bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of tofacitinib on residual pain in patients with rheumatoid arthritis and psoriatic arthritis
Authors: Dougados Maxime , Taylor Peter C , Bingham Clifton O , Fallon Lara , Brault Yves , Roychoudhury Satrajit , Wang Lisy , Kessouri Meriem 
Published: September 2022

ObjectivePost hoc analysis of pooled data from nine randomised controlled trials to assess the effect of tofacitinib (oral Janus kinase inhibitor for treatment of rheumatoid arthritis (RA) and psoriatic arthritis (PsA)) on residual pain in patients with RA or PsA with abrogated inflammation.MethodsPatients who received ≥1 dose of tofacitinib 5 mg twice daily, adalimumab or placebo with/without background conventional synthetic disease-modifying antirheumatic drugs and had abrogated inflammation (swollen joint count (SJC)=0 and C reactive protein (CRP)<6 mg/L) after 3 months’ therapy were included. Assessments included Patient’s Assessment of Arthritis Pain at month 3 (Visual Analogue Scale [VAS] 0–100 mm). Scores were summarised descriptively; treatment comparisons assessed by Bayesian network meta-analyses (BNMA).ResultsFrom the total population with RA/PsA, 14.9% (382 of 2568), 17.1% (118 of 691) and 5.5% (50 of 909) of patients receiving tofacitinib, adalimumab and placebo, respectively, had abrogated inflammation after 3 months’ therapy. Patients with RA/PsA with abrogated inflammation receiving tofacitinib/adalimumab had higher baseline CRP versus placebo; patients with RA receiving tofacitinib/adalimumab had lower SJC and longer disease duration versus placebo. Median residual pain (VAS) at month 3 was 17.0, 19.0 and 33.5 in patients with RA treated with tofacitinib, adalimumab or placebo, and 24.0, 21.0 and 27.0 in patients with PsA, respectively. Residual pain reductions with tofacitinib/adalimumab versus placebo were less prominent in patients with PsA versus patients with RA, with no significant differences between tofacitinib/adalimumab, per BNMA.ConclusionPatients with RA/PsA with abrogated inflammation receiving tofacitinib/adalimumab had greater residual pain reduction versus placebo at month 3. Results were similar between tofacitinib and adalimumab.Trial registration numberClinicalTrials.gov registry (NCT00960440;NCT00847613;NCT00814307;NCT00856544;NCT00853385;NCT01039688;NCT02187055;NCT01877668;NCT01882439).
The generalized fractional NU method for the diatomic molecules in the Deng–Fan model
Authors: Abu-Shady M. , Khokha E. M. , Abdel-Karim T. A. 
Published: September 2022

AbstractA solution of the fractionalN-dimensional radial Schrödinger equation (SE) with the Deng–Fan potential (DFP) is investigated by the generalized fractional Nikiforov–Uvarov (NU) method. The analytical formulas of energy eigenvalues and corresponding eigenfunctions for the DFP are generated. Furthermore, the current results are applied to several diatomic molecules (DMs) for the DFP as well as the shifted Deng–Fan potential (SDFP). For both the DFP and its shifted potential, the effect of the fractional parameter ($${\delta }$$δ) on the energy levels of various DMs is examined numerically and graphically. We found that the energy eigenvalues are gradually improved when the fractional parameter increases. The energy spectra of various DMs are also evaluated in three-dimensional space and higher dimensions. It is worthy to note that the energy spectrum raises as the number of dimensions increases. In addition, the dependence of the energy spectra of the DFP and its shifted potential on the reduced mass, screening parameter, equilibrium bond length and rotational and vibrational quantum numbers is illustrated. To validate our findings, the energy levels of the DFP and SDFP are estimated at the classical case ($${\delta =1}$$δ=1) for various DMs and found that they are entirely compatible with earlier studies.Graphical abstractIn this study, a new algorithm of the generalized fractional Nikiforov–Uvarov method is employed to obtain new solutions to the fractional N-dimensional radial Schrödinger equation with the Deng–Fan potential. In addition, the results are applied to several diatomic molecules. The impact of the fractional parameter on the energy levels of various diatomic molecules is investigated. We found that the energy of the diatomic molecule is more bounded at lower fractional parameter values than in the classical case.
A New View of Activating Mutations in Cancer
Authors: Nussinov Ruth , Tsai Chung-Jung , Jang Hyunbum 
Published: September 2022

