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Background: Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is a poorly understood condition with symptoms across a range of biological domains that often have debilitating consequences. Some have recently suggested that lingering SARS-CoV-2 virus particles in the gut may impede serotonin production and that low serotonin may drive many Long COVID symptoms across a range of biological systems. Therefore, selective serotonin reuptake inhibitors (SSRIs), which increase synaptic serotonin availability, may be used to prevent or treat Long COVID. SSRIs are commonly prescribed for depression, therefore restricting a study sample to only include patients with depression can reduce the concern of confounding by indication. Methods: In an observational sample of electronic health records from patients in the National COVID Cohort Collaborative (N3C) with a COVID-19 diagnosis between September 1, 2021, and December 1, 2022, and a comorbid depressive disorder, the leading indication for SSRI use, we evaluated the relationship between SSRI use during acute COVID-19 and subsequent 12-month risk of Long COVID (defined by ICD-10 code U09.9). We defined SSRI use as a prescription for SSRI medication beginning at least 30 days before acute COVID-19 and not ending before SARS-CoV-2 infection. To minimize bias, we estimated relationships using nonparametric targeted maximum likelihood estimation to aggressively adjust for high-dimensional covariates. Results: We analyzed a sample (n = 302,626) of patients with a diagnosis of a depressive condition before COVID-19 diagnosis, where 100,803 (33%) were using an SSRI. We found that SSRI users had a significantly lower risk of Long COVID compared to nonusers (adjusted causal relative risk 0.92, 95% CI (0.86, 0.99)) and we found a similar relationship comparing new SSRI users (first SSRI prescription 1 to 4 months before acute COVID-19 with no prior history of SSRI use) to nonusers (adjusted causal relative risk 0.89, 95% CI (0.80, 0.98)). Conclusions: These findings suggest that SSRI use during acute COVID-19 may be protective against Long COVID, supporting the hypothesis that serotonin may be a key mechanistic biomarker of Long COVID. [ABSTRACT FROM AUTHOR]

Objective: Although olfactory dysfunction is one of the most common presenting signs of COVID‐19 infection, little is known about which populations are most susceptible. The aim of this study is to evaluate the risk of COVID‐19‐induced chemosensory dysfunction in malnourished individuals. Methods: The N3C database was queried for adults having positive COVID‐19 test result, diagnosis of chemosensory dysfunction within 2 weeks of positive test date, and overnutrition or undernutrition (i.e., deficiency or excess of micro‐ and macronutrients) related diagnoses prior to COVID‐19 infection. Individuals previously diagnosed with chemosensory dysfunction were excluded. COVID‐19‐positive adults without olfactory dysfunction were similarly analyzed. Statistical analysis was performed using odds ratio calculations (95% confidence interval [CI]). Results: Of 3,971,536 patients with COVID‐19, 73,211 adults were identified with a diagnosis of undernutrition and 428,747 adults were identified with a diagnosis of overnutrition prior to infection. Of those with undernutrition, 264 (0.36%) individuals were identified with a diagnosis of olfactory dysfunction within 2 weeks of infection. Of those with overnutrition, 2851 (0.66%) individuals were identified with a diagnosis of olfactory dysfunction within 2 weeks of infection. The calculated odds ratio for undernutrition and olfactory dysfunction was 0.731 (p < 0.0001, 95% CI [0.0647, 0.0825]). The calculated odds ratio for overnutrition and olfactory dysfunction was 1.419 (p < 0.0001, 95% CI [1.3359, 1.5081]). Conclusion: Overnutrition may increase the risk of COVID‐19‐related olfactory dysfunction, while undernutrition may slightly protect. While reasons are unclear, baseline differences in metabolic, inflammatory, and structural biochemistry deserve closer inspection. Level of Evidence: 3 Laryngoscope, 134:4338–4343, 2024 [ABSTRACT FROM AUTHOR]

We investigate risk factors for severe COVID-19 in persons living with HIV (PWH), including among racialized PWH, using the U.S. population-sampled National COVID Cohort Collaborative (N3C) data released from January 1, 2020 to October 10, 2022. We defined severe COVID-19 as hospitalized with invasive mechanical ventilation, extracorporeal membrane oxygenation, discharge to hospice or death. We used machine learning methods to identify highly ranked, uncorrelated factors predicting severe COVID-19, and used multivariable logistic regression models to assess the associations of these variables with severe COVID-19 in several models, including race-stratified models. There were 3 241 627 individuals with incident COVID-19 cases and 81 549 (2.5%) with severe COVID-19, of which 17 445 incident COVID-19 and 1 020 (5.8%) severe cases were among PWH. The top highly ranked factors of severe COVID-19 were age, congestive heart failure (CHF), dementia, renal disease, sodium concentration, smoking status, and sex. Among PWH, age and sodium concentration were important predictors of COVID-19 severity, and the effect of sodium concentration was more pronounced in Hispanics (aOR 4.11 compared to aOR range: 1.47–1.88 for Black, White, and Other non-Hispanics). Dementia, CHF, and renal disease was associated with higher odds of severe COVID-19 among Black, Hispanic, and Other non-Hispanics PWH, respectively. Our findings suggest that the impact of factors, especially clinical comorbidities, predictive of severe COVID-19 among PWH varies by racialized groups, highlighting a need to account for race and comorbidity burden when assessing the risk of PWH developing severe COVID-19. [ABSTRACT FROM AUTHOR]

Solid organ transplant recipients (SOTR) are at increased risk from COVID-19. Over time, the absolute risk of adverse outcomes after COVID-19 has decreased in both the nonimmunosuppressed/immunocompromised (non-ISC) general population, and amongst SOTR. Using the N3C, we examined the absolute risk of mortality, major adverse renal or cardiac events, and hospitalization after COVID-19 diagnosis amongst non-ISC and SOTR populations over five waves of the pandemic (Wave 1: Ancestral COVID; Wave 2: Alpha; Wave 3: Delta; Wave 4: Omicron; Wave 5: Omicron). Within each wave, we determined the relative risk of each outcome for SOTR versus the non-ISC population based on crude event rates, and then used multivariable cox proportional hazards models and logistic regression to determine the adjusted risk of each outcome based on SOT status. Throughout the pandemic, including during the Omicron wave (Wave 5), SOTR were at greater absolute risk for each outcome than non-ISC patients (p-values all <0.001). The adjusted risk of SOT status for each outcome was relatively stable over time (aHR 1.28-1.61 for mortality; aHR 1.31-1.47 for MACE; aHR 1.72-1.90 for MARCE; aHR 1.75-2.07 for AKI; and aOR 1.53-1.81 for hospitalization). Despite a reduction in the absolute risk of COVID-19 complications, the relative risk for SOTR versus the non-ISC population has not improved. [ABSTRACT FROM AUTHOR]

