Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B.

Background: Xalnesiran, a small interfering RNA molecule that targets a conserved region of the hepatitis B virus (HBV) genome and silences multiple HBV transcripts, may have efficacy, with or without an immunomodulator, in patients with chronic HBV infection.

Methods: We conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 μg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5) in participants with chronic HBV infection who had virologic suppression with NA therapy. The primary efficacy end point was hepatitis B surface antigen (HBsAg) loss (HBsAg level, <0.

A cis-acting ligase ribozyme generates circular RNA in vitro for ectopic protein functioning.

Delivering synthetic protein-coding RNA bypassing the DNA stage for ectopic protein functioning is a novel therapeutic strategy. Joining the linear RNA head-to-tail covalently could be a state-of-the-art strategy for functioning longer. Here we enroll a cis-acting ligase ribozyme (RzL) to generate circular RNA (circRNA) in vitro for ectopic protein expression.

"Maintain Professionalism": Nurses' Experiences in Caring for Patients with Malignant Fungating Wounds in Taiwan.

Context: Malignant fungating wounds (MFWs) occur among 5%-15% of patients with terminal cancers, the uncontrollable symptoms result in serious psychosocial issues, thereby reducing the quality of life. Caring for MFWs impacts caregivers, including healthcare personnel. While existing studies are patient-focused, the impact of care experiences and associated support for nurses has not been examined.

Pilot-scale production of a highly efficacious and stable monoglycosylated influenza split virus vaccine.

The yearly epidemics and unpredictable outbreaks of influenza have raisedserious concernsglobally and led to prioritizing the development of an effective vaccine toprotectagainst newly emerging variants. Previously, we demonstrated that monoglycosylated influenza virus vaccines derived from A/California/7/2009 or an updated A/Brisbane/02/2018 (IVR-190) vaccine strain recommended by WHO are superior to fully glycosylated vaccines and could broadly protect against past and new coming H1N1 variants. However, whether such a monoglycosylated virus vaccine can be mass-produced to meet clinical demands and stable enough to provide consistent efficacy against H1N1 viruses remains unclear.

Combining a wireless radar sleep monitoring device with deep machine learning techniques to assess obstructive sleep apnea severity.

Study Objectives: The gold standard for diagnosing obstructive sleep apnea (OSA) is polysomnography (PSG). However, PSG is a time-consuming method with clinical limitations. This study aimed to create a wireless radar framework to screen the likelihood of 2 levels of OSA severity (ie, moderate-to-severe and severe OSA) in accordance with clinical practice standards.

Intestinal dual-specificity phosphatase 6 regulates the cold-induced gut microbiota remodeling to promote white adipose browning.

Gut microbiota rearrangement induced by cold temperature is crucial for browning in murine white adipose tissue. This study provides evidence that DUSP6, a host factor, plays a critical role in regulating cold-induced gut microbiota rearrangement. When exposed to cold, the downregulation of intestinal DUSP6 increased the capacity of gut microbiota to produce ursodeoxycholic acid (UDCA).

Efficacy evaluation of a bivalent subunit vaccine against classical swine fever virus and porcine circovirus type 2.

Classical swine fever virus (CSFV) and porcine circovirus type 2 (PCV2) are two of the most devastating and economically significant pathogens affecting pig populations worldwide. Administration of a combination of vaccines against swine pathogens has been demonstrated to be as efficacious as the administration of single vaccines. In this study, we developed and tested a novel bivalent subunit vaccine against CSFV and PCV2.

Monoglycosylated SARS-CoV-2 receptor binding domain fused with HA-scaffolded protein vaccine confers broad protective immunity against SARS-CoV-2 and influenza viruses.

The SARS-CoV-2 and influenza pandemics have posed a devastating threat to global public health. The best strategy for preventing the further spread of these respiratory viruses worldwide is to administer a vaccine capable of targeting both viruses. Here, we show that a novel monoglycosylated vaccine designed based on the influenza virus HA conserved domain fused with the SARS-CoV-2 spike-RBD domain (HSSR) can present proper antigenicity that elicits sufficient neutralization efficacy against various SARS-CoV-2 variants while simultaneously providing broad protection against H1N1 viruses in mice.

Pilot-scale production of inactivated monoglycosylated split HN influenza virus vaccine provides cross-strain protection against influenza viruses.

Influenza epidemics and pandemics caused by newly emerging virus strains highlight an urgent need to develop a universal vaccine against viruses. Previously, a monoglycosylated X-181 vaccine demonstrated that the HA possessing a single N-acetylglucosamine at each N-glycosylation site is superior to confer broader protection in mice than conventional vaccines. However, the greatest challenge in conducting clinical trials is the need to develop robust manufacturing processes capable of producing vaccines at the pilot scale with the desired stability, potency, and efficacy.

