bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Rate of Return to Preinjury Tegner Activity Level Among Recreational Athletes: Results at 1 Year After Primary ACL Reconstruction
Authors: Kim Su-Hyun , Lee Ja-Woon , Kim Sang-Gyun , Cho Hyun-Woo , Bae Ji-Hoon 
Published: January 2021

Background: There is limited information about the functional recovery and rate of return to preinjury levels of sports among recreational athletes after anterior cruciate ligament reconstruction (ACLR). Purpose: To investigate the recovery of quadriceps or hamstring strength, assess functional performance, and determine the rate of return to preinjury sports levels among recreational athletes at 1 year after ACLR. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 91 recreational-level athletes who underwent anatomic single-bundle ACLR were enrolled. We evaluated the limb symmetry index (LSI) of the quadriceps and hamstring peak torque strength at 60°, in addition to hop test performance (single-leg, triple, crossover, and 6-m timed), patient-reported outcomes, and pre- versus postoperative Tegner activity levels. Outcomes were compared between younger (age <25 years) and older patients (age ≥25 years). Results: There were 48 patients in the younger group and 43 patients in the older group. At 1-year follow-up, the overall LSIs for quadriceps strength and hamstring strength were 77% and 86%, respectively, and the LSIs of the hop tests were 79% for single-leg, 81% for triple, 84% for crossover, and 85% for 6-m timed hop. Overall, only 24% patients returned to their preinjury Tegner level, and only 8% of patients met the criteria for return to pivoting, cutting, and jumping sports. At 1-year follow-up, the younger group showed significantly more quadriceps strength than the older group (85% vs 64%; P = .0001), better single, triple, crossover, and 6-m timed hop test results (85% vs 69%, P = .003; 84% vs 75%, P = .046; 91% vs. 74%, P < .001; and 91% vs 76%, P = .003, respectively), higher Lysholm score (87 vs 74; P < 0.001) and International Knee Document Committee score (82 vs 66; P < .001), and a higher rate of return to preinjury Tegner level (35% vs 12%; P = .009). Conclusion: Only 24% of patients returned to the preinjury Tegner level at 1 year after ACLR (35% younger group vs 12% older group; P = .009). This information might be helpful in setting realistic expectations for recreational athletes after surgery.
Impaired ribosome biogenesis checkpoint activation induces p53-dependent MCL-1 degradation and MYC-driven lymphoma death
Authors: Domostegui Ana , Peddigari Suresh , Mercer Carol A. , Iannizzotto Flavia , Rodriguez Marta L. , Garcia-Cajide Marta , Amador Virginia , Diepstraten Sarah T. , Kelly Gemma L. , Salazar Ramón , Kozma Sara C. , Kusnadi Eric P. , Kang Jian , Gentilella Antonio , Pearson Richard B. , Thomas George , Pelletier Joffrey 
Published: January 2021

AbstractMYC-driven B-cell lymphomas are addicted to increased levels of ribosome biogenesis (RiBi), offering the potential for therapeutic intervention. However, it is unclear whether inhibition of RiBi suppresses lymphomagenesis by decreasing translational capacity and/or by p53 activation mediated by the impaired RiBi checkpoint (IRBC). Here we generated Eμ-Myc lymphoma cells expressing inducible short hairpin RNAs to either ribosomal protein L7a (RPL7a) or RPL11, the latter an essential component of the IRBC. The loss of either protein reduced RiBi, protein synthesis, and cell proliferation to similar extents. However, only RPL7a depletion induced p53-mediated apoptosis through the selective proteasomal degradation of antiapoptotic MCL-1, indicating the critical role of the IRBC in this mechanism. Strikingly, low concentrations of the US Food and Drug Administration–approved anticancer RNA polymerase I inhibitor Actinomycin D (ActD) dramatically prolonged the survival of mice harboring Trp53+/+;Eμ-Myc but not Trp53–/–;Eμ-Myc lymphomas, which provides a rationale for treating MYC-driven B-cell lymphomas with ActD. Importantly, the molecular effects of ActD on Eμ-Myc cells were recapitulated in human B-cell lymphoma cell lines, highlighting the potential for ActD as a therapeutic avenue for p53 wild-type lymphoma.
ASH ISTH NHF WFH 2021 guidelines on the management of von Willebrand disease
Authors: Connell Nathan T. , Flood Veronica H. , Brignardello-Petersen Romina , Abdul-Kadir Rezan , Arapshian Alice , Couper Susie , Grow Jean M. , Kouides Peter , Laffan Michael , Lavin Michelle , Leebeek Frank W. G. , O’Brien Sarah H. , Ozelo Margareth C. , Tosetto Alberto , Weyand Angela C. , James Paula D. , Kalot Mohamad A. , Husainat Nedaa , Mustafa Reem A. 
Published: January 2021

