bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analyzing urban parks’ spatial integration in Budapest to understand changes in visitation patterns during the COVID-19 pandemic
Authors: Bereczki Zoltán , Csomós György , Farkas Jenő Zsolt 
Published: November 2023

Globally, dramatic changes in park visitation have accompanied the COVID-19 pandemic. In general, cities have experienced an overall increase in park visitation after strict lockdowns imposed in the pandemic’s first wave have been removed. However, previous research conducted in Hungary has demonstrated that park visitation varied across parks with different sizes and locations in the city. We hypothesized that the degree of the park’s integration into the urban fabric significantly affected changes in visitation. To test this hypothesis, we conducted a space syntax analysis. Findings show that community parks with an area of 10.01–50.00 hectares and a mean spatial integration of 83.37 experienced the highest increase in the number of visitors (based on mobile devices’ GNSS data). Surprisingly, large metropolitan parks providing highly complex ecosystem services lost many visitors during the pandemic, which might be due to their low spatial integration.
Mortality surrogates in combined pulmonary fibrosis and emphysema
Authors: Zhao An , Gudmundsson Eyjolfur , Mogulkoc Nesrin , van Moorsel Coline , Corte Tamera J. , Vasudev Pardeep , Romei Chiara , Chapman Robert , Wallis Tim J.M. , Denneny Emma , Goos Tinne , Savas Recep , Ahmed Asia , Brereton Christopher J. , van Es Hendrik W. , Jo Helen , De Liperi Annalisa , Duncan Mark , Pontoppidan Katarina , De Sadeleer Laurens J. , van Beek Frouke , Barnett Joseph , Cross Gary , Procter Alex , Veltkamp Marcel , Hopkins Peter , Moodley Yuben , Taliani Alessandro , Taylor Magali , Verleden Stijn , Tavanti Laura , Vermant Marie , Nair Arjun , Stewart Iain , Janes Sam M. , Young Alexandra L. , Barber David , Alexander Daniel C. , Porter Joanna C. , Wells Athol U. , Jones Mark G. , Wuyts Wim A. , Jacob Joseph 
Published: November 2023

BackgroundIdiopathic pulmonary fibrosis (IPF) with coexistent emphysema, termed combined pulmonary fibrosis and emphysema (CPFE) may associate with reduced forced vital capacity (FVC) declines compared to non-CPFE IPF patients. We examined associations between mortality and functional measures of disease progression in two IPF cohorts.MethodsVisual emphysema presence (>0% emphysema) scored on computed tomography identified CPFE patients (CPFE/non-CPFE: derivation cohort n=317/n=183, replication cohort n=358/n=152), who were subgrouped using 10% or 15% visual emphysema thresholds, and an unsupervised machine-learning model considering emphysema and interstitial lung disease extents. Baseline characteristics, 1-year relative FVC and diffusing capacity of the lung for carbon monoxide (DLCO) decline (linear mixed-effects models), and their associations with mortality (multivariable Cox regression models) were compared across non-CPFE and CPFE subgroups.ResultsIn both IPF cohorts, CPFE patients with ≥10% emphysema had a greater smoking history and lower baselineDLCOcompared to CPFE patients with <10% emphysema. Using multivariable Cox regression analyses in patients with ≥10% emphysema, 1-yearDLCOdecline showed stronger mortality associations than 1-year FVC decline. Results were maintained in patients suitable for therapeutic IPF trials and in subjects subgrouped by ≥15% emphysema and using unsupervised machine learning. Importantly, the unsupervised machine-learning approach identified CPFE patients in whom FVC decline did not associate strongly with mortality. In non-CPFE IPF patients, 1-year FVC declines ≥5% and ≥10% showed strong mortality associations.ConclusionWhen assessing disease progression in IPF,DLCOdecline should be considered in patients with ≥10% emphysema and a ≥5% 1-year relative FVC decline threshold considered in non-CPFE IPF patients.
Inhaled recombinant GM-CSF reduces the need for whole lung lavage and improves gas exchange in autoimmune pulmonary alveolar proteinosis patients
Authors: Campo Ilaria , Carey Brenna C. , Paracchini Elena , Kadija Zamir , De Silvestri Annalisa , Rodi Giuseppe , De Amici Mara , Torre Cristina , Zorzetto Michele , Griese Matthias , Meloni Federica , Corsico Angelo Guido , Trapnell Bruce C. , Mariani Francesca 
Published: November 2023

