bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and risk factors of chronic cough in an adult community-dwelling portuguese population
Authors: Martins Pedro Carreiro , Caires Iolanda , Almeida Isabel , Afonso Ricardo A. , Dezerto Raquel , Tomé André , Rodrigues Ana M. , Henriques Ana Rita , Neuparth Nuno 
Published: January 2025

BackgroundChronic cough is associated with high individual and social costs, mainly due to doctor visits and diagnostic investigations.AimTo estimate the prevalence of chronic cough and identify risk factors associated with chronic cough in a community-based sample in the scope of the EpiCOUGH study.MethodsFrom June 1st to August 31st 2023, we recruited adults from the largest primary healthcare centres in Lisbon, Portugal, and invited them to participate in an online survey. Participants aged ≥20 years with a registered email address were eligible. Data collection included a health questionnaire that recorded the presence, duration, frequency and impact of cough on daily activities. Chronic cough was defined as lasting longer than eight weeks.ResultsOf the 7285 adult healthcare users who agreed to participate, 2309 (31.7%) completed the questionnaire. Most were female (59.2%), and the mean age was 51.6 (sd: 13.5) years. The estimated prevalence of chronic cough was 7.23% (CI 95%: 6.24%-8.36%). Chronic cough was associated with older age, being divorced/widowed, current smoking, obesity, asthma, working in a dusty environment and pet ownership. No cause was diagnosed in 23.36% of patients who consulted a doctor.ConclusionChronic cough was relatively common in the population studied. Our data emphasise the need to treat patients with chronic cough with strategies that address risk factors. This study also highlights the complexity of chronic cough management and the need for further research and diagnostic tools to improve patient outcomes.
Dysregulation of lipid mediators in patients with frequent exacerbations of chronic obstructive pulmonary disease
Authors: Fisk Marie , Gomez Esteban A , Sun Yuan , Mickute Monika , McEniery Carmel , Cockcroft John R , Bolton Charlotte , Fuld Jonathan , Cheriyan Joseph , MacNee Yasmin,William , Tal-Singer Ruth , Polkey Michael , Wilkinson Ian , Dalli Jesmond 
Published: January 2025

Specialised pro-resolving mediators (SPMs) are endogenously produced lipid mediators that regulate the propagation of inflammation and promote tissue repair. We hypothesised that SPM production is dysregulated in COPD; and associated with disease severity, defined by patients with stable COPD (no exacerbations)versuspatients with frequent exacerbations.MethodsLipid mediators were measured in plasma samples from patients with COPD (stable and frequent exacerbators) and age, sex, BMI-matched healthy controls using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Lipid mediator (LM) profiles were compared between controls and stable COPD patients, and stable COPD patients compared with frequent exacerbators. Exploratory association with ever occurrence of severe exacerbation over 4.1 years of follow up was examined. Data are presented as mean±semin pg·mL−1for LMs, or mean±sd.ResultsForty-nine stable COPD patients had increased levels of pro-inflammatory mediators and some SPMs compared with 28 controls (prostaglandin (PG)D2: 13.97±2.44versus0.53±0.13, p<0.001, lipoxins: 226.83±23.84versus59.84±20.25, p<0.01, respectively). Fifty-two frequent exacerbators had lower PGD2(3.07±0.97versus13.97±2.44, p<0.01) and SPMs (D-resolvins: 8.73±1.25versus34.53±8.95, p<0.01, lipoxins: 53.93±9.23versus226.83±23.84, p<0.01, respectively) compared with stable COPD patients, despite a higher neutrophil count (5.28±2.16versus4.28±1.60×109/L, p=0.004).In exacerbators, D-resolvins levels were independently, inversely associated with occurrence of severe exacerbation (OR:0.88 (95%CI: 0.79,0.97), p=0.03, over follow-up.ConclusionThese findings demonstrate distinct LM profiles of stable COPD and frequent exacerbator patients. In exacerbators, D-resolvins were downregulated compared with stable COPD patients and associated with future risk of severe exacerbations over follow up. Further work is needed to understand these findings.
Real-world usage and response to gefapixant in refractory chronic cough
Authors: Matsumoto Hisako , Kanemitsu Yoshihiro , Ohe Motoki , Tanaka Hiroshi , Terada Kunihiko , Nishi Koichi , Atsuta Ryo , Hara Johsuke , Saito Junpei , Ohmichi Mitsuhide , Ishizuka Tamotsu , Nishiuma Teruaki , Inoue Hideki , Watanabe Naoto , Nagano Tatsuya , Ueda Tetsuya , Ogawa Haruhiko , Endo Shigeru , Suzuki Takeshi , Kita Toshiyuki , Fujimori Katsuya , Ishiura Yoshihisa , Fujimura Masaki , Niimi Akio 
Published: January 2025

