Rheumatoid Arthritis and Its Implications on Inflammatory Bowel Disease.

Background: The association between inflammatory bowel disease (IBD) and arthritis has long been known, but it was not until the 1950s that IBD-associated arthritis was recognized as a distinct pathology independent from rheumatoid arthritis (RA). There is evidence that RA and other autoimmune conditions exist at higher rates in patients with IBD compared to the general population. We aimed to determine if the presence of RA in IBD patients is a factor for mortality and IBD-related surgery in this population. Methods: Using Epic's Slicer Dicer function, we queried the International Classification of Diseases, 10th Revision (ICD-10) codes K50 and K51 to identify patients with IBD. Duplicates and those with incomplete information were excluded, leaving a total of 3,613 patients. Data collected included basic demographic information, surgical history, and the presence of RA. We used Student's t-test to analyze between group differences for the continuous variables. When it was determined that variances for the comparisons of continuous data were unequal, Welch-Satterthwaite t-test statistics were used. We used the Chi-square test to analyze between group differences for the categorical variables. The Fisher's exact test was employed when any of the expected frequencies was 5 or less. All tests were two-sided with criterion for statistical significance at a P value less than 0.05. All the analyses were done by SAS 9.4 (SAS Institute, Cary, NC). Results: Of the approximately 2.7 million adults in Slicer Dicer, there were 3,613 patients (0.13%) identified with IBD. Patients with ulcerative colitis (UC) accounted for 37% of the total group (n = 1,343) and 2,270 patients (62.8%) had Crohn's disease (CD). From the total, 2,084 were women (57.68%) and 1,529 (42.32%) were men. More than 90% of the patients were white (n = 3,321). The mean age was 53.3 ± 18.5. Eight hundred forty-eight patients (23.47%) had documented RA. Mortality was higher in patients with IBD and RA than those with IBD alone (7.31% vs. 3.98%, P value ≤ 0.0001). Conclusions: IBD patients with RA have higher mortality rates and need for IBD-related surgery than patients with IBD alone.

How have US colorectal cancer mortality trends changed in the past 20 years?

In the last two decades, colorectal cancer (CRC) mortality has been decreasing in the United States. However, the mortality trends for the different subtypes of CRC, including different sides of colon, rectosigmoid, and rectal cancer remain unclear. We analyzed the mortality trends of different subtypes of CRC based on Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research data from 1999 to 2020. We calculated age-adjusted mortality rates (AAMR) per 100,000 individuals and examined the trends over time by estimating the average annual percent change (AAPC) using the Joinpoint Regression Program. Our study shows that the overall CRC rates decreased significantly from 26.42 to 15.98 per 100,000 individuals, with an AAPC of -2.41. However, the AAMR of rectosigmoid cancer increased significantly from 0.82 to 1.08 per 100,000 individuals, with the AAPC of +1.10. Men and Black individuals had the highest AAMRs respectively (23.90 vs. 26.93 per 100,000 individuals). The overall AAMR of CRC decreased for those aged ≥50 years but increased significantly from 1.02 to 1.58 per 100,000 individuals for those aged 15-49 years, with an AAPC of +0.75. Rural populations had a higher AAMR than the urban populations (22.40 vs. 19.60 per 100,000 individuals). Although overall CRC mortality declined, rising trends in young-onset CRC and rectosigmoid cancer warrant attention. Disparities persist in terms of sex, race, and geographic region, and urbanization level, emphasizing the need for targeted public health measures.

Chronic chikungunya disease (CCD): clinical insights, immunopathogenesis, and therapeutic perspectives.

Chikungunya virus, an arthropod-borne pathogen is recognised by the World Health Organization as a top priority Emerging Infectious Disease and is ranked fourth in public health needs according to the Coalition for Epidemic Preparedness Innovations (CEPI). Despite its substantial impact, as evidenced by an annual estimate of 120,274 disability-adjusted life years, our understanding of the chronic aspects of chikungunya disease remains limited. This review focuses on Chronic Chikungunya Disease (CCD), emphasising its clinical manifestations, immunopathogenesis, therapeutic options, and disease burden.