Introduction: Despite their adverse environmental effects, modern agriculture relies heavily on agrochemicals to manage diseases and pests and enhance plant growth and productivity. Some of these functions could instead be fulfilled by endophytes from the plant microbiota, which have diverse activities beneficial for plant growth and health. Methods: We therefore used a microbiome-guided top-down approach to select ten bacterial strains from different taxa in the core microbiome of tomato plants in the production chain for evaluation as potential bioinoculants. High-quality genomes for each strain were obtained using Oxford Nanopore long-read and Illumina short-read sequencing, enabling the dissection of their genetic makeup to identify phyto-beneficial traits. Results: Bacterial strains included both taxa commonly used as biofertilizers and biocontrol agents (i.e. Pseudomonas and Bacillus) as well as the less studied genera Leclercia, Chryseobacterium, Glutamicibacter, and Paenarthorbacter. When inoculated in the tomato rhizosphere, these strains promoted plant growth and reduced the severity of Fusarium Crown and Root Rot and Bacterial Spot infections. Genome analysis yielded a comprehensive inventory of genes from each strain related to processes including colonization, biofertilization, phytohormones, and plant signaling. Traits directly relevant to fertilization including phosphate solubilization and acquisition of nitrogen and iron were also identified. Moreover, the strains carried several functional genes putatively involved in abiotic stress alleviation and biotic stress management, traits that indirectly foster plant health and growth. Discussion: This study employs a top-down approach to identify new plant growth-promoting rhizobacteria (PGPRs), offering an alternative to the conventional bottom-up strategy. This method goes beyond the traditional screening of the strains and thus can expand the range of potential bioinoculants available for market application, paving the way to the use of new still underexplored genera. [ABSTRACT FROM AUTHOR]

Background Patients with coronavirus disease 2019 (COVID-19) often experience persistent symptoms, known as postacute sequelae of COVID-19 or long COVID, after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Chronic lung disease (CLD) has been identified in small-scale studies as a potential risk factor for long COVID. Methods This large-scale retrospective cohort study using the National COVID Cohort Collaborative data evaluated the link between CLD and long COVID over 6 months after acute SARS-CoV-2 infection. We included adults (aged ≥18 years) who tested positive for SARS-CoV-2 during any of 3 SARS-CoV-2 variant periods and used logistic regression to determine the association, considering a comprehensive list of potential confounding factors, including demographics, comorbidities, socioeconomic conditions, geographical influences, and medication. Results Of 1 206 021 patients, 1.2% were diagnosed with long COVID. A significant association was found between preexisting CLD and long COVID (adjusted odds ratio [aOR], 1.36). Preexisting obesity and depression were also associated with increased long COVID risk (aOR, 1.32 for obesity and 1.29 for depression) as well as demographic factors including female sex (aOR, 1.09) and older age (aOR, 1.79 for age group 40–65 [vs 18–39] years and 1.56 for >65 [vs 18–39] years). Conclusions CLD is associated with higher odds of developing long COVID within 6 months after acute SARS-CoV-2 infection. These data have implications for identifying high-risk patients and developing interventions for long COVID in patients with CLD. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea (OSA) is a prevalent sleep disorder characterized by repeated episodes of partial or complete obstruction of the upper airway during sleep. While the systemic implications of OSA are well documented, the dental consequences are less frequently discussed yet equally significant. This review aims to elucidate the oral health impacts of OSA, emphasizing the importance of interdisciplinary care. Methods: A comprehensive literature search was conducted across several databases to identify studies examining the relationship between OSA and various oral health parameters. The review included observational studies, clinical trials, and systematic reviews published in English up to January 2024. Results: OSA was significantly associated with heightened risks of bruxism, dry mouth, periodontal disease, temporomandibular joint disorders, palatal and dental changes, and alterations in taste sensation. Mouth breathing associated with OSA was a critical factor in exacerbating xerostomia and dental caries. Furthermore, the systemic inflammation induced by OSA appeared to correlate with the severity of periodontal disease. Patients using oral appliance therapy for OSA also showed notable changes in dental occlusion and required ongoing dental monitoring. Conclusions: The findings underscore the bidirectional relationship between OSA and oral health, highlighting the need for dental professionals to be integral participants in the management of OSA. Early dental evaluation and intervention can contribute to the overall health and quality of life of individuals with OSA. The review advocates for the development of clinical guidelines to facilitate the early identification and management of OSA-related oral health issues within dental practice and encourages a collaborative approach to patient care. [ABSTRACT FROM AUTHOR]

Background: Infants and toddlers with kidney failure are susceptible to neurodevelopmental delays due to medical comorbidities and rapid brain development in early childhood. However, research on the neuropsychological development of this patient population has been limited over the past 10 years. Methods: We performed a retrospective study to evaluate the neurodevelopmental functioning of infants/toddlers with kidney failure who completed the Bayley Scales of Infant and Toddler Development (3rd and 4th Edition) as part of a pretransplant evaluation between 2010 and 2022 (n = 23; Mage = 18 months, SD = 8.53; 16 males) using t-tests, linear model, and Pearson correlations. Results: Mean Bayley scores of participants were below normative means for cognition (M = 86.74, 95% CI = 80.53–92.94, p < 0.001), language (M = 79.20, 95% CI = 73.32–85.08, p < 0.001), and motor (M = 78.00, 95% CI = 70.15–85.85, p < 0.001) domains. After adjusting for prematurity and epilepsy, patients on dialysis had significantly lower cognitive (78.7 vs. 93.8; p = 0.001) and motor scores (67.1 vs. 85.5; p = 0.01) compared to no dialysis. Pretransplant cognitive scores were positively correlated with posttransplant Full-Scale IQ (r(8) = 0.65 p = 0.04), verbal comprehension (r(8) = 0.75 p = 0.02), and fluid reasoning (r(7) = 0.68 p = 0.045). Similarly, pretransplant language scores were positively correlated with posttransplant Full-Scale IQ (r(7) = 0.74 p = 0.03) and verbal comprehension (r(7) = 0.73 p = 0.03). Of the 16 participants who reached age > 5 years during the study period, seven were diagnosed with a neurodevelopmental disorder, including three with autism spectrum disorder. Conclusions: Infants and toddlers with kidney failure are at risk of developmental delays and later neurodevelopmental disorders. Dialysis is associated with cognitive and motor delays independent of prematurity and epilepsy. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

Background: this prospective study investigated the correlation between the oral bacterial microflora and the microflora found in voice prostheses (VPs) among 20 patients who had undergone laryngectomy. The aim was to explore the associations between the microflora's presence and the malfunction of VPs, along with the association between the predominant microorganism and the longevity of VPs. Methods: the research process included gathering medical histories, conducting ENT examinations, replacing VPs, and performing check-ups every four months for a period of 15.5 months. Additionally, microbiological examinations, blood tests, and voice change surveys were conducted. Results: a correlation between the microflora isolated from VPs and that from oral rinses was demonstrated in a large percentage of patients who experienced a loss of prosthetic functional efficiency. The correlation analysis between the type of microorganism and the lifespan of VPs showed a non-significant Pearson correlation coefficient (r = 0.043, p = 0.678). Conclusions: there is no significant linear correlation between the predominant microorganism and the average lifespan of VPs. [ABSTRACT FROM AUTHOR]

