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ABSTRACTIntroduction Pseudoviruses are recombinant, replication-incompetent, viral particles designed to mimic the surface characteristics of native enveloped viruses. They are a safer, and cost-effective research alternative to live viruses. With the potential emergence of the next major infectious disease, more vaccine scientists must become familiar with the pseudovirus platform as a vaccine development tool to mitigate future outbreaks.Areas Covered This review aims at vaccine developers to provide a basic understanding of pseudoviruses, list their production methods, and discuss their utility to assess vaccine efficacy against enveloped viral pathogens. We further illustrate their usefulness as wet-lab simulators for emerging mutant variants, and new viruses to help prepare for current and future viral outbreaks, minimizing the need for gain-of-function experiments with highly infectious or lethal enveloped viruses.Expert opinion With this platform, researchers can better understand the role of virus–receptor interactions and entry in infections, prepare for dangerous mutations, and develop effective vaccines.

Abstract Perovskite solar cells have attracted much attention as next-generation solar cells. However, a typical hole-transport material, spiro-OMeTAD, has associated difficulties including tedious synthesis and high cost. To overcome these shortcomings, an easily synthesized and low-cost hole-transport material has been developed: HND-2NOMe. Although HND-2NOMe has high local charge mobility because of the quasi-planar structure, its lower device performance is a weak point, the cause of which has not yet been clarified. Here, we analyse the source of the lower performance by clarifying the internal states from a microscopic viewpoint using electron spin resonance. We observe hole diffusion from perovskite to HND-2NOMe under dark conditions, indicating hole barrier formation at the perovskite/HND-2NOMe interface, leading to lower performance. Although such a barrier is formed, less hole accumulation for the HND-2NOMe-based cells under solar irradiation occurs, which is related to the stable performance. The sources of the lower but stable performance are crucially important for providing guidelines for improving the device performance.

Abstract Background Electrocardiograms (ECGs) in athletes commonly reveal findings related to physiologic adaptations to exercise, that may be difficult to discern from true underlying cardiovascular abnormalities. North American and European societies have published consensus statements for normal, borderline, and abnormal ECG findings for athletes, but these criteria are not based on established correlation with disease states. Additionally, data comparing ECG findings in athletes to non-athlete control subjects are lacking. Our objective was to compare the ECGs of collegiate athletes and non-athlete controls using Z-scores for digital ECG variables to better identify significant differences between the groups and to evaluate the ECG variables in athletes falling outside the normal range. Methods Values for 102 digital ECG variables on 7206 subjects aged 17–22 years, including 672 athletes, from Hawaii Pacific Health, University of Hawaii, and Rady Children’s Hospital San Diego were obtained through retrospective review. Age and sex-specific Z-scores for ECG variables were derived from normal subjects and used to assess the range of values for specific ECG variables in young athletes. Athletes with abnormal ECGs were referred to cardiology consultation and/or echocardiogram. Results Athletes had slower heart rate, longer PR interval, more rightward QRS axis, longer QRS duration but shorter QTc duration, larger amplitude and area of T waves, prevalent R’ waves in V1, and higher values of variables traditionally associated with left ventricular hypertrophy (LVH): amplitudes of S waves (leads V1-V2), Q waves (V6, III) and R waves (II, V5, V6). Z-scores of these ECG variables in 558 (83%) of the athletes fell within − 2.5 and 2.5 range derived from the normal population dataset, and 60 (8.9%) athletes had a Z-score outside the − 3 to 3 range. While 191 (28.4%) athletes met traditional voltage criteria for diagnosis of LVH on ECG, only 53 athletes (7.9%) had Z-scores outside the range of -2.5 to 2.5 for both S amplitude in leads V1-V2 and R amplitude in leads V5-6. Only one athlete was diagnosed with hypertrophic cardiomyopathy with a Z-score of R wave in V6 of 2.34 and T wave in V6 of -5.94. Conclusion The use of Z-scores derived from a normal population may provide more precise screening to define cardiac abnormalities in young athletes and reduce unnecessary secondary testing, restrictions and concern.