Background:von Willebrand disease (VWD) is a common inherited bleeding disorder. Significant variability exists in management options offered to patients.Objective:These evidence-based guidelines from the American Society of Hematology (ASH), the International Society on Thrombosis and Haemostasis (ISTH), the National Hemophilia Foundation (NHF), and the World Federation of Hemophilia (WFH) are intended to support patients, clinicians, and health care professionals in their decisions about management of VWD.Methods:ASH, ISTH, NHF, and WFH formed a multidisciplinary guideline panel. Three patient representatives were included. The panel was balanced to minimize potential bias from conflicts of interest. The University of Kansas Outcomes and Implementation Research Unit and the McMaster Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process, including performing and updating systematic evidence reviews (through November 2019). The panel prioritized clinical questions and outcomes according to their importance to clinicians and patients. The panel used the GRADE approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment.Results:The panel agreed on 12 recommendations and outlined future research priorities.Conclusions:These guidelines make key recommendations regarding prophylaxis for frequent recurrent bleeding, desmopressin trials to determine therapy, use of antiplatelet agents and anticoagulant therapy, target VWF and factor VIII activity levels for major surgery, strategies to reduce bleeding during minor surgery or invasive procedures, management options for heavy menstrual bleeding, management of VWD in the context of neuraxial anesthesia during labor and delivery, and management in the postpartum setting.
Adjunctive treatment with oral dexamethasone in non-ICU patients hospitalised with community-acquired pneumonia: a randomised clinical trial
Authors: Wittermans Esther , Vestjens Stefan M.T. , Spoorenberg Simone M.C. , Blok Willem L. , Grutters Jan C. , Janssen Rob , Rijkers Ger T. , Smeenk Frank W.J.M. , Voorn G. Paul , van de Garde Ewoudt M.W. , Bos Willem Jan W. ,   the Santeon-CAP Study Group
Published: January 2021

BackgroundAdjunctive intravenous corticosteroid treatment has been shown to reduce length of stay (LOS) in adults hospitalised with community-acquired pneumonia (CAP). We aimed to assess the effect of oral dexamethasone on LOS and whether this effect is disease severity dependent.MethodsIn this multicentre, stratified randomised, double-blind, placebo-controlled trial, immunocompetent adults with CAP were randomly assigned (1:1 ratio) to receive oral dexamethasone (6 mg once daily) or placebo for 4 days in four teaching hospitals in the Netherlands. Randomisation (blocks of four) was stratified by CAP severity (pneumonia severity index class I–III and IV–V). The primary outcome was LOS.ResultsBetween December 2012 and November 2018, 401 patients were randomised to receive dexamethasone (n=203) or placebo (n=198). Median LOS was shorter in the dexamethasone group (4.5 days, 95% CI 4.0–5.0 days) than in the placebo group (5.0 days, 95% CI 4.6–5.4 days; p=0.033). Within both CAP severity subgroups, differences in LOS between treatment groups were not statistically significant. The secondary ICU admission rate was lower in the dexamethasone arm (5 (3%)versus14 (7%); p=0.030); 30-day mortality did not differ between groups. In the dexamethasone group the rate of hospital readmission tended to be higher (20 (10%)versus9 (5%); p=0.051) and hyperglycaemia (14 (7%)versus1 (1%); p=0.001) was more prevalent.ConclusionOral dexamethasone reduced LOS and ICU admission rate in adults hospitalised with CAP. It remains unclear for which patients the risk–benefit ratio is optimal.
Unsupervised phenotypic clustering for determining clinical status in children with cystic fibrosis
Authors: Filipow Nicole , Davies Gwyneth , Main Eleanor , Sebire Neil J. , Wallis Colin , Ratjen Felix , Stanojevic Sanja 
Published: January 2021