FHL1 promotes chikungunya and o'nyong-nyong virus infection and pathogenesis with implications for alphavirus vaccine design.

Arthritogenic alphaviruses are positive-strand RNA viruses that cause debilitating musculoskeletal diseases affecting millions worldwide. A recent discovery identified the four-and-a-half-LIM domain protein 1 splice variant A (FHL1A) as a crucial host factor interacting with the hypervariable domain (HVD) of chikungunya virus (CHIKV) nonstructural protein 3 (nsP3). Here, we show that acute and chronic chikungunya disease in humans correlates with elevated levels of FHL1. We generated FHL1-/- mice, which when infected with CHIKV or o'nyong-nyong virus (ONNV) displayed reduced arthritis and myositis, fewer immune infiltrates, and reduced proinflammatory cytokine/chemokine outputs, compared to infected wild-type (WT) mice. Interestingly, disease signs were comparable in FHL1-/- and WT mice infected with arthritogenic alphaviruses Ross River virus (RRV) or Mayaro virus (MAYV). This aligns with pull-down assay data, which showed the ability of CHIKV and ONNV nsP3 to interact with FHL1, while RRV and MAYV nsP3s did not. We engineered a CHIKV mutant unable to bind FHL1 (CHIKV-ΔFHL1), which was avirulent in vivo. Following inoculation with CHIKV-ΔFHL1, mice were protected from disease upon challenge with CHIKV and ONNV, and viraemia was significantly reduced in RRV- and MAYV-challenged mice. Targeting FHL1-binding as an approach to vaccine design could lead to breakthroughs in mitigating alphaviral disease.

Pseudo-Progression of Melanoma Treated with Nivolumab/Ipilimumab: A Case Report.

BACKGROUND Melanoma is an aggressive skin cancer that can be difficult to manage. Its treatment has been transformed by immunotherapy. Melanoma cells frequently have mutations that make them vulnerable to attack by the immune system, and this is how immunotherapy can fight this cancer. Immunotherapy with checkpoint inhibitors targets mechanisms that malignant cells use to evade immune system detection, blocking proteins produced by the tumor, and allowing the immune system to identify and attack cancerous cells. CASE REPORT A 74-year-old woman presented with a lump on the right side of her chest. Tests revealed a metastatic malignant tumor with melanocytic differentiation. Stage IV melanoma was diagnosed, and the patient started therapy with nivolumab/ipilimumab for palliative intent, which she tolerated without adverse effects. However, she was hospitalized for Clostridioides difficile colitis after 3 treatment cycles, and computed tomography (CT) scan findings suggested disease progression. Positron emission tomography (PET)-CT obtained after her discharge from the hospital showed a complete metabolic response at all disease sites, indicating the initial progression was most likely a pseudo-progression from the use of immunotherapy. The patient continued with nivolumab as a single agent and has been doing well. CONCLUSIONS This case highlights the importance of careful evaluation of immunotherapy response in patients with melanoma. The initial progression noted in this patient was most likely pseudo-progression, which resolved with further immunotherapy. Clinicians should consider PET-CT imaging in cases of suspected pseudo-progression to avoid unnecessary changes in therapy. Patient response to immunotherapy demonstrates the effectiveness of immunotherapy in treating advanced melanoma.

Association of Elevated Glycated Hemoglobin (HbA1c) in COVID-19 Patients Admitted to the Intensive Care Unit and Their Clinical Outcomes.

