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1.
Nature ; 605(7908): 41-45, 2022 05.
Article in English | MEDLINE | ID: mdl-35508781

ABSTRACT

Over a dozen millisecond pulsars are ablating low-mass companions in close binary systems. In the original 'black widow', the eight-hour orbital period eclipsing pulsar PSR J1959+2048 (PSR B1957+20)1, high-energy emission originating from the pulsar2 is irradiating and may eventually destroy3 a low-mass companion. These systems are not only physical laboratories that reveal the interesting results of exposing a close companion star to the relativistic energy output of a pulsar, but are also believed to harbour some of the most massive neutron stars4, allowing for robust tests of the neutron star equation of state. Here we report observations of ZTF J1406+1222, a wide hierarchical triple hosting a 62-minute orbital period black widow candidate, the optical flux of which varies by a factor of more than ten. ZTF J1406+1222 pushes the boundaries of evolutionary models5, falling below the 80-minute minimum orbital period of hydrogen-rich systems. The wide tertiary companion is a rare low-metallicity cool subdwarf star, and the system has a Galactic halo orbit consistent with passing near the Galactic Centre, making it a probe of formation channels, neutron star kick physics6 and binary evolution.

2.
Nature ; 612(7940): 430-434, 2022 12.
Article in English | MEDLINE | ID: mdl-36450988

ABSTRACT

Tidal disruption events (TDEs) are bursts of electromagnetic energy that are released when supermassive black holes at the centres of galaxies violently disrupt a star that passes too close1. TDEs provide a window through which to study accretion onto supermassive black holes; in some rare cases, this accretion leads to launching of a relativistic jet2-9, but the necessary conditions are not fully understood. The best-studied jetted TDE so far is Swift J1644+57, which was discovered in γ-rays, but was too obscured by dust to be seen at optical wavelengths. Here we report the optical detection of AT2022cmc, a rapidly fading source at cosmological distance (redshift z = 1.19325) the unique light curve of which transitioned into a luminous plateau within days. Observations of a bright counterpart at other wavelengths, including X-ray, submillimetre and radio, supports the interpretation of AT2022cmc as a jetted TDE containing a synchrotron 'afterglow', probably launched by a supermassive black hole with spin greater than approximately 0.3. Using four years of Zwicky Transient Facility10 survey data, we calculate a rate of [Formula: see text] per gigapascals cubed per year for on-axis jetted TDEs on the basis of the luminous, fast-fading red component, thus providing a measurement complementary to the rates derived from X-ray and radio observations11. Correcting for the beaming angle effects, this rate confirms that approximately 1 per cent of TDEs have relativistic jets. Optical surveys can use AT2022cmc as a prototype to unveil a population of jetted TDEs.

3.
Proc Natl Acad Sci U S A ; 120(33): e2305704120, 2023 08 15.
Article in English | MEDLINE | ID: mdl-37549277

ABSTRACT

Biocompatible and morphable hydrogels capable of multimode reprogrammable, and adaptive shape changes are potentially useful for diverse biomedical applications. However, existing morphable systems often rely on complicated structural designs involving cumbersome and energy-intensive fabrication processes. Here, we report a simple electric-field-activated protein network migration strategy to reversibly program silk-protein hydrogels with controllable and reprogrammable complex shape transformations. The application of a low electric field enables the convergence of net negatively charged protein cross-linking networks toward the anode (isoelectric point plane) due to the pH gradient generated in the process, facilitating the formation of a gradient network structure and systems suitable for three-dimensional shape change. These tunable protein networks can be reprogrammed or permanently fixed by control of the polymorphic transitions. We show that these morphing hydrogels are capable of conformally interfacing with biological tissues by programming the shape changes and a bimorph structure consisting of aligned carbon nanotube multilayers and the silk hydrogels was assembled to illustrate utility as an implantable bioelectronic device for localized low-voltage electrical stimulation of the sciatic nerve in a rabbit.


