bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ventricular activation patterns during intrinsic conduction and right ventricular pacing in cardiac resynchronization therapy patients
Authors: O'Donnell David , Manyam Harish , Pappone Carlo , Park Seung‐Jung , Leclercq Christophe , Lunati Maurizio , Lercher Peter , Rordorf Roberto , Landolina Maurizio , Badie Nima , McSpadden Luke C. , Ryu Kyungmoo , Mangual Jan O. , Singh Jagmeet P. , Varma Niraj , Niazi Imran K. 
Published: July 2021

AbstractBackgroundCardiac resynchronization therapy (CRT) involves stimulation of both right ventricle (RV) and left ventricle (LV). LV pacing from the sites of delayed electrical activation improves CRT response. The RV‐LV conduction is typically measured in intrinsic rhythm. The differences in RV‐LV conduction patterns and timing between intrinsic rhythm and during paced RV activation, these differences are not fully understood.MethodsEnrolled patients were implanted with a de novo CRT device and quadripolar LV lead, with lead implant locations at the implanting physician's discretion. QRS duration and conduction delay between the RV lead and each of the four LV electrodes (D1, M2, M3, and P4) were measured during intrinsic conduction and RV pacing.ResultsConduction measurements were collected from 275 patients across 14 international centers (68 ± 13 years of age, 73% male, 45% ischemic, 158 ± 22 ms QRS duration). Mean RV‐LV conduction time was shorter during intrinsic conduction versus RV pacing by 59.6 ms (106.5 ± 36.5 versus 166.1 ± 32.1 ms, p < 0.001). The intra‐LV activation delay between the latest and earliest activating LV electrode was also shorter during intrinsic conduction versus RV pacing by 6.6 ms (20.6 ± 13.1 vs. 27.2 ± 21.2 ms, p < 0.001). Intrinsic conduction and RV pacing resulted in a different activation order in 72.7% of patients, and the same LV activation order in 27.3%.ConclusionsDifferences in RV‐LV conduction time, intra‐LV conduction time, and activation pattern were observed between intrinsic conduction and RV pacing. These findings highlight the importance of evaluating intrinsic versus paced ventricular activation to guide LV pacing site selection in CRT patients.
Go large or go conical: allometric trajectory of an early Cambrian acrotretide brachiopod
Authors: Zhang Zhiliang , Topper Timothy P. , Chen Yanlong , Strotz Luke C. , Chen Feiyang , Holmer Lars E. , Brock Glenn A. , Zhang Zhifei 
Published: July 2021

AbstractAcrotretides are extinct micromorphic brachiopods that exhibited considerable morphological variation during their rapid evolution in the early Palaeozoic. The plano‐conical shells of acrotretides are distinct in comparison to other brachiopod groups and despite their diversity and abundance in early Palaeozoic communities, their origins, early evolution, life history and phylogeny are poorly understood. Here, we employ advanced geometric morphometrics to quantitatively investigate ontogenetic variation and allometry in the ventral valve of the oldest known acrotretide species from the early Cambrian of South China. Our results identify substantial shape variation forEohadrotreta zhenbaensis, along with a parabolic morphological trajectory through ontogeny, demonstrating a remarkable reversal to PC1 values equivalent to those obtained for juveniles, during later ontogenetic stages. The evolutionary novel body plan (diminutive and plano‐conical) of Acrotretida was established gradually during two phases of allometry, formed initially during the final stage of the Cambrian evolutionary radiation from an ancestral low, equivalved lingulide body plan. The development of a conical shaped valve seems to have resulted in an overall smaller body size, when compared with non‐conical forms. The heterochronic processes responsible for generating these ontogenetic modifications at different allometric phases may have facilitated the evolutionary diversification of acrotretide brachiopods during the early Palaeozoic.
The prognostic significance of neuroendocrine markers and somatostatin receptor 2 in hepatocellular carcinoma
Authors: Murakami Keigo , Kumata Hiroyuki , Miyagi Shigehito , Kamei Takashi , Sasano Hironobu 
Published: July 2021

