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Background There are few reports on kidney complications after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccination, especially in the pediatric population. We report a pediatric case diagnosed with crescentic glomerulonephritis (CrGN) after the second dose of the SARS-CoV-2 mRNA vaccine. Case-diagnosis/treatment A 16-year-old girl was admitted due to dyspnea and headache approximately 6 weeks after receiving the second SARS-CoV-2 mRNA vaccine (Pfizer-BioNTech). She had previously experienced fever, nausea, vomiting, and dyspnea after the first vaccination, which persisted for a week. On admission, her blood pressure was 155/89 mmHg with a 7 kg weight gain in a month. She had microhematuria and proteinuria. Laboratory findings were as follows: blood urea nitrogen/creatinine, 66/9.57 mg/dL; and brain natriuretic peptide, 1,167 pg/mL. Anti-neutrophil cytoplasmic antibody (ANCA), anti-glomerular basement membrane (GBM) antibody, and antinuclear antibody findings were negative. Kidney doppler sonography revealed swelling and increased echogenicity of both kidneys with increased resistive index. Cardiac magnetic resonance imaging results showed early minimal fibrosis of myocarditis. We then started hemodialysis. Kidney biopsy showed diffuse extra capillary proliferative glomerulonephritis with diffuse crescent formation. We treated the patient with methylprednisolone pulse therapy with subsequent oral steroids and mycophenolate mofetil. Although dialysis was terminated, the patient remained in the chronic kidney disease stage. Conclusions This is the first case of ANCA-negative CrGN after SARS-CoV-2 mRNA vaccination in the pediatric population. As children are increasingly vaccinated with SARS-CoV-2 mRNA vaccines, monitoring for kidney complications is warranted., Author(s): Sujeong Kim [sup.1] , Jiwon Jung [sup.1] , Haeyon Cho [sup.2] , Jina Lee [sup.1] , Heounjeong Go [sup.2] , Joo Hoon Lee [sup.1] Author Affiliations: (1) grid.267370.7, 0000 [...]

Aim: To develop a family‐centred end‐of‐life care protocol and evaluate its feasibility. Design: The draft protocol was created by integrating literature review results and existing protocols and interviewing bereaved parents. A Delphi study and an experts' review were conducted to refine the draft, followed by feasibility testing with neonatal intensive care unit nurses. Results: A 71‐item protocol based on an integrated end‐of‐life care model and the family‐centred care concept was developed, comprising three sections: principal guidelines, communication during end‐of‐life care and five substeps (4, 17 and 71 items, respectively) according to changes in an infant's condition. The feasibility was confirmed by an increase in competency and a positive attitude towards infant end‐of‐life care participants who completed the protocol education. Conclusion: The protocol was feasible and improved nurses' competency and attitude in providing end‐of‐life care for infants and parents requiring support due to the loss of their infants. It can positively impact the well‐being of parents who have experienced the loss of their infants in neonatal intensive care units and enhance family‐centred care within the units. Implications for the Profession and/or Patient Care: Application of the family‐cantered end‐of‐life care could support infants' dying process and improve bereaved parents' quality of life in neonatal intensive care units. Impact: This study increased neonatal end‐of‐life nursing needs' awareness among nurses and parents during bereavement. It offered preliminary evidence regarding the feasibility of a neonatal end‐of‐life care protocol developed in this study. Reporting Method: AGREE Reporting Checklist 2016. Patient or Public Contribution: We interviewed bereaved parents to develop the draft protocol and involved neonatal care experts for the Delphi study and neonatal nurses (who would use the protocol) as feasibility test subjects. Trial Registration: This was a doctoral dissertation and did not require protocol registration as the feasibility test involved a single neonatal intensive care unit. [ABSTRACT FROM AUTHOR]

