bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between respiratory pathogens and lung function in primary ciliary dyskinesia: cross-sectional analysis from the PROVALF-PCD cohort
Authors: Rubbo Bruna , Kant Avni , Zhang Kewei , Allegorico Annalisa , Basilicata Simona , Boon Mieke , Borrelli Melissa , Calogero Claudia , Carr Siobhán B. , Carroll Mary , Constant Carolina , Castillo Corullón Silvia , Corvol Harriet , Cutrera Renato , Dillenhöfer Stefanie , Emiralioglu Nagehan , Eralp Ela , Eryilmaz Polat Sanem , Gardner Laura , Gokdemir Yasemin , Harris Amanda , Hogg Claire , Karadag Bulent , Kobbernagel Helene , Koerner-Rettberg Cordula , Kouis Panayiotis , Lorent Natalie , Marcou Markella , Mathin June K. , Martinu Vendula , Moreno-Galdó Antonio , Morgan Lucy , Nielsen Kim G. , Omran Heymut , Ozcelik Ugur , Pohunek Petr , Raidt Johanna , Robinson Phil , Rovira-Amigo Sandra , Santamaria Francesca , Schlegtendal Anne , Tamalet Aline , Thouvenin Guillaume , Ullmann Nicola , Walker Woolf , Yiallouros Panayiotis , Kuehni Claudia E. , Latzin Philipp , Beydon Nicole , Lucas Jane S. 
Published: August 2024

IntroductionRespiratory pathogens are frequently isolated from airway samples in primary ciliary dyskinesia (PCD) patients. Few studies have investigated associations between these pathogens and lung function, with current management based on evidence from cystic fibrosis. We investigated the association between commonly isolated respiratory pathogens and lung function in PCD patients.MethodsUsing a cross-sectional design, we prospectively collected clinical and concurrent microbiology data from 408 participants with probable or confirmed PCD, aged ≥5 years, from 12 countries. We used Global Lung Function Initiative 2012 references to calculate forced expiratory volume in 1 s (FEV1) z-scores. For 351 patients (86%) with complete data, we assessed the association of the four most frequently isolated pathogens with lung function by fitting multilevel linear models with country as random intercept, adjusted for age at diagnosis, age at lung function, use of antibiotic prophylaxis and body mass index z-scores.ResultsIndividuals withPseudomonas aeruginosagrowth in culture had significantly lower FEV1z-scores (β= −0.87, 95% CI −1.40– −0.34), adjusted for presence ofHaemophilus influenzae, methicillin-sensitiveStaphylococcus aureusandStreptococcus pneumoniae, and for covariates. When stratified by age, associations remained strong for adults but not for children. Results were similar when ciliary defects by transmission electron microscopy were included in the models and when restricting analysis to only confirmed PCD cases.ConclusionsWe found thatP. aeruginosawas associated with worse lung function in individuals with PCD, particularly adults. These findings suggest that it is prudent to aim forP. aeruginosaeradication in the first instance, and to treat exacerbations promptly in colonised patients.
Effects of nintedanib on circulating biomarkers of idiopathic pulmonary fibrosis
Authors: Jenkins R. Gisli , Cottin Vincent , Nishioka Yasuhiko , Noth Imre , White Eric S. , Ittrich Carina , Diefenbach Claudia , Rohr Klaus B. , Selman Moisés , Maher Toby M. 
Published: August 2024

BackgroundBiomarkers that change in response to nintedanib in subjects with idiopathic pulmonary fibrosis (IPF) would be valuable. We investigated the effects of nintedanib on circulating biomarkers in subjects with IPF in the INMARK trial.MethodsSubjects with IPF were randomised 1:2 to receive nintedanib 150 mg twice daily or placebo for 12 weeks, after which all patients received open-label nintedanib for 40 weeks. Fold changes in adjusted mean levels of circulating biomarkers were analysed using a linear mixed model for repeated measures.Results346 subjects were treated (116 randomised to nintedanib, 230 to placebo). Surfactant protein D (SP-D) and cancer antigen 125 (CA-125), markers of epithelial injury, decreased in subjects treated with nintedanibversusplacebo. Fold changes from baseline in SP-D at week 12 corresponded to a 4% decrease and 3% increase in the nintedanib and placebo groups, respectively (ratio 0.94, 95% CI 0.89–0.99; p=0.024). Fold changes in CA-125 at week 12 corresponded to a 22% decrease and 4% increase in the nintedanib and placebo groups, respectively (ratio 0.75, 95% CI 0.71–0.81; p<0.0001). A mediation analysis suggested that 42.1% of the effect of nintedanib on change in forced vital capacity over 12 weeks was attributable to the change in CA-125. A small increase in C3A (collagen 3 degraded by ADAMTS-1/4/8) and a small decrease in C3M (collagen 3 degraded by matrix metalloproteinase-9), markers of extracellular matrix turnover, were observed in subjects treated with nintedanibversusplacebo.ConclusionsEffects of nintedanib on circulating markers of epithelial dysfunction and collagen degradation, most notably CA-125, were observed in patients with IPF.
Variability in disease severity among cystic fibrosis patients carrying residual-function variants: data from the European Cystic Fibrosis Society Patient Registry
Authors: Mei-Zahav Meir , Orenti Annalisa , Jung Andreas , Kerem Eitan 
Published: August 2024

