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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 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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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

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.

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.

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.

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.

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.

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.

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.

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.

In this paper, I present a Foucauldian reflection on our datafied present. Following others, I characterize this present as a condition of “digital capitalism” and proceed to explore whether and how digital conditions present an important change of episteme and, accordingly, an importantly different mode of subjectivity. I answer both of these concerns affirmatively. In the process, I engage with Colin Koopman’s recent work on infopower and argue that, despite changes in episteme and modes of subjectivity, the digital capitalist present is continuous with biopolitics as Foucault understood it, though it does raise serious worries about the possibility of transgressive resistance.

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.

Due to a high aspect ratio and enhanced mechanical strength, cellulose nanofibrils can be used as reinforcing elements in biocomposite films. In this study, cellulose nanofibrils were isolated from sugarcane bagasse using TEMPO-mediated oxidation and used to reinforce polyvinyl alcohol (PVA) films. The carboxyl group content, functional groups, crystallinity, thermal properties, and morphology of the nanofibrils were investigated. The influence of TOCNF content on the transmittance, swelling, and tensile strength of PVA-TOCNF films were investigated by varying the TOCNF content of PVA films. The fibrils had a carboxyl content of 12.2 ± 0.6 mg/g CE due to the presence of carboxylic groups, an increased degree of crystallinity, and highly porous nanofibrils with lengths between 150 nm and 600 nm. Incorporation of the isolated fiber on PVA films increased the swelling capacity, tensile strength, and UV absorption but a decrease in the solubility of the composite. An increase in the TOCNF content increased the tensile strength of the films with the highest tensile strength of 6.6 ± 2.2 kPa being observed when the TOCNF content was 30%. The improvement in films properties implies that the films can be used as a packaging material due to enhanced water absorption and light-barrier properties.

Abstract Qualitative NMR spectroscopic and quantitative calorimetric binding studies were performed to characterize the interaction of nontoxic mimics of the V-type nerve agent VX (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate) and the Novichok nerve agent A-234 (ethyl (1-(diethylamino)ethylidene)phosphoramidofluoridate) with a series of receptors in 100 mM aqueous phosphate buffer at pH 7.4 and 37 °C. These investigations provided information about the preferred geometry with which the nerve agent mimics are included into the receptor cavities and about the stability of the complexes formed. According to the results, the positively charged VX mimic prefers to bind to cation receptors such as sulfonated calixarenes and an acyclic cucurbituril but does not noticeably interact with cyclodextrins. While binding to the acyclic cucurbituril is stronger than that to calixarenes, the mode of inclusion into the sulfonatocalix[4]arene cavity is better suited for the development of scavengers that bind and detoxify V-type nerve agents. The neutral Novichok mimic, on the other hand, only interacts with the acyclic cucurbituril with a strength required for scavenger development. These binding studies thus provided guidelines for the further development of nerve agent scavengers.

Health care workers (HCWs) are more than ten times more likely to be infected with coronavirus infectious disease 2019 (COVID-19) than the general population, thus demonstrating the burden of COVID-19 among HCWs. Factors that expose HCWs to a differentially high-risk of COVID-19 acquisition are important to elucidate, enable appropriate public health interventions to mitigate against high risk and reduce adverse outcomes from the infection. We conducted a systematic review and meta-analysis to summarize and critically analyze the existing evidence on SARS-CoV-2 risk factors among HCWs. With no geographical limitation, we included studies, in any country, that reported (i) the PCR laboratory diagnosis of COVID-19 as an independent variable (ii) one or more COVID-19 risk factors among HCWs with risk estimates (relative risk, odds ratio, or hazard ratio) (iii) original, quantitative study design, and published in English or Mandarian. Our initial search resulted in 470 articles overall, however, only 10 studies met the inclusion criteria for this review. Out of the 10 studies included in the review, inadequate/lack of protective personal equipment, performing tracheal intubation, and gender were the most common risk factors of COVID-19. Based on the random effects adjusted pooled relative risk, HCWs who reported the use of protective personal equipment were 29% (95% CI: 16% to 41%) less likely to test positive for COVID-19. The study also revealed that HCWs who performed tracheal intubations were 34% (95% CI: 14% to 57%) more likely to test positive for COVID-19. Interestingly, this study showed that female HCWs are at 11% higher risk (RR 1.11 95% CI 1.01–1.21) of COVID-19 than their male counterparts. This article presents initial findings from a living systematic review and meta-analysis, therefore, did not yield many studies; however, it revealed a significant insight into better understanding COVID-19 risk factors among HCWs; insights important for devising preventive strategies that protect them from this infection. PROSPERO registration number: CRD42020193508 available for public comments via the link below https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020193508).