RationaleWhole lung lavage (WLL) is a widely accepted palliative treatment for autoimmune pulmonary alveolar proteinosis (aPAP) but does not correct myeloid cell dysfunction or reverse the pathological accumulation of surfactant. In contrast, inhaled recombinant granulocyte–macrophage colony-stimulating factor (rGM-CSF) is a promising pharmacological approach that restores alveolar macrophage functions including surfactant clearance. Here, we evaluate WLL followed by inhaled rGM-CSF (sargramostim) as therapy of aPAP.Methods18 patients with moderate-to-severe aPAP were enrolled, received baseline WLL, were randomised into either the rGM-CSF group (receiving inhaled sargramostim) or control group (no scheduled therapy) and followed for 30 months after the baseline WLL. Outcome measures included additional unscheduled “rescue” WLL for disease progression, assessment of arterial blood gases, pulmonary function, computed tomography, health status, biomarkers and adverse events. Patients requiring rescue WLL were considered to have failed their assigned intervention group.ResultsThe primary end-point of time to first rescue WLL was longer in rGM-CSF-treated patients than controls (30versus18 months, n=9 per group, p=0.0078). Seven control patients (78%) and only one rGM-CSF-treated patient (11%) required rescue WLL, demonstrating a 7-fold increase in relative risk (p=0.015). Compared to controls, rGM-CSF-treated patients also had greater improvement in peripheral arterial oxygen tension, alveolar–arterial oxygen tension difference, diffusing capacity of the lungs for carbon monoxide and aPAP biomarkers. One patient from each group withdrew for personal reasons. No serious adverse events were reported.ConclusionsThis long-term, prospective, randomised trial demonstrated inhaled sargramostim following WLL reduced the requirement for WLL, improved lung function and was safe in aPAP patients. WLL plus inhaled sargramostim may be useful as combined therapy for aPAP.
Sputum microbiome α-diversity is a key feature of the COPD frequent exacerbator phenotype
Authors: Pragman Alexa A. , Hodgson Shane W. , Wu Tianhua , Zank Allison , Reilly Cavan S. , Wendt Chris H. 
Published: November 2023

BackgroundThe lung microbiome is an inflammatory stimulus whose role in COPD pathogenesis is incompletely understood. We hypothesised that the frequent exacerbator phenotype is associated with decreased α-diversity and increased lung inflammation. Our objective was to assess correlations between the frequent exacerbator phenotype, the microbiome and inflammation longitudinally during exacerbation-free periods.MethodsWe conducted a case–control longitudinal observational study of the frequent exacerbator phenotype and characteristics of the airway microbiome. 81 subjects (41 frequent and 40 infrequent exacerbators) provided nasal, oral and sputum microbiome samples at two visits over 2–4 months. Exacerbation phenotype, relevant clinical factors and sputum cytokine values were associated with microbiome findings.ResultsThe frequent exacerbator phenotype was associated with lower sputum microbiome α-diversity (p=0.0031). This decrease in α-diversity among frequent exacerbators was enhanced when the sputum bacterial culture was positive (p<0.001). Older age was associated with decreased sputum microbiome α-diversity (p=0.0030). Between-visit β-diversity was increased among frequent exacerbators and those who experienced a COPD exacerbation between visits (p=0.025 and p=0.014, respectively). Sputum cytokine values did not differ based on exacerbation phenotype or other clinical characteristics. Interleukin (IL)-17A was negatively associated with α-diversity, while IL-6 and IL-8 were positively associated with α-diversity (p=0.012, p=0.012 and p=0.0496, respectively). IL-22, IL-17A and IL-5 levels were positively associated withMoraxellaabundance (p=0.027, p=0.0014 and p=0.0020, respectively).ConclusionsEven during exacerbation-free intervals, the COPD frequent exacerbator phenotype is associated with decreased sputum microbiome α-diversity and increased β-diversity. Decreased sputum microbiome α-diversity andMoraxellaabundance are associated with lung inflammation.
Phytochemical analysis and anti-infective potential of fungal endophytes isolated from Nigella sativa seeds
Authors: Shady Nourhan Hisham , Sobhy Sara Khalid , Mostafa Yaser A. , Yahia Ramadan , Glaeser Stefanie P. , Kämpfer Peter , El-Katatny Mo’men H. , Abdelmohsen Usama Ramadan 
Published: November 2023