BackgroundPeople with cystic fibrosis (CF) variants that exhibit residual function (RF) of the CF transmembrane conductance regulator are considered to have a milder disease; however, the spectrum of CF phenotype within the different RF variants has not been extensively investigated. The aim of the present study was to characterise the spectrum of CF disease severity in people with CF (pwCF) carrying different RF variants, using the European Cystic Fibrosis Society Patient Registry (ECFSPR) data.MethodsA retrospective cross-sectional and longitudinal cohort study included data from the ECFSPR during 2008–2016. Demographic and clinical characteristics of pwCF carrying different RF variants were compared with the characteristics of pwCF who are homozygous for F508del. Among those with RF, a distinction was made between pwCF carrying class IV or class V variants and pwCF carrying specific RF variants.ResultsOut of 56 701 pwCF in the ECFSPR, 6192 carried RF variants and 22 766 were homozygous for F508del. Class IV/F508del variants were associated with a milder course than class V/F508del; both were milder than pwCF homozygous for F508del. Forced expiratory volume in 1 s % predicted (FEV1pp) declined in childhood in all groups. For adults, the hazard ratio of death for class V/F508delversusclass IV/F508del was 2.14 (95% confidence interval 0.99–4.63, p=0.052). PwCF carrying 3849+10 kb C→T/F508del and pwCF carrying R334W/F508del had age-specific FEV1pp and chronic bacterial colonisation similar to those of pwCF homozygous for F508del.ConclusionThere is a wide spectrum of disease severity between the different RF variants. Some, such as those carrying 3849+10 kb C→T, have severe disease, similar to that of pwCF homozygous for F508del.
CLDN6 inhibits breast cancer growth and metastasis through SREBP1-mediated RAS palmitoylation
Authors: Jin Qiu , Qi Da , Zhang Mingzi , Qu Huinan , Dong Yuan , Sun Minghao , Quan Chengshi 
Published: August 2024

Abstract
Background
Breast cancer (BC) ranks as the third most fatal malignant tumor worldwide, with a strong reliance on fatty acid metabolism. CLDN6, a candidate BC suppressor gene, was previously identified as a regulator of fatty acid biosynthesis; however, the underlying mechanism remains elusive. In this research, we aim to clarify the specific mechanism through which CLDN6 modulates fatty acid anabolism and its impact on BC growth and metastasis.

Methods
Cell function assays, tumor xenograft mouse models, and lung metastasis mouse models were conducted to evaluate BC growth and metastasis. Human palmitic acid assay, triglyceride assay, Nile red staining, and oil red O staining were employed to investigate fatty acid anabolism. Reverse transcription polymerase chain reaction (RT–PCR), western blot, immunohistochemistry (IHC) assay, nuclear fractionation, immunofluorescence (IF), immunoprecipitation and acyl–biotin exchange (IP-ABE), chromatin immunoprecipitation (ChIP), dual luciferase reporter assay, and co-immunoprecipitation (Co-IP) were applied to elucidate the underlying molecular mechanism. Moreover, tissue microarrays of BC were analyzed to explore the clinical implications.

Results
We identified that CLDN6 inhibited BC growth and metastasis by impeding RAS palmitoylation both in vitro and in vivo. We proposed a unique theory suggesting that CLDN6 suppressed RAS palmitoylation through SREBP1-modulated de novo palmitic acid synthesis. Mechanistically, CLDN6 interacted with MAGI2 to prevent KLF5 from entering the nucleus, thereby restraining SREBF1 transcription. The downregulation of SREBP1 reduced de novo palmitic acid synthesis, hindering RAS palmitoylation and subsequent endosomal sorting complex required for transport (ESCRT)-mediated plasma membrane localization required for RAS oncogenic activation. Besides, targeting inhibition of RAS palmitoylation synergized with CLDN6 to repress BC progression.

