bluuebunny/crossref_metadata_2025_split huggingface dataset:
Usage of compromised lung volume in monitoring steroid therapy on severe COVID-19
Authors: Su Ying , Qiu Ze-song , Chen Jun , Ju Min-jie , Ma Guo-guang , He Jin-wei , Yu Shen-ji , Liu Kai , Lure Fleming Y. M. , Tu Guo-wei , Zhang Yu-yao , Luo Zhe 
Published: April 2022

Abstract
Background
Quantitative computed tomography (QCT) analysis may serve as a tool for assessing the severity of coronavirus disease 2019 (COVID-19) and for monitoring its progress. The present study aimed to assess the association between steroid therapy and quantitative CT parameters in a longitudinal cohort with COVID-19.

Methods
Between February 7 and February 17, 2020, 72 patients with severe COVID-19 were retrospectively enrolled. All 300 chest CT scans from these patients were collected and classified into five stages according to the interval between hospital admission and follow-up CT scans: Stage 1 (at admission); Stage 2 (3–7 days); Stage 3 (8–14 days); Stage 4 (15–21 days); and Stage 5 (22–31 days). QCT was performed using a threshold-based quantitative analysis to segment the lung according to different Hounsfield unit (HU) intervals. The primary outcomes were changes in percentage of compromised lung volume (%CL, − 500 to 100 HU) at different stages. Multivariate Generalized Estimating Equations were performed after adjusting for potential confounders.

Results
Of 72 patients, 31 patients (43.1%) received steroid therapy. Steroid therapy was associated with a decrease in %CL (− 3.27% [95% CI, − 5.86 to − 0.68, P = 0.01]) after adjusting for duration and baseline %CL. Associations between steroid therapy and changes in %CL varied between different stages or baseline %CL (all interactions, P < 0.01). Steroid therapy was associated with decrease in %CL after stage 3 (all P < 0.05), but not at stage 2. Similarly, steroid therapy was associated with a more significant decrease in %CL in the high CL group (P < 0.05), but not in the low CL group.

Conclusions
Steroid administration was independently associated with a decrease in %CL, with interaction by duration or disease severity in a longitudinal cohort. The quantitative CT parameters, particularly compromised lung volume, may provide a useful tool to monitor COVID-19 progression during the treatment process.
Trial registration Clinicaltrials.gov, NCT04953247. Registered July 7, 2021, https://clinicaltrials.gov/ct2/show/NCT04953247
Active secretion of a thermostable transglutaminase variant in Escherichia coli
Authors: Wang Xinglong , Zhao Beichen , Du Jianhui , Xu Yameng , Zhu Xuewen , Zhou Jingwen , Rao Shengqi , Du Guocheng , Chen Jian , Liu Song 
Published: April 2022

Abstract
Background
Streptomyces mobaraenesis transglutaminase (smTG) is widely used to generate protein crosslinking or attachment of small molecules. However, the low thermostability is a main obstacle for smTG application. In addition, it is still hard to achieve the secretory expression of active smTG in E. coli, which benefits the enzyme evolution. In this study, a combined strategy was conducted to improve the thermostability and secretory expression of active smTG in E. coli.

Results
First, the thermostable S. mobaraenesis transglutaminase variant S2P-S23V-Y24N-S199A-K294L (TGm1) was intracellularly expressed in pro-enzyme form in E. coli. Fusing the pro-region of Streptomyces hygroscopicus transglutaminase (proH) and TrxA achieved a 9.78 U/mL of intracellular smTG activity, 1.37-fold higher than the TGm1 fused with its native pro-region. After in vitro activation by dispase, the TGm1 with proH yielded FRAPD-TGm1, exhibiting 0.95 ℃ and 94.25% increases in melting temperature and half-life at 60 ℃ compared to FRAP-TGm1 derived from the expression using its native pro-region, respectively. Second, the TGm1 with proH was co-expressed with transglutaminase activating protease and chaperones (DnaK, DnaJ, and GrpE) in E. coli, achieving 9.51 U/mL of intracellular FRAPD-TGm1 without in vitro activation. Third, the pelB signal peptide was used to mediate the secretory expression of active TGm in E. coli, yielding 0.54 U/mL of the extracellular FRAPD-TGm1. A script was developed to shuffle the codon of pelB and calculate the corresponding mRNA folding energy. A 1.8-fold increase in the extracellular expression of FRAPD-TGm1 was achieved by the Top-9 pelB sequence derived from the coding sequences with the lowest mRNA folding energy. Last, deleting the gene of Braun’s lipoprotein further increased the extracellular yield of FRAPD-TGm1 by 31.2%, reached 1.99 U/mL.