BackgroundThe real-world efficacy of the P2X3 antagonist gefapixant, a new class of antitussive for refractory chronic cough, is not yet fully understood. This study aimed to evaluate the real-world usage and response to gefapixant in patients with refractory chronic cough.MethodsThis multicentre, retrospective study involved patients with refractory chronic cough who visited cough clinics and were prescribed gefapixant. Data collected included baseline demographics, cough characteristics, response to gefapixant, degree of taste disturbance (both assessed by cough specialists), and the course of cough after discontinuation, if applicable.ResultsA total of 272 cases were analysed. The population was predominantly middle-aged females, with most patients having asthmatic cough as a comorbidity, dry cough, and predominantly daytime cough. Half of the patients reported a response rate of at least 5 on a 0 to 10 scale, with 25% reporting a response rate of ≥8. Among responders (response rate≥5), improvement was largely seen within 2 weeks. The median treatment duration with gefapixant was 32 days (interquartile range: 14–175), with longer treatment periods observed in responders. Responders typically had more severe pretreatment cough, dry cough, asthmatic cough as a comorbidity, and specific laryngeal sensations. In patients who discontinued gefapixant, sustained improvement was observed in responders. Taste disturbance was not associated with response to gefapixant and was less frequent in patients with cough triggers like smoke, dry air, or scents than in those without these triggers.ConclusionsGefapixant demonstrated a rapid and effective antitussive effect in this multicentre, real-world study.
Short term effects of e-cigarettes smoking on cardio-respiratory parameters, volatile organic compounds and inflammatory markers
Authors: Rizik Suha , Bar-Yoseph Ronen , Hanna Moneera , Hakim Fahed , Broza Yoav , Sader Amir , Toukan Yazeed , Haick Hossam , Bentur Lea , Gur Michal 
Published: January 2025

BackgroundElectronic cigarettes (e-cigarettes) have gained popularity in recent years. While initially introduced as a safe alternative for tobacco and a bridge for smoking cessation, subsequent studies found that they contain toxic substances. We aimed to assess the acute effect of a single e-cigarettes smoking session on cardio-respiratory parameters, exhaled volatile organic compounds (VOCs) and markers of inflammation.MethodsA prospective single center study. Participants (healthy volunteers, former e-cigarette users) were assessed before and after a 30-minutes session of e-cigarette smoking. Evaluations included vital signs, pulmonary functions – spirometry & fractional exhaled nitric oxide (FeNO), blood & exhaled breath condensate (EBC) cytokines, and electronic nose (e-nose) for analysis of exhaled VOCs profile.ResultsThirty participants, age 27.9±4.4 years. Post smoking revealed a significant increase in heart rate (77.5±10.9 to 85.5±12.1 beats/minute, p=0.002), respiratory rate (15.4±2.2 to 17.1±1.8 breaths/minute, p=0.002) and blood pressure (systolic 118±8.1 to 123.5±11.9, p=0.017; diastolic 73.9±8.4 to 78.5±6.3 mmHg. p=0.011). FeNO decreased significantly (median of 11 [7.5–15.5] to 9.7 [7.3–17.3[ ppb, p=0.024). Analysis of e-nose found a significant change of exhaled VOCs pattern after e-cigarettes smoking. No significant changes were found in spirometry and cytokine levels in blood or EBC.ConclusionsA single session of 30 min e-cigarettes smoking caused significant cardio-respiratory effects, decreased FeNO and altered exhaled VOCs patter, similar to the effect seen with cigarette and water-pipe smoking.‏ The observed acute effects, together with the well known chronic risks, highlight the importance of effectIve regulation of e-cigarettes.
The role and mechanism of HMGB1-mediated Notch1/Hes-1 pathway in anxiety and depression-like behaviors in mice with chronic rhinosinusitis
Authors: Zhou Fangwei , Jiang Yiting , Li Yangsong , Li Jianyao , Zhang Tian , Yu Guodong 
Published: January 2025

Abstract
Background
Chronic rhinosinusitis (CRS) is a global health issue, with some patients experiencing anxiety and depression-like symptoms. This study investigates the role of HMGB1 in anxiety and depression-like behaviors associated with the microglial Notch1/Hes-1 pathway in CRS mice.