Conclusions
Our findings provide compelling evidence that CLDN6 suppresses the palmitic acid-induced RAS palmitoylation through the MAGI2/KLF5/SREBP1 axis, thereby impeding BC malignant progression. These results propose a new insight that monitoring CLDN6 expression alongside targeting inhibition of palmitic acid-mediated palmitoylation could be a viable strategy for treating oncogenic RAS-driven BC.

Graphical Abstract
Navigating global collaboration: challenges faced by the international network on esophageal atresia
Authors: Gottrand Frédéric , Krishnan Usha , Widenmann Anke , Blom Michaela Dellenmark , Dall’Oglio Luigi , Wijnen Rene , van Wijk Michiel , Fruithof JoAnne , von Allmen Daniel , Kovesi Tom , Faure Christophe 
Published: August 2024

AbstractThe International Network on Esophageal Atresia (INoEA) stands as a beacon of collaboration in addressing the complexities of this congenital condition on a global scale. The eleven board members, from various countries (USA, Canada, France, Australia, Italy, Sweden, Germany, and The Netherlands) and backgrounds (pediatric gastroenterology, pediatric surgery, pediatric pulmonology, nursing, and parents) met in a face-to-face symposium in Lille in November 2023, to identify challenges and solutions for improving global collaboration of the network.
Association of prenatal Cleft Lip and Palate ultrasound abnormalities with copy number variants at a single Chinese tertiary center
Authors: Yan Shujuan , Yu Qiuxia , Zhou Hang , Huang Ruibin , Wang You , Ma Chunling , Guo Fei , Fu Fang , Li Ru , Li Fucheng , Jin Xiangyi , Zhen Li , Pan Min , Li Dongzhi , Liao Can 
Published: August 2024

Abstract
Backgroud
A systematic analysis was conducted to investigate the molecular etiology of fetal cleft lip and/or palate (CL/P) and the association between various types of CL/P and copy number variations (CNVs), as well as their impact on birth outcomes.

Methods
In this retrospective study conducted between January 2016 and July 2022, a cohort of pregnancies diagnosed with fetal CL/P was enrolled and comprehensive clinical data for all cases were extracted from our medical record database, including demographic data about the pregnancies, ultrasound findings, results of Chromosomal microarray (CMA), as well as relevant pregnant and perinatal outcomes.

Results
Among the 358 cases, 32 clinically significant variants in 29 (8.1%) fetuses with CL/P were detected by CMA. In 338 singleton pregnancies, the diagnostic yield of CMA in the context of CL/P fetuses was determined to be 7.7% (26/338). CP cases exhibited a relatively higher prevalence of pathogenic/likely pathogenic CNVs at a rate of 25% (3/12), followed by CLP cases at 8.0% (23/288). Notably, the CL group did not demonstrate any pathogenic/likely pathogenic CNV findings among the examined cases (0/38). The diagnostic rate of clinically significant variants was notably higher in the non-isolated CL/P group than in the isolated CL/P group (11/33, 33.3% vs. 15/305, 4.9%, p < 0.001). Within the remaining 20 twin pregnancies, three clinically significant variants (15%) were observed.

Conclusions
This study provides powerful evidence supporting the efficacy of CMA as a valuable tool for facilitating the prenatal genetic diagnosis of fetal CL/P. The presence of CP and CLP in fetal cases demonstrated a relatively higher incidence of pathogenic/likely pathogenic CNVs. Moreover, when these cases were accompanied by additional ultrasound abnormalities, the likelihood of identifying diagnostic CNVs significantly increased. Conversely, cases of CL alone might not be associated with positive CNVs. The present data may significantly enhance prenatal diagnosis accuracy and facilitate informed genetic counseling for cases of fetal CL/P.
Utilizing a balloon sheath and miniprobe for diagnostic endoscopic ultrasound in eosinophilic esophagitis: a case series
Authors: Rabinowitz Simon S. , Candava Rheu , Kady Blair , Arostegui Dalia , Grossman Evan 
Published: August 2024

Abstract
Background
Endoscopic ultrasound (EUS) is a unique example of POCUS, which allows the gastroenterologist to discuss subepithelial pathology immediately after an endoscopy. The challenges that are encountered to create an acoustic interface by adding free water during the endoscopy may be curtailing the full utilization of EUS during endoscopic procedures. Eosinophilic esophagitis (EoE) is a progressive inflammatory condition whose morbidity is related to esophageal wall remodeling. However, in clinical practice, in clinical guidelines, and in many trials, EoE outcomes are based on esophageal eosinophilia and symptoms. Hence, a method to identify and quantitate the thickening of the esophageal wall, could contribute to the management of this disease.

