bluuebunny/crossref_metadata_2025_split huggingface dataset:
Talar and Subtalar T1ρ Relaxation Times in Limbs with and without Chronic Ankle Instability
Authors: Song Kyeongtak , Pietrosimone Brian , Tennant Joshua N. , Nissman Daniel B. , Dederer Katherine M. , Paranjape Chinmay , Wikstrom Erik A. 
Published: February 2021

Objective The primary aim was to determine differences in talocrural and subtalar joint (STJ) articular cartilage composition, using T1ρ magnetic resonance imaging (MRI) relaxation times, between limbs in individuals with unilateral chronic ankle instability (CAI) and compare with an uninjured control. Our secondary purpose was to determine the association between talocrural and STJ composition in limbs with and without CAI. Design T1ρ MRI relaxation times were collected on 15 CAI (11 females, 21.13 ± 1.81 years, body mass index [BMI] = 23.96 ± 2.74 kg/m2) and 15 uninjured control individuals (11 females, 21.07 ± 2.55 years, BMI = 24.59 ± 3.44 kg/m2). Talocrural cartilage was segmented manually to identify the overall talar dome. The SJT cartilage was segmented manually to identify the anterior, medial, and posterior regions of interest consistent with STJ anatomical articulations. For each segmented area, a T1ρ relaxation time mean and variability value was calculated. Greater T1ρ relaxation times were interpreted as decreased proteoglycan content. Results Individuals with CAI demonstrated a higher involved limb talocrural T1ρ mean and variability relative to their contralateral limb ( P < 0.05) and the healthy control limb ( P < 0.05). The CAI-involved limb also had a higher posterior STJ T1ρ mean relative to the healthy control limb ( P < 0.05). In healthy controls ( P < 0.05), but not the CAI-involved or contralateral limbs (p>0.05), talocrural and posterior STJ composition measures were positively associated. Conclusions Individuals with CAI have lower proteoglycan content in both the talocrural and posterior STJ in their involved limbs relative to the contralateral and a healthy control limb. Cartilage composition findings may be consistent with the early development of posttraumatic osteoarthritis.
Factor XII plays a pathogenic role in organ failure and death in baboons challenged withStaphylococcus aureus
Authors: Silasi Robert , Keshari Ravi S. , Regmi Girija , Lupu Cristina , Georgescu Constantin , Simmons Joe H. , Wallisch Michael , Kohs Tia C. L. , Shatzel Joseph J. , Olson Sven R. , Lorentz Christina U. , Puy Cristina , Tucker Erik I. , Gailani David , Strickland Sidney , Gruber András , McCarty Owen J. T. , Lupu Florea 
Published: February 2021

AbstractActivation of coagulation factor (F) XI promotes multiorgan failure in rodent models of sepsis and in a baboon model of lethal systemic inflammation induced by infusion of heat-inactivated Staphylococcus aureus. Here we used the anticoagulant FXII-neutralizing antibody 5C12 to verify the mechanistic role of FXII in this baboon model. Compared with untreated control animals, repeated 5C12 administration before and at 8 and 24 hours after bacterial challenge prevented the dramatic increase in circulating complexes of contact system enzymes FXIIa, FXIa, and kallikrein with antithrombin or C1 inhibitor, and prevented cleavage and consumption of high-molecular-weight kininogen. Activation of several coagulation factors and fibrinolytic enzymes was also prevented. D-dimer levels exhibited a profound increase in the untreated animals but not in the treated animals. The antibody also blocked the increase in plasma biomarkers of inflammation and cell damage, including tumor necrosis factor, interleukin (IL)-1β, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, nucleosomes, and myeloperoxidase. Based on clinical presentation and circulating biomarkers, inhibition of FXII prevented fever, terminal hypotension, respiratory distress, and multiorgan failure. All animals receiving 5C12 had milder and transient clinical symptoms and were asymptomatic at day 7, whereas untreated control animals suffered irreversible multiorgan failure and had to be euthanized within 2 days after the bacterial challenge. This study confirms and extends our previous finding that at least 2 enzymes of the contact activation complex, FXIa and FXIIa, play critical roles in the development of an acute and terminal inflammatory response in baboons challenged with heat-inactivated S aureus.
Clinical factors and outcomes of subsegmental pulmonary embolism in cancer patients
Authors: Yan Melissa , Kieser Ryan , Wu Carol C. , Qiao Wei , Rojas-Hernandez Cristhiam M. 
Published: February 2021

