A Deep Learning Approach to Classify Fabry Cardiomyopathy from Hypertrophic Cardiomyopathy Using Cine Imaging on Cardiac Magnetic Resonance.

A challenge in accurately identifying and classifying left ventricular hypertrophy (LVH) is distinguishing it from hypertrophic cardiomyopathy (HCM) and Fabry disease. The reliance on imaging techniques often requires the expertise of multiple specialists, including cardiologists, radiologists, and geneticists. This variability in the interpretation and classification of LVH leads to inconsistent diagnoses. LVH, HCM, and Fabry cardiomyopathy can be differentiated using T1 mapping on cardiac magnetic resonance imaging (MRI). However, differentiation between HCM and Fabry cardiomyopathy using echocardiography or MRI cine images is challenging for cardiologists. Our proposed system named the MRI short-axis view left ventricular hypertrophy classifier (MSLVHC) is a high-accuracy standardized imaging classification model developed using AI and trained on MRI short-axis (SAX) view cine images to distinguish between HCM and Fabry disease. The model achieved impressive performance, with an F1-score of 0.846, an accuracy of 0.909, and an AUC of 0.914 when tested on the Taipei Veterans General Hospital (TVGH) dataset. Additionally, a single-blinding study and external testing using data from the Taichung Veterans General Hospital (TCVGH) demonstrated the reliability and effectiveness of the model, achieving an F1-score of 0.727, an accuracy of 0.806, and an AUC of 0.918, demonstrating the model's reliability and usefulness. This AI model holds promise as a valuable tool for assisting specialists in diagnosing LVH diseases.

Detection of Cadmium in Human Biospecimens by a Cadmium-Selective Whole-Cell Biosensor Based on Deoxyviolacein.

Cadmium poses a severe health risk, impacting various bodily systems. Monitoring human exposure is vital. Urine and blood cadmium serve as critical biomarkers. However, current urine and blood cadmium detection methods are expensive and complex. Being cost-effective, user-friendly, and efficient, visual biosensing offers a promising complement to existing techniques. Therefore, we constructed a cadmium whole-cell biosensor using CadR10 and deoxyviolacein pigment in this study. We assessed the sensor for time-dose response, specific response to cadmium, sensitivity response to cadmium, and stability response to cadmium. The results showed that (1) the sensor had a preferred signal-to-noise ratio when the incubation time was 4 h; (2) the sensor showed excellent specificity for cadmium compared to the group 12 metals and lead; (3) the sensor was responsive to cadmium down to 1.53 nM under experimental conditions and had good linearity over a wide range from 1.53 nM to 100 µM with good linearity (R2 = 0.979); and (4) the sensor had good stability. Based on the excellent results of the performance tests, we developed a cost-effective, high-throughput method for detecting urinary and blood cadmium. Specifically, this was realized by adding the blood or urine samples into the culture system in a particular proportion. Then, the whole-cell biosensor was subjected to culture, n-butanol extraction, and microplate reading. The results showed that (1) at 20% urine addition ratio, the sensor had an excellent curvilinear relationship (R2 = 0.986) in the range of 3.05 nM to 100 µM, and the detection limit could reach 3.05 nM. (2) At a 10% blood addition ratio, the sensor had an excellent nonlinear relationship (R2 = 0.978) in the range of 0.097-50 µM, and the detection limit reached 0.195 µM. Overall, we developed a sensitive and wide-range method based on a whole-cell biosensor for the detection of cadmium in blood and urine, which has the advantages of being cost-effective, ease of operation, fast response, and low dependence on instrumentation and has the potential to be applied in the monitoring of cadmium exposure in humans as a complementary to the mainstream detection techniques.

Fibroblast expression of transmembrane protein smoothened governs microenvironment characteristics after acute kidney injury.

