bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluctuations in mHealth engagement following receipt of goal-discrepant feedback messages
Authors: Hurley Lex , O’Shea Nisha G , Nezami Brooke T , Valle Carmina G , Tate Deborah F
Published: January 2025

Objective

Digital behavior change interventions can successfully promote change in behavioral outcomes, but often suffer from steep decreases in engagement over time, which hampers their effectiveness. Providing feedback on goal performance is an established technique to promote goal attainment; however, theory indicates that sending goal-discrepant feedback messages could cause some users to respond more negatively than others. This analysis assessed whether goal-discrepant messaging was negatively associated with participant engagement, and if this relationship was exacerbated by baseline depressive symptoms within the context of a three-month weight loss pilot mHealth intervention.

Methods

This analysis applied a generalization of log-linear regression analysis with n = 52 participants (78.8% female, 61.5% white, ages 21–35) to assess the likelihood of reading consecutive program messages following receipt of messages with goal-discrepant content.

Results

Receipt of goal-discrepant messages was associated with a significantly lower likelihood (RR = 0.89) of participants reading the next program message sent, compared to receiving positive/neutral messages or no message, but these relationships were not influenced by depressive symptoms in this sample.

Conclusion

Feedback on goal performance remains an important behavior change technique; however, sending push messages that alert participants to their goal-discrepant status seems to reduce the likelihood that participants will read future program messages. Sending messages containing positive or neutral content does not seem to carry this negative risk among individuals in goal-discrepant states.
Beyond the watery grave: death and water reminders as (un)expected ways to increase environmental identity / Más allá de la tumba acuática: recordatorios de muerte y agua como formas (in)esperadas para fomentar la identidad ambiental
Authors: Smith Lauren K. M. , Wolfe Sarah E.
Published: January 2025

Climate change increasingly stresses global water availability and reliability via either too much (e.g., floods) or too little (e.g., droughts). To ensure safe and equitable water access and management, significant behaviour changes are needed among both water consumers and decision-makers. Yet discussing water vulnerabilities can be existentially threatening because these water crises involve considering potential physical harm or death from a life-sustaining resource. According to Terror Management Theory (TMT), implicit or explicit awareness of existential threats may result in contradictory identity reinforcements that may actually limit positive water solutions. We examined how three life-threatening water messages — specifically drowning, contaminated water consumption, dehydration — influenced environmental identity compared to a standard mortality threat and a control among 455 Canadian and American adults. Our results indicated that existentially threatening messages significantly increased environmental identity polarization ( p < .05). Given these findings, we discuss implications for sustainable water management within an increasingly threatening global environment.
Pay Takes Flight! An Experiential Compensation Exercise
Authors: Conroy Samantha A. , Downes Patrick E.
Published: January 2025

Teaching compensation system principles to undergraduate students who have limited practical experience can be challenging. We describe an exercise that puts students in the roles of compensation system designer and organization employee. This one-session exercise prompts students to create a compensation system for a fictitious paper airplane organization, then work as an employee (i.e., make paper airplanes). The exercise is particularly useful for demonstrating the sorting and incentive effects of compensation systems. This exercise is intended for undergraduate students in a human resource management or compensation course.
The Future Face of Surgery—Demographics of Students Interested in Surgery at an Academic Medical Center
Authors: Birney Jalee , Vance Dylan T , Veach Jodi A. , Sanner Dixon Katelyn , Adkins Sarah E. , Wilson Sarah C. , Minchew Heather M , Baker Jordan , Chollet-Hinton Lynn , Berbel German , Kilgore Lyndsey J
Published: January 2025

Background

The demographics of medical schools reveal a growing trend towards greater gender and underrepresented in medicine (UIM) representation among students, yet surgical residency lags behind. This study explores the demographics of first-year medical students (M1s) and their initial career interests.

Methods

A panel of faculty physicians and fourth-year medical students in surgical and nonsurgical specialties was held for M1s during orientation week. Demographic differences and career interests were collected.

Results

Fifty-six M1s, 31 (55%) female and 13 (24%) UIM, attended the event. While 35 students (62.5%) reported interest in surgery, only 7 (20%) identified as UIM and 16 (46%) as female.

