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Winogradsky columns were invented by Sergei Winogradsky in the 1880s and have commonly been used as a microbiology classroom learning tool in K-12 and collegiate education. However, they can be challenging to examine with microscopy. We scaled down Winogradsky columns into nuclear magnetic resonance (NMR) tubes and replaced the natural sediment with a transparent soil substitute toward the goal of observing the microbial growth under a bright-field microscope without column disassembly. Using this "Mini Winnie" approach, students can practice their microscopy skills while observing microbial growth inside the column after only days of incubation on the laboratory windowsill. Overall, we believe that the Mini Winnies provide a simple method for maximizing student engagement while giving them a greater understanding of how microorganisms interact in the environment.

Much has been written on the skills and capabilities of a new generation raised with social media, smartphones, and immediate access to data and information via the Internet. Today's college students grew up using the Internet, where they both generate and consume data. But do incoming college students have the skills necessary to thrive in a digital world that requires the ability to generate, analyze, and share insights from data? This paper presents a study, performed at two small New England institutions each with a business focus, which examines the digital skill sets of first-year college students in relation to the skills they have developed before entering college. The authors also consider whether there is a "digital divide" among first-year college students in relation to their previous technology skills. When applying the Databilities framework for evaluating data literacy competencies, results show that teaching data literacy skills to first-year college students will be critical to their academic success as future information technology workers.

Implementation of online education pedagogy and practice has expanded rapidly at colleges and universities in recent years, most notably in response to COVID-19. This innovative teaching/learning modality provides benefits to both faculty and students through dynamic teaching/learning content, immense flexibility, and technological investments to support teaching and learning. Academic dishonesty in higher education is a persistent concern emphasized and extensively explored in traditional face-to-face courses, less so in online learning environments. The present work, drawing on a large sample of students and faculty (n=1,640) at a Midwestern university, employs an esurvey and both qualitative and quantitative responses on cheating behavior in the emergent area of online courses/online education. Results expose significant faculty and student disagreement and uncertainty about cheating behaviors in the online environment. Academic integrity is essential to fair and equitable high-quality higher education. The stakes are high to better understand the transformative shifts in academic dishonesty occurring in the online educational environment.

A growing body of research demonstrates the effectiveness of computerized cognitive training (CCT) in building specific abilities (e.g., working memory) among school-age children. As a result, CCT is increasingly cited as a means to enhance and support students’ academic performance and school experience. However, many studies exploring CCT as an intervention have done so outside of the school setting, limiting its potential impact with regard to students who may benefit from it but cannot access such supports. This project examined the efficacy of a CCT program implemented within the academic day for all students attending a private school. The findings showed that two CCT programs resulted in improvements in working memory, cognitive flexibility, and/or processing speed among third graders through sixth graders (N = 95). Furthermore, this project demonstrates a model for the effective integration of CCT into a school day without interrupting the academic curriculum. The present results have important implications for the current ideological shift in education that focuses on how to more broadly address students’ learning differences.

We analyzed spectral cubes of Callisto’s leading and trailing hemispheres, collected with the NIRSpec Integrated Field Unit (G395H) on the James Webb Space Telescope. These spatially resolved data show strong 4.25 μ m absorption bands resulting from solid-state ^12 CO _2 , with the strongest spectral features at low latitudes near the center of its trailing hemisphere, consistent with radiolytic production spurred by magnetospheric plasma interacting with native H _2 O mixed with carbonaceous compounds. We detected CO _2 rovibrational emission lines between 4.2 and 4.3 μ m over both hemispheres, confirming the global presence of CO _2 gas in Callisto’s tenuous atmosphere. These results represent the first detection of CO _2 gas over Callisto’s trailing side. The distribution of CO _2 gas is offset from the subsolar region on either hemisphere, suggesting that sputtering, radiolysis, and geologic processes help sustain Callisto’s atmosphere. We detected a 4.38 μ m absorption band that likely results from solid-state ^13 CO _2 . A prominent 4.57 μ m absorption band that might result from CN-bearing organics is present and significantly stronger on Callisto’s leading hemisphere, unlike ^12 CO _2 , suggesting these two spectral features are spatially antiassociated. The distribution of the 4.57 μ m band is more consistent with a native origin and/or accumulation of dust from Jupiter’s irregular satellites. Other, more subtle absorption features could result from CH-bearing organics, CO, carbonyl sulfide, and Na-bearing minerals. These results highlight the need for preparatory laboratory work and improved surface–atmosphere interaction models to better understand carbon chemistry on the icy Galilean moons before the arrival of NASA’s Europa Clipper and ESA’s JUICE spacecraft.