The smoothened (Smo) receptor facilitates hedgehog signaling between kidney fibroblasts and tubules during acute kidney injury (AKI). Tubule-derived hedgehog is protective in AKI, but the role of fibroblast-selective Smo is unclear. Here, we report that Smo-specific ablation in fibroblasts reduced tubular cell apoptosis and inflammation, enhanced perivascular mesenchymal cells activities, and preserved kidney function after AKI. Global proteomics of these kidneys identified extracellular matrix proteins, and nidogen-1 glycoprotein in particular, as key response markers to AKI. Intriguingly, Smo was bound to nidogen-1 in cells, suggesting that loss of Smo could impact nidogen-1 accessibility. Phosphoproteomics revealed that the 'AKI protector' Wnt signaling pathway was activated in these kidneys. Mechanistically, nidogen-1 interacted with integrin ß1 to induce Wnts in tubules to mitigate AKI. Altogether, our results support that fibroblast-selective Smo dictates AKI fate through cell-matrix interactions, including nidogen-1, and offers a robust resource and path to further dissect AKI pathogenesis.

Multifunctional interaction of CihC/FbpC orthologs of relapsing fever spirochetes with host-derived proteins involved in adhesion, fibrinolysis, and complement evasion.

Introduction: Relapsing fever (RF) remains a neglected human disease that is caused by a number of diverse pathogenic Borrelia (B.) species. Characterized by high cell densities in human blood, relapsing fever spirochetes have developed plentiful strategies to avoid recognition by the host defense mechanisms. In this scenario, spirochetal lipoproteins exhibiting multifunctional binding properties in the interaction with host-derived molecules are known to play a key role in adhesion, fibrinolysis and complement activation. Methods: Binding of CihC/FbpC orthologs to different human proteins and conversion of protein-bound plasminogen to proteolytic active plasmin were examined by ELISA. To analyze the inhibitory capacity of CihC/FbpC orthologs on complement activation, a microtiter-based approach was performed. Finally, AlphaFold predictions were utilized to identified the complement-interacting residues. Results and discussion: Here, we elucidate the binding properties of CihC/FbpC-orthologs from distinct RF spirochetes including B. parkeri, B. hermsii, B. turicatae, and B. recurrentis to human fibronectin, plasminogen, and complement component C1r. All CihC/FbpC-orthologs displayed similar binding properties to fibronectin, plasminogen, and C1r, respectively. Functional studies revealed a dose dependent binding of plasminogen to all borrelial proteins and conversion to active plasmin. The proteolytic activity of plasmin was almost completely abrogated by tranexamic acid, indicating that lysine residues are involved in the interaction with this serine protease. In addition, a strong inactivation capacity toward the classical pathway could be demonstrated for the wild-type CihC/FbpC-orthologs as well as for the C-terminal CihC fragment of B. recurrentis. Pre-incubation of human serum with borrelial molecules except CihC/FbpC variants lacking the C-terminal region protected serum-susceptible Borrelia cells from complement-mediated lysis. Utilizing AlphaFold2 predictions and existing crystal structures, we mapped the putative key residues involved in C1r binding on the CihC/FbpC orthologs attempting to explain the relatively small differences in C1r binding affinity despite the substitutions of key residues. Collectively, our data advance the understanding of the multiple binding properties of structural and functional highly similar molecules of relapsing fever spirochetes proposed to be involved in pathogenesis and virulence.

Antiviral activity of Vigna radiata extract against feline coronavirus in vitro.

Feline infectious peritonitis (FIP) is a fatal illness caused by a mutated feline coronavirus (FCoV). This disease is characterized by its complexity, resulting from systemic infection, antibody-dependent enhancement (ADE), and challenges in accessing effective therapeutics. Extract derived from Vigna radiata (L.) R. Wilczek (VRE) exhibits various pharmacological effects, including antiviral activity. This study aimed to investigate the antiviral potential of VRE against FCoV, addressing the urgent need to advance the treatment of FIP. We explored the anti-FCoV activity, antiviral mechanism, and combinational application of VRE by means of in vitro antiviral assays. Our findings reveal that VRE effectively inhibited the cytopathic effect induced by FCoV, reduced viral proliferation, and downregulated spike protein expression. Moreover, VRE blocked FCoV in the early and late infection stages and was effective under in vitro ADE infection. Notably, when combined with VRE, the polymerase inhibitor GS-441524 or protease inhibitor GC376 suppressed FCoV more effectively than monotherapy. In conclusion, this study characterizes the antiviral property of VRE against FCoV in vitro, and VRE possesses therapeutic potential for FCoV treatment.

CRF08_BC subtype is more prone to ART failure and new generation NNRTI-resistance under long-term first line ART.