Conclusion

Initial interest in surgery is comprised of mostly male and non-UIM students. Throughout medical school, this pattern persists, with current match rates into surgery not reflecting the population of students. Focusing on initial interest to surgery is crucial as it is the foundation for the pipeline of diversifying future surgeons.
Clinical outcomes and risk factors of post-polypectomy microperforation in patients with colorectal neoplasia: a case-control study
Authors: Shin Seung Yong , Cho Min Soo , Nam Jinhoon , Kim Jie-Hyun , Yoon Young Hoon , Park Hyojin , Kang Jeonghyun , Park Jae Jun
Published: January 2025

Background:

Colonoscopic polypectomy significantly reduces the incidence of colorectal cancer, but it carries potential risks, with colonic perforation being the most common and associated with significant morbidity.

Objectives:

This study evaluated the clinical outcomes and risk factors of microperforation during colonoscopic polypectomy.

Design:

A retrospective cohort study.

Methods:

We retrospectively reviewed the patients’ records who underwent colonoscopic polypectomy and subsequent plain radiographic examination to monitor perforation. Patients with pneumoperitoneum detected on plain radiography were enrolled. Patients who underwent adverse event-free colonoscopic polypectomies within 1 week of each case and were matched 2:1 by age and sex to the cases were selected as controls.

Results:

Microperforations occurred in 12 patients (8 males; age: median 64.5 years). Polyps with microperforations were more frequent in the right colon (83.3% vs 33.3%). Endoscopic mucosal resection with precutting (EMR-P; 16.7% vs 0.0%) or hot-snare polypectomy (8.3% vs 0.0%) was more frequently performed in the microperforation group. Muscle fibers at the polypectomy site were more frequently visible in the microperforation group (58.3% vs 8.3%). By multivariate analysis, right colon location and visible muscle fibers were independent risk factors for microperforation. All patients with microperforation received intravenous antibiotics and were advised to fast. Patients responded well to these conservative treatments and were discharged after a median of 3 (2–6.75) days of hospital stay.

Conclusion:

Our data suggest that conservative treatment is feasible and could be the primary management option for selected patients with microperforations postcolonoscopic polypectomy. Right-sided colonic polyps and visible muscle fibers predispose to microperforations.
‘You wake up sore, you wake up angry’: A commentary on why sleep quality is important in institutional settings
Authors: O’Mara Oscar , Bonser Thomas
Published: January 2025

Sleep is a key factor in health and well-being outcomes, but its issues and opportunities are underexplored in institutions. The prevalence of poor sleep quality and insomnia is higher in institutionalised populations than in the general population, stimulating adverse mental and physical health and well-being outcomes, including violence. With supporting evidence from an ethnographic study in an adult male prison, this policy-oriented commentary discusses the relationship between sleep and behaviour, the lived experience of sleeping in institutions, and the opportunities to improve behavioural outcomes. It concludes that sleep deprivation contributes to a downward spiral and proposes three areas of intervention to promote a more person-centred sleeping environment for health and safety.
‘I hate calling it a disability’: Exploring how labels impact adults with dyslexia through an intersectional lens
Authors: Wissell Shae , Hudson Judith , Flower Rebecca L , Goh William
Published: January 2025

Background

Limited research exists on the intricate relationship between dyslexia diagnoses and the impact of associated labels on adults. Dyslexia, affecting one in 10 adults, forming one of the largest neurodivergent groups, involves a diagnostic label that communicates difficulties but can also perpetuate stigma. This multifaceted condition includes biological, psychological, and social factors, with diverse terms used globally shaping societal perceptions.

Methods

This qualitative study, part of broader Australian research on dyslexic adults in employment, aims to explore preferences and perspectives on dyslexia-related labels. Involving 14 dyslexic individuals and 4 employers/managers, the study uses semi-structured interviews, employing discourse content analysis and interpretative repertoires methodology within an Intersectionality Framework. Four repertoires emerge, addressing Dyslexia the Label, Disability Label Paradigm, Dyslexia Is Not a Superpower, and The Impact of Labels on Sense of Self. Participants preferred ‘dyslexia’ over broader labels like ‘disability’, rejecting the superpower notion, while employers see dyslexia positively within work environments.