Abstract
In the cancer population, patients diagnosed with venous thromboembolism (VTE) are considered to have a threefold increased risk of mortality compared with those without VTE. With the advent of modern computed tomography (CT), the rate of diagnosis of subsegmental pulmonary embolism (SSPE) has increased, likely as a result of improved visualization of the peripheral pulmonary arteries. The clinical significance of SSPE remains unclear because of the lack of randomized controlled clinical trials. The aim of this study was to identify the incidence and risk factors of recurrent proximal PE within 12 months of diagnosis of SSPE in cancer. We performed a retrospective analysis of 206 adult cancer patients who were diagnosed with SSPE from 2014 to 2016 at the University of Texas MD Anderson Cancer Center. At the time of SSPE diagnosis, the majority had metastatic cancer, 108 patients (53.2%) were undergoing chemotherapy, and 23 patients (11.2%) had a history of VTE. Most patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Sixty-seven percent of SSPE was discovered incidentally on restaging CT scans, with the majority being a single and isolated event (70.9%). Within 12 months of SSPE diagnosis, 18 patients (8.7%) were found to have a recurrent PE. The patients treated with anticoagulation had a lower rate of PE recurrence (8% vs 13% in those not treated with anticoagulation). Treatment with anticoagulation did not appear to have a significant impact on overall survival (P = .48) when adjusted for ECOG performance status and cancer stage.
Arthroscopic rotator cuff repair in patients over 70 years of age: a systematic review
Authors: Fossati Chiara , Stoppani Carlo , Menon Alessandra , Pierannunzii Luca , Compagnoni Riccardo , Randelli Pietro S. 
Published: February 2021

Abstract
Background
Failure of conservative treatment in patients over 70 years of age with a rotator cuff tear makes surgery a possible option, considering the increase in life expectancy and the high functional demands of elderly patients. The purpose of this systematic review of the literature was to evaluate the subjective and objective outcomes after arthroscopic rotator cuff repair in patients over 70 years of age.

Methods
A systematic review was performed to identify all the studies reporting subjective and objective outcomes in patients aged 70 years or older undergoing arthroscopic rotator cuff repair. Constant Murley Score (CMS), visual analog scale (VAS), American Shoulder and Elbow Surgeons Score (ASES), and Simple Shoulder Test (SST) were used to detect any clinical improvement after surgery. Retear and satisfaction were also analyzed.

Results
Out of 941 studies identified, only 6 papers have been included in the review. All studies reported improvements in postoperative functional outcome scores that exceed the minimal clinically relevant difference. The mean retear rate amounts to 21.9%, which is in line with the failure rate of rotator cuff repair in general population. Moreover, postoperative satisfaction is very high (95%).

Conclusion
This systematic review suggests that arthroscopic rotator cuff repair in patients over 70 years of age could be a valid treatment option after failure of conservative approach.
Level of evidence: 4
Trial registration The study was registered on PROSPERO (registration ID: CRD42018088613)
Time trends of socioeconomic inequalities in adolescent smoking in Okinawa, Japan, 2008–2016: a repeated cross-sectional study
Authors: Takakura Minoru , Miyagi Masaya , Kyan Akira 
Published: February 2021

Abstract
Background
Smoking among Japanese adolescents has decreased noticeably. However, little is known whether the decreasing trend in adolescent smoking can be seen across all socioeconomic status (SES) groups. This study aimed to examine trends in socioeconomic inequalities in smoking among Japanese adolescents between 2008 and 2016.

Methods
We conducted a repeated cross-sectional study using data from three surveys of high school students in Okinawa, Japan, in 2008, 2012, and 2016. The study participants consisted of 7902 students in grades 10 through 12 (15–18 years). Smoking was assessed as current cigarette use. SES indicators included familial SES (parental education and family structure) and student’s own SES (school type). To evaluate absolute and relative inequalities, prevalence differences (PDs) and ratios (PRs) between low and high SES groups were estimated. The slope index of inequality (SII) and relative index of inequality (RII) were also calculated.

