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IntroductionFungal fruit rots are a perennial threat to the production of cranberries. Eleven genera of fungi have been reported to cause cranberry rot in the field and/or during cold storage. Oregon and Washington rank fourth and fifth in the production of cranberries in the USA, but much of the research on cranberry fruit rots has been conducted in Wisconsin, New Jersey, and Massachusetts.ObjectiveThe primary objective of this project was to describe the current composition of cranberry fruit rot complex in Oregon and Washington.MethodsA survey of fungal fruit rot pathogens was conducted over four years in commercial cranberry farms located in the Pacific Ocean coastal zone in Oregon and Washington.ResultsYield, rot incidence, and fungal pathogens isolated varied year-to-year. Pathogens isolated frequently from field-rotted cranberries included the cranberry fruit rot genera described in other cranberry production regions of the USA, such as Colletotrichum, Coleophoma, and Physalospora. Neofabraea actinidiae, a recently described cranberry fruit rot, was isolated consistently from field-rotted cranberries from beds with specific fungicide usage patterns. N. actinidiae also was one of the more common storage rot pathogens in this region, alongside other well-established storage rots like Coleophoma and black rots caused by Allantophomopsis cytisporea, A. lycopodina, and Strasseria geniculata.ConclusionsThese findings may have important implications for Washington cranberry production because a large proportion of the crop is dry-harvested, placed in cold storage, and then sold as fresh cranberries. Climatic differences among the cranberry production areas across the United States may affect the disease incidence and prevalence of different genera of cranberry fruit rot pathogens, as summer months in Oregon and Washington are often much cooler and dryer than in Wisconsin and east coast states and may account for differing presence of various cranberry fruit rot fungi.

The current clinical management of Extranodal NK/T-cell lymphoma (ENKTL) primarily depends on conventional chemotherapy and radiotherapy, underscoring the need for innovative therapeutic strategies. This study explores the clinical significance and therapeutic implication of c-MYC (MYC) in ENKTL. Initially, we identified MYC protein overexpression in approximately 75% of cases within a large cohort of 111 patients. MYC overexpression was strongly correlated with lymphoma cell proliferation and poor clinical outcomes. Intriguingly, integrating MYC expression into the PINK-E prognostic model significantly enhanced its predictive power. Subsequently, we implemented MYC knockdown (KD) in NK malignancy cell lines with MYC overexpression, resulting in significant viability reduction. RNA-sequencing (RNA-seq) used to determine MYC function revealed a high overlap with canonical MYC-regulated genes and enrichment in metabolism and cell cycle regulation. Integrative analysis of the RNA-seq data upon MYC KD with gene expression profiles of primary ENKTL cases identified a subset of genes closely associated with MYC overexpression. Among these, CDK4 emerged as a potential therapeutic target, and its inhibition not only abrogated MYC function but also decreased MYC expression in NK malignancy cells. Furthermore, the clinical-grade CDK4/6 inhibitor palbociclib exhibited a potent anti-tumor effect in xenograft mouse models, especially when combined with gemcitabine. In summary, our study firmly establishes MYC as an oncogene with prognostic significance in ENKTL and highlights CDK4 inhibition as a promising therapeutic strategy for treating ENKTL with MYC overexpression.

Abstract Background Large-river decision-makers are charged with maintaining diverse ecosystem services through unprecedented social-ecological transformations as climate change and other global stressors intensify. The interconnected, dendritic habitats of rivers, which often demarcate jurisdictional boundaries, generate complex management challenges. Here, we explore how the Resist–Accept–Direct (RAD) framework may enhance large-river management by promoting coordinated and deliberate responses to social-ecological trajectories of change. The RAD framework identifies the full decision space of potential management approaches, wherein managers may resist change to maintain historical conditions, accept change toward different conditions, or direct change to a specified future with novel conditions. In the Upper Mississippi River System, managers are facing social-ecological transformations from more frequent and extreme high-water events. We illustrate how RAD-informed basin-, reach-, and site-scale decisions could: (1) provide cross-spatial scale framing; (2) open the entire decision space of potential management approaches; and (3) enhance coordinated inter-jurisdictional management in response to the trajectory of the Upper Mississippi River hydrograph. Results The RAD framework helps identify plausible long-term trajectories in different reaches (or subbasins) of the river and how the associated social-ecological transformations could be managed by altering site-scale conditions. Strategic reach-scale objectives may reprioritize how, where, and when site conditions could be altered to contribute to the basin goal, given the basin’s plausible trajectories of change (e.g., by coordinating action across sites to alter habitat connectivity, diversity, and redundancy in the river mosaic). Conclusions When faced with long-term systemic transformations (e.g., > 50 years), the RAD framework helps explicitly consider whether or when the basin vision or goals may no longer be achievable, and direct options may open yet unconsidered potential for the basin. Embedding the RAD framework in hierarchical decision-making clarifies that the selection of actions in space and time should be derived from basin-wide goals and reach-scale objectives to ensure that site-scale actions contribute effectively to the larger river habitat mosaic. Embedding the RAD framework in large-river decisions can provide the necessary conduit to link flexibility and innovation at the site scale with stability at larger scales for adaptive governance of changing social-ecological systems.

