from an established IR spectrometer for airborne measurements, the TRacer In Situ TDLAS (tunable diode laser absorption spectroscopy) for Atmospheric Research (TRISTAR), at a 10 s time resolution. First dynamical characteristics and tracer distributions of CO and methane (CH4) over the Amazon rainforest can be identified with ATTILA measurements with a total measurement uncertainty of 10.1 % and 17.5 % for calibration gas mixing ratios of 153 and 1990 ppbv and a data accuracy of 0.3 % and 5.5 % for a data acquisition frequency of 1 Hz for CO and CH4, respectively.

The article deals with a feminist critique of the secular notion of autonomy as a normative basis for the emancipation of the subject. It does so on the basis of discussions related to the so-called post-secular turn in feminist thought. The text is based on a comparison and interpretation of the theoretical insights of Saba Mahmood and Judith Butler. According to Mahmood, the poststructuralist critique of the Enlightenment conception of the subject, as seen in Butler, still places too much emphasis on secular detachment from tradition. In contrast, Saba Mahmood's approach seeks to rehabilitate a 'consolidationist' conception of the subject through which a more positive interpretation of religious ethics can be made, especially (but not only) in the case of Muslim women. The text alsoshows, however, that while Mahmood's reflections challenge Judith Butler's notion of performative identity they connect wellto her later reflections on the precarity of life. The arcticle concludes by assessing to what extent and in what sense the critique of the autonomy of the subjectput forward here can be evaluated as post-secular.

Abstract Background The clinical decision-making of non-conveyance is perceived as complex and difficult by emergency medical services (EMS) professionals. Patients with a transient loss of consciousness (TLOC) based on syncope constitute a significant part of the non-conveyance population. Risk stratification is the basis of the clinical decision-making process by EMS professionals. This risk stratification is based on various patient factors. This study aimed to explore patient factors significantly associated with conveyance decision-making by EMS professionals in patients with a TLOC based on syncope. Methods A cross-sectional vignette study with a factorial survey design was conducted. Patient factors were derived from the “National Protocol Ambulance Care”, and all possible combinations of these factors and underlying categories were combined, resulting in 256 unique vignettes (2*4*4*4*2 = 256). Patient factors presented either low-risk or high-risk factors for adverse events. Data were collected through an online questionnaire, in which participants received a random sample of 15 vignettes. For each vignette, the respondent indicated whether the patient would need to be conveyed to the emergency department or not. A multilevel logistic regression analysis with stepwise backward elimination was performed to analyse factors significantly associated with conveyance decision-making. In the logistic model, we modelled the probability of non-conveyance. Results 110 respondents were included, with 1646 vignettes being assessed. Mean age 45.5 (SD 9.3), male gender 63.6%, and years of experience 13.2 (SD 8.9). Multilevel analysis showed two patient factors contributing significantly to conveyance decision-making: ‘red flags’ and ‘prehospital electrocardiogram (ECG)’. Of these patient factors, three underlying categories were significantly associated with non-conveyance: ‘sudden cardiac death

Objectives:This study aimed to adapt and validate the HIV PrEP Stigma Scale (HPSS) in French and German languages (HPSS-FR/DE) and assess its applicability across diverse linguistic and cultural contexts.Methods:The original scale was adapted to French and German and administered through an online survey in multiple European nations. A four-factor structure was extracted from the data, including negative social consequences, social pressure, self-support, and external support. The scale’s construct validity, reliability, and cross-linguistic consistency were evaluated.Results:The adapted HPSS-FR/DE demonstrated robust psychometric properties, good construct validity, acceptable reliability, and consistent measurement across different languages. This adaptation enhances its utility in multicultural settings, offering a comprehensive tool to assess PrEP-related stigma.Conclusion:This study provides a suitable tool to address PrEP stigma in multicultural environments to enhance PrEP uptake and adherence among men who have sex with men. Moreover, it lays the groundwork for further investigations into PrEP stigma across diverse populations and cultural settings, enabling the development of targeted public health interventions and policies to combat this issue effectively.

A profound understanding of brain disorders is essential for developing more effective treatments, targeted therapies, and reliable diagnoses. Electrical in vitro long-term and repetitive measurements give insight to neural activity of more complex neural circuits and, thus, into malfunctioning caused by illness. Flexible microelectrode arrays (flexMEAs) enable the recording of neural activity with promising spatial and temporal resolution over longer durations. The present study aims to combine the long-term recording by flexMEAs with the cultivation of brain slices inside an incubator. An 8 μm-thin flexMEA with up to 256 electrodes with 30 μm in diameter and interelectrode spacing of 200 μm was fabricated. Characterization showed uniform and reproducible electronic characteristics. Coating with PEDOT:PSS by electropolymerization formed stable low-impedance spectra. The platform is ready for future experiments with brain slices inside an incubator.