Abstract Background The proportion of patients with post-traumatic stress disorder (PTSD) that remain undiagnosed may be substantial. Without an accurate diagnosis, these patients may lack PTSD-targeted treatments and experience adverse health outcomes. This study used a machine learning approach to identify and describe civilian patients likely to have undiagnosed PTSD in the US commercial population. Methods The IBM® MarketScan® Commercial Subset (10/01/2015–12/31/2018) was used. A random forest machine learning model was developed and trained to differentiate between patients with and without PTSD using non–trauma-based features. The model was applied to patients for whom PTSD status could not be confirmed to identify individuals likely and unlikely to have undiagnosed PTSD. Patient characteristics, symptoms and complications potentially related to PTSD, treatments received, healthcare costs, and healthcare resource utilization were described separately for patients with PTSD (Actual Positive PTSD cohort), patients likely to have PTSD (Likely PTSD cohort), and patients without PTSD (Without PTSD cohort). Results A total of 44,342 patients were classified in the Actual Positive PTSD cohort, 5683 in the Likely PTSD cohort, and 2,074,471 in the Without PTSD cohort. While several symptoms/comorbidities were similar between the Actual Positive and Likely PTSD cohorts, others, including depression and anxiety disorders, suicidal thoughts/actions, and substance use, were more common in the Likely PTSD cohort, suggesting that certain symptoms may be exacerbated among those without a formal diagnosis. Mean per-patient-per-6-month healthcare costs were similar between the Actual Positive and Likely PTSD cohorts ($11,156 and $11,723) and were higher than those of the Without PTSD cohort ($3616); however, cost drivers differed between cohorts, with the Likely PTSD cohort experiencing more inpatient admissions and less outpatient visits than the Actual Positive PTSD cohort. Conclusions These findings suggest that the lack of a PTSD diagnosis and targeted management of PTSD may result in a greater burden among undiagnosed patients and highlights the need for increased awareness of PTSD in clinical practice and among the civilian population.

The oil sands mining operations in Alberta have produced billions of m3 of tailings which must be reclaimed and integrated into various mine closure landforms, including terrestrial landforms. Microorganisms play a central role in nutrient cycling during the reclamation of disturbed landscapes, contributing to successful vegetation restoration and long-term sustainability. However, microbial community succession and response in reconstructed and revegetated tailings remain largely unexplored. This study aimed to monitor the structural and functional responses of microbial communities in tailings subjected to different capping and vegetation strategies over two growing seasons (GS). To achieve this, a column-based greenhouse experiment was conducted to investigate microbial communities in tailings that were capped with a layer (10 or 30 cm) of peat-mineral mix (PMM) and planted with either upland or wetland communities. DNA metabarcoding analysis of the bacterial 16S rRNA gene and fungal ITS2 region as well as shotgun metagenomics were used to asses the impact of treatments on microbial taxonomy and functions, respectively. Results showed that tailings microbial diversity and community composition changed considerably after two GS compared to baseline samples, while communities in the PMM capping layer were much more stable. Likewise, several microbial functions were significantly enriched in tailings after two GS. Interestingly, the impact of capping on bacterial communities in tailings varied depending on the plant community, leading to a higher number of differentially abundant taxa and to a decrease in Shannon diversity and evenness in the upland treatment but not in the wetland treatment. Moreover, while capping in the presence of wetland vegetation increased the energy-related metabolic functions (carbon, nitrogen, and sulfur), these functions were depleted by capping in the upland treatment. Fungi represented a small proportion of the microbial community in tailings, but the relative abundance of several taxa changed over time, while the capping treatments favored the growth of some beneficial taxa, notably the root endophyte Serendipita, in both upland and wetland columns. The results suggest that selecting the right combination of capping material and vegetation type may contribute to improve below-ground microbial processes and sustain plant growth in harsh environments such as oil sands tailings.