Periodontal diseases are among the most common bacterial-related pathologies affecting the oral cavity of dogs. Nevertheless, the canine oral ecosystem and its correlations with oral disease development are still far from being fully characterized. In this study, the species-level taxonomic composition of saliva and dental plaque microbiota of 30 healthy dogs was investigated through a shallow shotgun metagenomics approach. The obtained data allowed not only to define the most abundant and prevalent bacterial species of the oral microbiota in healthy dogs, including members of the genera Corynebacterium and Porphyromonas , but also to identify the presence of distinct compositional motifs in the two oral microniches as well as taxonomical differences between dental plaques collected from anterior and posterior teeth. Subsequently, the salivary and dental plaque microbiota of 18 dogs affected by chronic gingival inflammation and 18 dogs with periodontitis were compared to those obtained from the healthy dogs. This analysis allowed the identification of bacterial and metabolic biomarkers correlated with a specific clinical status, including members of the genera Porphyromonas and Fusobacterium as microbial biomarkers of a healthy and diseased oral status, respectively, and genes predicted to encode for metabolites with anti-inflammatory properties as metabolic biomarkers of a healthy status. [ABSTRACT FROM AUTHOR]

Background: To describe high-resolution brain vessel wall MRI (VW-MRI) patterns and morphological brain findings in central nervous system (CNS) vasculitis patients. Methods: Fourteen patients with confirmed CNS Vasculitis from two tertiary centers underwent VW-MRI using a 3T scanner. The images were reviewed by two neuroradiologists to assess vessel wall enhancement characteristics and locations. Results: Fourteen patients were included (six females; average age 48 ± 19 years). Diagnoses included primary CNS vasculitis (PCNSV) in six patients and secondary CNS vasculitis (SCNSV) in eight, half of which were infection-related. Thirteen patients showed vessel wall enhancement, which was intense in eleven patients (84.6%) and concentric in twelve (92.3%), affecting the anterior circulation in nine patients (69.2%), posterior in two patients (15.4%), and both circulations in two patients (15.4%). The enhancement patterns were similar across different CNS vasculitis types. DWI changes corresponded with areas of vessel wall enhancement in 77% of patients. Conclusions: CNS vasculitis is often associated with intense, concentric vessel wall enhancement in VW-MRI, especially in the anterior circulation. The consistent presence of DWI alterations in affected territories suggests a possible link to microembolization or hypoperfusion. These imaging findings complement parenchymal brain MRI and MRA/DSA data, potentially increasing the possibility of a clinical diagnosis of CNS vasculitis. [ABSTRACT FROM AUTHOR]

The bacterial genus Hafnia has recently attracted attention due to its complex metabolic features and host‐interaction capabilities, which are associated with health benefits, primarily weight loss. However, significant gaps remain in our understanding of the genomic characteristics of this emerging microbial group. In this study, we utilized all available high‐quality genomes of Hafnia alvei and Hafnia paralvei to uncover the broad distribution of Hafnia in human and honeybee guts, as well as in dairy products, by analysing 1068 metagenomic datasets. We then investigated the genetic traits related to Hafnia's production of vitamins and short‐chain fatty acids (SCFAs) through a comparative genomics analysis that included all dominant bacterial species in the three environments under study. Our findings underscore the extensive metabolic capabilities of Hafnia, particularly in the production of vitamins such as thiamine (B1), nicotinate (B3), pyridoxine (B6), biotin (B7), folate (B9), cobalamin (B12), and menaquinone (K2). Additionally, Hafnia demonstrated a conserved genetic makeup associated with SCFA production, including acetate, propanoate, and butanoate. These metabolic traits were further confirmed using RNAseq analyses of a newly isolated H. paralvei strain T10. Overall, our study illuminates the ecological distribution and genetic attributes of this bacterial genus, which is of increasing scientific and industrial relevance. [ABSTRACT FROM AUTHOR]

Cloud cover assessment is crucial for meteorology, Earth observation, and environmental monitoring, providing valuable data for weather forecasting, climate modeling, and remote sensing activities. Depending on the specific purpose, identifying and accounting for pixels affected by clouds is essential in spectral remote sensing imagery. In applications such as land monitoring and various remote sensing activities, detecting/removing cloud-contaminated pixels is crucial to ensuring the accuracy of advanced processing of satellite imagery. Typically, the objective of cloud masking is to produce an image where every pixel in a satellite spectral image is categorized as either clear or cloudy. Nevertheless, there is also a prevalent approach in the literature that yields a multi-class output. With the progress in Machine and Deep Learning, coupled with the accelerated capabilities of GPUs, and the abundance of available remote sensing data, novel opportunities and methods for cloud detection have emerged, improving the accuracy and the efficiency of the algorithms. This paper provides a review of these last methods for cloud masking in multispectral satellite imagery, with emphasis on the Deep Learning approach, highlighting their benefits and challenges. [ABSTRACT FROM AUTHOR]

Stable isotopes (SI) and fatty acid (FA) biomarkers can provide insights regarding trophic pathways and habitats associated with contaminant bioaccumulation. We assessed relationships between SI and FA biomarkers and published data on concentrations of two pesticides [dichlorodiphenyltrichloroethane and degradation products (DDX) and bifenthrin] in juvenile Chinook Salmon (Oncorhynchus tshawytscha) from the Sacramento River and Yolo Bypass floodplain in Northern California near Sacramento. We also conducted SI and FA analyses of zooplankton and macroinvertebrates to determine whether particular trophic pathways and habitats were associated with elevated pesticide concentrations in fish. Relationships between DDX and both sulfur (δ34S) and carbon (δ13C) SI ratios in salmon indicated that diet is a major exposure route for DDX, particularly for individuals with a benthic detrital energy base. Greater use of a benthic detrital energy base likely accounted for the higher frequency of salmon with DDX concentrations > 60 ng/g dw in the Yolo Bypass compared to the Sacramento River. Chironomid larvae and zooplankton were implicated as prey items likely responsible for trophic transfer of DDX to salmon. Sulfur SI ratios enabled identification of hatchery-origin fish that had likely spent insufficient time in the wild to substantially bioaccumulate DDX. Bifenthrin concentration was unrelated to SI or FA biomarkers in salmon, potentially due to aqueous uptake, biotransformation and elimination of the pesticide, or indistinct biomarker compositions among invertebrates with low and high bifenthrin concentrations. One FA [docosahexaenoic acid (DHA)] and DDX were negatively correlated in salmon, potentially due to a greater uptake of DDX from invertebrates with low DHA or effects of DDX on FA metabolism. Trophic biomarkers may be useful indicators of DDX accumulation and effects in juvenile Chinook Salmon in the Sacramento River Delta. [ABSTRACT FROM AUTHOR]

Genetically engineered mouse models only capture a small fraction of the genetic lesions that drive human cancer. Current CRISPR–Cas9 models can expand this fraction but are limited by their reliance on error-prone DNA repair. Here we develop a system for in vivo prime editing by encoding a Cre-inducible prime editor in the mouse germline. This model allows rapid, precise engineering of a wide range of mutations in cell lines and organoids derived from primary tissues, including a clinically relevant Kras mutation associated with drug resistance and Trp53 hotspot mutations commonly observed in pancreatic cancer. With this system, we demonstrate somatic prime editing in vivo using lipid nanoparticles, and we model lung and pancreatic cancer through viral delivery of prime editing guide RNAs or orthotopic transplantation of prime-edited organoids. We believe that this approach will accelerate functional studies of cancer-associated mutations and complex genetic combinations that are challenging to construct with traditional models. Prime-editing mouse models enable the study of specific cancer mutations in vivo. [ABSTRACT FROM AUTHOR]

