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In molecular biology, it is a general assumption that the ensemble of expressed molecules, their activities and interactions determine biological function, cellular states and phenotypes. Stable protein complexes-or macromolecular machines-are, in turn, the key functional entities mediating and modulating most biological processes. Although identifying protein complexes and their subunit composition can now be done inexpensively and at scale, determining their function remains challenging and labor intensive. This study describes Protein Complex Function predictor (PCfun), the first computational framework for the systematic annotation of protein complex functions using Gene Ontology (GO) terms. PCfun is built upon a word embedding using natural language processing techniques based on 1 million open access PubMed Central articles. Specifically, PCfun leverages two approaches for accurately identifying protein complex function, including: (i) an unsupervised approach that obtains the nearest neighbor (NN) GO term word vectors for a protein complex query vector and (ii) a supervised approach using Random Forest (RF) models trained specifically for recovering the GO terms of protein complex queries described in the CORUM protein complex database. PCfun consolidates both approaches by performing a hypergeometric statistical test to enrich the top NN GO terms within the child terms of the GO terms predicted by the RF models. The documentation and implementation of the PCfun package are available at https://github.com/sharmavaruns/PCfun. We anticipate that PCfun will serve as a useful tool and novel paradigm for the large-scale characterization of protein complex function.

Abstract The study of microbial communities of the plant phyllosphere in remote locations using DNA-based approaches is limited by the challenges associated with their preservation in the field and during transportation. Freezing is a common DNA preservation strategy, but it may be unsuitable for leaf samples, or inaccessible in some locations. Other methods such as desiccation, ethanol or commercial preservatives are potential alternative DNA preservation methods for ambient temperature storage. In this study, we assessed the efficacy of desiccation (with silica gel packs), and of three preservation solutions (95% ethanol, RNAlater, LifeGuard) for the preservation of epiphytic phyllosphere communities of Populus tremuloides and Picea glauca at ambient indoor temperature (21 °C) for up to three weeks. We assessed effects on DNA concentration and quality and used metabarcoding to detect changes in bacterial and fungal communities between treatments over time. A secondary study was conducted on leaves of Populus grandidentata to further test the ability of the desiccation treatment to resolve differences between sampling sites. Silica gel packs were identified as effective ambient temperature preservative of phyllosphere bacterial and fungal communities. There were some changes in the communities compared to immediate extraction due to this treatment, but these changes did not affect the ability to distinguish tree species and sampling locations. Overall, our study supports the use of silica gel pack short term preservation at ambient temperature for phyllosphere samples intended for DNA-based microbial community analyses.

Abstract Background Rwanda has made remarkable progress in scaling up HIV testing, treatment, and healthcare services. Recent data show that 95% of people living with HIV (PLWH) were aware of their status, 97.5% of them are on antiretroviral therapy (ART), and 98% of those who are on treatment have achieved viral suppression. Importantly, growing body of evidence supports the Undetectable = Untransmittable (U = U) concept, affirming that PLWH who maintain an undetectable viral load do not transmit HIV to their sexual partners. This pivotal breakthrough in HIV care has transformed public health strategies and stigma reduction efforts. This study aimed to explore the perspectives of PLWH on the U = U concept in health facilities in Rwanda. Methods An exploratory qualitative study was conducted at three purposively selected health facilities in Rwanda from December 1 to 30, 2023. An interview guide was used to collect data, and data saturation was reached after enrolling 43 PLWH. The data was analyzed using conventional thematic analysis. Results The majority of participants demonstrated good knowledge of HIV transmission, with the U = U concept being particularly well-understood among discordant couples and individuals who have been on treatment for over 10 years. Three themes emerged from the analysis: [1] comprehensive knowledge of HIV transmission among PLWH; [2] reasons for disclosing HIV status and linking to care; and [3] acceptability of the U = U concept. Conclusion Our findings highlight the necessity for broader dissemination of the U = U concept across all PLWH subpopulations. Further research is essential to better understand the challenges faced by PLWH, which is critical for achieving the UNAIDS goal of ending the HIV/AIDS epidemic by 2030.

In Morbihan, three natural cavities, caves and rock shelters, explored briefly at the end of the 19th century and the beginning of the following century, yielded a wealth of archaeological material from the Roman period, mainly made up of white clay statuettes (Venus, mother goddesses, etc.). In all likelihood, these were places where underground divinities were worshipped in order to obtain abundant harvests. To date, there are no other known examples of such use of underground sites in the Roman period in the Armorican peninsula.

Abstract Background The clinical benefit of locking plates in distal fibula fractures has not yet been proven. In addition, the risk of wound complications appears to be higher than with conventional tubular plates. We hypothesize that the benefits of locking plates in terms of biomechanical properties are outweighed by a higher risk of wound complications. Methods We conducted a retrospective review of fibula fractures treated by osteosynthesis with either a conventional one-third tubular plate or an anatomically shaped locking plate from January 1, 2015 to December 31, 2021. We recorded baseline data and relevant comorbidities and defined the need for revision surgery due to wound-related or mechanical complications as primary endpoints. Results A total of 595 out of 727 patients were eligible for our study. Of these 595 fractures, 526 were fixed with a one-third tubular plate, 69 with a locking plate. Revision surgery was required in 54 patients, in 51 cases due to wound complications. Three patients required revision surgery for mechanical reasons and all of them were younger than 40 years of age, have not been diagnosed with osteoporosis, but experienced complex fracture types. As the third tubular plate and locking plate groups differed in terms of age and comorbidities, we performed a 2:1 matching based on age and gender, leaving data from 138 patients receiving a third tubular plate. While the two groups were comparable in many aspects, the rate of wound complications was significantly higher in the locking plate group. Although the locking plate group had a higher percentage of diabetes mellitus, there was no correlation between this comorbidity and the higher revision rate in this group. Conclusions Our data do not support the general use of locking plates in the treatment of distal fibular fractures. The risk of mechanical complications in osteoporotic ankle fractures seems to be overrated, as there were no mechanical revisions in the osteoporotic subgroup. The rate of wound-related revision surgery was significantly higher after the use of locking plates. This might be attributed to the greater thickness of locking plates.

Abstract In conservation strategies, getting precise and repeatable information on the species’ diet and health without relying on invasive or laborious methods is challenging. Here, we developed an efficient and non-invasive workflow for the sequencing and analysis of four taxonomic markers from fecal DNA to characterize the gut microbiota, parasites, and plants and lichens composing the winter diet of caribou (Rangifer tarandus), Canada’s most iconic endangered species. Sequencing of the 18S rRNA gene of eukaryotes from seven locations in Manitoba and Saskatchewan, Canada, allowed for the detection of five genera of parasites in caribou feces (including Nematodirella and Parelaphostrongylus) with variable frequency of occurrence depending on sampling location and sex. Our workflow also revealed a rich winter plant and lichen diet in caribou, with respectively 29 and 18 genera identified across all samples through plant and fungal ITS2 sequencing. Relationships between the gut microbiota and both the diet and parasite richness were also identified. Of note, the Central Saskatchewan sampling location was characterized by a clearly distinct gut microbiota which could be linked to an epiphytic lichen-rich diet. Overall, our results showed the potential of this multi-marker DNA metabarcoding workflow as an efficient tool to provide insights into the species biology and ecology.

