bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRISPR‐based assessment of genomic structure in the conserved SQUAMOSA promoter‐binding‐like gene clusters in rice
Authors: Jiang Mengmeng , He Ying , Chen Xiaonan , Zhang Xiaohui , Guo Yanru , Yang Sihai , Huang Ju , Traw M. Brian 
Published: September 2020

SUMMARYAlthough SQUAMOSA promoter‐binding‐like (SPL) transcription factors are important regulators of development in rice (Oryza sativa), prior assessments of the SPL family have been limited to single genes. A functional comparison across the full gene family in standardized genetic backgrounds has not been reported previously. Here, we demonstrate that the SPL gene family in rice is enriched due to the most recent whole genome duplication (WGD). Notably, 10 of 19 rice SPL genes (52%) cluster in four units that have persisted for at least 50 million years. We show that SPL gene grouping and retention following WGD is widespread in angiosperms, suggesting the conservatism and importance of this gene arrangement. We used Cas9 editing to generate transformation lines for all 19 SPL genes in a common set of backgrounds, and found that knockouts of 14 SPL genes exhibited defects in plant height, 10 exhibited defects in panicle size, and nine had altered grain lengths. We observed subfunctionalization of genes in the paleoduplicated pairs, but little evidence of neofunctionalization. Expression of OsSPL3 was negatively correlated with that of its closest neighbor in its synteny group, OsSPL4, and its sister paired gene, OsSPL12, in the opposing group. Nucleotide diversity was lower in eight of the nine singleton genes in domesticated rice, relative to wild rice, whereas the reverse was true for the paired genes. Together, these results provide functional information on eight previously unexamined OsSPL family members and suggest that paleoduplicate pair redundancy benefits plant survival and innovation.
Biomechanical comparison of ex vivo lumbar vertebral fracture luxations stabilized with tension band or polymethylmethacrylate in cats
Authors: Beer Patricia , Knell Sebastian C. , Pozzi Antonio , Park Brian H. 
Published: September 2020

AbstractObjectiveTo evaluate spinal stabilization with tension band stabilization (TS) in cats compared to screw and polymethylmethacrylate fixation (SP).Study designEx vivo study.Sample populationSixteen feline thoracolumbar spinal specimens.MethodsThe intact specimens were mounted in a six‐degree‐of‐freedom biaxial testing machine for nondestructive testing to obtain the neutral zones (NZ) and range of motion (ROM) in flexion and extension. Thereafter, nondestructive testing was consecutively performed after destabilization by disc fenestration and partial L1 corpectomy and after treatment with either TS or SP. Load to failure was compared after surgical treatment in flexion. Significance was assessed by Student's t test or Wilcoxon signed‐rank test.ResultsRange of motion was 26.4° ± 2.2° in TS constructs and 13.4° ± 2.1° in SP constructs (P = .0005). When flexion and extension were analyzed separately, no difference was found for ROM in flexion (SP, 7.0° ± 3.7°; TS, 8.3° ± 2.1°; P = .38). In extension, the mean displacement was 6.4° ± 2.7° and 18.1° ± 5.1° in SP and TS constructs, respectively (P = .0001). Neutral zone was 2.9° ± 0.6° and 7.5° ± 0.8° for the SP and TS groups, respectively (P = .0003). Screw and polymethylmethacrylate fixation constructs were two times stiffer (P = .045).ConclusionTension band stabilization provided stability comparable to SP in flexion. In extension, ROM of SP constructs was half that of TS constructs. The mode of failure of TS was related to the limited dorsal bone stock of feline lumbar vertebrae.Clinical significanceSurgeons should be aware of the limited stability in extension provided by TS when it is used to stabilize thoracolumbar spinal injuries. Our results provide evidence to justify additional studies to clarify the type of fractures amenable to TS.
To Run or Not to Run? Automatic Evaluations and Reflective Attitudes Toward Exercise
Authors: Limmeroth Julia , Hagemann Norbert 
Published: September 2020