Conclusion

This study highlights the need for targeted support, advocating for strength-based labels to enhance self-perception and workplace environments, while addressing ableism. It calls for the dismantling of discriminatory practices in education, employment, and society for dyslexics. The research's novelty lies in its focus on adult dyslexic experiences within Australian workplaces.
Inhibition of AXL ameliorates pulmonary fibrosisviaattenuation of M2 macrophage polarization
Authors: Kim Dong Ha , Im Kyungtaek , Baek In-Jeoung , Choi Yun Jung , Lee Hyeonjeong , Kim Da-Som , Lee Chae Won , Jeong JaeYi , Ban Kyosun , Kim Sang-Yeob , Ji Wonjun , Lee Jae Cheol , Kim Hyun-Yi , Lee Yoonji , Yang Yeongin , Yun Miyong , Kim Ho Cheol , Choi Chang Min , Rho Jin Kyung
Published: January 2025

Rationale

Although a relationship between the Gas6/AXL pathway and pulmonary fibrosis (PF) has been suggested, the precise mechanisms and clinical implications of the AXL pathway in idiopathic pulmonary fibrosis (IPF) are still unclear.

Methods

Constitutive and conditional AXL-knockout mice were generated and injected with bleomycin (BLM) to induce pulmonary fibrosis. The expression of AXL and macrophage subtypes in BLM-injected mice and patients with IPF was analysed using flow cytometry. The therapeutic effects of the AXL inhibitors were examined.

Results

AXL-deficient mice were resistant to BLM-induced pulmonary fibrosis and had a lower degree of M2-like macrophage differentiation than wild-type mice. Interestingly, AXL expression in monocytes was enhanced according to the progression of BLM-induced pulmonary fibrosis (PF), and these results were especially prominent in Ly6Chighmonocytes. Gene silencing or inhibitor treatment with AXL inhibited the differentiation of M2-like macrophages during bone marrow-derived macrophage (BMDMs) differentiation. These results were confirmed through experiments usingAXLfl/flLysMCre+mice and systems with depletion and reconstitution of macrophages. In line with these results, patients with severe IPF had higher AXL expression in monocytes, high GAS6 levels, and an enhanced population of M2-like macrophages than those with mild IPF. Lastly, treatment with AXL inhibitors ameliorated BLM-induced PF and improved survival rate.

Conclusions

The AXL pathway in classical monocytes contributed to PF progression through the induction of M2-like macrophage differentiation. Therefore, targeting AXL may be a promising therapeutic option for PF.
Increased delay to lung transplantation for women candidates: gender-based disparity matters in the lung transplant trajectory
Authors: Tissot Adrien , Coatanea Anne-Sophie , Rousseau Olivia , Roux Antoine , Coiffard Benjamin , Demant Xavier , Renaud-Picard Benjamin , Le Pavec Jérôme , Magnan Antoine , Mornex Jean-François , Villeneuve Thomas , Falque Loïc , Salpin Mathilde , Boussaud Véronique , Knoop Christiane , Reynaud-Gaubert Martine , Kessler Romain , Dauriat Gaëlle , Lair David , Foureau Aurore , Blanc François-Xavier , Karakachoff Mathilde , Lemarchand Patricia
Published: January 2025

Background

Lung transplantation (LT) is a highly dynamic segment of solid organ transplantation in which gender plays a central role.Our objective was to investigate the causes of outcome differences between women and men all along the LT pathway.

Methods

We used data from the COhort in Lung Transplantation (COLT) study (12 participating LT centers). Analyses were performed in three phases: baseline clinical characteristics, peri-transplantation period, and post-transplantation follow-up.

Results

Overall, 1710 participants (802 women and 908 men) were included in this study. Women were less likely than men to undergo transplantation (91.6%versus95.6%, p=0.001) and waited longer before transplantation (115versus73 days, p<0.001). Female gender and pre-transplant class I anti-HLA antibodies were identified as independent factors associated with longer waiting time duration. Female LT recipients commonly received lungs from height- and sex-matched donors, despite higher female waiting-list mortality and a higher proportion of male donors. Importantly, women with oversized lung transplantation (defined by predicted TLC ratio and weight mismatch) did not have worse survival. The overall post-transplant survival of female recipients was significantly higher than that of male recipients (65.6%versus57.3%, p<0.001), although the prevalence of specific major LT outcomes did not differ according to gender.