Abstract The mixed-valence compound YbB12 displays paradoxical quantum oscillations in electrical resistivity and magnetic torque in a regime with a well-developed insulating charge gap and in the absence of an electronic Fermi surface. However, signatures of such unusual fermionic quasiparticles in other bulk thermodynamic observables have been missing. Here we report the observation of a series of sharp double-peak features in the specific heat as a function of the magnetic field. The measured Hall resistivity evolves smoothly across the field values at which the characteristic anomalies appear in the thermodynamic response and rules out the possibility of conventional electrons as their origin. Our observations of thermodynamic anomalies in a bulk three-dimensional electrical insulator provide the evidence for the presence of emergent dispersing fermionic excitations within the insulating bulk, which sets the stage for further investigation of electron fractionalization in other correlated mixed-valence compounds.

Abstract The development of broad-spectrum coronavirus vaccines is essential to prepare for future respiratory virus pandemics. We demonstrated broad neutralization by a trivalent subunit vaccine, formulating the receptor-binding domains of SARS-CoV, MERS-CoV, and SARS-CoV-2 XBB.1.5 with Alum and CpG55.2. Vaccinated mice produced cross-neutralizing antibodies against all three human Betacoronaviruses and others currently exclusive to bats, indicating the epitope preservation of the individual antigens during co-formulation and the potential for epitope broadening.

Introduction A previous report has shown that cyclooxygenase‐2 inhibitors can prevent the recurrence of cystitis glandularis postoperatively. Herein, we present a case of cystitis glandularis in which the tumor volume was markedly reduced by preoperative oral administration of a cyclooxygenase‐2 inhibitor. Case presentation A 45‐year‐old man with voiding difficulty and lower abdominal pain during urination was referred to our hospital. Cystoscopy revealed multiple cystitis glandularis‐like edematous masses on the trigone and the neck of the bladder, completely involving the bilateral ureteral orifices. Cyclooxygenase‐2 inhibitor was orally administered at the patient's request. Six weeks later, the tumor volume was markedly reduced, bilateral ureteral orifices were identified, and the voiding difficulty and pain on urination disappeared. Complete transurethral resection of the residual tumor was performed, and the pathological diagnosis was intestinal‐type cystitis glandularis. Conclusion Cyclooxygenase‐2 inhibition can be considered a useful therapeutic strategy for cystitis glandularis.

The COVID-19 pandemic demonstrated the strength of massive sequencing or next generation sequencing (NGS) techniques in viral genomic characterization. Millions of complete SARS-CoV-2 genomes were sequenced in almost real time. Laboratories around the world dedicated to the molecular diagnosis of infectious diseases were equipped with cutting-edge technologies for deep sequencing, coupled with strengthening or development of previously limited bioinformatics capacities. Almost 5 years have passed from the initiation of the COVID pandemic, and, opposed to what could be envisioned as an opportunity for viral genomics to expand, this has essentially scaled back in most clinical settings. Most of NGS equipment and capacities in many regions of the world have been repurposed for the study of cancer driver mutations, microbiome-related diseases, and pharmacogenomics, as the most important applications in health. Although financial constraints can limit their implementation, technical, regulatory, medical and data management factors are also part of the equation that will or will not make NGS a real game changer for advancing healthcare and guiding clinical decisions related to viral infections.

Introduction We encountered a case of urinary retention caused by a urethral caruncle. Case presentation An 86‐year‐old woman presented to our hospital with urinary retention. When the urinary bladder catheter was placed, a smooth, well‐defined mass 20 mm in diameter was detected on the posterior wall of the external urethral meatus. The patient was diagnosed with urinary retention due to a urethral caruncle, and the mass was resected. The mass was pathologically compatible with a urethral caruncle. The patient could urinate postoperatively. Ultrasound test after surgery showed residual urine volume was 100 mL. Conclusion Inspecting the urethral meatus is vital in the clinical examination of older women with voiding symptoms. A urethral caruncle is a rare cause of urinary retention. However, large urethral caruncles are at risk of causing urinary retention suggesting that resecting the urethral caruncles at an appropriate time is desirable.