AbstractA vast effort has been invested in the identification of driver mutations of cancer. However, recent studies and observations call into question whether the activating mutations or the signal strength are the major determinant of tumor development. The data argue that signal strength determines cell fate, not the mutation that initiated it. In addition to activating mutations, factors that can impact signaling strength include (i) homeostatic mechanisms that can block or enhance the signal, (ii) the types and locations of additional mutations, and (iii) the expression levels of specific isoforms of genes and regulators of proteins in the pathway. Because signal levels are largely decided by chromatin structure, they vary across cell types, states, and time windows. A strong activating mutation can be restricted by low expression, whereas a weaker mutation can be strengthened by high expression. Strong signals can be associated with cell proliferation, but too strong a signal may result in oncogene-induced senescence. Beyond cancer, moderate signal strength in embryonic neural cells may be associated with neurodevelopmental disorders, and moderate signals in aging may be associated with neurodegenerative diseases, like Alzheimer's disease. The challenge for improving patient outcomes therefore lies in determining signaling thresholds and predicting signal strength.
Swimming Exercise Alleviates Endothelial Mitochondrial Fragmentation via Inhibiting Dynamin-Related Protein-1 to Improve Vascular Function in Hypertension
Authors: Li Guohua , Xu Ke , Xing Wenjuan , Yang Hongyan , Li Youyou , Wang Xinpei , Zhou Jiaheng , An Jiong , Dong Ling , Zhang Xing , Wang Li , Li Jia , Gao Feng 
Published: September 2022

BACKGROUND:
Regular exercise has been recommended clinically for all individuals to protect against hypertension but the underlying mechanisms are not fully elucidated. We recently found a significant mitochondrial fragmentation in the vascular endothelium of hypertensive human subjects. In this study, we investigated whether exercise could restore endothelial mitochondrial dynamics and thus improve vascular function in hypertension.

METHODS:
Vascular endothelial mitochondrial morphological alterations were examined in patients with hypertension and hypertensive animal models. Furthermore, swimming exercise-induced endothelial mitochondrial dynamics and vascular function changes were investigated in spontaneously hypertensive rats (SHRs).

RESULTS:
Mitochondrial fragmentation with an elevated mitochondrial fission mediator Drp1 (dynamin-related protein-1) was observed in the mesenteric artery endothelium from hypertensive patients. A similar mitochondrial fragmentation with increased Drp1 expression were exhibited in the aortic endothelium of angiotensin II-induced hypertensive mice and SHRs. Interestingly, swimming exercise significantly reduced vascular Drp1 expression and alleviated endothelial mitochondrial fragmentation, thus improving blood pressure in SHRs. In cultured endothelial cells, angiotensin II exposure induced Drp1 upregulation, mitochondrial fragmentation and dysfunction, and reduced nitric oxide production, which was blunted by Drp1 genetic reduction or its inhibitor Mdivi-1. Mdivi-1 administration also ameliorated endothelial mitochondrial fragmentation, vascular dysfunction and blood pressure elevation in SHRs while swimming exercise plus Mdivi-1 treatment provided no additional benefits, suggesting that Drp1 inhibition may partially contribute to swimming exercise-conferred anti-hypertensive effects.

CONCLUSIONS:
These findings suggest that swimming exercise alleviates endothelial mitochondrial fragmentation via inhibiting Drp1, which may contribute to exercise-induced improvement of vascular function and blood pressure in hypertension.
Mineralocorticoid Receptor Antagonism by Finerenone Attenuates Established Pulmonary Hypertension in Rats
Authors: Tu Ly , Thuillet Raphaël , Perrot Julie , Ottaviani Mina , Ponsardin Emy , Kolkhof Peter , Humbert Marc , Viengchareun Say , Lombès Marc , Guignabert Christophe 
Published: September 2022

Background:
We studied the ability of the nonsteroidal MR (mineralocorticoid receptor) antagonist finerenone to attenuate vascular remodeling and pulmonary hypertension using two complementary preclinical models (the monocrotaline and sugen/hypoxia rat models) of severe pulmonary hypertension.

