bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world evidence of the use of glucocorticoids for severe COVID-19
Authors: Albarrán-Sánchez Alejandra , Ramírez-Rentería Claudia , Mercado Moisés , Sánchez-García Miriam , de Jesús Barrientos-Flores Corazón , Ferreira-Hermosillo Aldo 
Published: January 2022

Introduction: Currently, only glucocorticoids have proved to impact adverse outcomes in COVID-19. However, their risk/benefit balance remains inconclusive and populations’ characteristics should be considered. Objective: The objective was to evaluate the real-life use of glucocorticoids in patients with severe COVID-19 hospitalized in a third-level referral center and to determine the type, accumulated doses, and the in-hospital outcomes related with their use. Methods: We evaluated a retrospective cohort of 737 patients with criteria for severe COVID-19 and a positive polymerase chain reaction (PCR) test for SARS-CoV-2. We extracted data for epidemiological analysis, medical history, and medications, as well as baseline laboratory tests. Data were analyzed using SPSS 21.0 and nonparametric tests, medians, and interquartile ranges (IQR). A p < 0.05 was considered significant. Results: A total of 65.3% were men, with a median age of 59 years (IQR 46–70) and a median of 10 days of hospital stay (IQR 6–16), more than 40% had diabetes, hypertension, and/or obesity, and 0.8% used steroids chronically. At the time of the study, 54.0% had been discharged due to improvement and 40.8% died. The most common treatment used was dexamethasone 6 mg/day/10 days (46.6%). Patients with a complete dexamethasone scheme [as proposed by the Randomized Evaluation of COVID-19 Therapy (RECOVERY) study] had a lower mortality risk [hazard ratio (HR) 0.441, 95% confidence interval (CI) 0.232–0.840] in comparison with patients with lower doses (HR 1.803, 95% CI 1.080–3.012). Patients with methylprednisolone or several steroids tended to have higher cumulative doses (equivalent to >675 mg of prednisolone). Conclusion: The use of steroids in severe COVID-19 reduces mortality only at the dose proposed in the RECOVERY study in the younger population. No benefit of the use of steroids was observed in patients with older age or higher number of comorbidities.
Full-Thickness Quadriceps Tendon Autograft for Anterior Cruciate Ligament Reconstruction
Authors: Deroche Etienne , Erasmus Pieter , Roberts Cecilia 
Published: January 2022

Background: Quadriceps tendon autograft is used increasingly worldwide for primary anterior cruciate ligament (ACL) reconstruction, but remains at the third place after patellar tendon and hamstring grafts. It has shown very good results in biomechanical and clinical studies, but most of the authors describe a partial thickness tendon graft. Indications: This presentation describes the technique for a full-thickness quadriceps tendon autograft with an original technique of fixation on the femur and provides tips and tricks to avoid pitfalls. Technique Description: Arthroscopic preparation of the tunnel is performed before graft harvesting, to obtain the exact length of the graft needed. The femoral tunnel is drilled through the anteromedial portal, 30 to 40 mm long. For the tibial tunnel, a classic drill guide system is used, set at an inclination of 40°. The total length from the tibia to the femur is measured, which allows to position the femoral fixation on the cortex without pulling it into the soft tissue. Harvesting of the graft is done using a double-bladed scalpel, using the entire thickness of the quadriceps tendon. The bone block is detached with an oscillating saw and osteotome, and the defect in the quadriceps tendon closed in 2 layers. The graft is calibrated according to the tunnel preparation and sutured on the bony end with non-absorbable sutures tied to an endobutton. Tibial fixation is achieved by tying 2 non-absorbable sutures over a cortical screw in maximum tension with a sliding type knot, to automatically adjust the tension. Final fixation is performed with a titanium interference screw. Results: In the senior author series over the last 20 years, there was only 1 intraoperative patella fracture, treated with osteosynthesis. In accordance with the literature, full-thickness quadriceps tendon graft is strong and allows back to play at the same level as before the injury, in most cases, with lower donor site morbidity than patellar tendon and hamstrings grafts, without a difference in muscle strength compared with partial thickness grafts. Discussion/Conclusion: ACL reconstruction with full-thickness quadriceps tendon has shown very good clinical outcomes, with very few complications. It can be recommended for primary and revision ACL reconstruction.
Targeting peptidyl-prolyl isomerase 1 in experimental pulmonary arterial hypertension
Authors: Rai Nabham , Sydykov Akylbek , Kojonazarov Baktybek , Wilhelm Jochen , Manaud Grégoire , Veeroju Swathi , Ruppert Clemens , Perros Frédéric , Ghofrani Hossein Ardeschir , Weissmann Norbert , Seeger Werner , Schermuly Ralph T. , Novoyatleva Tatyana 
Published: January 2022

