Enabling next-generation engineered TCR-T therapies based on high-throughput TCR discovery from diagnostic tumor biopsies.

Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) can mediate tumor regression, including complete and durable responses, in a range of solid cancers, most notably in melanoma. However, its wider application and efficacy has been restricted by the limited accessibility, proliferative capacity and effector function of tumor-specific TIL. Here, we develop a platform for the efficient identification of tumor-specific TCR genes from diagnostic tumor biopsies, including core-needle biopsies frozen in a non-viable format, to enable engineered T cell therapy.

Repeated 5-aminolevulinic acid mediated sonodynamic therapy using magnetic resonance guided focused ultrasound in rat brain tumour models.

Sonodynamic therapy is an emerging therapeutic approach against brain tumours. However, the treatment scheme and ultrasound parameters have yet to be explored for clinical translation. Our study aimed to optimize ultrasound parameters for sonodynamic therapy (SDT) with 5-ALA as a sonosensitizing agent and to evaluate its therapeutic outcome on the rodent 9L gliosarcoma and the human U87 glioblastoma models.

A novel 4,4-dimethylcytidine in the archaeal ribosome enhances hyperthermophily.

Ribosome structure and activity are challenged at high temperatures, often demanding modifications to ribosomal RNAs (rRNAs) to retain translation fidelity. LC-MS/MS, bisulfite-sequencing, and high-resolution cryo-EM structures of the archaeal ribosome identified an RNA modification, 4,4-dimethylcytidine (mC), at the universally conserved C918 in the 16S rRNA helix 31 loop. Here, we characterize and structurally resolve a class of RNA methyltransferase that generates mC whose function is critical for hyperthermophilic growth.

The Comparison of Lifestyles, Mental Risks, and Physical Indices among Individuals with Ultra-High Risk of Psychosis, Patients with Schizophrenia, and the General Public.

(1) Background: Early interventions may effectively reduce the risk of mental disorders in individuals with ultra-high risk. Specifying the health needs of individuals with ultra-high risk is crucial before the implementation of successful early intervention. This study aimed to explore the differences in lifestyles, mental risks, and physical indices among individuals with ultra-high risk, patients with schizophrenia, and healthy subjects.

Selective haematological cancer eradication with preserved haematopoiesis.

Haematopoietic stem cell (HSC) transplantation (HSCT) is the only curative treatment for a broad range of haematological malignancies, but the standard of care relies on untargeted chemotherapies and limited possibilities to treat malignant cells after HSCT without affecting the transplanted healthy cells. Antigen-specific cell-depleting therapies hold the promise of much more targeted elimination of diseased cells, as witnessed in the past decade by the revolution of clinical practice for B cell malignancies. However, target selection is complex and limited to antigens expressed on subsets of haematopoietic cells, resulting in a fragmented therapy landscape with high development costs.

Prognostic Impact of Heart Rhythm Shockability Trajectory in Out-of-Hospital Cardiac Arrest: A Multicenter Retrospective Study.

Background: This study aimed to investigate the association between the temporal transitions in heart rhythms during cardiopulmonary resuscitation (CPR) and outcomes after out-of-hospital cardiac arrest.

Methods: This was an analysis of the prospectively collected databases in 3 academic hospitals in northern and central Taiwan. Adult patients with out-of-hospital cardiac arrest transported by emergency medical service between 2015 and 2022 were included.

Efficacy and Safety of Radiation Segmentectomy with Y Resin Microspheres for Hepatocellular Carcinoma.

Background Limited data are available on radiation segmentectomy (RS) for treatment of hepatocellular carcinoma (HCC) using yttrium 90 (Y) resin microsphere doses determined by using a single-compartment medical internal radiation dosimetry (MIRD) model. Purpose To evaluate the efficacy and safety of RS treatment of HCC with Y resin microspheres using a single-compartment MIRD model and correlate posttreatment dose with outcomes. Materials and Methods This retrospective single-center study included adult patients with HCC who underwent RS with Y resin microspheres between July 2014 and December 2022.

Tumour-selective activity of RAS-GTP inhibition in pancreatic cancer.

Broad-spectrum RAS inhibition has the potential to benefit roughly a quarter of human patients with cancer whose tumours are driven by RAS mutations. RMC-7977 is a highly selective inhibitor of the active GTP-bound forms of KRAS, HRAS and NRAS, with affinity for both mutant and wild-type variants. More than 90% of cases of human pancreatic ductal adenocarcinoma (PDAC) are driven by activating mutations in KRAS.

Characterizing Metabolic Heterogeneity of Hepatocellular Carcinoma with Hyperpolarized C Pyruvate MRI and Mass Spectrometry.

Purpose To characterize the metabolomic profiles of two hepatocellular carcinoma (HCC) rat models, track evolution of these profiles to a stimulated tumor state, and assess their effect on lactate flux with hyperpolarized (HP) carbon 13 (C) MRI. Materials and Methods Forty-three female adult Fischer rats were implanted with N1S1 or McA-RH7777 HCC tumors. In vivo lactate-to-pyruvate ratio (LPR) was measured with HP C MRI at 9.

Healthcare Costs and Healthcare Utilization Outcomes of Vitamin D3 Supplementation at 5000 IU Daily during a 10.9 Month Observation Period within a Pragmatic Randomized Clinical Trial.

Vitamin D insufficiency has been linked to multiple conditions including bone disease, respiratory disease, cardiovascular disease, diabetes, and cancer. Observational studies indicate lower healthcare costs and healthcare utilization with sufficient vitamin D levels. The secondary aims of our previously published pragmatic clinical trial of vitamin D3 supplementation were comparisons of healthcare costs and healthcare utilization.