Recent studies have identified a urinary microbiome, dispelling the myth of urine sterility. Intravesical bacillus Calmette–Guérin (BCG) therapy is the preferred treatment for intermediate to high-risk non-muscle-invasive bladder cancer (BCa), although resistance occurs in 30–50% of cases. Progression to muscle-invasive cancer necessitates radical cystectomy. Our research uses 16S rRNA gene sequencing to investigate how the urinary microbiome influences BCa and its response to BCG therapy. Urine samples were collected via urethral catheterization from patients with benign conditions and non-muscle-invasive BCa, all of whom underwent BCG therapy. We utilized 16S rRNA gene sequencing to analyze the bacterial profiles and metabolic pathways in these samples. These pathways were validated using a real metabolite dataset, and we developed predictive models for malignancy and BCG response. In this study, 87 patients participated, including 29 with benign diseases and 58 with BCa. We noted distinct bacterial compositions between benign and malignant samples, indicating the potential role of the toluene degradation pathway in mitigating BCa development. Responders to BCG had differing microbial compositions and higher quinolone synthesis than non-responders, with two Bifidobacterium species being prevalent among responders, associated with prolonged recurrence-free survival. Additionally, we developed highly accurate predictive models for malignancy and BCG response. Our study delved into the mechanisms behind malignancy and BCG responses by focusing on the urinary microbiome and metabolic pathways. We pinpointed specific beneficial microbes and developed clinical models to predict malignancy and BCG therapy outcomes. These models can track recurrence and facilitate early predictions of treatment responses. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors have substantial advanced tumor treatment, but their limited benefits and strong responses in only a subset of patients remain challenging. In this study, we explored the immunomodulatory function of contactin-4 (CNTN4). CNTN4 was highly expressed in tumor tissues, and expression impaired the antitumor function of T cells. CNTN4 bound to amyloid precursor protein (APP) on T cells, which attenuated conjugation between cancer cells and T cells, and diminished T cell receptor signaling cascades. We developed an anti-CNTN4 antibody (GENA-104A16) and an anti-APP antibody (5A7) that blocked the binding between CNTN4 and APP. Administration of either GENA-104A16 or 5A7 promoted antitumor T cell responses in a syngeneic mouse model and increased tumor-infiltrating lymphocytes in vivo. Furthermore, elevated CNTN4 levels were associated with poor prognosis and negatively correlated with various cytotoxic immune-related markers. These results suggest that CNTN4-APP is an inhibitory checkpoint in T cells and represents a promising therapeutic strategy for cancer immunotherapy. Editor's summary: Contactin-4 (CNTN4) is an adhesion molecule known to engage amyloid precursor protein (APP) in the brain, but the function of this axis in T cells and antitumor immunity is not known. Jeon et al. explored the immunomodulatory role of CNTN4-APP, finding that CNTN4 expressed on tumor cells prevents T cell activation by engaging APP on T cells. They developed an anti-CNTN4 antibody (GENA-104A16) and an anti-APP antibody (5A7) and found that blocking the CNTN4-APP interaction promoted tumor killing. Expression of APP on T cells negatively correlated with response to immune checkpoint inhibitors in patients with cancer. These findings indicate that CNTN4-APP functions as an inhibitory checkpoint in T cells. —Hannah Isles [ABSTRACT FROM AUTHOR]

Resultative constructions show a wide range of cross-linguistic variation, which may pose nontrivial challenges to L2 learners. This study investigates how syntactic and semantic differences between L1 and L2 affect L2 acquisition of resultatives. In particular, we investigate how L1-Korean learners project the syntax and semantics of L2-English resultative constructions. Two different experiments are presented. The first is a comprehension test that employs an acceptability judgment task and an elicited choice task, and the second is a production test using an elicited writing task. Our experimental results consistently show that Korean learners project English resultatives with adjunct structures and interpret them as atelic events, in sharp contrast to native speakers of English. This finding is in line with previous studies in demonstrating that L1 syntax plays a crucial role in projecting L2 syntax. More importantly, this study provides novel evidence that L1 semantics (i.e., telicity) crucially influences L2 acquisition, in tandem with (but "over and above") L1 syntax. The study's results imply that a proper theory of L2 acquisition of resultatives must consider not only syntactic transfer effects but also subtle semantic differences between L1 and L2. [Paper presented at the Generative Approaches to Second Language Acquisition (14th, Southampton, UK, Apr 7 2020).]