bluuebunny/crossref_metadata_2025_split huggingface dataset:
Species variation in the hydrogen isotope composition of leaf cellulose is mostly driven by isotopic variation in leaf sucrose
Authors: Holloway‐Phillips Meisha , Baan Jochem , Nelson Daniel B. , Lehmann Marco M. , Tcherkez Guillaume , Kahmen Ansgar 
Published: May 2022

AbstractExperimental approaches to isolate drivers of variation in the carbon‐bound hydrogen isotope composition (δ2H) of plant cellulose are rare and current models are limited in their application. This is in part due to a lack in understanding of how 2H‐fractionations in carbohydrates differ between species. We analysed, for the first time, the δ2H of leaf sucrose along with the δ2H and δ18O of leaf cellulose and leaf and xylem water across seven herbaceous species and a starchless mutant of tobacco. The δ2H of sucrose explained 66% of the δ2H variation in cellulose (R2 = 0.66), which was associated with species differences in the 2H enrichment of sucrose above leaf water (: −126% to −192‰) rather than by variation in leaf water δ2H itself. was positively related to dark respiration (R2 = 0.27), and isotopic exchange of hydrogen in sugars was positively related to the turnover time of carbohydrates (R2 = 0.38), but only when was fixed to the literature accepted value of ‰. No relation was found between isotopic exchange of hydrogen and oxygen, suggesting large differences in the processes shaping post‐photosynthetic fractionation between elements. Our results strongly advocate that for robust applications of the leaf cellulose hydrogen isotope model, parameterization utilizing δ2H of sugars is needed.
VAR2/AtFtsH2 and EVR2/BCM1/CBD1 synergistically regulate the accumulation of PSII reaction centre D1 protein during de‐etiolation in Arabidopsis
Authors: Wang Xiaomin , Li Qinglong , Zhang Yalin , Pan Mi , Wang Ruijuan , Sun Yifan , An Lijun , Liu Xiayan , Yu Fei , Qi Yafei 
Published: May 2022

AbstractThylakoid FtsH complex participates in PSII repair cycle during high light‐induced photoinhibition. The Arabidopsis yellow variegated2 (var2) mutants are defective in the VAR2/AtFtsH2 subunit of thylakoid FtsH complex. Taking advantage of the var2 leaf variegation phenotype, dissections of genetic enhancer loci have yielded novel paradigms in understanding functions of thylakoid FtsH complex. Here, we report the isolation of a new var2 enhancer, enhancer of variegation2‐1 (evr2‐1). We confirmed that EVR2 encodes a chloroplast protein that was known as BALANCE OF CHLOROPHYLL METABOLISM 1 (BCM1), or CHLOROPHYLL BIOSYNTHETIC DEFECT 1 (CBD1). We showed that EVR2/BCM1/CBD1 was involved in the oligomerization of photosystem I complexes. Genetic assays indicated that general defects in chlorophyll biosynthesis and the accumulation of photosynthetic complexes do not necessarily enhance var2 leaf variegation. In addition, we found that VAR2/AtFtsH2 is required for the accumulation of photosynthetic proteins during de‐etiolation. Moreover, we identified PSII core proteins D1 and PsbC as potential EVR2‐associated proteins using Co‐IP/MS. Furthermore, the accumulation of D1 protein was greatly compromised in the var2‐5 evr2‐1 double mutant during de‐etiolation. Together, our findings reveal a functional link between VAR2/AtFtsH2 and EVR2/BCM1/CBD1 in regulating chloroplast development and the accumulation of PSII reaction centre D1 protein during de‐etiolation.
Why ‘Is’ Must Entail ‘Ought’
Authors: Lyon Ardon 
Published: May 2022

AbstractI argue below for the view that non‐moral truths entail moral ones. I first argue that moral claims do have truth values which are objectively true or false. I then argue that this objectivism does not entail non‐relativism. I produce a simple possible worlds argument for the entailment view. I then give some examples where p entails q but many intelligent people have thought it does not, and where it does not, but many intelligent people have thought that it does. I also try to evaluate a somewhat neglected argument by Hume. In the final section, I further consider some moral and meta‐moral opinions.
Expression of ERβ induces bovine ovarian granulosa cell autophagy via the AKT/mTOR pathway
Authors: Liu Guangyu , Zheng Yuxin , Gao Huimin , Cui Wenfei , Zhao Fan , Liu Ning , Tang Xiaorong , Jiang Zhongliang 
Published: May 2022