A long-standing debate among cognitive scientists has focused on describing the underlying nature of executive functions, which has important implications for both theoretical and applied research. Miyake et al.’s three-factor model has often been considered the gold-standard representation of executive functions and has driven much research in the field. More recently, however, there have been increasing concerns that the three-factor model does not adequately describe a highly complex construct such as executive functions. The current project presents two studies that examine the veracity of Miyake et al.’s model and propose a new approach (i.e., network modeling) for detecting the underlying nature of executive functions. The current results raise questions about the psychometric strength and adequacy of the three-factor model. Further, the studies presented here provide evidence that network modeling provides a better understanding of executive functions as it better captures (relative to latent variable modeling) the complexity of cognitive processes. Theoretical and applied implications are discussed.

Streptococcal siglec-like binding regions (SLBRs) selectively bind cell surface glycans, but the basis for this selectivity is not understood. Here, the authors identify selectivity-modulating SLBR regions and study how changes in SLBR glycan selectivity affect interactions with human glycoprotein receptors.

Abstract Background The COVID-19 pandemic has considerably disrupted nearly all aspects of daily life, including healthcare delivery and clinical research. Because pragmatic clinical trials are often embedded within healthcare delivery systems, they may be at high risk of disruption due to the dual impacts on the conduct of both care and research. Methods We collected qualitative data using multiple methods to characterize the impact of COVID-19 on the research activities of 14 active pragmatic clinical trials in the National Institutes of Health (NIH) Health Care Systems Research Collaboratory. A COVID-19 impact questionnaire was administered electronically to principal investigators in June 2020. Text responses were analyzed thematically, and qualitative summaries were subsequently reviewed by five independent reviewers, who made iterative revisions. Additional COVID-19-related impacts were identified during virtual meetings with trial teams during April–July 2020 and combined with questionnaire responses for analysis. Results Impacts of the pandemic were broadly classified into two main types: healthcare operations and social distancing. In some instances, trial delays created statistical challenges, particularly with trials using stepped-wedge designs, and necessitated changing data collection strategies or modifying interventions. The majority of projects used existing stakeholder-driven approaches to adapt interventions. Several benefits of these adaptions were identified, including expanded outreach capabilities and ability to study virtual intervention delivery. All trial teams were able to adapt to pandemic-related modifications. Conclusion In a group of 14 ongoing pragmatic clinical trials, there was significant impact of COVID-19 on trial activities. Engaging appropriate stakeholders was critical to designing and implementing trial modifications and making continued safe progress toward meeting research objectives.

Abstract The continental-rifting of Arabia from Nubia, and the initial evolution of the Red Sea spreading center includes many of the continental-rifting to ocean-spreading processes, in particular transform formation, and the eventual development of a mid-ocean ridge. The recent occurrence of this rifting and the multi-stage evolution of the plate boundary has preserved of key components of the early-stage plate boundary development. We find that the Makkah–Madinah Transform Zone (MMTZ) represents a rift-to-rift continental transform fault that served as a primary component of the initial plate boundary between Arabia and Nubia. It connected the more evolved southern Red Sea mid-ocean ridge to the initially dominant Sirhan Rift. During this time, the MMTZ served as a primary lithospheric-scale boundary between the Arabia and Nubia plates. The Sirhan Rift and the MMTZ connection to the Red Sea spreading center was mostly abandoned with the development of the Dead Sea fault, and localization of extension in the present-day northern Red Sea. The transition to the present tectonic setting suggests an ephemeral rift–rift–transform triple junction within the central Red Sea connecting the localized southern Red Sea rift, a developing northern Red Sea rift, and the MMTZ transform.