Abnormal Conduction Zone Detected by Isochronal Late Activation Mapping Accurately Identifies the Potential Atrial Substrate and Predicts the Atrial Fibrillation Ablation Outcome After Pulmonary Vein Isolation.

Background: The presence of abnormal substrate of left atrium is a predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation. We aimed to investigate the isochronal late activation mapping to access the abnormal conduction velocity for predicting AF ablation outcome.

Methods: Forty-five paroxysmal AF patients (30 males, 57.

Health-Related Quality of Life in Older Patients With Heart Failure From Before to Early After Advanced Surgical Therapies: Findings From the SUSTAIN-IT Study.

Background: Restoring health-related quality of life (HRQOL) is a therapeutic goal for older patients with advanced heart failure. We aimed to describe change in HRQOL in older patients (60-80 years) awaiting heart transplantation (HT) with or without pretransplant mechanical circulatory support (MCS) or scheduled for long-term MCS, if ineligible for HT, from before to 6 months after these surgeries and identify factors associated with change.

Methods: Patients from 13 US sites completed the EuroQol 5-dimension 3L questionnaire and Kansas City Cardiomyopathy Questionnaire-12 at baseline and 3 and 6 months after HT or long-term MCS.

Edoxaban Versus Dual Antiplatelet Therapy for Leaflet Thrombosis and Cerebral Thromboembolism After TAVR: The ADAPT-TAVR Randomized Clinical Trial.

Background: It is unknown whether the direct oral anticoagulant edoxaban can reduce leaflet thrombosis and the accompanying cerebral thromboembolic risk after transcatheter aortic valve replacement. In addition, the causal relationship of subclinical leaflet thrombosis with cerebral thromboembolism and neurological or neurocognitive dysfunction remains unclear.

Methods: We conducted a multicenter, open-label randomized trial comparing edoxaban with dual antiplatelet therapy (aspirin plus clopidogrel) in patients who had undergone successful transcatheter aortic valve replacement and did not have an indication for anticoagulation.

Paradoxical mortality of high estimated glomerular filtration rate reversed by 24-h urine creatinine excretion rate adjustment: sarcopenia matters.

Background: Muscle wasting may explain the paradoxical mortality of patients with high estimated glomerular filtration rates (eGFRs) derived from equation methods. However, empirical evidence and solutions remain insufficient.

Methods: In this retrospective cohort study, we compared the performance of equation methods for predicting all-cause mortality; we used 24-h creatinine clearance (24-h CrCl), equation-based eGFRs, and a new eGFR estimating equation weighting for population 24-h urine creatinine excretion rate (U-CER).

Lightweight deep neural networks for cholelithiasis and cholecystitis detection by point-of-care ultrasound.

Background And Objective: Emergency physicians (EPs) frequently deal with abdominal pain, including that is caused by either gallstones or acute cholecystitis. Easy access and low cost justify point-of-care ultrasound (POCUS) use as a first-line test to detect these diseases; yet, the detection performance of POCUS by EPs is unreliable, causing misdiagnoses with serious impacts. This study aimed to develop a machine learning system to detect and localize gallstones and to detect acute cholecystitis by ultrasound (US) still images taken by physicians or technicians for preliminary diagnoses.

One-year Fibrosis-4 index helps identify minimal HCC risk in non-cirrhotic chronic hepatitis B patients with antiviral treatment.

Background And Aims: Fibrosis-4 (FIB-4) index is a HCC predictor in chronic hepatitis B (CHB) patients. However, little is known about whether FIB-4 helps identify non-cirrhotic CHB patients with minimal HCC risk after prolonged nucleos(t)ide analogue (NA) therapy.

Methods: A total of 1936 ethnically diverse, non-cirrhotic CHB patients were enrolled in this retrospective multi-national study.

Incidence, Factors, and Patient-Level Data for Spontaneous HBsAg Seroclearance: A Cohort Study of 11,264 Patients.

Introduction: Spontaneous hepatitis B surface antigen (HBsAg) seroclearance, the functional cure of hepatitis B infection, occurs rarely. Prior original studies are limited by insufficient sample size and/or follow-up, and recent meta-analyses are limited by inclusion of only study-level data and lack of adjustment for confounders to investigate HBsAg seroclearance rates in most relevant subgroups. Using a cohort with detailed individual patient data, we estimated spontaneous HBsAg seroclearance rates through patient and virologic characteristics.