AbstractProstatic and colon carcinomas with neuroendocrine differentiation are reported to behave more aggressively than those without such differentiation. In hepatocellular carcinomas (HCCs), however, only a few studies have reported the expression status of neuroendocrine markers and somatostatin receptor 2, the main target of a somatostatin analog. Furthermore, the prognostic significance of the markers in HCCs has not been fully explored. We evaluated the expression of the neuroendocrine makers (chromogranin A, synaptophysin, and CD56) and somatostatin receptor 2 (SSTR2) in 95 HCCs, and investigated the correlation between the expression of these markers and clinicopathological findings. Chromogranin A was immunolocalized in 2 cases, synaptophysin in 15 cases, CD56 in 11 cases, and SSTR2 in 19 cases. Immunoreactivity of synaptophysin and CD56 were the significant unfavorable prognostic factors in terms of 2‐year disease‐free survival (DFS) and the overall survival (OS) along with a high nuclear mitosis level (>10/10 high‐power field), a larger tumor size (>5 cm), the presence of vascular and/or biliary invasion, and high TNM stage (III/IV). Multivariate Cox proportional hazards analysis identified synaptophysin as an independent prognostic factor for 2‐year DFS and OS. Synaptophysin expression can be used to predict an unfavorable prognosis in patients with HCC.
Arterial stiffness in underweight and weight‐restored anorexia nervosa
Authors: Jenkins Zoe M. , Phillipou Andrea , Castle David J. , Eikelis Nina , Lambert Elisabeth A. 
Published: July 2021

AbstractCardiovascular complications have been demonstrated in patients with anorexia nervosa (AN) in both the state of starvation and during weight restoration, however, the underlying mechanisms remain unclear. The current study aimed to assess arterial stiffness via carotid‐femoral pulse wave velocity (cfPWV) in the acute and weight‐restored states of AN. The study also aimed to determine the association between psychological distress and cfPWV. The sample included 37 participants; 10 participants with AN, 17 who were weight‐restored (AN‐WR; minimum body mass index >18.5 for at least 12 months) and 10 healthy controls (HCs). cfPWV via applanation tonometry was conducted to assess arterial stiffness. Psychological distress was assessed using the depression anxiety stress scale (DASS‐21) and the state‐trait anxiety inventory (STAI). Between‐group comparisons were performed to determine differences between groups, a two‐stage hierarchical regression model was performed to determine the contribution of physiological and psychological variables on cfPWV and correlation analyses were also performed. Vascular stiffness was significantly increased in the AN and AN‐WR groups, relative to HCs. The total DASS score was the only significant predictor of cfPWV across the sample. There were positive associations between cfPWV and depression, anxiety and stress, as assessed by the DASS. Furthermore, cfPWV was positively associated with STAI trait anxiety. Arterial stiffness was increased in individuals in the acute and weight‐restored states of AN, demonstrating early signs of the development of arteriosclerotic cardiovascular disease. Increased arterial stiffness was associated with increased psychological distress, which may be a contributing mechanism to the increased cardiovascular risk in AN.
Is maternal employment detrimental to children’s nutritional status? Evidence from Bangladesh
Authors: Jakaria Mohammad , Bakshi Rejaul Karim , Hasan M. Mehedi 
Published: July 2021

AbstractThis paper explores the effect of maternal employment on the nutritional status of children below age 5 years in Bangladesh using data from the 2014 Bangladesh Demographic and Health Survey. Since mothers’ choice to participate in the labor market is endogenous, the estimation of the causal effect of maternal employment on child health is statistically challenging. To correct for the endogeneity of maternal employment, we employ instrumental variable (IV) estimation. While our ordinary least squares results show that mothers’ employment has no significant effect on children's nutritional outcome, the IV estimates suggest that maternal employment significantly decreases children's height‐for‐age Z‐score. This result is contrary to conventional wisdom advocating for maternal employment to positively affect child health and well‐being. We, therefore, argue for effective policy interventions—such as childcare centers at workplaces, flexibility in working hours including part‐time options for mothers, restraining child marriages, and strengthening maternal and child health‐care services through community health centers—to foster children's health as well as maternal employment in the country.
Effect of winter cereal sowing time on yield and nitrogen leaching based on experiments and modelling
Authors: Vogeler Iris , Thomsen Ingrid Kaag , Taube Friedhelm , Poulsen Henrik Vestergaard , Loges Ralf , Hansen Elly Møller 
Published: July 2021

