This study aimed to evaluate whether MYCN amplification enhances ferroptosis susceptibility in retinoblastoma (RB) and to elucidate the key regulatory mechanisms.

MYCN-amplified Y79 and MYCN copy-number gain WERI-RB1 cells were treated with ferroptosis inducers imidazole ketone erastin (IKE) and RSL3. MYCN was silenced using short hairpin RNA (shRNA) lentiviral transduction, followed by RNA sequencing, real-time quantitative PCR, and western blot. Amino acid deprivation and propargylglycine (PAG) treatment were applied to probe cysteine metabolic pathways. Glutathione (GSH), malondialdehyde (MDA), and ferrous iron (Fe2+) levels were measured, and ultrastructural changes were examined by transmission electron microscopy. An orthotopic xenograft model was used to assess the effect of IKE, PAG, and their combination on tumor growth.

MYCN amplification correlated with increased ferroptosis sensitivity, which was reduced by MYCN knockdown. Transcriptome analysis identified dysregulation of cysteine/methionine metabolism, with decreased xCT subunits and cystathionine γ-lyase (CTH) expression. PAG potentiated IKE-induced ferroptosis and triggered cell death alone, while MYCN depletion attenuated lipid peroxidation, restored GSH, and reduced Fe2+ accumulation. In vivo, IKE, PAG, and IKE+PAG all significantly inhibited intraocular tumor growth.

MYCN promotes ferroptosis in RB via xCT and transsulfuration pathways. Targeting the MYCN-xCT-transsulfuration axis may offer a novel therapeutic approach for MYCN-amplified RB.

Asbestos is a risk factor for occupational lung cancer. This article reported a case of asbestosis. During regular chest CT scans, an enlargement of nodules in the left lower lobe was observed. After undergoing relevant examinations, the patient underwent left lower lobe resection. Postoperative pathology confirmed the diagnosis as SMARCA4-deficient undifferentiated tumor. The patient was subsequently treated with immunotherapy, radiotherapy and chemotherapy and currently has a good prognosis.

Hydroxychloroquine (HCQ) usage in COVID patients was a popular topic of study, especially during the first wave of the pandemic. However, the long-term impact of HCQ therapy on infected COVID-19 patients remains unclear.

Holding a PROSPERO registration (CRD42025113906), this study aimed to investigate the impact of long-term treatment with HCQ in patients with autoimmune diseases on mortality, as well as on the development of disease-related complications.

A comprehensive search was conducted across multiple databases. Full-text reports were included for clinical trials and observational studies on adult patients with autoimmune disease and confirmed COVID-19 infection subjected to HCQ therapy.

The search process has identified 1,126 studies, of which 17 observational studies were included.No randomized controlled trials meeting the inclusion criteria were found. Eligible studies involved 229,142 autoimmune patients treated with HCQ, of which 197,118 patients were diagnosed with COVID-19. In 14 observational studies (196,965 patients), HCQ use was associated with a lower overall mortality rate by 21% in patients with autoimmune diseases and COVID-19 (RR 0.79; 95% CI: 0.64-0.97, p = 0.02). This association may reflect a potential survival benefit; however, given the observational nature of the studies included, causal inference cannot be established, and the findings should be interpreted cautiously. There was no significant difference between HCQ-treated patients and untreated patients regarding hospitalization (12 studies with 2,238 patients included), ICU admission (8 studies with 527 patients included), mechanical ventilation (8 studies with 546 patients included), sepsis (2 studies with 132 patients included), or thrombo-embolic events rates (2 studies with 195 patients included) (RR 0.92, 95% CI 0.75- 1.14; p = 0.46), (RR 1.45; 95% CI; 0.82- 2.56, p = 0.2) and (RR 1.28; 95% CI; 0.68- 2.4, p = 0.44), (RR 1.44; 95% CI; 0.57 - 3.65, p = 0.44), (RR 0.89; 95% CI; 0.16-4.97, p = 0.89), respectively. Nonetheless, the incidence of Acute Kidney Injury (AKI) in 2 studies (136 patients) was higher in HCQ-treated groups compared to the untreated groups (RR 2.31; 95% CI; 1.29-4.12, p = 0.0047).