Results
Smoking prevalence among boys and girls significantly declined from 11.5% and 6.2% in 2008 to 4.7% and 1.9% in 2016, respectively. Similar decreasing trends in smoking were found among most of the SES groups. The PDs and SII for parental education in boys and family structure in girls decreased over time while those for school type persisted among boys and girls. The PRs and RII for school type in boys increased while those for other SES indicators among both sexes remained stable over time.

Conclusions
Smoking among Japanese adolescents has been declining and time trends of socioeconomic inequalities in smoking varied by absolute and relative measures. Further policies and/or interventions to reduce smoking inequalities should focus on the context of schools, especially in vocational high schools.
Single dose of testosterone in children with hypospadias: any effect on the diameter of the glans penis?
Authors: Chukwubuike Kevin Emeka 
Published: February 2021

Abstract
Background
The purpose of this study was to assess the effect of a single dose of testosterone on the diameter of the glans penis.

Methods
This was a prospective evaluation of the effect of a single dose of testosterone on the diameter of the glans penis of children with hypospadias. The diameter of the glans penis was measured transversely at the level of the coronal sulcus using Vernier calipers. The patients were categorized into two groups: Group A and Group B. Group A received intramuscular testosterone at the dose of 2 mg per kilogram body weight. Group B did not receive any testosterone and served as control. The diameter of the glans penis was evaluated at the beginning of the study and at 4 weeks after the testosterone injection.

Results
Overall, 64 patients were evaluated. There were 32 patients in group A (50%) and 32 patients in group B (50%). The mean diameter in group A before and after testosterone injection was 17.6 mm ± 2.5 SD and 17.8 ± 2.3 SD, respectively. The mean diameter in group B at onset and after 4 weeks was 17.6 mm ± 2.4 SD and 17.7 ± 2.4 SD, respectively. p = 0.12 which is statistically insignificant.

Conclusion
Single dose of testosterone in children with hypospadias does not produce significant increase in the diameter of the glans penis.
Risk factors of premature ejaculation and its influence on sexual function of spouse
Authors: Li Hu , Gao Pan , Gao Jingjing , Wu Xu , Liu Guodong , Dai Yutian , Jiang Hui , Zhang Xiansheng 
Published: February 2021

Abstract
Background
Premature ejaculation (PE) is a multifactorial problem with a complicated aetiology that has detrimental effects on female partners’ sexual function. However, there is a lack of studies on the relationship between the factors related to PE and female sexual dysfunction (FSD) in China. We aimed to identify and explore the relationship between the factors associated with PE and FSD.

Results
Ultimately, information was collected from 761 couples: 445 couples with PE complaints and 316 couples without PE complaints. The mean ages of the men with and without PE complaints were 36.29 ± 9.87 years and 31.48 ± 10.77 years, respectively. Female partners in the group with PE complaints reported lower total and subdomain female sexual function index (FSFI) scores, and approximately 65% of them were diagnosed with FSD (vs. control group: 31.96%). A PE duration of more than 14 months, a self-estimated intravaginal ejaculation latency time (self-estimated IELT) less than 2 min, a negative attitude towards PE problems, men’s introversion, and men’s depression were risk factors for FSD in the PE group.

Conclusions
PE affects not only the patient himself but also the spouse. Comprehensive analysis reveals a clear relationship and interaction between female sexual function and PE. Moreover, in PE treatment, we should not ignore the occurrence of FSD and its impact and should emphasize the treatment of couples together.
Global transcriptome profile of the developmental principles of in vitro iPSC-to-motor neuron differentiation
Authors: Solomon Emilia , Davis-Anderson Katie , Hovde Blake , Micheva-Viteva Sofiya , Harris Jennifer Foster , Twary Scott , Iyer Rashi 
Published: February 2021

Abstract
Background
Human induced pluripotent stem cells (iPSC) have opened new avenues for regenerative medicine. Consequently, iPSC-derived motor neurons have emerged as potentially viable therapies for spinal cord injuries and neurodegenerative disorders including Amyotrophic Lateral Sclerosis. However, direct clinical application of iPSC bears in itself the risk of tumorigenesis and other unforeseeable genetic or epigenetic abnormalities.