Abstract The Ebola virus (EBOV) remains a major public health challenge due to its complex structure and the lack of appropriate and effective vaccines and therapies. This review characterizes the Ebola virus, its immune response, and its therapeutic challenges. Structural EBOV proteins include the envelope glycoprotein, nucleoprotein, RNA polymerase L, and viral proteins VP30, VP24, VP35, and VP40. The proteins play a role in the virus’s pathogenesis by evading the host's immune response. The immune system evasion mechanisms of EBOV are critical in its pathogenesis. Some vaccines, such as the recombinant vesicular stomatitis virus-Zaire Ebola virus (RVSV-ZEBOV), have proven to be very effective and have been approved by the Food and Drug Administration (FDA) additionally, four other vaccines have been approved including Gam Evac-Combi (licensed in Russia), ad5-EBOV (approved in China), Zabdeno and Mvabea (approved in Europe). However, some challenges remain in developing effective vaccines, such as the selection of immunogens, cross-protecting immunity, long-term protection, mechanism of protection, and rapid response vaccination. Despite the progress made, there is still a need for an effective vaccine that offers durable and broad protection against multiple strains of the Ebola virus. This will be achieved through the collaboration of various organizations and government and Non-Governmental Organization (NGO) agencies.

Abstract Background Gut microbes are important to the health and fitness of many animals. Many factors have been shown to affect gut microbial communities including diet, lifestyle, and age. Most animals have very complex physiologies, lifestyles, and microbiomes, making it virtually impossible to disentangle what factors have the largest impact on microbiota composition. Honeybees are an excellent model to study host-microbe interactions due to their relatively simple gut microbiota, experimental tractability, and eusociality. Worker honey bees have distinct gut microbiota from their queen mothers despite being close genetic relatives and living in the same environment. Queens and workers differ in numerous ways including development, physiology, pheromone production, diet, and behavior. In the prolonged absence of a queen or Queen Mandibular Pheromones (QMP), some but not all workers will develop ovaries and become “queen-like”. Using this inducible developmental change, we aimed to determine if diet and/or reproductive development impacts the gut microbiota of honey bee workers. Results Microbiota-depleted newly emerged workers were inoculated with a mixture of queen and worker gut homogenates and reared under four conditions varying in diet and pheromone exposure. Three weeks post-emergence, workers were evaluated for ovary development and their gut microbiota communities were characterized. The proportion of workers with developed ovaries was increased in the absence of QMP but also when fed a queen diet (royal jelly). Overall, we found that diet, rather than reproductive development or pheromone exposure, led to more “queen-like” microbiota in workers. However, we revealed that diet alone cannot explain the microbiota composition of workers. Conclusion The hypothesis that reproductive development explains microbiota differences between queens and workers was rejected. We found evidence that diet is one of the main drivers of differences between the gut microbial community compositions of queens and workers but cannot fully explain the distinct microbiota of queens. Thus, we predict that behavioral and other physiological differences dictate microbiota composition in workers and queens. Our findings not only contribute to our understanding of the factors affecting the honey bee microbiota, which is important for bee health, but also illustrate the versatility and benefits of utilizing honeybees as a model system to study host-microbe interactions.

There is a general agreement among scholars that bundling Climate Information Services (CIS), Climate Smart Agriculture (CSA), and other agricultural products and services can positively impact agriculture. However, many questions still need to be answered regarding how the bundling can be achieved through scalable and farmer-centric CIS-CSA bundled business models. This study narrowed the knowledge gap by revealing 1) how CIS, CSA, and other agricultural products and services may be bundled to support sustainable agriculture, 2) what types of CIS-CSA bundled business models are successfully reaching and benefiting farmers and entrepreneurs, and 3) proposing an evaluation framework for assessing CIS-CSA bundled business models ready for scaling. Drawing on the synthesis analysis of available relevant publications, we devised a 1–5 scale evaluation framework based on nine scaling readiness indicators—technology, impact, bundling, infrastructure, relevance, evidence, barriers, sustainability, and value addition—to assign scalability scores to 29 business cases with bundled CIS-CSA products and services across Africa and Asia. Eleven CIS-CSA bundled business models with publicly available quantitative scaling readiness data (financial capacity, the number of customers, customer categories, and the number of beneficiaries) were used to quantitatively model how different CIS-CSA products and services bundling strategies, the revenue stream structure of a CIS-CSA business, and the structure of a CIS-CSA business’s stakeholder network (the diversity of its stakeholders) affect its scaling readiness. Based on the scaling readiness evaluation framework, of the 29 identified CIS-CSA bundled business cases, 12 were ready for scaling. The quantitative analysis revealed that the type of a CIS-CSA model significantly determines its scalability— for example, a government-to-donor-to-business-to-consumer (G2D2B2C) CIS-CSA bundled business model would have 10 million USD more invested capital than a government-to-business-to-consumer (G2B2C) bundled business model type. Additionally, the G2D2B2C bundled business model type would serve 5 million farmers and three customer categories and gain ten partners more than the G2B2C. The finding also suggests that multi-stakeholder CIS-CSA business models, which provide a more diverse package of CIS-CSA products and services and have many revenue sources, have the potential to benefit all categories of farmers and entrepreneurs. This study reveals a reason for optimism about the future of agriculture; it suggests that scalable bundled CIS-CSA products and services can contribute significantly to attaining climate resilience and food security.

ABSTRACT Honey bees are the third most economically important agricultural animal in the world due to their role as pollinators. Honey bee pollination services and all hive duties are performed by female workers, while the male drones have one job to mate and share their genetics with a virgin queen from another colony. Thus, drone fitness is directly tied to queen success and colony survival, yet they have been severely understudied compared to their female counterparts. In other insects, microbes discovered in the gut and reproductive organs have been shown to be important for reproductive success and/or overall host health. To our knowledge, the existence of microbes in drone reproductive tissues has never been investigated. Moreover, our understanding of the gut microbiota of drones is severely limited, especially when compared to honey bee workers. Here, we sampled conventional drones from healthy colonies and used 16S amplicon sequencing to identify and characterize bacteria in the reproductive organs of immature and mature drones. After identifying bacteria in drone reproductive tissues, we performed a controlled experiment in which newly emerged drones were exposed to different rearing conditions in order to determine when and how they acquire their reproductive and gut microbiota. Overall, we discovered a set of core bacteria in the reproductive and gut tissues of conventionally reared drones and revealed that social interactions are important for the proper development of the drone microbiota. Determining if these bacteria play a role in drone fecundity and health should be a goal of future research efforts.IMPORTANCEOver the last decade, annual honey bee colony loss has increased, resulting in a critical need to determine what factors contribute to honey bee and colony health. Gut microbes have been shown to play important roles in the health of the nonreproductive female honey bee workers, which make up 90% or more of a honey bee colony. However, we currently know very little about the impact of microbes on the health of male honey bees (drones), who only make up a small portion of the colony population but play a very key role in the success of future colonies by mating with virgin queens. Here, we discovered microbes within the reproductive organs of drones and illustrated that social interactions with worker bees are necessary for the proper development of the gut and reproductive tissue microbial communities in drones. Further studies are needed to determine if microbes play an important role in honey bee reproductive health and fitness.

Polysorbates, in particular polysorbate (PS) 20 and 80, are the most commonly used surfactants for stabilising biotherapeutics produced by biotechnological processes. PSs are derived from ethoxylated sorbitan (a derivative of sorbitol) esterified with fatty acids of varying chain length and degree of saturation. In the past, these surfactants have been reported to have specific liabilities. Chemical (oxidations and hydrolyses) and enzymatic degradations have been reported to affect the stability of PS in drug products. Specifically, the presence of trace amounts (sub-ppm) of certain host cell proteins (HCPs) can induce enzymatic PS degradation, which can lead to the release of free fatty acids during storage over time. Enzymatic polysorbate degradation may impair the functionality of the surfactant in stabilising therapeutic proteins, leading to the formation of visible and/or sub-visible particles in biopharmaceutical drug products. This review summarises the enzymes currently known to be involved in the degradation of polysorbate in mammalian biotechnological processes for therapeutic proteins. In recent years, advanced analytical methods have been developed to qualify and quantify the PS-degrading enzymes. Most of these assays are based on mass spectrometry with a preceding HCP enrichment approach. Efforts were made to measure the enzyme activity and correlate it with observed PS degradation. The impact on drug product quality attributes, including fatty acid solubility and phase separation, up to the formation of visible particles, and the potential induction of protein and protein/fatty acid mixed particles as well as the sensitivity of specific PS quality towards enzymatic degradation, was considered. Various drug substance (DS) mitigation strategies related to the occurrence of PS degrading enzymes are discussed as amongst them the generation of stable HCP knockout cell lines, which are also carefully analysed. The underlying opinion article reflects the undergoing discussions related to PS degrading enzymes and focusses on (i) impact on drug product, (ii) analytics for identification/quantification (characterisation) of the PS degrading enzymes, (iii) enzyme activity (iv) currently identified enzymes, and (v) potential mitigation strategies to avoid enzymatic PS degradation during DS manufacturing.