Subject(s)
Hydrogels , Silk , Animals , Rabbits , Silk/chemistry , Hydrogels/chemistry , Isoelectric Point , Biocompatible Materials/chemistry
4.
Hepatology ; 79(4): 844-856, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-37625139

ABSTRACT

BACKGROUND AND AIMS: Although refractory hepatic hydrothorax (RH) is a serious complication of cirrhosis, waitlisted patients do not receive standardized Model for End-stage Liver Disease (MELD) exemption because of inadequate evidence suggesting mortality above biochemical MELD. This study aimed to examine liver-related death (LRD) associated with RH compared to refractory ascites (RA). APPROACH AND RESULTS: This was a retrospective cohort study of Veterans with cirrhosis. Eligibility criteria included participants with RH or RA, followed from their first therapeutic thoracentesis/second paracentesis until death or transplantation. The primary outcome was LRD with non-LRD or transplantation as competing risk. Of 2552 patients with cirrhosis who underwent therapeutic thoracentesis/paracentesis, 177 met criteria for RH and 422 for RA. RH was associated with a significantly higher risk of LRD (adjusted HR [aHR] 4.63, 95% CI 3.31-6.48) than RA overall and within all MELD-sodium (MELD-Na) strata (<10 aHR 4.08, 95% CI 2.30-7.24, 10-14.9 aHR 5.68, 95% CI 2.63-12.28, 15-24.9 aHR 4.14, 95% CI 2.34-7.34, ≥25 aHR 7.75, 95% CI 2.99-20.12). LRD was higher among participants requiring 1 (aHR 3.54, 95% CI 2.29-5.48), 2-3 (aHR 4.39, 95% CI 2.91-6.63), and ≥4 (aHR 7.89, 95% CI 4.82-12.93) thoracenteses relative to RA. Although participants with RH and RA had similar baseline MELD-Na, LRD occurred in RH versus RA at a lower MELD-Na (16.5 vs. 21.82, p =0.002) but higher MELD 3.0 (27.85 vs. 22.48, p <0.0001). CONCLUSIONS: RH was associated with higher risk of LRD than RA at equivalent MELD-Na. By contrast, MELD 3.0 may better predict risk of LRD in RH.


Subject(s)
End Stage Liver Disease , Hydrothorax , Humans , Hydrothorax/etiology , End Stage Liver Disease/complications , Ascites/etiology , Retrospective Studies , Severity of Illness Index , Liver Cirrhosis/complications , Sodium
5.
Chem Rev ; 123(5): 2242-2275, 2023 Mar 08.
Article in English | MEDLINE | ID: mdl-36603542

ABSTRACT

Engineered materials are ubiquitous throughout society and are critical to the development of modern technology, yet many current material systems are inexorably tied to widespread deterioration of ecological processes. Next-generation material systems can address goals of environmental sustainability by providing alternatives to fossil fuel-based materials and by reducing destructive extraction processes, energy costs, and accumulation of solid waste. However, development of sustainable materials faces several key challenges including investigation, processing, and architecting of new feedstocks that are often relatively mechanically weak, complex, and difficult to characterize or standardize. In this review paper, we outline a framework for examining sustainability in material systems and discuss how recent developments in modeling, machine learning, and other computational tools can aid the discovery of novel sustainable materials. We consider these through the lens of materiomics, an approach that considers material systems holistically by incorporating perspectives of all relevant scales, beginning with first-principles approaches and extending through the macroscale to consider sustainable material design from the bottom-up. We follow with an examination of how computational methods are currently applied to select examples of sustainable material development, with particular emphasis on bioinspired and biobased materials, and conclude with perspectives on opportunities and open challenges.

6.
Nature ; 571(7766): 528-531, 2019 07.
Article in English | MEDLINE | ID: mdl-31341301

ABSTRACT

General relativity1 predicts that short-orbital-period binaries emit considerable amounts of gravitational radiation. The upcoming Laser Interferometer Space Antenna2 (LISA) is expected to detect tens of thousands of such systems3 but few have been identified4, of which only one5 is eclipsing-the double-white-dwarf binary SDSS J065133.338+284423.37, which has an orbital period of 12.75 minutes. Here we report the discovery of an eclipsing double-white-dwarf binary system, ZTF J153932.16+502738.8, with an orbital period of 6.91 minutes. This system has an orbit so compact that the entire binary could fit within the diameter of the planet Saturn. The system exhibits a deep eclipse, and a double-lined spectroscopic nature. We see rapid orbital decay, consistent with that expected from general relativity. ZTF J153932.16+502738.8 is a strong source of gravitational radiation close to the peak of LISA's sensitivity, and we expect it to be detected within the first week of LISA observations, once LISA launches in approximately 2034.