BackgroundCystic fibrosis (CF) is a multisystem disease in which the assessment of disease severity based on lung function alone may not be appropriate. The aim of the study was to develop a comprehensive machine-learning algorithm to assess clinical status independent of lung function in children.MethodsA comprehensive prospectively collected clinical database (Toronto, Canada) was used to apply unsupervised cluster analysis. The defined clusters were then compared by current and future lung function, risk of future hospitalisation, and risk of future pulmonary exacerbation treated with oral antibiotics. A k-nearest-neighbours (KNN) algorithm was used to prospectively assign clusters. The methods were validated in a paediatric clinical CF dataset from Great Ormond Street Hospital (GOSH).ResultsThe optimal cluster model identified four (A–D) phenotypic clusters based on 12 200 encounters from 530 individuals. Two clusters (A and B) consistent with mild disease were identified with high forced expiratory volume in 1 s (FEV1), and low risk of both hospitalisation and pulmonary exacerbation treated with oral antibiotics. Two clusters (C and D) consistent with severe disease were also identified with low FEV1. Cluster D had the shortest time to both hospitalisation and pulmonary exacerbation treated with oral antibiotics. The outcomes were consistent in 3124 encounters from 171 children at GOSH. The KNN cluster allocation error rate was low, at 2.5% (Toronto) and 3.5% (GOSH).ConclusionMachine learning derived phenotypic clusters can predict disease severity independent of lung function and could be used in conjunction with functional measures to predict future disease trajectories in CF patients.
Risk factors associated with the development of interstitial lung abnormalities
Authors: Buendía-Roldán Ivette , Fernandez Rosario , Mejía Mayra , Juarez Fortunato , Ramirez-Martinez Gustavo , Montes Eduardo , Pruneda Ana Karem S. , Martinez-Espinosa Karen , Alarcon-Dionet Aime , Herrera Iliana , Becerril Carina , Chavez-Galan Leslie , Preciado Mario , Pardo Annie , Selman Moisés 
Published: January 2021

BackgroundAround 8–10% of individuals over 50 years of age present interstitial lung abnormalities (ILAs), but their risk factors are uncertain.MethodsFrom 817 individuals recruited in our lung ageing programme at the Mexican National Institute of Respiratory Diseases, 80 (9.7%) showed ILAs and were compared with 564 individuals of the same cohort with normal high-resolution computed tomography to evaluate demographic and functional differences, and with 80 individuals randomly selected from the same cohort for biomarkers. We evaluatedMUC5Bvariant rs35705950, telomere length, and serum levels of matrix metalloproteinase (MMP)-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MMP-13, interleukin (IL)-6, surfactant protein (SP)-D, α-Klotho and resistin.ResultsIndividuals with ILAs were usually males (p<0.005), older than controls (p<0.0001), smokers (p=0.01), with a greater frequency ofMUC5Brs35705950 (OR 3.5, 95% CI 1.3–9.4; p=0.01), and reduced diffusing capacity of the lung for carbon monoxide and oxygen saturation. Resistin, IL-6, SP-D, MMP-1, MMP-7 and MMP-13 were significantly increased in individuals with ILAs. Resistin (12±5versus9±4 ng·mL−1; p=0.0005) and MMP-13 (357±143versus298±116 pg·mL−1; p=0.004) were the most increased biomarkers. On follow-up (24±18 months), 18 individuals showed progression which was associated with gastro-oesophageal reflux disease (OR 4.1, 95% CI 1.2–12.9; p=0.02) and in females with diabetes mellitus (OR 5.3, 95% CI 1.0–27.4; p=0.01).ConclusionsAround 10% of respiratory asymptomatic individuals enrolled in our lung ageing programme show ILAs. Increased serum concentrations of pro-inflammatory molecules and MMPs are associated with ILAs.
Long-term adherence to inhaled corticosteroids and asthma control in adult-onset asthma
Authors: Vähätalo Iida , Kankaanranta Hannu , Tuomisto Leena E. , Niemelä Onni , Lehtimäki Lauri , Ilmarinen Pinja 
Published: January 2021