Methods:
We first examined the distribution pattern of MR in the lungs of patients with pulmonary arterial hypertension (PAH) and in monocrotaline and sugen/hypoxia rat lungs. Subsequent studies were performed to explore the effect of MR inhibition on proliferation of pulmonary artery smooth muscle cells derived from patients with idiopathic PAH. To validate the functional importance of MR activation in the pulmonary vascular remodeling characteristic of pulmonary hypertension, mice overexpressing human MR (hMR+) were studied, and curative treatments with finerenone (1 mg/kg per day by gavage), started 2 weeks after monocrotaline injection or 5 weeks after Sugen injection were realized.

Results:
We demonstrated that MR is overexpressed in experimental and human PAH and that its inhibition following small interfering RNA-mediated MR silencing or finerenone treatment attenuates proliferation of pulmonary artery smooth muscle cells derived from patients with idiopathic PAH. In addition, we obtained evidence that hMR+ mice display increased right ventricular systolic pressure, right ventricular hypertrophy, and remodeling of pulmonary arterioles. Consistent with these observations, curative treatments with finerenone partially reversed established pulmonary hypertension, reducing total pulmonary vascular resistance and vascular remodeling. Finally, we found that continued finerenone treatment decreases inflammatory cell infiltration and vascular cell proliferation in monocrotaline and sugen/hypoxia rat lungs.

Conclusions:
Finerenone treatment appears to be a potential therapy for PAH worthy of investigation and evaluation for clinical use in conjunction with current PAH treatments.
Blood Pressure Fluctuation During Hospitalization and Clinical Outcomes Within 3 Months After Ischemic Stroke
Authors: Wang Ruirui , Liu Yang , Yang Pinni , Zhu Zhengbao , Shi Mengyao , Peng Yanbo , Zhong Chongke , Wang Aili , Xu Tan , Peng Hao , Xu Tian , Chen Jing , Zhang Yonghong , He Jiang 
Published: September 2022

BACKGROUND:
Increased blood pressure (BP) variability is positively associated with the risks of cerebral small-vessel disease, cardiovascular events and death. However, no large clinical trials have been published to demonstrate the effect of BP fluctuations during hospitalization on clinical outcomes after ischemic stroke.

METHODS:
A total of 3972 patients with acute ischemic stroke from 26 participating hospitals were included in this study, and BP fluctuations were calculated using BP data collected during the hospitalization. The primary outcome was composite outcome of death or major disability (modified Rankin Scale score ≥3) within 3 months and secondary outcomes included death, vascular events, and composite outcomes (death or vascular events).

RESULTS:

Compared with the lowest quartile of systolic BP fluctuations, the adjusted odds ratio associated with the highest quartile was 1.33 ([95% CI, 1.05–1.68];
P
trend
=0.011) for primary outcome; the adjusted hazard ratios were 2.89 ([95% CI, 1.58–5.32];
P
trend
<0.001) for death, 1.48 ([95% CI, 0.83–2.65];
P
trend
=0.071) for vascular events, and 2.06 ([95% CI, 1.32–3.23];
P
trend
<0.001) for composite outcome. Similar results were found for diastolic BP. Multivariable adjusted restricted cubic spline analysis showed a linear relationship between systolic BP fluctuations and the primary outcome (
P
for linearity=0.0009).

CONCLUSIONS:
Larger BP fluctuations during hospitalization were associated with an increased risk of adverse outcomes at 3 months after ischemic stroke onset, independent of mean BP. These findings suggested that BP fluctuation should be a risk factor of adverse outcomes after ischemic stroke, which provided a new insight for BP management strategy.
Smartphone Application-Assisted Home Blood Pressure Monitoring Compared With Office and Ambulatory Blood Pressure Monitoring in Patients With Hypertension: the AMUSE-BP Study
Authors: Groenland Eline H. , Vendeville Jean-Paul A.C. , Bemelmans Remy H.H. , Monajemi Houshang , Bots Michiel L. , Visseren Frank L.J. , Spiering Wilko 
Published: September 2022

Background:
The development of automated, smartphone application (app)-assisted home blood pressure monitoring (HBPM) allows for standardized measurement of blood pressure (BP) at home. The aim of this study was to evaluate the (diagnostic) agreement between app-assisted HBPM, automated office BP (OBP), and the reference standard 24-hour ambulatory BP monitoring (ABPM).

Methods:
In this open randomized 5-way cross-over study, patients diagnosed with hypertension were randomized to one of 10 clusters, each containing 5 BP measurement methods (ABPM, HBPM, attended OBP, unattended OBP, and unattended 30-minute BP) in different order.