AbstractEndophytic fungi, particularly from higher plants have proven to be a rich source of antimicrobial secondary metabolites. The purpose of this study is to examine the antimicrobial potential of three endophytic fungiAspergillussp. SA1,Aspergillussp. SA2, andAspergillussp. SA3, cultivated fromNigella sativaseeds againstStaphylococcus aureus(ATCC 9144),Escherichia coli(ATCC 25922),Pseudomonas aeruginosa(ATCC 27853),Klebsiella pneumoniae(ATCC 13883), MRSA (ATCC 33591), and human pathogenCandida albicans(ATCC 10231). Furthermore, the most active cultivated endophytic fungi were molecularly identified via internal transcribed spacer (ITS) sequencing. HR-ESIMS guided approach has been used successfully in chemical profiling of 26 known bioactive secondary metabolites (1–26), which belongs to different classes of natural compounds such as polyketides, benzenoids, quinones, alcohols, phenols or alkaloids. Finally,in-silicointeractions within active site of fungal Cyp51 and bacterial DNA gyrase revealed possibility of being a hit-target for such metabolites as antimicrobials.
Micro- and macrocirculatory effects of norepinephrine on anaesthesia-induced hypotension: a prospective preliminary study
Authors: Kindermans Manuel , Joachim Jona , Manquat Elsa , Levé Charlotte , Hong Alex , Mateo Joachim , Mebazaa Alexandre , Gayat Etienne , De Backer Daniel , Vallée Fabrice 
Published: November 2023

Abstract
Background
Intraoperative arterial hypotension (IOH) leads to increased postoperative morbidity. Norepinephrine is often use to treat IOH. The question regarding the mode of administration in either a bolus or continuous infusion remains unanswered. The aim of the present study was to describe and compare the effects on macrocirculation and microcirculation of a bolus and a continuous infusion of norepinephrine to treat IOH.

Methods
We conducted a prospective observational study with adult patients who underwent neurosurgery. Patients with invasive arterial blood pressure and cardiac output (CO) monitoring were screened for inclusion. All patients underwent microcirculation monitoring by video-capillaroscopy, laser doppler, near-infrared spectroscopy technology, and tissular CO2. In case of IOH, the patient could receive either a bolus of 10 µg or a continuous infusion of 200 µg/h of norepinephrine. Time analysis for comparison between bolus and continuous infusion were at peak of MAP. The primary outcome was MFI by videocapillaroscopy.

Results
Thirty-five patients were included, with 41 boluses and 33 continuous infusion.
Bolus and continuous infusion induced an maximal increase in mean arterial pressure of +30[20-45] and +23[12-34] %, respectively (P=0,07). For macrocirculatory parameters, continuous infusion was associated with a smaller decrease in CO and stroke volume (p<0.05).
For microcirculatory parameters, microvascular flow index (-0,1 vs. + 0,3, p=0,03), perfusion index (-12 vs. +12%, p=0,008), total vessel density (-0,2 vs. +2,3 mm2/mm2, p=0,002), showed significant opposite variations with bolus and continuous infusion, respectively.

Conclusions
These results on macro and microcirculation enlighten the potential benefits of a continuous infusion of norepinephrine rather than a bolus to treat anaesthesia-induced hypotension.

Trial registration
(NOR-PHARM: 1-17-42 Clinical Trials: NCT03454204), 05/03/2018
Changes of serum TSH, FT3, and FT4 levels in infants received surgical correction of congenital heart disease under cardiopulmonary bypass
Authors: Lin Wen-Hao , Zhou Si-Jia , Chen Xiu-Hua , Cao Hua , Chen Qiang 
Published: November 2023

Abstract
Objective
This study aimed to explore the fluctuations and clinical relevance of serum thyrotropin (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels in infants undergoing surgical correction for congenital heart disease (CHD) using cardiopulmonary bypass (CPB).

Methods
In a retrospective design, 58 infants who underwent CHD surgical correction under CPB between January 2021 and January 2022 at our institution were incorporated. These infants were categorized into two groups: simple CHD (n = 34) and complex CHD (n = 24). TSH, FT3, and FT4 serum concentrations were assessed at four intervals: 24 h pre-surgery (T0) and 24 h (T1), 48 h (T2), and 72 h (T3) post-surgery.