OBJECTIVE: To investigate the characteristics of drug resistance mutations (DRMs) and their contextual influence on drug susceptibility in CRF07_BC and CRF_08BC subtypes. METHODS: Patients with virological failure were genotyped using phylogenetic analysis. DRMs and susceptibility to antiretroviral drugs were analyzed using the Stanford University HIV Drug Resistance Database. RESULTS: Six HIV subtypes were identified among 1296 successfully amplified sequences, with the CRF07_BC subtype prevailing at a rate of 91.7%, followed by CRF08_BC. Overall, the CRF07_BC and CRF08_BC subtypes were similar in the distribution and frequency of DRMs, the most common DRMs were K103N and M184V. However, among patients with ART duration of ≥3 years who developed resistance, CRF08_BC exhibited a higher mutation frequency at sites 184, 138, 221, and 188 (Chi-square test, p<0.05), and compared with CRF07_BC, patients with CRF08_BC had higher prevalence of abacavir, emtricitabine, lamivudine, doravirine, etravirine, and rilpivirine resistance. Moreover, there was an increased prevalence of cross-resistance between efavirenz/nevirapine and new generation NNRTIs in patients with CRF08_BC; doravirine (r=1.0), rilpivirine (r=0.93), and etravirine (r=0.86) resistance highly correlated with efavirenz/nevirapine. CONCLUSIONS: The present study provides valuable insights into the profile of DRMs and resistance patterns in patients with CRF07_BC and CRF08_BC experiencing treatment failure in Butuo. These findings have the potential to contribute to future strategies for HIV control and treatment.

Virtual reality-based simulation learning on geriatric oral health care for nursing students: a pilot study.

BACKGROUND: There is a great need for training and education in the nursing curriculum to improve nurses' knowledge and skills to provide oral health care. METHODS: A pilot study was conducted to evaluate the use of a virtual reality (VR)-based Oral Health Care Learning System to train geriatric oral health care among nursing students. Fifty undergraduate nursing students were randomly assigned to experimental (n = 25) and control (n = 25) groups. The experimental group received the VR-based simulation training on geriatric oral health care and the training was implemented twice at two weeks apart from March to November 2021. The control group did not receive the training intervention. Knowledge, attitude, and self-efficacy of geriatric oral health care as well as the intention to assist oral health care for older adults were assessed at the beginning, second, and fourth weeks. Generalized estimating equations were used to analyze the effectiveness of the VR-based simulation training. RESULTS: After the first round of training, students in the experimental group had significantly greater improvements in knowledge and self-efficacy of geriatric oral health care than in the control group. After the second round of training, students in the experimental group had significantly greater improvements in knowledge, attitude, and self-efficacy of geriatric oral health care as well as the intention to assist oral health care for older adult than in the control group. CONCLUSIONS: The VR-based simulation training was effective to improve undergraduate nursing students' knowledge, attitudes and self-efficacy of geriatric oral health as well as the intention to assist oral health care for older adults. The VR-based simulation learning system is an effective tool to provide practice experiences to build confidence and skills and to bridge the gap of understudied geriatric oral health content in entry-level nursing curricula. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05248542; registration date 21/02/2022).

A comprehensive bibliometric analysis of global research on the role of acrolein in Alzheimer's disease pathogenesis: involvement of amyloid-beta.

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive and behavioral decline. Acrolein, an environmental pollutant and endogenous compound, is implicated in AD development. This research employs bibliometric analysis to assess current trends and key areas concerning acrolein-AD interaction. Methods: The Web of Science was used to extensively review literature on acrolein and AD. Relevant data were systematically gathered and analyzed using VOSviewer, CiteSpace, and an online bibliometric tool. Results: We identified 120 English publications in this specialized field across 19 journals. The Journal of Alzheimer's Disease was the most prominent. The primary contributors, both in terms of scientific output and influence, were the USA, the University of Kentucky, and Ramassamy C, representing countries/regions, institutions, and authors, respectively. In this field, the primary focus was on thoroughly studying acrolein, its roles, and its mechanisms in AD utilizing both in vivo and in vitro approaches. A significant portion of the research was based on proteomics, revealing complex molecular processes. The main focuses in the field were "oxidative stress," "lipid peroxidation," "amyloid-beta," and "cognitive impairment." Anticipated future research trajectories focus on the involvement of the internalization pathway, covering key areas such as synaptic dysfunction, metabolism, mechanisms, associations, neuroinflammation, inhibitors, tau phosphorylation, acrolein toxicity, brain infarction, antioxidants, chemistry, drug delivery, and dementia. Our analysis also supported our previous hypothesis that acrolein can interact with amyloid-beta to form a protein adduct leading to AD-like pathology and altering natural immune responses. Conclusion: This study provides a broad and all-encompassing view of the topic, offering valuable insights and guidance to fellow researchers. These emerging directions underscore the continuous exploration of the complexities associated with AD. The analyses and findings aim to enhance our understanding of the intricate relationship between acrolein and AD for future research.