Sustainable school feeding programs (SFPs) in sub-Saharan Africa play a vital role in addressing malnutrition and poor educational outcomes among children. It is critical to contextualize SFPs to local needs and resources, while retaining the twin universal goals of alleviating hunger and promoting education, and the associated strengthening of health, nutrition and social protection. The effective implementation and continuity of such programs, however, present challenges. Key hurdles to establishing and maintaining effective SFPs in sub-Saharan Africa were assessed, as well as strategies to address these challenges. We searched three databases for articles published between 2012 and 2023 with combinations of the keywords: “school feeding,” “school meals,” “sustainability,” “sustainable,” and “long-term.” Of >25,000 identified articles, 21 focused on quantitative and qualitative evaluations of sustainability in primary school SFPs with children aged 6–14. Themes discussed in these articles fall into four broad areas: policy, operations, community involvement and ancillary activities. Successful SFPs in sub-Saharan Africa differ substantively from those in higher income countries. Home grown SFPs are a common route to follow to transition from external donor support, and increase community involvement. The SMP+ meal planner from the World Food Program is widely used to develop nutritious, acceptable meals based on locally available foodstuffs. School gardens and means to access sufficient fuel, usually firewood, for cooking are important concerns in sub-Saharan Africa, but are not usually a concern in higher income countries. By utilizing locally sourced foods and involving students in school gardens and meal planning activities, more comprehensive nutrition education can occur and students can better understand ways to utilize the food available to their household. In conclusion, we provide target areas for policymakers and practitioners to address when designing SFPs that can be sustained for the long term in sub-Saharan Africa and other low and middle-income countries.

Cellulose is a strong contender for the development of sustainably resourced biodegradable material composites supporting circular economy. Nanofibrillar cellulose-comprising materials are among the most promising lignocellulose derivatives. Currently, their production capacity and economy are hindered by high chemical and energy consumption, the latter primarily during mechanical fibrillation of native fiber in aqueous suspension and the negative limitation of very low solid content associated with the gel-like properties of the resulting final product. The application of oxygen gas barrier discharge (DBD) plasma on dry cellulose fiber, as reported here, is considered novel in achieving onward nanofibrillation. At this early stage, though, simple laboratory DBD equipment precludes the study of overall efficiency. Example fiber was taken from paper pulp manufacture but may not be limited to wood source. The oxygen plasma was seen to etch the microcellulose fiber structure, simultaneously oxidizing the glue-functioning hemicellulose, rendering it soluble, so that nanopolymer crystalline-based cellulose fibrils can be readily released at the surface of the host refined microfiber at the point of application, forming micro nanofibrillated cellulose structure (MNFC) at previously uneconomic higher solid content. Eliminating the need for liquid water during precursor process treatment is considered potentially transformative with respect to production feasibility, end-product transportation and application.

Protein formulation development relies on the selection of excipients that inhibit protein–protein interactions preventing aggregation. Empirical strategies involve screening many excipient and buffer combinations by physicochemical characterization using forced degradation or temperature-induced stress, mostly under accelerated conditions. Such methods do not readily provide information on the inter- and intramolecular interactions responsible for the effects of excipients. Here, we describe a combined experimental and computational approach for investigating the effect of protein–excipient interactions on formulation stability, which allows the identification of preferential interaction sites and thus can aid in the selection of excipients to be experimentally screened. Model systems composed of two marketed therapeutic IgG1 monoclonal antibodies with identical Fc domain sequences, trastuzumab and omalizumab, were investigated with commonly used excipients arginine, glutamate, and equimolar arginine/glutamate mixtures. Protein–excipient interactions were studied using all-atom molecular dynamics (MD) simulations, which show accumulation of the excipients at specific antibody regions. Preferential excipient-interaction sites were particularly found for charged and aromatic residues and in the complementary-determining regions, with more pronounced arginine contacts for omalizumab than trastuzumab. These computational findings are in line with the more pronounced stabilizing effects of arginine observed in the long-term storage stability study. Furthermore, the aggregation and solubility propensity predicted by commonly used in silico tools do not align with the preferential excipient-interaction sites identified by the MD simulations, suggesting that different physicochemical mechanisms are at play.

In the third APOKASC catalog, we present data for the complete sample of 15,808 evolved stars with APOGEE spectroscopic parameters and Kepler asteroseismology. We used 10 independent asteroseismic analysis techniques and anchor our system on fundamental radii derived from Gaia L and spectroscopic T _eff . We provide evolutionary state, asteroseismic surface gravity, mass, radius, age, and the data used to derive them for 12,418 stars. This includes 10,036 exceptionally precise measurements, with median fractional uncertainties in ${\nu }_{{\rm{\max }}}$ , Δ ν , mass, radius, and age of 0.6%, 0.6%, 3.8%, 1.8%, and 11.1%, respectively. We provide more limited data for 1624 additional stars that either have lower-quality data or are outside of our primary calibration domain. Using lower red giant branch (RGB) stars, we find a median age for the chemical thick disk of 9.14 ± 0.05(ran) ± 0.9(sys) Gyr with an age dispersion of 1.1 Gyr, consistent with our error model. We calibrate our red clump (RC) mass loss to derive an age consistent with the lower RGB and provide asymptotic GB and RGB ages for luminous stars. We also find a sharp upper-age boundary in the chemical thin disk. We find that scaling relations are precise and accurate on the lower RGB and RC, but they become more model dependent for more luminous giants and break down at the tip of the RGB. We recommend the use of multiple methods, calibration to a fundamental scale, and the use of stellar models to interpret frequency spacings.

Abstract Introduction When performance data are provided as feedback to healthcare professionals, they may use it to significantly improve care quality. However, the question of how to provide effective feedback remains unanswered, as decades of evidence have produced a consistent pattern of effects—with wide variation. From a coaching perspective, feedback is often based on a learner's objectives and goals. Furthermore, when coaches provide feedback, it is ideally informed by their understanding of the learner's needs and motivation. We anticipate that a “coaching”‐informed approach to feedback may improve its effectiveness in two ways. First, by aligning feedback with healthcare professionals' chosen goals and objectives, and second, by enabling large‐scale feedback systems to use new types of data to learn what kind of performance information is motivating in general. Our objective is to propose a conceptual model of precision feedback to support these anticipated enhancements to feedback interventions. Methods We iteratively represented models of feedback's influence from theories of motivation and behavior change, visualization, and human‐computer interaction. Through cycles of discussion and reflection, application to clinical examples, and software development, we implemented and refined the models in a software application to generate precision feedback messages from performance data for anesthesia providers. Results We propose that precision feedback is feedback that is prioritized according to its motivational potential for a specific recipient. We identified three factors that influence motivational potential: (1) the motivating information in a recipient's performance data, (2) the surprisingness of the motivating information, and (3) a recipient's preferences for motivating information and its visual display. Conclusions We propose a model of precision feedback that is aligned with leading theories of feedback interventions to support learning about the success of feedback interventions. We plan to evaluate this model in a randomized controlled trial of a precision feedback system that enhances feedback emails to anesthesia providers.

