The COVID-19 pandemic has accelerated the integration of metabolomics and Machine Learning in biomedical research, resulting in the creation of numerous datasets with high potential for reuse. However, information regarding their accessibility, quality, and usability remains scattered and inconsistent. This systematic review aims to identify and evaluate publicly available human metabolomic datasets related to COVID-19, providing detailed information on their main characteristics and how to access them, with the goal to inform their potential for reuse in future research. Following PRISMA guidelines and the Kitchenham methodology, we conducted a comprehensive search of the scientific literature and specialized metabolomics repositories, identifying 110 unique datasets. Each dataset was assessed based on 15 variables related to data availability, accessibility, collection methodologies, sample sizes, and the extent of participant metadata provided. These datasets offer significant value for secondary analyses and ML applications, contributing to insights into disease mechanisms, early diagnosis, and patient stratification. By offering a structured overview of dataset characteristics, this review aims to support researchers in identifying suitable resources, encourages data reuse, and promotes best practices for data sharing and standardization in the context of COVID-19 and metabolomics. Nonetheless, our findings reveal critical limitations, including the underuse of dedicated repositories, frequent unavailability of raw data, lack of standardization in processed data, and insufficient metadata-particularly regarding participant demographics and clinical information. Inconsistencies in data formats and reporting standards further hinder dataset findability, interoperability, and reuse. To enhance the value and impact of future metabolomic research, we recommend adopting standardized reporting guidelines, improving metadata completeness, ensuring the availability of raw data, and promoting the use of interoperable repositories to facilitate reproducibility, integration, and broader application of shared datasets.

This study evaluated the real-world effectiveness and safety of extrafine single-inhaler triple therapy (SITT) with beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB) in chronic obstructive pulmonary disease (COPD) patients with diverse comorbidity burdens, cardiovascular (CV) history, or CV risk.

A pooled analysis of six observational studies assessed outcomes in subgroups with 1-2 or ≥3 comorbidities, CV history, or CV risk. Endpoints included COPD Assessment Test (CAT) scores, exacerbation, lung function (FEV₁), adherence (TAI-10), and cardiopulmonary events, evaluated at 3, 6, and 12 months. Comparisons were made with reference populations (0 comorbidities, no CV history, and no CV risk).

Among 5356 patients, 2431 had 1-2 comorbidities, 1087 had ≥3, 312 had a CV history, and 117 met CV-risk criteria. CAT scores decreased significantly in all subgroups following SITT initiation. Patients with comorbidities showed smaller CAT improvements vs those without, while CV history/risk groups showed greater CAT improvements than their reference groups up to month 6. Regardless of comorbidity burden or CV history, most patients remained exacerbation-free and FEV₁ improved, with no long-term differences between groups. Adherence improved as well, with patients with ≥3 comorbidities potentially showing higher adherence over the long term. Cardiopulmonary events were more frequent in higher-comorbidity groups early on but became similar over time. Patients with a CV history consistently reported more cardiopulmonary events than those without, while those with CV risk achieved similar results compared to no-risk group at any time point.

This analysis provides real-world evidence supporting extrafine BDP/FF/GB SITT as an effective and safe option for COPD patients with comorbidities, including CV history or risk. These findings help address an evidence gap in vulnerable populations and support timely initiation of SITT in high-risk patients in clinical practice.

Despite optimized dual-bronchodilator therapy, many chronic obstructive pulmonary disease (COPD) patients continue to experience refractory breathlessness. This study aimed to identify the factors contributing to refractory breathlessness in patients with COPD, and to construct a clinically useful risk stratification tool, the Refractory Breathlessness Score (RB-Score).

In this retrospective cohort study conducted at a single teaching hospital between January 2014 and December 2023, patients with COPD who maintained the same type of dual-bronchodilator therapy, with or without inhaled corticosteroids, for one year were included. Refractory breathlessness was defined as the absence of at least a 1-point improvement in the mMRC dyspnea score at 12 months following treatment initiation. Independent predictors for refractory breathlessness were identified, and weighted points were assigned based on adjusted odds ratios (aORs) to develop the RB-Score.

Among 405 eligible patients, 244 (60.2%) had refractory breathlessness. Significant contributors included exacerbation events during treatment, comorbidities (severe anemia, cardiovascular disease, depression/anxiety, pulmonary hypertension), structural abnormalities (giant bulla, endobronchial stenosis), and inhaler-related factors (poor adherence, improper technique, multiple device use). In adjusted restricted cubic spline curve, RB-Score <1.92 was associated with a decreased risk of refractory breathlessness (aOR=0.77, 95% CI=0.59-1.00), while RB-Score >3.51 indicated increased risk (aOR=1.53, 95% CI=1.00-2.35). The RB-Score achieved good predictive performance (AUROC=0.854 [95% CI=0.818-0.891], AUPRC=0.899 [95% CI=0.865-0.928]).

