bluuebunny/crossref_metadata_2025_split huggingface dataset:
Moderate‐intensity aerobic training reduces cardiac damage attributable to experimental iron overload in rats
Authors: Ávila Renata Andrade , Rossi Emilly Martinelli , de Carvalho Guilherme Mendes , Krause Maiara , Leopoldo André Soares , Carneiro Maria Tereza W. D. , dos Santos Leonardo 
Published: June 2021

New Findings
What is the central question of this study?
The current literature indicates that oxidative stress plays a major role in iron overload. Although exercise is a well‐established approach to treat/prevent cardiovascular diseases, its effects on iron overload are not known.

What is the main finding and its importance?
Moderate‐intensity aerobic training had benefits in a rodent model of iron‐overload cardiomyopathy by improving the antioxidant capacity of the heart. After further confirmation by translational and clinical studies, we should consider using this non‐pharmacological, highly accessible and easily executable adjuvant approach allied to other therapies to improve the quality of life of iron‐overloaded patients.

AbstractIron is an essential micronutrient for several life processes, but its excess can damage organs owing to oxidative stress, with cardiomyopathy being the leading cause of death in iron‐overloaded patients. Although exercise has long been considered as a cardioprotective tool, its effects on iron overload are not known. This study was designed to investigate the effects of moderate‐intensity aerobic training in rats previously submitted to chronic iron overload. Wistar rats received i.p. injections of iron dextran (100 mg/kg, 5 days/week for 4 weeks); thereafter, the rats were kept sedentary or exercised (60 min/day, progressive aerobic training, 60–70% of maximal speed, 5 days/week on a treadmill) for 8 weeks. At the end of the experimental period, haemodynamics were recorded and blood samples, livers and hearts harvested. Myocardial mechanics of papillary muscles were assessed in vitro, and cardiac remodelling was evaluated by histology and immunoblotting. Iron overload led to liver iron deposition, liver fibrosis and increased serum alanine aminotransferase and aspartate aminotransferase. Moreover, cardiac iron accumulation was accompanied by impaired myocardial mechanics, increased cardiac collagen type I and lipid peroxidation (TBARS), and release of creatine phosphokinase‐MB to the serum. Although exercise did not influence iron levels, tissue injury markers were significantly reduced. Likewise, myocardial contractility and inotropic responsiveness were improved in exercised rats, in association with an increase in the endogenous antioxidant enzyme catalase. In conclusion, moderate‐intensity aerobic exercise was associated with attenuated oxidative stress and cardiac damage in a rodent model of iron overload, thereby suggesting its potential role as a non‐pharmacological adjuvant therapy for iron‐overload cardiomyopathy.
Muscarinic regulation of the neuronal Na+/K+‐ATPase in rat hippocampus
Authors: Mohan Sandesh , Tiwari Manindra Nath , Stanojević Marija , Biala Yoav , Yaari Yoel 
Published: June 2021

Key points
Stimulation of postsynaptic muscarinic receptors was shown to excite principal hippocampal neurons by modulating several membrane ion conductances.
We show here that activation of postsynaptic muscarinic receptors also causes neuronal excitation by inhibiting Na+/K+‐ATPase activity.
Muscarinic Na+/K+‐ATPase inhibition is mediated by two separate signalling pathways that lead downstream to enhanced Na+/K+‐ATPase phosphorylation by activating protein kinase C and protein kinase G.
Muscarinic excitation through Na+/K+‐ATPase inhibition is probably involved in cholinergic modulation of hippocampal activity and may turn out to be a widespread mechanism of neuronal excitation in the brain.
AbstractStimulation of muscarinic cholinergic receptors on principal hippocampal neurons enhances intrinsic neuronal excitability by modulating several membrane ion conductances. The electrogenic Na+/K+‐ATPase (NKA; the ‘Na+ pump’) is a ubiquitous regulator of intrinsic neuronal excitability, generating a hyperpolarizing current to thwart excessive neuronal firing. Using electrophysiological and pharmacological methodologies in rat hippocampal slices, we show that neuronal NKA pumping activity is also subjected to cholinergic regulation. Stimulation of postsynaptic muscarinic, but not nicotinic, cholinergic receptors activates membrane‐bound phospholipase C and hydrolysis of membrane‐integral phosphatidylinositol 4,5‐bisphosphate into diacylglycerol (DAG) and inositol 1,4,5‐triphosphate (IP3). Along one signalling pathway, DAG activates protein kinase C (PKC). Along a second signalling pathway, IP3 causes Ca2+ release from the endoplasmic reticulum, facilitating nitric oxide (NO) production. The rise in NO levels stimulates cGMP synthesis by guanylate‐cyclase, activating protein kinase G (PKG). The two pathways converge to cause partial NKA inhibition through enzyme phosphorylation by PKC and PKG, leading to a marked increase in intrinsic neuronal excitability. This novel mechanism of neuronal NKA regulation probably contributes to the cholinergic modulation of hippocampal activity in spatial navigation, learning and memory.
Development of 3D Cerebral Aggregates in the Brain Ventricles of Adult Mice
Authors: Sukhinich K. K. , Shakirova K. M. , Dashinimaev E. B. , Aleksandrova M. A. 
Published: June 2021