Results:
In total, 113 patients were included. The average 24-hour ABPM was 126±11/73±8 mm Hg compared with 141±14/82±10 mm Hg with app-assisted HBPM, 134±13/80±9 mm Hg with unattended 30-minute BP, 137±16/81±11 mm Hg with attended OBP, and 135±15/81±10 mm Hg with unattended OBP monitoring. Diagnostic agreement between app-assisted HBPM and 24-hour ABPM for diagnosing sustained (OBP >140/90 mm Hg and ABPM ≥130/80 mm Hg or HBPM ≥135/85 mm Hg), white-coat (OBP ≥140/90 mm Hg and ABPM <130/80 mm Hg or HBPM <135/85 mm Hg), and masked hypertension (OBP <140/90 mm Hg and ABPM ≥130/80 mm Hg or HBPM ≥135/85 mm Hg) was fair-to-moderate (κ statistics ranging from 0.34 to 0.40). App-assisted HBPM had high sensitivities (78%–91%) and negative predictive values (90%–97%) for diagnosing sustained and masked hypertension.

Conclusions:
This study showed a considerable (diagnostic) disagreement between app-assisted HBPM and ABPM. App-assisted HBPM had high sensitivity in the diagnosis of sustained and masked hypertension and may therefore be used as complementary to, but not a replacement of, ABPM.
High HDL (High-Density Lipoprotein) Cholesterol Increases Cardiovascular Risk in Hypertensive Patients
Authors: Trimarco Valentina , Izzo Raffaele , Morisco Carmine , Mone Pasquale , Virginia Manzi Maria , Falco Angela , Pacella Daniela , Gallo Paola , Lembo Maria , Santulli Gaetano , Trimarco Bruno 
Published: September 2022

Background:
Emerging evidence suggests that elevated circulating levels of HDL-C (high-density lipoprotein cholesterol) could be linked to an increased mortality risk. However, to the best of our knowledge, the relationship between HDL-C and specific cardiovascular events has never been investigated in patients with hypertension.

Methods:
To fill this knowledge gap, we analyzed the relationship between HDL-C levels and cardiovascular events in hypertensive patients within the Campania Salute Network in Southern Italy.

Results:
We studied 11 987 patients with hypertension, who were followed for 25 534 person-years. Our population was divided in 3 groups according to the HDL-C plasma levels: HDL-C<40 mg/dL (low HDL-C); HDL-C between 40 and 80 mg/dL (medium HDL-C); and HDL-C>80 mg/dL (high HDL-C). At the follow-up analysis, adjusting for potential confounders, we observed a total of 245 cardiovascular events with a significantly increased risk of cardiovascular events in the low HDL-C group and in the high HDL-C arm compared with the medium HDL-C group. The spline analysis revealed a nonlinear U-shaped association between HDL-C levels and cardiovascular outcomes. Interestingly, the increased cardiovascular risk associated with high HDL-C was not confirmed in female patients.

Conclusions:
Our data demonstrate that there is a U-shaped association between HDL-C and the risk of cardiovascular events in male patients with hypertension.
Neural Basis of the Implicit Learning of Complex Artificial Grammar with Nonadjacent Dependencies
Authors: Ling Xiaoli , Sun Peng , Zhao Lu , Jiang Shan , Lu Yang , Cheng Xuemei , Guo Xiuyan , Zhu Xia , Zheng Li 
Published: September 2022

Abstract
The capacity for the implicit learning/processing of complex grammar with nonadjacent dependencies is an important feature of human language learning. In this fMRI study, using an implicit AGL paradigm, we explored the neural basis of the implicit learning of the nonadjacent dependency rule, disentangling from sequence-based chunk knowledge (i.e., local sequential regularities or substring) by focusing on the low chunk strength items (which were naturally less similar to training strings), based on tracking neural responses during training and test phases. After listening to and memorizing a series of strings of 10 syllables generated from nonadjacent artificial grammar in the training phase, participants implicitly acquired the knowledge of grammar and chunks. Regarding grammaticality, Broca's area was specifically related to low chunk strength grammatical strings relative to nongrammatical strings in the test phase. This region showed decreased activity with time in the training phase, and a lesser decrease in activity was associated with higher performance in grammar learning. Furthermore, Broca's area showed significantly higher strength of functional connectivity with the left superior temporal gyrus in the low chunk strength grammatical string compared with nongrammatical strings, and this functional connectivity increased with the training time. For the chunks, the performance of accurate discrimination of high chunk strength from low chunk strength nongrammatical strings was predicted by hippocampal activity in the training phase. Converging evidence from the training and test phases showed that Broca's area and its functional connectivity with the left superior temporal gyrus were engaged in the implicit learning/processing of the nonadjacent dependency rule, separating the effects of chunks.
Dissociation of Writing Processes: A Functional Magnetic Resonance Imaging Study on the Neural Substrates for the Handwritten Production of Chinese Characters
Authors: He Jieying , Brehm Laurel , Zhang Qingfang 
Published: September 2022