BackgroundPulmonary arterial hypertension (PAH) is a progressive disease characterised by pro-proliferative and anti-apoptotic phenotype in vascular cells, leading to pulmonary vascular remodelling and right heart failure. Peptidyl-prolylcis/transisomerase, NIMA interacting 1 (Pin1), a highly conserved enzyme, which binds to and catalyses the isomerisation of specific phosphorylated Ser/Thr-Pro motifs, acts as a molecular switch in multiple coordinated cellular processes. We hypothesised that Pin1 plays a substantial role in PAH, and its inhibition with a natural organic compound, Juglone, would reverse experimental pulmonary hypertension.ResultsWe demonstrated that the expression of Pin1 was markedly elevated in experimental pulmonary hypertension (i.e.hypoxia-induced mouse and Sugen/hypoxia-induced rat models) and pulmonary arterial smooth muscle cells of patients with clinical PAH.In vitroPin1 inhibition by either Juglone treatment or short interfering RNA knockdown resulted in an induction of apoptosis and decrease in proliferation of human pulmonary vascular cells. Stimulation with growth factors induced Pin1 expression, while its inhibition reduced the activity of numerous PAH-related transcription factors, such as hypoxia-inducible factor (HIF)-α and signal transducer and activator of transcription (STAT). Juglone administration lowered pulmonary vascular resistance, enhanced right ventribular function, improved pulmonary vascular and cardiac remodelling in the Sugen/hypoxia rat model of PAH and the chronic hypoxia-induced pulmonary hypertension model in mice.ConclusionOur study demonstrates that targeting of Pin1 with small molecule inhibitor, Juglone, might be an attractive future therapeutic strategy for PAH and right heart disease secondary to PAH.
Cigarette smoke augments CSF3 expression in neutrophils to compromise alveolar–capillary barrier function during influenza infection
Authors: McGrath Joshua J.C. , Vanderstocken Gilles , Dvorkin-Gheva Anna , Cass Steven P. , Afkhami Sam , Fantauzzi Matthew F. , Thayaparan Danya , Reihani Amir , Wang Peiyao , Beaulieu Ashley , Shen Pamela , Morissette Mathieu , Jiménez-Saiz Rodrigo , Revill Spencer D. , Tabuchi Arata , Zabini Diana , Lee Warren L. , Richards Carl D. , Miller Matthew S. , Ask Kjetil , Kuebler Wolfgang M. , Simpson Jeremy A. , Stämpfli Martin R. 
Published: January 2022