AbstractEarly sowing of winter cereals has been promoted as an alternative to catch crops for reducing nitrogen (N) leaching in intensively managed cropping systems. Underlying data for this are, however, scarce and it is unclear how year‐to‐year variations affect potential reductions in N leaching. Well‐tested cropping system models can be used to assess the impact of early sowing on crop yield and N leaching. We tested the ability of the Agricultural Production System Simulator (APSIM) to simulate grain yield, biomass, phenology, N uptake and N leaching from timely and early‐sown winter cereals. The evaluation was based on two extensive field experiments carried out in Denmark in continuous winter cereals systems with different N fertilization applications, and a farm experiment in Germany with a grass ley/winter wheat crop sequence and two different N fertilization rates. Additionally, observations from growth stages throughout Denmark were used. After changing a few crop model parameters, APSIM reproduced the general effects of N fertilization and crop sequence on yields and N uptake, as well as N leaching. The model was then used to simulate the effect of sowing time on grain yield over a period of 10 years, to capture year‐to‐year variability and enable a better evaluation of the efficacy of early sowing for reducing N leaching. In the continuous winter cereal systems, early sowing reduced N leaching at both sites in Denmark. In contrast, in the grass ley/winter wheat system in Germany early sowing increased N leaching, due to enhanced mineralization of grass residues.
Contrastive Hinge Epistemology
Authors: Volpe Giorgio 
Published: July 2021

AbstractIn this paper, I outline an account of the structure of perceptual justification that develops Wittgenstein's thought that the possibility of acquiring any degree of justification for our beliefs depends on placing certain propositions outside the route of empirical inquiry, turning them into the “hinges” of our rational evaluations. The proposal is akin to “moderate” accounts of the structure of perceptual justification; however, it conjoins Wittgenstein's insight with explanationist and contrastivist ideas and thus differs in important respects both from such accounts and from other versions of hinge epistemology. I maintain that the basic presuppositions of the epistemic practice of taking experience at face value are not totally refractory to evidential assessment, arguing that they can receive some degree of second‐order empirical justification via inference to the best explanation. And I address the worry that the account may face the problem of “easy knowledge” by helping myself to the contrastivist view that empirical knowledge is best understood as a three‐place, contrastive relation between an agent, a proposition (or fact), and a contrast. This leads me to replace the usual closure principles for epistemic justification and knowledge with corresponding contrastive principles, filling in the final details of contrastive hinge epistemology.
Elusive partners: a review of the auxiliary proteins guiding metabolic flux in flavonoid biosynthesis
Authors: Dastmalchi Mehran 
Published: July 2021

SUMMARYFlavonoids are specialized metabolites widely distributed across the plant kingdom. They are involved in the growth and survival of plants, conferring the ability to filter ultra‐violet rays, conduct symbiotic partnerships, and respond to stress. While many branches of flavonoid biosynthesis have been resolved, recent discoveries suggest missing auxiliary components. These overlooked elements can guide metabolic flux, enhance production, mediate stereoselectivity, transport intermediates, and exert regulatory functions. This review describes several families of auxiliary proteins from across the plant kingdom, including examples from specialized metabolism. In flavonoid biosynthesis, we discuss the example of chalcone isomerase‐like (CHIL) proteins and their non‐catalytic role. CHILs mediate the cyclization of tetraketides, forming the chalcone scaffold by interacting with chalcone synthase (CHS). Loss of CHIL activity leads to derailment of the CHS‐catalyzed reaction and a loss of pigmentation in fruits and flowers. Similarly, members of the pathogenesis‐related 10 (PR10) protein family have been found to differentially bind flavonoid intermediates, guiding the composition of anthocyanins. This role comes within a larger body of PR10 involvement in specialized metabolism, from outright catalysis (e.g., (S)‐norcoclaurine synthesis) to controlling stereochemistry (e.g., enhancing cis‐trans cyclization in catnip). Both CHILs and PR10s hail from larger families of ligand‐binding proteins with a spectrum of activity, complicating the characterization of their enigmatic roles. Strategies for the discovery of auxiliary proteins are discussed, as well as mechanistic models for their function. Targeting such unanticipated components will be crucial in manipulating plants or engineering microbial systems for natural product synthesis.
Apera spica‐venti in the Czech Republic develops resistance to three herbicide modes of action
Authors: Košnarová Pavlína , Hamouz Pavel , Hamouzová Kateřina , Linn Alexander , Sen Madhab K. , Mikulka Jakub , Šuk Jaromír , Soukup Josef 
Published: July 2021

