bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advanced respiratory mechanics assessment in mechanically ventilated obese and non-obese patients with or without acute respiratory distress syndrome
Authors: Beloncle François M. , Richard Jean-Christophe , Merdji Hamid , Desprez Christophe , Pavlovsky Bertrand , Yvin Elise , Piquilloud Lise , Olivier Pierre-Yves , Chean Dara , Studer Antoine , Courtais Antonin , Campfort Maëva , Rahmani Hassene , Lesimple Arnaud , Meziani Ferhat , Mercat Alain 
Published: September 2023

Abstract
Background
Respiratory mechanics is a key element to monitor mechanically ventilated patients and guide ventilator settings. Besides the usual basic assessments, some more complex explorations may allow to better characterize patients’ respiratory mechanics and individualize ventilation strategies. These advanced respiratory mechanics assessments including esophageal pressure measurements and complete airway closure detection may be particularly relevant in critically ill obese patients. This study aimed to comprehensively assess respiratory mechanics in obese and non-obese ICU patients with or without ARDS and evaluate the contribution of advanced respiratory mechanics assessments compared to basic assessments in these patients.

Methods
All intubated patients admitted in two ICUs for any cause were prospectively included. Gas exchange and respiratory mechanics including esophageal pressure and end-expiratory lung volume (EELV) measurements and low-flow insufflation to detect complete airway closure were assessed in standardized conditions (tidal volume of 6 mL kg−1 predicted body weight (PBW), positive end-expiratory pressure (PEEP) of 5 cmH2O) within 24 h after intubation.

Results
Among the 149 analyzed patients, 52 (34.9%) were obese and 90 (60.4%) had ARDS (65.4% and 57.8% of obese and non-obese patients, respectively, p = 0.385). A complete airway closure was found in 23.5% of the patients. It was more frequent in obese than in non-obese patients (40.4% vs 14.4%, p < 0.001) and in ARDS than in non-ARDS patients (30% vs. 13.6%, p = 0.029). Respiratory system and lung compliances and EELV/PBW were similarly decreased in obese patients without ARDS and obese or non-obese patients with ARDS. Chest wall compliance was not impacted by obesity or ARDS, but end-expiratory esophageal pressure was higher in obese than in non-obese patients. Chest wall contribution to respiratory system compliance differed widely between patients but was not predictable by their general characteristics.

Conclusions
Most respiratory mechanics features are similar in obese non-ARDS and non-obese ARDS patients, but end-expiratory esophageal pressure is higher in obese patients. A complete airway closure can be found in around 25% of critically ill patients ventilated with a PEEP of 5 cmH2O. Advanced explorations may allow to better characterize individual respiratory mechanics and adjust ventilation strategies in some patients.
Trial registration NCT03420417 ClinicalTrials.gov (February 5, 2018).
Anti-Ro52 positivity is associated with progressive interstitial lung disease in systemic sclerosis—an exploratory study
Authors: Hamberg Viggo , Sohrabian Azita , Volkmann Elizabeth R. , Wildt Marie , Löfdahl Anna , Wuttge Dirk M. , Hesselstrand Roger , Dellgren Göran , Westergren-Thorsson Gunilla , Rönnelid Johan , Andréasson Kristofer 
Published: September 2023

Abstract
Background
Interstitial lung disease (ILD) is the most common cause of death in patients with systemic sclerosis (SSc). Prognostic biomarkers are needed to identify SSc-ILD patients at risk for progressive pulmonary fibrosis. This study investigates autoantibodies measured in bronchoalveolar lavage (BAL) fluid and in serum in reference to the clinical disease course of SSc-ILD.

Methods
Fifteen patients with new onset SSc-ILD underwent bronchoscopy. Autoantibody levels were analyzed using addressable laser bead immunoassay from BAL fluid and the serum. In a separate longitudinal cohort of 43 patients with early SSc-ILD, autoantibodies in serum were measured at baseline and pulmonary function tests were performed at least 2 times over the course of at least 2 or more years. Linear mixed effect models were created to investigate the relationship between specific autoantibodies and progression of SSc-ILD. Finally, lung tissue from healthy controls and from subjects with SSc was analyzed for the presence of the Ro52 antigen using immunohistochemistry.