Neurodevelopmental disorders (NDD) are a group of conditions affecting children's neurodevelopment with consequences on personal, social, and educational functioning. Social robots have been used in the rehabilitation of children with NDD with encouraging results on learning outcomes. This study aims at understanding how a social robot should act to support caregivers during the rehabilitation of children with NDD. Through a Design-Based-Research approach, we investigate this question by considering the point of view of the most concerned and expert people, i.e., children with NDD and their caregivers. We present here the collaborative and iterative design of R2C3, a social robot used to support caregivers and children during rehabilitation sessions in a learning-by-teaching scenario. 27 caregivers and 6 children participated in the iterative design and/or the evaluation of R2C3, that resulted in the development of a Wizard-of-Oz interface and a library containing 120 robot behaviors. We then studied how caregivers used such behaviors during the rehabilitation sessions. We found they mainly used the robot to provide positive reinforcements to children, to elicit their reflection and knowledge toward shared handwriting activities, and to support children's error acceptance. However, the utilization of Positive Reinforcement by caregivers tends to decrease significantly as the sessions progress. [ABSTRACT FROM AUTHOR]

Members of the genus Bifidobacterium are among the first microorganisms colonizing the human gut. Among these species, strains of Bifidobacterium breve are known to be commonly transmitted from mother to her newborn, while this species has also been linked with activities supporting human wellbeing. In the current study, an in silico approach, guided by ecology- and phylogenome-based analyses, was employed to identify a representative strain of B. breve to be exploited as a novel health-promoting candidate. The selected strain, i.e., B. breve PRL2012, was found to well represent the genetic content and functional genomic features of the B. breve taxon. We evaluated the ability of PRL2012 to survive in the gastrointestinal tract and to interact with other human gut commensal microbes. When co-cultivated with various human gut commensals, B. breve PRL2012 revealed an enhancement of its metabolic activity coupled with the activation of cellular defense mechanisms to apparently improve its survivability in a simulated ecosystem resembling the human microbiome. [ABSTRACT FROM AUTHOR]

Background Real-world evidence of coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) booster effectiveness among patients with immune dysfunction are limited. Methods We included data from patients in the United States National COVID Cohort Collaborative (N3C) who completed ≥2 doses of mRNA vaccination between 10 December 2020 and 27 May 2022. Immune dysfunction conditions included human immunodeficiency virus infection, solid organ or bone marrow transplant, autoimmune diseases, and cancer. We defined incident COVID-19 BTI as positive results from laboratory tests or diagnostic codes 14 days after at least 2 doses of mRNA vaccination; and severe COVID-19 BTI as hospitalization, invasive cardiopulmonary support, and/or death. We used propensity scores to match boosted versus nonboosted patients and evaluated hazards of incident and severe COVID-19 BTI using Cox regression after matching. Results Among patients without immune dysfunction, the relative effectiveness of booster (3 doses) after 6 months from the primary (2 doses) vaccination against BTI ranged from 69% to 81% during the Delta-predominant period and from 33% to 39% during the Omicron-predominant period. Relative effectiveness against BTI was lower among patients with immune dysfunction but remained statistically significant in both periods. Boosted patients had lower risk of COVID-19–related hospitalization (hazard ratios [HR] ranged from 0.5 [95% confidence interval {CI},.48–.53] to 0.63 [95% CI,.56–.70]), invasive cardiopulmonary support, or death (HRs ranged from 0.46 [95% CI,.41–.52] to 0.63 [95% CI,.50–.79]) during both periods. Conclusions Booster vaccines remain effective against severe COVID-19 BTI throughout the Delta- and Omicron-predominant periods, regardless of patients' immune status. [ABSTRACT FROM AUTHOR]

Realizing the promise of prime editing for the study and treatment of genetic disorders requires efficient methods for delivering prime editors (PEs) in vivo. Here we describe the identification of bottlenecks limiting adeno-associated virus (AAV)-mediated prime editing in vivo and the development of AAV-PE vectors with increased PE expression, prime editing guide RNA stability and modulation of DNA repair. The resulting dual-AAV systems, v1em and v3em PE-AAV, enable therapeutically relevant prime editing in mouse brain (up to 42% efficiency in cortex), liver (up to 46%) and heart (up to 11%). We apply these systems to install putative protective mutations in vivo for Alzheimer's disease in astrocytes and for coronary artery disease in hepatocytes. In vivo prime editing with v3em PE-AAV caused no detectable off-target effects or significant changes in liver enzymes or histology. Optimized PE-AAV systems support the highest unenriched levels of in vivo prime editing reported to date, facilitating the study and potential treatment of diseases with a genetic component. Prime editors are efficiently delivered to mouse organs with AAV vectors. [ABSTRACT FROM AUTHOR]

Nowadays, there is contrasting evidence between the ongoing continuing and widespread environmental degradation and the many means to implement environmental sustainability actions starting from good policies (e.g. EU New Green Deal, CAP), powerful technologies (e.g. new satellites, drones, IoT sensors), large databases and large stakeholder engagement (e.g. EIP‐AGRI, living labs). Here, we argue that to tackle the above contrasting issues dealing with land degradation, it is very much required to develop and use friendly and freely available web‐based operational tools to support both the implementation of environmental and agriculture policies and enable to take positive environmental sustainability actions by all stakeholders. Our solution is the S‐DSS LANDSUPPORT platform, consisting of a free web‐based smart Geospatial CyberInfrastructure containing 15 macro‐tools (and more than 100 elementary tools), co‐designed with different types of stakeholders and their different needs, dealing with sustainability in agriculture, forestry and spatial planning. LANDSUPPORT condenses many features into one system, the main ones of which were (i) Web‐GIS facilities, connection with (ii) satellite data, (iii) Earth Critical Zone data and (iv) climate datasets including climate change and weather forecast data, (v) data cube technology enabling us to read/write when dealing with very large datasets (e.g. daily climatic data obtained in real time for any region in Europe), (vi) a large set of static and dynamic modelling engines (e.g. crop growth, water balance, rural integrity, etc.) allowing uncertainty analysis and what if modelling and (vii) HPC (both CPU and GPU) to run simulation modelling 'on‐the‐fly' in real time. Two case studies (a third case is reported in the Supplementary materials), with their results and stats, covering different regions and spatial extents and using three distinct operational tools all connected to lower land degradation processes (Crop growth, Machine Learning Forest Simulator and GeOC), are featured in this paper to highlight the platform's functioning. Landsupport is used by a large community of stakeholders and will remain operational, open and free long after the project ends. This position is rooted in the evidence showing that we need to leave these tools as open as possible and engage as much as possible with a large community of users to protect soils and land. [ABSTRACT FROM AUTHOR]