Introduction We present the case of a rapidly growing inferior vena cava tumor thrombus in renal cell carcinoma. Case presentation We present a case of a 66‐year‐old woman with right renal cell carcinoma with a tumor thrombus extending 2 cm into the inferior vena cava on an initial Imaging. Radical surgery was performed 6 weeks after the first visit. Intraoperatively, the tumor thrombus was confirmed to have grown near the diaphragm. The tumor was resected using an inferior vena cava clamping just below the diaphragm. The tumor thrombus and renal cell carcinoma were completely removed. There was no recurrence 6 months postoperatively. Conclusion Inferior vena cava tumor thrombus in renal cell carcinoma can grow in a short period, suggesting that preoperative imaging evaluation at the appropriate time is important. Once inferior vena cava tumor thrombus of renal cell carcinoma occurs, surgery should not be delayed unless there is an urgent reason.

Shiga toxin (Stx)-producing Escherichia coli (STEC) causes serious gastrointestinal illness, including hemorrhagic colitis and hemolytic uremic syndrome. Two types of Stxs (Stx1 and Stx2) are known and both are encoded by bacteriophages (Stx phages), but the production of Stx2 is known to be a major risk factor for severe STEC infections. The production of Stx2, but not Stx1, is tightly coupled with the induction of Stx phages, and Stx2 production levels vary between STEC strains even within the same serotype. Here, we analyzed the genomic diversity of all Stx phages in 71 strains representing the entire O145:H28 lineage, one of the often highly pathogenic STECs, and the relationship between the variations in Stx phage genomes and the levels of Stx2 production by host strains. Our analysis reveals highly dynamic natures of Stx phages in O145:H28, including the independent acquisition of similar Stx phages by different sublineages, the recent transfer of Stx phage between different sublineages, and the frequent gain and loss of Stx phages in some sublineages. We also show the association of the Stx2 phage types with the Stx2 production levels of host strains: strains carrying short-tailed Stx2 phages exhibited significantly higher Stx2 production levels than those carrying long-tailed Stx2 phages. Detailed analyses of the Stx2 phage genomes revealed that both of short- and long-tailed phages exhibited sequence diversification and they were divided into two groups, respectively, based on the sequence similarity of the phage early region encoding genes responsible for phage induction, short-tailed phages contained early regions clearly different in genetic organization from those in long-tailed phages. Therefore, the variations in the early regions between short-and long-tailed Stx2 phages appeared to be linked to a striking difference in Stx2 production levels in their host strains. These results broaden our understanding of the diversification and dynamism of Stx phages in O145:H28 and the association of Stx2 phage types with the Stx2 production level in this STEC lineage.

Prodigiosin, a red pigment produced by numerous bacterial species, exerts various antibiotic effects on prokaryotic and eukaryotic organisms. For instance, human carcinoma cell lines appear to suffer from endoplasmic reticulum (ER) stress in the presence of prodigiosin. Here, we demonstrated that prodigiosin also triggers the unfolded-protein response (UPR), which is a cytoprotective response against ER stress, in yeast Saccharomyces cerevisiae. An S. cerevisiae mutant carrying a UPR-deficient mutation was hypersensitive to prodigiosin. Our observations cumulatively indicate that protein folding in the ER is impaired by prodigiosin, illustrating a new mode of action.

