bluuebunny/crossref_metadata_2025 huggingface dataset:
ON SOME AMBIGUITIES IN IBN SĪNĀ’S ANALYSIS OF THE QUANTIFIED HYPOTHETICAL PROPOSITIONS
Authors: Chatti Saloua
Published: February 2022

In his analysis of the hypothetical (šarṭīyya) connected (muttaṣila) and disjunctive (munfaṣila) propositions (Al-qiyās, section V), Ibn Sīnā suggests that they can be quantified and presents in section VI a hypothetical system containing the conditional ones, which is exactly parallel to categorical syllogistic and makes use of the same conversion rules and the same proofs. In section VII, he provides four lists of hypothetical quantified propositions whose clauses are themselves quantified and says that the relations of the Aristotelian square of opposition hold for them. In addition, he says that some conditional universal affirmative propositions are equivalent to some universal negative ones with opposed consequents, and to some quantified disjunctive ones. The problem is that these claims are incompatible with each other, since they require two different readings of the universal affirmative conditional proposition, which Ibn Sīnā does not distinguish clearly. In this paper we solve the problem by distinguishing explicitly between these two readings and showing that the first one satisfies the conversion rule of the universal affirmative and the relations of the logical square, and validates all the admitted moods, while the second one satisfies the contraposition rule and the equivalences stated by Ibn Sīnā. This accounts for all Ibn Sīnā’s claims and makes the system coherent.
Inverting the Lens: White Privilege Denial in Evaluations of Politicians and Policy
Authors: Dobbs Reagan , Nicholson Stephen P.
Published: February 2022

Public understandings of race in the United States have evolved, at least among some, to acknowledge that whiteness confers privilege. In contrast to the negative racial stereotypes that animate racial resentment, white privilege inverts the lens by focusing on whites and the notion that whiteness confers unearned advantages. Given the centrality of race in American politics, we investigate white privilege denial and whether it matters politically. Our inquiry shows white privilege denial is a distinct racial construct and that nearly half of whites are at least somewhat in denial with nearly one-third rejecting all the white privilege items. We found that white privilege denial is politically consequential, helping explain white attitudes across a range of political attitudes including support for political leaders, parties, and public policy. To capture the range and complexity of racial attitudes among whites, we recommend that studies of racial attitudes in politics include white privilege denial.
Are Significant Tornadoes Occurring Later in the Year in Southern Ontario?
Authors: Sills D. M. L. , Durfy C. S. , de Souza C. P. E.
Published: February 2022

Using a long‐term data set (1875–2019), we investigate whether the month having peak tornado frequency changes over time in southern Ontario, Canada. Using only F/EF2+ tornadoes and 10‐year rolling periods having modes at 5‐year intervals, we find a statistically significant (99% confidence interval) moderate positive trend. However, we identify no statistically significant trend (positive or negative) using the same methods with tornado data from neighboring US states Michigan and New York. Though we do not investigate causes here, the study is the first to identify a robust long‐term trend in the frequency of significant tornadoes for any region of Canada. Such a shift also has implications for public safety, with the occurrence of such tornadoes later in the year having the potential for greater impacts.
Generation of Reflections and PKP Precursors From a Scattering Layer in D″
Authors: Hiemer Vanessa , Thomas Christine
Published: February 2022

The D″ region consists of many different structures on many length‐scales and here we test whether an inhomogeneous scattering region could potentially explain two of these seismic observables, namely PKP precursors, which are generated by scattering near the core‐mantle boundary, and reflections of a seismic discontinuity in the lowermost mantle. The focus of this study is on modeling PKP precursors and lower mantle reflections. Testing different heterogeneity models with a range of correlation lengths and velocity perturbations for D″, we find that some of our models can produce both waves. Comparing our synthetic seismograms to real data for precursors in adjacent locations beneath the mid‐Atlantic near South America we find the best fitting model with correlation length of 10 km and velocity perturbation of 5% with a gradual increase of scattering defined by a taper from 200 to 400 km above the core‐mantle boundary.
A Systematic Look at the Temperature Gradient Contribution to the Dayside Magnetopause Current
Authors: Beedle J. M. H. , Gershman D. J. , Uritsky V. M. , Phan T. D. , Giles B. L.
Published: February 2022

Magnetopause diamagnetic currents arise from density and temperature driven pressure gradients across the boundary layer. While theoretically recognized, the temperature contributions to the magnetopause current system have not yet been systematically studied. To bridge this gap, we used a database of Magnetospheric Multiscale magnetopause crossings to analyze diamagnetic current densities and their contributions across the dayside and flank magnetopause. Our results indicate that the ion temperature gradient component makes up to 37% of the ion diamagnetic current density along the magnetopause and typically opposes the classical Chapman‐Ferraro current direction, interfering destructively with the density gradient component, thus lowering the total diamagnetic current density. This effect is most pronounced on the flank magnetopause. The electron diamagnetic current was found to be 5–14 times weaker than the ion diamagnetic current on average.
Climate Rather Than Vegetation Changes Dominate Changes in Effective Vegetation Available Water Capacity
Authors: Liu Meixian , Zhang Baoqing , He Xiaogang
Published: February 2022