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This article discusses the use of liquid biopsy of cerebrospinal fluid (CSF) to detect and target the BRAFV600E mutation in a patient with overlapping Erdheim-Chester Disease (ECD) and Rosai-Dorfman Disease (RDD). ECD and RDD are rare histiocytic disorders driven by genetic alterations in the MAP kinase pathway. The patient in this case had CNS involvement, and the liquid biopsy of CSF and plasma was crucial in driving the diagnostic work-up and identifying the BRAFV600E mutation. This case highlights the potential value of liquid biopsies in diagnosing and targeting therapeutic interventions in patients with histiocytoses and CNS involvement. [Extracted from the article]

Introduction: Freeze-drying techniques give alternative preservation mammalian spermatozoa without liquid nitrogen. However, most of the work has been conducted in the laboratory mouse, while little information has been gathered on large animals that could also benefit from this kind of storage. Methods: This work adapted a technique known as vacuum-drying encapsulation (VDE), originally developed for nucleic acid conservation in anhydrous state, to ram spermatozoa, and compared it to canonical lyophilization (FD), testing longterm storage at room temperature (RT) and 4°C. Results and discussion: The results demonstrated better structural stability, namely lipid composition and DNA integrity, in VDE spermatozoa than FD ones, with outcomes at RT storage comparable to 4°C. Likewise, in VDE the embryonic development was higher than in FD samples (12.8% vs. 8.7%, p < 0.001, respectively). Our findings indicated that in large mammals, it is important to consider dehydration-related changes in sperm polyunsaturated fatty acids coupled with DNA alterations, given their crucial role in embryonic development. [ABSTRACT FROM AUTHOR]

Study Objective: To estimate the prevalence of potential moderate to severe drug–drug interactions (DDIs) involving nirmatrelvir/ritonavir, identify interacting medications, and evaluate risk factors associated with potential DDIs. Design: Cross‐sectional study. Data Source: Electronic health records from the National COVID Cohort Collaborative Enclave, one of the largest COVID‐19 data resources in the United States. Patients: Outpatients aged ≥18 years and started nirmatrelvir/ritonavir between December 23, 2021 and March 31, 2022. Intervention: Nirmatrelvir/ritonavir. Measurements: The outcome is potential moderate to severe DDIs, defined as starting interacting medications reported by National Institutes of Health 30 days before or 10 days after starting nirmatrelvir/ritonavir. Main Results: Of 3214 outpatients who started nirmatrelvir/ritonavir, the mean age was 56.8 ± 17.1 years, 39.5% were male, and 65.8% were non‐Hispanic white. Overall, 521 (16.2%) were potentially exposed to at least one moderate to severe DDI, most commonly to atorvastatin (19.2% of all DDIs), hydrocodone (14.0%), or oxycodone (14.0%). After adjustment for covariates, potential DDIs were more likely among individuals who were older (odds ratio [OR] 1.16 per 10‐year increase, 95% confidence interval [CI] 1.08–1.25), male (OR 1.36, CI 1.09–1.71), smokers (OR 1.38, CI 1.10–1.73), on more co‐medications (OR 1.35, CI 1.31–1.39), and with a history of solid organ transplant (OR 3.63, CI 2.05–6.45). Conclusions: One in six of individuals receiving nirmatrelvir/ritonavir were at risk of a potential moderate or severe DDI, underscoring the importance of clinical and pharmacy systems to mitigate such risks. [ABSTRACT FROM AUTHOR]

This paper describes the results obtained from an archaeometric study of a bronze Nuragic small boat model (Sardinia, Italy) dating from the Early Iron Age (presumably 9th–7th centuries BC). The artifact comes from an unknown location in Sardinia and is one of the objects that came to the Museum of Turin in the 19th century. This model is of particular interest as it is a unique Nuragic boat model containing a human figure among its decorations. The artifact is kept in the collection of the Royal Museum of Turin (Italy) and is a typical example of Sardinian manufacture from the Early Iron Age. This study was carried out using a combination of non-invasive techniques with energy dispersive X-ray fluorescence spectrometry (ED-XRF) integrated with Monte Carlo (MC) simulations and Raman spectroscopy, which allowed the characterization of the alloy of the artifact. [ABSTRACT FROM AUTHOR]

Purpose: Vessel wall imaging (VWI) with black-blood (BB) technique can demonstrate aneurysmal enhancement preluding to growth/rupture in treatment-naive cerebral aneurysms. Interestingly, recent works showed that BB enhancement may also occur in endovascularly treated aneurysms, though its meaning is controversial. Hypothesizing a flow-related mechanism of BB enhancement, we explored its relationship with incomplete occlusion status and coil packing density at DSA. Methods: We analyzed the subjects undergoing 3T MRI between January 2017 and October 2020 for a previous aneurysmal coiling. All the MRI studies included pre- and post-contrast 3D BB sequences. The presence of intra-aneurysmal pre-contrast BB signal was assessed. BB enhancement (when present) was classified as follows: (1) enhancement at the neck, (2) intrasaccular/intra-coil enhancement, and (3) peripheral enhancement. Coil packing density and aneurysmal occlusion status (according to the modified Raymond-Roy classification, MRRC) were determined on post-treatment DSA and compared with BB findings using generalized linear mixed-effect model and ANOVA. Significant p values were <0.05. Results: Forty-eight aneurysms from 44 patients were eligible for analysis. Pre-contrast BB signal was observed in 50% of the aneurysms and showed a relationship with baseline aneurysmal size. BB enhancement was detectable in 31 aneurysms (65%), being significantly associated with incomplete aneurysmal occlusion and reduced coil packing density at DSA. Conclusion: BB enhancement of coiled aneurysms is related with increasing degrees of post-coiling aneurysmal remnants and with loose coil packing density at DSA. This supports a hemodynamic interpretation of BB enhancement in long-term coiled aneurysms. [ABSTRACT FROM AUTHOR]

Rationale: Severe TBI (sTBI) is a devastating neurological injury that comprises a significant global trauma burden. Early comprehensive neurocritical care and rehabilitation improve outcomes for such patients, although better diagnostic and prognostic tools are necessary to guide personalized treatment plans. Methods: In this study, we explored the feasibility of conducting resting state magnetoencephalography (MEG) in a case series of sTBI patients acutely after injury (~7 days), and then about 1.5 and 8 months after injury. Synthetic aperture magnetometry (SAM) was utilized to localize source power in the canonical frequency bands of delta, theta, alpha, beta, and gamma, as well as DC-80 Hz. Results: At the first scan, SAM source maps revealed zones of hypofunction, islands of preserved activity, and hemispheric asymmetry across bandwidths, with markedly reduced power on the side of injury for each patient. GCS scores improved at scan 2 and by scan 3 the patients were ambulatory. The SAM maps for scans 2 and 3 varied, with most patients showing increasing power over time, especially in gamma, but a continued reduction in power in damaged areas and hemispheric asymmetry and/or relative diminishment in power at the site of injury. At the group level for scan 1, there was a large excess of neural generators operating within the delta band relative to control participants, while the number of neural generators for beta and gamma were significantly reduced. At scan 2 there was increased beta power relative to controls. At scan 3 there was increased group-wise delta power in comparison to controls. Conclusion: In summary, this pilot study shows that MEG can be safely used to monitor and track the recovery of brain function in patients with severe TBI as well as to identify patient-specific regions of decreased or altered brain function. Such MEG maps of brain function may be used in the future to tailor patient-specific rehabilitation plans to target regions of altered spectral power with neurostimulation and other treatments. [ABSTRACT FROM AUTHOR]