Abstract Background The Lentivirus human immunodeficiency virus (HIV) causes chronic inflammation and AIDS in humans, with variable rates of disease progression between individuals driven by both host and viral factors. Similarly, simian lentiviruses vary in their pathogenicity based on characteristics of both the host species and the virus strain, yet the immune underpinnings that drive differential Lentivirus pathogenicity remain incompletely understood. Methods We profile immune responses in a unique model of differential lentiviral pathogenicity where pig-tailed macaques are infected with highly genetically similar variants of SIV that differ in virulence. We apply longitudinal single-cell transcriptomics to this cohort, along with single-cell resolution cell-cell communication techniques, to understand the immune mechanisms underlying lentiviral pathogenicity. Results Compared to a minimally pathogenic lentiviral variant, infection with a highly pathogenic variant results in a more delayed, broad, and sustained activation of inflammatory pathways, including an extensive global interferon signature. Conversely, individual cells infected with highly pathogenic Lentivirus upregulated fewer interferon-stimulated genes at a lower magnitude, indicating that highly pathogenic Lentivirus has evolved to partially escape from interferon responses. Further, we identify CXCL10 and CXCL16 as important molecular drivers of inflammatory pathways specifically in response to highly pathogenic Lentivirus infection. Immune responses to highly pathogenic Lentivirus infection are characterized by amplifying regulatory circuits of pro-inflammatory cytokines with dense longitudinal connectivity. Conclusions Our work presents a model of lentiviral pathogenicity where failures in early viral control mechanisms lead to delayed, sustained, and amplifying pro-inflammatory circuits, which in turn drives disease progression.

Abstract The potential spin-triplet heavy-fermion superconductor UTe2 exhibits signatures of multiple distinct superconducting phases. For field aligned along the b axis, a metamagnetic transition occurs at μ 0 H m ≈ 35 T. It is associated with magnetic fluctuations that may be beneficial for the field-reinforced superconductivity surviving up to H m. Once the field is tilted away from the b towards the c axis, a reentrant superconducting phase emerges just above H m. In order to better understand this remarkably field-resistant superconducting phase, we conducted magnetic-torque and magnetotransport measurements in pulsed magnetic fields. We determine the record-breaking upper critical field of μ 0 H c2 ≈ 73 T and its evolution with angle. Furthermore, the normal-state Hall effect experiences a drastic suppression indicative of a reduced band polarization above H m in the angular range around 30° caused by a partial compensation between the applied field and an exchange field. This promotes the Jaccarino-Peter effect as a likely mechanism for the reentrant superconductivity above H m.

Abstract Introduction Molnupiravir is an orally available prodrug of N-hydroxycytidine that received special approval for emergency treatment of coronavirus disease 2019 (COVID-19) in Japan in December 2021 and full approval in April 2023. To assess the real-world safety and effectiveness of molnupiravir in Japanese patients with COVID-19, we conducted nationwide post-marketing surveillance to collect data at registered institutions in Japan. Methods The surveillance data were collected from December 27, 2021, to May 2, 2023. All reported adverse events were collected for safety analysis. Adverse drug reactions (ADRs) were assessed by the treating physicians. Effectiveness was assessed by the composite of hospitalization or all-cause death in outpatients and the composite of oxygen/mechanical ventilation initiation or all-cause death in inpatients. The observation period was from molnupiravir initiation through day 29. Results Of 3214 patients enrolled in the survey, 3179 were analyzed for safety. At baseline, 52.31% (1663/3179) of patients were male, the median (range) age was 69.0 (18–107) years, 82.38% (2619/3179) received COVID-19 vaccines, and 95.72% (3043/3179) had risk factors for severe COVID-19 illness. COVID-19 severity at baseline was mild in 86.44% (2748/3179) and moderate I in 10.22% (325/3179). A total of 205 ADRs occurred in 5.50% (175/3179) of patients; ADRs that occurred in > 0.5% of patients were diarrhea (1.86% [59/3179]) and rash (0.69% [22/3179]). Seven serious ADRs were reported in seven patients. In the effectiveness analysis population, the incidence of all-cause death through day 29 was 1.14% (34/2988), and the incidence of death through day 29 related to COVID-19 was 0.40% (12/2988). The cumulative incidence of the composite endpoint was 2.34% (47/2006) in outpatients and 4.60% (38/826) in inpatients. Conclusions This large-scale survey showed that molnupiravir was safe and effective in real-world settings in highly vaccinated Japanese patients with COVID-19, including older patients and those with comorbidities.