Summary: Lecanemab, an anti-amyloid antibody with effects on biomarker and clinical endpoints in early Alzheimer's Disease (AD), was granted accelerated approval by the FDA in 2023 and regulatory review in Europe is ongoing. We estimate the population potentially eligible for treatment with lecanemab in the 27 EU countries to 5.4 million individuals. Treatment costs would exceed 133 billion EUR per year if the drug is priced similarly as in the United States, amounting to over half of the total pharmaceutical expenditures in the EU. This pricing would be unsustainable; the ability to pay for high-priced therapies varies substantially across countries. Pricing similarly to what has been announced for the United States may place the drug out of reach for patients in some European countries. Disparities in access to novel amyloid-targeting agents may further deepen the inequalities across Europe in health outcomes. As representatives of the European Alzheimer's Disease Consortium Executive Committee, we call for pricing policies that allow eligible patients across Europe to access important innovations, but also continued investments in research and development. Infrastructure to follow up the usage of new therapies in routine care and new payment models may be needed to address affordability and inequalities in patient access.

Background: Trabeculae in vertebral bodies are unequally distributed within the cervical spine (CS), the thoracic spine (TS), and lumbar spine (LS). Such structures are also unequally distributed within the individual vertebrae. Exact knowledge of the microstructure of these entities could impact our understanding and treatment of fractures caused by osteoporosis and possibly improve surgical approaches. Appropriate investigations could help clarify the pathomechanisms of different forms of osteoporotic vertebral fractures, as well as different changes in morphological findings like the trabecular bone score (TBS). In the present study, we applied punctures to the craniocaudal and ventrocaudal directions and obtained cylinders of cancellous bone from the central portions and marginal regions of cervical vertebrae 5 and 6, thoracic vertebrae 8 and 12, and lumbar vertebrae 1 and 3. We systematically analyzed these samples to determine the bone volume fraction, trabecular thickness, separation, connectivity density, degree of anisotropy, and structure model index. Methods: Using an 8-gauge Jamshidi needle, we obtained samples from three quadrants (Q I: right margin; Q II: central; Q III: left margin) in the frontal and transverse plane and prepared these samples with a moist cloth in a 1.5 mL Eppendorf reaction vessel. The investigations were performed on a micro-CT device (SKYSCAN 1172, RJL Micro & Analytic Company, Karlsdorf-Neuthard, Germany). All collected data were analyzed using the statistical software package SPSS (version 24.0, IBM Corp., Armonk, NY, USA). Student’s t test, the Wilcoxon–Mann–Whitney test, the Chi-squared test, and univariate analysis were used for between-group comparisons. The selection of the test depended on the number of investigated groups and the result of the Shapiro–Wilk test of normal distribution. In the case of statistically significant results, a post hoc LSD test was performed. Results: In total, we obtained 360 bone samples from 20 body donors. The craniocaudal puncture yielded data of similar magnitudes for all investigated parameters in all three quadrants, with the highest values observed in the CS. Comparisons of the ventrodorsal and craniocaudal microstructure revealed a significantly lower trabecular density and a significantly higher degree of anisotropy in the craniocaudal direction. Conclusions: The results presented different distributions and behaviors of trabecular density, with lower density in the mid-vertebral region over the entire breadth of the vertebrae. Reduced trabecular density caused a higher degree of anisotropy and was, therefore, associated with a lower capacity to sustain biomechanical loads. Fractures in fish vertebrae were easily explained by this phenomenon. The different changes in these structures could be responsible, in part, for the changes in the TBS determined using dual-energy X-ray absorptiometry. These results confirm the clinical relevance of the TBS.

We present three-dimensional (3D) maps of Jupiter’s atmospheric circulation at cloud-top level from Doppler-imaging data obtained in the visible domain with JIVE, the second node of the JOVIAL network, which is mounted on the Dunn Solar Telescope at Sunspot, New Mexico. We report on 12 nights of observations between 2018 May 4 and May 30, representing a total of about 80 hr. First, the average zonal wind profile derived from our data is compatible with that derived from cloud-tracking measurements performed on Hubble Space Telescope images obtained in 2018 April from the Outer Planet Atmospheres Legacy program. Second, we present the first ever 2D maps of Jupiter’s atmospheric circulation from Doppler measurements. The zonal velocity map highlights well-known atmospheric features, such as the equatorial hot spots and the Great Red Spot (GRS). In addition to zonal winds, we derive meridional and vertical velocity fields from the Doppler data. The motions attributed to vertical flows are mainly located at the boundary between the equatorial belts and tropical zones, which could indicate active motion in theses regions. Qualitatively, these results compare well to recent Juno data that have unveiled the 3D structure of Jupiter’s wind field. To the contrary, the motions attributed to meridional circulation are very different from what is obtained by cloud tracking, except at the GRS. Because of limitations with data resolution and processing techniques, we acknowledge that our measurements of the vertical or meridional flows of Jupiter are still to be confirmed.