Results
The simple CHD group displayed a significantly reduced CPB duration compared to the complex CHD group (P < 0.001). Both groups exhibited a notable decline in serum thyroid hormone concentrations at T1 compared to T0. However, from T1 to T3, an upward trend in hormone levels was observed. By T3, though the levels in both groups had risen notably from T1, they remained significantly diminished from T0 (P < 0.01). In both the simple and complex CHD cohorts, significant fluctuations in thyroid hormone levels (TSH, FT3, FT4) were noted across the different timepoints (T0, T1, T3) (P < 0.01). While no significant disparities were found between the two groups’ hormone concentrations at T0 and T1 (P > 0.05), at T2 and T3, the simple CHD group manifested higher TSH, FT3, and FT4 levels compared to the complex CHD group (P < 0.05).

Conclusions
Infants undergoing CHD surgical correction under CPB experience significant declines in TSH, FT3, and FT4 serum levels. The post-surgery thyroid hormone recovery was more pronounced in infants with simple CHD compared to those with complex CHD. As such, vigilant monitoring of thyroid hormone levels during the perioperative phase is imperative, and timely intervention measures should be employed when necessary.
Integrating scRNA-seq to explore novel macrophage infiltration-associated biomarkers for diagnosis of heart failure
Authors: Li Shengnan , Ge Tiantian , Xu Xuan , Xie Liang , Song Sifan , Li Runqian , Li Hao , Tong Jiayi 
Published: November 2023

Abstract
Objective
Inflammation and immune cells are closely intertwined mechanisms that contribute to the progression of heart failure (HF). Nonetheless, there is a paucity of information regarding the distinct features of dysregulated immune cells and efficient diagnostic biomarkers linked with HF. This study aims to explore diagnostic biomarkers related to immune cells in HF to gain new insights into the underlying molecular mechanisms of HF and to provide novel perspectives for the detection and treatment of HF.

Method
The CIBERSORT method was employed to quantify 22 types of immune cells in HF and normal subjects from publicly available GEO databases (GSE3586, GSE42955, GSE57338, and GSE79962). Machine learning methods were utilized to screen for important cell types. Single-cell RNA sequencing (GSE145154) was further utilized to identify important cell types and hub genes. WGCNA was employed to screen for immune cell-related genes and ultimately diagnostic models were constructed and evaluated. To validate these predictive results, blood samples were collected from 40 normal controls and 40 HF patients for RT-qPCR analysis. Lastly, key cell clusters were divided into high and low biomarker expression groups to identify transcription factors that may affect biomarkers.

Results
The study found a noticeable difference in immune environment between HF and normal subjects. Macrophages were identified as key immune cells by machine learning. Single-cell analysis further showed that macrophages differed dramatically between HF and normal subjects. This study revealed the existence of five subsets of macrophages that have different differentiation states. Based on module genes most relevant to macrophages, macrophage differentiation-related genes (MDRGs), and DEGs in HF and normal subjects from GEO datasets, four genes (CD163, RNASE2, LYVE1, and VSIG4) were identified as valid diagnostic markers for HF. Ultimately, a diagnostic model containing two hub genes was constructed and then validated with a validation dataset and clinical samples. In addition, key transcription factors driving or maintaining the biomarkers expression programs were identified.

Conclusion
The analytical results and diagnostic model of this study can assist clinicians in identifying high-risk individuals, thereby aiding in guiding treatment decisions for patients with HF.
Methods, strategies, and incentives to increase response to mental health surveys among adolescents: a systematic review
Authors: Bidonde Julia , Meneses-Echavez Jose F. , Hafstad Elisabet , Brunborg Geir Scott , Bang Lasse 
Published: November 2023

Abstract
Background
This systematic review aimed to identify effective methods to increase adolescents’ response to surveys about mental health and substance use, to improve the quality of survey information.

Methods
We followed a protocol and searched for studies that compared different survey delivery modes to adolescents. Eligible studies reported response rates, mental health score variation per survey mode and participant variations in mental health scores. We searched CENTRAL, PsycINFO, MEDLINE and Scopus in May 2022, and conducted citation searches in June 2022. Two reviewers independently undertook study selection, data extraction, and risk of bias assessments. Following the assessment of heterogeneity, some studies were pooled using meta-analysis.

Results
Fifteen studies were identified, reporting six comparisons related to survey methods and strategies. Results indicate that response rates do not differ between survey modes (e.g., web versus paper-and-pencil) delivered in classroom settings. However, web surveys may yield higher response rates outside classroom settings. The largest effects on response rates were achieved using unconditional monetary incentives and obtaining passive parental consent. Survey mode influenced mental health scores in certain comparisons.

