Efficacy and safety of daprodustat in patients on peritoneal dialysis in the ASCEND-D trial.

Background And Hypothesis: Daprodustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, is approved for treatment of anemia in dialysis patients with CKD in some parts of the world. This subgroup analysis examined the efficacy and safety of daprodustat versus darbepoetin alfa in patients with anemia of CKD undergoing peritoneal dialysis (PD).

Methods: ASCEND-D (NCT02879305) was an open-label, Phase 3 trial; patients with CKD were randomized to daprodustat daily and epoetin alfa (HD patients) or darbepoetin alfa (PD patients).

Governance and resilience as entry points for transforming food systems in the countdown to 2030.

Due to complex interactions, changes in any one area of food systems are likely to impact-and possibly depend on-changes in other areas. Here we present the first annual monitoring update of the indicator framework proposed by the Food Systems Countdown Initiative, with new qualitative analysis elucidating interactions across indicators. Since 2000, we find that 20 of 42 indicators with time series have been trending in a desirable direction, indicating modest positive change.

Inosine monophosphate dehydrogenase 2 (IMPDH2) modulates response to therapy and chemo-resistance in triple negative breast cancer.

Triple negative breast cancer (TNBC) is one of the deadliest subtypes of breast cancer, whose high frequency of relapse is often due to resistance to chemotherapy. Here, we identify inosine monophosphate dehydrogenase 2 (IMPDH2) as a contributor to doxorubicin resistance, in multiple TNBC models. Analysis of publicly available datasets reveals elevated IMPDH2 expression to associate with worse overall TNBC prognosis in the clinic, including lower recurrence-free survival post adjuvant/neoadjuvant therapy.

Targeting pleuro-alveolar junctions reverses lung fibrosis in mice.

Lung fibrosis development utilizes alveolar macrophages, with mechanisms that are incompletely understood. Here, we fate map connective tissue during mouse lung fibrosis and observe disassembly and transfer of connective tissue macromolecules from pleuro-alveolar junctions (PAJs) into deep lung tissue, to activate fibroblasts and fibrosis. Disassembly and transfer of PAJ macromolecules into deep lung tissue occurs by alveolar macrophages, activating cysteine-type proteolysis on pleural mesothelium.

Endoscopic Monitoring of Treatment of Indeterminate Intestinal Lesions in a Prospective "Real-Life" Cohort in Eastern India Where Tuberculosis Remains Endemic: Distinguishing Intestinal Tuberculosis From Crohn's Disease.

Introduction It is sometimes difficult to differentiate between intestinal tuberculosis (ITB) and Crohn's disease (CD) in India, as both conditions may mimic each other. The aim was to differentiate ITB from CD in indeterminate intestinal lesions with a therapeutic trial of anti-tubercular therapy (ATT) and follow-up to find out the clinical, endoscopic, radiological, and histological predictors for differentiation between ITB and CD. Methods A prospective observational cohort study of patients diagnosed with ITB and CD according to the Asia-Pacific Guidelines in a "real-life" clinical setting was conducted.

Secondary haemophagocytic lymphohistiocytosis associated with scrub typhus: A case report with a brief review of literature.

Scrub typhus is a very important cause of acute undifferentiated febrile illness in the Asia-Pacific region. Haemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition characterised by widespread immune system activation, resulting in tissue damage throughout multiple organ systems. HLH is categorised into primary HLH, arising from intrinsic defects in lymphocytes and macrophages, and secondary HLH, primarily triggered by infections or connective tissue disorders.

Serum Uric Acid and Iron Status: Exploring a Complex Interaction in Metabolic Syndrome Patients of Eastern India.

Background: Metabolic syndrome, a cluster of illnesses including insulin resistance, hyperlipidemia, hypertension, and central obesity, is affecting roughly a quarter of the world population. Dysregulation of iron homeostasis may be associated with insulin resistance, leading to metabolic syndrome. Uric acid is an antioxidant currently studied in relation to several metabolic disorders.

Intracellular metabolomic profiling of Picochlorum sp. under diurnal conditions mimicking outdoor light, temperature, and seasonal variations.

Introduction: This study focuses on metabolic profiling of a robust marine green algal strain Picochlorum sp. MCC39 that exhibits resilient growth under diverse outdoor open pond conditions. Given its potential for producing high-value chemicals through metabolic engineering, understanding its metabolic dynamics is crucial for pathway modification.

Clinical Utility of Recently Food and Drug Administration-Approved IntelliSep Test (Sepsis Biomarker) for Early Diagnosis of Sepsis: Comparison with Other Biomarkers.

IntelliSep by Cytovale has received United States (U.S.) Food and Drug Administration (FDA) approval as a sepsis biomarker test.

Anaemia and quality of life in chronic kidney disease: a consensus document from the European Anaemia of CKD Alliance.

Anaemia is common in chronic kidney disease (CKD) and has a significant impact on quality of life (QoL), work productivity and outcomes. Current management includes oral or intravenous iron and erythropoiesis-stimulating agents (ESAs), to which hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have been recently added, increasing the available therapeutic options. In randomised controlled trials, only intravenous iron improved cardiovascular outcome, while some ESAs were associated with increased adverse cardiovascular events.

Cytomegalovirus immunity in high-risk liver transplant recipients following preemptive antiviral therapy versus prophylaxis.