Conclusion

Women waited longer and were less likely to undergo transplant. Women transplanted with an oversized lung did not have worse survival after transplantation, suggesting that size matching criteria based on pTLC ratio and weight mismatch may be less stringent in this context.
Effectiveness of a long-term acupuncture treatment in patients with chronic obstructive pulmonary disease: a randomised controlled trial
Authors: Suzuki Masao , Takahashi Yoshimitsu , Inoue Daiki , Kitajima Takamasa , Maekura Tomonori , Miki Keisuke , Ikeoka Kiyomitsu , Konishi Miki , Maekura Ryoji , Fukui Motonari
Published: January 2025

Objective

We conducted a 1-year acupuncture intervention trial for patients with chronic obstructive pulmonary disease (COPD) and evaluated measures of quality of life (QOL).

Methods

This 52-week randomised clinical trial was conducted in outpatient settings at two general hospitals and two clinics in Japan from January 2013 to October 2018. Forty-five patients were randomly assigned to the usual care group (UG) or the acupuncture treatment group (AG). Participants were patients with COPD classified as stage II or higher according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. The UG received usual care in accordance with the guidelines, and the AG received acupuncture treatment once a week for 48 times in addition to usual care. Changes in outcome measures were compared using analysis of covariance, with the total domain score from the St. George's Respiratory Questionnaire (SGRQ) measured at baseline and in week 52 as the primary outcome measure.

Result

The 45 participants comprised 21 patients in the UG and 24 patients in the AG. In week 52, SGRQ total domain score was significantly improved in the AG compared with the UG (mean [standard deviation] difference from baseline: −22.8 [19.0] in the AGversus6.8 [13.5] in the UG; regression coefficient between groups: −26.9; 95% confidence interval: −35.8 to −17.9). No severe adverse events were reported.

Conclusion

This study clearly suggested the long-term effectiveness of acupuncture. Acupuncture may offer a useful adjunctive therapy to improve QOL in COPD patients.
Chronic lung allograft dysfunction after lung transplantation - prevention, diagnosis and treatment in 44 European centers
Authors: Gottlieb Jens , Vos Robin , Jaksch Peter , Hellemons Merel , Martin Holm Are , Corinna Morlacchi Letizia , Magnusson Jesper , Alonso Moralejo Rodrigo , Mora-Cuesta Víctor M. , Ennekes Vera , Reed Anna , Merveilleux Claire , Vignaux Du , Hettich Ina , Bennett David , Hecker Matthias , Wald Alexandra , Guk Svitlana , Skride Andris , Nolde Anna , Knoop Christiane , Meloni Federica , Tikkanen Jussi , Larsson Hillevi , Tissot Adrien , Riddell Peter , Le Pavec Jérôme , Perch Michael , Renaud-Picard Benjamin , Carlier François M. , Müller Veronika , Parmar Jasvir , Havlin Jan , Laporta Rosalía , Matthew Schuurmans Macé , Harlander Matevž , Zenglen Slavomir , Brugiere Olivier , Kneidinger Nikolaus , Fisher Andrew , Saez-Gimenez Berta
Published: January 2025

Background

There is limited data on optimal management of chronic lung allograft dysfunction (CLAD). We aimed to describe the variability of diagnostic and therapeutic practices in Europe.

Methods

A structured questionnaire was sent to 71 centers in 24 countries. Questions were related to contemporary clinical practices for work-up, monitoring and treatment of CLAD. Number of lung transplant (LTx) procedures, patients in follow-up were collected.

Results

Forty-four centers (62%) responded from 20 countries, representing 74% of European activity. The prevalence of CLAD was estimated at 9.1 cases per million population (25th and 75th percentiles 4.4–15.7). Preferred initial work-up for probable CLAD consisted of chest CT (inspiratory 91%, expiratory 74%), donor-specific antibody (DSA) measurement (86%), bronchoalveolar lavage (BAL) (85%), and transbronchial biopsy (81%). For monitoring of definite CLAD, inspiratory CT (67%), DSA (61%), and BAL (43%) were preferred. Body plethysmography was unavailable for 16% of cases. Prophylaxis was based on preventing infections (CMV 99%, inhaled antibiotics 70% and antifungals 65%), tacrolimus-based immunosuppression (96%), azithromycin (72%), and universal proton pump inhibitor treatment (84%). First-line treatment of CLAD was based on azithromycin (82%) and steroid augmentation (74%). Photopheresis was used in 26% of cases.