Transcriptomic and proteomic assessment of tocilizumab response in a randomized controlled trial of patients hospitalized with COVID-19.

High interleukin (IL)-6 levels are associated with greater COVID-19 severity. IL-6 receptor blockade by tocilizumab (anti-IL6R; Actemra) is used globally for the treatment of severe COVID-19, yet a molecular understanding of the therapeutic benefit remains unclear. We characterized the immune profile and identified cellular and molecular pathways modified by tocilizumab in peripheral blood samples from patients enrolled in the COVACTA study, a phase 3, randomized, double-blind, placebo-controlled trial of the efficacy and safety of tocilizumab in hospitalized patients with severe COVID-19.

Totality of evidence of the effectiveness of repurposed therapies for COVID-19: Can we use real-world studies alongside randomized controlled trials?

Rapid and robust strategies to evaluate the efficacy and effectiveness of novel and existing pharmacotherapeutic interventions (repurposed treatments) in future pandemics are required. Observational "real-world studies" (RWS) can report more quickly than randomized controlled trials (RCTs) and would have value were they to yield reliable results. Both RCTs and RWS were deployed during the coronavirus disease 2019 (COVID-19) pandemic.

Evaluation of a Sample-to-Result POCKIT Central SARS-CoV-2 PCR System.

The emergence of COVID-19 has caused unprecedented impacts on global public health and many other aspects. Meanwhile, many types of methods have been developed to detect the causative agent, SARS-CoV-2; this has greatly advanced the technologies in the diagnostic field. Here, we describe the development and validation of a sample-in-result-out POCKIT Central SARS-CoV-2 PCR system for detecting SARS-CoV-2 in comparison with a commercial reference real-time RT-PCR assay (TaqPath COVID-19 Combo Kit).

Prognostic value of severe acute respiratory syndrome coronavirus-2 viral load and antibodies in patients hospitalized with COVID-19.

Observational studies have identified the potential prognostic value for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load and anti-SARS-CoV-2 antibodies in coronavirus disease 2019 (COVID-19). However, viral load in nasopharyngeal (NP) swabs produced inconsistent results in prognostic analyses, and the prognostic value of viral load or antibodies has not been confirmed in large clinical trials. COVACTA and REMDACTA were double-blind, randomized, controlled trials with a combined enrollment of 1078 patients hospitalized with COVID-19 treated with tocilizumab or placebo in COVACTA or tocilizumab plus remdesivir or placebo plus remdesivir in REMDACTA.

Real-World Evidence of Effectiveness and Safety of Vedolizumab for Inflammatory Bowel Disease in Taiwan: A Prospective Nationwide Registry (VIOLET) Study.

Background: This nationwide prospective registry study investigated the real-world effectiveness, safety, and persistence of vedolizumab (VDZ) in inflammatory bowel disease (IBD) patients in Taiwan. Disease relapse rates after VDZ discontinuation due to reimbursement restriction were assessed.

Methods: Data were collected prospectively (January 2018 to May 2020) from the Taiwan Society of IBD registry.

Vitamin D3 Supplementation at 5000 IU Daily for the Prevention of Influenza-like Illness in Healthcare Workers: A Pragmatic Randomized Clinical Trial.

Vitamin D supplementation has been shown to reduce the incidence of acute respiratory infections in populations at risk. The COVID-19 pandemic has highlighted the importance of preventing viral infections in healthcare workers. The aim of this study was to assess the hypothesis that vitamin D3 supplementation at 5000 IU daily reduces influenza-like illness (ILI), including COVID-19, in healthcare workers.

Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.

Background And Objectives: COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.

Methods: This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection.

Reproducibility of the Magnitude of Lens Rotation Following Implantation of a Toric Intraocular Lens with Modified Haptics.

Purpose: To evaluate the reproducibility of magnitude of postoperative IOL rotation following implantation of a toric intraocular lens (IOL) with modified haptics, in comparison with a Proof-of-Concept (POC) study of prototype IOLs featuring the same haptic design.

Patients And Methods: A post-market, prospective, multicenter, single-arm, open-label clinical study was conducted. TECNIS Toric II IOL (Johnson & Johnson Vision, Irvine, CA, USA, Models ZCU150 to 600) were implanted in 125 subjects and evaluated at 1-day and 1-week postoperatively.

Blood-based tumor mutational burden as a biomarker for atezolizumab in non-small cell lung cancer: the phase 2 B-F1RST trial.

Tumor mutational burden (TMB) in circulating tumor DNA (ctDNA) has shown promise in predicting benefit from PD-L1/PD-1 inhibitors in retrospective studies. Aiming to assess blood TMB (bTMB) prospectively, we conducted B-F1RST ( NCT02848651 ), an open-label, phase 2 trial that evaluated bTMB as a predictive biomarker for first-line atezolizumab monotherapy in locally advanced or metastatic stage IIIB-IVB non-small cell lung cancer (n = 152). The co-primary endpoints were investigator-assessed objective response rate (ORR) per RECIST version 1.

Spectrum of MRI Features of Mucin-producing Neoplasms in the Abdomen and Pelvis.

Mucin-producing neoplasms in the abdomen and pelvis are a distinct entity, separate from simple fluid-containing neoplasms and loculated fluid collections. Mucin is a thick gelatinous substance and-owing to its high water content-has imaging features that can be mistaken for those of simple fluid-containing neoplasms with multiple imaging modalities. However, mucin-producing neoplasms arise from specific organs in the abdomen and pelvis, with unique imaging appearances, knowledge of which is important to guide accurate diagnosis and management.