Conclusions
The stabilized FRAPD-smTG here could benefit the enzyme application in food and non-food sectors, while the E. coli system that enables secretory expression of active smTG will facilitate the directed evolution for further improved catalytic properties. The combined strategy (N-terminal modification, co-expression with chaperones, mRNA folding energy optimization of signal peptide, and lipoprotein deletion) may also improve the secretory expression of other functional proteins in E. coli.
Early versus delay oral feeding for patients after upper gastrointestinal surgery: a systematic review and meta-analysis of randomized controlled trials
Authors: Deng Huachu , Li Baibei , Qin Xingan 
Published: April 2022

Abstract
Purpose
To evaluate the efficacy and safety of early oral feeding (EOF) in patients after upper gastrointestinal surgery through meta-analysis of randomized controlled trials (RCTs).

Methods
We analyzed the endpoints of patients including the length of stay (LOS), time of first exhaust, anastomotic leakage and pneumonia from included studies. And we retrieved RCTs from medical literature databases. Weighted mean difference (WMD), risk ratios (RR) and 95% confidence intervals (CI) were calculated to compare the endpoints.

Results
In total, we retrieved 12 articles (13 trial comparisons) which contained 1771 patients. 887 patients (50.1%) were randomized to EOF group whereas 884 patients (49.9%) were randomized to delay oral feeding group. The result showed that compared with the delay oral feeding group, EOF after upper gastrointestinal surgery significantly shorten the LOS [WMD = − 1.30, 95% CI − 1.79 to − 0.80, I2 = 0.0%] and time of first exhaust [WMD = − 0.39, 95% CI − 0.58 to − 0.20, I2 = 62.1%]. EOF also reduced the risk of pneumonia (RR: 0.74, 95% CI 0.55 to 0.99, I2 = 0.0%). There is no significant difference in the risk of anastomotic leak, anastomotic bleeding, abdominal abscess, reoperation, readmission and mortality.

Conclusions
Overall, compared with the traditional oral feeding, EOF could shorten the LOS and time of first exhaust without increasing complications after upper gastrointestinal surgery.
Genomic and immunological profiles of small-cell lung cancer between East Asians and Caucasian
Authors: Lin Anqi , Zhou Ningning , Zhu Weiliang , Zhang Jiexia , Wei Ting , Guo Linlang , Luo Peng , Zhang Jian 
Published: April 2022

AbstractThe characterization of immunological and genomic differences in small-cell lung cancer (SCLC) between East Asian (EA) and Caucasian patients can reveal important clinical therapies for EA patients with SCLC. By sequencing and analyzing a molecular and immunological dataset of 98-SCLC patients of EA ancestry, immunogenicity, including DNA damage repair alterations and tumor mutation burden (TMB), was found to be significantly higher in the EA cohort than in the Caucasian cohort. The epithelial-mesenchymal transition (EMT) was the signaling signature with the predominant frequency of mutations across all patients in the EA cohort. Analysis of tumor-infiltrated immune cells revealed that resting lymphocytes were significantly enriched in the EA cohort. Compound-targeting analysis showed that topoisomerase inhibitors might be capable of targeting TP53 and RB1 comutations in EA SCLC patients. EA SCLC patients who harbored COL6A6 mutations had poor survival, while Caucasian SCLC patients with OTOF, ANKRD30B, and TECPR2 mutations were identified to have a shorter survival.
Interaction between non-coding RNAs, mRNAs and G-quadruplexes
Authors: Ghafouri-Fard Soudeh , Abak Atefe , Baniahmad Aria , Hussen Bashdar Mahmud , Taheri Mohammad , Jamali Elena , Dinger Marcel E. 
Published: April 2022