Conclusion

Current European practice CLAD detection is based on spirometry, inspiratory CT and DSA, with limited access to plethysmography and expiratory CT. Prophylactic treatment is based on azithromycin, tacrolimus-based immunosuppression, and treatment of risk factors. No single treatment strategy is universally used, highlighting the need for an effective treatment of CLAD. The preferred first-line strategy is azithromycin and steroid augmentation.
The effect of moderate to late preterm birth on lung function over the first 5 years of life in a South African birth cohort
Authors: Chaya Shaakira , Simpson Shannon J , Marozva Nicola , Jacobs Carvern , Botha Maresa , Workman Lesley , Hantos Zoltán , Zar Heather J , Gray Diane
Published: January 2025

Background

Preterm birth is associated with increased mortality and morbidity, particularly due to lung disease. Low-middle income countries (LMIC) have the highest rates of preterm birth. Infants born extremely preterm rarely survive, so the largest burden is amongst moderate to late preterm (MLP) infants. The long-term health impact on MLP children in LMIC is poorly understood.

Aim

To assess the effect of MLP birth on lung function trajectories from birth to 5 years in the birth cohort Drakenstein Child Health Study.

Methods

Children were followed from birth with lung function measurements at 6 weeks and annually until 5 years. Exposures were longitudinally collected from the antenatal period through 5 years of age. Lung function tests included spectral and intra-breath oscillometry, tidal breathing and multiple breath washout. Mixed-effect models adjusted using a minimum set of variables were used.

Results

Of 923 children, 119 (13%) were born MLP [32-<37 weeks gestation; median gestational age (GA) 35 weeks] and 19 (2%)<32 weeks gestation. Children born MLP had altered lung function trajectories. Spectral oscillometry demonstrated a 13% reduction in compliance (0.87, 95% CI: 0.82; 0.92), 5% increase in resistance at end expiration (1.05, 95% CI: 1.01;1.09) and 1.74 Hz (95% CI: 1.10; 2.39) increase in resonance frequency over 5 years compared to term children. The proportion of children hospitalised for lower respiratory tract infections (LRTI) was higher in preterm born children (29 (23.6%) MLP; 18 (94.7%) extreme to very preterm; 109 (14%) term born children;p<0.01). LRTI and tobacco smoke exposure were associated with impaired lung function, but the impact of MLP on lung function was independent of these.

Conclusion

MLP born children have impaired lung function trajectories over the first 5 years of life, highlighting the importance of strengthening maternal health, perinatal care and strategies to reduce tobacco smoke exposure and early life LRTI.
Performance of two portable FeNO devices compared to a “Gold Standard” chemiluminescence device
Authors: Thanikkel Leo , Vogt Andreas , Micic Srdjan J. , Delliehausen Nadja , Vogt Simon , Moeller Alexander
Published: January 2025

Recent guidelines for the diagnosis of asthma in school children recommend the measurement of exhaled nitric oxide (FeNO) as part of the diagnostic algorithm. However, implementation may be hampered by the lack of FeNO devices that are affordable and usable in all health care settings. We aimed to compare the performance of two portable FeNO devices (Evernoa (EVE) and NObreath® (NOB)) to a stationary gold standard device (CLD 88 sp) in children.

One hundred and six (106) children aged 6–17 years under investigation or monitoring for asthma underwent FeNO measurements using the three devices in randomised order. All devices showed high repeatability across a wide FeNO range (2.5–191.9 ppb). Median FeNO levels were significantly lower with the portable devices (20.8 ppb [interquartile range: 9.5–43.5], 16 ppb [9–36], 22.8 ppb [13.2–55.2] for NOB, EVE and CLD, respectively (p<0.0001). Despite the proportional bias (−20% (NOB) and −40% (EVE), both devices demonstrated good overall agreement with CLD (>94%) at a cut-off level 25 ppb but lower agreement for the cut-off 35ppb. EVE required a greater number of attempts compared to NOB and CLD to achieve 2 valid measurements.

Both portable devices showed limited interchangeability with the gold standard, making them less applicable for research and disease monitoring purposes. However, good overall agreement at the ERS cut-off level suggests potential as a simple and convenient screening tool in clinical settings for initial asthma diagnosis.
Low molecular weight hyaluronic acid improves regeneration of CF airway epithelium
Authors: Adam Damien , Luczka-Majérus Emilie , Cellier Julie , Dos Santos-Dietz Charline , Kileztky Claire , Bonnomet Arnaud , Ruaux Christophe , Sage Edouard , Polette Myriam , Abély Michel , Coraux Christelle
Published: January 2025

Background

Cystic fibrosis (CF) is characterized by defective mucociliary clearance (MCC), chronic lung infection and exaggerated neutrophilic inflammation. Airway epithelium damage and remodelling are important components of the lung pathology progression in CF by affecting its defence functions. Identification of compounds favouring MCC through an improvement of airway epithelial structure and regeneration is therefore crucial for patients with CF (pwCF).