Results
Among SSc-ILD patients who were positive for anti-Ro52 (N = 5), 3 (60%) had enrichment of anti-Ro52 in BAL fluid at a ratio exceeding 50x. In the longitudinal cohort, 10/43 patients (23%) were anti-Ro52 positive and 16/43 (37%) were anti-scl-70 positive. Presence of anti-Scl-70 was associated with a lower vital capacity (VC) at baseline (-12.6% predicted VC [%pVC]; 95%CI: -25.0, -0.29; p = 0.045), but was not significantly associated with loss of lung function over time (-1.07%pVC/year; 95%CI: -2.86, 0.71; p = 0.230). The presence of anti-Ro52 was significantly associated with the loss of lung function over time (-2.41%pVC/year; 95% CI: -4.28, -0.54; p = 0.013). Rate of loss of lung function increased linearly with increasing anti-Ro52 antibody levels (-0.03%pVC per arbitrary units/mL and year; 95%CI: -0.05, -0.02; p < 0.001). Immunohistochemical staining localized the Ro52 antigen to alveolar M2 macrophages in peripheral lung tissue both in subjects with and without SSc.

Conclusions
This study suggests that antibodies targeting Ro52 are enriched in the lungs of patients with new-onset SSc-ILD, linking Ro52 autoimmunity to the pulmonary pathology of SSc. Clinical and immunohistochemical data corroborates these findings and suggest that anti-Ro52 may serve as a potential biomarker of progressive SSc-ILD.
SARS-CoV-2 infection induces epigenetic changes in the LTR69 subfamily of endogenous retroviruses
Authors: Arora Ankit , Kolberg Jan Eric , Srinivasachar Badarinarayan Smitha , Savytska Natalia , Munot Daksha , Müller Martin , Krchlíková Veronika , Sauter Daniel , Bansal Vikas 
Published: September 2023

AbstractAccumulating evidence suggests that endogenous retroviruses (ERVs) play an important role in the host response to infection and the development of disease. By analyzing ChIP-sequencing data sets, we show that SARS-CoV-2 infection induces H3K27 acetylation of several loci within the LTR69 subfamily of ERVs. Using functional assays, we identified one SARS-CoV-2-activated LTR69 locus, termed Dup69, which exhibits regulatory activity and is responsive to the transcription factors IRF3 and p65/RELA. LTR69_Dup69 is located about 500 bp upstream of a long non-coding RNA gene (ENSG00000289418) and within the PTPRN2 gene encoding a diabetes-associated autoantigen. Both ENSG00000289418 and PTPRN2 showed a significant increase in expression upon SARS-CoV-2 infection. Thus, our study sheds light on the interplay of exogenous with endogenous viruses and helps to understand how ERVs regulate gene expression during infection.
Frequencies of mobilized colistin resistance (mcr-1, 2) genes in clinically isolated Escherichia coli; a cross sectional study
Authors: Mirzaei Bahman , Ebrahimi Aida , Hariri Bahareh , Sokouti Zahra , Kazemi Niloufar , Moradi Narges 
Published: September 2023

Abstract
Objective
Escherichia coli (E. coli) is an opportunistic bacterium, which is globally recognized for its high prevalence and antimicrobial resistance (AMR). The presence of colistin-resistant representative mcr- 1, 2 genes in multi-drug resistant (MDR) clinically isolated E. coli is the main goal of this survey. After biochemically and molecular confirmation tests, susceptibility testing, biofilm formation, and minimum inhibitory concentration to colistin were performed on 100 E. coli isolates. Subsequently, taking advantage of uniplex-PCR, the presence of some responsible genes (mcr- 1, mcr- 2) to colistin-resistant phenotypes in mentioned bacterium was assessed.

Results
Disc diffusion methods indicated that the highest resistance rate was against ampicillin (80.0%), and trimethoprim/sulfamethoxazole (63%). Among the E. coli isolates, 72 (72.0%) was determined as MDR, respectively. Moreover, 47 (47%) strains were determined as extreme beta-lactamase (ESBL) phenotypes. Among 41 slime-producing E. coli strains, 7 (17.07%), 14 (34.14%), and 20 (48.78%) strains exhibited high, moderate, and weak levels of biofilm formation, respectively. Fifty-nine (81.94%), and 1(100%) of MDR isolates were assessed as colistin resistant (MIC > 2) and susceptible (MIC ≤ 2) as well. In 26(36.11%) of colistin-resistant isolates and 1(1.38%) of colistin, susceptible isolate mcr-1 gene was found. There is no mcr- 2 gene was detected in isolates.