AbstractG-quadruplexes are secondary helical configurations established between guanine-rich nucleic acids. The structure is seen in the promoter regions of numerous genes under certain situations. Predicted G-quadruplex-forming sequences are distributed across the genome in a non-random way. These structures are formed in telomeric regions of the human genome and oncogenic promoter G-rich regions. Identification of mechanisms of regulation of stability of G-quadruplexes has practical significance for understanding the molecular basis of genetic diseases such as cancer. A number of non-coding RNAs such as H19, XIST, FLJ39051 (GSEC), BC200 (BCYRN1), TERRA, pre-miRNA-1229, pre-miRNA-149 and miR-1587 have been found to contain G-quadraplex-forming regions or affect configuration of these structures in target genes. In the current review, we outline the recent research on the interaction between G-quadruplexes and non-coding RNAs, other RNA transcripts and DNA molecules.
Oral administration of turmeric-derived exosome-like nanovesicles with anti-inflammatory and pro-resolving bioactions for murine colitis therapy
Authors: Liu Cui , Yan Xiangji , Zhang Yujie , Yang Mei , Ma Yana , Zhang Yuanyuan , Xu Qiuran , Tu Kangsheng , Zhang Mingzhen 
Published: April 2022

Abstract
Background
Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by diffuse inflammation of the colonic mucosa and a relapsing and remitting course. The current therapeutics are only modestly effective and carry risks for unacceptable adverse events, and thus more effective approaches to treat UC is clinically needed.

Results
For this purpose, turmeric-derived nanoparticles with a specific population (TDNPs 2) were characterized, and their targeting ability and therapeutic effects against colitis were investigated systematically. The hydrodynamic size of TDNPs 2 was around 178 nm, and the zeta potential was negative (− 21.7 mV). Mass spectrometry identified TDNPs 2 containing high levels of lipids and proteins. Notably, curcumin, the bioactive constituent of turmeric, was evidenced in TDNPs 2. In lipopolysaccharide (LPS)-induced acute inflammation, TDNPs 2 showed excellent anti-inflammatory and antioxidant properties. In mice colitis models, we demonstrated that orally administrated of TDNPs 2 could ameliorate mice colitis and accelerate colitis resolution via regulating the expression of the pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and antioxidant gene, HO-1. Results obtained from transgenic mice with NF-κB-RE-Luc indicated that TDNPs 2-mediated inactivation of the NF-κB pathway might partially contribute to the protective effect of these particles against colitis.

Conclusion
Our results suggest that TDNPs 2 from edible turmeric represent a novel, natural colon-targeting therapeutics that may prevent colitis and promote wound repair in colitis while outperforming artificial nanoparticles in terms of low toxicity and ease of large-scale production.
Complement C5a induces the generation of neutrophil extracellular traps by inhibiting mitochondrial STAT3 to promote the development of arterial thrombosis
Authors: Chen Yejia , Li Xiaobo , Lin Xinxin , Liang Hongbin , Liu Xuewei , Zhang Xinlu , Zhang Qiuxia , Zhou Fengyun , Yu Chen , Lei Li , Xiu Jiancheng 
Published: April 2022

Abstract
Background
Thrombotic events cannot be completely prevented by antithrombotics, implicating a therapeutic gap due to inflammation, a not yet sufficiently addressed mechanism. Neutrophil extracellular traps (NETs) are an essential interface between inflammation and thrombosis, but exactly how the NETotic process is initiated and maintained during arterial thrombosis remains incompletely understood.

Methods and results
We found that the plasma concentrations of C5a were higher in patients with ST-elevation myocardial infarction (STEMI) than in patients with angina and higher in mice with left common carotid artery (LCCA) thrombosis induced by FeCl3 than in control mice. We observed that the thrombus area and weight were decreased and that NET formation in the thrombi was reduced in the group treated with the selective C5aR1 receptor inhibitor PMX53 compared with the NaCl group. In vitro, NETosis was observed when C5a was added to neutrophil cultures, and this effect was reversed by PMX53. In addition, our data showed that C5a increased the production of mitochondrial reactive oxygen species (ROS) and that the promotion of NET formation by C5a was mitochondrial ROS (Mito-ROS) dependent. Furthermore, we found that C5a induced the production of Mito-ROS by inhibiting mitochondrial STAT3 activity.