Abstract Background Patients with a syncope constitute a challenge for risk stratification in (prehospital) emergency care. Professionals in EMS and ED need to differentiate the high-risk from the low-risk syncope patient, with limited time and resources. Clinical decision rules (CDRs) are designed to support professionals in risk stratification and clinical decision-making. Current CDRs seem unable to meet the standards to be used in the chain of emergency care. However, the need for a structured approach for syncope patients remains. We aimed to generate a broad overview of the available risk stratification tools and identify key elements, scoring systems and measurement properties of these tools. Methods We performed a scoping review with a literature search in MEDLINE, CINAHL, Pubmed, Embase, Cochrane and Web of Science from January 2010 to May 2022. Study selection was done by two researchers independently and was supervised by a third researcher. Data extraction was performed through a data extraction form, and data were summarised through descriptive synthesis. A quality assessment of included studies was performed using a generic quality assessment tool for quantitative research and the AMSTAR-2 for systematic reviews. Results The literature search identified 5385 unique studies; 38 were included in the review. We discovered 19 risk stratification tools, one of which was established in EMS patient care. One-third of risk stratification tools have been validated. Two main approaches for the application of the tools were identified. Elements of the tools were categorised in history taking, physical examination, electrocardiogram, additional examinations and other variables. Evaluation of measurement properties showed that negative and positive predictive value was used in half of the studies to assess the accuracy of tools. Conclusion A total of 19 risk stratification tools for syncope patients were identified. They were primarily established in ED patient care; most are not validated properly. Key elements in the risk stratification related to a potential cardiac problem as cause for the syncope. These insights provide directions for the key elements of a risk stratification tool and for a more advanced process to validate risk stratification tools.

Abstract ACT‐1014‐6470 is an orally available complement factor 5a receptor 1 antagonist and a novel treatment option in auto‐inflammatory diseases. The in vitro inhibition potential of ACT‐1014‐6470 on cytochrome P450 isozymes (CYPs) and its effect on the pharmacokinetics (PK) of the CYP2C19 and CYP3A4 substrates omeprazole and midazolam, respectively, in humans were assessed. In vitro assays were conducted with isoform‐specific substrates in human liver microsomes. In an open‐label, two‐period, fixed‐sequence cocktail study, single doses of 20 mg omeprazole and 2 mg midazolam were administered concomitantly to 20 healthy male subjects alone (treatment A) and after a single dose of 100 mg ACT‐1014‐6470 (treatment B) under fed conditions. Safety and PK assessments were performed. Geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of noncompartmental PK parameters of treatment B versus treatment A were calculated. In vitro, no time‐dependent inhibition was observed and the lowest inhibition constant of 4.3 μM ACT‐1014‐6470 was recorded for CYP2C19. In humans, GMRs (90% CI) of omeprazole PK were 1.9 (1.5–2.5) for maximum plasma concentration (Cmax) and 1.9 (1.5–2.3) for area under the plasma concentration‐time curve from 0 to 12 h (AUC0‐12 h). Midazolam PK showed GMRs (90% CI) of 1.1 (1.1–1.2) for Cmax and 1.5 (1.4–1.6) for AUC0‐24 h. All treatments were well‐tolerated. In line with in vitro results and regulatory risk factor calculation, the increased exposure to omeprazole and midazolam in humans after concomitant administration with a single dose of 100 mg ACT‐1014‐6470 reflected a weak inhibition of CYP2C19 and CYP3A4.

INTRODUCTION: Influenza infections are challenging to monitor at the population level due to many mild and asymptomatic cases and similar symptoms to other common circulating respiratory diseases, including COVID-19. Methods for tracking cases outside of typical reporting infrastructure could improve monitoring of influenza transmission dynamics. Influenza shedding into wastewater represents a promising source of information where quantification is unbiased by testing or treatment-seeking behaviours. METHODS: We quantified influenza A and B virus loads from influent at Switzerland’s three largest wastewater treatment plants, serving about 14% of the Swiss population (1.2 million individuals). We estimated trends in infection incidence and the effective reproductive number (Re) in these catchments during a 2021/22 epidemic and compared our estimates to typical influenza surveillance data. RESULTS: Wastewater data captured the same overall trends in infection incidence as laboratory-confirmed case data at the catchment level. However, the wastewater data were more sensitive in capturing a transient peak in incidence in December 2021 than the case data. The Re estimated from the wastewater data was roughly at or below the epidemic threshold of 1 during work-from-home measures in December 2021 but increased to at or above the epidemic threshold in two of the three catchments after the relaxation of these measures. The third catchment yielded qualitatively the same results but with wider confidence intervals. The confirmed case data at the catchment level yielded comparatively less precise R_e estimates before and during the work-from-home period, with confidence intervals that included one before and during the work-from-home period. DISCUSSION: Overall, we show that influenza RNA in wastewater can help monitor nationwide influenza transmission dynamics. Based on this research, we developed an online dashboard for ongoing wastewater-based influenza surveillance in Switzerland.