Abstract Inadequate drinking water quality is among the major causes of preventable mortality, predominantly in young children. Identifying contaminated water sources remains a significant challenge, especially where resources are limited. The current methods for measuring Escherichia coli (E. coli), the WHO preferred indicator for measuring fecal contamination of water, involve overnight incubation and require specialized training. In 2016, UNICEF released a Target Product Profile (TPP) to incentivize product innovations to detect low levels of viable E. coli in water samples in the field in less than 6 h. Driven by this challenge, we developed a phage-based assay to detect and semi-quantify E. coli. We formulated a phage cocktail containing a total of 8 phages selected against an extensive bacterial strain library and recombined with the sensitive NanoLuc luciferase reporter. The assay was optimized to be processed in a microfluidic chip designed in-house and was tested against locally sourced sewage samples and on drinking water sources in Nairobi, Kenya. With this assay, combined with the microfluidic chip platform, we propose a complete automated solution to detect and semi-quantify E. coli at less than 10 MPN/100 mL in 5.5 h by minimally trained personnel.

We carried out a literature search in MEDLINE (PubMed) and EMBASE literature databases to provide a concise review of the role of viscoelastic testing in assessing peri-interventional platelet function and coagulation. The search identified 130 articles that were relevant for the review, covering the basic science of VHA and VHA in clinical settings including cardiac surgery, cardiology, neurology, trauma, non-cardiac surgery, obstetrics, liver disease, and COVID-19. Evidence from these articles is used to describe the important role of VHAs and platelet function testing in various peri-interventional setups. VHAs can help us to comprehensively assess the contribution of platelets and coagulation dynamics to clotting at the site-of-care much faster than standard laboratory measures. In addition to standard coagulation tests, VHAs are beneficial in reducing allogeneic transfusion requirements and bleeding, in predicting ischemic events, and improving outcomes in several peri-interventional care settings. Further focused studies are needed to confirm their utility in the peri-interventional case.

The net-zero global carbon target for 2050 needs both expansion of renewable energy and substantive energy consumption reduction. Many of the solutions needed are expensive. Controlling HVAC systems in buildings based upon thermal comfort, not just temperature, uniquely offers a means for deep savings at virtually no cost. In this study, a more accurate means to quantify the savings potential in any building in which smart WiFi thermostats are present is developed. Prior research by Alhamayani et al. leveraging such data for individual residences predicted cooling energy savings in the range from 33 to 47%, but this research was based only upon a singular data-based model of indoor temperature. The present research improves upon this prior research by developing LSTM neural network models for both indoor temperature and humidity. Validation errors are reduced by nearly 22% compared to the prior work. Simulations of thermal comfort control for the residences considered yielded potential savings in the range of 29–43%, dependent upon both solar exposure and insulation characteristics of each residence. This research paves the way for smart Wi-Fi thermostat-enabled thermal comfort control in buildings of all types.