AbstractThe aim of our study was to determine whether silencing or overexpression of estrogen receptor β (ERβ) regulates cell proliferation, steroidogenesis, autophagy and signalling pathways in bovine ovarian granulosa cells in vitro. In this study, bovine ovarian granulosa cells (BGCs) were cultured and transfected with ERβ siRNA (si‐ERβ) or a plasmid overexpressing ERβ (oe‐ERβ), and CCK‐8 kit was used to assess cell proliferation. Real‐time PCR was used to measure gene transcription. Western blotting was used to measure protein expression, and a specific kit was used to measure the production of steroid hormones. The results showed the expression level of ERβ affects BGC proliferation according to the gene transcription levels of FSHR, CYP19A1, HSD3β1 and STAR and the production of E2 and P4. ERβ was identified as an important nuclear receptor that induced BGC autophagy based on the mRNA and protein expression of autophagy‐related genes. Furthermore, the role of ERβ in BGC autophagy was confirmed through treatment with rapamycin (RAPA) or 3‐methyladenine (3‐MA) in BGCs by cotransfection with si‐ERβ or oe‐ERβ in BGCs. The results related to AKT/mTOR signalling and phosphorylation suggested that ERβ induces BGC autophagy through attenuating AKT/mTOR signalling. In summary, this study demonstrates that silencing or overexpression of ERβ regulates BGC proliferation and function and induces BGC autophagy by targeting AKT/mTOR signalling. These data reveal a novel regulatory mechanism of autophagy via ERβ and provide insights into the role of autophagy in BGCs.
Hamstring muscle activation strategies during eccentric contractions are related to the distribution of muscle damage
Authors: Goreau Valentin , Pigne Robin , Bernier Nathan , Nordez Antoine , Hug François , Lacourpaille Lilian 
Published: May 2022

Large inter‐individual variability of activation strategies is observed during hamstring strengthening exercises but their consequences remain unexplored. The objective of this study was to determine whether individual activation strategies are related to the distribution of damage across the hamstring muscle heads semimembranosus (SM), semitendinosus (ST), and biceps femoris (BF) after eccentric contractions. 24 participants performed 5 sets of 15 maximal eccentric contractions of knee flexors on a dynamometer, while activation of each muscle head was assessed using surface electromyography. Knee flexion maximal isometric strength was assessed before exercise and 48 h afterward. Shear modulus was measured using shear wave elastography before exercise and 30 min afterward to quantify the distribution of damage across the hamstring muscle heads. At 48 h, maximal knee flexion torque had decreased by 15.9% ± 16.9% (p < 0.001). Although no differences between activation ratios of each muscle were found during the eccentric exercise (all p > 0.364), we reported a heterogeneous distribution of damage, with a larger change in shear modulus of ST/Hams than SM/Hams (+70.8%, p < 0.001) or BF/Hams (+50.3%, p < 0.001). A large correlation was found between the distribution of activation and the distribution of damage for ST/Hams (r = 0.69; p < 001). This study provides evidence that the distribution of activation during maximal eccentric contractions has mechanical consequences for synergist muscles. Further studies are needed to understand whether individual activation strategies influence the distribution of structural adaptations after a training program.
FLCSS: A fuzzy‐based longest common subsequence method for uncertainty management in trajectory similarity measures
Authors: Boroumand Faraz , Alesheikh Ali Asghar , Sharif Mohammad , Farnaghi Mahdi 
Published: May 2022

AbstractThe large quantity of movement data collected from various sources can be inherently uncertain and heterogeneous. In the movement data analysis and mining spectrum, computing the similarity of trajectories while considering the uncertainty and heterogeneity has been less addressed. Generally, two factors of sampling and positioning error cause uncertainty in trajectory databases. Therefore, in this research, a method based on the longest common subsequence (LCSS), named FLCSS, is proposed that uses fuzzy theory and the bead model to consider the uncertainty of trajectories originated from positioning and sampling errors. The performance of FLCSS is evaluated by implementations on real and synthetic datasets, and compared with six important and commonly used similarity measurement methods, namely, LCSS, edit distance on real sequence (EDR), dynamic time warping (DTW), edit distance with real penalty (ERP), Hausdorff distance (HD), and Fréchet distance (FD). The results show that FLCSS has a better performance compared to other methods, in terms of sensitivity to point displacement, noise, and different sampling rates. Furthermore, the high correlation between FLCSS and LCSS (ρ = 0.91) confirms the robustness of the proposed method in considering uncertainty in the trajectory databases.
A physiology‐based trigger score to guide perioperative transfusion of allogeneic red blood cells: A multicentre randomised controlled trial
Authors: Lu Kejian , Huang Zehan , Liang Shucong , Pan Fengting , Zhang Chunying , Wei Jingqing , Wei Huijun , Wang Yafeng , Liao Ren , Huang Ailan , Huang Yanjuan 
Published: May 2022