BackgroundIn short-term studies, poor adherence to inhaled corticosteroids (ICS) has been associated with worse asthma control, but the association of long-term adherence and disease control remains unclear.ObjectiveTo assess the relationship between 12-year adherence to ICS and asthma control in patients with adult-onset asthma.MethodsAs part of the Seinäjoki Adult Asthma Study, 181 patients with clinically confirmed new-onset adult asthma and regular ICS medication were followed-up for 12 years. Adherence (%) to ICS was assessed individually ((µg dispensed/µg prescribed)×100) during the follow-up. Asthma control was evaluated after 12 years of treatment according to the Global Initiative for Asthma 2010 guideline.ResultsAsthma was controlled in 31% and not controlled (partly controlled or uncontrolled) in 69% of the patients. Patients with not-controlled asthma were more often male, older, nonatopic and used higher doses of ICS than those with controlled disease. The mean±sd12-year adherence to ICS was 63±38% in patients with controlled asthma and 76±40% in patients with not-controlled disease (p=0.042). Among patients with not-controlled asthma, those with lower 12-year adherence (<80%) had more rapid decline in forced expiratory volume in 1 s (−47 mL·year−1) compared to patients with better adherence (≥80%) (−40 mL·year−1) (p=0.024). In contrast, this relationship was not seen in patients with controlled asthma.ConclusionsIn adult-onset asthma, patients with not-controlled disease showed better 12-year adherence to ICS treatment than those with controlled asthma. In not-controlled disease, adherence <80% was associated with more rapid lung function decline, underscoring the importance of early recognition of such patients in routine clinical practice.
The Fungal Effector Avr-Pita Suppresses Innate Immunity by Increasing COX Activity in Rice Mitochondria
Authors: Han Jingluan , Wang Xiaoyu , Wang Fengpin , Zhao Zhe , Li Gousi , Zhu Xiaoyuan , Su Jing , Chen Letian 
Published: January 2021

AbstractBackgroundAvr-Pita was the first effector identified in the blast fungus (Magnaporthe oryzae)–rice (Oryza sativa) pathosystem. However, the molecular mechanism underlying its effects on the host plant has remained a long-standing mystery.ResultsHere, we report that ectopically expressingAvr-Pitain rice enhances susceptibility toM. oryzaeand suppresses pathogen-associated molecular pattern (PAMP)-triggered defense responses. Avr-Pita targets the host mitochondria and interacts with the cytochromecoxidase (COX) assembly protein OsCOX11, a key regulator of mitochondrial reactive oxygen species (ROS) metabolism in rice. OverexpressingAvr-PitaorOsCOX11increased COX activity and decreased ROS accumulation triggered by the fungal PAMP chitin.OsCOX11-overexpressing plants showed increased susceptibility toM. oryzae, whereasOsCOX11-knockdown plants showed resistance toM. oryzae.ConclusionsTaken together, these findings suggest that the fungal pathogenM. oryzaedelivers the effector Avr-Pita to the host plant, where it enhances COX activity thus decreasing ROS accumulation. Therefore, this effector suppresses host innate immunity by perturbing ROS metabolism in the mitochondria.
Alternative Polyadenylation in response to temperature stress contributes to gene regulation in Populus trichocarpa
Authors: Yan Chao , Wang Yupeng , Lyu Tao , Hu Zhikang , Ye Ning , Liu Weixin , Li Jiyuan , Yao Xiaohua , Yin Hengfu 
Published: January 2021

Abstract
Background
Genome-wide change of polyadenylation (polyA) sites (also known as alternative polyadenylation, APA) is emerging as an important strategy of gene regulation in response to stress in plants. But little is known in woody perennials that are persistently dealing with multiple abiotic stresses.

Results
Here, we performed a genome-wide profiling of polyadenylation sites under heat and cold treatments in Populus trichocarpa. Through a comprehensive analysis of polyA tail sequences, we identified 25,919 polyA-site clusters (PACs), and revealed 3429 and 3139 genes shifted polyA sites under heat and cold stresses respectively. We found that a small proportion of genes possessed APA that affected the open reading frames; and some shifts were commonly identified. Functional analysis of genes displaying shifted polyA tails suggested that pathways related to RNA metabolism were linked to regulate the APA events under both heat and cold stresses. Interestingly, we found that the heat stress induced a significantly more antisense PACs comparing to cold and control conditions. Furthermore, we showed that a unique cis-element (AAAAAA) was predominately enriched downstream of PACs in P. trichocarpa genes; and this sequence signal was only absent in shifted PACs under the heat condition, indicating a distinct APA mechanism responsive to heat tolerance.