Abstract Background Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder affecting approximately 10.0% of children and 6.5% of adolescents in the United States (US). A comprehensive assessment of the current treatment landscape is warranted to highlight potential unmet needs of children and adolescents with ADHD. Therefore, this study described treatment patterns and healthcare costs among commercially insured children and adolescents with ADHD in the US. Methods Children and adolescents with ADHD initiating pharmacological treatment indicated for ADHD were identified from IBM MarketScan Commercial Database (2014–2018). A treatment sequence algorithm was used to examine treatment patterns, including discontinuation (≥ 180 days following the last day of supply of any ADHD treatment), switch, add-on, and drop (discontinuation of an agent in combination therapy), during the 12-month study period following the index date (i.e., first observed ADHD treatment). Total adjusted annual healthcare costs were compared between patients with and without treatment changes. Results Among 49,756 children and 29,093 adolescents included, mean age was 9 and 15 years, respectively, and 31% and 38% were female. As the first treatment regimen observed, 92% of both children and adolescents initiated a stimulant and 11% initiated combination therapy. Over half of the population had a treatment change over 12 months—59% of children and 68% of adolescents. Treatment discontinuation over 12 months was common in both populations—21% of children and 36% of adolescents discontinued treatment. Healthcare costs increased with the number of treatment changes observed; children and adolescents with treatment changes (i.e., 1, 2, or ≥ 3) incurred an incremental annual cost of up to $1,443 and $2,705, respectively, compared to those without a treatment change (p

Viral enteric pathogens remain an important cause of diarrhoeal outbreaks among children in sub-Saharan Africa (SSA). Consequently, diarrhoeal illness remains a significant cause of morbidity and mortality in the under-fives in SSA. These outbreaks associated with viral pathogens tend to be seasonal and early warning systems for impending outbreaks could be very crucial for triggering preventive public health response and building public health resilience to deal with increased demand for medical services. Wastewater surveillance for pathogens is an important epidemiological component that could inform early warning systems. The objective of this rapid review was to evaluate the use of wastewater for epidemiology surveillance of enteric viral pathogens. Nine studies met the inclusion criteria. Eight viral pathogens were reviewed and analysed from 6 countries that performed wastewater analysis. Six studies explored the epidemiologic significance of viral pathogens in wastewater. The findings of this review revealed that monitoring of wastewater can provide an additional tool to determine the epidemiology of viral pathogens circulating in the community thereby providing early warning of potential outbreaks using wastewater-based epidemiology methods. Five of the included studies revealed the occurrence of viral pathogens in raw sewage and treated wastewater as an indication of inefficient elimination of viruses leading to potential release into water sources which presents a public health risk, increasing the risk of inducing gastroenteritis in the population. Six studies revealed the need for public health authorities to realise the potential benefit of environmental surveillance (ES) as an additional tool to determine the epidemiology of viral pathogens circulating in each community. Despite the significant public health challenge associated with enteric viral pathogens in sub-Saharan Africa, there remains remarkable underinvestment in potentially epidemiologically beneficial research, including wastewater-based epidemiology for these infections.

Background: The relationship between HIV infection and COVID-19 clinical outcomes remains a significant public health research problem. We aimed to determine the association of HIV comorbidity with COVID-19 mortality. Methods: We searched PubMed, Google Scholar and World Health Organization library databases for relevant studies. All searches were conducted from 1st to 7th December 2021. Title, abstract and full text screening was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The relative risk of mortality in HIV-infected COVID-19 patients was computed using a random-effects model. All analyses were performed using Meta and Metasens statistical packages available in R version 4.2.1 software package. The quality of included studies was assessed using the GRADE approach, Egger’s test was employed to determine the risk of bias. Results: A total of 16 studies were included in this review. Among the COVID-19 patients with HIV infection, the mortality rate due to COVID-19 was 7.97% (4 287/53,801), and among the COVID-19 patients without HIV infection, the mortality rate due to COVID-19 was 0.69% (127, 961/18, 513, 747). In the random effects model, we found no statistically significant relative risk of mortality in HIV-infected COVID-19 patients (RR 1.07, 95% CI 0.86–1.32). The between-studies heterogeneity was substantial (I2 = 91%, P