Conclusions
By inhibiting mitochondrial STAT3 to elicit Mito-ROS generation, C5a triggers the generation of NETs to promote the development of arterial thrombosis. Hence, our study identifies complement C5a as a potential new target for the treatment and prevention of thrombosis.
Sepsis-associated brain injury: underlying mechanisms and potential therapeutic strategies for acute and long-term cognitive impairments
Authors: Sekino Nobufumi , Selim Magdy , Shehadah Amjad 
Published: April 2022

AbstractSepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis causes cerebral dysfunction in the short and long term and induces disruption of the blood–brain barrier (BBB), neuroinflammation, hypoperfusion, and accumulation of amyloid β (Aβ) and tau protein in the brain. White matter changes and brain atrophy can be detected using brain imaging, but unfortunately, there is no specific treatment that directly addresses the underlying mechanisms of cognitive impairments in sepsis. Here, we review the underlying mechanisms of sepsis-associated brain injury, with a focus on BBB dysfunction and Aβ and tau protein accumulation in the brain. We also describe the neurological manifestations and imaging findings of sepsis-associated brain injury, and finally, we propose potential therapeutic strategies for acute and long-term cognitive impairments associated with sepsis. In the acute phase of sepsis, we suggest using antibiotics (such as rifampicin), targeting proinflammatory cytokines, and preventing ischemic injuries and hypoperfusion. In the late phase of sepsis, we suggest targeting neuroinflammation, BBB dysfunction, Aβ and tau protein phosphorylation, glycogen synthase kinase-3 beta (GSK3β), and the receptor for advanced glycation end products (RAGE). These proposed strategies are meant to bring new mechanism-based directions for future basic and clinical research aimed at preventing or ameliorating acute and long-term cognitive impairments in patients with sepsis.
CyberLimb: a novel robotic prosthesis concept with shared and intuitive control
Authors: Seppich Nicolas , Tacca Nicholas , Chao Kuo-Yi , Akim Milan , Hidalgo-Carvajal Diego , Pozo Fortunić Edmundo , Tödtheide Alexander , Kühn Johannes , Haddadin Sami 
Published: April 2022

Abstract

Background

Existing assistive technologies attempt to mimic biological functions through advanced mechatronic designs. In some occasions, the information processing demands for such systems require substantial information bandwidth and convoluted control strategies, which make it difficult for the end-user to operate. Instead, a practical and intuitive semi-automated system focused on accomplishing daily tasks may be more suitable for end-user adoption.

Methods

We developed an intelligent prosthesis for the Cybathlon Global Edition 2020. The device was designed in collaboration with the prosthesis user (pilot), addressing her needs for the competition and aiming for functionality. Our design consists of a soft robotic-based two finger gripper controlled by a force-sensing resistor (FSR) headband interface, automatic arm angle dependent wrist flexion and extension, and manual forearm supination and pronation for a shared control system. The gripper is incorporated with FSR sensors to relay haptic information to the pilot based on the output of a neural network model that estimates geometries and objects material.

Results

As a student team of the Munich Institute of Robotics and Machine Intelligence, we achieved 12th place overall in the Cybathlon competition in which we competed against state-of-the-art prosthetic devices. Our pilot successfully accomplished two challenging tasks in the competition. During training sessions, the pilot was able to accomplish the remaining competition tasks except for one. Based on observation and feedback from training sessions, we adapted our developments to fit the user’s preferences. Usability ratings indicated that the pilot perceived the prosthesis to not be fully ergonomic due to the size and weight of the system, but argued that the prosthesis was intuitive to control to perform the tasks from the Cybathlon competition.

Conclusions

The system provides an intuitive interface to conduct common daily tasks from the arm discipline of the Cybathlon competition. Based on the feedback from our pilot, future improvements include the prosthesis’ reduction in size and weight in order to enhance its mobility. Close collaboration with our pilot has allowed us to continue with the prosthesis development. Ultimately, we developed a simple-to-use solution, exemplifying a new paradigm for prosthesis design, to help assist arm amputees with daily activities.
The compound LG283 inhibits bleomycin-induced skin fibrosis via antagonizing TGF-β signaling
Authors: Utsunomiya Akira , Chino Takenao , Kasamatsu Hiroshi , Hasegawa Takumi , Utsunomiya Natsuko , Luong Vu Huy , Matsushita Takashi , Sasaki Yoko , Ogura Dai , Niwa Shin-ichiro , Oyama Noritaka , Hasegawa Minoru 
Published: April 2022

Abstract
Background
Systemic sclerosis (SSc) is a collagen disease that exhibits intractable fibrosis and vascular injury of the skin and internal organs. Transforming growth factor-β (TGF-β)/Smad signaling plays a central role in extracellular matrix (ECM) production by α-SMA-positive myofibroblasts. Myofibroblasts may be partially derived from various precursor cells in addition to resident fibroblasts. Recently, our high-throughput in vitro screening discovered a small compound, LG283, that may disrupt the differentiation of epithelial cells into myofibroblasts. This compound was originally generated as a curcumin derivative.