Abstract Objectives Cisplatin‐based chemoradiation is an established organ‐preserving strategy for locally advanced laryngeal cancer, but long‐term survival remains suboptimal. Immunotherapy has been studied in the metastatic and unresectable recurrent settings. However, additional data are needed to assess its role in organ preservation for locally advanced laryngeal cancer. Methods This trial was an open‐label, single‐arm, multi‐institutional study with a Phase I run‐in portion followed by a planned Phase II component, which closed early due to low accrual. Study patients had Stage III or IV (T2–3; N0–3; M0) laryngeal squamous cell carcinoma and were candidates for larynx preservation. Pembrolizumab was given 2–3 weeks prior to chemoradiation and then, q21 days concurrently with high‐dose cisplatin and radiation prescribed to a total dose of 70 Gy. The primary endpoint of the trial was organ‐preservation rate (OPR) at 18 months. Results A total of nine patients were enrolled with a median follow‐up of 30.1 months. No patient required laryngectomy, resulting in 100% OPR at 18 months. The 12‐month overall survival (OS) rate was 77.8% and the median duration of OS was not reached. All acute Grade 4 (n = 3) toxicities occurred in a single patient with poorly controlled diabetes at baseline. One patient had late Grade 4 laryngeal edema requiring tracheostomy 8 months after chemoradiation, which self‐resolved. Conclusion UCCI‐HN‐15‐02 demonstrated the safety of the addition of immunotherapy to definitive chemoradiation and the patient outcomes suggest the potential for improving long‐term survival while minimizing negative impact from treatment. While results from this trial were promising, a randomized study with a larger number of patients and longer follow‐up is warranted to verify this treatment approach prior to wider adoption. NCT #: NCT02759575. Level of evidence: 2b

Abstract Background Monoacylglycerol lipase (MAGL) is a key serine hydrolase which terminates endocannabinoid signaling and regulates arachidonic acid driven inflammatory responses within the central nervous system. To develop [11C]PF-06809247 into a clinically usable MAGL positron emission tomography (PET) radioligand, we assessed the occupancy of MAGL by an inhibitor in the non-human primate (NHP) brain. Additionally, we measured the whole-body distribution of [11C]PF-06809247 in NHP and estimated human effective radiation doses. Methods Seven cynomolgus monkeys were enrolled for brain PET measurements. Two PET measurements along with arterial blood sampling were performed in each NHP: one baseline and one pretreatment condition with intravenous administration of PF-06818883, a pro-drug of a selective MAGL inhibitor (total of seven doses between 0.01 and 1.27 mg/kg). Kinetic parameters K 1, k 2 and k 3 were estimated by a two tissue compartment (2TC) model using metabolite corrected plasma radioactivity as the input function. k 4 was set as 0 according to the irreversible binding of [11C]PF-06809247. K i by 2TC and Patlak analysis were calculated as the influx constant. The target occupancy was calculated using K i at baseline and pretreatment conditions. Two cynomolgus monkeys were enrolled for whole-body PET measurements. Estimates of the absorbed radiation dose in humans were calculated with OLINDA/EXM 1.1 using the adult male reference model. Results Radioactivity retention was decreased in all brain regions following pretreatment with PF-06818883. Occupancy was measured as 25.4–100.5% in a dose dependent manner. Whole-body PET showed high radioactivity uptake values in the liver, small intestine, kidney, and brain. The effective dose of [11C]PF-06809247 was calculated as 4.3 μSv/MBq. Conclusions [11C]PF-06809247 is a promising PET ligand for further studies of MAGL in the human brain.

Abstract Background The fungal pathogen Batrachochytrium dendrobatidis (Bd) threatens amphibian biodiversity and ecosystem stability worldwide. Amphibian skin microbial community structure has been linked to the clinical outcome of Bd infections, yet its overall functional importance is poorly understood. Methods Microbiome taxonomic and functional profiles were assessed using high-throughput bacterial 16S rRNA and fungal ITS2 gene sequencing, bacterial shotgun metagenomics and skin mucosal metabolomics. We sampled 56 wild midwife toads (Alytes obstetricans) from montane populations exhibiting Bd epizootic or enzootic disease dynamics. In addition, to assess whether disease-specific microbiome profiles were linked to microbe-mediated protection or Bd-induced perturbation, we performed a laboratory Bd challenge experiment whereby 40 young adult A. obstetricans were exposed to Bd or a control sham infection. We measured temporal changes in the microbiome as well as functional profiles of Bd-exposed and control animals at peak infection. Results Microbiome community structure and function differed in wild populations based on infection history and in experimental control versus Bd-exposed animals. Bd exposure in the laboratory resulted in dynamic changes in microbiome community structure and functional differences, with infection clearance in all but one infected animal. Sphingobacterium, Stenotrophomonas and an unclassified Commamonadaceae were associated with wild epizootic dynamics and also had reduced abundance in laboratory Bd-exposed animals that cleared infection, indicating a negative association with Bd resistance. This was further supported by microbe-metabolite integration which identified functionally relevant taxa driving disease outcome, of which Sphingobacterium and Bd were most influential in wild epizootic dynamics. The strong correlation between microbial taxonomic community composition and skin metabolome in the laboratory and field is inconsistent with microbial functional redundancy, indicating that differences in microbial taxonomy drive functional variation. Shotgun metagenomic analyses support these findings, with similar disease-associated patterns in beta diversity. Analysis of differentially abundant bacterial genes and pathways indicated that bacterial environmental sensing and Bd resource competition are likely to be important in driving infection outcomes. Conclusions Bd infection drives altered microbiome taxonomic and functional profiles across laboratory and field environments. Our application of multi-omics analyses in experimental and field settings robustly predicts Bd disease dynamics and identifies novel candidate biomarkers of infection. Video Abstract