7.
Proc Natl Acad Sci U S A ; 119(40): e2209524119, 2022 10 04.
Article in English | MEDLINE | ID: mdl-36161946

ABSTRACT

Collagen is the most abundant structural protein in humans, providing crucial mechanical properties, including high strength and toughness, in tissues. Collagen-based biomaterials are, therefore, used for tissue repair and regeneration. Utilizing collagen effectively during materials processing ex vivo and subsequent function in vivo requires stability over wide temperature ranges to avoid denaturation and loss of structure, measured as melting temperature (Tm). Although significant research has been conducted on understanding how collagen primary amino acid sequences correspond to Tm values, a robust framework to facilitate the design of collagen sequences with specific Tm remains a challenge. Here, we develop a general model using a genetic algorithm within a deep learning framework to design collagen sequences with specific Tm values. We report 1,000 de novo collagen sequences, and we show that we can efficiently use this model to generate collagen sequences and verify their Tm values using both experimental and computational methods. We find that the model accurately predicts Tm values within a few degrees centigrade. Further, using this model, we conduct a high-throughput study to identify the most frequently occurring collagen triplets that can be directly incorporated into collagen. We further discovered that the number of hydrogen bonds within collagen calculated with molecular dynamics (MD) is directly correlated to the experimental measurement of triple-helical quality. Ultimately, we see this work as a critical step to helping researchers develop collagen sequences with specific Tm values for intended materials manufacturing methods and biomedical applications, realizing a mechanistic materials by design paradigm.


Subject(s)
Deep Learning , Amino Acid Sequence , Biocompatible Materials , Collagen/chemistry , Humans , Molecular Dynamics Simulation
8.
Proc Natl Acad Sci U S A ; 119(4)2022 01 25.
Article in English | MEDLINE | ID: mdl-35074913

ABSTRACT

The exceptional elastic resilience of some protein materials underlies essential biomechanical functions with broad interest in biomedical fields. However, molecular design of elastic resilience is restricted to amino acid sequences of a handful of naturally occurring resilient proteins such as resilin and elastin. Here, we exploit non-resilin/elastin sequences that adopt kinetically stabilized, random coil-dominated conformations to achieve near-perfect resilience comparable with that of resilin and elastin. We also show a direct correlation between resilience and Raman-characterized protein conformations. Furthermore, we demonstrate that metastable conformation of proteins enables the construction of mechanically graded protein materials that exhibit spatially controlled conformations and resilience. These results offer insights into molecular mechanisms of protein elastomers and outline a general conformation-driven strategy for developing resilient and functional protein materials.


Subject(s)
Models, Molecular , Protein Conformation , Proteins/chemistry , Amino Acid Sequence , Fibroins/chemistry , Spectrum Analysis , Structure-Activity Relationship
9.
Proc Natl Acad Sci U S A ; 119(4)2022 01 25.
Article in English | MEDLINE | ID: mdl-35058364

ABSTRACT

While there have been recent improvements in reducing bycatch in many fisheries, bycatch remains a threat for numerous species around the globe. Static spatial and temporal closures are used in many places as a tool to reduce bycatch. However, their effectiveness in achieving this goal is uncertain, particularly for highly mobile species. We evaluated evidence for the effects of temporal, static, and dynamic area closures on the bycatch and target catch of 15 fisheries around the world. Assuming perfect knowledge of where the catch and bycatch occurs and a closure of 30% of the fishing area, we found that dynamic area closures could reduce bycatch by an average of 57% without sacrificing catch of target species, compared to 16% reductions in bycatch achievable by static closures. The degree of bycatch reduction achievable for a certain quantity of target catch was related to the correlation in space and time between target and bycatch species. If the correlation was high, it was harder to find an area to reduce bycatch without sacrificing catch of target species. If the goal of spatial closures is to reduce bycatch, our results suggest that dynamic management provides substantially better outcomes than classic static marine area closures. The use of dynamic ocean management might be difficult to implement and enforce in many regions. Nevertheless, dynamic approaches will be increasingly valuable as climate change drives species and fisheries into new habitats or extended ranges, altering species-fishery interactions and underscoring the need for more responsive and flexible regulatory mechanisms.