Abstract
Writing is an important way to communicate in everyday life because it can convey information over time and space, but its neural substrates remain poorly known. Although the neural basis of written language production has been investigated in alphabetic scripts, it has rarely been examined in nonalphabetic languages such as Chinese. The present functional magnetic resonance imaging study explored the neural substrates of handwritten word production in Chinese and identified the brain regions sensitive to the psycholinguistic factors of word frequency and syllable frequency. To capture this, we contrasted neural activation in “writing” with “speaking plus drawing” and “watching plus drawing.” Word frequency (high, low) and syllable frequency (high, low) of the picture names were manipulated. Contrasts between the tasks showed that writing Chinese characters was mainly associated with brain activation in the left frontal and parietal cortex, whereas orthographic processing and the motor procedures necessary for handwritten production were also related to activation in the right frontal and parietal cortex as well as right putamen/thalamus. These results demonstrate that writing Chinese characters requires activation in bilateral cortical regions and the right putamen/thalamus. Our results also revealed no brain activation associated with the main effects of word frequency and syllable frequency as well as their interaction, which implies that word frequency and syllable frequency may not affect the writing of Chinese characters on a neural level.
Assessing the importance of artificial canopy bridge design for Costa Rican monkeys in an experimental setting
Authors: Narváez-Rivera Giselle M. , Lindshield Stacy M. 
Published: September 2022

Abstract
Although artificial crossing structures are increasingly implemented by conservationists and wildlife managers to connect fragmented wildlife habitat, the study of artificial crossing structure design, particularly of canopy bridges, is an emerging field of study in primatology. We address this issue by evaluating five competing bridge models with varying width, material stiffness, and substrate spacing. We assessed bridge preference and performance by sampling the behavior of three species of Costa Rican monkeys (Alouatta palliata: n = 4, Ateles geoffroyi: n = 3, Cebus imitator: n = 3). In a semi-wild setting, we used focal individual sampling with instantaneous recording once every minute for ten-minute intervals and all occurrences sampling whenever study subjects used the bridge. We hypothesized that monkeys prefer bridges that are more stable, and that are made of materials that resemble tree branches. During nearly 37 sampling hours we observed 119 crossing events. We found that study subjects prefer bridge models that are built using more rigid materials, such as the bamboo pole bridge, or wider bridges that offer more stability than narrower bridges. The bridge type and the materials used to build the bridges are both significant predictors of bridge use. While preference for bridges and their performance varies by species, the bamboo pole bridge model and the horizontal mesh bridge were preferred and performed best in our study. The simple liana bridge model was the least preferred by all species and performed poorly in comparison to the other models. Our findings will help us better understand how design and materials impact the use of canopy bridges by monkeys, which can help improve biological corridors and offer new information for the management and conservation of primates living near infrastructure corridors and other kinds of dangerous matrix.
Aristotle’s Account of the Immobility of Place: A Cold Case
Authors: Quarantotto Diana 
Published: September 2022

Abstract
At least since the Neoplatonic commentators, Aristotle’s thesis that place is immobile has been considered a serious problem for his theory of place and locomotion. This diagnosis, however, is essentially based on a single passage (212a14–21)—the famous passage on the boat moving in a river—which interpreters find both central and obscure or imprecise, and which has so far resisted a literal reading. I tackle this issue by considering texts hitherto neglected by scholars and propose a new and charitable interpretation, showing the consistency of Aristotle’s thesis of the immobility of place with his general theory of change, as well as a fresh reading of ll. 212a14–21 that stays close to the text. Further, I argue that there are good reasons to believe that the interpretation I put forward is the most ancient one.