Functional and structural investigation of a broadly neutralizing SARS-CoV-2 antibody.

Since its emergence, SARS-CoV-2 has been continuously evolving, hampering the effectiveness of current vaccines against COVID-19. mAbs can be used to treat patients at risk of severe COVID-19. Thus, the development of broadly protective mAbs and an understanding of the underlying protective mechanisms are of great importance. Here, we isolated mAbs from donors with breakthrough infection with Omicron subvariants using a single-B cell screening platform. We identified a mAb, O5C2, which possesses broad-spectrum neutralization and antibody-dependent cell-mediated cytotoxic activities against SARS-CoV-2 variants, including EG.5.1. Single-particle analysis by cryo-electron microscopy revealed that O5C2 targeted an unusually large epitope within the receptor-binding domain of spike protein that overlapped with the angiotensin-converting enzyme 2 binding interface. Furthermore, O5C2 effectively protected against BA.5 Omicron infection in vivo by mediating changes in transcriptomes enriched in genes involved in apoptosis and interferon responses. Our findings provide insights into the development of pan-protective mAbs against SARS-CoV-2.

Transcriptome and metabolome analysis reveal key genes and metabolic pathway responses in Leersia hexandra Swartz under Cr and Ni co-stress.

Phytoremediation, an eco-friendly approach for mitigating heavy metal contamination, is reliant on hyperaccumulators. This study focused on Leersia hexandra Swart, a known chromium (Cr) hyperaccumulator with demonstrated tolerance to multiple heavy metals. Our objective was to investigate its response to simultaneous Cr and nickel (Ni) stress over 12 days. Results from physiological experiments demonstrated a significant increase in the activities of antioxidant enzymes (APX, SOD, CAT) and glutathione (GSH) content under Cr and Ni stress, indicating enhanced antioxidant mechanisms. Transcriptome analysis revealed that stress resulted in the differential expression of 27 genes associated with antioxidant activity and metal binding, including APX, SOD, CAT, GSH, metallothionein (MT), and nicotinamide (NA). Among them, twenty differentially expressed genes (DEGs) related to GSH metabolic cycle were identified. Notably, GSTU6, GND1, and PGD were the top three related genes, showing upregulation with fold changes of 4.57, 6.07, and 3.76, respectively, indicating their crucial role in metal tolerance. The expression of selected DEGs was validated by quantitative real-time PCR, confirming the reliability of RNA-Seq data. Metabolomic analysis revealed changes in 1121 metabolites, with amino acids, flavonoids, and carbohydrates being the most affected. Furthermore, glucosinolate biosynthesis and amino acid biosynthesis pathways were represented in the KEGG pathway of differentially expressed metabolites (DEMs). This study provides insights into the tolerance mechanisms of L. hexandra under the co-stress of Cr and Ni, offering a new perspective for enhancing its remediation performance.

Multiple instance learning for eosinophil quantification of sinonasal histopathology images: A hierarchical determination on whole slide images.

KEY POINTS: We proposed a hierarchical framework including an unsupervised candidate image selection and a weakly supervised patch image detection based on multiple instance learning (MIL) to effectively estimate eosinophil quantities in tissue samples from whole slide images. MIL is an innovative approach that can help deal with the variability in cell distribution detection and enable automated eosinophil quantification from sinonasal histopathological images with a high degree of accuracy. The study lays the foundation for further research and development in the field of automated histopathological image analysis, and validation on more extensive and diverse datasets will contribute to real-world application.

Hyperglycemia facilitates EV71 replication: Insights into miR-206-mediated regulation of G3BP2 promoting EV71 IRES activity.