Conclusion
The diversity of high antibiotic-resistant rates could be avoided by developing appropriate healthcare policies and community awareness. Alarming resistance rates were observed in colistin and ampicillin, which should be taken into account in therapy guidelines.
Performance of plasma Aβ42/40, measured using a fully automated immunoassay, across a broad patient population in identifying amyloid status
Authors: Bun Shogyoku , Ito Daisuke , Tezuka Toshiki , Kubota Masahito , Ueda Ryo , Takahata Keisuke , Moriguchi Sho , Kurose Shin , Momota Yuki , Suzuki Natsumi , Morimoto Ayaka , Hoshino Yuka , Seki Morinobu , Mimura Yu , Shikimoto Ryo , Yamamoto Yasuharu , Hoshino Takayuki , Sato Yoshiaki , Tabuchi Hajime , Mimura Masaru 
Published: September 2023

Abstract
Background
Plasma biomarkers have emerged as promising screening tools for Alzheimer’s disease (AD) because of their potential to detect amyloid β (Aβ) accumulation in the brain. One such candidate is the plasma Aβ42/40 ratio (Aβ42/40). Unlike previous research that used traditional immunoassay, recent studies that measured plasma Aβ42/40 using fully automated platforms reported promising results. However, its utility should be confirmed using a broader patient population, focusing on the potential for early detection.

Methods
We recruited 174 participants, including healthy controls (HC) and patients with clinical diagnoses of AD, frontotemporal lobar degeneration, dementia with Lewy bodies/Parkinson’s disease, mild cognitive impairment (MCI), and others, from a university memory clinic. We examined the performance of plasma Aβ42/40, measured using the fully automated high-sensitivity chemiluminescence enzyme (HISCL) immunoassay, in detecting amyloid-positron emission tomography (PET)-derived Aβ pathology. We also compared its performance with that of Simoa-based plasma phosphorylated tau at residue 181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL).

Results
Using the best cut-off derived from the Youden Index, plasma Aβ42/40 yielded an area under the receiver operating characteristic curve (AUC) of 0.949 in distinguishing visually assessed 18F-Florbetaben amyloid PET positivity. The plasma Aβ42/40 had a significantly superior AUC than p-tau181, GFAP, and NfL in the 167 participants with measurements for all four biomarkers. Next, we analyzed 99 participants, including only the HC and those with MCI, and discovered that plasma Aβ42/40 outperformed the other plasma biomarkers, suggesting its ability to detect early amyloid accumulation. Using the Centiloid scale (CL), Spearman’s rank correlation coefficient between plasma Aβ42/40 and CL was -0.767. Among the 15 participants falling within the CL values indicative of potential future amyloid accumulation (CL between 13.5 and 35.7), plasma Aβ42/40 categorized 61.5% (8/13) as Aβ-positive, whereas visual assessment of amyloid PET identified 20% (3/15) as positive.

Conclusion
Plasma Aβ42/40 measured using the fully automated HISCL platform showed excellent performance in identifying Aβ accumulation in the brain in a well-characterized cohort. This equipment may be useful for screening amyloid pathology because it has the potential to detect early amyloid pathology and is readily applied in clinical settings.
Exosomal miR-17-5p from human embryonic stem cells prevents pulmonary fibrosis by targeting thrombospondin-2
Authors: Liu Qun , Bi Youkun , Song Shaole , Zhu Keqi , Qiao Xinlong , Wang Huiwen , Ji Guangju 
Published: September 2023

Abstract
Background
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible lung disease characterized by pulmonary fibrosis and lung dysfunction, ultimately leading to respiratory failure. Many preclinical studies have investigated the therapeutic potential of stem cell-derived exosomes in this disease, particularly mesenchymal stem cell-derived exosomes. However, the effects of embryonic stem cell-derived exosomes in IPF remain unclear.