Aim The study aimed to collect retrospective data to investigate the association between elevated glycated hemoglobin (HbA1c) levels and clinical outcomes in COVID-19 patients admitted to the ICU, including in-hospital mortality and 90-day mortality.  Methods This is an observational retrospective study using electronic health records of patients with diabetes admitted to the ICU with COVID-19 across the University of Pittsburgh Medical Center (UPMC) in Central PA Hospitals. Our retrospective analysis was performed on patients admitted to the ICU between May 1st, 2021, to May 1st, 2022. The HbA1c level obtained within three months before their admission was evaluated and stratified to show their association with clinical outcomes, including in-hospital mortality and 90-day mortality. Additionally, the need for insulin drip and ICU and hospital length of stay were compared among these patients.  Results We analyzed 384 patients, which were distributed in three groups. The majority of the patients (183 patients or 47.66%) had an HbA1c below 7%, 113 patients (29.43%) had an HbA1c between 7-9%, and 88 patients (22.92%) had an HbA1c above 9%. The group with an HbA1c<7% had a mortality rate of 54.1% during the hospital stay, with a median stay of 13 days. The patients with an HbA1c between 7-9% had a higher mortality rate of 65.49% with a median stay of 12 days. The patients with HbA1c>9% had a mortality rate of 43.18% with a median stay of 11.5 days.  Conclusion This retrospective study found that there was no linear association between higher HbA1c levels and a higher risk of mortality during hospitalization. The 90-day mortality rate was not statistically different among the three HbA1c groups. The need for insulin drip was higher in patients with higher HbA1c levels. The majority of patients in all three groups were classified as low-risk based on their BMI, and there were no significant differences in the distribution of patients across BMI categories in the HbA1c groups.

N-Heteroacenes as an Organic Gain Medium for Room-Temperature Masers.

The development of future quantum devices such as the maser, i.e., the microwave analog of the laser, could be well-served by the exploration of chemically tunable organic materials. Current iterations of room-temperature organic solid-state masers are composed of an inert host material that is doped with a spin-active molecule. In this work, we systematically modulated the structure of three nitrogen-substituted tetracene derivatives to augment their photoexcited spin dynamics and then evaluated their potential as novel maser gain media by optical, computational, and electronic paramagnetic resonance (EPR) spectroscopy. To facilitate these investigations, we adopted an organic glass former, 1,3,5-tri(1-naphthyl)benzene to act as a universal host. These chemical modifications impacted the rates of intersystem crossing, triplet spin polarization, triplet decay, and spin-lattice relaxation, leading to significant consequences on the conditions required to surpass the maser threshold.

Role of MXRA8 in Ross River Virus Disease Pathogenesis.

Arthritogenic alphaviruses such as Ross River virus (RRV) and Chikungunya virus (CHIKV) are responsible for large-scale epidemics that cause debilitating acute and chronic musculoskeletal diseases. MXRA8 was recently discovered as an entry receptor for multiple alphaviruses including CHIKV, RRV, Mayaro virus (MAYV), and O'nyong-nyong virus (ONNV). However, the role of MXRA8 in the development of alphavirus-induced musculoskeletal inflammation has not yet been fully studied. Here, we attempt to fully characterize the contribution of MXRA8 to RRV disease in an established mouse model. MXRA8 knockout (MXRA8-/-) mice generated on a C57BL/6J background, showed abrogated disease signs and reduced viral replication, which correlated with lower viral load, diminished proinflammatory cytokines, and limited cell infiltrates in inflamed tissues. Immunomodulation genes were upregulated to higher levels in RRV-infected wild-type (WT) mice than in MXRA8-/- mice. Intriguingly, Cdkn1a and Ifi44 genes in blood and CD127/IL7RA, CD45, BatF3, IFNGR, Ly6G/Ly6C, CD40, CD127, F4/80, and MHC-II genes in quadriceps were found to be upregulated in RRV-infected MXRA8-/- mice compared to WT mice. Our results showed an essential role of MXRA8 in the immune response of mice infected with RRV and, more importantly, demonstrated novel changes in immunomodulation genes, which shed light on the immunopathogenesis of alphavirus-induced disease. IMPORTANCE Previous studies have shown the importance of the cell surface protein MXRA8 as an entry receptor for several different prominent alphaviruses such as CHIKV, RRV, MAYV, and ONNV. In particular, the role of MXRA8 in the tissue tropism, viral pathogenesis, and immune response of a CHIKV mouse model have already been briefly characterized. However, the role of MXRA8 warrants further characterization in RRV disease background, since there are noticeable differences in the disease profile between CHIKV and RRV. For example, patients infected with CHIKV are usually affected by sudden onset of severe arthritis and fever, whereas RRV-infected patients generally only have minor joint pain and mild fever. Here, we characterized the role of MXRA8 in RRV disease and assessed several key mechanisms of MXRA8 that may contribute to the disease progression.