Methods
A CRS mouse model was developed, and behavioral assessments were conducted to evaluate anxiety and depression-like behaviors. Techniques including 18F-FDG PET, Nissl staining, and immunofluorescence were used to assess hippocampal metabolic activity in CRS mice. Western Blot and RT-qPCR were employed to measure HMGB1 and Notch1/Hes-1 expression in the hippocampus, while ELISA determined inflammatory cytokine levels. The study also examined the effects of metformin on these behaviors and its mechanisms.

Results
CRS mice exhibited increased anxiety and depression-like behaviors, accompanied by enhanced hippocampal metabolic activity. HMGB1-siRNA treatment reduced these behaviors. Hippocampal glucose metabolism was markedly higher in CRS mice than in controls. Nissl staining revealed hippocampal neuron damage, and immunofluorescence indicated microglial activation in CRS mice. Reducing HMGB1 expression inhibited Notch1/Hes-1 pathway activation. In microglia, HMGB1 knockdown suppressed the Notch1/Hes-1 pathway, reducing inflammatory cytokine secretion. Metformin improved neuropsychiatric symptoms in CRS mice by inhibiting the Notch1/Hes-1 pathway after HMGB1 downregulation.

Conclusion
HMGB1 activates the microglial Notch1/Hes-1 pathway in CRS mice, promoting neuroinflammation and anxiety and depression-like behaviors. Metformin alleviates these effects.
Clinical and bacteriological characteristics of Corynebacterium keratitis
Authors: Inoue Hidenori , Toriyama Koji , Murakami Shinobu , Miyamoto Hitoshi , Ikegawa Wakako , Takezawa Yuki , Sakane Yuri , Hara Yuko , Shiraishi Atsushi 
Published: January 2025

Abstract
Purpose
Corynebacterium species are commensals of human skin and mucous membranes and are recognized as important pathogens in ocular infections. This study investigated the clinical characteristics of Corynebacterium keratitis.

Methods
We retrospectively reviewed cases of bacterial keratitis in which Corynebacterium species were solely isolated from corneal scraping cultures collected at Ehime University Hospital between January 2010 and February 2024. The clinical findings of Corynebacterium keratitis were divided into two types: adherent and infiltrative, which are defined as adhesion to the corneal surface or stromal infiltration, respectively.

Results
Of the 232 culture-positive cases of bacterial keratitis, 23 (9.9%) were positive for Corynebacterium species alone. The mean patient age was 60.1 ± 21.0 years, and the cohort included 12 males and 11 females. Adherent type was found in 13 patients (56.5%) and infiltrative type was observed in 10 patients (43.5%). Fluoroquinolone eye drops were used by 14 (60.9%) patients and steroid eye drops by 12 (52.2%). Corynebacterium macginleyi was the most commonly identified species (85.7%). 91% of Corynebacterium isolates were resistant to fluoroquinolones. All of C. macginleyi isolates were fluoroquinolone-resistant, and 93.3% of the isolates were highly resistant (minimal inhibitory concentrations > 32 µg/mL). All cases were treated with frequent antimicrobial eye drops, mainly cephalosporins, and the mean treatment duration was 21.6 days. Although no patient required therapeutic keratoplasty, five adherent types required multiple therapeutic debridements to physically remove the bacteria.