Methods
In this study, we investigated the effect of LG283 on inhibiting fibrosis and its mechanism. The action of LG283 on TGF-β-dependent fibrogenic activity and epithelial-mesenchymal transition (EMT) was analyzed in vitro. The effects of LG283 were also examined in a bleomycin-induced skin fibrosis mouse model.

Results
LG283 suppressed TGF-β-induced expression of ECM, α-SMA, and transcription factors Snail 1 and 2, and Smad3 phosphorylation in cultured human dermal fibroblasts. LG283 was also found to block EMT induction in cultured human epithelial cells. During these processes, Smad3 phosphorylation and/or expression of Snail 1 and 2 were inhibited by LG283 treatment. In the bleomycin-induced skin fibrosis model, oral administration of LG283 efficiently protected against the development of fibrosis and decrease of capillary vessels without significantly affecting cell infiltration or cytokine concentrations in the skin. No apparent adverse effects of LG283 were found. LG283 treatment remarkably inhibited the enhanced expression of α-SMA and phosphorylated Smad3, as well as those of Snail 1 and 2, in the bleomycin-injected skin.

Conclusions
The LG283 compound exhibits antagonistic activity on fibrosis and vascular injury through inhibition of TGF-β/Smad/Snail mesenchymal transition pathways and thus, may be a candidate therapeutic for the treatment of SSc. Although the involvement of EMT in the pathogenesis of SSc remains unclear, the screening of EMT regulatory compounds may be an attractive approach for SSc therapy.
Elevation of α-1,3 fucosylation promotes the binding ability of TNFR1 to TNF-α and contributes to osteoarthritic cartilage destruction and apoptosis
Authors: Yu Hanjie , Li Mingxiu , Wen Xiaodong , Yang Jie , Liang Xiaojun , Li Xia , Bao Xiaojuan , Shu Jian , Ren Xiameng , Chen Wentian , Li Zheng , Li Yi 
Published: April 2022

AbstractBackgroundOsteoarthritis (OA) is the most common form of arthritis and is characterized by the degradation of articular cartilage and inflammation of the synovial membrane. Fucosylation is an important feature of protein N/O-glycosylation and is involved in a variety of pathological processes, including inflammation and cancer. However, whether fucosylation impacts the OA pathological process is unknown.MethodsTotal proteins were extracted from cartilage samples obtained from patients with OA (n= 11) and OA rabbit models at different time points (n= 12). OA-associated abnormal glycopatterns were evaluated by lectin microarrays and lectin blots. The expression of fucosyltransferases involved in the synthesis of α-1,3 fucosylation was assessed by semi-qPCR. The synthesis of α-1,3 fucosylation mediated by FUT10 was interrupted by the transfection of siRNA, and the effect of α-1,3 fucosylation on OA-associated events was assessed. Then, immunoprecipitation and lectin blotting were used to investigate the relationship between the α-1,3 fucosylation level of tumor necrosis factor receptor superfamily member 1A (TNFR1) and OA. Finally, a TNFR1 antibody microarray was fabricated to evaluate the effect of α-1,3 fucosylation on the ability of TNFR1 to bind to tumor necrosis factor-α (TNF-α).ResultsElevated α-1,3 fucosylation was observed in cartilage from OA patients, rabbit models, and chondrocytes induced by TNF-α (fold change> 2,p< 0.01). Our results and the GEO database indicated that the overexpression of FUT10 contributed to this alteration. Silencing the expression of FUT10 impaired the ability of TNFR1 to bind to TNF-α, impeded activation of the NF-κB and P38/JNK-MAPK pathways, and eventually retarded extracellular matrix (ECM) degradation, senescence, and apoptosis in chondrocytes exposed to TNF-α.ConclusionThe elevation of α-1,3 fucosylation is not only a characteristic of OA but also impacts the OA pathological process. Our work provides a new positive feedback loop of “inflammation conditions/TNF-α/FUT10/α-1,3 fucosylation of TNFR1/NF-κB and P38/JNK-MAPK pathways/proinflammatory processes” that contributes to ECM degradation and chondrocyte apoptosis.