Move Aside Pentacene: Diazapentacene-Doped para-Terphenyl, a Zero-Field Room-Temperature Maser with Strong Coupling for Cavity Quantum Electrodynamics.

Masers can deliver ultralow-noise amplification of microwave signals in medical imaging and deep-space communication, with recent research being rekindled through the discovery of gain media operating at room-temperature, eschewing bulky cryogenics that hindered their use. This work shows the discovery of 6,13-diazapentacene doped in para-terphenyl (DAP:PTP) as a maser gain medium that can operate at room-temperature, without an external magnetic field. With a maser output power of -10 dBm, it is on par with pentacene-doped para-terphenyl in masing power, while possessing compelling advantages such as faster amplification startup times, being pumped by longer wavelength light at 620 nm and greater chemical stability from nitrogen groups. Furthermore, the maser bursts from DAP:PTP allow one to reach the strong coupling regime for cavity quantum electrodynamics, with a high cooperativity of 182. The optical and microwave spin dynamics of DAP:PTP are studied in order to evaluate its capabilities as a maser gain medium, where it features fast intersystem crossing and an advantageously higher triplet quantum yield. The results pave the way for the future discovery of similar maser materials and help designate them as promising candidates for quantum sensors, optoelectronic devices and the study of cavity quantum electrodynamic effects at room-temperature.

Repurposing of drugs targeting the cytokine storm induced by SARS-CoV-2.

A cytokine storm is one of the leading causes of acute respiratory distress syndrome (ARDS) and sepsis-associated multiple organ failure in many respiratory viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The coronavirus disease 2019 (COVID-19) pandemic has caused millions of deaths worldwide, resulting in an urgent need for effective therapeutic interventions. Repurposing immunosuppressive drugs that target cytokines with immunomodulatory properties is a promising approach to counteract SARS-CoV-2-induced ARDS at the infective and post-infective stages. In this minireview, we examine drugs targeting IL-1ß, IL-4/IL-13, IL-6 and TNF-α tested in COVID-19 patients.

Adverse events of immune checkpoint therapy alone versus when combined with vascular endothelial growth factor inhibitors: a pooled meta-analysis of 1735 patients.