AbstractBackgroundRestrictive blood transfusion is recommended by major guidelines for perioperative management, but requires objective assessment at 7–10 g/dl haemoglobin (Hb). A scoring system that considers the physiological needs of the heart may simply the practice and reduce transfusion.MethodsPatients (14–65 years of age) undergoing non‐cardiac surgery were randomised at a 1:1 ratio to a control group versus a Perioperative Transfusion Trigger Score (POTTS) group. POTTS (maximum of 10) was calculated as 6 plus the following: adrenaline infusion rate (0 for no infusion, 1 for ≤0.05 μg·kg−1·min−1, and 2 for higher rate), FiO2 to keep SpO2 at ≥95% (0 for ≤35%, 1 for 36%–50%, and 2 for higher), core temperature (0 for <38°C, 1 for 38–40°C, and 2 for higher), and angina history (0 for no, 1 for exertional, and 2 for resting). Transfusion is indicated when actual Hb is lower than the calculated POTTS in individual patients. Transfusion in the control group was based on the 2012 American Association for Blood Banks (AABB) guideline. The primary outcome was the proportion of the patients requiring transfusion of allogeneic red blood cells (RBCs) during the perioperative period (until discharge from hospital), as assessed in the intention‐to‐treat (ITT) population (all randomised subjects).ResultA total of 864 patients (mean age 44.4 years, 244 men and 620 women) were enrolled from December 2017 to January 2021 (433 in the control and 431 in the POTTS group). Baseline Hb was 9.2 ± 1.8 and 9.2 ± 1.7 g/dl in the control and POTTS groups, respectively. In the ITT analysis, the proportion of the patients receiving allogeneic RBCs was 43.9% (190/433) in the control group versus 36.9% (159/431) in the POTTS group (p = 0.036). Lower rate of allogeneic RBCs transfusion in the POTTS group was also evident in the per‐protocol analysis (42.8% vs. 35.5%, p = 0.030). Transfusion volume was 4.0 (2.0, 6.0) and 3.5 (2.0, 5.5) units (200 ml/unit) in the control and POTTS groups, respectively (p = 0.25). The rate of severe postoperative complications (Clavien‐Dindo grade IIIa and higher) was 3.9% in the control group versus 1.2% in the POTTS group (p = 0.010).ConclusionTransfusion of allogeneic RBCs based on the POTTS was safe and reduced the transfusion requirement in patients undergoing non‐cardiac surgery.
Incisor enamel microstructure places New and Old World Eomyidae outside Geomorpha (Rodentia, Mammalia)
Authors: Kalthoff Daniela C. , Fejfar Oldrich , Kimura Yuri , Bailey Bruce E. , Mörs Thomas 
Published: May 2022

AbstractThe lower incisor enamel microstructure of the fossil rodent family Eomyidae was believed to be three‐layered and highly derived but rather uniform throughout the clade. Here, we describe a new four‐layered schmelzmuster in Eomyidae consisting of a three‐fold portio interna with longitudinal oriented, uniserial Hunter‐Schreger bands and a one‐fold portio externa, accounting for a unique enamel microstructure character combination in Rodentia. This new schmelzmuster type has developed early in eomyid evolution and is detectable already in the late Eocene (Chadronian) of North America. In European eomyids, it first occurs in the early Miocene (MN 3), implying that this four‐layered schmelzmuster was not present in all members of the family but restricted to species included in Eomyini and some genera currently considered Eomyidae incertae sedis within Eomyidae. Additionally, our analysis recognizes three taxa with schmelzmuster divergent from all other eomyids. Incisor enamel microstructure does not advocate a close phylogenetic relationship of Eomyidae to either fossil or extant Heteromyidae and Geomyidae, nor to fossil Heliscomyidae and Florentiamyidae. Our results rather support the view that Eomyidae are placed outside Geomorpha.
Design a Multifunctional Soft Tactile Sensor Enhanced by Machine Learning Approaches
Authors: Yang Wu-Te , Tomizuka Masayoshi 
Published: May 2022