Abstract The Plastid Terminal Oxidase (PTOX) is a chloroplast localized plastoquinone oxygen oxidoreductase suggested to have the potential to act as a photoprotective safety valve for photosynthesis. However, PTOX overexpression in plants has been unsuccessful at inducing photoprotection, and the factors that control its activity remain elusive. Here, we show that significant PTOX activity is induced in response to high light in the model species Eutrema salsugineum and Arabidopsis thaliana. This activation correlates with structural reorganization of the thylakoid membrane. Over-expression of PTOX in mutants of Arabidopsis thaliana perturbed in thylakoid stacking also results in such activity, in contrast to wild type plants with normal granal structure. Further, PTOX activation protects against photoinhibition of Photosystem II and reduces reactive oxygen production under stress conditions. We conclude that structural re-arrangements of the thylakoid membranes, bringing Photosystem II and PTOX into proximity, are both required and sufficient for PTOX to act as a Photosystem II sink and play a role in photoprotection.

Abstract Soil sampling for environmental DNA in remote and semi-remote locations is often limited due to logistical constraints surrounding sample preservation, including no or limited access to a freezer. Freezing at − 20 °C is a common DNA preservation strategy, however, other methods such as desiccation, ethanol or commercial preservatives are available as potential alternative DNA preservation methods for room temperature storage. In this study, we assessed five preservation methods (CD1 solution, 95% Ethanol, Dry & Dry silica gel packs, RNAlater, LifeGuard) along with freezing at − 20 °C, against immediate extraction on organic and mineral soils for up to three weeks of preservation. We assessed direct effects on DNA concentration and quality, and used DNA metabarcoding to assess effects on bacterial and fungal communities. Drying with Dry & Dry led to no significant differences from immediate extraction. RNAlater led to lower DNA concentrations, but effects on community structures were comparable to freezing. CD1, LifeGuard and Ethanol either caused immediate significant shifts in community structure, degradation of DNA quality or changes in diversity metrics. Overall, our study supports the use of drying with silica gel packs as a cost-effective, and easily applied method for the short-term storage at room temperature for DNA-based microbial community analyses.

This study evaluated the impact of precision feeding and bump feeding strategies during gestation on the reproductive performance of sows monitored over three cycles. Four treatments were compared: two constant-concentration feeding strategies (0.53% standardized ileal digestible lysine content; SID Lys) with the feed supply remaining constant (flat feeding; FF) or variable (bump feeding; BF) and two precision feeding strategies based on the InraPorc model considering performance by parity (precision feeding per parity; PFP) or the weight of each sow at breeding (precision feeding by individual; PFI). Sows were followed over three gestation and lactation cycles. In the first cycle (n = 502), the birth-to-weaning piglet mortality for PFP (8.7%) and PFI (10.3%) was lower than for BF (13.8%), with FF (11.3%) being intermediate (p = 0.001). No differences were observed in litter performance during the second cycle (n = 340). During the third cycle (n = 274), the stillborn rate was lower for PFP (6.2%) than for BF (9.1%) and FF (10.4%), with PFI (7.0%) being intermediate (p = 0.01). The BF strategy did not significantly improve sow or litter performance during lactation. Meanwhile, precision feeding could reduce nitrogen (10–13%) and total phosphorus intake (6–9%) with PFP and PFI strategies. Also, the results showed that it could even reduce piglet mortality during lactation.

Sickle cell disease (SCD) is a prevalent inherited blood disorder, particularly affecting populations in Africa. This review examined the disease’s burden, its diverse clinical presentations, and the challenges associated with its management in African settings. Africa bears a significant burden of SCD, with prevalence varying across countries and age groups. Newborn screening programs have highlighted the high prevalence of SCD at birth, emphasizing the need for early diagnosis and intervention. The clinical manifestations of SCD in Africa are multifaceted, encompassing acute complications like vaso-occlusive crises, acute chest syndrome, and stroke, as well as chronic complications such as organ damage and leg ulcers. Biological factors, including fetal hemoglobin levels, and demographic factors, like age and sex, influence disease severity and outcomes. The management of SCD in Africa faces numerous challenges. Limited access to resources, including diagnostic tools, medications, and trained healthcare professionals, hinders optimal care. The high cost of advanced therapies further restricts patient access. Cultural stigma and a lack of awareness create additional barriers to effective management. To address these challenges, early diagnosis through newborn screening programs and point-of-care testing is crucial. Comprehensive care models, including hydroxyurea therapy, pain management, and patient education, are essential for improving outcomes. Collaboration with international networks and leveraging local resources can enhance the sustainability of SCD programs. In conclusion, SCD significantly impacts African populations. Overcoming the challenges associated with its management requires addressing resource limitations, affordability issues, and cultural barriers. Early diagnosis, comprehensive care models, and ongoing research focused on affordability and accessibility are crucial for improving the lives of individuals living with SCD in Africa.

The Africa Centers for Disease Control and Prevention declared mpox a Public Health Emergency of Continental Security (PHECS) in Africa. African public health systems have moved to mobilize a response against a backdrop of inherent significant challenges. With this commentary, we discuss how lessons from past public health emergencies, particularly COVID-19 and Ebola outbreaks, have prepared the region for improved disease surveillance, rapid response strategies, and effective public health communication and how these lessons can be applied to the mpox response, emphasizing the importance of strong healthcare infrastructure, effective data sharing, community engagement, targeted interventions, and robust contact tracing. Additionally, addressing misinformation and building public trust are crucial for controlling the spread of any disease. By leveraging these strategies, African countries can enhance their response to mpox. This includes improving diagnostic capabilities, strengthening cross-border collaborations, and prioritizing vaccination campaigns where needed. Ultimately, by applying the hard-earned lessons from the COVID-19 pandemic and Ebola outbreak, the East Africa region can better address the challenges posed by mpox and safeguard public health.

Abstract The internal variability pertains to fluctuations originating from processes inherent to the climate component and their mutual interactions. On the other hand, forced variability delineates the influence of external boundary conditions on the physical climate system. A methodology is formulated to distinguish between internal and forced variability within the surface air temperature. The noise‐to‐noise approach is employed for training a neural network, drawing an analogy between internal variability and image noise. A large training data set is compiled using surface air temperature data spanning from 1901 to 2020, obtained from an ensemble of Atmosphere‐Ocean General Circulation Model simulations. The neural network utilized for training is a U‐Net, a widely adopted convolutional network primarily designed for image segmentation. To assess performance, comparisons are made between outputs from two single‐model initial‐condition large ensembles, the ensemble mean, and the U‐Net's predictions. The U‐Net reduces internal variability by a factor of four, although notable discrepancies are observed at the regional scale. While demonstrating effective filtering of the El Niño Southern Oscillation, the U‐Net encounters challenges in capturing the changes in the North Atlantic Ocean. This methodology holds potential for extension to other physical variables, facilitating insights into the climate change triggered by external forcings over the long term.