Background: Combining immune checkpoint therapy (ICT) and vascular endothelial growth factor inhibitors (VEGFi) may result in increased treatment-related and immune-related adverse events (TRAEs and irAEs) compared to ICT alone. This metanalysis was conducted to identify prospective phase II or III clinical studies that evaluated the toxicity profile of ICT + VEGFi compared to ICT alone. Methods: A systematic search was performed across all cancer types and major databases until August 10, 2022, and screening was done by two independent investigators. Inclusion criteria included phase 2 or 3 studies with at least one arm of patients treated with combination therapy and one arm treated with monotherapy. Adverse event data were pooled using a restricted maximum likelihood fixed effects model, and heterogeneity using Cochran's Q (chi-square) test. Results: 7 out of 9366 studies met the inclusion criteria, and 808 and 927 patients were treated with ICT monotherapy and a combination of ICT with VEGFi, respectively. Only one study reported irAEs, so the analysis was restricted to TRAEs. The total number of TRAEs was significantly higher in the ICT + VEGFi group (RR:1.49; 95% CI 1.37 -1.62; p=1.5×10-21), and more frequent treatment withdrawals were attributed to TRAEs (RR:3.10; 95% CI 1.12-8.59; p=0.029). The highest TRAE effect size increases noted for rash (RR 6.50; 95% CI 3.76 - 11.25; p=2.1×10-11), hypertension (RR:6.07; 95% CI 3.69-10.00; p=1.3×10-12), hypothyroidism (RR:5.02; 95% CI 3.08 - 8.19; p=8.9×10-11), and diarrhea (RR:4.94; 95% CI 3.21-7.62; p=3.8×10-13). Other significantly more frequent TRAEs included nausea, anemia, anorexia, and proteinuria. Conclusion: Combination therapy with ICT and VEGFi carries a higher risk of certain TRAEs, such as rash, hypertension, hypothyroidism, diarrhea, nausea, anorexia, and proteinuria, compared to ICT monotherapy. More granular details on the cause of AEs, particularly irAEs, should be provided in future trials of such regimens.

Ocular tropism of SARS-CoV-2 in animal models with retinal inflammation via neuronal invasion following intranasal inoculation.

Although ocular manifestations are reported in patients with COVID-19, consensus on ocular tropism of SARS-CoV-2 is lacking. Here, we infect K18-hACE2 transgenic mice with SARS-CoV-2 using various routes. We observe ocular manifestation and retinal inflammation with production of pro-inflammatory cytokines in the eyes of intranasally (IN)-infected mice. Intratracheal (IT) infection results in dissemination of the virus from the lungs to the brain and eyes via trigeminal and optic nerves. Ocular and neuronal invasions are confirmed using intracerebral (IC) infection. Notably, the eye-dropped (ED) virus does not cause lung infection and becomes undetectable with time. Ocular and neurotropic distribution of the virus in vivo is evident in fluorescence imaging with an infectious clone of SARS-CoV-2-mCherry. The ocular tropic and neuroinvasive characteristics of SARS-CoV-2 are confirmed in wild-type Syrian hamsters. Our data can improve the understanding regarding viral transmission and clinical characteristics of SARS-CoV-2 and help in improving COVID-19 control procedures.

Insights into the tumor microenvironment of B cell lymphoma.

The standard therapies in lymphoma have predominantly focused on targeting tumor cells with less of a focus on the tumor microenvironment (TME), which plays a critical role in favoring tumor growth and survival. Such an approach may result in increasingly refractory disease with progressively reduced responses to subsequent treatments. To overcome this hurdle, targeting the TME has emerged as a new therapeutic strategy. The TME consists of T and B lymphocytes, tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), cancer-associated fibroblasts (CAFs), and other components. Understanding the TME can lead to a comprehensive approach to managing lymphoma, resulting in therapeutic strategies that target not only cancer cells, but also the supportive environment and thereby ultimately improve survival of lymphoma patients. Here, we review the normal function of different components of the TME, the impact of their aberrant behavior in B cell lymphoma and the current TME-direct therapeutic avenues.

Treating Hypertriglyceridemia-Induced Pancreatitis With Intravenous Insulin and Plasmapheresis.

Hypertriglyceridemic pancreatitis (HTGP) is well-known but it is extremely rare, especially in younger patients. The main treatment modalities for HTGP are apheresis and intravenous insulin. However, apheresis in severe HTGP is not well established and the efficacy of the treatment is lacking. Herein, we discuss a case of a 17-year-old female patient with no significant past medical history who initially presented to the emergency department with severe diabetic ketoacidosis (DKA) and was intubated due to severe metabolic acidosis and impending respiratory failure on arrival. Further investigation showed evidence of HTGP. Initially, her condition did not improve with intravenous insulin. However, a course of apheresis along with supportive care improved her condition drastically. Hence, this is a case report which showed the efficacy of concomitant use of insulin infusion and plasmapheresis in regard to treating HTGP. Outcomes of HTGP based on different treatment modalities are discussed in this literature as well. However, to date, there are no randomized studies to draw a solid treatment algorithm, thus further research on the most efficient treatment regimes is required for the management of HTGP.