Refractory breathlessness in COPD results from multiple factors, including pulmonary, comorbid, and inhaler-related issues. The RB-Score may facilitate risk stratification and guide individualized interventions though external validation is required.

Allergic rhinitis (AR) is a prevalent chronic inflammatory condition characterized by nasal itching, sneezing, and congestion, significantly impairing patients' quality of life. Despite the availability of various therapeutic options, treatment efficacy remains suboptimal for certain patients, and long-term use may be accompanied by adverse effects.

This study examined the role of transient receptor potential melastatin 2 (TRPM2) in AR-like inflammation, focusing on its associations with T cell functionality, Th2 inflammatory responses, Treg/Th17 balance, and upstream Ca²⁺-NFAT signaling pathways.

Using TRPM2 knockout and WT mice within an ovalbumin-induced AR model, this research integrated behavioral assessments, histopathological analyses, immunological assays, qPCR, and Western blotting to evaluate the implications of TRPM2 deficiency for clinical symptoms, inflammatory responses, immune cell differentiation, and related signaling pathways.

TRPM2 knockout mice exhibited reduced clinical symptoms and nasal inflammation, lower serum OVA-specific IgE levels, and reduced expression of key inflammatory cytokines, including IL-4, IL-5, and IL-33. Furthermore, TRPM2 deficiency was associated with expansion of Treg cells, reduced Ca²⁺ influx, decreased NFATc1 nuclear translocation, and lower IL-2 production. Although IL-17 expression was reduced, the decrease in Th17 cell frequency did not reach statistical significance.

These findings suggest that TRPM2 participates in OVA-induced AR-like inflammation through immune and Ca²⁺-NFAT-associated mechanisms, while the mechanistic and translational implications require cautious interpretation.

This study aims to thoroughly investigate the protective effects of various breastfeeding rates on bronchopulmonary dysplasia (BPD), clarify the relationship between them, and further determine the minimum protective threshold.

This prospective study enrolled 276 preterm infants who were born in the obstetrics department of a tertiary Grade A hospital in Zhejiang, China, and were directly admitted to the NICU.

This study involved 276 infants, categorized into three breastfeeding groups based on proportion: low (100 infants, 36.2%), medium (98 infants, 35.5%), and high (78 infants, 28.3%). Notably, the incidence of BPD in the high-proportion breastfeeding group (19.5%) was significantly lower than that in the medium-proportion group (44.5%) and the low-proportion group (55%) (p < 0.05); however, there was no statistically significant difference in the incidence of BPD between the medium-proportion group and the low-proportion group (p > 0.05). Exploratory nonlinear analyses suggested a possible candidate inflection point around 0.31, above which the inverse association between breastfeeding proportion and BPD appeared stronger.

Breastfeeding plays a crucial role in protecting premature infants from BPD. However, this protective effect does not increase linearly but becomes significant only when the breastfeeding rate reaches 31%. However, this threshold-related finding should be interpreted cautiously and requires validation in larger studies with more comprehensive confounder adjustment.

Within one week of the Food and Drug Administration granting the COVID-19 vaccine Emergency Use Authorization, the HERO-Together study launched. We describe how the study utilized novel methods for streamlined enrollment and longitudinal data collection to efficiently monitor early and long-term safety of the COVID-19 vaccine.

HERO-Together is a fully remote, prospective observational cohort study, conducted through an online portal. Participants were recruited from an existing online community of healthcare workers that expanded to family and community members as vaccine eligibility expanded, as well as through marketing and point-of-vaccination efforts. Individuals received notifications to submit data at scheduled intervals for two years, and automated reminders prompted participants with missed check-ins, with centralized call center outreach for non-responders.

Multiple recruitment approaches were adopted, including direct outreach, national and local media campaigns, downloadable enrollment toolkits (e.g., social media), social media influencer partnerships, and pharmacy referrals. A study population of n = 19, 858 was enrolled within nine months of emergency use authorization, most self-reporting as white, female, working in healthcare, and all for whom variable survey completion was observed.

Collectively, diverse recruitment strategies, data collection through the online portal, and electronic consent enabled rapid, decentralized enrollment of study participants in order to remotely monitor COVID-19 vaccine safety during the early days of the pandemic.

EUPAS38671.