Using an evaluative priming procedure, this study tested whether automatic evaluations of running differ among groups based on their amount of exercise and whether they were runners or not. Ninety-five participants (26 ± 5.06 years; 46% female) were divided into five groups: an inactive group, active exercisers, highly active exercisers, active runners, and highly active runners. A priming effect score was calculated based on the concept of response facilitation or inhibition: the reaction is faster when the target and prime are valence congruent and becomes slower if they are incongruent. The highly active runner group differed significantly from the inactive group (p < .01) and from the active exerciser group (p < .05). Furthermore, reflective evaluations were measured via questionnaires. The results show that priming effect scores can detect automatic evaluations of running, and they differ not only because of the amounts of physical exercise but also because of their preferred type of exercise.
Oral administration of NPC43 counters hyperglycemia and activates insulin receptor in streptozotocin-induced type 1 diabetic mice
Authors: Lan Zi-Jian , Lei Zhenmin , Nation Lucinda , Li Xian , Yiannikouris Alexandros , Yerramreddy Thirupathi Reddy , Kincaid Hayley , Eastridge Katie , Xiao Rijin , Goettl Ryan , Power Ronan 
Published: September 2020

IntroductionAdenosine, 5’-Se-methyl-5’-seleno-,2’,3’-diacetate (NPC43) is a recently identified small, non-peptidyl molecule which restores normal insulin signaling in a mouse model of type 2 diabetes (Lanet al). The present study investigated the ability of NPC43 as an oral and injectable insulin-replacing agent to activate insulin receptor (INSR) and counter hyperglycemia in streptozotocin (STZ)-induced type 1 diabetic (T1D) mice.Research design and methodsIn this study, STZ was intraperitoneally injected into wild-type mice to induce hyperglycemia and hypoinsulinemia, the main features of T1D. These STZ-induced T1D mice were given NPC43 orally or intraperitoneally and blood glucose levels were measured using a glucometer. Protein levels of phosphorylated and total Insrβ, protein kinase B (Akt) and AS160 (critical for glucose uptake) in the skeletal muscle and liver of STZ-induced T1D mice following oral NPC43 treatment were determined by western blot analysis. In addition, hepatic expression of activated Insr in STZ-induced T1D mice after intraperitoneal NPC43 treatment was measured by ELISA. Student’s t-test was used for statistical analysis.ResultsOral administration of NPC43 at a dose of 5.4 or 10.8 mg/kg body weight (mpk) effectively lowered blood glucose levels in STZ-induced T1D mice at ≥1 hour post-treatment and the glucose-lowering activity of oral NPC43 persisted for 5 hours. Blood glucose levels were also reduced in STZ-induced T1D mice following intraperitoneal NPC43 (5.4 mpk) treatment. Protein levels of phosphorylated Insrβ, Akt and AS160 were significantly increased in the skeletal muscle and liver of STZ-induced T1D mice after oral NPC43 (5.4 mpk) treatment. In addition, activation of hepatic Insr was observed in STZ-induced T1D mice following intraperitoneal NPC43 (5.4 mpk) treatment.ConclusionsWe conclude that NPC43 is a de facto fast-acting oral and injectable insulin mimetic which activates Insr and mitigates hyperglycemia in a mouse model of T1D.
Recurrence rates suggest delayed identification of plantar ulceration for patients in diabetic foot remission
Authors: Petersen Brian J , Bus Sicco A , Rothenberg Gary M , Linders David R , Lavery Lawrence A , Armstrong David G 
Published: September 2020

IntroductionFoot ulcers are a common and costly complication of diabetes, and delays in treatment can result in impaired healing, infection, hospitalization, and lower extremity amputation.Research design and methodsWe aimed to determine whether patterns in plantar diabetic foot ulcer (DFU) recurrence coincided with typical intervals between routine preventive care appointments, which would suggest that delays exist between ulcer development and identification. We completed an analysis of existing data from two multicenter studies in 300 total participants. We analyzed unadjusted counts of DFU binned in weekly intervals and defined ‘exam periods’ as intervals from 2 to 4 weeks, from 6 to 8 weeks, within 1 week of 3 months and within 1 week of 6 months. We tested whether recurrence rates during exam periods were equivalent to rates outside exam periods. We estimated the delay between DFU development and DFU identification such that the rate of development would have been constant.ResultsDuring exam periods, a total of 43 DFUs were identified (43/86=50%) despite the fact that these periods represent only 23.5% of follow-up in aggregate. Accounting for censoring, the annualized incidence during exam periods was 0.68 DFU/year (CI 0.48 to 0.89) in contrast to 0.25 DFU/year (CI 0.18 to 0.32) outside exam periods (incidence ratio=2.8, CI 1.8 to 4.3). We estimated delays between DFU occurrence and identification to average 15.3 days (IQR 7.4–23.7 days).ConclusionsThese findings have potential implications for practice, particularly related to the value of telehealth and in-home monitoring of patients in diabetic foot remission. Additionally, there are implications for study design, which should consider the impact of interval censoring and attempt to control for confounders related to frequency and timing of exams.
High prevalence of exercise-induced stridor during Parkrun: a cross-sectional field-based evaluation
Authors: Sails Joe , Hull James H , Allen Hayden , Darville Liam , Walsted Emil S , Price Oliver J 
Published: September 2020