Continued large-scale public investment in declining ecosystems depends on demonstrations of “success”. While the public conception of “success” often focuses on restoration to a pre-disturbance condition, the scientific community is more likely to measure success in terms of improved ecosystem health. Using a combination of literature review, workshops and expert solicitation we propose a generalized framework to improve ecosystem health in highly altered river basins by reducing ecosystem stressors, enhancing ecosystem processes and increasing ecosystem resilience. We illustrate the use of this framework in the Mississippi-Atchafalaya River Basin (MARB) of the central United States (U.S.), by (i) identifying key stressors related to human activities, and (ii) creating a conceptual ecosystem model relating those stressors to effects on ecosystem structure and processes. As a result of our analysis, we identify a set of landscape-level indicators of ecosystem health, emphasizing leading indicators of stressor removal (e.g., reduced anthropogenic nutrient inputs), increased ecosystem function (e.g., increased water storage in the landscape) and increased resilience (e.g., changes in the percentage of perennial vegetative cover). We suggest that by including these indicators, along with lagging indicators such as direct measurements of water quality, stakeholders will be better able to assess the effectiveness of management actions. For example, if both leading and lagging indicators show improvement over time, then management actions are on track to attain desired ecosystem condition. If, however, leading indicators are not improving or even declining, then fundamental challenges to ecosystem health remain to be addressed and failure to address these will ultimately lead to declines in lagging indicators such as water quality. Although our model and indicators are specific to the MARB, we believe that the generalized framework and the process of model and indicator development will be valuable in an array of altered river basins.

Rehabilitation of large Anthropocene rivers requires engagement of diverse stakeholders across a broad range of sociopolitical boundaries. Competing objectives often constrain options for ecological restoration of large rivers whereas fewer competing objectives may exist in a subset of tributaries. Further, tributaries contribute toward building a “portfolio” of river ecosystem assets through physical and biological processes that may present opportunities to enhance the resilience of large river fishes. Our goal is to review roles of tributaries in enhancing mainstem large river fish populations. We present case histories from two greatly altered and distinct large-river tributary systems that highlight how tributaries contribute four portfolio assets to support large-river fish populations: 1) habitat diversity, 2) connectivity, 3) ecological asynchrony, and 4) density-dependent processes. Finally, we identify future research directions to advance our understanding of tributary roles and inform conservation actions. In the Missouri River United States, we focus on conservation efforts for the state endangered lake sturgeon, which inhabits large rivers and tributaries in the Midwest and Eastern United States. In the Colorado River, Grand Canyon United States, we focus on conservation efforts for recovery of the federally threatened humpback chub. In the Missouri River, habitat diversity focused on physical habitats such as substrate for reproduction, and deep-water habitats for refuge, whereas augmenting habitat diversity for Colorado River fishes focused on managing populations in tributaries with minimally impaired thermal and flow regimes. Connectivity enhancements in the Missouri River focused on increasing habitat accessibility that may require removal of physical structures like low-head dams; whereas in the Colorado River, the lack of connectivity may benefit native fishes as the disconnection provides refuge from non-native fish predation. Hydrologic variability among tributaries was present in both systems, likely underscoring ecological asynchrony. These case studies also described density dependent processes that could influence success of restoration actions. Although actions to restore populations varied by river system, these examples show that these four portfolio assets can help guide restoration activities across a diverse range of mainstem rivers and their tributaries. Using these assets as a guide, we suggest these can be transferable to other large river-tributary systems.