Subject(s)
Fisheries , Conservation of Natural Resources , Ecosystem , Oceanography
10.
Article in English | MEDLINE | ID: mdl-38906442

ABSTRACT

BACKGROUND AND AIMS: Cirrhosis patients are at increased risk for postoperative complications. It remains unclear whether preoperative nonsurgical clinician visits improve postoperative outcomes. We assessed the impact of preoperative primary care physician (PCP) and/or Gastroenterologist/Hepatologist (GI/Hep) visits on postoperative mortality in cirrhosis patients undergoing surgery and explored differences in medication changes and paracentesis rates as potential mediators. METHODS: This was a retrospective cohort study of cirrhosis patients in the Veterans Health Administration who underwent surgery between 2008 and 2016. We compared 1982 patients with preoperative PCP and/or GI/Hep visits with 1846 propensity matched patients without preoperative visits. We used Cox regression and Fine and Gray competing risk regression to evaluate the association between preoperative visit type and postoperative mortality at 6 months. RESULTS: Patients with preoperative GI/Hep and PCP visits had a 45% lower hazard of postoperative mortality compared to those without preoperative visits (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.35-0.87). A smaller effect size was noted with GI/Hep preoperative visit alone (HR, 0.69; 95% CI, 0.48-0.99) or PCP visit alone (HR, 0.70; 95% CI, 0.53-0.93). Patients with preoperative PCP/GI/Hep visits were more likely to have diuretics, spontaneous bacterial peritonitis prophylaxis, and hepatic encephalopathy medications newly initiated and/or dose adjusted and more likely to receive preoperative paracentesis as compared to those without preoperative visits. CONCLUSION: Preoperative PCP/GI/Hep visits are associated with a reduced risk of postoperative mortality with the greatest risk reduction observed in those with both PCP and GI/Hep visits. This synergistic effect highlights the importance of a multidisciplinary approach in the preoperative care of cirrhosis patients.

11.
Clin Gastroenterol Hepatol ; 22(4): 778-788.e7, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38061410

ABSTRACT

BACKGROUND & AIMS: Patients with cirrhosis secondary to chronic hepatitis C virus (HCV) are at risk for hepatocellular carcinoma (HCC) despite a sustained virological response (SVR). We examined whether post-SVR liver stiffness measurement (LSM) could be used to stratify HCC risk. METHODS: This was a retrospective cohort study of 1850 participants identified from the Veterans Health Administration, with HCV cirrhosis and SVR, followed up over 5099 person-years, from the time of post-SVR elastography until death, HCC, or the end of the study. RESULTS: The risk of HCC increased by 3% with every 1-kPa increase in LSM (adjusted hazard ratio [aHR], 1.03, 95% confidence interval [CI], 1.01-1.04; P < .001) and decreased with the number of years from SVR (aHR, 0.79; 95% CI, 0.70-0.90; P = .0003). The adjusted annual risk of HCC was 2.03% among participants with post-SVR LSM <10 kPa, 2.48% in LSM 10-14.9 kPa (aHR, 1.71; 95% CI, 1.01-2.88; P = .046), 3.22% for LSM 15-19.9 kPa (aHR, 1.59; 95% CI, 0.78-3.20; P = .20), 5.07% among LSM 20-24.9 kPa (aHR, 2.55; 95% CI, 1.30-5.01; P = .01), and 5.44% in LSM ≥25 kPa (aHR, 3.03; 95% CI, 1.74-5.26; P < .0001). The adjusted annual risk of HCC was < 0.4% in participants with LSM <5 kPa and without diabetes mellitus. CONCLUSIONS: LSM predicts rates of HCC in patients with HCV cirrhosis after SVR at multiple cutoff levels and offers a single test to predict portal hypertension-related complications and HCC. Patients with LSM <5 kPa in the absence of diabetes mellitus had a low risk of HCC in which surveillance could be discontinued.