Background and objectiveThe differential diagnosis for exercise-associated breathlessness is broad, however, when a young athletic individual presents with respiratory symptoms, they are most often prescribed inhaler therapy for presumed exercise-induced asthma (EIA). The purpose of this study was therefore to use a novel sound-based approach to assessment to evaluate the prevalence of exertional respiratory symptoms and characterise abnormal breathing sounds in a large cohort of recreationally active individuals.MethodsCross-sectional field-based evaluation of individuals completing Parkrun.Phase 1Prerace, clinical assessment and baseline spirometry were conducted. At peak exercise and immediately postrace, breathing was monitored continuously using a smartphone. Recordings were analysed retrospectively and coded for signs of the predominant respiratory noise.Phase 2A subpopulation that reported symptoms with at least one audible sign of respiratory dysfunction was randomly selected and invited to attend the laboratory on a separate occasion to undergo objective clinical workup to confirm or refute EIA.ResultsForty-eight participants (22.6%) had at least one audible sign of respiratory dysfunction; inspiratory stridor (9.9%), expiratory wheeze (3.3%), combined stridor+wheeze (3.3%), cough (6.1%). Over one-third of the cohort (38.2%) were classified as symptomatic. Ten individuals attended a follow-up appointment, however, only one had objective evidence of EIA.ConclusionsThe most common audible sign, detected in approximately 1 in 10 individuals, was inspiratory stridor, a characteristic feature of upper airway closure occurring during exercise. Further work is now required to further validate the precision and feasibility of this diagnostic approach in cohorts reporting exertional breathing difficulty.
Exploring prognostic indicators in the pathological images of hepatocellular carcinoma based on deep learning
Authors: Shi Jie-Yi , Wang Xiaodong , Ding Guang-Yu , Dong Zhou , Han Jing , Guan Zehui , Ma Li-Jie , Zheng Yuxuan , Zhang Lei , Yu Guan-Zhen , Wang Xiao-Ying , Ding Zhen-Bin , Ke Ai-Wu , Yang Haoqing , Wang Liming , Ai Lirong , Cao Ya , Zhou Jian , Fan Jia , Liu Xiyang , Gao Qiang 
Published: September 2020

ObjectiveTumour pathology contains rich information, including tissue structure and cell morphology, that reflects disease progression and patient survival. However, phenotypic information is subtle and complex, making the discovery of prognostic indicators from pathological images challenging.DesignAn interpretable, weakly supervised deep learning framework incorporating prior knowledge was proposed to analyse hepatocellular carcinoma (HCC) and explore new prognostic phenotypes on pathological whole-slide images (WSIs) from the Zhongshan cohort of 1125 HCC patients (2451 WSIs) and TCGA cohort of 320 HCC patients (320 WSIs). A ‘tumour risk score (TRS)’ was established to evaluate patient outcomes, and then risk activation mapping (RAM) was applied to visualise the pathological phenotypes of TRS. The multi-omics data of The Cancer Genome Atlas(TCGA) HCC were used to assess the potential pathogenesis underlying TRS.ResultsSurvival analysis revealed that TRS was an independent prognosticator in both the Zhongshan cohort (p<0.0001) and TCGA cohort (p=0.0003). Thepredictive abilityof TRS was superior to and independent of clinical staging systems, and TRS could evenly stratify patients into up to five groups with significantly different prognoses. Notably, sinusoidal capillarisation, prominent nucleoli and karyotheca, the nucleus/cytoplasm ratio and infiltrating inflammatory cells were identified as the main underlying features of TRS. The multi-omics data of TCGA HCC hint at the relevance of TRS to tumour immune infiltration and genetic alterations such as theFAT3andRYR2mutations.ConclusionOur deep learning framework is an effective and labour-saving method for decoding pathological images, providing a valuable means for HCC risk stratification and precise patient treatment.
TP53, a gene for colorectal cancer predisposition in the absence of Li-Fraumeni-associated phenotypes
Authors: Terradas Mariona , Mur Pilar , Belhadj Sami , Woodward Emma R , Burghel George J , Munoz-Torres Pau M , Quintana Isabel , Navarro Matilde , Brunet Joan , Lazaro Conxi , Pineda Marta , Moreno Victor , Capella Gabriel , Evans D Gareth R , Valle Laura 
Published: September 2020