Increasing tissue requirements in lymphoma trials may exclude patients with high-risk disease or worse prognosis.

An enhanced understanding of the molecular heterogeneity of diffuse large B-cell lymphoma (DLBCL) has opened the door to clinical trials evaluating novel agents with subtype-specific activity. It is an emerging question whether core needle biopsies (CNB) can adequately meet the increasing tissue requirements of these clinical trials. This can potentially lead to selective enrollment of patients who can undergo excisional biopsy (EB). It is also important to know whether patients who can undergo extensive diagnostic work up differ in their disease characteristics and outcomes from those who cannot. In this observational study, we describe the characteristics, outcomes, and adequacy of diagnostic tissue in patients with newly diagnosed DLBCL and primary mediastinal large B-cell lymphoma who underwent EB vs CNB. Of the 1061 patients, 532 (49.8%) underwent EB and 529 (50.1%) underwent CNB. A significantly higher proportion of patients with CNB had advanced stage disease, an international prognostic index of ≥3, and inadequate tissue for molecular analyses. Patients with CNB had significantly worse 5-year event-free survival (67.6% vs 56.9%; hazard ratio [HR], 0.76; confidence interval [CI]95, 0.6-0.9, P < .001) and 5-year overall survival (76.4% vs 69.2%; HR, 0.8; CI95, 0.6-0.9, P < .001). Thus, patients who underwent CNB have poor-risk features and inferior outcomes on frontline chemoimmunotherapy, are more likely to have inadequate tissue for molecular analyses, and might not meet the tissue requirements of biomarker-driven clinical trials. Thus, the increasing tissue requirements of biomarker-driven clinical trials may result in the exclusion of patients with high-risk DLBCL who need novel agents.

The Delta SARS-CoV-2 Variant of Concern Induces Distinct Pathogenic Patterns of Respiratory Disease in K18-hACE2 Transgenic Mice Compared to the Ancestral Strain from Wuhan.

Compared to the original ancestral strain of SARS-CoV-2, the Delta variant of concern has shown increased transmissibility and resistance toward COVID-19 vaccines and therapies. However, the pathogenesis of the disease associated with Delta is still not clear. In this study, using K18-hACE2 transgenic mice, we assessed the pathogenicity of the Delta variant by characterizing the immune response following infection. We found that Delta induced the same clinical disease manifestations as the ancestral SARS-CoV-2, but with significant dissemination to multiple tissues, such as brain, intestine, and kidney. Histopathological analysis showed that tissue pathology and cell infiltration in the lungs of Delta-infected mice were the same as in mice infected with the ancestral SARS-CoV-2. Delta infection caused perivascular inflammation in the brain and intestinal wall thinning in K18-hACE2 transgenic mice. Increased cell infiltration in the kidney was observed in both ancestral strain- and Delta-infected mice, with no clear visible tissue damage identified in either group. Interestingly, compared with mice infected with the ancestral strain, the numbers of CD45+ cells, T cells, B cells, inflammatory monocytes, and dendritic cells were all significantly lower in the lungs of the Delta-infected mice, although there was no significant difference in the levels of proinflammatory cytokines between the two groups. Our results showed distinct immune response patterns in the lungs of K18-hACE2 mice infected with either the ancestral SARS-CoV-2 or Delta variant of concern, which may help to guide therapeutic interventions for emerging SARS-CoV-2 variants. IMPORTANCE SARS-CoV-2 variants, with the threat of increased transmissibility, infectivity, and immune escape, continue to emerge as the COVID-19 pandemic progresses. Detailing the pathogenesis of disease caused by SARS-CoV-2 variants, such as Delta, is essential to better understand the clinical threat caused by emerging variants and associated disease. This study, using the K18-hACE2 mouse model of severe COVID-19, provides essential observation and analysis on the pathogenicity and immune response of Delta infection. These observations shed light on the changing disease profile associated with emerging SARS-CoV-2 variants and have potential to guide COVID-19 treatment strategies.