China has experienced significant vegetation greening over recent decades. Vegetation greening may regulate the effective vegetation available water capacity (EVAWC), which determines the root zone water availability for evapotranspiration. EVAWC is one of the most important factors controlling vegetation growth and ecosystem resilience. Despite its importance, quantifying EVAWC at large scale is challenging due to limited observations of soil properties and insufficient understanding of underlying physical processes. Thus, to what extent changes in EVAWC are driven by vegetation and climate change is still unclear. Here, we establish a physics‐based, data‐driven stochastic approach to examine the spatiotemporal variability of the EVAWC and its potential drivers over China, with the consideration of vegetation and climate dynamics. The major strength of our approach is that it does not require observations related to soil properties as inputs, but only needs a few simple hydrometeorological and remotely sensed vegetation parameters that can be easily obtained. On average, we find that vegetation changes tend to increase EVAWC over 71.0 ± 3.9% of the total land area in China, while climate variabilities tend to reduce EVAWC over 73.7 ± 9.5% of the land area. More importantly, the potential increase in EVAWC resulting from vegetation changes is offset by climate variability. As a result, the changes in EVAWC over recent decades are generally dominated by climate variabilities (relative contribution of 82.7 ± 9.6%) rather than vegetation changes, especially in humid and semihumid areas. Our results suggest that vegetation greening in China has subordinate impacts on EVAWC, and ecosystem resilience is mainly dominated by the local climate.
Randomised phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer
Authors: Roque Dana M. , Siegel Eric R. , Buza Natalia , Bellone Stefania , Silasi Dan-Arin , Huang Gloria S. , Andikyan Vaagn , Clark Mitchell , Azodi Masoud , Schwartz Peter E. , Rao Gautam G. , Reader Jocelyn C. , Hui Pei , Tymon-Rosario Joan R. , Harold Justin , Mauricio Dennis , Zeybek Burak , Menderes Gulden , Altwerger Gary , Ratner Elena , Santin Alessandro D.
Published: February 2022

Background

This multi-center RP2 study assessed activity/safety of ixabepilone + bevacizumab compared to ixabepilone in platinum-resistant/refractory ovarian/fallopian tube/primary peritoneal cancer. Additional objectives were to examine the role of prior bevacizumab and taxanes, and explore class III-ß-tubulin (TUBB3) as a predictive biomarker.

Methods

Participants were randomised to receive ixabepilone 20 mg/m2 days 1, 8, 15 with (IXA + BEV) or without (IXA) bevacizumab 10 mg/kg days 1, 15 every 28 days. Patients were stratified by prior BEV. The primary endpoint was PFS. OS, safety, and ORR served as secondary endpoints.

Results

Among 76 evaluable patients who received IXA + BEV (n = 39) compared to IXA (n = 37), the ORR was 33% (n = 13) versus 8% (n = 3)(P = 0.004), durable at 6 months in 37% (n = 14) and 3% (n = 1) (P < 0.001). BEV significantly improved PFS (median:5.5 vs 2.2 months, HR = 0.33, 95%CI 0.19–0.55, P < 0.001) and OS (median:10.0 vs 6.0 months, HR = 0.52, 95%CI 0.31–0.87, P = 0.006). Both regimens were well-tolerated. TUBB3 expression did not predict response. Subgroup analyses revealed minimal effect of prior BEV or taxane resistant/refractory status on response to IXA + BEV.

Conclusions

IXA + BEV is a well-tolerated, effective combination for platinum/taxane-resistant ovarian cancer that extends PFS and likely OS relative to IXA monotherapy. Prior receipt of BEV should not preclude the use of IXA + BEV. TUBB3 is not a predictive biomarker.

Clinical trial registration

NCT3093155.
Autolysosomes and caspase-3 control the biogenesis and release of immunogenic apoptotic exosomes
Authors: Beillevaire Déborah , Migneault Francis , Turgeon Julie , Gingras Diane , Rimbaud Annie Karakeussian , Marcoux Geneviève , Spino Crysta , Thibodeau Nicolas , Bonneil Eric , Thibault Pierre , Boilard Éric , Dieudé Mélanie , Hébert Marie-Josée
Published: February 2022

Apoptotic exosome-like vesicles (ApoExos) are a novel type of extracellular vesicle that contribute to the propagation of inflammation at sites of vascular injury when released by dying cells. ApoExos are characterized by the presence of the C-terminal perlecan LG3 fragment and 20S proteasome, and they are produced downstream of caspase-3 activation. In the present study, we assessed the relative roles of autophagy and caspase-3-mediated pathways in controlling the biogenesis and secretion of immunogenic ApoExos. Using electron microscopy and confocal immunofluorescence microscopy in serum-starved endothelial cells, we identified large autolysosomes resulting from the fusion of lysosomes, multivesicular bodies, and autophagosomes as a site of ApoExo biogenesis. Inhibition of autophagy with ATG7 siRNA or biochemical inhibitors (wortmannin and bafilomycin) coupled with proteomics analysis showed that autophagy regulated the processing of perlecan into LG3 and its loading onto ApoExos but was dispensable for ApoExo biogenesis. Caspase-3 activation was identified using caspase-3-deficient endothelial cells or caspase inhibitors as a pivotal regulator of fusion events between autolysosomes and the cell membrane, therefore regulating the release of immunogenic ApoExos. Collectively, these findings identified autolysosomes as a site of ApoExo biogenesis and caspase-3 as a crucial regulator of autolysosome cell membrane interactions involved in the secretion of immunogenic ApoExos.
Ultrafast charge transfer dynamics in 2D covalent organic frameworks/Re-complex hybrid photocatalyst
Authors: Pan Qinying , Abdellah Mohamed , Cao Yuehan , Lin Weihua , Liu Yang , Meng Jie , Zhou Quan , Zhao Qian , Yan Xiaomei , Li Zonglong , Cui Hao , Cao Huili , Fang Wenting , Tanner David Ackland , Abdel-Hafiez Mahmoud , Zhou Ying , Pullerits Tonu , Canton Sophie E. , Xu Hong , Zheng Kaibo
Published: February 2022