ObjectiveGermlineTP53pathogenic (P) variants cause Li-Fraumeni syndrome (LFS), an aggressive multitumor-predisposing condition. Due to the implementation of multigene panel testing,TP53variants have been detected in individuals without LFS suspicion, for example, patients with colorectal cancer (CRC). We aimed to decipher whether these findings are the result of detecting the background population prevalence or the aetiological basis of CRC.DesignWe analysedTP53in 473 familial/early-onset CRC cases and evaluated the results together with five additional studies performed in patients with CRC (total n=6200). Control population and LFS data were obtained from Genome Aggregation Database (gnomAD V.2.1.1) and the International Agency for Research on Cancer (IARC)TP53database, respectively. All variants were reclassified according to the guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP), following the ClinGenTP53Expert Panel specifications.ResultsP or likely pathogenic (LP) variants were identified in 0.05% of controls (n=27/59 095) and 0.26% of patients with CRC (n=16/6200) (p<0.0001) (OR=5.7, 95% CI 2.8 to 10.9), none of whom fulfilled the clinical criteria established forTP53testing. This association was still detected when patients with CRC diagnosed at more advanced ages (>50 and>60 years) were excluded from the analysis to minimise the inclusion of variants caused by clonal haematopoiesis. Loss-of-function and missense variants were strongly associated with CRC as compared with controls (OR=25.44, 95% CI 6.10 to 149.03, for loss of function and splice-site alleles, and OR=3.58, 95% CI 1.46 to 7.98, for missense P or LP variants).ConclusionTP53P variants should not be unequivocally associated with LFS. Prospective follow-up of carriers of germlineTP53P variants in the absence of LFS phenotypes will define how surveillance and clinical management of these individuals should be performed.
Interaction of bacterial metagenome and virome in patients with cirrhosis and hepatic encephalopathy
Authors: Bajaj Jasmohan S , Sikaroodi Masoumeh , Shamsaddini Amirhossein , Henseler Zachariah , Santiago-Rodriguez Tasha , Acharya Chathur , Fagan Andrew , Hylemon Phillip B , Fuchs Michael , Gavis Edith , Ward Tonya , Knights Dan , Gillevet Patrick M 
Published: September 2020

ObjectiveAltered bacterial composition is associated with disease progression in cirrhosis but the role of virome, especially phages, is unclear.DesignCross-sectional and pre/post rifaximin cohorts were enrolled. Cross-sectional: controls and cirrhotic outpatients (compensated, on lactulose (Cirr-L), on rifaximin (Cirr-LR)) were included and followed for 90-day hospitalisations. Pre/post: compensated cirrhotics underwent stool collection pre/post 8 weeks of rifaximin. Stool metagenomics for bacteria and phages and their correlation networks were analysed in controls versus cirrhosis, within cirrhotics, hospitalised/not and pre/post rifaximin.ResultsCross-sectional: 40 controls and 163 cirrhotics (63 compensated, 43 Cirr-L, 57 Cirr-LR) were enrolled. Cirr-L/LR groups were similar on model for end-stage liver disease (MELD) score but Cirr-L developed greater hospitalisations versus Cirr-LR (56% vs 30%, p=0.008). Bacterial alpha/beta diversity worsened from controls through Cirr-LR. While phage alpha diversity was similar, beta diversity was different between groups. Autochthonous bacteria linked negatively, pathobionts linked positively with MELD but only modest phage-MELD correlations were seen. Phage–bacterial correlation network complexity was highest in controls, lowest in Cirr-L and increased in Cirr-LR.MicroviridaeandFaecalibacteriumphages were linked with autochthonous bacteria in Cirr-LR, but not Cirr-L hospitalised patients had greater pathobionts, lower commensal bacteria and phages focused onStreptococcus, Lactococcusand Myoviridae. Pre/post: No changes in alpha/beta diversity of phages or bacteria were seen postrifaximin. Phage–bacterial linkages centred around urease-producingStreptococcusspecies collapsed postrifaximin.ConclusionUnlike bacteria, faecal phages are sparsely linked with cirrhosis characteristics and 90-day outcomes. Phage and bacterial linkages centred on urease-producing, ammonia-generatingStreptococcusspecies were affected by disease progression and rifaximin therapy and were altered in patients who experienced 90-day hospitalisations.
Progress on 3+1D Glasma simulations
Authors: Ipp Andreas , Müller David I. 
Published: September 2020