HCQ was associated with a significantly lower overall mortality rate in patients with autoimmune diseases and COVID-19; this association is consistent with its known immunomodulatory properties. On the other hand, it does not prevent COVID-19-related complications and could be associated with an increased risk for developing AKI. However, given the observational nature of all included studies, causal inference cannot be established. Future research is needed to confirm these observed survival benefits and to establish clear safety parameters regarding renal toxicity.

Depressive symptoms and sleep problems are prevalent among older adults with depression. To reduce their adverse impact, it is important to understand the changes in symptom patterns as the Coronavirus disease 2019 (COVID-19) pandemic emerged. This longitudinal study examined the interactive changes between depressive symptoms and sleep problems among older adults with depression before and during the COVID-19 pandemic from a network perspective in the USA.

This network analysis study was based on data from the three waves (2016, 2018, and 2020) of the Health and Retirement Study (HRS). Depressive symptoms were measured using the eight-item version of the Center for Epidemiologic Studies Depression Scale (CESD-8), and sleep problems were assessed with the four-item Jenkins Sleep Scale (JSS-4). The study examined central symptoms and bridge symptoms within the network model.

A total of 2905 older adults with depression were included in the analyses. The prevalence of depressive symptoms did not significantly change in the study wave during the COVID-19 compared to the pre-pandemic waves. "Feeling Depressed" was the most central symptom of the depression-sleep problems network in the 2016 wave, while "Feeling Sad" was the most central symptom in both the 2018 and 2020 waves. Additionally, "Feeling Loneliness" was the key bridge symptom of the depression-sleep problems network in the 2016 wave, while "Not Enjoying Life" was the key bridge symptom in the 2018 wave, and "Feeling Rested in Morning" was the key bridge symptom in the 2020 wave.

The findings highlighted that central and bridge symptoms were potential targets in treating depressive symptoms and sleep problems among older adults with depression across the study period in the USA.

The risk of neonatal respiratory distress increases in planned cesarean section (CS), due to elevated lung liquid resulting from the absence of labor. The knee-to-chest flexion (KCF) maneuver is a novel, low-resource technique intended to mimic the uterine contraction by flexing the newborn's legs against the chest to aid lung fluid expulsion. Although the maneuver has shown to be feasible and safe, its acceptability among healthcare providers is unknown. The study aimed to understand how healthcare providers perceive and accept the KCF intervention for preventing neonatal respiratory distress following planned CS.

The study used an exploratory qualitative approach, with semi-structured interviews at a tertiary referral hospital in Moshi, Tanzania. Fifteen interviews were conducted with obstetricians and resident doctors who had observed and/or performed the maneuver as part of an ongoing clinical trial which aims to test effectiveness of KCF maneuver in reducing newborn respiratory distress (ClinicalTrials.gov: NCT06270823). The data was first analyzed thematically using the Theoretical Framework of Acceptability as guidance, and later by inductive coding.

The KCF maneuver was generally viewed as acceptable, supported by its simplicity, compatibility with routine workflows, and observed clinical benefits, such as visible lung fluid expulsion. Its physiological rationale further contributed to clinicians' confidence in the procedure. However, acceptability remains closely tied to perceptions of effectiveness, with several providers awaiting trial results before they would endorse its use.

This study suggests that the KCF maneuver could be an acceptable intervention for improving newborn outcomes following planned CS, provided that efficacy is confirmed.