Conclusions
Corynebacterium keratitis presented as adherent and infiltrative types of lesions. The main characteristics of the patient included the use of fluoroquinolone and steroid eye drops.
Epidemiology and clinicopathological features of soft tissue tumors in adolescents: a cross-sectional study
Authors: Ofiaeli Ogochukwu Chioma , Menkiti Felix Emeka , Modekwe Victor Ifeanyichukwu , Chukwurah Shirley Nneka , Ofiaeli Ogochukwu Robinson , Odita Amalachukwu Okwukweka 
Published: January 2025

Abstract
Background
Soft tissue tumors (STTs) in adolescents are relatively rare, and their characteristics and behavior have not been well studied in this age group. The aim of this study was to describe the clinicopathologic patterns of STTs in adolescents aged 10–19 years according to the 2020 WHO classification.

Method
A 10-year retrospective cross-sectional study of 632 surgical samples from adolescents was conducted at a tertiary health facility to determine the frequency, histological patterns and characteristics of STTs in this population. The data were analyzed via SPSS 23.

Results
STTs accounted for 12.5% of all histologically diagnosed lesions in adolescents, with a mean age of 15 ± 2.9 years, 54.4% occurring in females and 35.4% in middle adolescents. The majority (64.56%) of STTs were benign, while malignant and intermediate-grade neoplasms accounted for 25.32% and 10.13%, respectively. Vascular tumours were the most common, followed by adipocytic and fibroblastic/myofibroblastic tumours, with hemangiomas being the most common. The most prevalent symptom was a painless mass (82.3%), with the head and neck (25.3%) being the most commonly involved body site. Most of the STTs patients presented within the first two years of occurrence (36.7%, n = 29/79). However, age, age group and sex were not significantly associated with the WHO grades of these STTs.

Conclusion
This study provided valuable insights into the characteristics and behavior of STTs in adolescents, highlighting the importance of early diagnosis and management. These findings suggest that adolescent STTs affect females more than males , involve the head and neck more and are more benign, with vascular tumours being the most common type of STT in this age group.
The most appropriate indicators of successful ovarian stimulation
Authors: Roque Matheus , Sunkara Sesh K. 
Published: January 2025

AbstractOvarian stimulation (OS) is a crucial component of clinical IVF treatment that strongly influences outcomes. As such, it is useful to understand the indicators for successful OS during IVF. As OS leads to multiple follicular recruitment, it can be quantified as number of oocytes retrieved. Optimal OS should help to maximize the number of oocytes, thus improving preclinical laboratory outcomes. Optimal preclinical outcomes should ultimately lead to clinical outcomes with maximal efficacy, safety, and cost-effectiveness. To help guide successful OS, this review details prognostic factors and appropriate endpoints for an optimal OS at each stage of the IVF cycle.
Effect of eicosapentaenoic acid on innate immune responses in Atlantic salmon cells infected with infectious salmon anemia virus
Authors: Holmlund Ingrid , Ahmadi Samira , Ruyter Bente , Østbye Tone-Kari , Bou Marta , Gjøen Tor 
Published: January 2025

AbstractAquaculture is one of the world's fastest-growing sectors in food production but with multiple challenges related to animal handling and infections. The disease caused by infectious salmon anemia virus (ISAV) leads to outbreaks of local epidemics, reducing animal welfare, and causing significant economic losses. The composition of feed has shifted from marine ingredients such as fish oil and fish meal towards a more plant-based diet causing reduced levels of eicosapentaenoic acid (EPA). The aim of this study was to investigate whether low or high levels of EPA affect the expression of genes related to the innate immune response 48 h after infection with ISAV. The study includes seven experimental groups: ± ISAV and various levels of EPA up to 200 µM. Analysis of RNA sequencing data showed that more than 3000 genes were affected by ISAV alone (without additional EPA). In cells with increasing levels of EPA, more than 2500 additional genes were differentially expressed. This indicates that high levels of EPA concentration have an independent effect on gene expression in virus-infected cells, not observed at lower levels of EPA. Analyses of enriched biological processes and molecular functions (GO and KEGG analysis) revealed that EPA had a limited impact on the innate immune system alone, but that many processes were affected by EPA when cells were virus infected. Several biological pathways were affected, including protein synthesis (ribosomal transcripts), peroxisome proliferator activated receptor (PPAR) signaling, and ferroptosis. Cells exposed to both increasing concentrations of EPA and virus displayed gene expression patterns indicating increased formation of oxygen radicals and that cell death via ferroptosis was activated. This gene expression pattern was not observed during infection at low EPA levels or when Atlantic salmon kidney (ASK) cells were exposed to the highest EPA level (200 μM) without virus infection. Cell death via ferroptosis may therefore be a mechanism for controlled cell death and thus reduction of virus replication when there are enough polyunsaturated fatty acids (PUFAs) in the membrane.
A machine learning model accurately identifies glycogen storage disease Ia patients based on plasma acylcarnitine profiles
Authors: Groen Joost , de Haan Bas M. , Overduin Ruben J. , Haijer-Schreuder Andrea B. , Derks Terry GJ , Heiner-Fokkema M. Rebecca 
Published: January 2025