Subject(s)
Carcinoma, Hepatocellular , Diabetes Mellitus , Elasticity Imaging Techniques , Hepatitis C, Chronic , Liver Neoplasms , Veterans , Humans , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/etiology , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Liver Neoplasms/epidemiology , Liver Neoplasms/etiology , Retrospective Studies , Antiviral Agents/therapeutic use , Liver Cirrhosis/complications , Liver Cirrhosis/drug therapy , Sustained Virologic Response
12.
Am J Gastroenterol ; 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38534167

ABSTRACT

BACKGROUND: Weight loss is the mainstay of management for patients with metabolic dysfunction-associated steatotic liver disease. We studied the impact of referral to MOVE!, a nationally-implemented behavioral weight loss program, on weight in MASLD patients. METHODS: This retrospective cohort study included 102,294 MASLD patients from 125 Veterans Health Administration centers from 2008-2022. RESULTS: Most patients lost no significant weight or gained weight. Increased engagement with MOVE! was associated with greater hazard of significant weight loss compared to no engagement. CONCLUSION: A minority of patients experienced significant weight loss through 5 years using lifestyle interventions alone.

13.
Am J Gastroenterol ; 119(2): 297-305, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37782293

ABSTRACT

INTRODUCTION: Homelessness adversely affects patient outcomes in broad cohort studies; however, its impact on key liver-related outcomes in patients with cirrhosis is understudied. We aimed to address this knowledge gap using data from the Veterans Health Administration, a cohort disproportionately affected by homelessness. METHODS: This was a retrospective cohort study of the Veterans Health Administration patients with incident cirrhosis diagnosis between January 2008 and February 2022. Homeless status was classified at baseline and as time-updating variable during follow-up. Inverse probability treatment weighted Cox regression was performed to evaluate the association between homelessness and outcomes of all-cause mortality, cirrhosis decompensation, and hepatocellular carcinoma. RESULTS: A total of 117,698 patients were included in the cohort, of whom 14,243 (12.1%) were homeless at baseline. In inverse probability treatment weighted Cox regression, homelessness was associated with a 24% higher hazard of all-cause mortality (hazard ratio [HR] 1.24, 95% confidence interval [CI] 1.22-1.26, P < 0.001). However, in competing risk regression models, homelessness was associated with a reduced subhazard of decompensation (subhazard ratio 0.86, 95% CI 0.84-0.88, P < 0.001) and hepatocellular carcinoma (subhazard ratio 0.86, 95% CI 0.83-0.89, P < 0.001). In cause-specific mortality analysis, homeless patients had significantly increased non-liver-related and liver-related mortality; however, the magnitude of effect size was greater for non-liver-related mortality (csHR 1.38, 95% CI 1.35-1.40, P < 0.001). DISCUSSION: Homelessness in veterans with cirrhosis is associated with increased all-cause mortality; however, this is likely mediated primarily through non-liver-related factors. Future studies are needed to explore drivers of mortality and improve mitigation strategies in these patients.


Subject(s)
Carcinoma, Hepatocellular , Ill-Housed Persons , Liver Neoplasms , Veterans , Humans , Carcinoma, Hepatocellular/epidemiology , Retrospective Studies , Liver Cirrhosis/complications , Liver Cirrhosis/epidemiology , Liver Neoplasms/epidemiology
14.
Nat Mater ; 22(1): 18-35, 2023 01.
Article in English | MEDLINE | ID: mdl-36446962

ABSTRACT

Next-generation structural materials are expected to be lightweight, high-strength and tough composites with embedded functionalities to sense, adapt, self-repair, morph and restore. This Review highlights recent developments and concepts in bioinspired nanocomposites, emphasizing tailoring of the architecture, interphases and confinement to achieve dynamic and synergetic responses. We highlight cornerstone examples from natural materials with unique mechanical property combinations based on relatively simple building blocks produced in aqueous environments under ambient conditions. A particular focus is on structural hierarchies across multiple length scales to achieve multifunctionality and robustness. We further discuss recent advances, trends and emerging opportunities for combining biological and synthetic components, state-of-the-art characterization and modelling approaches to assess the physical principles underlying nature-inspired design and mechanical responses at multiple length scales. These multidisciplinary approaches promote the synergetic enhancement of individual materials properties and an improved predictive and prescriptive design of the next era of structural materials at multilength scales for a wide range of applications.