AbstractWe review our progress on 3+1D Glasma simulations to describe the earliest stages of heavy-ion collisions. In our simulations we include nuclei with finite longitudinal extent and describe the collision process as well as the evolution of the strongly interacting gluonic fields in the laboratory frame in 3+1 dimensions using the colored particle-in-cell method. This allows us to compute the 3+1 dimensional Glasma energy-momentum tensor, whose rapidity dependence can be compared to experimental pion multiplicity data from RHIC. An improved scheme cures the numerical Cherenkov instability and paves the way for simulations at higher energies used at LHC.
The influence of low-intensity resistance training combined with neuromuscular electrical stimulation on autonomic activity in healthy adults: A randomized controlled cross-over trial
Authors: Kutsuna Toshiki , Sugawara Hitoshi , Kurita Hideaki , Kusaka Satomi , Takahashi Tetsuya 
Published: September 2020

Background: Low-intensity resistance training (RT) combined with neuromuscular electrical stimulation (NMES) is one method of exercise to improve the deterioration of physical function. However, it is unclear whether low-intensity RT combined with NMES (RT + NMES) can be safely implemented.Objective: This study aimed to examine the influence of low-intensity RT + NMES on autonomic activity and cardiovascular responses in healthy adults.Methods: This study was an open-label, randomized controlled cross-over trial. The exercise intensity of isometric knee extension RT was set to 40% of the maximum voluntary contraction (peak torque). NMES was adjusted to a biphasic asymmetrical waveform with the frequency maintained at 50 Hz and a phase duration of 300 [Formula: see text]s. The difference in the change in autonomic activity and cardiovascular responses was compared by assessing heart rate variability, blood pressure, and heart rate during RT and [Formula: see text].Results: Twenty healthy male college students (mean age [Formula: see text] years) participated in this study. The ratio of low- and high-frequency components of heart rate variability, systolic blood pressure, and heart rate increased during exercise in the RT and [Formula: see text] sessions ([Formula: see text]). There were no significant differences in autonomic activity and cardiovascular responses throughout the sessions during RT and [Formula: see text].Conclusion: In conclusion, our results demonstrated that low-intensity [Formula: see text] was safe and did not induce excessive autonomic and cardiovascular responses in healthy adults.
The clinical application of a traditional Chinese medicine prescription issued by Professor Liangduo Jiang in the prevention of coronavirus disease 2019 (COVID-19)
Authors: Yao Jinfang , Yang Jian , Yu Zhenping , Chui Jinwei , Lee Simin , Zhang Xiaomei , Jiang Liangduo 
Published: September 2020

Objective: To summarize the clinical experience of Professor Liangduo Jiang in the prevention and control of the new coronavirus disease COVID-19. Methods: Between January 2020 and February 2020, 87 subjects who have had contact with patients tested positive for COVID-19 in an isolated observation site in Tianjin were given the Chinese medicine prescription for prevention prescribed by Professor Liangduo Jiang continuously for three days. Their basic information, clinical manifestations and medication adherence were statistically analyzed, and the clinical manifestations, temperature changes and infection status after medication were summarized. Results: After the 14-day isolation observation period, only one patient who had close contact with confirmed patients developed a positive test for COVID-19 after taking the preventive Chinese medicine prescription, with the infection rate of 1.149%. Conclusion: The preventive treatment by Professor Liangduo Jiang is effective in the prevention and control of the epidemic.