Complex tracheal anomalies are life threatening without intervention and often require surgery in the neonatal period to establish a stable airway. Variations of slide tracheoplasty using all autologous tissue are the gold standard in tracheal reconstruction. We have encountered 9 patients whose complex tracheal anomalies required significant variations to slide tracheoplasty. Six of these patients presented with bronchus suis with extreme long segment tracheobronchial stenosis which were effectively repaired using a side-to-side bronchus suis tracheobronchoplasty. This technique has the advantage of providing an all-autologous reconstruction with significantly less tension. Recently, we have encountered 3 patients with even more radical anatomies consisting of long segment tracheobronchial stenosis in the context of bilateral bronchus suis or Christmas-tree trachea. We employed bilateral side-to-side bronchus suis tracheoplasty in one and anterior-posterior bilateral bronchus suis tracheoplasty in the remaining 2 cases. These techniques have proven extremely effective in stabilizing the airway while preserving growth potential. Early management of these patients remains challenging, and complications are exponentially magnified by the interplay between complex cardiac physiology and complex tracheal reconstruction.

Respiratory syncytial virus (RSV) is a significant cause of respiratory infections in young children. Since 2021, RSV has been a notifiable disease in Australia. However, current surveillance systems focus on hospitalised RSV, with limited surveillance at a community level through primary care clinics. This approach only captures RSV requiring hospitalisation. Less severe illnesses, while not captured, may have significant social and economic impacts including the associated cost of care and absenteeism. The aim of this study is to establish an understanding of the broader burden of RSV in young children in a community setting.

The PATROL (Parents Actively Tracking RSV in Little Ones) project is a prospective longitudinal observational study of RSV and other respiratory viruses in children <5 years in community settings in metropolitan Perth, Western Australia. Over a 12-month surveillance period, parent/guardians will collect a mid-nasal swab from their child any time they meet the case definition or during one of the four screening points aligned with key points in the RSV season. Swabs will be tested for RSV and other respiratory viruses by PCR, with results returned to the parent/guardian. Rapid antigen tests for RSV, SARS-CoV-2 and Influenza A/B are provided for at-home testing in addition to PCR. Symptoms are reported by parents/guardians using MyCap, a phone-based application for REDCap.Incidence rates of RSV illness and asymptomatic carriage will be calculated and compared with the incidence rate ratios of other respiratory viruses.

The Government of Western Australia Child and Adolescent Health Service Human Research Ethics Committee approved all study materials. Results and findings will be disseminated through manuscripts, conference abstracts and presentations, participant newsletters and appropriate general news media items.

Accurately capturing social contact data is essential for developing effective mathematical models to forecast disease trends and evaluate interventions. There are limited population-based data of social contacts in the USA which limits our ability to accurately model infectious disease transmission.

To fill in this gap, we conducted a staggered longitudinal cohort study in metropolitan Atlanta, Georgia, USA. We aimed to characterise contact patterns and examine how they varied by (1) participant demographics, (2) seasonality and (3) self-managed and medically-attended symptoms. Once per month for 6 months, participants reported individual contacts they can name, individual contacts they cannot name and contacts that occurred in group settings. We defined individual contacts as a two-way conversation with five or more words in the physical presence of another person or physical skin-to-skin contact and group contacts as contacts with a group of people with whom participants talked, interacted or shared space. Participants were enrolled on a rolling basis, and data is collected from November 2024 through April 2026. Data analysis will generate age-specific contact matrices using individual contacts and compare contact rates by symptoms. We will also analyse the number and characteristics (eg, indoor/outdoor) of each type of contact. The contact matrices and results will be publicly available for the wider modelling community.

Kaiser Permanente Interregional Institutional Review Board (IRB) reviewed and approved all submitted study documents. An IRB Authorization Agreement was established with the Emory University IRB documenting the roles and responsibilities of each study site. On study completion, de-identified individual level contact data as well as contact matrices and analytical code will be made publicly available on GitHub/Zenodo platform. Study findings will be published in scientific journals and presented at conferences.