Background: The COVID-19 pandemic has wrought a profound impact on mental health in Sub- Saharan Africa, exacerbating existing disparities and rendering individuals undergoing treatment particularly susceptible. This comprehensive critical review delves into the scope, nature, and extent of COVID-19 impact on mental health services in Sub- Saharan Africa, while concurrently elucidating pivotal lessons and exemplary practices learnt from periods of lockdown. Methods: The methodology was guided by Jesson & Laccy's guide on how to conduct critical literature reviews. Articles were comprehensively sought through two academic databases (PubMed and Google Scholar), complemented by targeted searches on the WHO website and official public health websites of relevant Sub-Saharan African countries. Results: The investigation reveals a surge in mental health challenges, notably marked by a significant escalation in anxiety, depression, and post-traumatic stress disorder. Disruptions to care services, financial hardships, and the pervasive effects of social isolation further compound this escalation. The pre-existing inequalities in access to and quality of care were accentuated during this crisis, with marginalized groups encountering heightened impediments to essential services. In navigating this unprecedented challenge, communities emerged as integral agents in establishing supportive networks and implementing culturally sensitive interventions. Technology, such as telemedicine and online resources, played a pivotal role in bridging access gaps, particularly in remote areas. The synthesis of best practices for supporting mental health patients during lockdowns encompasses targeted interventions for vulnerable groups, including adolescents and pregnant women. Empowering communities through economic support and mental health literacy programs was identified as crucial. The integration of technology, such as the development of robust telemedicine frameworks, virtual training in curricula, and the utilization of digital platforms for interventions and public messaging, emerged as a cornerstone in addressing access disparities. Community engagement and resilience-building strategies gained prominence, emphasizing the necessity of collaboration between healthcare providers and communities. Promotion of peer support groups, home-based care, and the preservation of traditional healing practices were underscored as essential components. Conclusion: The study underscores the need to adapt and optimize mental health services during emergencies. This entails prioritizing mental health within emergency response frameworks, exploring alternative service delivery methods, and fortifying data collection and research efforts.

Objective: Leadership discussion, including leadership development programs, is common. However, discussion of followership as a component of leadership seems less frequently discussed. With a focus on leadership and followership, this investigation reviewed the health-professions education literature and characterized leadership-followership within health-professions education. Methods: Using PubMed, ERIC, and Google Scholar, two investigators independently and systematically searched health-professions education literature for articles related to leadership and followership. Reports were categorized based on the articles by type, application, profession, leadership, and followership qualities. Results: Eighty-one articles were included. More than half (48/81, 59%) were theoretical, 27% (22/81) empirical, 7% (6/81) commentaries, and 6% (5/81) letters-to-the-editor). Empirical studies did not share outcomes that could be meaningfully combined quantitatively by meta-analysis; however, the vast majority (96%) of theoretical articles discussed a healthcare-related application of leadership and followership (e.g., improving patient care, improving communication, improving organizational efficiency). Thus, a qualitative review was completed. Of the 81 articles, 57% (n=46) involved multiple professions, while 43% (n=35) focused on a specific profession [Nursing (n=16), Medicine (n=7), Others (n=5) Surgery (n=3), Pharmacy (n=2), Veterinary Medicine (n=2)]. While most articles (75%) discussed leadership qualities (with top qualities of effective communication, visionary, and delegating tasks), fewer (57%) discussed followership qualities (with top qualities of being responsible, committed, and supportive). Of note, some qualities overlapped in both leadership and followership (with top qualities of effective communication, being supportive, and providing/receiving feedback). Conclusions: Leadership-Followership was described in many health-professions’ education literature. However, Pharmacy and Veterinary Medicine had substantially fewer articles published on this topic. Notably, followership did not receive nearly as much attention as leadership. Leadership has a dynamic and complex interaction with followership highlighting that an effective leader must know how to be an effective follower and vice versa. To improve leadership within healthcare teamwork, education should focus on both leadership-followership.

Rodents have remained a menace to humans, hence there is need to evaluate for anti-rodent activity of cheap and environment friendly control methods. This study aimed at evaluating the anti-rodenticidal activity of Thevetia (T.) peruviana fruit methanol extract. T. peruviana fruit was sampled, dried and extracted using methanol/water in the ratio of 3:1 by volume. Phytochemicals; alkaloids, phenols, flavonoids, glycosides, saponins, and tannins were determined qualitatively and quantitatively in the fruit extract. The extract was then characterized using Fourier Transform Infrared (FTIR) and Gas Chromatography Mass Spectrophotometer (GC-MS). Anti-rodent activity of the extracts was determined on a total of 25 mice with body weights of 20–25 g. The animals 8–12 weeks' old were grouped into 5 cages (5 animals per cage), marked and allowed to acclimatize with laboratory conditions of 25 °C, warm or less humid for 5 days with enough water and food. Extract dose (between 0.3 and 0.5 g of extract/kg body weight) was then administered in a single dose by gavage using intubation canula for 7 days and the animals observed for any toxicity and mortality. The data was subjected to probit analysis and ANOVA. Phytochemical screening showed that the extracts contained glycosides, phenols, saponins, alkaloids, triterpenoids, and flavonoids in different abundance. T. peruviana fruit contained 125.13 ± 1.04 mg/g in GAE phenolic content, 85.70 mg/g in RE of dry weight of flavonoids, 10.50 ± 0.01 mg/g in TAE of Tannins, 16.50± 0.21 mg/g alkaloid content, and 8.28± 0.11 mg/g saponin content. The FTIR spectrophotometer depicted O – H, CH2, CO, C–O–C functional groups in wave numbers of 3335, 2932, 1599, and 1001 cm−1 respectively. The T. peruviana fruit methanol extracts depicted high acute toxicity with an average of 300 mg/kg upon oral administration in Balb C mice species. The fruit extract from T. peruviana revealed presence of alkaloids, phenols, glycosides, saponins, tannins. These participated synergistically in killing the rats and the postmortem examination report indicated that the tested extract induced a number of physical changes in the mice and therefore the T. peruviana's fruit extract can be utilized as a natural alternative anti-rodent in agriculture production before and after harvesting.

Abstract MIS-C is a systemic inflammation disorder with poorly characterised immunopathological mechanisms. We compared changes in the systemic immune response in children with MIS-C (n = 12, 5–13 years) to healthy controls (n = 14, 5–15 years). Analysis was done in whole blood treated with LPS. Expression of CD11b and Toll-like receptor-4 (TLR4) in neutrophils and monocytes were analysed by flow cytometry. Serum cytokines (IL-1β, IL-2, IL-6, IL-8, IL-10, IL-Ira, TNF-α, TNF-β, IFN-Υ, VEGF, EPO and GM-CSF) and mRNA levels of inflammasome molecules (NLRP3, ASC and IL-1β) were evaluated. Subpopulations of lymphocytes (CD3+, CD19+, CD56+, CD4+, CD8+, TCR Vδ1+, TCR Vδ2+) were assessed at basal levels. Absolute counts of neutrophils and NLR were high in children with MIS-C while absolute counts of lymphocytes were low. Children with MIS-C had increased levels of IL-6, IL-10, TNF-β and VEGF serum cytokines at the basal level, and significantly increased TNF-β post-LPS, compared to controls. IL-1RA and EPO decreased at baseline and post-LPS in MIS-C patients compared to controls. The percentage of CD3+ cells, NK cells and Vδ1 was lower while B cells were higher in children with MIS-C than in controls. Dysregulated immune response in children with MIS-C was evident and may be amenable to immunomodulation.

Abstract In recent ages, green nanotechnology has gained attraction in the synthesis of metallic nanoparticles due to their cost-effectiveness, simple preparation steps, and environmentally-friendly. In the present study, copper oxide nanoparticles (CuO NPs) were prepared using Parthenium hysterophorus whole plant aqueous extract as a reducing, stabilizing, and capping agent. The CuO NPs were characterized via UV–Vis Spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), powder X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and Dynamic Light Scattering (DLS). The UV–Vis spectra of CuO NPs showed a surface plasmonic resonance band to occur at 340 nm. FTIR analysis revealed the presence of secondary metabolites on the surface of CuO NPs, with a characteristic Cu–O stretching band being identified at 522 cm−1. Scanning electron micrographs and transmission electron micrographs showed that CuO NPs were nearly spherical, with an average particle of 59.99 nm obtained from the SEM micrograph. The monoclinic crystalline structure of CuO NPs was confirmed using XRD, and crystallite size calculated using the Scherrer-Debye equation was found to be 31.58 nm. DLS showed the presence of nanoparticle agglomeration, which revealed uniformity of the CuO NPs. Furthermore, the degradation ability of biosynthesized nanoparticles was investigated against rifampicin antibiotic. The results showed that the optimum degradation efficiency of rifampicin at 98.43% was obtained at 65℃ temperature, 50 mg dosage of CuO NPs, 10 mg/L concentration of rifampicin solution, and rifampicin solution at pH 2 in 8 min. From this study, it can be concluded that CuO NPs synthesized from Parthenium hysterophorus aqueous extract are promising in the remediation of environmental pollution from antibiotics. In this light, the study reports that Parthenium hysterophorus-mediated green synthesis of CuO NPs can effectively address environmental pollution in cost-effective, eco-friendly, and sustainable ways.