Methods
We established a bleomycin (BLM)-induced pulmonary fibrosis mice model and administered human embryonic stem cell exosomes (hESC-exo) from the first day after BLM treatment. The effects of hESC-exo were assessed by pulmonary function tests, biochemical analysis, histochemistry, quantitative real-time polymerase chain reaction (qPCR), and western blot (WB). RNA-seq was used to screen for the potential therapeutic targets of hESC-exo in fibrotic lungs; the identified signaling axis was characterized using a luciferase assay, qPCR, and WB.

Results
Results indicated hESC-exo administration notably alleviated inflammation, removed deposited collagen, and rescued alveolar architecture in the lungs of BLM-induced mice. In vivo and in vitro tests revealed that hESC-exo-derived miR-17-5p directly bound thrombospondin-2 (Thbs2) to regulate inflammation and fibrosis; thus, hESC-exo protected against BLM toxicity in the lungs via the miR-17-5p/Thbs2 axis.

Conclusion
These results suggest a promising new treatment for fibrosis-associated diseases.
Low-glucose culture environment can enhance the wound healing capability of diabetic adipose-derived stem cells
Authors: Li Chun-Wei , Young Tai-Horng , Wang Mu-Hui , Pei Ming-Ying , Hsieh Tsung-Yu , Hsu Chia-Lang , Cheng Nai-Chen 
Published: September 2023

Abstract
Background
Application of autologous adipose-derived stem cells (ASC) for diabetic chronic wounds has become an emerging treatment option. However, ASCs from diabetic individuals showed impaired cell function and suboptimal wound healing effects. We proposed that adopting a low-glucose level in the culture medium for diabetic ASCs may restore their pro-healing capabilities.

Methods
ASCs from diabetic humans and mice were retrieved and cultured in high-glucose (HG, 4.5 g/L) or low-glucose (LG, 1.0 g/L) conditions. Cell characteristics and functions were investigated in vitro. Moreover, we applied diabetic murine ASCs cultured in HG or LG condition to a wound healing model in diabetic mice to compare their healing capabilities in vivo.

Results
Human ASCs exhibited decreased cell proliferation and migration with enhanced senescence when cultured in HG condition in vitro. Similar findings were noted in ASCs derived from diabetic mice. The inferior cellular functions could be partially recovered when they were cultured in LG condition. In the animal study, wounds healed faster when treated with HG- or LG-cultured diabetic ASCs relative to the control group. Moreover, higher collagen density, more angiogenesis and cellular retention of applied ASCs were found in wound tissues treated with diabetic ASCs cultured in LG condition.

Conclusions
In line with the literature, our study showed that a diabetic milieu exerts an adverse effect on ASCs. Adopting LG culture condition is a simple and effective approach to enhance the wound healing capabilities of diabetic ASCs, which is valuable for the clinical application of autologous ASCs from diabetic patients.
First clinical experience with fractionated intracavitary radioimmunotherapy using [177Lu]Lu-6A10-Fab fragments in patients with glioblastoma: a pilot study
Authors: Roll Wolfgang , Müther Michael , Böning Guido , Delker Astrid , Warneke Nils , Gildehaus Franz-Josef , Schäfers Michael , Stummer Walter , Zeidler Reinhard , Reulen Hans-Jürgen , Stegger Lars 
Published: September 2023

Abstract
Background
Following resection and standard adjuvant radio- and chemotherapy, approved maintenance therapies for glioblastoma are lacking. Intracavitary radioimmunotherapy (iRIT) with 177Lu-labeled 6A10-Fab fragments targeting tumor-associated carbonic anhydrase XII and injected into the resection cavity offers a novel and promising strategy for improved tumor control.

Methods
Three glioblastoma patients underwent tumor resection followed by standard radio- and chemotherapy. These patients with stable disease following completion of standard therapy underwent iRIT on compassionate grounds. After surgical implantation of a subcutaneous injection reservoir with a catheter into the resection cavity, a leakage test with [99mTc]Tc-DTPA was performed to rule out leakage into other cerebral compartments. IRIT comprised three consecutive applications over three months for each patient, with 25%, 50%, 25% of the total activity injected. A dosimetry protocol was included with blood sampling and SPECT/CT of the abdomen to calculate doses for the bone marrow and kidneys as potential organs at risk.