Seasonal influenza causes substantial illness and death in adults 50 years of age or older, even with current vaccines. An investigational messenger RNA (mRNA)-based vaccine called mRNA-1010 encodes hemagglutinin glycoproteins from World Health Organization-recommended influenza strains.

In this phase 3, double-blind, active-controlled trial, we randomly assigned adults 50 years of age or older to receive trivalent mRNA-1010 (37.5 μg, which includes 12.5 μg of each strain) or a licensed standard-dose comparator. The primary efficacy end point was relative vaccine efficacy against reverse-transcriptase-polymerase-chain-reaction (RT-PCR)-confirmed, protocol-defined influenza-like illness caused by influenza A or B, from at least 14 days after vaccination through the end of the influenza season. Hypothesis testing was conducted hierarchically to assess noninferiority (lower boundary of the 95% confidence interval [CI], >-10%), superiority (lower boundary of the 95% CI, >0%), and a higher level of superiority (lower boundary of the 95% CI, >9.1%).

A total of 40,703 participants received mRNA-1010 (20,350 participants) or the standard-dose comparator (20,353 participants); the median follow-up was 181 days (range, 1 to 227). RT-PCR-confirmed, protocol-defined influenza-like illness was observed in 411 of 20,179 recipients of mRNA-1010 (2.0%) and 557 of 20,124 recipients of the standard-dose comparator (2.8%), which corresponds to a relative vaccine efficacy of 26.6% (95% CI, 16.7 to 35.4), thereby meeting the criteria for noninferiority, superiority, and higher-level superiority. Solicited adverse reactions were more frequent with mRNA-1010 than with the standard-dose comparator (injection-site pain in 65.8% vs. 29.8%, fatigue in 45.1% vs. 20.3%, headache in 37.8% vs. 18.0%, and myalgia in 35.4% vs. 11.6%); most reactions were mild to moderate and transient. Serious adverse events were reported in 2.2% of the recipients of mRNA-1010 (with three events considered by the investigator to be vaccine-related) and in 1.9% of the recipients of the standard-dose comparator (with two events considered by the investigator to be vaccine-related).

In this trial, mRNA-1010 was superior to standard-dose licensed vaccines for prevention of RT-PCR-confirmed, protocol-defined influenza-like illness in adults 50 years of age or older. Solicited adverse reactions were more frequent with mRNA-1010. (Funded by Blackstone Life Sciences and Moderna; Fluent ClinicalTrials.gov number, NCT06602024.).

To analyze the monitoring of an intervention for expanding testing, isolation, quarantine, and telemonitoring of Covid-19 (TQT-Covid-Strategy) in an administrative health region of a municipality in Northeastern Brazil.

This is an evaluative study, whose object of analysis were data produced in the monitoring of a health intervention (TQT-Covid-Strategy), for six months, in 17 health units, namely 12 Family Health Units and five Health Centers. Monitoring matrices created through field reports, workshops with professionals and managers, and permanent education activities were analyzed. Monitoring took place in the three components of the TQT-Covid-Strategy intervention: expansion of accessibility to testing, monitoring of cases and surveillance strategies, and digital platform. The actions in each component were considered adequate (A), partially adequate (P), and inadequate (I) in relation to the activities determined in the action plan and in the protocol of the TQT-Covid-Strategy.

The component of the expansion of accessibility to testing was considered adequate, while the monitoring of cases and surveillance strategies presented partially adequate or inadequate results in many units. As for the digital platform component, there was predominantly adequate performance in relation to registration and access to test results and case reporting. However, the use of other surveillance-related resources, such as contact tracing, was inadequate.

Boosting the institutionalization of monitoring can be an important instrument for the implementation and improvement of health interventions. The regular presence of enablers and a widely disseminated protocol, in addition to community health agents, enhanced the intervention. However, partially adequate or inadequate results reinforced the importance of qualification of the work process in primary health care regarding surveillance actions and the use of information and communication technologies.