CMV-specific T cells, NK cells, and neutralizing antibodies (nAbs) were assessed in a randomized trial of CMV prevention with preemptive antiviral therapy (PET) versus prophylactic antiviral therapy (PRO) in donor-seropositive/recipient-seronegative (D+R-) liver transplant recipients (LTxR) at 100 days (end of intervention) and at 6 and 12 months after transplant. The PET group had significantly increased numbers of circulating polyfunctional T cells, NK cells, and nAbs compared with the PRO group at day 100, and several CMV immune parameters remained significantly higher by 12 months after transplant. Among PET recipients, preceding CMV viremia (vs.

Motility driven glassy dynamics in confluent epithelial monolayers.

As wounds heal, embryos develop, cancer spreads, or asthma progresses, the cellular monolayer undergoes a glass transition between solid-like jammed and fluid-like flowing states. During some of these processes, the cells undergo an epithelial-to-mesenchymal transition (EMT): they acquire in-plane polarity and become motile. Thus, how motility drives the glassy dynamics in epithelial systems is critical for the EMT process.

Clinical Utility of Tumor-Naïve Presurgical Circulating Tumor DNA Detection in Early-Stage NSCLC.

Objectives: The use of tumor-informed circulating tumor DNA (ctDNA) testing in patients with early-stage disease before surgery is limited, mainly owing to restricted tissue access and extended turnaround times. This study aimed to evaluate the clinical value of a tumor-naïve, methylation-based cell-free DNA assay in a large cohort of patients with resected NSCLC.

Method: We analyzed presurgical plasma samples from 895 patients with EGFR and anaplastic lymphoma kinase-wild-type, clinical stage I or II NSCLC.

Comparative evaluation of osseodensification drilling versus conventional drilling technique on dental implant stability: A systematic review.

Aim: The present systematic review compares the stability, crestal bone levels and efficacy of osseodensification (OD) drilling techniques for dental implant placement to traditional drilling methods.

Settings And Design: The Cochrane online library, PubMed, Scopus, and other well-known online resources are used in the research. Using a systematic review design, the current study examines published qualitative studies with an emphasis on analysis.

Urinary MicroRNA biomarkers of nephrotoxicity in Macaca fascicularis.

Drug-induced kidney injury (DIKI) refers to kidney damage resulting from the administration of medications. The aim of this project was to identify reliable urinary microRNA (miRNAs) biomarkers that can be used as potential predictors of DIKI before disease diagnosis. This study quantified a panel of six miRNAs (miRs-210-3p, 423-5p, 143-3p, 130b-3p, 486-5p, 193a-3p) across multiple time points using urinary samples from a previous investigation evaluating effects of a nephrotoxicant in cynomolgus monkeys.

Hepatocyte-macrophage crosstalk via the PGRN-EGFR axis modulates ADAR1-mediated immunity in the liver.

ADAR1-mediated RNA editing establishes immune tolerance to endogenous double-stranded RNA (dsRNA) by preventing its sensing, primarily by MDA5. Although deleting Ifih1 (encoding MDA5) rescues embryonic lethality in ADAR1-deficient mice, they still experience early postnatal death, and removing other MDA5 signaling proteins does not yield the same rescue. Here, we show that ablation of MDA5 in a liver-specific Adar knockout (KO) murine model fails to rescue hepatic abnormalities caused by ADAR1 loss.

Iron-(Fe3+)-Dependent Reactivation of Telomerase Drives Colorectal Cancers.

Over-consumption of iron-rich red meat and hereditary or genetic iron overload are associated with an increased risk of colorectal carcinogenesis, yet the mechanistic basis of how metal-mediated signaling leads to oncogenesis remains enigmatic. Using fresh colorectal cancer samples we identify Pirin, an iron sensor, that overcomes a rate-limiting step in oncogenesis, by reactivating the dormant human telomerase reverse transcriptase (hTERT) subunit of the telomerase holoenzyme in an iron-(Fe3+)-dependent manner and thereby drives colorectal cancers. Chemical genetic screens combined with isothermal dose-response fingerprinting and mass spectrometry identified a small molecule SP2509 that specifically inhibits Pirin-mediated hTERT reactivation in colorectal cancers by competing with iron-(Fe3+) binding.

Prognostic implication of methylation-based circulating tumor DNA detection prior to surgery in stage I non-small cell lung cancer.

Background: Circulating tumor DNA (ctDNA) positivity at diagnosis, which is associated with worse outcomes in multiple solid tumors including stage I-III non-small cell lung cancer (NSCLC), may have utility to guide (neo)adjuvant therapy.

Methods: In this retrospective study, 260 patients with clinical stage I NSCLC (180 adenocarcinoma, 80 squamous cell carcinoma) were allocated (2:1) to high- and low-risk groups based on relapse versus disease-free status ≤5 years post-surgery. We evaluated the association of preoperative ctDNA detection by a plasma-only targeted methylation-based multi-cancer early detection (MCED) test with NSCLC relapse ≤5 years post-surgery in the overall population, followed by histology-specific subgroup analyses.

A Single-Institution Review of the Use of Radiation in the Adjuvant and Definitive Management of Keloids.

Aims: Many individuals suffer from keloids that are refractory to standard treatment modalities, including surgical excision alone. Radiation therapy can be used to reduce the risk of recurrent keloids post-operatively, as well as be used as primary treatment for keloids not amenable to surgical resection. The purpose of this study was to review our institutional experience of radiation therapy for keloid management.