Abstract
Tactile sensors are essential to robot hands that deal with various objects and interact with the environment. Soft tactile sensors are especially important to capture tactile information about delicate, irregular-shaped, or unknown objects. This paper introduces a soft tactile sensor that can simultaneously estimate the contact force, contact feature, and contact point. Inspired by multifunctional human skin, the proposed design has a dual-layer structure and is multifunctional. The top layer consists of a group of sensing elements that detect the contact location and contact feature enhanced by the bagging classifier based on the k-nearest neighbors. The sensor elements were biomimetically and analytically designed as a pyramid shape that mimicked the mountain ridge-like structure in human skin to improve sensitivity. The bottom layer was made by a piece of Velostat sandwiched between conductive fabrics that can measure the contact force. The relationship between the sensing voltage and the contact force was modeled by the Nadaraya–Watson regressor. The performance of the proposed sensor was verified by a repeatability test. Furthermore, we demonstrated the effectiveness of the proposed sensor on a robotic gripper. The experimental results show that this sensor is able to detect contact information of fragile objects.
Mathematical modelling of the most effective goal of cholesterol-lowering treatment in primary prevention
Authors: Soran Handrean , Adam Safwaan , Iqbal Zohaib , Durrington Paul 
Published: May 2022

ObjectiveTo compare quantitatively different recommended goals for cholesterol-lowering treatment in the primary prevention of atherosclerotic cardiovascular disease (ASCVD).DesignOutcomes at pretreatment low-density lipoprotein (LDL) cholesterol concentrations from 2 to 5 mmol/L and 10-year ASCVD risk from 5% to 30% were modelled, using the decrease in risk ratio per mmol/L reduction in LDL cholesterol derived from randomised controlled trials (RCTs) of cholesterol-lowering medication.Data sourceSummary statistics from 26 RCTs comparing treatment versus placebo or less versus more effective treatment and 12 RCTs in which statin was compared with a higher dose of the same statin or with a similar statin dose to which an adjunctive cholesterol-lowering drug was added.SettingThe different recommended goals are: (1) LDL cholesterol≤2.6 mmol/L (100 mg/dL); (2) LDL cholesterol≤1.8 mmol/L (70 mg/dL); (3) non-high density lipoprotein (HDL) cholesterol decrease of ≥40%; or (4) LDL cholesterol≤1.8 mmol/L (70 mg/dL) or decreased by ≥50% whichever is lower.ParticipantsRCT participants.InterventionsStatins alone or in combination with ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors.Main outcome measuresFor each of the recommended therapeutic goals, our primary outcome was the number of events prevented per 100 people treated for 10 years (N100) and the number of needed to treat (NNT) to prevent one event over 10 years.ResultsAt pretreatment LDL cholesterol 4–5 mmol/L, all four goals provided similar benefit with N100 1.47–16.45 (NNT 6–68), depending on ASCVD risk and pretreatment LDL cholesterol. With initial LDL cholesterol in the range 2–3 mmol/L, the target of 2.6 mmol/L was the least effective with N100 between 0 and 2.84 (NNT 35–infinity). The goal of 1.8 mmol/L was little better. However, reductions in non-HDL cholesterol by ≥40% or of LDL cholesterol to 1.8 mmol/L and/or by 50%, whichever is lower, were more effective, delivering N100 of between 0.9 and 9.33 (NNT 11–111). Percentage decreases in LDL cholesterol or non-HDL cholesterol concentration are more effective targets than absolute change in concentration in people with initial values of <4 mmol/L.ConclusionsThe LDL cholesterol target of 1.8 mmol/L is most effective when initial LDL cholesterol is >4 mmol/L. The time has probably come for the LDL cholesterol goal of <2.6 mmol/L to be abandoned.
Phase 2a randomised controlled feasibility trial of a new ‘balanced binocular viewing’ treatment for unilateral amblyopia in children age 3–8 years: trial protocol
Authors: Dahlmann-Noor Annegret Hella , Greenwood John A , Skilton Andrew , Baker Daniel , Ludden Siobhan , Davis Amanda , Dehbi Hakim-Moulay , Dakin Steven C 
Published: May 2022

