Challenges of COVID-19 Case Forecasting in the US, 2020-2021.

During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making.

Differentiating Giant Bullous Emphysema From Tension Pneumothorax: A Case Report.

Giant bullous emphysema (GBE) is a progressive disease that commonly presents with severe progressive dyspnea attributed to the progressive destruction of alveolar walls and the formation of large air pockets, resulting in impaired gas exchange. This presentation is most commonly seen in young, thin male smokers. GBE poses an interesting and unique clinical challenge due to its radiologic findings, which can be easily mistaken for tension pneumothorax. Despite the decreased acuity of GBE as compared to tension pneumothorax, inadequate treatment in a severe case can lead to spontaneous pneumothorax, infection, and/or respiratory failure. In this report, we highlight a case of severe GBE that presents similarly to tension pneumothorax in both symptomatology and radiologic findings. The case at hand is of a 50-year-old male patient with a history of chronic obstructive pulmonary disease (COPD) with complaints of dyspnea and subsequent findings of tachycardia, tachypnea, and hypoxemia with significantly decreased breath sounds in the right lung. Radiologic findings showed increased lucency of the right hemithorax and a mass effect with a mediastinal shift to the left. History and further imaging with CT led to an ultimate diagnosis of severe GBE and COPD exacerbations. The patient was treated with non-invasive medical management. With the challenges of overlapping presentations, landing on the correct diagnosis is imperative to accurately and adequately treat the patient since GBE and tension pneumothorax significantly differ in acuity and overall management, hence the need for a high level of suspicion based on the clinical picture and the use of high-resolution CT.

Job Satisfaction within the Grassroots Healthcare System in Vietnam's Key Industrial Region-Binh Duong Province: Validating the Vietnamese Version of the Minnesota Satisfaction Questionnaire Scale.

Background: The grassroots healthcare system is the closest and most community-oriented force, working as an extended arm of the primary healthcare network to implement healthcare programs at the household level. Its comprehensive development is a crucial task set by the Vietnamese government. Job satisfaction significantly influences the performance of healthcare staff within this system. Objective: to assess job satisfaction among healthcare staff using the short-form of the Minnesota Satisfaction Questionnaire while also evaluating the Vietnamese translation of this scale. Methods: A descriptive cross-sectional study with analysis based on the responses of 587 healthcare staff using the Vietnamese-translated version of the MSQ short-form scale. The response data from the participants were subjected to CFA, and if the proposed CFA model did not fit the data, EFA was conducted. Results: The results indicate that the new model, which evaluates job-related factors in three distinct groups, is more suitable than the original model. The 14 questions of the MSQ scale were analyzed and categorized into Autonomy, Obligation, and Specificity based on the participants' responses. The confirmatory factor analysis (CFA) conducted on the new model demonstrated favorable fit indices: CFI = 0.934, TLI = 0.917, GFI = 0.919, and RMSEA = 0.093 (90% CI: 0.085-0.102). Conclusions: The Vietnamese version of the MSQ short form demonstrates reliability and validity. It also provides additional data on the effectiveness of the MSQ short form in measuring job satisfaction.

Preventing Static Biofilm Formation of Staphylococcus aureus on Different Types of Surfaces Using Microbubbles.

Bacterial fouling and biofilm formation on surfaces have been ongoing problems in real life as well as in the medical field. Different approaches have been taken to tackle the issues, from costly surface modification to antibiotic-delivering strategies. In this study, we examined the potential of using stabilized microbubbles (MBs) to shield against bacterial adhesion. Three types of surfaces were tested: hydrophilic glass (hydrophilic surface), neutral hydrophobic polystyrene (PS)-coated surfaces, and negatively charged hydrophobic octadecyltrichlorosilane (OTS)-coated surfaces. By evaluating the colony-forming unit (CFU) values from each surface, MBs stabilized by 0.05 mM SDS were shown to only produce significant reduction of Staphylococcus aureus adhesion on PS surfaces, up to 60.29 and 82.32% compared to no-MB PS surfaces, and no-MB uncoated surfaces, correspondingly, due to the appropriate size, stability, and negative charges of the MB shielding layer. On the other hand, OTS coatings had an intrinsic antiadhesion effect (69.83% compared to uncoated surface), given that the negatively charged OTS-aqueous interface or surface porosity nature of the coating prohibited the attachment of MBs, leading to the elimination of the antifouling effect of MBs. Ultimately, MBs gave better shielding results than surface modification when compared to uncoated surfaces and hence can be applied more widely.

