Long non-coding RNAs (lncRNAs) are critical regulatory elements in cellular functions in states of both normalcy and disease, including cancer. LncRNAs can influence not only tumorigenesis but also cancer features such as metastasis, angiogenesis and resistance to chemo-and immune-mediated apoptotic signals. Several lncRNAs have been demonstrated to control directly or indirectly the number, type and activities of distinct immune cell populations of adaptive and innate immunities within and without the tumor microenvironment. The disruption of lncRNA expression in both cancer and immune cells may reflect alterations in tumor responses to cancer immunosurveillance and immunotherapy, thus providing new insights into lncRNA biomarker-based prognostic and therapeutic cancer assessment. Here we present an overview on lncRNAs’ functions and underlying molecular mechanisms related to cancer immunity and conventional immunotherapy, with the expectation that any elucidations may lead to a better understanding and management of cancer immune escape and response to current and future immunotherapeutics.

Dalbavancin is a semisynthetic lipoglycopeptide, which possesses great potential for bactericidal activity similar to antimicrobials with the same mechanism of action, such as vancomycin and teicoplanin. Due to its very prolonged half-life, it can be used in a single or two-dose regimen to treat infections by Gram-positive microorganisms, even resistant ones, such as methicillin-resistant Staphylococcus aureus (MRSA). Currently, it is approved only for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). The aim of this study was to investigate the clinical and microbiological characteristics of patients to whom dalbavancin was administered at the University Hospital of Heraklion and evaluate its use in regard to the COVID-19 pandemic. In total, 146 patients were included in this retrospective cohort study evaluating the use of dalbavancin from the first time it was used in 2017 until the end of 2022. The median age was 68 years (range: 21–96 years), and 86 (59%) patients were male. The most common indications for dalbavancin use were osteoarticular infections in 43%, followed by ABSSSIs in 37%, and cardiovascular infections in 10%. Dalbavancin was used empirically in one out of three patients, most commonly with the indication of ABSSSIs, and most commonly in the post-COVID-19 era. The most frequently isolated pathogens were coagulase-negative staphylococci in 70%, S. aureus in 27%, Enterococcus spp. in 22%, and Streptococcus spp. in 8%, while one out of three infections were polymicrobial. In 12% of patients, the infection was not cured, but no patients died. For patients with ABSSSIs, endocarditis and vascular infections, and bacteremia, the cure rates were more than 90%, and in osteoarticular infections, the cure rate was 76%. Thus, dalbavancin has great potential for use in complicated and invasive infections that may require prolonged intravenous antimicrobial treatment. However, further studies are required to formally investigate its role in such infections.

Neonatal hypoxia (Hx) causes white matter (WM) injury, particularly in the cerebellum. We previously demonstrated that Hx-induced reduction of cerebellar Purkinje cell (PC) activity results in locomotor deficits. Yet, the mechanism of Hx-induced cerebellar WM injury and associated locomotor abnormalities remains undetermined. Here, we show that the cerebellar WM injury and linked locomotor deficits are driven by PC activity and are reversed when PC activity is restored. Using optogenetics and multielectrode array recordings, we manipulated PC activity and captured the resulting cellular responses in WM oligodendrocyte precursor cells and GABAergic interneurons. To emulate the effects of Hx, we used light-activated halorhodopsin targeted specifically to the PC layer of normal mice. Suppression of PC firing activity at P13 and P21 phenocopied the locomotor deficits observed in Hx. Moreover, histopathologic analysis of the developing cerebellar WM following PC inhibition (P21) revealed a corresponding reduction in oligodendrocyte maturation and myelination, akin to our findings in Hx mice. Conversely, PC stimulation restored PC activity, promoted oligodendrocyte maturation, and enhanced myelination, resulting in reversed Hx-induced locomotor deficits. Our findings highlight the crucial role of PC activity in cerebellar WM development and locomotor performance following neonatal injury.