Abstract The western tarnished plant bug, Lygus hesperus, is a key hemipteran pest of numerous agricultural, horticultural, and industrial crops in the western United States and Mexico. A lack of genetic tools in L. hesperus hinders progress in functional genomics and in developing innovative pest control methods such as gene drive. Here, using RNA interference (RNAi) against cardinal (LhCd), cinnabar (LhCn), and white (LhW), we showed that knockdown of LhW was lethal to developing embryos, while knockdown of LhCd or LhCn produced bright red eye phenotypes, in contrast to wild-type brown eyes. We further used CRISPR/Cas9 (clustered regularly interspaced palindromic repeats/CRISPR-associated) genome editing to generate germline knockouts of both LhCd (Card) and LhCn (Cinn), producing separate strains of L. hesperus characterized by mutant eye phenotypes. Although the cardinal knockout strain Card exhibited a gradual darkening of the eyes to brown typical of the wild-type line later in nymphal development, we observed bright red eyes throughout all life stages in the cinnabar knockout strain Cinn, making it a viable marker for tracking gene editing in L. hesperus. These results provide evidence that CRISPR/Cas9 gene editing functions in L. hesperus and that eye pigmentation genes are useful for tracking the successful genetic manipulation of this insect.

This study finds that foreign firms tend to shy away from countries with higher physical climate risks than do local firms. Chinese FDI is significantly more exposed to most physical climate risks than non-Chinese FDI across countries.

In 2021, the United Nations Committee on Development Policy adopted a resolution that Bangladesh would graduate from least developed country (LDC) status after a period of 5 years. This means that in 2026 Bangladesh would have to forego its exemption to intellectual property (IP) provisions of the World Trade Organization (WTO). Bangladesh has taken advantage of the policy space it was granted under the LDC exemption to build a generic medicines industry that not only serves Bangladesh but also other LDCs. We examine how IP provisions in the WTO will impact the price of insulin in Bangladesh and the subsequent impacts on welfare and poverty. We find that LDC graduation will trigger a significant jump in insulin prices that could cause about a 15% decline in the welfare of households in Bangladesh with one or more members living with diabetes, increasing the poverty rate of such households unless policy adjustments are carried out.

The management of atrial septal defects (ASDs) has been revolutionized by the advent of percutaneous transvenous occlusion devices. This case series describes techniques required to perform a transeptal puncture safely and effectively in patients postimplantation of an atrial septal defect occluder to facilitate catheter ablation of atrial arrhythmias. (Level of Difficulty: Intermediate.)

Flow chemistry was initially used for speed to early phase material delivery in the development laboratories, scaling up chemical transformations that we would not or could not scale up batch for safety reasons. Some early examples included a Newman Kwart Rearrangement, Claisen rearrangement, hydroformylation, and thermal imidazole cyclization. Next, flow chemistry was used to enable safe scale up of hazardous chemistries to manufacturing plants. Examples included high pressure hydrogenation, aerobic oxidation, and Grignard formation reactions. More recently, flow chemistry was used in Small Volume Continuous (SVC) processes, where highly potent oncolytic molecules were produced by fully continuous processes at about 10 kg/day including reaction, extraction, distillation, and crystallization, using disposable equipment contained in fume hoods.