Spray-dried Solid Lipid Nanoparticles for Enhancing Berberine Bioavailability via Oral Administration.

BACKGROUND: Berberine (BBR), an Eastern traditional medicine, has expressed novel therapeutic activities, especially for chronic diseases like diabetes, hyperlipemia, hypertension, and Alzheimer's disease. However, the low oral bioavailability of BBR has limited the applications of these treatments. Hence, BBRloaded solid lipid nanoparticles (BBR-SLNs) were prepared to improve BBR absorption into systemic circulations via this route. METHODS: BBR-loaded solid lipid nanoparticles (BBR-SLNs) were prepared by ultrasonication and then transformed into solid form via spray drying technique. The size morphology of BBR-SLNs was evaluated by dynamic light scattering (DLS) and scanning electron microscope (SEM). Crystallinity of BBR and interaction of BBR with other excipients were checked by spectroscopic methods. Entrapment efficiency of BBR-SLNs as well as BBR release in gastrointestinal conditions were also taken into account. Lastly, SLN's cytotoxicity for loading BBR was determined with human embryonic kidney cells (HEK293). RESULTS: Stearic acid (SA), glyceryl monostearate (GMS), and poloxamer 407 (P407) were selected for BBRSLNs fabrication. BBR-SLNs had homogenous particle sizes of less than 200 nm, high encapsulation efficiency of nearly 90% and loading capacity of above 12%. BBR-SLN powder could be redispersed without significant changes in physicochemical properties and was stable for 30 days. Spray-dried BBR-SLNs showed a better sustained in vitro release profile than BBR-SLNs suspension and BBR during the initial period, followed by complete dissolution of BBR over 24 hours. Notably, cell viability on HEK293 even increased up to 150% compared to the control sample at 100 µg/mL BBR-unloaded SLNs. CONCLUSION: Hence, SLNs may reveal a promising drug delivery system to broaden BBR treatment for oral administration.

Functional characterization of melanocortin 2 receptor (Mc2r) from a lobe-finned fish (Protopterus annectens) and insights into the molecular evolution of melanocortin receptors.

Recent studies from our group on melanocortin 2 receptors (Mc2r) from basal families of actinopterygians have served to resolve that Mrap1 dependence and ACTH selectivity are features of even the most basal ray-finned fishes. However, there have been no studies on Mc2r function of the basal sarcopterygians, the lobe-finned fishes, represented by the extant members coelacanths and lungfishes. Here, we offer the first molecular and functional characterization of an Mc2r from a lobe-finned fish, the West African lungfish (Protopterus annectens). Plasmids containing cDNA constructs of lungfish (lf) Mc2r and Mrap1 were expressed in mammalian and zebrafish cell lines. Cells were then stimulated by human ACTH(1-24) and melanocyte stimulating hormone (α-MSH), as well as alanine-substituted analogs of hACTH(1-24) targeting residues within the H6F7R8W9 and K15K16R17R18P19 motifs. Activation of lfMc2r was assessed using a cAMP-responsive luciferase reporter gene assay. In these assays, lfMc2r required co-expression with lfMrap1, was selective for ACTH over α-MSH at physiological concentrations of the ligands, and was completely inhibited by multiple-alanine substitutions of the HFRW (A6-9) and KKRRP (A15-19) motifs. Single- and partial-alanine substitutions of the HFRW and KKRRP motifs varied in their impacts on receptor-ligand affinity from having no effect to completely inhibiting lfMc2r activation. This characterization of the Mc2r of a lobe-finned fish fulfills the last major extant vertebrate group for which Mc2r function had yet to be characterized. In doing so, we resolve that all basal bony vertebrate groups exhibit Mc2r function that substantially differs from that of the cartilaginous fishes, indicating that rapid and dramatic shift in Mc2r function occurred between the radiation of cartilaginous fishes and the emergence of bony fishes. We support this interpretation with a molecular clock analysis of the melanocortin receptors, which demonstrates the uniquely high rate of sequence divergence in Mc2r. Much remains to be understood regarding the molecular evolution of Mc2r during the early radiation of vertebrates that resulted in the derived functional characteristics of Mrap1 dependence and exclusive selectivity for ACTH.