JEM-EUSO is an international program for the development of space-based Ultra-High Energy Cosmic Ray observatories. The program consists of a series of missions which are either under development or in the data analysis phase. All instruments are based on a wide-field-of-view telescope, which operates in the near-UV range, designed to detect the fluorescence light emitted by extensive air showers in the atmosphere. We describe the simulation software ESAF in the framework of the JEM-EUSO program and explain the physical assumptions used. We present here the implementation of the JEM-EUSO, POEMMA, K-EUSO, TUS, Mini-EUSO, EUSO-SPB1 and EUSO-TA configurations in ESAF. For the first time ESAF simulation outputs are compared with experimental data. [ABSTRACT FROM AUTHOR]

Introduction: Mycotic pseudoaneurysms are rare but severe sequelae of an arterial wall infection. If undiagnosed and untreated they can lead to significant morbidity and mortality through complications such as arterial rupture or dissection. Case report: This report details the case of a 64-year-old-male who developed a left common iliac artery mycotic pseudoaneurysm from Proteus mirabilis, which was associated with a prevertebral abscess. The patient presented with isolated, left lower extremity edema and intermittent fevers. The case is unique in both the pathogen (P mirabilis) and in its association with presumed direct arterial wall infection from an adjacent prevertebral abscess. Conclusion: The obscure presentation highlights the need for a high clinical suspicion of such a diagnosis when a patient presents with a certain constellation of symptoms and the right predisposing risk factors in their history. [ABSTRACT FROM AUTHOR]

Little data is available regarding the incidence of gastrointestinal bleeding in adults hospitalized with COVID‐19 infection and the influence of patient comorbidities and demographics, COVID‐19 therapies, and typical medications used. In this retrospective study, we utilized the National COVID Cohort Collaborative to investigate the primary outcome of the development of gastrointestinal bleeding in 512 467 hospitalized US adults (age >18 years) within 14 days of a COVID‐19 infection and the influence of demographics, comorbidities, and selected medications. Gastrointestinal bleeding developed in 0.44% of patients hospitalized with COVID‐19. Comorbidities associated with gastrointestinal bleeding include peptic ulcer disease (adjusted odds ratio [aOR] 10.2), obesity (aOR 1.27), chronic kidney disease (aOR 1.20), and tobacco use disorder (aOR 1.28). Lower risk of gastrointestinal bleeding was seen among women (aOR 0.76), Latinx (aOR 0.85), and vaccinated patients (aOR 0.74). Dexamethasone alone or with remdesivir was associated with lower risk of gastrointestinal bleeding (aOR 0.69 and aOR 0.83, respectively). Remdesivir monotherapy was associated with upper gastrointestinal bleeding (aOR 1.25). Proton pump inhibitors were more often prescribed in patients with gastrointestinal bleeding, likely representing treatment for gastrointestinal bleeding rather than a risk factor for its development. In adult patients hospitalized with COVID‐19, the use of dexamethasone alone or in combination with remdesivir is negatively associated with gastrointestinal bleeding. Remdesivir monotherapy is associated with increased risk of upper gastrointestinal bleeding. [ABSTRACT FROM AUTHOR]

Purpose: Primary central nervous system lymphoma (PCNSL) is a rare, aggressive form of extranodal non-Hodgkin lymphoma. To predict the overall survival (OS) in advance is of utmost importance as it has the potential to aid clinical decision-making. Though radiomics-based machine learning (ML) has demonstrated the promising performance in PCNSL, it demands large amounts of manual feature extraction efforts from magnetic resonance images beforehand. deep learning (DL) overcomes this limitation. Methods: In this paper, we tailored the 3D ResNet to predict the OS of patients with PCNSL. To overcome the limitation of data sparsity, we introduced data augmentation and transfer learning, and we evaluated the results using r stratified k-fold cross-validation. To explain the results of our model, gradient-weighted class activation mapping was applied. Results: We obtained the best performance (the standard error) on post-contrast T1-weighted (T1Gd)—area under curve = 0.81 (0.03) , accuracy = 0.87 (0.07) , precision = 0.88 (0.07) , recall = 0.88 (0.07) and F1-score = 0.87 (0.07) , while compared with ML-based models on clinical data and radiomics data, respectively, further confirming the stability of our model. Also, we observed that PCNSL is a whole-brain disease and in the cases where the OS is less than 1 year, it is more difficult to distinguish the tumor boundary from the normal part of the brain, which is consistent with the clinical outcome. Conclusions: All these findings indicate that T1Gd can improve prognosis predictions of patients with PCNSL. To the best of our knowledge, this is the first time to use DL to explain model patterns in OS classification of patients with PCNSL. Future work would involve collecting more data of patients with PCNSL, or additional retrospective studies on different patient populations with rare diseases, to further promote the clinical role of our model. [ABSTRACT FROM AUTHOR]

Introduction: The differential diagnosis of brain diseases becomes challenging in cases where imaging is not sufficiently informative, and surgical biopsy is impossible or unacceptable to the patient. Methods: An elderly patient with progressive short-term memory loss and cognitive impairment presented with a normal brain CT scan, a brain FDG-PET that indicated symmetrical deterioration of the white matter in the frontal lobes, and inconclusive results of a molecular marker analysis of suspected dementia in cerebrospinal fluid (CSF). Brain MRI suggested the diagnosis of lower grade glioma. The patient refused surgical biopsy. In order to investigate whether somatic mutations associated with gliomas existed, we performed a "liquid biopsy" by the targeted sequencing of cell-free DNA (cfDNA) from his CSF. Results: Deep sequencing of the cfDNA from CSF revealed somatic mutations characteristically found in gliomas, including mutations of the TP53 (Arg282Trp), BRAF (Val600Glu), and IDH1 (Arg132His) genes. The patient is currently treated with temozolomide, and his clinical and MRI findings suggest the stabilization of his disease. Conclusion: Neurological patients may benefit from liquid biopsy diagnostic work-up as it can reveal therapeutically targetable mutations. [ABSTRACT FROM AUTHOR]

The lower female reproductive tract is notoriously dominated by Lactobacillus species, among which Lactobacillus crispatus emerges for its protective and health‐promoting activities. Although previous comparative genome analyses highlighted genetic and phenotypic diversity within the L. crispatus species, most studies have focused on the presence/absence of accessory genes. Here, we investigated the variation at the single nucleotide level within protein‐encoding genes shared across a human‐derived L. crispatus strain selection, which includes 200 currently available human‐derived L. crispatus genomes as well as 41 chromosome sequences of such taxon that have been decoded in the framework of this study. Such data clearly pointed out the presence of intra‐species micro‐diversities that could have evolutionary significance contributing to phenotypical diversification by affecting protein domains. Specifically, two single nucleotide variations in the type II pullulanase gene sequence led to specific amino acid substitutions, possibly explaining the substantial differences in the growth performances and competition abilities observed in a multi‐strain bioreactor culture simulating the vaginal environment. Accordingly, L. crispatus strains display different growth performances, suggesting that the colonisation and stable persistence in the female reproductive tract between the members of this taxon is highly variable. [ABSTRACT FROM AUTHOR]