BackgroundCigarette smokers are at increased risk of acquiring influenza, developing severe disease and requiring hospitalisation/intensive care unit admission following infection. However, immune mechanisms underlying this predisposition are incompletely understood, and therapeutic strategies for influenza are limited.MethodsWe used a mouse model of concurrent cigarette smoke exposure and H1N1 influenza infection, colony-stimulating factor (CSF)3 supplementation/receptor (CSF3R) blockade and single-cell RNA sequencing (scRNAseq) to investigate this relationship.ResultsCigarette smoke exposure exacerbated features of viral pneumonia such as oedema, hypoxaemia and pulmonary neutrophilia. Smoke-exposed infected mice demonstrated an increase in viral (v)RNA, but not replication-competent viral particles, relative to infection-only controls. Interstitial rather than airspace neutrophilia positively predicted morbidity in smoke-exposed infected mice. Screening of pulmonary cytokines using a novel dysregulation score identified an exacerbated expression of CSF3 and interleukin-6 in the context of smoke exposure and influenza. Recombinant (r)CSF3 supplementation during influenza aggravated morbidity, hypothermia and oedema, while anti-CSF3R treatment of smoke-exposed infected mice improved alveolar–capillary barrier function. scRNAseq delineated a shift in the distribution ofCsf3+cells towards neutrophils in the context of cigarette smoke and influenza. However, although smoke-exposed lungs were enriched for infected, highly activated neutrophils, gene signatures of these cells largely reflected an exacerbated form of typical influenza with select unique regulatory features.ConclusionThis work provides novel insight into the mechanisms by which cigarette smoke exacerbates influenza infection, unveiling potential therapeutic targets (e.g.excess vRNA accumulation, oedematous CSF3R signalling) for use in this context, and potential limitations for clinical rCSF3 therapy during viral infectious disease.
Identifying biomarkers for breast cancer by gene regulatory network rewiring
Authors: Wang Yijuan , Liu Zhi-Ping 
Published: January 2022

Abstract
Background
Mining gene regulatory network (GRN) is an important avenue for addressing cancer mechanism. Mutations in cancer genome perturb GRN and cause a rewiring in an orchestrated network. Hence, the exploration of gene regulatory network rewiring is significant to discover potential biomarkers and indicators for discriminating cancer phenotypes.

Results
Here, we propose a new bioinformatics method of identifying biomarkers based on network rewiring in different states. It firstly reconstructs GRN in different phenotypic conditions from gene expression data with a priori background network. We employ the algorithm based on path consistency algorithm and conditional mutual information to delete false-positive regulatory interactions between independent nodes/genes or not closely related gene pairs. And then a differential gene regulatory network (D-GRN) is constructed from the rewiring parts in the two phenotype-specific GRNs. Community detection technique is then applied for D-GRN to detect functional modules. Finally, we apply logistic regression classifier with recursive feature elimination to select biomarker genes in each module individually. The extracted feature genes result in a gene set of biomarkers with impressing ability to distinguish normal samples from controls. We verify the identified biomarkers in external independent validation datasets. For a proof-of-concept study, we apply the framework to identify diagnostic biomarkers of breast cancer. The identified biomarkers obtain a maximum AUC of 0.985 in the internal sample classification experiments. And these biomarkers achieve a maximum AUC of 0.989 in the external validations.

Conclusion
In conclusion, network rewiring reveals significant differences between different phenotypes, which indicating cancer dysfunctional mechanisms. With the development of sequencing technology, the amount and quality of gene expression data become available. Condition-specific gene regulatory networks that are close to the real regulations in different states will be established. Revealing the network rewiring will greatly benefit the discovery of biomarkers or signatures for phenotypes. D-GRN is a general method to meet this demand of deciphering the high-throughput data for biomarker discovery. It is also easy to be extended for identifying biomarkers of other complex diseases beyond breast cancer.
MetaCRS: unsupervised clustering of contigs with the recursive strategy of reducing metagenomic dataset’s complexity
Authors: Jiang Zhongjun , Li Xiaobo , Guo Lijun 
Published: January 2022

Abstract
Background
Metagenomics technology can directly extract microbial genetic material from the environmental samples to obtain their sequencing reads, which can be further assembled into contigs through assembly tools. Clustering methods of contigs are subsequently applied to recover complete genomes from environmental samples. The main problems with current clustering methods are that they cannot recover more high-quality genes from complex environments. Firstly, there are multiple strains under the same species, resulting in assembly of chimeras. Secondly, different strains under the same species are difficult to be classified. Thirdly, it is difficult to determine the number of strains during the clustering process.

Results
In view of the shortcomings of current clustering methods, we propose an unsupervised clustering method which can improve the ability to recover genes from complex environments and a new method for selecting the number of sample’s strains in clustering process. The sequence composition characteristics (tetranucleotide frequency) and co-abundance are combined to train the probability model for clustering. A new recursive method that can continuously reduce the complexity of the samples is proposed to improve the ability to recover genes from complex environments. The new clustering method was tested on both simulated and real metagenomic datasets, and compared with five state-of-the-art methods including CONCOCT, Maxbin2.0, MetaBAT, MyCC and COCACOLA. In terms of the number and quality of recovered genes from metagenomic datasets, the results show that our proposed method is more effective.