Conclusions
Despite the mixed quality of the studies, the low volume for some comparisons and the limit to studies in high income countries, several effective methods and strategies to improve adolescents’ response rates to mental health surveys were identified.
Characterization of genomic instability-related genes predicts survival and therapeutic response in lung adenocarcinoma
Authors: Li Shuyang , Wang Wei , Yu Huihan , Zhang Siyu , Bi Wenxu , Sun Suling , Hong Bo , Fang Zhiyou , Chen Xueran 
Published: November 2023

Abstract
Background
Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC) and is the leading cause of cancer death worldwide. Its progression is characterized by genomic instability. In turn, the level of genomic instability affects the prognosis and immune status of patients with LUAD. However, the impact of molecular features associated with genomic instability on the tumor microenvironment (TME) has not been well characterized. In addition, the effect of the genes related to genomic instability in LUAD on individualized treatment of LUAD is unknown.

Methods
The RNA-Sequencing, somatic mutation, and clinical data of LUAD patients were downloaded from publicly available databases. A genetic signature associated with genomic instability (GSAGI) was constructed by univariate Cox regression, Lasso regression, and multivariate Cox regression analysis. Bioinformatics analysis investigated the differences in prognosis, immune characteristics, and the most appropriate treatment strategy among different subtypes of LUAD patients. CCK-8 and colony formation verified the various effects of Etoposide on different subtypes of LUAD cell lines. Cell-to-cell communication analysis was performed using the “CellChat” R package. The expression of the risk factors in the GSAGI was verified using real-time quantitative PCR (qRT-PCR) and Immunohistochemistry (IHC).

Results
We constructed and validated the GSAGI, consisting of five genes: ANLN, RHOV, KRT6A, SIGLEC6, and KLRG2. The GSAGI was an independent prognostic factor for LUAD patients. Patients in the high-risk group distinguished by the GSAGI are more suitable for chemotherapy. More immune cells are infiltrating the tumor microenvironment of patients in the low-risk group, especially B cells. Low-risk group patients are more suitable for receiving immunotherapy. The single-cell level analysis confirmed the influence of the GSAGI on TME and revealed the Mode of action between tumor cells and other types of cells. qRT-PCR and IHC showed increased ANLN, RHOV, and KRT6A expression in the LUAD cells and tumor tissues.

Conclusion
This study confirms that genes related to genomic instability can affect the prognosis and immune status of LUAD patients. The GSAGI we identified has the potential to guide clinicians in predicting clinical outcomes, assessing immunological status, and even developing personalized treatment plans for LUAD patients.
Altered fractional amplitude of low-frequency fluctuations in the superior temporal gyrus: a resting-state fMRI study in anxious depression
Authors: Zhao Peng , Wang Xinyi , Wang Qiang , Yan Rui , Chattun Mohammad Ridwan , Yao Zhijian , Lu Qing 
Published: November 2023

Abstract
Background
Anxious depression, which is a common subtype of major depressive disorder, has distinct clinical features from nonanxious depression. However, little is known about the neurobiological characteristics of anxious depression. In this study, we explored resting-state regional brain activity changes between anxious depression and nonanxious depression.

Method
Resting-state functional magnetic resonance (rs-fMRI) imaging data were collected from 60 patients with anxious depression, 38 patients with nonanxious depression, and 60 matched healthy controls (HCs). One-way analysis of variance was performed to compare the whole-brain fractional amplitude of low-frequency fluctuation (fALFF) in the three groups. The correlation between the fALFF values and the clinical measures was examined.

Results
Compared with those of HCs, the fALFF values in the left superior temporal gyrus (STG) in patients with anxious depression were significantly increased, while the fALFF values in the left middle temporal gyrus (MTG), left STG, and right STG in patients with nonanxious depression were significantly increased. Patients with anxious depression showed reduced fALFF values in the right STG compared with patients with nonanxious depression (p < 0.001, corrected). Within the anxious depression group, fALFF value in the right STG was positively correlated with the cognitive disturbance score (r = 0.36, p = 0.005 corrected).

Conclusion
The bilateral STG and left MTG, which are related to the default mode network, appear to be key brain regions in nonanxious depression, while the right STG plays an essential role in the neuropathological mechanism of anxious depression.