Rhenium(I)-carbonyl-diimine complexes have emerged as promising photocatalysts for carbon dioxide reduction with covalent organic frameworks recognized as perfect sensitizers and scaffold support. Such Re complexes/covalent organic frameworks hybrid catalysts have demonstrated high carbon dioxide reduction activities but with strong excitation energy-dependence. In this paper, we rationalize this behavior by the excitation energy-dependent pathways of internal photo-induced charge transfer studied via transient optical spectroscopies and time-dependent density-functional theory calculation. Under band-edge excitation, the excited electrons are quickly injected from covalent organic frameworks moiety into catalytic RheniumI center within picosecond but followed by fast backward geminate recombination. While under excitation with high-energy photon, the injected electrons are located at high-energy levels in RheniumI centers with longer lifetime. Besides those injected electrons to RheniumI center, there still remain some long-lived electrons in covalent organic frameworks moiety which is transferred back from RheniumI. This facilitates the two-electron reaction of carbon dioxide conversion to carbon monoxide.
Genomic variants affecting homoeologous gene expression dosage contribute to agronomic trait variation in allopolyploid wheat
Authors: He Fei , Wang Wei , Rutter William B. , Jordan Katherine W. , Ren Jie , Taagen Ellie , DeWitt Noah , Sehgal Deepmala , Sukumaran Sivakumar , Dreisigacker Susanne , Reynolds Matthew , Halder Jyotirmoy , Sehgal Sunish Kumar , Liu Shuyu , Chen Jianli , Fritz Allan , Cook Jason , Brown-Guedira Gina , Pumphrey Mike , Carter Arron , Sorrells Mark , Dubcovsky Jorge , Hayden Matthew J. , Akhunova Alina , Morrell Peter L. , Szabo Les , Rouse Matthew , Akhunov Eduard
Published: February 2022

Allopolyploidy greatly expands the range of possible regulatory interactions among functionally redundant homoeologous genes. However, connection between the emerging regulatory complexity and expression and phenotypic diversity in polyploid crops remains elusive. Here, we use diverse wheat accessions to map expression quantitative trait loci (eQTL) and evaluate their effects on the population-scale variation in homoeolog expression dosage. The relative contribution of cis- and trans-eQTL to homoeolog expression variation is strongly affected by both selection and demographic events. Though trans-acting effects play major role in expression regulation, the expression dosage of homoeologs is largely influenced by cis-acting variants, which appear to be subjected to selection. The frequency and expression of homoeologous gene alleles showing strong expression dosage bias are predictive of variation in yield-related traits, and have likely been impacted by breeding for increased productivity. Our study highlights the importance of genomic variants affecting homoeolog expression dosage in shaping agronomic phenotypes and points at their potential utility for improving yield in polyploid crops.
A computed tomography based survey study investigating the agreement of the therapeutic strategy for fragility fractures of the pelvis
Authors: Pieroh Philipp , Hohmann Tim , Gras Florian , Märdian Sven , Pflug Alexander , Wittenberg Silvan , Ihle Christoph , Blankenburg Notker , Dallacker-Losensky Kevin , Schröder Tanja , Herath Steven C. , Palm Hans-Georg , Josten Christoph , Stuby Fabian M. , Wagner Daniel , Höch Andreas
Published: February 2022

Treatment recommendations for fragility fractures of the pelvis (FFP) have been provided along with the good reliable FFP classification but they are not proven in large studies and recent reports challenge these recommendations. Thus, we aimed to determine the usefulness of the FFP classification determining the treatment strategy and favored procedures in six level 1 trauma centers. Sixty cases of FFP were evaluated by six experienced pelvic surgeons, six inexperienced surgeons in training, and one surgeon trained by the originator of the FFP classification during three repeating sessions using computed tomography scans with multiplanar reconstruction. The intra-rater reliability and inter-rater reliability for therapeutic decisions (non-operative treatment vs. operative treatment) were moderate, with Fleiss kappa coefficients of 0.54 (95% confidence interval [CI] 0.44–0.62) and 0.42 (95% CI 0.34–0.49). We found a therapeutic disagreement predominantly for FFP II related to a preferred operative therapy for FFP II. Operative treated cases were generally treated with an anterior–posterior fixation. Despite the consensus on an anterior–posterior fixation, the chosen procedures are highly variable and most plausible based on the surgeon’s preference.
Building a planter system using waste materials using value engineering environmental assessment
Authors: Al-Anzi Fawaz S.
Published: February 2022