Conclusions
A new contigs clustering method is proposed, which can recover more high-quality genes from complex environmental samples.
Comparison of pneumococcal colonization density among healthy children and children with respiratory symptoms using real time PCR (RT-PCR)
Authors: Vidanapathirana G , Angulmaduwa A L S K , Munasinghe T S , Ekanayake E W M A , Harasgama P , Kudagammana S T , Dissanayake B N , Liyanapathirana L V C 
Published: January 2022

Abstract
Background
Nasopharyngeal colonization is considered a necessary step in the initiation of pneumococcal diseases. Real time PCR (RT-PCR) is an alternative approach for the identification and quantification of pneumococci directly from samples.

Objectives
To compare pneumococcal detection rates using culture-based method versus RT-PCR direct detection and to quantify pneumococcal colonization in two study cohorts (healthy children and hospitalized children with respiratory symptoms) using quantitation through RT-PCR.

Methodology
A total of 101 nasopharyngeal swabs (NPS) from healthy children and 183 NPSs from hospitalized children with respiratory symptoms were included in the study. None of the children were vaccinated. All children were between 2 months to 2 years. In parallel to routine culture and identification, a RT-PCR assay targeting the lytA gene was done.

Results
Considering all 284 samples tested, colonization rate by conventional culture was 41.2% (n = 117) while positive colonization using RT-PCR was 43.7% (n = 124). The colonization rate detected by RT-PCR in the healthy cohort was 33.7% (n = 34) and it was 49.2% (n = 90) in the hospitalized cohort. It was 37.6% (n = 38) and 43.2% (n = 79) for the two cohorts by culture. The mean Cq value for the healthy cohort is 29.61 (SD 2.85) and 28.93 (SD 3.62) for the hospitalized cohort.
With the standard curve obtained from amplifying a dilution series of control DNA, the mean amount of genomic DNA copy numbers detected in children with respiratory symptoms was log10 7.49 (SD 1.07) while it was log10 7.30 (SD 0.23) in healthy children and the difference was not statistically significant.

Conclusions
The overall colonization rate was higher when detected using RT-PCR compared to culture. However, it was lower in the healthy group when detected with RT-PCR compared to culture. Even though there was a higher detection of pneumococcal colonization density in children with respiratory symptoms, this was not significantly higher unlike many previous studies. Therefore, the use of RT-PCR to detect pneumococcal colonization needs further evaluation with careful analysis of interpretation and confounders.
Role of cassava CC-type glutaredoxin MeGRXC3 in regulating sensitivity to mannitol-induced osmotic stress dependent on its nuclear activity
Authors: Ruan Meng-Bin , Yu Xiao-Ling , Guo Xin , Zhao Ping-Juan , Peng Ming 
Published: January 2022

Abstract
Background
We previously identified six drought-inducible CC-type glutaredoxins in cassava cultivars, however, less is known about their potential role in the molecular mechanism by which cassava adapted to abiotic stress.

Results
Herein, we investigate one of cassava drought-responsive CC-type glutaredoxins, namely MeGRXC3, that involved in regulation of mannitol-induced inhibition on seed germination and seedling growth in transgenic Arabidopsis. MeGRXC3 overexpression up-regulates several stress-related transcription factor genes, such as PDF1.2, ERF6, ORA59, DREB2A, WRKY40, and WRKY53 in Arabidopsis. Protein interaction assays show that MeGRXC3 interacts with Arabidopsis TGA2 and TGA5 in the nucleus. Eliminated nuclear localization of MeGRXC3 failed to result mannitol-induced inhibition of seed germination and seedling growth in transgenic Arabidopsis. Mutation analysis of MeGRXC3 indicates the importance of conserved motifs for its transactivation activity in yeast. Additionally, these motifs are also indispensable for its functionality in regulating mannitol-induced inhibition of seed germination and enhancement of the stress-related transcription factors in transgenic Arabidopsis.