Uvsq-Sat NG is a French 6U CubeSat (10 × 20 × 30 cm) of the International Satellite Program in Research and Education (INSPIRE) designed primarily for observing greenhouse gases (GHG) such as CO2 and CH4, measuring the Earth’s radiation budget (ERB), and monitoring solar spectral irradiance (SSI) at the top-of-atmosphere (TOA). It epitomizes an advancement in CubeSat technology, showcasing its enhanced capabilities for comprehensive Earth observation. Scheduled for launch in 2025, the satellite carries a compact and miniaturized near-infrared (NIR) spectrometer capable of performing observations in both nadir and solar directions within the wavelength range of 1100 to 2000 nm, with a spectral resolution of 7 nm and a 0.15° field of view. This study outlines the preflight calibration process of the Uvsq-Sat NG NIR spectrometer (UNIS), with a focus on the spectral response function and the absolute calibration of the instrument. The absolute scale of the UNIS spectrometer was accurately calibrated with a quartz-halogen lamp featuring a coiled-coil tungsten filament, certified by the National Institute of Standards and Technology (NIST) as a standard of spectral irradiance. Furthermore, this study details the ground-based measurements of direct SSI through atmospheric NIR windows conducted with the UNIS spectrometer. The measurements were obtained at the Pommier site (45.54°N, 0.83°W) in Charentes–Maritimes (France) on 9 May 2024. The objective of these measurements was to verify the absolute calibration of the UNIS spectrometer conducted in the laboratory and to provide an extraterrestrial solar spectrum using the Langley-plot technique. By extrapolating the data to AirMass Zero (AM0), we obtained high-precision results that show excellent agreement with SOLAR-HRS and TSIS-1 HSRS solar spectra. At 1.6 μm, the SSI was determined to be 238.59 ± 3.39 mW.m−2.nm−1 (k = 2). These results demonstrate the accuracy and reliability of the UNIS spectrometer for both SSI observations and GHG measurements, providing a solid foundation for future orbital data collection and analysis.

We used lipid, fatty acid, and stable isotope analyses to investigate variation, over nine months, in the trophodynamics of 10 dominant cryptofaunal, macroalgal/algal, and environmental components from two sites within a rhodolith (Lithothamnion glaciale) bed in southeastern Newfoundland (Canada). There was an overall shift from a diatom-based food web following the spring phytoplankton bloom to a kelp/algae-based food web during fall, accompanied by preferred use of EPA (20:5ω3) over DHA (22:6ω3) in most cryptofauna. The food web contained three trophic levels that encompassed: (1) direct feeding relationships from primary producers (e.g., rhodoliths, macroalgae) to second-order consumers (e.g., sea stars, polychaetes); (2) trophic subsidy from within and outside the rhodolith bed via settlement, resuspension, and consumption of macroalgal fragments and other detrital organic matter; and (3) strong pelagic/benthic coupling. Riverine input did not affect cryptofaunal diets, as shown by the lack of terrestrial biomarkers at the study site nearest to the riverine input, and there were minor differences in trophodynamics between both study sites. The present study’s findings, applicable to relatively broad spatial and temporal domains, as well as those of complementary studies of the same rhodolith bed, uncover high spatio-temporal stability of the rhodolith bed framework and of resident cryptofaunal abundance, diversity, and trophodynamics.

Land and water degradation caused by soil erosion and climate change pose major environmental threats, particularly in agricultural watersheds. Soil erosion in a catchment leads to low crop yields due to declining soil quality (SQ), productivity and sustainability. However, very few studies have been done to assess soil health in Kenya, and none in Narok County. Thus, the aim of this study was to evaluate the soil sustainability status in Kakia-Esamburmbur catchment, based on the identification of key indicators (IKI) from a large dataset (LDS) of 23 indicators, across three land use types designated as grass land (GL), crop land (CL) and forest land (FL). To achieve the stated objective, two soil quality indexing methods were employed: the Additive Soil Quality Index (A-SQI) using the LDS; and the Weighted Soil Quality Index (W-SQI) using Principal Component Analysis (PCA) as a reduction tool to obtain the IKI set. The results show that at a depth of 20 cm, the catchment's soils characteristics did not differ significantly. The two methods (A-SQI and W-SQI) resulted in FL having the highest SQI mean values (0.61, 0.57), followed by CL (0.59, 0.55), while the lowest SQI mean value was recorded in GL (0.58, 0.53). Additionally, the sensitivity analysis showed W-SQI as the most sensitive and superior method in the evaluation of SQI changes due to its high sensitivity and coefficient of variation (CV), at 2.25 and >12 %, respectively. Among the ten IKI, CEC made the greatest contribution to SQ (18.68 %), followed by BD (15.61 %), BIR (14.71 %), Mg (14.26 %), MBN (8.30 %), MBC (8.26 %), Sand (6.77 %), Moisture (5.75 %), TOC (5.16 %), and PMN (2.63 %). The findings show that the catchment belongs to the ''medium'' category of SQ. The IKI can help save time and reduce the cost of intensive lab works for temporal assessment and monitoring of the effects of different land use on SQ.

We present a case of a patient known for dextrotransposition of the great arteries corrected with a Mustard procedure, in whom severe mitral valve regurgitation secondary to transvenous lead extraction was successfully repaired with transcatheter edge-to-edge repair using the TriClip device (Abbott Vascular).

Background: While significant gains were made in the management of heart failure (HF), most patients are still diagnosed when they are acutely ill in hospital, often with advanced disease. Earlier diagnosis in the community could lead to improved outcomes. Whether a partnership and an educational program for primary care providers (PCP) increase HF awareness and management is unknown. Methods: We conducted an observational study between March 2019 and June 2020 during which HF specialists gave monthly HF conferences to PCP. Using a pre-post design, medical charts and administrative databases were reviewed and a questionnaire was completed by participating PCP. Primary and secondary endpoints included: 1) the number of patients diagnosed with HF, 2) implementation of GDMT for patients with HFrEF; 3) PCPs’ experience and confidence. Results: Six PCP agreed to participate. Amongst the 11,909 patients of the clinic, 70 (0.59 %) patients met the criteria for HF. This number increased by 28.6 % (n = 90) after intervention. Increased use of GDMT for HFrEF patients at baseline (n = 35) was observed for all class of agents, with doubling of patients on triple therapies, from 8 (22.9 %) to 16 (45.7 %), p = 0.0047. Self-confidence on HF management was low (1, 16.7 %) but increased after the educational intervention of physicians (3, 50 %). Conclusion: An educational and collaborative approach between HF specialists and community PCP increased the number of new HF cases diagnosed, enhanced implementation of GDMT in patients with HFrEF and increase PCPs’ confidence in treating HF, despite being conducted during the COVID-19 pandemic.

Plant proteases are essential enzymes that play key roles during crucial phases of plant life. Some proteases are mainly involved in general protein turnover and recycle amino acids for protein synthesis. Other proteases are involved in cell signalling, cleave specific substrates and are key players during important genetically controlled molecular processes. Cathepsin B is a cysteine protease that can do both because of its exopeptidase and endopeptidase activities. Animal cathepsin B has been investigated for many years, and much is known about its mode of action and substrate preferences, but much remains to be discovered about this potent protease in plants. Cathepsin B is involved in plant development, germination, senescence, microspore embryogenesis, pathogen defence and responses to abiotic stress, including programmed cell death. This review discusses the structural features, the activity of the enzyme and the differences between the plant and animal forms. We discuss its maturation and subcellular localisation and provide a detailed overview of the involvement of cathepsin B in important plant life processes. A greater understanding of the cell signalling processes involving cathepsin B is needed for applied discoveries in plant biotechnology.