Environmental challenges are significant threats to the planet; most of them are human-made hazards. Researchers are studying various environmental threats and trying to flourish sustainable policy for protecting the environment from various challenges worldwide. In Kuwait, researchers are paying attention to these various challenges and trying to reduce these issues in the most effective, economically innovative, and localized ways. Desertification and lack of water are the major significant examples of natural challenges faced by the environment. The fundamental goal of this study was to propose and implement a more cost-effective and economical alternative to the commercial Waterboxx kits technology. In this proposed work, the research team rebuilt a new prototype based on Value Engineering, whose functionalities are homogeneous to the most popular Waterboxx kits technology. Unlike the Waterboxx kits method, the new proposed framework decreased operational and capital expenditures and reduced the complexity of development and implementation by regular farmers. Since recycled plastic sheets and used tires are employed in the new method as grist, this method helps us fight against desertification and provide a better way to handle the ever-growing massive dumpsters of tires in the region of Kuwait; hence it helps us in getting rid of hazards due to the tire fires and bring in a more safe and friendly environment. A better substitute has been identified concerning the value from various substitutes considered for developing the prototype using a thorough examination with the help of the Function Analysis System Technique (FAST). A prototype of the proposed method was constructed and tested in a controlled lab atmosphere followed by an actual environment. Analysis of both soil and water on the experiment site was performed before and after the proposed prototype testing for conducting a cross-comparison of soil. This evaluation was performed to ensure the method we fabricated and tested is an effective environment-safe model. The simulation and analysis of the proposed method are very effective as the already existing model reduced and saved the cost of implementation. The cost reduced by the new proposed VE method than the already available model was 43.84% without paying attention to the intangible costs related to another environmental challenge, recycling waste materials that may also build up the cost-saving. This study illustrates how the proposed Value Engineering-based model became the foremost baseline method for developing a new innovative model to reduce cost and patentable design.
Pre-emptive analgesia with methylprednisolone and gabapentin in total knee arthroplasty in the elderly
Authors: Liszka Henryk , Zając Małgorzata , Gądek Artur
Published: February 2022

The aim of this study is to assess whether administration of gabapentin and methylprednisolone as “pre-emptive analgesia” in a group of patients above 65 years of age would be effective in complex pain management therapy following total knee arthroplasty (TKA). One hundred seventy patients above 65 years were qualified for the study, with exclusion of 10 patients due to clinical circumstances. One hundred sixty patients were randomly double-blinded into two groups: the study group (80 patients) and the control group (80 patients). The study group received as “pre-emptive” analgesia a single dose of 300 mg oral (PO) gabapentin and 125 mg intravenous (IV) methylprednisolone, while the control received a placebo. All patients received opioid and non-opioid analgesic agents perioperatively calculated for 1 kg of total body weight. We measured (1) pain intensity level at rest (numerical rating scale, NRS), (2) life parameters, (3) levels of inflammatory markers (leukocytosis, C reactive protein CRP), and (4) all complications. Following administration of gabapentin and methylprednisolone as “pre-emptive” analgesia, the NRS score at rest was calculated at 6, 12 (p < 0.000001), 18 (p < 0.00004) and 24 (p = 0.005569) h postoperatively. Methylprednisolone with gabapentin significantly decreased the dose of parenteral opioid preparations (p = 0.000006). The duration time of analgesia was significantly longer in study group (p < 0.000001), with CRP values lower on all postoperative days (1, 2 days—p < 0.00001, 3 days—p = 0.00538), and leukocytosis on day 2 (p < 0.0086) and 3 (p < 0.00042). No infectious complications were observed in the first postoperative days; in the control group, one patient manifested transient ischemic attack (TIA). The use of gabapentin and methylprednisolone as a single dose decreased the level of postoperative pain on the day of surgery, the dose of opioid analgesic preparations, and the level of inflammatory parameters without infectious processes.
Characterization and phylogenetic analysis of the complete mitochondrial genome of the pathogenic fungus Ilyonectria destructans
Authors: Androsiuk Piotr , Okorski Adam , Paukszto Łukasz , Jastrzębski Jan Paweł , Ciesielski Sławomir , Pszczółkowska Agnieszka
Published: February 2022

Ilyonectria destructans is a pathogenic fungus causing root rot and other symptoms on trees and many crops. This paper analyses the mitochondrial genome of I. destructans and compares it with other published Nectriaceae mitogenomes. The I. destructans mitogenome appears as a circular DNA molecule of 42,895 bp and an overall GC content of 28.23%. It contains 28 protein-coding genes (15 core protein genes and 13 free-standing ORFs), two rRNAs and 27 tRNAs. The gene content and order were found to be conserved in the mitogenome of I. destructans and other Nectriaceae, although the genome size varies because of the variation in the number and length of intergenic regions and introns. For most core protein-coding genes in Nectriaceae species, Ka/Ks < 1 indicates purifying selection. Among some Nectriaceae representatives, only the rps3 gene was found under positive selection. Phylogenetic analyses based on nucleotide sequences of 15 protein-coding genes divided 45 Hypocreales species into six major clades matching the families Bionectriaceae, Cordycipitaceae, Clavicipitaceae, Ophiocordycipitaceae, Hypocreaceae and Nectriaceae. I. destructans appeared as a sister species to unidentified Ilyonectia sp., closely related to C. ilicicola, N. cinnabarina and a clad of ten Fusarium species and G. moniliformis. The complete mitogenome of I. destructans reported in the current paper will facilitate the study of epidemiology, biology, genetic diversity of the species and the evolution of family Nectriace and the Hypocreales order.
Model-based learning retrospectively updates model-free values
Authors: Doody Max , Van Swieten Maaike M. H. , Manohar Sanjay G.
Published: February 2022