Subject(s)
Biomimetic Materials , Nanocomposites , Biomimetic Materials/chemistry , Nanocomposites/chemistry , Water/chemistry
15.
Hepatology ; 77(2): 489-500, 2023 02 01.
Article in English | MEDLINE | ID: mdl-35984731

ABSTRACT

BACKGROUND AND AIMS: Little is known about the effectiveness of nonselective beta blockers (NSBBs) in preventing hepatic decompensation in routine clinical settings. We investigated whether NSBBs are associated with hepatic decompensation or liver-related mortality in a national cohort of veterans with Child-Turcotte-Pugh (CTP) A cirrhosis with no prior decompensations. APPROACH AND RESULTS: In an active comparator, new user (ACNU) design, we created a cohort of new users of carvedilol ( n = 123) versus new users of selective beta blockers (SBBs) ( n = 561) and followed patients for up to 3 years. An inverse probability treatment weighting (IPTW) approach balanced demographic and clinical confounders. The primary analysis simulated intention-to-treat ("pseudo-ITT") with IPTW-adjusted Cox models; secondary analyses were pseudo-as-treated, and both were adjusted for baseline and time-updating drug confounders. Subgroup analyses evaluated NSBB effects by HCV viremia status, CTP class, platelet count, alcohol-associated liver disease (ALD) etiology, and age. In pseudo-ITT analyses of carvedilol versus SBBs, carvedilol was associated with a lower hazard of any hepatic decompensation (HR 0.59, 95% CI 0.42-0.83) and the composite outcome of hepatic decompensation/liver-related mortality (HR 0.56, 95% CI 0.41-0.76). Results were similar in pseudo-as-treated analyses (hepatic decompensation: HR 0.55, 95% CI 0.33-0.94; composite outcome: HR 0.62, 95% 0.38-1.01). In subgroup analyses, carvedilol was associated with lower hazard of primary outcomes in the absence of HCV viremia, higher CTP class and platelet count, younger age, and ALD etiology. CONCLUSIONS: There is an ongoing need to noninvasively identify patients who may benefit from NSBBs for the prevention of hepatic decompensation.


Subject(s)
Hepatitis C , Viremia , Humans , Cohort Studies , Carvedilol/therapeutic use , Viremia/complications , Adrenergic beta-Antagonists/therapeutic use , Liver Cirrhosis/complications , Hepatitis C/drug therapy , Retrospective Studies
16.
Hepatology ; 77(1): 186-196, 2023 01 01.
Article in English | MEDLINE | ID: mdl-35712794

ABSTRACT

BACKGROUND AND AIMS: Immunity to SARS-CoV-2 can be infection or vaccine-induced. Cirrhosis is associated with vaccine hyporesponsiveness, but whether there is decreased immunity after SARS-CoV-2 infection in unvaccinated patients with cirrhosis is unknown.The objective of our study was to compare infection-induced and vaccine-induced immunity against COVID-19 among patients with cirrhosis. METHODS: This was a retrospective cohort study among US Veterans with cirrhosis between November 27, 2020, and November 16, 2021, comparing a vaccine-induced immunity group, defined as participants without a documented SARS-CoV-2 infection but fully vaccinated with two doses of an mRNA vaccine, and infection-associated immunity group, defined as unvaccinated participants who had a positive SARS-CoV-2 polymerase chain reaction (PCR). Both groups were propensity score matched for observed characteristics, including location, and the date of the immunity acquiring event, to control for the community prevalence of COVID-19 variants. The outcome was a positive SARS-CoV-2 PCR more than 60 days after previous infection in the infection-induced, or after full vaccination in the vaccine-induced immunity group. RESULTS: We compared 634 participants in the infection-induced immunity group with 27,131 participants in the vaccine-induced immunity group using inverse propensity of treatment weighting. Vaccine-induced immunity was associated with a reduced odds of developing SARS-CoV-2 infection (adjusted hazard ratio [aHR], 0.18; 95% confidence interval [CI], 0.16-0.20, p < 0.0001). On multivariable logistic regression, vaccine-induced immunity was associated with reduced odds of developing symptomatic (adjusted odds ratio [aOR], 0.36; 95% CI, 0.33-0.41, p < 0.0001), moderate/severe/critical (aOR, 0.27; 95% CI, 0.22-0.31, p < 0.0001), and severe or critical COVID-19 (aOR, 0.20; 95% CI, 0.16-0.26, p < 0.001), compared with infection-induced immunity. CONCLUSIONS: In participants with cirrhosis, vaccine-induced immunity is associated with reduced risk of developing COVID-19, compared with infection-induced immunity.