IntroductionTreatments for amblyopia, the most common vision deficit in children, often have suboptimal results. Occlusion/atropine blurring are fraught with poor adherence, regression and recurrence. These interventions target only the amblyopic eye, failing to address imbalances of cortical input from the two eyes (‘suppression’). Dichoptic treatments manipulate binocular visual experience to rebalance input. Poor adherence in early trials of dichoptic therapies inspired our development of balanced binocular viewing (BBV), using movies as child-friendly viewable content. Small observational studies indicate good adherence and efficacy. A feasibility trial is needed to further test safety and gather information to design a full trial.Methods/analysisWe will carry out an observer-masked parallel-group phase 2a feasibility randomised controlled trial at two sites, randomising 44 children aged 3–8 years with unilateral amblyopia to either BBV or standard occlusion/atropine blurring, with 1:1 allocation ratio. We will assess visual function at baseline, 8 and 16 weeks. The primary outcome is intervention safety at 16 weeks, measured as change in interocular suppression, considered to precede the onset of potential diplopia. Secondary outcomes include safety at other time points, eligibility, recruitment/retention rates, adherence, clinical outcomes. We will summarise baseline characteristics for each group and assess the treatment effect using analysis of covariance. We will compare continuous clinical secondary endpoints between arms using linear mixed effect models, and report feasibility endpoints using descriptive statistics.Ethics/disseminationThis trial has been approved by the London-Brighton & Sussex Research Ethics Committee (18/LO/1204), National Health Service Health Research Authority and Medicines and Healthcare products Regulatory Agency. A lay advisory group will be involved with advising on and disseminating the results to non-professional audiences, including on websites of funder/participating institutions and inputting on healthcare professional audience children would like us to reach. Reporting to clinicians and scientists will be via internal and external meetings/conferences and peer-reviewed journals.Trial registration numberNCT03754153.
Reporting quality of clinical trial protocols: a repeated cross-sectional study about the Adherence to SPIrit Recommendations in Switzerland, CAnada and GErmany (ASPIRE-SCAGE)
Authors: Gryaznov Dmitry , von Niederhäusern Belinda , Speich Benjamin , Kasenda Benjamin , Ojeda-Ruiz Elena , Blümle Anette , Schandelmaier Stefan , Mertz Dominik , Odutayo Ayodele , Tomonaga Yuki , Amstutz Alain , Pauli-Magnus Christiane , Gloy Viktoria , Lohner Szimonetta , Bischoff Karin , Wollmann Katharina , Rehner Laura , Meerpohl Joerg J , Nordmann Alain , Klatte Katharina , Ghosh Nilabh , Taji Heravi Ala , Wong Jacqueline , Chow Ngai , Hong Patrick , McCord - De Iaco Kimberly A , Sricharoenchai Sirintip , Busse Jason W , Agarwal Arnav , Saccilotto Ramon , Schwenkglenks Matthias , Moffa Giusi , Hemkens Lars , Hopewell Sally , Von Elm Erik , Briel Matthias 
Published: May 2022

ObjectivesComprehensive protocols are key for the planning and conduct of randomised clinical trials (RCTs). Evidence of low reporting quality of RCT protocols led to the publication of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist in 2013. We aimed to examine the quality of reporting of RCT protocols from three countries before and after the publication of the SPIRIT checklist.DesignRepeated cross sectional study.SettingSwiss, German and Canadian research ethics committees (RECs).ParticipantsRCT protocols approved by RECs in 2012 (n=257) and 2016 (n=292).Primary and secondary outcome measuresThe primary outcomes were the proportion of reported SPIRIT items per protocol and the proportion of trial protocols reporting individual SPIRIT items. We compared these outcomes in protocols approved in 2012 and 2016, and built regression models to explore factors associated with adherence to SPIRIT. For each protocol, we also extracted information on general trial characteristics and assessed whether individual SPIRIT items were reportedResultsThe median proportion of reported SPIRIT items among RCT protocols showed a non-significant increase from 72% (IQR, 63%–79%) in 2012 to 77% (IQR, 68%–82%) in 2016. However, in a preplanned subgroup analysis, we detected a significant improvement in investigator-sponsored protocols: the median proportion increased from 64% (IQR, 55%–72%) in 2012 to 76% (IQR, 64%–83%) in 2016, while for industry-sponsored protocols median adherence was 77% (IQR 72%–80%) for both years. The following trial characteristics were independently associated with lower adherence to SPIRIT: single-centre trial, no support from a clinical trials unit or contract research organisation, and investigator-sponsorship.ConclusionsIn 2012, industry-sponsored RCT protocols were reported more comprehensively than investigator-sponsored protocols. After publication of the SPIRIT checklist, investigator-sponsored protocols improved to the level of industry-sponsored protocols, which did not improve.