Reinforcement learning (RL) is widely regarded as divisible into two distinct computational strategies. Model-free learning is a simple RL process in which a value is associated with actions, whereas model-based learning relies on the formation of internal models of the environment to maximise reward. Recently, theoretical and animal work has suggested that such models might be used to train model-free behaviour, reducing the burden of costly forward planning. Here we devised a way to probe this possibility in human behaviour. We adapted a two-stage decision task and found evidence that model-based processes at the time of learning can alter model-free valuation in healthy individuals. We asked people to rate subjective value of an irrelevant feature that was seen at the time a model-based decision would have been made. These irrelevant feature value ratings were updated by rewards, but in a way that accounted for whether the selected action retrospectively ought to have been taken. This model-based influence on model-free value ratings was best accounted for by a reward prediction error that was calculated relative to the decision path that would most likely have led to the reward. This effect occurred independently of attention and was not present when participants were not explicitly told about the structure of the environment. These findings suggest that current conceptions of model-based and model-free learning require updating in favour of a more integrated approach. Our task provides an empirical handle for further study of the dialogue between these two learning systems in the future.
Cell surface expression of GRP78 and CXCR4 is associated with childhood high-risk acute lymphoblastic leukemia at diagnostics
Authors: Angeles-Floriano Tania , Rivera-Torruco Guadalupe , García-Maldonado Paulina , Juárez Esmeralda , Gonzalez Yolanda , Parra-Ortega Israel , Vilchis-Ordoñez Armando , Lopez-Martinez Briceida , Arriaga-Pizano Lourdes , Orozco-Ruíz Dario , Torres-Nava José Refugio , Licona-Limón Paula , López-Sosa Francisco , Bremer Alhelí , Alvarez-Arellano Lourdes , Valle-Rios Ricardo
Published: February 2022

Acute lymphocytic leukemia is the most common type of cancer in pediatric individuals. Glucose regulated protein (GRP78) is an endoplasmic reticulum chaperone that facilitates the folding and assembly of proteins and regulates the unfolded protein response pathway. GRP78 has a role in survival of cancer and metastasis and cell-surface associated GRP78 (sGRP78) is expressed on cancer cells but not in normal cells. Here, we explored the presence of sGRP78 in pediatric B-ALL at diagnosis and investigated the correlation with bona fide markers of leukemia. By using a combination of flow cytometry and high multidimensional analysis, we found a distinctive cluster containing high levels of sGRP78, CD10, CD19, and CXCR4 in bone marrow samples obtained from High-risk leukemia patients, which was absent in the compartment of Standard-risk leukemia. We confirmed that sGRP78+CXCR4+ blood-derived cells were more frequent in High-risk leukemia patients. Finally, we analyzed the dissemination capacity of sGRP78 leukemia cells in a model of xenotransplantation. sGRP78+ cells emigrated to the bone marrow and lymph nodes, maintaining the expression of CXCR4. Testing the presence of sGRP78 and CXCR4 together with conventional markers may help to achieve a better categorization of High and Standard-risk pediatric leukemia at diagnosis.
Ant Lasius niger joining one-way trails go against the flow
Authors: Sakamoto Yuta , Sakiyama Tomoko
Published: February 2022

Social insects, such as ants, use various pheromones as their social signal. In addition, they use the presence of other ants for decision-making. In this study, we attempted to evaluate if individual decision-making is influenced by the complementary use of pheromones and presence of other ants. Ants were induced to form a one-way flow system. We found that when ants entered such a system at a right angle, they tended to move in the opposite direction of the one-way flow system. Interestingly, the target ants moved randomly in the experiments in which no ant and/or no pheromone trails were present. We also developed simulation algorithms and found that artificial ant foragers could reach a certain goal more often if they adopted the reverse run (similar mechanism found in ant experiments) over the forward run (moving in the same direction as their nestmates).
LPIN1 promotes triglycerides synthesis and is transcriptionally regulated by PPARG in buffalo mammary epithelial cells
Authors: Zhou Fangting , Fan Xinyang , Miao Yongwang
Published: February 2022

Studies on 3T3-L1 cells and HepG2 hepatocytes have shown that phosphatidic acid phosphohydrolase1 (LPIN1) plays a key role in adipogenesis, acting as a co-activator of peroxisome proliferator-activated receptor gamma coactivator 1a (PGC-1a) to regulate fatty acid metabolism. However, the functional role and regulatory mechanism of LPIN1 gene in milk fat synthesis of buffalo are still unknown. In this study, overexpression of buffalo LPIN1 gene transfected with recombinant fusion expression vector significantly increased the expression of AGPAT6, DGAT1, DGAT2, GPAM and BTN1A1 genes involved in triglyceride (TAG) synthesis and secretion, as well as PPARG and SREBF1 genes regulating fatty acid metabolism in the buffalo mammary epithelial cells (BMECs), while the lentivirus-mediated knockdown of buffalo LPIN1 dramatically decreased the relative mRNA abundance of these genes. Correspondingly, total cellular TAG content in the BMECs increased significantly after LPIN1 overexpression, but decreased significantly after LPIN1 knockdown. In addition, the overexpression or knockdown of PPARG also enhanced or reduced the expression of LPIN1 and the transcriptional activity of its promoter. The core region of buffalo LPIN1 promoter spans from − 666 bp to + 42 bp, and two PPAR response elements (PPREs: PPRE1 and PPRE2) were identified in this region. Site mutagenesis analysis showed that PPARG directly regulated the transcription of buffalo LPIN1 by binding to the PPRE1 and PPRE2 on its core promoter. The results here reveal that the LPIN1 gene is involved in the milk fat synthesis of BMECs, and one of the important pathways is to participate in this process through direct transcriptional regulation of PPARG, which in turn significantly affects the content of TAG in BMECs.
Nonlinear refinement of functional brain connectivity in golf players of different skill levels
Authors: Chen Tai-Ting , Wang Kuo-Pin , Huang Chung-Ju , Hung Tsung-Min
Published: February 2022