Conclusions
MeGRXC3 overexpression confers mannitol sensitivity in transgenic Arabidopsis possibly through interaction with TGA2/5 in the nucleus, and nuclear activity of MeGRXC3 is required for its function.
Overlapping infection of Nocardia farcinica and Aspergillus fumigatus in a child with X-linked chronic granulomatous disease: a case report
Authors: Tian Xiyan , Shi Qingmiao , Liu Peng , Pang Lulu , Jia Peisheng , Xie Lei , Ma Xiaoxu , Li Ang , Yu Zujiang , Wang Huaili 
Published: January 2022

Abstract
Background
Chronic granulomatous disease (CGD) is a rare inherited primary immunodeficiency syndrome, manifested as recurrent infections and inflammatory complications. Although prophylactic treatment with antibiotics and antifungals improved the outcome of CGD patients, infections remain the major cause of mortality.

Case presentation
A boy aged 3 years and 8 months was admitted to hospital complaining of lip swelling with fever for half a month and neck abscess for 11 days. After a thorough examination, severe pneumonia, respiratory failure, oral and maxillofacial space infection, and perianal abscess were confirmed. However, his condition didn’t improve after initial comprehensive therapy. Subsequently, overlapping infections of Nocardia farcinica and Aspergillus fumigatus were identified by metagenomic next-generation sequencing. He was treated with imipenem, linezolid, and voriconazole intravenously, plus taking oral compound sulfamethoxazole. Later, his condition improved. Through whole-exome sequencing, the child was ultimately diagnosed as X-linked chronic granulomatous disease (X-CGD) caused by CYBB gene mutation. Allogeneic hematopoietic stem cell transplantation was the potential sanative approach but there were no available human leukocyte antigen compatible donors for the child. The family requested to transfer to a superior hospital for further treatment. Two months later, we followed up the child’s family. Unfortunately, the child had expired due to severe infection.

Conclusion
To our knowledge, this is the first case of overlapping infection of Nocardia farcinica and Aspergillus fumigatus identified by metagenomic next-generation sequencing in a child with X-CGD from China. For infectious pathogens that are hard to diagnosis by traditional detection methods, metagenomic next-generation sequencing is recommended as an adminicle or indispensable approach for microbial identification. Patients with X-CGD have poor prognosis, early diagnosis and intervention of X-CGD may reduce the mortality.
A case of brucellosis-induced Guillain–Barre syndrome
Authors: Li Qian , Liu Jianfeng , Jiang Wenhui , Jiang Lisheng , Lu Mengzhi , Xiao Linping , Li Yukun , Lan Yinghua , Li Yongguo 
Published: January 2022

Abstract
Background
Guillain–Barre syndrome (GBS) is a rare neurological complication of brucellosis, and neurobrucellosis is the most common, but they have many similarities in clinical manifestations. Many clinicians are accustomed to merely explaining the manifestations of nervous system involvement with neurobrucellosis, but they ignore the possibility of GBS, and this leads to misdiagnosis, untimely treatment, and serious consequences.

Case presentation
A 55-year-old male patient was admitted to The First Affiliated Hospital of Harbin Medical University for intermittent fever, fatigue, and waist pain more than three months. Brucellosis was diagnosed from the blood test. Although anti-brucella treatment was given at the time of diagnosis, the disease continued to progress. At the time of the cerebrospinal fluid systematic physical examination and the neuroelectrophysiological test, acute motor sensory axonal neuropathy was diagnosed. The patient was given immediately administered immunoglobulin therapy. After three months of systemic treatment, the patient's muscle strength of the distal limbs gradually recovered. The numbness of the limbs eased slowly, and urination function and respiratory function returned to normal. He could sit by himself.

Conclusions
The possibility of GBS should be closely monitored for when a brucellosis patient shows typical clinical manifestations of progressive muscle weakness, protein-cell separation of the cerebral spinal fluid, and typical demyelinating sensorimotor polyneuropathy.