Excess Transforming Growth Factor-α Changed the Cell Properties of Corneal Epithelium and Stroma.

Purpose: This study is to investigate the corneal anomaly caused by excess transforming growth factor-α (TGF-α) during mouse development.

Methods: Bitransgenic KeraRT/TGF-α mice, generated via cross-mating tetO-TGF-α and KeraRT mice, were induced to overexpress TGF-α by doxycycline commencing at embryonic day 0 or postnatal day 0 to different developmental stages. Bitransgenic mice with doxycycline induction were defined as TGF-αECK mice (TGF-α excess expression by corneal keratocytes).

Sustained virological response to hepatitis C therapy does not decrease the incidence of systemic lupus erythematosus or rheumatoid arthritis.

In patients with chronic hepatitis C (CHC), the effects of baseline characteristics, virological profiles, and therapeutic outcome to pegylated interferon plus ribavirin (PR) therapy on autoimmune diseases are unknown. Taiwanese Chronic Hepatitis C Cohort is a nationwide hepatitis C virus registry cohort comprising 23 hospitals of Taiwan. A total of 12,770 CHC patients receiving PR therapy for at least 4 weeks between January 2003 and December 2015 were enrolled and their data were linked to the Taiwan National Health Insurance Research Database for studying the development of 10 autoimmune diseases.

Human megakaryocytic microparticles induce de novo platelet biogenesis in a wild-type murine model.

Platelet transfusions are used to treat idiopathic or drug-induced thrombocytopenia. Platelets are an expensive product in limited supply, with limited storage and distribution capabilities because they cannot be frozen. We have demonstrated that, in vitro, human megakaryocytic microparticles (huMkMPs) target human CD34+ hematopoietic stem and progenitor cells (huHSPCs) and induce their Mk differentiation and platelet biogenesis in the absence of thrombopoietin.

Behavioral and Structural Effects of Single and Repeat Closed-Head Injury.

Background And Purpose: The effects of multiple head impacts, even without detectable primary injury, on subsequent behavioral impairment and structural abnormality is yet well explored. Our aim was to uncover the dynamic changes and long-term effects of single and repetitive head injury without focal contusion on tissue microstructure and macrostructure.

Materials And Methods: We introduced a repetitive closed-head injury rodent model ( = 70) without parenchymal lesions.

Noninvasive sub-organ ultrasound stimulation for targeted neuromodulation.

Tools for noninvasively modulating neural signaling in peripheral organs will advance the study of nerves and their effect on homeostasis and disease. Herein, we demonstrate a noninvasive method to modulate specific signaling pathways within organs using ultrasound (U/S). U/S is first applied to spleen to modulate the cholinergic anti-inflammatory pathway (CAP), and US stimulation is shown to reduce cytokine response to endotoxin to the same levels as implant-based vagus nerve stimulation (VNS).

Acoustic Radiation Force Impulse US Imaging: Liver Stiffness in Patients with Chronic Hepatitis B with and without Antiviral Therapy.

Purpose To investigate the clinical utility and longitudinal change of acoustic radiation force impulse (ARFI) ultrasonographic (US) imaging in patients with chronic hepatitis B. Materials and Methods A retrospective cohort study of patients with chronic hepatitis B who underwent serial ARFI examinations in a tertiary referral center in Taiwan between 2012 and 2016 was conducted. The clinical information and noninvasive liver stiffness measurement tests (ARFI, Fibrosis-4 index [FIB-4], and FibroScan) were collected.

Tissue distribution and subcellular localizations determine in vivo functional relationship among prostasin, matriptase, HAI-1, and HAI-2 in human skin.

The membrane-bound serine proteases prostasin and matriptase and the Kunitz-type protease inhibitors HAI-1 and HAI-2 are all expressed in human skin and may form a tightly regulated proteolysis network, contributing to skin pathophysiology. Evidence from other systems, however, suggests that the relationship between matriptase and prostasin and between the proteases and the inhibitors can be context-dependent. In this study the in vivo zymogen activation and protease inhibition status of matriptase and prostasin were investigated in the human skin.

Polycystic kidney disease is significantly associated with dementia risk.

Objective: Data on the risk of neurodegenerative diseases, including Alzheimer disease (AD) and Parkinson disease (PD), in patients with polycystic kidney disease (PKD) are lacking.

Methods: A total of 4,229 patients who were aged ≥20 years and had received a diagnosis of PKD were included in the PKD cohort. For each PKD case identified, 1 participant aged ≥20 years without a history of PKD, dementia, or PD was selected from the comparison cohort.