Different functional connectivities in the brain, specifically in the frontoparietal and motor cortex–sensorimotor circuits, have been associated with superior performance in athletes. However, previous electroencephalogram (EEG) studies have only focused on the frontoparietal circuit and have not provided a comprehensive understanding of the cognitive–motor processes underlying superior performance. We used EEG coherence analysis to examine the motor cortex–sensorimotor circuit in golfers of different skill levels. Twenty experts, 18 amateurs, and 21 novices performed 60 putts at individual putting distances (40–60% success rate). The imaginary inter-site phase coherence (imISPC) was used to compute 8–13 Hz coherence that can be used to distinguish expert-novice and expert-amateur differences during motor preparation. We assessed the 8–13 Hz imISPC between the Cz and F3, F4, C3, C4, T3, T4, P3, P4, O1, and O2 regions. (1) Amateurs had lower 8–13 Hz imISPC in the central regions (Cz–C3 and C4) than novices and experts, but experts had lower 8–13 Hz imISPC than novices. (2) Skilled golfers (experts and amateurs) had lower 8–13 Hz imISPC in the central–parietal regions (Cz–P3 and P4) than novices. (3) Experts had lower 8–13 Hz imISPC in the central–left temporal regions (Cz–T7) than amateurs and novices. Our study revealed that refinement of the motor cortex–sensorimotor circuit follows a U-shaped coherence pattern based on the stage of learning. The early learning stage (i.e., novice to amateur) is characterized by lower connectivity between the regions associated with motor control and visuospatial processes, whereas the late learning stage (i.e., amateur to expert) is characterized by lower connectivity in the regions associated with verbal-analytic and motor control processes.
Differential associations of regional cerebellar volume with gait speed and working memory
Authors: Won Junyeon , Callow Daniel D. , Purcell Jeremy J. , Smith J. Carson
Published: February 2022

The relationship between gait speed and working memory is well-understood in older adults. However, it remains to be determined whether this relationship also exists in younger adults; and there is little known regarding the possible neural mechanism underlying the association between gait speed and working memory. The aims of this study are to determine if there is: (1) an association between gait speed and working memory performance; and (2) a mediating role of cerebellar subregion volume in the correlation between gait speed and working memory in healthy younger adults. 1054 younger adults (28.7 ± 3.6 years) from the Human Connectome Project were included in the analyses. A four-meter gait test was used to assess gait speed. The 2-back task was used to measure working memory performance [accuracy and response time (RT)]. T1-weighted structural MRI data (obtained using Siemens 3 T MRI scanner) was used to assess cerebellar subregion volumes. Linear regression and mediation analysis were used to examine the relationships between the variables after controlling for age, sex, and education. There was no association between gait speed and 2-back working memory performance in younger adults. Greater Crus I and whole cerebellar volumes were associated with better 2-back working memory accuracy. Greater VIIIa volume was associated with faster gait speed. Greater Crus 1 and VIIIa volumes were also associated with higher fluid cognition. The present study suggests that specific subregions of the cerebellar volumes are distinctively associated with gait speed and working memory performance in healthy younger adults.
Prognosis of COVID-19 pneumonia can be early predicted combining Age-adjusted Charlson Comorbidity Index, CRB score and baseline oxygen saturation
Authors: Nuevo-Ortega Pilar , Reina-Artacho Carmen , Dominguez-Moreno Francisco , Becerra-Muñoz Victor Manuel , Ruiz-Del-Fresno Luis , Estecha-Foncea Maria Antonia ,   HOPE Group Hospital Universitario Virgen de la Victoria, Aguilar-Galvez A. M. , Barrera-Serrano R. , Becerra-Muñoz Victor Manuel , Cabrera-Cesar E. , Castillo-Caballero J. M. , Cordon-Alvarez S. , Cota-Delgado F. , Daga-Ruiz D. , De La Torre-Muñoz A. , Dominguez-Moreno Francisco , Doncel-Abad V. , Estecha-Foncea Maria Antonia , Estevez-Escobar E. , Fernandez-Villalba A. , Garcia-Aragon S. , Garcia-Cruz M. C. , Garcia-Gomez I. G. , Gomez-Perez A. M. , Gonzalez-Redondo P. , Lara-Dominguez P. , Martinez-Lopez P. , Martinez-Mesa A. , Mateos-Rodriguez M. , Moratalla-Cecilia G. , Murcia-Casas B. , Nieto-Gonzalez M. , Nuevo-Ortega Pilar , Perez-Lopez C. , Puerto-Morlan A. , Reina-Artacho Carmen , Rodriguez-Capitan J. , Rueda-Molina C. , Ruiz-Del-Fresno Luis , Salazar-Ramirez C. , Salido-Diaz L. , Sanchez-Alvarez E. , Sanchez-Calderon A. , Sanchez-Garcia A. , Segura-Gonzalez F. , Valera-Rubio M. , Vallejo-Baez A. , Vera-Sanchez M. C. , Zamboschi N. A.
Published: February 2022