Background: Neurotropic virus infections actively manipulate host cell metabolism to enhance virus neurovirulence. Although hyperglycemia is common during severe infections, its specific role remains unclear. This study investigates the impact of hyperglycemia on the neurovirulence of enterovirus 71 (EV71), a neurovirulent virus relying on internal ribosome entry site (IRES)-mediated translation for replication. Methods: Utilizing hSCARB2-transgenic mice, we explore the effects of hyperglycemia in EV71 infection and elucidate the underlying mechanisms. Results: Remarkably, administering insulin alone to reduce hyperglycemia in hSCARB2-transgenic mice results in a decrease in brainstem encephalitis and viral load. Conversely, induced hyperglycemia exacerbates neuropathogenesis, highlighting the pivotal role of hyperglycemia in neurovirulence. Notably, miR-206 emerges as a crucial mediator induced by viral infection, with its expression further heightened by hyperglycemia and concurrently repressed by insulin. The use of antagomiR-206 effectively mitigates EV71-induced brainstem encephalitis and reduces viral load. Mechanistically, miR-206 facilitates IRES-driven virus replication by repressing the stress granule protein G3BP2. Conclusions: Novel therapeutic approaches against severe EV71 infections involve managing hyperglycemia and targeting the miR-206-stress granule pathway to modulate virus IRES activity.

Neural representations of perspectival shapes and attentional effects: Evidence from fMRI and MEG.

Does the human brain represent perspectival shapes, i.e., viewpoint-dependent object shapes, especially in relatively higher-level visual areas such as the lateral occipital cortex? What is the temporal profile of the appearance and disappearance of neural representations of perspectival shapes? And how does attention influence these neural representations? To answer these questions, we employed functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and multivariate decoding techniques to investigate spatiotemporal neural representations of perspectival shapes. Participants viewed rotated objects along with the corresponding objective shapes and perspectival shapes (i.e., rotated round, round, and oval) while we measured their brain activities. Our results revealed that shape classifiers trained on the basic shapes (i.e., round and oval) consistently identified neural representations in the lateral occipital cortex corresponding to the perspectival shapes of the viewed objects regardless of attentional manipulations. Additionally, this classification tendency toward the perspectival shapes emerged approximately 200 ms after stimulus presentation. Moreover, attention influenced the spatial dimension as the regions showing the perspectival shape classification tendency propagated from the occipital lobe to the temporal lobe. As for the temporal dimension, attention led to a more robust and enduring classification tendency towards perspectival shapes. In summary, our study outlines a spatiotemporal neural profile for perspectival shapes that suggests a greater degree of perspectival representation than is often acknowledged.

The multifaceted role of autophagy in skin autoimmune disorders: a guardian or culprit?

Autophagy is a cellular process that functions to maintain intracellular homeostasis via the degradation and recycling of defective organelles or damaged proteins. This dynamic mechanism participates in various biological processes, such as the regulation of cellular differentiation, proliferation, survival, and the modulation of inflammation and immune responses. Recent evidence has demonstrated the involvement of polymorphisms in autophagy-related genes in various skin autoimmune diseases. In addition, autophagy, along with autophagy-related proteins, also contributes to homeostasis maintenance and immune regulation in the skin, which is associated with skin autoimmune disorders. This review aims to provide an overview of the multifaceted role of autophagy in skin autoimmune diseases and shed light on the potential of autophagy-targeting therapeutic strategies in dermatology.

Different Detection Strategies of Pediocin-Like Produced by Pediococcus pentosaceus.

In this study, Pediococcus pentosaceus C-2-1 and C23221 contained genes encoding penocin and pediocin PA-1, mined by antiSMASH. The penocin structural gene pedA from Pediococcus pentosaceus C-2-1 was successfully expressed in Escherichia coli BL21. The presence of a 6.5 kDa recombinant penocin was confirmed by Tricine-SDS-PAGE, and the specific activity increased by 1.54-fold. The bacteriocins produced by Pediococcus pentosaceus C23221 were purified using acetic ether extraction, Sepharose Fast Flow, Sephadex G-25 gel chromatography, and reversed-phase high-performance liquid chromatography (RP-HPLC); the amino acid sequence of this bacteriocin was identical to pediocin PA-1 by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), which confirmed the expression of pediocin PA-1 gene; and the specific activity increased by 24.39-fold. The heterologous expression and purification of bacteriocins have proved the expression of pediocin-like produced by Pediococcus pentosaceus. This provides a theoretical basis for the subsequent development and application of pediocin-like.