Introduction: The brain renin-angiotensin system (RAS) is dysregulated in dementia. We have previously shown that ACE-2, a central regulator of the protective counter-regulatory arm of RAS, is inversely associated with disease pathology in Alzheimer's disease (AD). We have investigated whether ACE-2 is similarly deficient in Vascular dementia (VaD) and mixed dementia (AD-VaD), in addition to AD. We also investigated whether ACE-2 is related to vascular pathology including CAA and SVD and explored whether ACE-2 varies according to gender, hypertension status, and ACE-2 genotype. Methods: We studied brain tissue (frontal cortex) from 147 dementia cases (AD (n=94), VaD (n=20) and AD-VaD (n=33)) and 104 age-matched non-demented controls from the South West Dementia Brain Bank, University of Bristol. Amyloid β (Aβ) and tau pathology and levels, had previously been measured by IHC and ELISA, respectively. ACE-2 protein levels were measured by ELISA, and ACE-2 enzyme activity was measured using a fluorometric sensolyte kit (Anaspec). ACE-1 activity was measured using a fluorogenic assay; Ang-II and Ang-(1-7) were measured by in-house direct ELISA. ACE-2 genotypes (rs2285666 and rs4240157) were obtained by PCR. Results: ACE-2 enzyme activity was significantly reduced in AD and AD-VaD cases (p

Several diseases have been reported as affecting endangered wild sea turtle population worldwide, including spirorchiidiasis. This parasitic infection results in serious circulatory disorders in sea turtles, as well as tissue damage due to the presence of spirorchiids eggs. However, few reports of organs severely affected by tissue replacement caused by granulomatous inflammatory processes due to spirorchiidiasis in sea turtles are available. In this regard, this study describes massive lesions in 16 juvenile green turtles from southeastern Brazil presenting no other detectable diseases or injuries, associated to parasitic compression of air spaces, parasitic thyroid atrophy, parasitic encephalic compression and parasitic splenic lymphoid depletion. These rare injuries were categorized as extremely severe, affecting most spirorchiidiasis-infected organs. Spirorchiidiasis was, thus, noted herein as capable of causing a variety of lethal injuries to vital or extremely important organs in sea turtles. Spirorchiidiasis should, therefore, also be considered a potential cause of death in stranded green sea turtle monitoring efforts.

Abstract Background Acute low energy pubic rami fractures in the elderly receive primarily conservative treatment. There is debate to what extent posterior ring involvement, which is detected superiorly by CT compared to X-ray, has an impact on outcome and may require modified treatment. We want to demonstrate if posterior ring involvement has an influence on different types of outcome in primarily conservatively treated acute FFP, questioning the usefulness of early CT. Additionally we analysed the early fracture pattern in cases where conservative treatment failed with need for secondary surgery. Methods A retrospective cohort study of 155 consecutive patients, recruited between 2009 and 2016, aged over 65 years diagnosed with an acute LE-PFr on X-ray at the emergency department of a single, level-one trauma centre and receiving an early CT. A set of outcome parameters was compared between patients with an isolated pubic rami fracture (CTia) and patients who had a combined posterior pelvic ring fracture (CTcp). Results There were 155 patients of whom 85.2% were female with a mean age of 83 years. 76.8% of patients living at home returned home and 15.5% moved to a nursing home. Mortality rate during hospitalisation was 6.4% and 14.8% at one year post-trauma. Secondary fracture displacement occurred in 22.6%. Secondary surgery was performed in 6 cases (3.9%). Median hospitalisation length of stay was 21 days (range 0 to 112 days). There was no significant association between the subgroups and change in residential status (p = 0.65), complications during hospitalisation (p = 0.75), mortality rate during admission (p = 0.75) and at 1 year (p = 0.88), readmission within 30 days (p = 0.46) and need for secondary surgery (p = 0.2). There was a significant increased median length of stay (p = 0.011) and rate of secondary displacement (p = 0.015) in subgroup CTcp. Secondary displacement had no impact on in-hospital complications (p = 0.7) nor mortality rate during admission (p = 0.79) or at 1 year (0.77). Early CT in patients who underwent secondary surgery showed stable B2.1 lesions in 4 of 6 cases. Conclusions Our data suggest that early CT in patients with conservatively treated acute LE-PFr in order to detect posterior lesions, has limited value in predicting failure of conservative treatment.

Visible light (400–800 nm) can lead to photooxidation of protein formulations, which might impair protein integrity. However, the relevant mechanism of photooxidation upon visible light exposure is still unclear for therapeutic proteins, since proteinogenic structures do not absorb light in the visible range. Here, we show that exposure of monoclonal antibody formulations to visible light, lead to the formation of reactive oxygen species (ROS), which subsequently induce specific protein degradations. The formation of ROS and singlet oxygen upon visible light exposure is investigated using electron paramagnetic resonance (EPR) spectroscopy. We describe the initial formation of ROS, most likely after direct reaction of molecular oxygen with a triplet state photosensitizer, generated from intersystem crossing of the excited singlet state. Since these radicals affect the oxygen content in the headspace of the vial, we monitored photooxidation of these mAb formulations. With increasing protein concentrations, we found (i) a decreasing headspace oxygen content in the sample, (ii) a higher relative number of radicals in solution and (iii) a higher protein degradation. Thus, the protein concentration dependence indicates the presence of higher concentration of a currently unknown photosensitizer.

To ensure the stability of biologicals over their entire shelf-life, non-ionic surface-active compounds (surfactants) are added to protect biologics from denaturation and particle formation. In this context, polysorbate 20 and 80 are the most used detergents. Despite their benefits of low toxicity and high biocompatibility, specific factors are influencing the intrinsic stability of polysorbates, leading to degradation, loss in efficacy, or even particle formation. Polysorbate degradation can be categorized into chemical or enzymatic hydrolysis and oxidation. Under pharmaceutical relevant conditions, hydrolysis is commonly originated from host cell proteins, whereas oxidative degradation may be caused by multiple factors such as light, presence of residual metal traces, peroxides, or temperature, which can be introduced upon manufacturing or could be already present in the raw materials. In this review, we provide an overview of the current knowledge on polysorbates with a focus on oxidative degradation. Subsequently, degradation products and key characteristics of oxidative-mediated polysorbate degradation in respect of different types and grades are summarized, followed by an extensive comparison between polysorbate 20 and 80. A better understanding of the radical-induced oxidative PS degradation pathway could support specific mitigation strategies. Finally, buffer conditions, various stressors, as well as appropriate mitigation strategies, reagents, and alternative stabilizers are discussed. Prior manufacturing, careful consideration and a meticulous risk-benefit analysis are highly recommended in terms of polysorbate qualities, buffers, storage conditions, as well as mitigation strategies.

AbstractHaving limited access to effective emotion regulation (ER) strategies, a construct commonly measured using the Difficulties in Emotion Regulation Scale (DERS; Gratz & Roemer, 2004), has been found to be strongly linked with non-suicidal self-injury (NSSI). However, the mechanisms that explain this association need more in-depth exploration. In this study, we investigated whether a cognitive mechanism (low self-perceived resilience) and/or a behavioral mechanism (insufficient repertoire of strategies used to resist NSSI) explained the association between limited access to ER strategies and the likelihood of recent (past-month) NSSI. Research questions were explored in a sample of 922 university students with a lifetime NSSI history (83.3% female). Study variables were measured using self-report questionnaires. Controlling for anxiety/depression, a path analytic model revealed that only low self-perceived resilience mediated the association between limited access to ER strategies and past-month NSSI. Participants who endorsed having limited access to ER strategies unexpectedly reported a higher number of coping strategies to resist NSSI. The results support the relevance of exploring resiliency beliefs in the association between ER capability and NSSI.