Results
Employing RNA-seq technology, we identified and characterized gene regulatory networks triggered by in vitro chemical reprogramming of iPSC into cells with the molecular features of motor neurons (MNs) whose function in vivo is to innervate effector organs. We present meta-transcriptome signatures of 5 cell types: iPSCs, neural stem cells, motor neuron progenitors, early motor neurons, and mature motor neurons. In strict response to the chemical stimuli, along the MN differentiation axis we observed temporal downregulation of tumor growth factor-β signaling pathway and consistent activation of sonic hedgehog, Wnt/β-catenin, and Notch signaling. Together with gene networks defining neuronal differentiation (neurogenin 2, microtubule-associated protein 2, Pax6, and neuropilin-1), we observed steady accumulation of motor neuron-specific regulatory genes, including Islet-1 and homeobox protein HB9. Interestingly, transcriptome profiling of the differentiation process showed that Ca2+ signaling through cAMP and LPC was downregulated during the conversion of the iPSC to neural stem cells and key regulatory gene activity of the pathway remained inhibited until later stages of motor neuron formation. Pathways shaping the neuronal development and function were well-represented in the early motor neuron cells including, neuroactive ligand-receptor interactions, axon guidance, and the cholinergic synapse formation. A notable hallmark of our in vitro motor neuron maturation in monoculture was the activation of genes encoding G-coupled muscarinic acetylcholine receptors and downregulation of the ionotropic nicotinic acetylcholine receptors expression. We observed the formation of functional neuronal networks as spontaneous oscillations in the extracellular action potentials recorded on multi-electrode array chip after 20 days of differentiation.

Conclusions
Detailed transcriptome profile of each developmental step from iPSC to motor neuron driven by chemical induction provides the guidelines to novel therapeutic approaches in the re-construction efforts of muscle innervation.
Genome-wide characterization of 2-oxoglutarate and Fe(II)-dependent dioxygenase family genes in tomato during growth cycle and their roles in metabolism
Authors: Wei Shuo , Zhang Wen , Fu Rao , Zhang Yang 
Published: February 2021

Abstract
Background
2-Oxoglutarate and Fe(II)-dependent dioxygenases (2ODDs) belong to the 2-oxoglutarate-dependent dioxygenase (2OGD) superfamily and are involved in various vital metabolic pathways of plants at different developmental stages. These proteins have been extensively investigated in multiple model organisms. However, these enzymes have not been systematically analyzed in tomato. In addition, type I flavone synthase (FNSI) belongs to the 2ODD family and contributes to the biosynthesis of flavones, but this protein has not been characterized in tomato.

Results
A total of 131 2ODDs from tomato were identified and divided into seven clades by phylogenetic classification. The Sl2ODDs in the same clade showed similar intron/exon distributions and conserved motifs. The Sl2ODDs were unevenly distributed across the 12 chromosomes, with different expression patterns among major tissues and at different developmental stages of the tomato growth cycle. We characterized several Sl2ODDs and their expression patterns involved in various metabolic pathways, such as gibberellin biosynthesis and catabolism, ethylene biosynthesis, steroidal glycoalkaloid biosynthesis, and flavonoid metabolism. We found that the Sl2ODD expression patterns were consistent with their functions during the tomato growth cycle. These results indicated the significance of Sl2ODDs in tomato growth and metabolism. Based on this genome-wide analysis of Sl2ODDs, we screened six potential FNSI genes using a phylogenetic tree and coexpression analysis. However, none of them exhibited FNSI activity.