Abstract
Background
Glycogen storage disease (GSD) Ia is an ultra-rare inherited disorder of carbohydrate metabolism. Patients often present in the first months of life with fasting hypoketotic hypoglycemia and hepatomegaly. The diagnosis of GSD Ia relies on a combination of different biomarkers, mostly routine clinical chemical markers and subsequent genetic confirmation. However, a specific and reliable biomarker is lacking. As GSD Ia patients demonstrate altered lipid metabolism and mitochondrial fatty acid oxidation, we built a machine learning model to identify GSD Ia patients based on plasma acylcarnitine profiles.

Methods
We collected plasma acylcarnitine profiles from 3958 patients, of whom 31 have GSD Ia. Synthetic samples were generated to address the problem of class imbalance in the dataset. We built several machine learning models based on gradient-boosted trees. Our approach included hyperparameter tuning and feature selection and generalization was checked using both nested cross-validation and a held-out test set.

Results
The binary classifier was able to correctly identify 5/6 GSD Ia patients in a held-out test set without generating significant amounts of false positive results. The best model showed excellent performance with a mean received operator curve (ROC) AUC of 0.955 and precision-recall (PR) curve AUC of 0.674 in nested CV.

Conclusions
This study demonstrates an innovative approach to applying machine learning to ultra-rare diseases by accurately identifying GSD Ia patients based on plasma free carnitine and acylcarnitine concentrations, leveraging subtle acylcarnitine abnormalities. Acylcarnitine features that were strong predictors for GSD Ia include C16-carnitine, C14OH-carnitine, total carnitine and acetylcarnitine. The model demonstrated high sensitivity and specificity, with selected parameters that were not only robust but also highly interpretable. Our approach offers potential prospect for the inclusion of GSD Ia in newborn screening. Rare diseases are underrepresented in machine learning studies and this work highlights the potential for these techniques, even in ultra-rare diseases such as GSD Ia.
Human migrations, anthropogenic changes, and insect-borne diseases in Latin America
Authors: Wilke André B. B. , Farina Priscilla , Ajelli Marco , Canale Angelo , Dantas-Torres Filipe , Otranto Domenico , Benelli Giovanni 
Published: January 2025

AbstractRapid urbanization and migration in Latin America have intensified exposure to insect-borne diseases. Malaria, Chagas disease, yellow fever, and leishmaniasis have historically afflicted the region, while dengue, chikungunya, and Zika have been described and expanded more recently. The increased presence of synanthropic vector species and spread into previously unaffected areas due to urbanization and climate warming have intensified pathogen transmission risks. This review examines recent outbreaks and reemergence of insect-borne diseases through five case studies: (i) malaria transmission linked to political instability and large-scale migration through the Amazon jungle; (ii) the expansion of triatomine bug habitats into overcrowded, substandard urban settlements, increasing Chagas disease incidence; (iii) the influence of movement and ecotourism in the Amazonia on yellow fever transmission in peri-urban areas; (iv) the spread of visceral leishmaniasis driven by deforestation and human–canine movement; and (v) dengue outbreaks in rural Amazon regions, spurred by urbanization and rural development. The findings underscore the complex interactions among vectors, pathogens, and shifting environmental and social conditions, complicating predictability and control. Addressing the social, economic, and political determinants of health is crucial to reducing disease transmission. Key measures include scaling vaccine coverage, especially for dengue and yellow fever; developing vaccines and treatments for neglected diseases; improving housing and sanitation; strengthening vector surveillance and control; fostering community engagement; enhancing data-driven interventions.
Graphical Abstract