Although compositional variation in the gut microbiome during human development has been extensively investigated, strain-resolved dynamic changes remain to be fully uncovered. In the current study, shotgun metagenomic sequencing data of 12,415 fecal microbiomes from healthy individuals are employed for strain-level tracking of gut microbiota members to elucidate its evolving biodiversity across the human life span. This detailed longitudinal meta-analysis reveals host sex-related persistence of strains belonging to common, maternally-inherited species, such as Bifidobacterium bifidum and Bifidobacterium longum subsp. longum. Comparative genome analyses, coupled with experiments including intimate interaction between microbes and human intestinal cells, show that specific bacterial glycosyl hydrolases related to host-glycan metabolism may contribute to more efficient colonization in females compared to males. These findings point to an intriguing ancient sex-specific host-microbe coevolution driving the selective persistence in women of key microbial taxa that may be vertically passed on to the next generation. Here, via analyses of shotgun metagenomic sequencing data of more than 12,000 fecal microbiomes from healthy individuals, the authors reveal the presence of microbiome genetic traits involved in host mucin metabolism, supporting colonization and persistence of specific bacterial strains preferentially in the intestinal environment of women compared to men. [ABSTRACT FROM AUTHOR]

Background: Vaccination is widely used in fish aquaculture for three primary reasons: to prevent bacterial disease spreading, minimize antibiotic use and fight antibiotic resistance. Vaccine production is an expensive and consuming process, mainly in terms of money, resources, and animals for quality control. The replace, reduce, and refine (3Rs) philosophy suggests developing and validates alternative methods to animal testing for scientific purposes, even for biologicals and vaccines. Aim: The current study explored the potential use of mouse and fish cells in the in vitro toxicity grade assessment through different methods, as an alternative assay to in vivo residual toxicity tests for autogenous fish vaccine control. Methods: BF2 and L929 cell lines were exposed to vaccine dilutions in two different ways of administration and toxicity grade was recorded by MTS assay, compared to the in vivo gold standard test. Results: Autogenous vaccines (AVs) caused no reactions in the in vivo test. In the in vitro assay, the different toxicity grade recorded was statistically significant between the cell lines adopted and the AVs way of administration. Conclusions: Data obtained represent the first application of 3Rs method to fish AVs produced in Italy, more investigations are needed to collect solid results and standardize new in vitro methods for vaccine quality control. [ABSTRACT FROM AUTHOR]

Objective An increasing scientific literature recognizes that traditional cut-off scores for cognitive screeners may not be optimal for use in patients who differ in race/ethnicity from the screeners' normative/reference group. There is also literature on how racial/ethnic contextual factors, such as stereotype threat or perceived discrimination, may influence performance on cognitive testing. The current study examined the characteristics of SLUMS (a cognitive screening measure) performance in a large (n  = 602) sample of Black (n  = 229) and White (n  = 373) veterans in a VA hospital located in the Southern United States. Method SLUMS data were gathered from retrospective electronic chart review between January 2013 and February 2020. Race/ethnicity of veterans was gathered by chart review and race of hospital providers who administered the SLUMS by personal communication. Results Black veterans were 1.99 times more likely to be classified by total SLUMS score as being within the dementia range compared with White veterans. Differences in item level performance were only found between Black and White veterans with ≥ high school education. Race of clinical provider (i.e. Black or White) administering the SLUMS did not significantly impact veteran performance on the SLUMS. Conclusion This is the first large sample study of differences in SLUMS performance between Black and White veterans. Findings replicate earlier research on Black and White performance differences on individual SLUMS items and provide an analysis of examiner–examinee racial discordance. This study underscores the importance of researching cognitive measures in groups who differ from the original normative/references samples. [ABSTRACT FROM AUTHOR]

Background: African Swine Fever (ASF) is an infectious disease that affects domestic pig and wild boar populations. The ASF Virus (ASFV) has a genome characterized by a very complex DNA (170-193 kb) that encodes for more than 200 different proteins. Among these, the highly immunogenic phosphoprotein p30 plays a fundamental role in the induction of specific antibodies. To date, the lack of a vaccine against the disease requires continuous studies to improve knowledge about the virus and the development of new tests in addition to virological ones. Aim: The aim of this work was to produce specific monoclonal antibodies (mAbs) against the p30 protein of ASFV, which could find useful applications in routine diagnostics and the implementation of new diagnostic tools. Methods: ASFV p30 encoding gene was amplified and used for the generation of the recombinant baculovirus by transfection of the Sf21 insect cells. The recombinant protein was analyzed by immunofluorescence assay, purified, and used for mice Balb-c immunization. The hybridomas obtained were cultured and screened, using an indirect Enzyme-linked Immunosorbent Assay (iELISA), in order to select clones that secrete the mAbs of interest. Results: The expression of recombinant p30 protein was assessed using direct immunofluorescence. The purified p30 protein fractions were analyzed by Coomassie gels staining confirming the presence of bands with a molecular weight of 30 kDa and used for the immunization of Balb-c mice. Six clones of pure hybridomas secreting the specific mAbs against recombinant p30 were obtained and tested in iELISA. The mAbs were also characterized by Western blot and immunofluorescence assay. The best results were obtained with the anti-p30 mAb 2B8E10 clone which showed high reactivity with both recombinant and viral p30 protein, respectively. Conclusion: In this work, a recombinant p30 protein produced in an insect cell system was purified and used to immunize Balb-c mice. Six anti-p30 mAbs-secreting hybridomas clone cells were obtained. These mAbs displayed high reactivity against the recombinant protein, but only 2B8E10 mAb showed excellent functionality against the p30 protein produced by ASFV. These results open the possibility to develop different diagnostic assays. [ABSTRACT FROM AUTHOR]

Genetic predisposition, environmental factors, and infectious agents interact in the development of gastric diseases. Helicobacter pylori (Hp) and Epstein–Barr virus (EBV) infection has recently been shown to be correlated with these diseases. A cross-sectional study was performed on 100 hospitalized Italian patients with and without gastric diseases. The patients were stratified into four groups. Significant methylation status differences among CDH1, DAPK, COX2, hMLH1 and CDKN2A were observed for coinfected (Hp-EBV group) patients; particularly, a significant presence of COX2 (p = 0.0179) was observed. For microsatellite instability, minor stability was described in the Hp-HBV group (69.23%, p = 0.0456). Finally, for p53 mutation in the EBV group, exon 6 was, significantly, most frequent in comparison to others (p = 0.0124), and in the Hp-EBV group exon 8 was, significantly, most frequent in comparison to others (p < 0.0001). A significant positive relationship was found between patients with infection (Hp, EBV or both) and p53 mutation (rho = 0.383, p = 0.0001), methylation status (rho = 0.432, p < 0.0001) and microsatellite instability (rho = 0.285, p = 0.004). Finally, we observed among infection and methylation status, microsatellite instability, and p53 mutation a significant positive relationship only between infection and methylation status (OR = 3.78, p = 0.0075) and infection and p53 mutation (OR = 6.21, p = 0.0082). According to our analysis, gastric disease in the Sicilian population has different pathways depending on the presence of various factors, including infectious agents such as Hp and EBV and genetic factors of the subject. [ABSTRACT FROM AUTHOR]