Conclusions
Our study provided a comprehensive understanding of the tomato 2ODD family and demonstrated the significant roles of these family members in plant metabolism. We also suggest that no FNSI genes in tomato contribute to the biosynthesis of flavones.
Trastuzumab immunogenicity development in patients’ sera and in laboratory animals
Authors: Kilany Lobna Abdel Aziz , Gaber Ayman Abdel Samie , Aboulwafa Mohammad Mabrouk , Zedan Hamdallah Hafez 
Published: February 2021

Abstract
Background
Immunogenicity is a major challenge in drug development and patient care. Clinicians and regulators are familiar with immunogenicity concerns of monoclonal antibody (mAb) therapeutics, growth factors and enzyme replacements. Although most small therapeutic molecules are unlikely to trigger undesirable immunogenic responses against themselves upon their administration, the biological therapeutic agents are likely to induce such kind of immunogenicity. This imparts a problem that has to be considered upon judging their risk–benefit ratio. In this article, we tested the immunogenicity developed in patients’ sera due to the use of trastuzumab and that developed in laboratory animals injected with this recombinant humanized IgG1 monoclonal antibody.

Methods
We studied trastuzumab immunogenicity by: I in vitro detection of anti-trastuzumab antibody (Ab) levels in patient’s serum samples withdrawn at different points during trastuzumab treatment course; I.1 using an Affinity Capture Elution (ACE) assay, the assay is both sensitive and highly tolerant to free drug; I.2 using MTT cytotoxicity method against MCF-7 cell line as confirmatory method used in sample showed high level of anti-trastuzumab Ab and to determine neutralizing activity of the anti-trastuzumab Ab. II in vivo immunogenicity testing of trastuzumab in lab animals.

Results
In vitro analysis of patients’ sera for antibodies developed against trastuzumab revealed that this monoclonal antibody has low immunogenicity since most samples showed low levels of anti-trastuzumab antibodies that decreased progressively along the treatment course. Only 1% of samples showed high levels of anti-trastuzumab antibodies which might affect treatment course. In vivo immunogenicity testing in mice showed also low immunogenicity of trastuzumab that could support the in vitro clinical assessment applied in our study.

Conclusions
The study gives an evidence for the low trastuzumab immunogenicity when assessed in Egyptian patients under treatment with this biological therapeutic agent. This supports its prescription and continuous use across the approved indications as biological therapeutic agent.
Straw retention efficiently improves fungal communities and functions in the fallow ecosystem
Authors: Zhang Caifang , Lin Zhaoli , Que Youxiong , Fallah Nyumah , Tayyab Muhammad , Li Shiyan , Luo Jun , Zhang Zichu , Abubakar Ahmad Yusuf , Zhang Hua 
Published: February 2021

Abstract
Background
Straw retention is a substitute for chemical fertilizers, which effectively maintain organic matter and improve microbial communities on agricultural land. The purpose of this study was to provide sufficient information on soil fungal community networks and their functions in response to straw retention. Hence, we used quantitative real-time PCR (qRT-PCR), Illumina MiSeq (ITS rRNA) and FUNGuild to examine ITS rRNA gene populations, soil fungal succession and their functions under control (CK) and sugarcane straw retention (SR) treatments at different soil layers (0–10, 10–20, 20–30, and 30–40 cm) in fallow fields.

Result
The result showed that SR significantly enhanced ITS rRNA gene copy number and Shannon index at 0–10 cm soil depth. Fungi abundance, OTUs number and ACE index decreased with the increasing soil depth. The ANOSIM analysis revealed that the fungal community of SR significantly differed from that of CK. Similarly, significant difference was also observed between topsoil (0–20 cm) and subsoil (20–40 cm). Compared with CK, SR decreased the relative abundance of the pathogen, while increased the proportion of saprotroph. Regarding soil depth, pathogen relative abundance in topsoil was lower than that in subsoil. Besides, both sugarcane straw retention and soil depths (topsoil and subsoil) significantly altered the co-occurrence patterns and fungal keystone taxa closely related to straw decomposition. Furthermore, both SR and topsoil had higher average clustering coefficients (aveCC), negative edges and varied modularity.

Conclusions
Overall, straw retention improved α-diversity, network structure and fungal community, while reduced soil pathogenic microbes across the entire soil profile. Thus, retaining straw to improve fungal composition, community stability and their functions, in addition to reducing soil-borne pathogens, can be an essential agronomic practice in developing a sustainable agricultural system.