Subject(s)
COVID-19 , Vaccines , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Retrospective Studies , SARS-CoV-2 , Liver Cirrhosis
17.
Eur J Clin Invest ; : e14207, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38558028

ABSTRACT

BACKGROUND: Cytometric analysis has been commonly used to delineate distinct cell subpopulations among peripheral blood mononuclear cells by the differential expression of surface receptors. This capability has reached its apogee with high-dimensional approaches such as mass cytometry and spectral cytometry that include simultaneous assessment of 20-50 analytes. Unfortunately, this approach also engenders significant complexity with analytical and interpretational pitfalls. METHODS: Here, we demonstrate a complementary approach with restricted-dimensionality to assess cell-type specific intracellular molecular expression levels at exceptional levels of precision. The expression of five analytes was individually assessed in four mononuclear cell-types from peripheral blood. RESULTS: Distinctions in expression levels were seen between cell-types and between samples from different donor groups. Mononuclear cell-type specific molecular expression levels distinguished pregnant from nonpregnant women and G-CSF-treated from untreated persons. Additionally, the precision of our analysis was sufficient to quantify a novel relationship between two molecules-Rel A and translocator protein-by correlational analysis. CONCLUSIONS: Restricted-dimensional cytometry can provide a complementary approach to define characteristics of cell-type specific intracellular protein and phosphoantigen expression in mononuclear cells.

18.
Phys Rev Lett ; 132(14): 141603, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38640394

ABSTRACT

I demonstrate how chiral fermions with an exact gauge symmetry can appear on the d-dimensional boundary of a finite volume (d+1)-dimensional manifold, without any light mirror partners. The condition for the d-dimensional boundary theory to be local is that gauge anomalies cancel and that the volume be large. This can likely be achieved on a lattice and provides a new paradigm for the lattice regularization of chiral gauge theories.

19.
Phys Rev Lett ; 132(14): 141604, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38640365

ABSTRACT

The phenomenon of unpaired Weyl fermions appearing on the sole 2n-dimensional boundary of a (2n+1)-dimensional manifold with massive Dirac fermions was recently analyzed in D. B. Kaplan [preceding Letter, Chiral gauge theory at the boundary between topological phases, Phys. Rev. Lett. 132, 141603 (2024).PRLTAO0031-900710.1103/PhysRevLett.132.141603]. In this Letter, we show that similar unpaired Weyl edge states can be seen on a finite lattice. In particular, we consider the discretized Hamiltonian for a Wilson fermion in (2+1) dimensions with a 1+1 dimensional boundary and continuous time. We demonstrate that the low lying boundary spectrum is indeed Weyl-like: it has a linear dispersion relation and definite chirality and circulates in only one direction around the boundary. We comment on how our results are consistent with Nielsen-Ninomiya theorem. This work removes one potential obstacle facing the program outlined in D. B. Kaplan, preceding Letter, for regulating chiral gauge theories.

20.
Phys Rev Lett ; 132(10): 101001, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38518313

ABSTRACT

We propose a novel experimental method for probing light dark matter candidates. We show that an electro-optical material's refractive index is modified in the presence of a coherently oscillating dark matter background. A high-precision resonant Michelson interferometer can be used to read out this signal. The proposed detection scheme allows for the exploration of an uncharted parameter space of dark matter candidates over a wide range of masses-including masses exceeding a few tens of microelectronvolts, which is a challenging parameter space for microwave cavity haloscopes.

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