AbstractInvestigation of molecular mechanisms of herbicide resistance to three modes of action was carried out in a population of Apera spica‐venti with resistance to herbicides inhibiting acetolactate synthase (ALS), acetyl‐CoA‐carboxylase (ACCase) and inhibitors of photosystem‐II (PSII). Greenhouse experiments were conducted to detect and characterize resistance pattern to pyroxsulam (ALS inhibitor), pinoxaden (ACCase) and chlorotoluron (PSII) using the recommended rate of each herbicide alone and in tank‐mix, sequential application and dose–response tests. Metabolic detoxification and/or reduced herbicide uptake and translocation studies were conducted using dose–response tests with the herbicides in combination with malathion. After treatment, leaves from surviving plants were collected for pyrosequencing to identify target‐site mutations in specific regions of ALS, ACCase and psbA genes. Among 32 analysed plants, target‐site mutations in specific regions were detected for ALS and ACCase gene, but no psbA mutations were found. Dose–response assay showed high resistance factors for pyroxsulam (RF = 269.4), pinoxaden (RF = 66.3), but lower for chlorotoluron (RF = 14.3). Testing for metabolic detoxification by pre‐treatment with malathion resulted in an increased susceptibility to pinoxaden in all doses, some increased susceptibility to chlorotoluron at the highest doses and no difference for pyroxsulam. Our results indicate that while target‐site mutations were present for ALS and ACCase sites of action, metabolic detoxification does play a role for pinoxaden resistance. This research provided key insights into the resistance mechanisms in Apera spica‐venti and will be important for developing control strategies for this weed in the Czech Republic.
Ovariectomy and high salt increase blood pressure and alter sodium transport proteins in peripheral blood mononuclear cells of adult Wistar rats
Authors: Vlachovsky Sandra G. , Di Ciano Luis A. , Oddo Elisabet M. , Azurmendi Pablo J. , Goette Nora P. , Arrizurieta Elvira E. , Silberstein Claudia , Ibarra Fernando R. 
Published: July 2021