Pseudo‐TORCH Syndrome (PTS) encompasses a heterogeneous group of genetic disorders that may clinically and radiologically resemble congenital TORCH infections. These mimickers present with overlapping features manifested as intracranial and systemic abnormalities. Collagen type IV alpha 1 chain (COL4A1)‐related diseases, characterized by autosomal dominant inheritance, exhibit a diverse phenotypic spectrum involving cerebrovascular, renal, ophthalmological, cardiac, and muscular abnormalities. Cerebrovascular manifestations range from small‐vessel brain disease to large vessel abnormalities, resulting in intracerebral hemorrhage, periventricular leukoencephalopathy, and ventriculomegaly. Additional features include cortical malformations, eye defects, arrhythmias, renal disease, muscular abnormalities, and hematological manifestations. Age of onset varies widely, and phenotypic variability exists even among individuals with the same variant. In this study, we present two cases of COL4A1‐related disorder mimicking congenital TORCH infections, highlighting the importance of recognizing genetic mimics in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Fungal fruit rots are a perennial threat to the production of cranberries. Eleven genera of fungi have been reported to cause cranberry rot in the field and/or during cold storage. Oregon and Washington rank fourth and fifth in the production of cranberries in the USA, but much of the research on cranberry fruit rots has been conducted in Wisconsin, New Jersey, and Massachusetts. Objective: The primary objective of this project was to describe the current composition of cranberry fruit rot complex in Oregon and Washington. Methods: A survey of fungal fruit rot pathogens was conducted over four years in commercial cranberry farms located in the Pacific Ocean coastal zone in Oregon and Washington. Results: Yield, rot incidence, and fungal pathogens isolated varied year-to-year. Pathogens isolated frequently from field-rotted cranberries included the cranberry fruit rot genera described in other cranberry production regions of the USA, such as Colletotrichum, Coleophoma, and Physalospora. Neofabraea actinidiae, a recently described cranberry fruit rot, was isolated consistently from field-rotted cranberries from beds with specific fungicide usage patterns. N. actinidiae also was one of the more common storage rot pathogens in this region, alongside other wellestablished storage rots like Coleophoma and black rots caused by Allantophomopsis cytisporea, A. lycopodina, and Strasseria geniculata. Conclusions: These findings may have important implications for Washington cranberry production because a large proportion of the crop is dry-harvested, placed in cold storage, and then sold as fresh cranberries. Climatic differences among the cranberry production areas across the United States may affect the disease incidence and prevalence of different genera of cranberry fruit rot pathogens, as summer months in Oregon and Washington are often much cooler and dryer than in Wisconsin and east coast states and may account for differing presence of various cranberry fruit rot fungi. [ABSTRACT FROM AUTHOR]

Effective management and conservation of fishes requires understanding habitat use across multiple life stages while ensuring necessary habitats are both available and accessible. Tributary habitats may play an important role in recruitment and dispersal of fishes in anthropogenically modified rivers such as the Mississippi and Illinois Rivers of the Midwest U.S.A. Identifying source locations that contribute to recruitment of fish populations can determine the importance of connectivity within river networks and pinpoint critical habitats that sustain fish populations. In the Upper Mississippi River System (UMRS), the environments that fish use in early life stages (i.e., natal origin) can be identified using otolith trace element analysis due to stability and distinctness in water chemistry (strontium: calcium [Sr:Ca]) among water bodies that is reflected in otoliths.Here, we used trace element analysis to determine natal origin of six small‐bodied fishes including bullhead minnow (Pimephales vigilax), emerald shiner (Notropis atherinoides), gizzard shad (Dorosoma cepedianum), bluegill (Lepomis macrochirus), orangespotted sunfish (Lepomis humilis), and yellow perch (Perca flavescens) across six reaches of the UMRS (Pools 4, 8, 13, 26, the Open River of the Middle Mississippi River, and the La Grange Pool of the Illinois River). Otolith core Sr:Ca for fishes was quantified using laser ablation inductively coupled plasma mass spectrometry. Using the resulting Sr:Ca chemical signatures of otolith cores, natal origin (tributary, immigrant, or potential resident) was determined for individual fish based on family‐specific relationships between otolith and water chemistries.We found that all species originated from tributaries and other reaches (i.e., were immigrants) to varying extents, which acted as evidence for network connectivity. Specifically, tributaries contributed up to 48% of individuals at a given reach. In certain reaches, Pool 26 and the Open River reach, up to 80% of individuals in a species immigrated from another mainstem river reach. Network connectivity was also important in both upstream and downstream directions. Contributions from network connectivity varied among species: bullhead minnow used less whereas orangespotted sunfish used more network connectivity than when all species were combined. Further, the use of network connectivity varied spatially where individuals captured in Pool 8 and the La Grange Pool less often and those from Pool 26 and the Open River more often originated from network connectivity compared to the whole assemblage across reaches.These results indicate that species' life history traits probably interacted with the physical environment, which differs spatially, to yield observed recruitment source patterns. Our results show that network connectivity contributes to established assemblages of native small‐bodied fishes throughout the UMRS and underscore the role of interjurisdictional management in maintaining network connectivity to sustain fish populations. [ABSTRACT FROM AUTHOR]