Release of lead, copper, zinc from the initial corrosion of brass water meter in drinking water: Influences of solution composition and electrochemical characterization.

Corrosion of brass plumbing materials may lead to metal release and deteriorate the drinking water quality. In this study, the initial corrosion of brass coupon cut from commercially available water meter was investigated. High rates of Pb, Cu and Zn release from the brass coupon were found during the early stage of corrosion (0-5 d) due to general corrosion and galvanic corrosion. The corrosion current density (Icorr) increased and resistance (RF) decreased during this period indicating that severe corrosion had occurred. In a later stage (5-30 d), a decreased Icorr and an increased RF were observed due to the development of a denser layer of Pb and Cu corrosion products which regulated the release of soluble Pb and Cu. The release of Zn continued and no significant Zn precipitation was found. Overall, particulate Pb, particulate Cu and soluble Zn dominated in the metal release during the initial corrosion of brass. The release of Pb, Cu and Zn was enhanced by a lower pH. Free chlorine was found to slightly reduce the release of Pb but promote the release of Cu and Zn. The presence of Pb on the brass surfaces was found to alleviate the dezincification process. A conceptual model based on metal release profile and electrochemical characterization was proposed to describe the initial corrosion of brass in typical drinking water.

Dextran-40 Reduces Partial Flap Failure: A Systematic Review and Meta-analysis for Antithrombotics after Free Flaps.

Background: Antithrombotic agents are used after free-flap surgery to prevent thrombus formation and improve flap outcomes. However, the reports vary. Therefore, this meta-analysis aimed to elucidate the need for antithrombotic agents in this context. Methods: We searched for studies that compared the outcomes of patients undergoing free-flap surgery with or without postoperative antithrombotic agents in the PubMed, Cochrane, and ClinicalTrials.gov databases. The primary outcome was total flap failure, with secondary outcomes including partial flap failure, pedicle thrombosis, and bleeding/hematoma. The relative risks (RRs) of outcomes with or without antithrombotic use were evaluated. Results: Fifteen studies (n = 6755 cases) were included. Antithrombotic agents did not reduce flap failure or pedicle thrombosis risks but increased bleeding and hematoma risks (RR, 1.535). Subgroup analyses by antiplatelet and anticoagulant use demonstrated results similar to those of antithrombotic use. The RR of bleeding/hematoma was 1.761 and 2.740 in the antiplatelet and anticoagulant groups, respectively. Postoperative dextran-40 administration reduced the risk of partial flap failure, with an RR of 0.535. Conclusions: Postoperative antithrombotic, antiplatelet, or anticoagulant use did not change the risk of total/partial flap failure or pedicle thrombosis but increased the risk of hematoma/bleeding. Postoperative use of dextran-40 reduced the risk of partial flap failure. Increased intraflap blood flow may decrease the risk of partial flap failure. However, dextran-40 may cause severe pulmonary distress. Further prospective studies are required to evaluate the effects of these agents on thrombus formation, intraflap blood flow, and partial flap failure risk.

Correction: REM-related obstructive sleep apnea and vertigo: A retrospective case-control study.

[This corrects the article DOI: 10.1371/journal.pone.0252844.].

Ultrafast creation of a light-induced semimetallic state in strongly excited 1T-TiSe2.

Screening, a ubiquitous phenomenon associated with the shielding of electric fields by surrounding charges, has been widely adopted as a means to modify a material's properties. While most studies have relied on static changes of screening through doping or gating thus far, here we demonstrate that screening can also drive the onset of distinct quantum states on the ultrafast timescale. By using time- and angle-resolved photoemission spectroscopy, we show that intense optical excitation can drive 1T-TiSe2, a prototypical charge density wave material, almost instantly from a gapped into a semimetallic state. By systematically comparing changes in band structure over time and excitation strength with theoretical calculations, we find that the appearance of this state is likely caused by a dramatic reduction of the screening length. In summary, this work showcases how optical excitation enables the screening-driven design of a nonequilibrium semimetallic phase in TiSe2, possibly providing a general pathway into highly screened phases in other strongly correlated materials.