Intrinsic programs shape brain maturation; however, which of these programs are perturbed by prematurity as well as the molecular pathways involved remain unknown. The human cerebellum serves as a paradigm of extrauterine development—its accelerated growth and circuit formation align with the third trimester, a period disrupted by preterm delivery. Using multimodal datasets encompassing in vivo neuroimaging and neurodevelopmental outcomes with postmortem spatial-transcriptomic and histopathological profiling, we show that prematurity diverts the cerebellar developmental trajectory. Cerebellar growth and functional outcomes scaled with gestational age, despite modifying perinatal exposures. Spatially resolved developmental programs underlying macroscopic trajectories were marked by incomplete granule cell maturation and impaired Purkinje cell structural refinement, which indicate lineage-specific developmental asynchrony. Thus, prematurity constitutes biologically displaced maturation, in which infants of equivalent postmenstrual age occupy divergent developmental states.

Importance: Preterm survivors of necrotizing enterocolitis (NEC) face substantial neurodevelopmental impairment, but the regional biology and timing of associated brain abnormalities remain poorly defined. Objective: To define the regional, cellular, molecular, and temporal features of NEC-associated brain pathology. Design: Prospective multimodal clinical cohort study (2012–2024), complemented by postmortem tissue analyses. Setting: Level IV neonatal intensive care unit at Children’s National Hospital, Washington, DC. Participants: Of 400 infants screened, 253 preterm infants born before 37 weeks’ gestation (128 with NEC and 125 without NEC) were included across neuroimaging, plasma metabolomic, and postmortem cohorts. Exposures: Medical or surgical NEC (modified Bell stage ≥II). Main Outcomes and Measures: Primary outcomes were term-equivalent magnetic resonance imaging (MRI) abnormalities and serial ultrasound hindbrain growth; secondary outcomes were postmortem histopathology, brain and intestinal transcriptomics, and plasma metabolomics. Results: Among 179 infants with term-equivalent MRI (89 NEC, 90 controls; 102 [57.0%] male; mean [SD] gestational age, 26.3 [2.2] weeks), NEC was associated with a higher prevalence of pontine abnormalities (12.4% vs 1.1%; adjusted prevalence ratio, 9.14; 95% CI, 1.16–71.92), alongside white matter, callosal, and cerebellar abnormalities. In postmortem tissue (n = 27), white matter pathology qualitatively resembled that of prematurity, whereas the hindbrain showed distinct regional phenotypes. The cerebellum exhibited external granular layer contraction (42% reduction; P = .04), while the pons showed neuronal injury with increased morphological apoptotic burden (P ≤ .05). Brain and intestinal transcriptomics (n = 14), complemented by plasma metabolomics (n = 29), revealed divergent inflammatory and metabolic signatures. The pons showed increased neuroinflammatory and reduced mitochondrial programs, whereas the cerebellum showed reduced metabolic and cell-cycle programs alongside circulating lysophospholipid depletion. Serial ultrasonography (n = 159), anchored to the cohort mean NEC onset age of 29 weeks’ postmenstrual age, identified earlier cerebellar dimensional deficits (P = .015) and later pontine growth deceleration ( P < .001). Conclusions and Relevance: In this cohort study, NEC-associated hindbrain pathology showed asynchronous growth patterns accompanied by distinct cellular and molecular phenotypes. These findings support investigation of regional vulnerability and stage-specific neuroprotection; individual injury timing and causal mechanisms remain unresolved. Key Points: Question: How does necrotizing enterocolitis (NEC) affect specific brain regions across the clinical course of disease in preterm infants? Findings: In this multimodal cohort study of 253 preterm infants, NEC was associated with asynchronous hindbrain abnormalities. Cerebellar dimensional deficits were detectable before the cohort mean age at NEC onset and persisted without detectable further slowing, alongside progenitor layer contraction and reduced growth-related programs. Pontine growth deceleration emerged after the mean onset age with neuronal injury and inflammatory transcriptomic enrichment. Meaning: Regional differences in growth, cellular pathology, and molecular programs support investigation of stage-specific neuroprotective approaches to NEC-associated brain injury.