Hand hygiene is critical in the food service industry. Bacteria can easily be transferred between different surfaces to food during food preparation. Common hygiene practices include hand washing and usage of disposable gloves. Food handlers are often susceptible to transferring pathogenic bacteria to food, thus proper hand hygiene can limit such transmission. While gloves serve as a barrier between bare hands and food, their misuse, including reuse or lack of change, can potentially result in cross-contamination, compromising on food safety. In Singapore, strict regulations and consumer perceptions have encouraged the use of gloves in food handling. This study assessed the microbiological profile of gloves used by food handlers across fifty randomly chosen food establishments, by swabbing samples from the inner and outer surfaces of gloves. Glove samples were also subjected to a watertight test to detect significant physical damage. The results revealed that gloves with damage exhibited significantly higher mean Standard Plate Counts (SPCs), suggesting the likelihood that damaged gloves promoted the transfer of bacteria. Damaged gloves used to handle certain types of food, like noodles and rice dishes, also had significantly higher mean SPC than those used for beverages and snacks. However, gloves without visible damage showed no significant difference in mean SPC across different food types. The study highlighted that proper glove use can help in preventing bacterial transfer and consequently, maintaining food safety. Regular glove changes, particularly when damaged, are imperative. The findings underscore the importance of proper glove use in conjunction with other hand hygiene practices to uphold food hygiene and safety standards.

Abstract A new detection and attribution method is presented and applied to the global mean surface air temperature (GSAT) from 1900 to 2014. The method aims at attributing the climate changes to the variations of greenhouse gases, anthropogenic aerosols, and natural forcings. A convolutional neural network (CNN) is trained using the simulated GSAT from historical and single‐forcing simulations of 12 climate models. Then, we perform a backward optimization with the CNN to estimate the attributable GSAT changes. Such a method does not assume additivity in the effects of the forcings. The uncertainty in the attributable GSAT is estimated by sampling different starting points from single‐forcing simulations and repeating the backward optimization. To evaluate this new method, the attributable GSAT changes are also calculated using the regularized optimal fingerprinting (ROF) method. Using synthetic non‐additive data, we first find that the neural network‐based method estimates attributable changes better than ROF. When using GSAT data from climate model, the attributable anomalies are similar for both methods, which might reflect that the influence of forcing is mainly additive for the GSAT. However, we found that the uncertainties given both methods are different. The new method presented here can be adapted and extended in future work, to investigate the non‐additive changes found at the local scale or on other physical variables.

A crucial challenge in critical settings like medical diagnosis is making deep learning models used in decision-making systems interpretable. Efforts in Explainable Artificial Intelligence (XAI) are underway to address this challenge. Yet, many XAI methods are evaluated on broad classifiers and fail to address complex, real-world issues, such as medical diagnosis. In our study, we focus on enhancing user trust and confidence in automated AI decision-making systems, particularly for diagnosing skin lesions, by tailoring an XAI method to explain an AI model’s ability to identify various skin lesion types. We generate explanations using synthetic images of skin lesions as examples and counterexamples, offering a method for practitioners to pinpoint the critical features influencing the classification outcome. A validation survey involving domain experts, novices, and laypersons has demonstrated that explanations increase trust and confidence in the automated decision system. Furthermore, our exploration of the model’s latent space reveals clear separations among the most common skin lesion classes, a distinction that likely arises from the unique characteristics of each class and could assist in correcting frequent misdiagnoses by human professionals.

Monitoring atmospheric concentrations of greenhouse gases (GHGs) like carbon dioxide and methane in near real time and with good spatial resolution is crucial for enhancing our understanding of the sources and sinks of these gases. A novel approach can be proposed using a constellation of small satellites equipped with miniaturized spectrometers having a spectral resolution of a few nanometers. The objective of this study is to describe expected results that can be obtained with a single satellite named Uvsq-Sat NG. The SolAtmos end-to-end simulator and its three tools (IRIS, OptiSpectra, and GHGRetrieval) were developed to evaluate the performance of the spectrometer of the Uvsq-Sat NG mission, which focuses on measuring the main GHGs. The IRIS tool was implemented to provide Top-Of-Atmosphere (TOA) spectral radiances. Four scenes were analyzed (pine forest, deciduous forest, ocean, snow) combined with different aerosol types (continental, desert, maritime, urban). Simulated radiance spectra were calculated based on the wavelength ranges of the Uvsq-Sat NG, which spans from 1200 to 2000 nm. The OptiSpectra tool was used to determine optimal observational settings for the spectrometer, including Signal-to-Noise Ratio (SNR) and integration time. Data derived from IRIS and OptiSpectra served as input for our GHGRetrieval simulation tool, developed to provide greenhouse gas concentrations. The Levenberg–Marquardt algorithm was applied iteratively to fine-tune gas concentrations and model inputs, aligning observed transmittance functions with simulated ones under given environmental conditions. To estimate gas concentrations (CO2, CH4, O2, H2O) and their uncertainties, the Monte Carlo method was used. Based on this analysis, this study demonstrates that a miniaturized spectrometer onboard Uvsq-Sat NG is capable of observing different scenes by adjusting its integration time according to the wavelength. The expected precision for each measurement is of the order of a few ppm for carbon dioxide and less than 25 ppb for methane.

Abstract Background There exists a vast number of surgical treatment options for acromioclavicular (AC) joint injuries, and the current literature has yet to determine an equivocally superior treatment. AC joint repair has a long history and dates back to the beginning of the twentieth century. Main body Since then, over 150 different techniques have been described, covering open and closed techniques. Low grade injuries such as Type I-II according to the modified Rockwood classification should be treated conservatively, while high-grade injuries (types IV-VI) may be indicated for operative treatment. However, controversy exists if operative treatment is superior to nonoperative treatment, especially in grade III injuries, as functional impairment due to scapular dyskinesia or chronic pain remains concerning following non-operative treatment. Patients with a stable AC joint without overriding of the clavicle and without significant scapular dysfunction (Type IIIA) may benefit from non-interventional approaches, in contrast to patients with overriding of the clavicle and therapy-resistant scapular dysfunction (Type IIIB). If these patients are considered non-responders to a conservative approach, an anatomic AC joint reconstruction using a hybrid technique should be considered. In chronic AC joint injuries, surgery is indicated after failed nonoperative treatment of 3 to 6 months. Anatomic AC joint reconstruction techniques along with biologic augmentation (e.g. Hybrid techniques, suture fixation) should be considered for chronic high-grade instabilities, accounting for the lack of intrinsic healing and scar-forming potential of the ligamentous tissue in the chronic setting. However, complication and clinical failure rates remain high, which may be a result of technical failures or persistent horizontal and rotational instability. Conclusion Future research should focus on addressing horizontal and rotational instability, to restore native physiological and biomechanical properties of the AC joint.

Abstract Recent findings of microplastics in marine food such as fish, crabs and shrimps necessitate the need to develop biodegradable packaging materials. This study reports on the development of a biodegradable packing material from cellulose nanofibril-polyvinyl alcohol nanocomposite embedded with silver nanoparticles. Microcrystalline cellulose was isolated from sugarcane bagasse via the kraft process followed by conversion of cellulose I to cellulose II using NaOH/urea/water solution. The nanofibrils were then isolated using (2,2,6,6-Tetramethylpiperidin-1-yl) oxyl (TEMPO) and used as a reinforcing element in polyvinyl alcohol composite prepared through solvent casting. The tensile strength, water solubility, optical properties, water vapor permeability and wettability of the prepared films were then evaluated. The antimicrobial potency of the films was evaluated using the disc diffusion antimicrobial assay against selected microorganisms.