Results
A modification of the approach employed to perform EUS during bronchoscopy was developed. An EUS miniprobe was positioned inside of a water filled balloon sheath. This technique permitted rapid and reproducible images acquisition of the total esophageal wall and its sublayers (mucosa, and submucosa + submucosa, which permitted derivation of the muscle layer). The presented series describes the results from 22 consecutive EoE patients. A full set of measurements from both the mid and distal esophagus were achieved in all EoE patients in an average time of less than 10 minutes.

Conclusions
This pilot study supports further investigations evaluating this economical, convenient, and safe technique to follow EoE patients. In addition, this approach could be potentially employed in all patients who are found to have subepithelial gastrointestinal pathology during routine endoscopic procedures.
Oculomotor behaviors in youth with an eating disorder: findings from a video-based eye tracking task
Authors: Kirkpatrick Ryan H. , Booij Linda , Riek Heidi C. , Huang Jeff , Pitigoi Isabell C. , Brien Donald C. , Coe Brian C. , Couturier Jennifer , Khalid-Khan Sarosh , Munoz Douglas P. 
Published: August 2024

AbstractBackgroundThe oculomotor circuit spans many cortical and subcortical areas that have been implicated in psychiatric disease. This, combined with previous findings, suggests that eye tracking may be a useful method to investigate eating disorders. Therefore, this study aimed to assess oculomotor behaviors in youth with and without an eating disorder.MethodsFemale youth with and without an eating disorder completed a structured task involving randomly interleaved pro-saccade (toward at a stimulus) and anti-saccade (away from stimulus) trials with video-based eye tracking. Differences in saccades (rapid eye movements between two points), eye blinks and pupil were examined.ResultsYouth with an eating disorder (n = 65,Mage= 17.16 ± 3.5 years) were compared to healthy controls (HC;n = 65,Mage= 17.88 ± 4.3 years). The eating disorder group was composed of individuals with anorexia nervosa (n = 49), bulimia nervosa (n = 7) and other specified feeding or eating disorder (n = 9). The eating disorder group was further divided into two subgroups: individuals with a restrictive spectrum eating disorder (ED-R;n = 43) or a bulimic spectrum eating disorder (ED-BP;n = 22). In pro-saccade trials, the eating disorder group made significantly more fixation breaks than HCs (F(1,128) = 5.33,p = 0.023). The ED-BP group made the most anticipatory pro-saccades, followed by ED-R, then HCs (F(2,127) = 3.38,p = 0.037). Groups did not differ on rate of correct express or regular latency pro-saccades. In anti-saccade trials, groups only significantly differed on percentage of direction errors corrected (F(2, 127) = 4.554,p = 0.012). The eating disorder group had a significantly smaller baseline pupil size (F(2,127) = 3.60,p = 0.030) and slower pro-saccade dilation velocity (F(2,127) = 3.30,p = 0.040) compared to HCs. The ED-R group had the lowest blink probability during the intertrial interval (ITI), followed by ED-BP, with HCs having the highest ITI blink probability (F(2,125) = 3.63,p = 0.029).ConclusionsThese results suggest that youth with an eating disorder may have different oculomotor behaviors during a structured eye tracking task. The oculomotor behavioral differences observed in this study presents an important step towards identifying neurobiological and cognitive contributions towards eating disorders.
Targeting mitochondrial quality control: new therapeutic strategies for major diseases
Authors: Hong Wei-Long , Huang He , Zeng Xue , Duan Chen-Yang 
Published: August 2024