Background and Purpose: Transcranial ultrasonography (TCU) can be a useful diagnostic tool in evaluating intracranial pathology in patients with limited or delayed access to routine neuroimaging in critical care or austere settings. We reviewed available literature investigating the diagnostic utility of TCU for detecting pediatric and adult patient's intracranial pathology in patients with intact skulls and reported diagnostic accuracy measures. Methods: We performed a systematic review of PubMed®, Cochrane Library, Embase®, Scopus®, Web of Science™, and Cumulative Index to Nursing and Allied Health Literature databases to identify articles evaluating ultrasound‐based detection of intracranial pathology in comparison to routine imaging using broad Medical Subject Heading sets. Two independent reviewers reviewed the retrieved articles for bias using the Quality Assessment of Diagnostic Accuracy Studies tools and extracted measures of diagnostic accuracy and ultrasound parameters. Data were pooled using meta‐analysis implementing a random‐effects approach to examine the sensitivity, specificity, and accuracy of ultrasound‐based diagnosis. Results: A total of 44 studies out of the 3432 articles screened met the eligibility criteria, totaling 2426 patients (Mean age: 60.1 ± 14.52 years). We found tumors, intracranial hemorrhage (ICH), and neurodegenerative diseases in the eligible studies. Sensitivity, specificity, and accuracy of TCU and their 95% confidence intervals were 0.80 (0.72, 0.89), 0.71 (0.59, 0.82), and 0.76 (0.71, 0.82) for neurodegenerative diseases; 0.88 (0.74, 1.02), 0.81 (0.50, 1.12), and 0.94 (0.92, 0.96) for ICH; and 0.97 (0.92, 1.03), 0.99 (0.96, 1.01), and 0.99 (0.97, 1.01) for intracranial masses. No studies reported ultrasound presets. Conclusions: TCU has a reasonable sensitivity and specificity for detecting intracranial pathology involving ICH and tumors with clinical applications in remote locations or where standard imaging is unavailable. Future studies should investigate ultrasound parameters to enhance diagnostic accuracy in diagnosing intracranial pathology. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has demonstrated the need for efficient and comprehensive, simultaneous assessment of multiple combined novel therapies for viral infection across the range of illness severity. Randomized Controlled Trials (RCT) are the gold standard by which efficacy of therapeutic agents is demonstrated. However, they rarely are designed to assess treatment combinations across all relevant subgroups. A big data approach to analyzing real-world impacts of therapies may confirm or supplement RCT evidence to further assess effectiveness of therapeutic options for rapidly evolving diseases such as COVID-19. Methods: Gradient Boosted Decision Tree, Deep and Convolutional Neural Network classifiers were implemented and trained on the National COVID Cohort Collaborative (N3C) data repository to predict the patients' outcome of death or discharge. Models leveraged the patients' characteristics, the severity of COVID-19 at diagnosis, and the calculated proportion of days on different treatment combinations after diagnosis as features to predict the outcome. Then, the most accurate model is utilized by eXplainable Artificial Intelligence (XAI) algorithms to provide insights about the learned treatment combination impacts on the model's final outcome prediction. Results: Gradient Boosted Decision Tree classifiers present the highest prediction accuracy in identifying patient outcomes with area under the receiver operator characteristic curve of 0.90 and accuracy of 0.81 for the outcomes of death or sufficient improvement to be discharged. The resulting model predicts the treatment combinations of anticoagulants and steroids are associated with the highest probability of improvement, followed by combined anticoagulants and targeted antivirals. In contrast, monotherapies of single drugs, including use of anticoagulants without steroid or antivirals are associated with poorer outcomes. Conclusions: This machine learning model by accurately predicting the mortality provides insights about the treatment combinations associated with clinical improvement in COVID-19 patients. Analysis of the model's components suggests benefit to treatment with combination of steroids, antivirals, and anticoagulant medication. The approach also provides a framework for simultaneously evaluating multiple real-world therapeutic combinations in future research studies. [ABSTRACT FROM AUTHOR]

Mal secco is a severe vascular citrus disease (MSD) caused by the mitosporic fungus Plenodomus tracheiphilus (Pt). The pathogen enters through wounds on the above- and below-ground parts of the tree. The susceptible species sour orange (Citrus aurantium) is the most commonly used rootstock for lemon trees in Italy. In this study, sour orange seedlings were wound-inoculated with P. tracheiphilus in leaves or roots. Six months post-inoculation, the microbial communities of rhizosphere, endorhizosphere, and xylem endosphere samples from inoculated and healthy plants were analyzed by 16S rRNA and ITS (internal transcribed spacer) amplicon sequencing. The DNA of Pt was quantified by real-time PCR in the three compartments. According to our results, the endorhizosphere of root-inoculated plants showed the highest concentration of the pathogen DNA. Bacterial populations of potentially beneficial taxa (e.g., Pseudomonas and Burkholderia) were depleted in the rhizosphere of the inoculated plants. Infection through leaves and roots also produced a network-wide rewiring of microbial associations in sour orange roots. Overall, our findings revealed community-level changes induced by Pt infection in the sour orange root and xylem microbiome, providing further insights into the beneficial multispecies interactions in Citrus-associated microbial communities. [ABSTRACT FROM AUTHOR]

Primary Central Nervous System Lymphoma (PCNSL) is an aggressive neoplasm with a poor prognosis. Although therapeutic progresses have significantly improved Overall Survival (OS), a number of patients do not respond to HD–MTX-based chemotherapy (15–25%) or experience relapse (25–50%) after an initial response. The reasons underlying this poor response to therapy are unknown. Thus, there is an urgent need to develop improved predictive models for PCNSL. In this study, we investigated whether radiomics features can improve outcome prediction in patients with PCNSL. A total of 80 patients diagnosed with PCNSL were enrolled. A patient sub-group, with complete Magnetic Resonance Imaging (MRI) series, were selected for the stratification analysis. Following radiomics feature extraction and selection, different Machine Learning (ML) models were tested for OS and Progression-free Survival (PFS) prediction. To assess the stability of the selected features, images from 23 patients scanned at three different time points were used to compute the Interclass Correlation Coefficient (ICC) and to evaluate the reproducibility of each feature for both original and normalized images. Features extracted from Z-score normalized images were significantly more stable than those extracted from non-normalized images with an improvement of about 38% on average (p-value < 10 − 12 ). The area under the ROC curve (AUC) showed that radiomics-based prediction overcame prediction based on current clinical prognostic factors with an improvement of 23% for OS and 50% for PFS, respectively. These results indicate that radiomics features extracted from normalized MR images can improve prognosis stratification of PCNSL patients and pave the way for further study on its potential role to drive treatment choice. [ABSTRACT FROM AUTHOR]