During the COVID-19 pandemic, selecting vaccination sites and allocating limited doses required balancing accessibility, disease control, and fairness. We formulate a multi-objective mixed-integer linear programming model that jointly determines the locations of mega-sites and allocates vaccine doses while explicitly incorporating travel inconvenience, disease dynamics, and equitable distribution. The model incorporates commuting patterns from both residential and workplace origins to more accurately capture population mobility, and employs a tractable objective formulation that proxies key public health goals, enabling efficient and equitable mass vaccination planning. Compared with the solution empirically used in Los Angeles County in 2020, we recommend more dispersed mega-site locations that result in a 26% reduction in travel inconvenience and avert an additional 200 infections.

Silica-induced pulmonary fibrosis is a debilitating condition with limited therapeutic options. Allicin, a bioactive compound derived from garlic, has shown potential anti-inflammatory and antifibrotic properties. However, its role in silica-induced pulmonary fibrosis remains unexplored. Human lung epithelial cells (BEAS-2B) and alveolar epithelial cells (A549) were exposed to silica particles, followed by allicin treatment. In vivo experiments, a murine model of silica-induced pulmonary fibrosis was established, and lentiviral tracheal instillation was employed to validate the impact of Serpinb2 knockdown on fibrotic progression. Fibrosis and ferroptosis markers, including GSH/GSSG, MDA and hydroxyproline content, were assessed. Molecular mechanisms were evaluated using Western blot, RT-PCR, and Immunofluorescence to analyze Serpinb2 expression and NF-κB pathway activation. Allicin can alleviate ferroptosis and pulmonary fibrosis induced by silica. In addition, Serpinb2 is upregulated under the induction of silicon dioxide. Inhibiting Serpinb2 can alleviate ferroptosis and pulmonary fibrosis induced by silicon dioxide. Meanwhile, the addition of allicin can inhibit Serpinb2 and thereby exert the same effect. NF-κB functions as a downstream pathway of Serpinb2. The addition of allicin can inhibit Serpinb2 and thereby suppress the NF-κB pathway, thereby exerting its inhibitory effect on ferroptosis and pulmonary fibrosis. This study demonstrates that allicin attenuates silica-induced pulmonary fibrosis by modulating Serpinb2/NF-κB pathway via inhibiting ferroptosis. These results highlight the therapeutic potential of allicin in treating pulmonary fibrosis and provide a novel mechanistic insight into its antifibrotic effects.

SARS-CoV-2 has caused a global pandemic, resulting in over two million deaths and creating an urgent need for effective treatments. Severe COVID-19 is frequently complicated by respiratory failure and acute respiratory distress syndrome (ARDS), the primary drivers of mortality. Indole-3-Carbinol (I3C), a natural compound derived from Brassicaceae that acts as an inhibitor of HECT family E3 ubiquitin ligases, exhibits potent anti-SARS-CoV-2 activity and inhibits viral egress. However, its in vivo therapeutic efficacy against SARS-CoV-2-induced lung injury remains unproven. We evaluated the therapeutic efficacy of I3C in reducing the severity of SARS-CoV-2 infection and associated lung lesions using the Syrian golden hamster (Mesocricetus auratus) model, which recapitulates the acute lung injury observed in human COVID-19. Treatment with a non-toxic dose of I3C (2 mg) significantly ameliorated disease across all parameters, reducing weight loss, improving clinical symptom scores and reducing histopathological lung damage observed post-mortem. A significant reduction in pulmonary TNF-α levels accompanied this. These findings indicate that I3C mitigates COVID-19-related morbidity at clinically relevant, non-toxic doses. Given its dual antiviral and anti-inflammatory mechanisms, I3C represents a compelling therapeutic candidate for further clinical investigation.

A woman in her 30s was administered linezolid treatment for pneumonia. Without continuous medical prescriptions, the patient self-administered linezolid for a total of 9 months, which subsequently led to symptoms of bilateral visual impairment and central scotomas. Fundus examination revealed blurred disc margins, accompanied with mild edema, flame-shaped hemorrhages around the optic disc, and mild tortuosity and dilation of retinal veins in both eyes. Visual field testing indicated the presence of central scotomas in both eyes. Visual evoked potentials testing showed reduced amplitudes in both eyes. After excluding other causes of optic neuropathy, the patient was tentatively diagnosed with bilateral toxic optic neuropathy (linezolid-associated optic neuropathy) based on these findings. After discontinuing linezolid, the patient's visual function gradually improved. This case suggests that close monitoring of visual function and neurological symptoms in patients receiving linezolid treatment is crucial, and early identification of relevant abnormalities and timely discontinuation of the drug can effectively improve patient prognosis.