In potentially severe diseases in general and COVID-19 in particular, it is vital to early identify those patients who are going to progress to severe disease. A recent living systematic review dedicated to predictive models in COVID-19, critically appraises 145 models, 8 of them focused on prediction of severe disease and 23 on mortality. Unfortunately, in all 145 models, they found a risk of bias significant enough to finally "not recommend any for clinical use". Authors suggest concentrating on avoiding biases in sampling and prioritising the study of already identified predictive factors, rather than the identification of new ones that are often dependent on the database. Our objective is to develop a model to predict which patients with COVID-19 pneumonia are at high risk of developing severe illness or dying, using basic and validated clinical tools. We studied a prospective cohort of consecutive patients admitted in a teaching hospital during the “first wave” of the COVID-19 pandemic. Follow-up to discharge from hospital. Multiple logistic regression selecting variables according to clinical and statistical criteria. 404 consecutive patients were evaluated, 392 (97%) completed follow-up. Mean age was 61 years; 59% were men. The median burden of comorbidity was 2 points in the Age-adjusted Charlson Comorbidity Index, CRB was abnormal in 18% of patients and basal oxygen saturation on admission lower than 90% in 18%. A model composed of Age-adjusted Charlson Comorbidity Index, CRB score and basal oxygen saturation can predict unfavorable evolution or death with an area under the ROC curve of 0.85 (95% CI 0.80–0.89), and 0.90 (95% CI 0.86 to 0.94), respectively. Prognosis of COVID-19 pneumonia can be predicted without laboratory tests using two classic clinical tools and a pocket pulse oximeter.
Persistence of the invasive bird-parasitic fly Philornis downsi over the host interbreeding period in the Galapagos Islands
Authors: Bulgarella Mariana , Lincango M. Piedad , Lahuatte Paola F. , Oliver Jonathan D. , Cahuana Andrea , Ramírez Ismael E. , Sage Roxanne , Colwitz Alyssa J. , Freund Deborah A. , Miksanek James R. , Moon Roger D. , Causton Charlotte E. , Heimpel George E.
Published: February 2022

Many parasites of seasonally available hosts must persist through times of the year when hosts are unavailable. In tropical environments, host availability is often linked to rainfall, and adaptations of parasites to dry periods remain understudied. The bird-parasitic fly Philornis downsi has invaded the Galapagos Islands and is causing high mortality of Darwin’s finches and other bird species, and the mechanisms by which it was able to invade the islands are of great interest to conservationists. In the dry lowlands, this fly persists over a seven-month cool season when availability of hosts is very limited. We tested the hypothesis that adult flies could survive from one bird-breeding season until the next by using a pterin-based age-grading method to estimate the age of P. downsi captured during and between bird-breeding seasons. This study showed that significantly older flies were present towards the end of the cool season, with ~ 5% of captured females exhibiting estimated ages greater than seven months. However, younger flies also occurred during the cool season suggesting that some fly reproduction occurs when host availability is low. We discuss the possible ecological mechanisms that could allow for such a mixed strategy.
Suppression of tumor metastasis by a RECK-activating small molecule
Authors: Yoshida Yoko , Yuki Kanako , Dan Shingo , Yamazaki Kanami , Noda Makoto
Published: February 2022

RECKencodes a membrane-anchored protease-regulator which is often downregulated in a wide variety of cancers, and reducedRECKexpression often correlates with poorer prognoses. In mouse models, forced expression of RECK in tumor xenografts results in suppression of tumor angiogenesis, invasion, and metastasis.RECKmutations, however, are rare in cancer genomes, suggesting that agents that re-activate dormantRECKmay be of clinical value. We found a potentRECK-inducer, DSK638, that inhibits spontaneous lung metastasis in our mouse xenograft model. Induction ofRECKexpression involves SP1 sites in its promoter and may be mediated by KLF2. DSK638 also upregulates MXI1, an endogenous MYC-antagonist, and inhibition of metastasis by DSK638 is dependent on both RECK and MXI1. This study demonstrates the utility of our approach (using a simple reporter assay followed by multiple phenotypic assays) and DSK638 itself (as a reference compound) in finding potential metastasis-suppressing drugs.
miR-520a-5p regulates Frizzled 9 expression and mediates effects of cigarette smoke and iloprost chemoprevention
Authors: Smith A. J. , Do P. , Sompel K. , Elango A. , Tennis M. A.
Published: February 2022