Diagnosis of tuberculosis (TB) among young children (

The trapping of Poly-ADP-ribose polymerase (PARP) on DNA caused by PARP inhibitors (PARPi) triggers acute DNA replication stress and synthetic lethality (SL) in BRCA2-deficient cells. Hence, DNA damage is accepted as a prerequisite for SL in BRCA2-deficient cells. In contrast, here we show that inhibiting ROCK in BRCA2-deficient cells triggers SL independently from acute replication stress. Such SL is preceded by polyploidy and binucleation resulting from cytokinesis failure. Such initial mitosis abnormalities are followed by other M phase defects, including anaphase bridges and abnormal mitotic figures associated with multipolar spindles, supernumerary centrosomes and multinucleation. SL was also triggered by inhibiting Citron Rho-interacting kinase, another enzyme that, similarly to ROCK, regulates cytokinesis. Together, these observations demonstrate that cytokinesis failure triggers mitotic abnormalities and SL in BRCA2-deficient cells. Furthermore, the prevention of mitotic entry by depletion of Early mitotic inhibitor 1 (EMI1) augmented the survival of BRCA2-deficient cells treated with ROCK inhibitors, thus reinforcing the association between M phase and cell death in BRCA2-deficient cells. This novel SL differs from the one triggered by PARPi and uncovers mitosis as an Achilles heel of BRCA2-deficient cells.

Summary: Background: There is paucity of data regarding prevalence and key harms of non-medical cannabis use in surgical patients. We investigated whether cannabis use in patients undergoing surgery or interventional procedures patients was associated with a higher degree of post-procedural healthcare utilisation. Methods: 210,639 adults undergoing non-cardiac surgery between January 2008 and June 2020 at an academic healthcare network in Massachusetts, USA, were included. The primary exposure was use of cannabis, differentiated by reported ongoing non-medical use, self-identified during structured, preoperative nursing/physician interviews, or diagnosis of cannabis use disorder based on International Classification of Diseases, 9th/10th Revision, diagnostic codes. The main outcome measure was the requirement of advanced post-procedural healthcare utilisation (unplanned intensive care unit admission, hospital re-admission or non-home discharge). Findings: 16,211 patients (7.7%) were identified as cannabis users. The prevalence of cannabis use increased from 4.9% in 2008 to 14.3% by 2020 (p

IMPORTANCE:. Early detection of illness trajectory in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients is crucial for patients and healthcare workers. An effective, noninvasive approach, with simple measurement for decision-making, is necessary in a pandemic to discriminate between high- and low-risk patients, even though both groups may exhibit mild symptoms in the beginning. OBJECTIVES:. To predict COVID-19 disease severity within 10 days, distinguishing cases that will progress to moderate or severe versus mild, patient urinary L-type fatty acid-binding protein (L-FABP) was assayed within 4 days of receiving a diagnosis. The study also examined whether L-FABP point of care (POC) test is helpful in risk screening. DESIGN:. Symptomatic subjects who tested positive for SARS-CoV-2 and were hospitalized were prospectively enrolled at the National Center for Global Health and Medicine (NCGM), Yamanashi Prefectural Central Hospital (YPCH), and Sinai Hospital in Maryland. The outcome of each case was evaluated 7 days after admission and the diagnostic performance of L-FABP was assessed. SETTING AND PARTICIPANTS:. Subjects were treated for COVID-19 at public healthcare centers in Japan from January 31, 2020, to January 31, 2021, to NCGM, YPCH, and at Sinai Hospital in Baltimore, MD, during the same period. MAIN OUTCOMES AND MEASURES:. The primary outcome was to determine whether urinary L-FABP within 48 hours of admission can predict the patient’s severity of COVID-19 1 week later. We obtained demographic data, information on clinical symptoms, radiographic images, and laboratory data. RESULTS:. Diagnostic performance was assessed using receiver operating characteristic analysis. Of the 224 participants in the study, 173 initially had a mild form of COVID-19. The area under the curve (AUC) for a severe outcome was 93.5%. L-FABP POC risk prediction of a severe outcome had an AUC of 88.9%. CONCLUSIONS AND RELEVANCE:. Urinary L-FABP can predict patient risk of COVID-19 illness severity. L-FABP POC is implementable for patient management. (ClinicalTrials.gov number, NCT04681040).