AbstractMitochondria play a crucial role in maintaining the normal physiological state of cells. Hence, ensuring mitochondrial quality control is imperative for the prevention and treatment of numerous diseases. Previous reviews on this topic have however been inconsistencies and lack of systematic organization. Therefore, this review aims to provide a comprehensive and systematic overview of mitochondrial quality control and explore the possibility of targeting the same for the treatment of major diseases. This review systematically summarizes three fundamental characteristics of mitochondrial quality control, including mitochondrial morphology and dynamics, function and metabolism, and protein expression and regulation. It also extensively examines how imbalances in mitochondrial quality are linked to major diseases, such as ischemia-hypoxia, inflammatory disorders, viral infections, metabolic dysregulations, degenerative conditions, and tumors. Additionally, the review explores innovative approaches to target mitochondrial quality control, including using small molecule drugs that regulate critical steps in maintaining mitochondrial quality, nanomolecular materials designed for precise targeting of mitochondria, and novel cellular therapies, such as vesicle therapy and mitochondrial transplantation. This review offers a novel perspective on comprehending the shared mechanisms underlying the occurrence and progression of major diseases and provides theoretical support and practical guidance for the clinical implementation of innovative therapeutic strategies that target mitochondrial quality control for treating major diseases.
Intelligent medicine in focus: the 5 stages of evolution in robot-assisted surgery for prostate cancer in the past 20 years and future implications
Authors: Li Jia-Kun , Tang Tong , Zong Hui , Wu Er-Man , Zhao Jing , Wu Rong-Rong , Zheng Xiao-Nan , Zhang Heng , Li Yi-Fan , Zhou Xiang-Hong , Zhang Chi-Chen , Zhang Zi-Long , Zhang Yi-Hang , Feng Wei-Zhe , Zhou Yi , Wang Jiao , Zhu Qi-Yu , Deng Qi , Zheng Jia-Ming , Yang Lu , Wei Qiang , Shen Bai-Rong 
Published: August 2024

AbstractRobot-assisted surgery has evolved into a crucial treatment for prostate cancer (PCa). However, from its appearance to today, brain-computer interface, virtual reality, and metaverse have revolutionized the field of robot-assisted surgery for PCa, presenting both opportunities and challenges. Especially in the context of contemporary big data and precision medicine, facing the heterogeneity of PCa and the complexity of clinical problems, it still needs to be continuously upgraded and improved. Keeping this in mind, this article summarized the 5 stages of the historical development of robot-assisted surgery for PCa, encompassing the stages of emergence, promotion, development, maturity, and intelligence. Initially, safety concerns were paramount, but subsequent research and engineering advancements have focused on enhancing device efficacy, surgical technology, and achieving precise multi modal treatment. The dominance of da Vinci robot-assisted surgical system has seen this evolution intimately tied to its successive versions. In the future, robot-assisted surgery for PCa will move towards intelligence, promising improved patient outcomes and personalized therapy, alongside formidable challenges. To guide future development, we propose 10 significant prospects spanning clinical, research, engineering, materials, social, and economic domains, envisioning a future era of artificial intelligence in the surgical treatment of PCa.
Identifying enthesitis in the sacroiliac joints in patients with axial spondyloarthritis by readers of varying experience: impact of the learning progress
Authors: Liu Dong , Zhao Jiaoshi , Lin Churong , Liu Budian , Li Jinwei , Zhang Yuxuan , Jin Ou , Gu Jieruo 
Published: August 2024

Abstract
Background
This study aimed to investigate the accuracy of identifying enthesitis along with other inflammatory lesions and structural lesions on the MRI of the sacroiliac joints (SIJ) by readers of varying experience and how training sessions and workshops could help improve the accuracy.

Methods
A total of 224 patients with clinical diagnosis of axial spondyloarthritis who underwent SIJ MRI examinations were retrospectively included in this study. Three readers with 5 years, 3 years and 1 year of experience in musculoskeletal imaging were invited to review the SIJ MRI images independently, while the imaging reports of a senior radiologist (> 10 years’ experience) were used as reference. After the first round of image review, a training session and a workshop on the imaging of SIJ in spondyloarthritis were held and the three readers were asked to review the images in the second round. We calculated the accuracy of identifying inflammatory and structural lesions of the three readers as well as the intra-reader agreement.

Results
Enthesitis could be observed in 52.23% of the axial spondyloarthritis patients, while 81.58% of the patients with enthesitis were accompanied with bone marrow edema. All the three readers showed better accuracy at identifying structural lesions than inflammatory lesions. In the first round of image review, the three readers only correctly identified 15.07%, 2.94% and 0.74% of the enthesitis sites. After the training session and workshop, the accuracy rose to 61.03%, 39.34% and 20.22%. The intra-reader agreement of enthesitis calculated as Cohen’s kappa was 0.23, 0.034 and 0.014, respectively.

Conclusion
Readers with less experience in musculoskeletal imaging showed lower accuracy of identifying inflammatory lesions, notably enthesitis. Training sessions and workshops could help improve the diagnostic accuracy of the junior readers.