New Findings
What is the central question of this study?
In a model of salt‐sensitive hypertension in ovariectomized (oVx) adult Wistar rats, what is the expression of proteins related to sodium transport in peripheral blood mononuclear cells (PBMCs), and how does the response of proteins to high sodium intake compare with changes in blood pressure in intact female rats?
What is the main finding and its importance?
Sodium transport proteins in PBMCs react to high sodium and blood pressure markedly differently in oVx versus intact female rats. Protein expression shows sodium and pressure sensitivity. Renal immune cells increase in oVx under high salt.
AbstractHypertension is a worldwide public health problem. High sodium consumption is associated with hypertension, and hypertensive mechanisms involve immunity cells. Peripheral blood mononuclear cells (PBMCs) are endowed with proteins related to sodium transport. We studied their abundance in PBMCs from intact (IF) or ovariectomized (oVx) adult Wistar rats under normal (NS) or high (HS) salt intake. Ovariectomy was performed at 60 days of life. At 145 days, one group of IF and oVx rats received NS or HS intake for 5 days. Another group of IF HS and oVx HS rats received hydralazine (HDZ) to reduce blood pressure (BP). Sodium balance and BP were recorded. Expression of Na+,K+‐ATPase (NKA), Na+–K+–2Cl− cotransporter 1 (NKCC1), serum/glucocorticoid‐regulated kinase 1 (SGK1), dopamine D1 like receptor (D1DR), CD4+ and CD8+ were determined in PBMCs and CD45+ leukocytes in renal tissue. IF HS rats showed increased natriuresis and normal BP. NKA and CD4+ expression diminished in IF HS. Instead, oVx HS rats had sodium retention and high BP and increased the expression of NKA, NKCC1, D1DR, CD4+ and CD8+ in PBMCs. Renal CD45+ leukocytes increased in oVx HS rats. HDZ decreased BP in all rats. Upon HDZ treatment, NKA did not change, NKCC1 decreased in oVx HS rats, while SGK1 increased in both IF HS and oVx HS rats. Hormonal background determines BP response and the expression of proteins related to sodium transport in PBMCs and renal immune cells at HS intake. The analysis of NKA, NKCC1 and SGK1 expression in PBMCs differentiated salt‐sensitivity from BP variations.
Integrated respiratory chemoreflex‐mediated regulation of cerebral blood flow in hypoxia: Implications for oxygen delivery and acute mountain sickness
Authors: Ogoh Shigehiko , Washio Takuro , Stacey Benjamin S. , Tsukamoto Hayato , Iannetelli Angelo , Owens Thomas S. , Calverley Thomas A. , Fall Lewis , Marley Christopher J. , Saito Shotaro , Watanabe Hironori , Hashimoto Takeshi , Ando Soichi , Miyamoto Tadayoshi , Bailey Damian M. 
Published: July 2021

New Findings
What is the central question of this study?
To what extent do hypoxia‐induced changes in the peripheral and central respiratory chemoreflex modulate anterior and posterior cerebral oxygen delivery, with corresponding implications for susceptibility to acute mountain sickness?
What is the main finding and its importance?
We provide evidence for site‐specific regulation of cerebral blood flow in hypoxia that preserves oxygen delivery in the posterior but not the anterior cerebral circulation, with minimal contribution from the central respiratory chemoreflex. External carotid artery vasodilatation might prove to be an alternative haemodynamic risk factor that predisposes to acute mountain sickness.
AbstractThe aim of the present study was to determine the extent to which hypoxia‐induced changes in the peripheral and central respiratory chemoreflex modulate anterior and posterior cerebral blood flow (CBF) and oxygen delivery (CDO2), with corresponding implications for the pathophysiology of the neurological syndrome, acute mountain sickness (AMS). Eight healthy men were randomly assigned single blind to 7 h of passive exposure to both normoxia (21% O2) and hypoxia (12% O2). The peripheral and central respiratory chemoreflex, internal carotid artery, external carotid artery (ECA) and vertebral artery blood flow (duplex ultrasound) and AMS scores (questionnaires) were measured throughout. A reduction in internal carotid artery CDO2 was observed during hypoxia despite a compensatory elevation in perfusion. In contrast, vertebral artery and ECA CDO2 were preserved, and the former was attributable to a more marked increase in perfusion. Hypoxia was associated with progressive activation of the peripheral respiratory chemoreflex (P < 0.001), whereas the central respiratory chemoreflex remained unchanged (P > 0.05). Symptom severity in participants who developed clinical AMS was positively related to ECA blood flow (Lake Louise score, r = 0.546–0.709, P = 0.004–0.043; Environmental Symptoms Questionnaires‐Cerebral symptoms score, r = 0.587–0.771, P = 0.001–0.027, n = 4). Collectively, these findings highlight the site‐specific regulation of CBF in hypoxia that maintains CDO2 selectively in the posterior but not the anterior cerebral circulation, with minimal contribution from the central respiratory chemoreflex. Furthermore, ECA vasodilatation might represent a hitherto unexplored haemodynamic risk factor implicated in the pathophysiology of AMS.