The article deals with the optimization of HVAC design coordination using building information modeling (BIM). The aim is to identify and compare ways of coordination in construction projects and to evaluate BIM method for clash detection. This method is verified by clash detection of HVAC design in practice using the BIM tool Trimble Connect. 3D clashes are detected between different project models according to selected parameters. The result is a quick and accurate identification of clashes. Timely solution prevents cost increases and schedule shifts of the construction project.

Management actions intended to benefit fish in large rivers can directly or indirectly affect multiple ecosystem components. Without consideration of the effects of management on non-target ecosystem components, unintended consequences may limit management efficacy. Monitoring can help clarify the effects of management actions, including on non-target ecosystem components, but only if data are collected to characterize key ecosystem processes that could affect the outcome. Scientists from across the U.S. convened to develop a conceptual model that would help identify monitoring information needed to better understand how natural and anthropogenic factors affect large river fishes. We applied the conceptual model to case studies in four large U.S. rivers. The application of the conceptual model indicates the model is flexible and relevant to large rivers in different geographic settings and with different management challenges. By visualizing how natural and anthropogenic drivers directly or indirectly affect cascading ecosystem tiers, our model identified critical information gaps and uncertainties that, if resolved, could inform how to best meet management objectives. Despite large differences in the physical and ecological contexts of the river systems, the case studies also demonstrated substantial commonalities in the data needed to better understand how stressors affect fish in these systems. For example, in most systems information on river discharge and water temperature were needed and available. Conversely, information regarding trophic relationships and the habitat requirements of larval fishes were generally lacking. This result suggests that there is a need to better understand a set of common factors across large-river systems. We provide a stepwise procedure to facilitate the application of our conceptual model to other river systems and management goals.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused considerable disruption worldwide. For efficient SARS-CoV-2 detection, new methods of rapid, non-invasive sampling are needed. This study aimed to investigate the stability of SARS-CoV-2 in a novel medium for gargle-lavage (GL) self-sampling and to compare the performance of SARS-CoV-2 detection in paired self-collected GL and clinician-obtained nasopharyngeal swab (NPS) samples. The stability study for SARS-CoV-2 preservation in a novel medium was performed over 14 days (4 °C, 24–27 °C, and 37 °C). In total, 494 paired GL and NPS samples were obtained at the University Hospital in Olomouc in April 2021. SARS-CoV-2 detection in paired samples was performed with a SARS-CoV-2 Nucleic Acid Detection Kit (Zybio, Chongqing Municipality, Chongqing, China), an Elecsys® SARS-CoV-2 Antigen assay (Roche Diagnostics, Mannheim, Germany), and a SARS-CoV-2 Antigen ELISA (EUROIMMUN, Lübeck, Germany). The stability study demonstrated excellent SARS-CoV-2 preservation in the novel medium for 14 days. SARS-CoV-2 was detected in 55.7% of NPS samples and 55.7% of GL samples using rRT-PCR, with an overall agreement of 91.9%. The positive percent agreement (PPA) of the rRT-PCR in the GL samples was 92.7%, and the negative percent agreement (NPA) was 90.9%, compared with the NPS samples. The PPA of the rRT-PCR in the NPS and GL samples was 93.2% when all positive tests were used as the reference standard. Both antigen detection assays showed poor sensitivity compared to rRT-PCR (33.2% and 36.0%). rRT-PCR SARS-CoV-2 detection in self-collected GL samples had a similar PPA and NPA to that of NPSs. GL self-sampling offers a suitable and more comfortable alternative for SARS-CoV-2 detection.

AbstractTranscriptomic, proteomic, and methylation aging clocks demonstrate that aging has a predictable preset program, while transcriptome trajectory turning points indicate that the 20–40 age range in humans is the likely stage at which the progressive loss of homeostatic control, and in turn aging, begins to have detrimental effects. Turning points in this age range overlapping with human aging clock genes revealed five candidates that we hypothesized could play a role in aging or age-related physiological decline. To examine these gene’s effects on lifespan and health-span, we utilized whole body and heart-specific gene knockdown of human orthologs in Drosophila melanogasterCDH1DrosophilaDrosophila