Materials and Methods

Using air-liquid interface (ALI) culture of human airway epithelial (HAE) cells obtained from pwCF, we examined the influence of low molecular weight-hyaluronic acid (LMW-HA) (∼40 kDa) on the regeneration and remodelling of the CF HAE.

Results

Our results show that LMW-HA normalizes the CF epithelial regeneration, even in an inflamed environment, by preventing remodelling in terms of epithelial height and basal cell hyperplasia, by avoiding inflammation-related goblet cell hyperplasia, and by stimulating multiciliated cell differentiation. As we previously reported that the remodelling was mainly due to either intrinsic inflammation of CF HAE cells or an extrinsic inflammatory environment, we examined the impact of LMW-HA on epithelial IL-8 pro-inflammatory chemokine and found that it exerts an anti-inflammatory function evidenced by a reduction in epithelial IL-8 expression and secretion.

Conclusion

We report here that LMW-HA prevents CF HAE remodelling and normalizes its cell structure probably through the modulation of epithelial cell inflammatory phenotype, and improves the multiciliated cell differentiation by a mechanism independent of its anti-inflammatory effect. These results allow to consider LMW-HA as a therapeutic candidate for the treatment of the CF lung disease.
Inhibition of IL-4Rα reduces CCL26 in bronchial epithelial cells from COPD patients
Authors: Pesic Jelena , Nieto Fontarigo Juan José , Tillgren Sofia Malm , Miguéns Suárez Pablo , Cerps Samuel , Pardali Katerina , Delaney Stephen , Uller Lena
Published: January 2025

Background

Anti-IL-4Rα monoclonal antibodies (mAb) improve lung function and decrease the number of exacerbations in patients with COPD type (T) 2 inflammation. However, the involvement of early innate immune responses underlying these treatment effects is not well known. We sought to understand the effect and mechanisms of IL-4Rα mAb treatment on bronchial epithelial cells from COPD patients under T2 inflammatory conditions with and without rhinoviral infection.

Methods

Primary bronchial epithelial cells (BECs) from healthy and COPD patients were grown at air–liquid interface (ALI) and stimulated with IL-4 or IL-13 cytokines in the presence of IL-4Rα mAb. Cells were infected with human rhinovirus 1B (HRV1B) and collected 24 h after infection. Anti-viral mediators (i.e., interferons (IFN) and pattern recognition receptors (PRR)), as well as chemokine and alarmin expression was measured by RT-qPCR and ELISA.

Results

Treatment with IL-4Rα mAb (100 nM) inhibited eotaxin-3 (CCL26) gene after IL-4/IL-13 induction (p<0.05) in COPD BECs. However, no significant changes in RV-induced IFN-β, PRRs or TSLP gene responses were observed with IL-4/IL-13 stimulation and IL-4Rα mAb treatment. Significant increase in MUC5AC gene expression was observed with both IL-4 and IL-13 stimulation, but it was not reduced with IL-4Rα treatment in BECs.

Conclusions

Inhibition of IL-4Rα reduced CCL26 levels without affecting anti-viral immune responses in bronchial epithelial cells from COPD patients. Inhibition of IL-4Rα reduced IL-4/IL-13 signaling without broadly suppressing the immune system, which might suggest that inhibition of the IL-4Rα pathways may prevent COPD exacerbations through reduction of eosinophil chemotaxis.
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

Background

Chronic cough is associated with high individual and social costs, mainly due to doctor visits and diagnostic investigations.

Aim

To 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.

Methods

From 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.

Results

Of 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.

Conclusion

Chronic 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.

Methods

Lipid 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.

Results

Forty-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.

Conclusion

These 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

Background

The 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.

Methods

This 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.

Results

A 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.

Conclusions

Gefapixant 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

Background

Electronic 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.

Methods

A 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.

Results

Thirty 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.

Conclusions

A 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

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

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

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

Ovarian 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

Aquaculture 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

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.