Conclusions
This work provides a comprehensive picture of global polyadenylation patterns in response to temperatures stresses in trees. We show that the frequent change of polyA tail is a potential mechanism of gene regulation responsive to stress, which are associated with distinctive sequence signatures.
Genome evolution during bread wheat formation unveiled by the distribution dynamics of SSR sequences on chromosomes using FISH
Authors: Zhang Yingxin , Fan Chengming , Chen Yuhong , Wang Richard R.-C. , Zhang Xiangqi , Han Fangpu , Hu Zanmin 
Published: January 2021

Abstract
Background
During the bread wheat speciation by polyploidization, a series of genome rearrangement and sequence recombination occurred. Simple sequence repeat (SSR) sequences, predominately located in heterochromatic regions of chromosomes, are the effective marker for tracing the genomic DNA sequence variations. However, to date the distribution dynamics of SSRs on chromosomes of bread wheat and its donors, including diploid and tetraploid Triticum urartu, Aegilops speltoides, Aegilops tauschii, Triticum turgidum ssp. dicocoides, reflecting the genome evolution events during bread wheat formation had not been comprehensively investigated.

Results
The genome evolution was studied by comprehensively comparing the distribution patterns of (AAC)n, (AAG)n, (AGC)n and (AG)n in bread wheat Triticum aestivum var. Chinese Spring and its progenitors T. urartu, A. speltoides, Ae. tauschii, wild tetroploid emmer wheat T. dicocoides, and cultivated emmer wheat T. dicoccum. Results indicated that there are specific distribution patterns in different chromosomes from different species for each SSRs. They provided efficient visible markers for identification of some individual chromosomes and SSR sequence evolution tracing from the diploid progenitors to hexaploid wheat. During wheat speciation, the SSR sequence expansion occurred predominately in the centromeric and pericentromeric regions of B genome chromosomes accompanied by little expansion and elimination on other chromosomes. This result indicated that the B genome might be more sensitive to the “genome shock” and more changeable during wheat polyplodization.

Conclusions
During the bread wheat evolution, SSRs including (AAC)n, (AAG)n, (AGC)n and (AG)n in B genome displayed the greatest changes (sequence expansion) especially in centromeric and pericentromeric regions during the polyploidization from Ae. speltoides S genome, the most likely donor of B genome. This work would enable a better understanding of the wheat genome formation and evolution and reinforce the viewpoint that B genome was originated from S genome.
Proteome-wide and lysine crotonylation profiling reveals the importance of crotonylation in chrysanthemum (Dendranthema grandiforum) under low-temperature
Authors: Lin Ping , Bai Hui-ru , He Ling , Huang Qiu-xiang , Zeng Qin-han , Pan Yuan-zhi , Jiang Bei-bei , Zhang Fan , Zhang Lei , Liu Qing-Lin 
Published: January 2021

AbstractBackgroundLow-temperature severely affects the growth and development of chrysanthemum which is one kind of ornamental plant well-known and widely used in the world. Lysine crotonylation is a recently identified post-translational modification (PTM) with multiple cellular functions. However, lysine crotonylation under low-temperature stress has not been studied.ResultsProteome-wide and lysine crotonylation of chrysanthemum at low-temperature was analyzed using TMT (Tandem Mass Tag) labeling, sensitive immuno-precipitation, and high-resolution LC-MS/MS. The results showed that 2017 crotonylation sites were identified in 1199 proteins. Treatment at 4 °C for 24 h and − 4 °C for 4 h resulted in 393 upregulated proteins and 500 downregulated proteins (1.2-fold threshold andP < 0.05). Analysis of biological information showed that lysine crotonylation was involved in photosynthesis, ribosomes, and antioxidant systems. The crotonylated proteins and motifs in chrysanthemum were compared with other plants to obtain orthologous proteins and conserved motifs. To further understand how lysine crotonylation at K136 affected APX (ascorbate peroxidase), we performed a site-directed mutation at K136 in APX. Site-directed crotonylation showed that lysine decrotonylation at K136 reduced APX activity, and lysine complete crotonylation at K136 increased APX activity.ConclusionIn summary, our study comparatively analyzed proteome-wide and crotonylation in chrysanthemum under low-temperature stress and provided insights into the mechanisms of crotonylation in positively regulated APX activity to reduce the oxidative damage caused by low-temperature stress. These data provided an important basis for studying crotonylation to regulate antioxidant enzyme activity in response to low-temperature stress and a new research ideas for chilling-tolerance and freezing-tolerance chrysanthemum molecular breeding.