TIR-Domain-Containing Adapter-Inducing Interferon-ß (TRIF)-Dependent Antiviral Responses Protect Mice against Ross River Virus Disease.

Ross River virus (RRV) is the major mosquito-borne virus in the South Pacific region. RRV infections are characterized by arthritic symptoms, which can last from several weeks to months. Type I interferon (IFN), the primary antiviral innate immune response, is able to modulate adaptive immune responses. The relationship between the protective role of type I IFN and the induction of signaling proteins that drive RRV disease pathogenesis remains poorly understood. In the present study, the role of TIR-domain-containing adapter-inducing interferon-ß (TRIF), an essential signaling adaptor protein downstream of Toll-like receptor (TLR) 3, a key single-stranded RNA (ssRNA)-sensing receptor, was investigated. We found that TRIF-/- mice were highly susceptible to RRV infection, with severe disease, high viremia, and a low type I IFN response early during disease development, which suggests the TLR3-TRIF axis may engage early in response to RRV infection. The number and the activation level of CD4+ T cells, CD8+ T cells, and NK cells were reduced in TRIF-/- mice compared to those in infected wild-type (WT) mice. In addition, the number of germinal center B cells was lower in TRIF-/- mice than WT mice following RRV infection, with lower titers of IgG antibodies detected in infected TRIF-/- mice compared to WT. Interestingly, the requirement for TRIF to promote immunoglobulin class switch recombination was at the level of the local immune microenvironment rather than B cells themselves. The slower resolution of RRV disease in TRIF-/- mice was associated with persistence of the RRV genome in muscle tissue and a continuing IFN response. IMPORTANCE RRV has been prevalent in the South Pacific region for decades and causes substantial economic and social costs. Though RRV is geographically restricted, a number of other alphaviruses have spread globally due to expansion of the mosquito vectors and increased international travel. Since over 30 species of mosquitoes have been implicated as potent vectors for RRV dissemination, RRV has the potential to further expand its distribution. In the pathogenesis of RRV disease, it is still not clear how innate immune responses synergize with adaptive immune responses. Type I IFN is crucial for bridging innate to adaptive immune responses to viral invasion. Hence, key signaling proteins in type I IFN induction pathways, which are important for type I IFN modulation, may also play critical roles in viral pathogenesis. This study provides insight into the role of TRIF in RRV disease development.

Bench-Top Cooling of a Microwave Mode Using an Optically Pumped Spin Refrigerator.

We experimentally demonstrate the temporary removal of thermal photons from a microwave mode at 1.45 GHz through its interaction with the spin-polarized triplet states of photo-excited pentacene molecules doped within a p-terphenyl crystal at room temperature. The crystal functions electromagnetically as a narrowband cryogenic load, removing photons from the otherwise room-temperature mode via stimulated absorption. The noise temperature of the microwave mode dropped to 50_{-32}^{+18} K (as directly inferred by noise-power measurements), while the metal walls of the cavity enclosing the mode remained at room temperature. Simulations based on the same system's behavior as a maser (which could be characterized more accurately) indicate the possibility of the mode's temperature sinking to ∼10 K (corresponding to ∼140 microwave photons). These observations, when combined with engineering improvements to deepen the cooling, identify the system as a narrowband yet extremely convenient platform-free of cryogenics, vacuum chambers, and strong magnets-for realizing low-noise detectors, quantum memory, and quantum-enhanced machines (such as heat engines) based on strong spin-photon coupling and entanglement at microwave frequencies.