Atomic insights of an up and down conformation of the Acinetobacter baumannii F1 -ATPase subunit ε and deciphering the residues critical for ATP hydrolysis inhibition and ATP synthesis.

The Acinetobacter baumannii F1 FO -ATP synthase (α3 :ß3 :γ:δ:ε:a:b2 :c10 ), which is essential for this strictly respiratory opportunistic human pathogen, is incapable of ATP-driven proton translocation due to its latent ATPase activity. Here, we generated and purified the first recombinant A. baumannii F1 -ATPase (AbF1 -ATPase) composed of subunits α3 :ß3 :γ:ε, showing latent ATP hydrolysis. A 3.0 Å cryo-electron microscopy structure visualizes the architecture and regulatory element of this enzyme, in which the C-terminal domain of subunit ε (Abε) is present in an extended position. An ε-free AbF1 -ɑßγ complex generated showed a 21.5-fold ATP hydrolysis increase, demonstrating that Abε is the major regulator of AbF1 -ATPase's latent ATP hydrolysis. The recombinant system enabled mutational studies of single amino acid substitutions within Abε or its interacting subunits ß and γ, respectively, as well as C-terminal truncated mutants of Abε, providing a detailed picture of Abε's main element for the self-inhibition mechanism of ATP hydrolysis. Using a heterologous expression system, the importance of Abε's C-terminus in ATP synthesis of inverted membrane vesicles, including AbF1 FO -ATP synthases, has been explored. In addition, we are presenting the first NMR solution structure of the compact form of Abε, revealing interaction of its N-terminal ß-barrel and C-terminal ɑ-hairpin domain. A double mutant of Abε highlights critical residues for Abε's domain-domain formation which is important also for AbF1 -ATPase's stability. Abε does not bind MgATP, which is described to regulate the up and down movements in other bacterial counterparts. The data are compared to regulatory elements of F1 -ATPases in bacteria, chloroplasts, and mitochondria to prevent wasting of ATP.

Independent Membrane Binding Properties of the Caspase Generated Fragments of the Beaded Filament Structural Protein 1 (BFSP1) Involves an Amphipathic Helix.

BACKGROUND: BFSP1 (beaded filament structural protein 1) is a plasma membrane, Aquaporin 0 (AQP0/MIP)-associated intermediate filament protein expressed in the eye lens. BFSP1 is myristoylated, a post-translation modification that requires caspase cleavage at D433. Bioinformatic analyses suggested that the sequences 434-452 were α-helical and amphipathic. METHODS AND RESULTS: By CD spectroscopy, we show that the addition of trifluoroethanol induced a switch from an intrinsically disordered to a more α-helical conformation for the residues 434-467. Recombinantly produced BFSP1 fragments containing this amphipathic helix bind to lens lipid bilayers as determined by surface plasmon resonance (SPR). Lastly, we demonstrate by transient transfection of non-lens MCF7 cells that these same BFSP1 C-terminal sequences localise to plasma membranes and to cytoplasmic vesicles. These can be co-labelled with the vital dye, lysotracker, but other cell compartments, such as the nuclear and mitochondrial membranes, were negative. The N-terminal myristoylation of the amphipathic helix appeared not to change either the lipid affinity or membrane localisation of the BFSP1 polypeptides or fragments we assessed by SPR and transient transfection, but it did appear to enhance its helical content. CONCLUSIONS: These data support the conclusion that C-terminal sequences of human BFSP1 distal to the caspase site at G433 have independent membrane binding properties via an adjacent amphipathic helix.

Deep bidirectional LSTM for disease classification supporting hospital admission based on pre-diagnosis: a case study in Vietnam.