Results
All three patients presented without relevant leakage after application of [99mTc]Tc-DTPA. Two patients underwent three full cycles of iRIT (592 MBq and 1228 MBq total activity). One patient showed histologically proven tumor progression after the second cycle (526 MBq total activity). No relevant therapy-associated toxicities or adverse events were observed. Dosimetry did not reveal absorbed doses above upper dose limits for organs at risk.

Conclusions
In first individual cases, iRIT with [177Lu]Lu-6A10-Fab appears to be feasible and safe, without therapy-related side effects. A confirmatory multicenter phase-I-trial was recently opened and is currently recruiting.
Process analysis and mitigation strategies for wetland degradation caused by increasing agricultural water demand: an ecology–economy nexus perspective
Authors: Jiang Lin , Wang Hui , Wang Saige , Zhang Wen 
Published: September 2023

Abstract
Background
Farmland expansion has played a major role in wetland degradation in Heilongjiang Province, China in recent decades. Farmland expansion increases the demands for water, thereby affecting wetland water cycles, and promoting the shrinkage of wetland areas and degradation of ecosystem functions. As an open system, agricultural production is limited by both ecological and socioeconomic conditions. However, our understanding of wetland degradation caused by farmland expansion from the perspective of the ecology–economy nexus is limited.

Methods
A correlation between farmland expansion and agricultural economic activities was established, and wetland degradation driven by agroeconomic activities was inversely derived using a multi-regional input–output (MRIO) analysis. We developed an ecology–economy nexus framework to explore the ecological process of the area and water demand tradeoffs between wetland degradation and farmland expansion, the economic process of wetland degradation driven by food consumption, and the nexus between the two processes. We finally explored strategies to mitigate wetland degradation due to increased agricultural water demand.

Results
Farmland expansion contributed to 93.76% of the total degraded wetland area. There was a significant negative correlation between wetland area and the water consumption for crop production, but no significant correlation between wetland area and the ecological footprint of croplands. The direct wetland degradation caused by local final demand accounted for 63.02%, while the indirect degradation caused by non-local final demand accounted for 36.98%. Hebei, Shandong, Liaoning, Inner Mongolia, and Shanghai were the top five provinces contributing to indirect wetland degradation in Heilongjiang. Our findings indicated that a mixed scenario combining water footprint reduction per unit yield with food export reduction could maximize wetland restoration while reducing local farmland–wetland competition for water.

Conclusions
Our research highlights the effects of economic processes in the agricultural sector on wetland degradation, and showed that the adjustment of food trade patterns can effectively promote wetland restoration.
Numerical and Experimental Analysis to Develop a SB6/H3 High Containment Level Concrete Median Barrier
Authors: Jeong Yoseok , Lee Ilkeun , Lee Jaeha , Kim Kyeongjin , Min Geunhyeong , Kim WooSeok 
Published: September 2023

AbstractAs the number of heavy vehicles on the road continues to increase, collisions involving heavy vehicles and concrete median barriers (CMB) occur more frequently than in the past. Consequently, there is a growing need for research into more stringent design standards and improvements to the current CMB and their performance under harsh conditions. High-performance CMB is required to in order to withstand such conditions. This paper presents the results of numerical simulations and full-scale field tests to develop a high-performance CMB. To facilitate the development of the high-performance CMB, the concept of a deformable CMB was applied to the rigid CMB. A new apparatus called the shock absorber composed of dowel bars surrounded by empty space were introduced to make the rigid CMB deformable. In order to prevent local failure at the top of the barrier from a sudden high increase in impact energy, the deformable CMB was strengthened by adding reinforcements and widening the top based on the results of numerical simulations. The full-scale field tests were conducted on the proposed deformable CMB and took into account three appraisal areas: (1) structural adequacy, (2) occupant risk, and (3) vehicle trajectory after collision. The results of these tests showed that the deformable CMB contained and redirected the vehicle without allowing it to penetrate or override the deformable CMB. No detached elements, fragmentation, or other debris from the barrier were present. Therefore, the proposed high-performance CMB fulfilled all of the requirements of the crash test guideline.