Here, we provide tips and tricks for running multisession experiments out of the lab using OpenSesame, a user-friendly experimental tool that is open source and runs on Windows, MacOS, and Linux. We focus on learning experiments that involve the measurement of reaction times. We show how such experiments can be run with traditional desktop-based experiment software on participants’ own notebooks (i.e., out-of-the-lab, but not in a browser). Learning experiments pose specific challenges: accessing individual identifying numbers, accessing session numbers, and counterbalancing conditions across participants. This article includes helpful code and provides hands-on implementation tips that will be useful also beyond the presented use case. The aim of this article is to illustrate how to create multisession learning experiments even with little technical expertise. We conclude that, if done right, out-of-the-lab experiments are a valid alternative to traditional lab testing.

Inflammatory bowel disease (IBD) is an umbrella term for two conditions (Crohn’s Disease and Ulcerative Colitis) that is characterized by chronic inflammation of the gastrointestinal tract. The use of pre-clinical animal models has been invaluable for the understanding of potential disease mechanisms. However, despite promising results of numerous therapeutics in mouse colitis models, many of these therapies did not show clinical benefits in patients with IBD. Single cell RNA-sequencing (scRNA-seq) has recently revolutionized our understanding of complex interactions between the immune system, stromal cells, and epithelial cells by mapping novel cell subpopulations and their remodeling during disease. This technology has not been widely applied to pre-clinical models of IBD. ScRNA-seq profiling of murine models may provide an opportunity to increase the translatability into the clinic, and to choose the most appropriate model to test hypotheses and novel therapeutics. In this review, we have summarized some of the key findings at the single cell transcriptomic level in IBD, how specific signatures have been functionally validated in vivo, and highlighted the similarities and differences between scRNA-seq findings in human IBD and experimental mouse models. In each section of this review, we highlight the importance of utilizing this technology to find the most suitable or translational models of IBD based on the cellular therapeutic target.

BackgroundSwitzerland ranks among the top three healthcare systems in the world with regards to healthcare access, suggesting a high degree of health equity. However, Switzerland has few preventive strategies against smoking abuse. The aim of this study is to clarify whether educational level and citizenship status have an influence on the prevalence of smoking in Switzerland and whether there is health inequity related to a lack of preventive strategies.MethodsWe based our analysis on publicly available health data published in the Swiss government's Swiss health survey (1992–2017). We compared the prevalence of smoking across the years and correlated these data with levels of educational attainment, citizenship status and age.ResultsA continuous significant decline in smokers is observed in the highest education group (TERT). Over time, prevalence was reduced from 29% in 1992 to 23% in 2017 (p < 0.001). The intermediate-level educational group (SEK 2) showed smaller but also significant decline on a 0.05 sigificance level over the same period, from 31% to 29% (p = 0.003). The lowest educational group showed a nonsignificant decline from 28% to 27% (p = 0.6). The population who holds Swiss citizenship showed a decrease in smoking from 28% to 26% within the time frame (p < 0.001). People without Swiss citizenship had a much higher prevalence of smokers, at 38% in 1992 and declining to 32% in 2017 (p < 0.001). All cohorts from age 15 to age 64 have a far higher prevalence of smokers than cohorts at an older age, with the highest prevalence in the 25–34 age group.ConclusionIn Switzerland, individuals with lower levels of education and non-Swiss populations are more susceptible to health risk of smoking. This is despite the existence of a high-quality healthcare system that has nevertheless failed to negated health inequities.

Abstract There is growing recognition that animal methods bias, a preference for animal‐based methods where they are not necessary or where nonanimal‐based methods may already be suitable, can impact the likelihood or timeliness of a manuscript being accepted for publication. Following April 2022 workshop about animal methods bias in scientific publishing, a coalition of scientists and advocates formed a Coalition to Illuminate and Address Animal Methods Bias (COLAAB). The COLAAB has developed this guide to be used by authors who use nonanimal methods to avoid and respond to animal methods bias from manuscript reviewers. It contains information that researchers may use during 1) study design, including how to find and select appropriate nonanimal methods and preregister a research plan, 2) manuscript preparation and submission, including tips for discussing methods and choosing journals and reviewers that may be more receptive to nonanimal methods, and 3) the peer review process, providing suggested language and literature to aid authors in responding to biased reviews. The author's guide for addressing animal methods bias in publishing is a living resource also available online at animalmethodsbias.org, which aims to help ensure fair dissemination of research that uses nonanimal methods and prevent unnecessary experiments on animals.