Expression of Frizzled 9 (FZD9) is critical to the activity of the lung cancer chemoprevention agent and prostacyclin analogue, iloprost. FZD9 is required in lung epithelial cells for iloprost to activate peroxisome proliferator activated receptor gamma (PPARG) and related anti-tumor signaling. We aimed to investigate which miRNA regulate FZD9 in the context of cigarette smoke exposure and iloprost treatment. We found that miR-520a-5p binds the FZD9 3’UTR in lung cell lines and alters activity and expression of FZD9 downstream targets. Cigarette smoke condensate (CSC) increases expression of miR-520a-5p, while iloprost decreases expression. Cancer promoting effects of a miR-520a-5p mimic were rescued with iloprost treatment, and effects of cigarette smoke were partially rescued with a miR-520a-5p inhibitor. Here we confirm miR-520a-5p as a regulator of FZD9 activity and a mediator of CSC and iloprost effects in the lung. Targeting miR-520a-5p could be an approach to restoring FZD9 expression and improving response to iloprost lung cancer chemoprevention.
Identification of the robust predictor for sepsis based on clustering analysis
Authors: Jang Jae Yeon , Yoo Gilsung , Lee Taesic , Uh Young , Kim Juwon
Published: February 2022

Sepsis is a life-threatening disorder with high incidence and mortality rate. However, the early detection of sepsis is challenging due to lack of specific marker and various etiology. This study aimed to identify robust risk factors for sepsis via cluster analysis. The integrative task of the automatic platform (i.e., electronic medical record) and the expert domain was performed to compile clinical and medical information for 2,490 sepsis patients and 16,916 health check-up participants. The subjects were categorized into 3 and 4 groups based on seven clinical and laboratory markers (Age, WBC, NLR, Hb, PLT, DNI, and MPXI) by K-means clustering. Logistic regression model was performed for all subjects including healthy control and sepsis patients, and cluster-specific cases, separately, to identify sepsis-related features. White blood cell (WBC), well-known parameter for sepsis, exhibited the insignificant association with the sepsis status in old age clusters (K3C3 and K4C3). Besides, NLR and DNI were the robust predictors in all subjects as well as three or four cluster-specific subjects including K3C3 or K4C3. We implemented the cluster-analysis for real-world hospital data to identify the robust predictors for sepsis, which could contribute to screen likely overlooked and potential sepsis patients (e.g., sepsis patients without WBC count elevation).
Influencing the body schema through the feeling of satiety
Authors: Baumann Patricia , Beckmann Nina , Herpertz Stephan , Trojan Jörg , Diers Martin
Published: February 2022

The body schema is a much discussed aspect of body awareness. Although there is still no single definition, there is widespread consensus that the body schema is responsible for movement and interaction with the environment. It usually remains outside of active consciousness. There are only few investigations on influences on the body schema and none of them investigated feeling of satiety or hunger. Thirty-two healthy women were investigated twice, one time sat and the other time hungry. To measure the body schema, we used a door-like-aperture and compared the critical aperture-to-shoulder-ratio (cA/S). A cover story was used to ensure that the unconscious body schema has been measured. We found a significantly higher cA/S for satiety compared to hungry, which indicates that during satiety participants rotate their shoulders for relatively larger door compared to hunger, unconsciously estimating their body size to be larger. We showed that even a moderate rated feeling of hunger or satiety leads to an adjustment in body-scaled action and consequently also an adaptation of body schema. It suggests that, in addition to the visual-spatial and the proprioceptive representation, somatic information can also be relevant for the body schema.
Providing early indication of regional anomalies in COVID-19 case counts in England using search engine queries
Authors: Yom-Tov Elad , Lampos Vasileios , Inns Thomas , Cox Ingemar J. , Edelstein Michael
Published: February 2022

Prior work has shown the utility of using Internet searches to track the incidence of different respiratory illnesses. Similarly, people who suffer from COVID-19 may query for their symptoms prior to accessing the medical system (or in lieu of it). To assist in the UK government’s response to the COVID-19 pandemic we analyzed searches for relevant symptoms on the Bing web search engine from users in England to identify areas of the country where unexpected rises in relevant symptom searches occurred. These were reported weekly to the UK Health Security Agency to assist in their monitoring of the pandemic. Our analysis shows that searches for “fever” and “cough” were the most correlated with future case counts during the initial stages of the pandemic, with searches preceding case counts by up to 21 days. Unexpected rises in search patterns were predictive of anomalous rises in future case counts within a week, reaching an Area Under Curve of 0.82 during the initial phase of the pandemic, and later reducing due to changes in symptom presentation. Thus, analysis of regional searches for symptoms can provide an early indicator (of more than one week) of increases in COVID-19 case counts.
Dipole pattern of meridional atmospheric internal energy transport across the Arctic gate
Authors: Latonin Mikhail M. , Bobylev Leonid P. , Bashmachnikov Igor L. , Davy Richard
Published: February 2022

High-latitude atmospheric meridional energy transport plays a fundamental role in the Arctic climate system. However, despite numerous studies, there are no established clear regional features of the atmospheric energy transport components from a large-scale perspective. This study aims at investigating the internal energy and its instantaneous sensible and latent heat transports in the troposphere across the Arctic gate at 70°N using the high-resolution climate reanalysis ERA5. We have done a regional analysis of the time series of heat fluxes across the zonal section and found by decomposing them into empirical orthogonal functions that they have opposing features for the Eastern and Western Hemispheres. In particular, the sensible heat transport dominates in the Western Hemisphere, whereas the latent heat transport dominates in the Eastern Hemisphere. Moreover, we detected the existence of an anti-phase dipole pattern for each of these components in the entire troposphere, which is robust because it continued during the entire studied period 1950–2019. The hemispheric net fluxes indicate that the Arctic gains internal energy mostly due to the latent heat transport.