We assessed vaccine-induced antibody responses to the SARS-CoV-2 ancestral virus and Omicron variant before and after booster immunization in 57 patients with B cell malignancies. Over one-third of vaccinated patients at the pre-booster time point were seronegative, and these patients were predominantly on active cancer therapies such as anti-CD20 monoclonal antibody. While booster immunization was able to induce detectable antibodies in a small fraction of seronegative patients, the overall booster benefit was disproportionately evident in patients already seropositive and not receiving active therapy. While ancestral virus– and Omicron variant–reactive antibody levels among individual patients were largely concordant, neutralizing antibodies against Omicron tended to be reduced. Interestingly, in all patients, including those unable to generate detectable antibodies against SARS-CoV-2 spike, we observed comparable levels of EBV- and influenza-reactive antibodies, demonstrating that B cell–targeting therapies primarily impair de novo but not preexisting antibody levels. These findings support rationale for vaccination before cancer treatment.

Abstract Autism spectrum disorder (ASD) is the fourth most common neurodevelopmental disorder, with a prevalence of 1 in 160 children. Accurate diagnosis relies on experts, but such individuals are scarce. This has led to increasing interest in the development of machine learning (ML) models that can integrate neuroimaging features from functional and structural MRI (fMRI and sMRI) to help reveal central nervous system alterations characteristic of ASD. We optimized and compared the performance of 12 of the most popular and powerful ML models. Each was separately trained using 15 different combinations of fMRI and sMRI features and optimized with an unbiased model search. Deep learning models predicted ASD with the highest diagnostic accuracy and generalized well to other MRI datasets. Our model achieves state-of-the-art 80% area under the ROC curve (AUROC) in diagnosis on test data from the IMPAC dataset; and 86% and 79% AUROC on the external ABIDE I and ABIDE II datasets (with further improvement to 93% and 90% after supervised domain adaptation). The highest performing models identified reproducible putative biomarkers for accurate ASD diagnosis in accord with known ASD markers as well as novel cerebellar biomarkers. Such reproducibility lends credence to their tremendous potential for defining and using a set of truly generalizable ASD biomarkers that will advance scientific understanding of neuronal changes in ASD.

With the rapidly increasing deployment of distributed energy resources (DERs), electric power systems across the world are moving towards more distributed designs and operations. While not every distributed device will be part of a microgrid, microgrids do offer solutions for scalability and interoperability, and for coordination with centralized utility control systems. The challenge is that the microgrids will be heterogenous with respect to ownership, operational objectives, resource mix, and control systems. Due to these variations within the population of microgrids, there will be significant challenges with coordinating their operations to achieve global objectives using existing centralized controls and optimizations. This paper presents a framework for the coordination of heterogeneous groups of microgrids using consensus algorithms. The framework enables the active engagement of utility and non-utility microgrids using a distributed architecture to support end-use loads during the loss of the bulk power system. Results from laboratory testing and preliminary implementations, as well as details of an ongoing operational deployment at the Electric Power Board of Chattanooga are presented in this paper.

During pyroptosis, gasdermin D (GSDMD) forms plasma membrane pores that initiate cell lysis. Here, the authors develop optogenetically activatable human GSDMD to assess GSDMD pore behavior and show that they are dynamic and can close, which can be a pyroptosis regulatory mechanism.