Overcrowding in hospitals in Vietnam has caused many disadvantages in receiving and treating patients. Especially at the stage of receiving and diagnosing procedures taking patients to the treatment departments in the hospital takes up much time. This study proposes a text-based disease diagnosis using text processing techniques (such as Bag of Words, Term Frequency- Inverse Document Frequency, and Tokenizer) combined with classifiers (such as Random Forests (RF), Multi-Layer Perceptron (MLP), Embeddings and Bidirectional Long Short-term memory (LSTM)) on symptoms. As observed from the results, deep Bidirectional LSTM can reach 0.982 in AUC in the classification of 10 diseases on 230,457 samples of pre-diagnosis collected from Vietnam hospitals used in the training and testing phases. The proposed approach is expected to provide a way to automate patient flow in hospitals to improve healthcare in the future.

Assembling Phenothiazine into a Porous Coordination Cage to Improve Its Photocatalytic Efficiency for Organic Transformations.

Photo-catalysis by small-molecules is often limited by catalyst degradation and low electron-transfer efficiency. Herein we report a stable N-phenyl-phenothiazine (PTH)-derived porous coordination cage (PCC) as a highly efficient photocatalyst. By the incorporation of the photocatalytic PTH moiety into a PCC, aggregation-induced quenching (AIQ) was shown to be reduced. An improvement in catalyst stability was discovered, ascribed to the synergistic effects of the PTH moieties. The catalyst, operating through a photolytic single-electron transfer, was utilized for photo-catalyzed dehalogenation and borylation. Evaluation of the catalytic mechanism in the borylation reaction showed that the improved performance results from the more efficient formation of the electron donor-acceptor (EDA) complex with the cage. This discovery provides a potential strategy to improve the photophysical properties and stabilities of small-molecule organic photocatalysts via supramolecular chemistry.

Electrical conductivity through π-π stacking in a two-dimensional porous gallium catecholate metal-organic framework.

Metal-organic frameworks (MOFs) are hybrid materials known for their nanoscale pores, which give them high surface areas but generally lead to poor electrical conductivity. Recently, MOFs with high electrical conductivity were established as promising materials for a variety of applications in energy storage and catalysis. Many recent reports investigating the fundamentals of charge transport in these materials focus on the role of the organic ligands. Less consideration, however, is given to the metal ion forming the MOF, which is almost exclusively a late first-row transition metal. Here, we report a moderately conductive porous MOF based on trivalent gallium and 2,3,6,7,10,11-hexahydroxytriphenylene. Gallium, a metal that has not been featured in electrically conductive MOFs so far, has a closed-shell electronic configuration and is present in its trivalent state-in contrast to most conductive MOFs, which are formed by open-shell, divalent transition metals. Our material, made without using any harmful solvents, displays conductivities on the level of 3 mS/cm and a surface area of 196 m2 /g, comparable to transition metal analogs.

Giant Hemorrhagic Pancreatic Pseudocyst: A Case Report and Guidelines for Care.

Pancreatic pseudocysts are potential sequelae of acute or chronic pancreatitis. In some cases, enzymatic degradation of the lining between a pseudocyst and the splenic artery, or surrounding vessels, can occur, resulting in a hemorrhagic pancreatic pseudocyst. Very few of these hemorrhagic pseudocysts meet the criteria for giant pseudocysts. We discuss the case of a 30-year-old male patient with a history of alcohol abuse who presented to the hospital with a giant hemorrhagic pancreatic pseudocyst; he was admitted for expectant management and was subsequently discharged. This case report seeks to shed light on the dearth of similar cases.

The United States COVID-19 Forecast Hub dataset.

Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident cases, incident hospitalizations, incident deaths, and cumulative deaths due to COVID-19 at county, state, and national, levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages.

Porous lanthanide metal-organic frameworks with metallic conductivity.

Metallic charge transport and porosity appear almost mutually exclusive. Whereas metals demand large numbers of free carriers and must have minimal impurities and lattice vibrations to avoid charge scattering, the voids in porous materials limit the carrier concentration, provide ample space for impurities, and create more charge-scattering vibrations due to the size and flexibility of the lattice. No microporous material has been conclusively shown to behave as a metal. Here, we demonstrate that single crystals of the porous metal-organic framework Ln1.5(2,3,6,7,10,11-hexaoxytriphenylene) (Ln = La, Nd) are metallic. The materials display the highest room-temperature conductivities of all porous materials, reaching values above 1,000 S/cm. Single crystals of the compounds additionally show clear temperature-deactivated charge transport, a hallmark of a metallic material. Lastly, a structural transition consistent with charge density wave ordering, present only in metals and rare in any materials, provides additional conclusive proof of the metallic nature of the materials. Our results provide an example of a metal with porosity intrinsic to its structure. We anticipate that the combination of porosity and chemical tunability that these materials possess will provide a unique handle toward controlling the unconventional states that lie within them, such as charge density waves that we observed, or perhaps superconductivity.

Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United States.

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks.

Utilization of Ultrafine Gas Bubbles to Investigate the Jones-Ray Effect of Diluted Salt Solutions.

The cause of the Jones-Ray effect has been controversially debated for years. Ultrafine gas bubbles were employed to lessen the surface excess of the surface-active impurities adsorbing to the air/water interface of the salt solutions, which would lead to a direct shift in surface tension observable by the Wilhelmy plate method. It was concluded in this study that once the surface excess of the inevitable impurities in the salts is lessened by the introduction of ultrafine gas bubbles, which possess great air/water interfacial area, the Jones-Ray effect becomes nonobservable. Therefore, our finding hypothesized that the Jones-Ray effect might not originate from salts.

Description and functional analysis of the transcriptome from malting barley.

The present study aimed to establish an early model of the malting barley transcriptome, which describes the expression of genes and their ontologies, identify the period during malting with the largest dynamic shift in gene expression for future investigation, and to determine the expression patterns of all starch degrading enzyme genes relevant to the malting and brewing industry. Large dynamic increases in gene expression occurred early in malting with differential expressed genes enriched for cell wall and starch hydrolases amongst many malting related categories. Twenty-five of forty starch degrading enzyme genes were differentially expressed in the malting barley transcriptome including eleven α-amylase genes, six ß-amylase genes, three α-glucosidase genes, and all five starch debranching enzyme genes. Four new or novel α-amylase genes, one ß-amylase gene (Bmy3), three α-glucosidase genes, and two isoamylase genes had appreciable expression that requires further exploration into their potential relevance to the malting and brewing industry.

Self-shaping liquid crystal droplets by balancing bulk elasticity and interfacial tension.

The shape diversity and controlled reconfigurability of closed surfaces and filamentous structures, universally found in cellular colonies and living tissues, are challenging to reproduce. Here, we demonstrate a method for the self-shaping of liquid crystal (LC) droplets into anisotropic and three-dimensional superstructures, such as LC fibers, LC helices, and differently shaped LC vesicles. The method is based on two surfactants: one dissolved in the LC dispersed phase and the other in the aqueous continuous phase. We use thermal stimuli to tune the bulk LC elasticity and interfacial energy, thereby transforming an emulsion of polydispersed, spherical nematic droplets into numerous, uniform-diameter fibers with multiple branches and vice versa. Furthermore, when the nematic LC is cooled to the smectic-A LC phase, we produce monodispersed microdroplets with a tunable diameter dictated by the cooling rate. Utilizing this temperature-controlled self-shaping of LCs, we demonstrate life-like smectic LC vesicle structures analogous to the biomembranes in living systems. Our experimental findings are supported by a theoretical model of equilibrium interface shapes. The shape transformation is induced by negative interfacial energy, which promotes a spontaneous increase of the interfacial area at a fixed LC volume. The method was successfully applied to many different LC materials and phases, demonstrating a universal mechanism for shape transformation in complex fluids.

The Zoltar forecast archive, a tool to standardize and store interdisciplinary prediction research.

Forecasting has emerged as an important component of informed, data-driven decision-making in a wide array of fields. We introduce a new data model for probabilistic predictions that encompasses a wide range of forecasting settings. This framework clearly defines the constituent parts of a probabilistic forecast and proposes one approach for representing these data elements. The data model is implemented in Zoltar, a new software application that stores forecasts using the data model and provides standardized API access to the data. In one real-time case study, an instance of the Zoltar web application was used to store, provide access to, and evaluate real-time forecast data on the order of 108 rows, provided by over 40 international research teams from academia and industry making forecasts of the COVID-19 outbreak in the US. Tools and data infrastructure for probabilistic forecasts, such as those introduced here, will play an increasingly important role in ensuring that future forecasting research adheres to a strict set of rigorous and reproducible standards.