Abstract Background Medications to treat opioid use disorder (OUD) including buprenorphine products are evidence-based and cost-effective tools for combating the opioid crisis. However, limited availability to buprenorphine is pervasive in the United States (US) and may serve to exacerbate the deadly epidemic. Although prior research points to rural counties as especially needy of strategies that improve buprenorphine availability, it is important to investigate the availability of waivered providers according to treatment need as defined by the county-level rate of opioid-overdose deaths (OOD). This study examined differences in buprenorphine provider availability relative to treatment need among rural and urban counties in the US. Methods Buprenorphine provider availability relative to need in each county was defined as the number of waivered providers divided by the rate of OODs (i.e., number of OODs/100,000 population), according to 2018 data. Counties with ratios in the bottom tertile of their state were classified as buprenorphine undersupplied. We estimated logit models to statistically test the association of rurality and state main effects and their interaction terms (independent variables) and the county classified as buprenorphine undersupplied (dependent variable). Results A total of 38 states and 2595 counties had sufficient non-suppressed data to remain in the analysis. A larger percent of urban counties (36.43%) than rural counties (32.01%) were classified as buprenorphine undersupplied (p = 0.001). The likelihood of a rural county being undersupplied varied considerably by state (Chi Square = 82.88, p = 0.000). All states with significant (p

Abstract An islanded microgrid is cyber‐physical system, and the control relies on the communication system significantly. Improper parameters of the cyber system can result in instability of a microgrid system. To evaluate the impact of a networked control system on control performance, a cyber model is developed to represent data acquisition periods and communication delays. Simplification of the networked control system model is proposed to enhance the computational performance, making the analytical method applicable for large‐scale systems. Based on the analysis, a two‐dimensional stability region of a microgrid in the space of cyber parameters can be obtained. To validate the proposed method, a microgrid control scheme is proposed for power dispatch and regulation based on the droop and proportional‐integral (PI) feedback control. The analytical method is compared to the time‐domain simulation, and it is shown that the stability regions are nearly identical. The critical values of cyber parameters are determined based on the analytical results. The proposed control strategy with the given cyber parameters is validated for transient stability following dynamic events. Simulation results indicate that the design of a microgrid as a cyber‐physical system needs to be guided by critical values for cyber parameters to prevent system instability.

Abstract Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) through direct lysis of infected lung epithelial cells, which releases damage-associated molecular patterns and induces a pro-inflammatory cytokine milieu causing systemic inflammation. Anti-viral and anti-inflammatory agents have shown limited therapeutic efficacy. Soluble CD24 (CD24Fc) blunts the broad inflammatory response induced by damage-associated molecular patterns via binding to extracellular high mobility group box 1 and heat shock proteins, as well as regulating the downstream Siglec10-Src homology 2 domain–containing phosphatase 1 pathway. A recent randomized phase III trial evaluating CD24Fc for patients with severe COVID-19 (SAC-COVID; NCT04317040) demonstrated encouraging clinical efficacy. Methods Using a systems analytical approach, we studied peripheral blood samples obtained from patients enrolled at a single institution in the SAC-COVID trial to discern the impact of CD24Fc treatment on immune homeostasis. We performed high dimensional spectral flow cytometry and measured the levels of a broad array of cytokines and chemokines to discern the impact of CD24Fc treatment on immune homeostasis in patients with COVID-19. Results Twenty-two patients were enrolled, and the clinical characteristics from the CD24Fc vs. placebo groups were matched. Using high-content spectral flow cytometry and network-level analysis, we found that patients with severe COVID-19 had systemic hyper-activation of multiple cellular compartments, including CD8+ T cells, CD4+ T cells, and CD56+ natural killer cells. Treatment with CD24Fc blunted this systemic inflammation, inducing a return to homeostasis in NK and T cells without compromising the anti-Spike protein antibody response. CD24Fc significantly attenuated the systemic cytokine response and diminished the cytokine coexpression and network connectivity linked with COVID-19 severity and pathogenesis. Conclusions Our data demonstrate that CD24Fc rapidly down-modulates systemic inflammation and restores immune homeostasis in SARS-CoV-2-infected individuals, supporting further development of CD24Fc as a novel therapeutic against severe COVID-19.