Abstract
The cerebral organoids are three-dimensional cell cultures formed from brain-specific cell types arising from embryonic or pluripotent stem cells. Organoids provide an opportunity to study the early stages of brain development and diseases of the central nervous system. However, the modeling of organoids is associated with a number of unsolved problems. Organoid production techniques involve a complex cell culture process that requires special media, growth factors, and often the use of a bioreactor. Even under standardized conditions, structures of different morphology are formed: from disorganized cell aggregates to structured minibrains, which are selected for study. For natural reasons, organoids grown in vitro do not have a blood supply, which limits their development. We tried to obtain cerebral aggregates similar to organoids in an in vivo model, where vascular growth and tissue blood supply are provided, for which we transplanted a cell suspension from the mouse embryonic neocortex into the lateral ventricles of the brain of adult mice. Therefore, the medium for cultivation was the cerebrospinal fluid, and the lateral ventricles of the brain, where it circulates, served as a bioreactor. The results showed that the neocortex from E14.5 is a suitable source of stem/progenitor cells that self-assemble into three-dimensional aggregates and vascularized in vivo. The aggregates consisted of a central layer of mature neurons, the marginal zone free of cells and a glia limitans, which resembled cerebral organoids. Thus, the lateral ventricles of the adult mouse brain can be used to obtain vascularized cell aggregates resembling cerebral organoids.
Off-tumor IDO1 target engagements determine the cancer-immune set point and predict the immunotherapeutic efficacy
Authors: Xie Lin , Hu Kuan , Duo Yanhong , Shimokawa Takashi , Kumata Katsushi , Zhang Yiding , Jiang Cuiping , Zhang Lulu , Nengaki Nobuki , Wakizaka Hidekatsu , Cao Yihai , Zhang Ming-Rong 
Published: June 2021

BackgroundIndoleamine-2,3-dioxygenase 1 (IDO1) has been intensively pursued as a therapeutic target to reverse the immunosuppressive cancer-immune milieu and promote tumor elimination. However, recent failures of phase III clinical trials with IDO1 inhibitors involved in cancer immunotherapies highlight the urgent need to develop appropriate methods for tracking IDO1 when the cancer-immune milieu is therapeutically modified.MethodsWe utilized a small-molecule radiotracer, 11C-l-1MTrp, to quantitatively and longitudinally visualize whole-body IDO1 dynamics. Specifically, we first assessed 11C-l-1MTrp in mice-bearing contralateral human tumors with distinct IDO1 expression patterns. Then, we applied 11C-l-1MTrp to longitudinally monitor whole-body IDO1 variations in immunocompetent melanoma-bearing mice treated with 1-methyl-l-tryptophan plus either chemotherapeutic drugs or antibodies targeting programmedcell death 1 and cytotoxic T-lymphocyte-associated protein 4.Results11C-l-1MTrp positron emission tomography (PET) imaging accurately delineated IDO1 expression in xenograft mouse models. Moreover, we were able to visualize dynamic IDO1 regulation in the mesenteric lymph nodes (MLNs), an off-tumor IDO1 target, where the percentage uptake of 11C-l-1MTrp accurately annotated the therapeutic efficacy of multiple combination immunotherapies in preclinical models. Remarkably, 11C-l-1MTrp signal intensity in the MLNs was inversely related to the specific growth rates of treated tumors, suggesting that IDO1 expression in the MLNs can serve as a new biomarker of the cancer-immune set point.ConclusionsPET imaging of IDO1 with 11C-l-1MTrp is a robust method to assess the therapeutic efficacy of multiple combinatorial immunotherapies, improving our understanding of the merit and challenges of IDO1 regimens. Further validation of this animal data in humans is ongoing. We envision that our results will provide a potential precision medicine paradigm for noninvasive visualizing each patient’s individual response in combinatorial cancer immunotherapy, and tailoring optimal personalized combination strategies.
Regularization ambiguity and van der Waals black hole in 2 + 1 dimensions
Authors: Gaete Patricio , Nicolini Piero , Spallucci Euro 
Published: June 2021

AbstractCharged black holes in a ($$2+1$$

2
+
1

)-dimensional anti-de Sitter space-time suffer from some limitations such as the ambiguity in the definition of the mass and the bad short distance behavior. In this paper we present a way to resolve such issues. By extending the parameter space of the BTZ geometry, we properly identify the integration constants in order to remove the conical singularity sitting at the origin. In such a way we obtain a well defined Minkowski limit and horizons also in the case of de Sitter background space. On the thermodynamic side, we obtain a proper internal energy, by invoking the consistency with the Area Law, even if the mass parameter does not appear in the metric coefficients. As a further improvement, we show that it is sufficient to assume a finite size of the electric charge to obtain a short scale regular geometry. The resulting solution, generalizing the charged BTZ metric, is dual to a van der Waals gas.
Anisotropic generalization of Buchdahl bound for specific stellar models
Authors: Sharma Ranjan , Ghosh Arpita , Bhattacharya Soumik , Das Shyam 
Published: June 2021

AbstractAnisotropy is one factor that appears to be significantly important in the studies of relativistic compact stars. In this paper, we make a generalization of the Buchdahl limit by incorporating an anisotropic effect for a selected class of exact solutions describing anisotropic stellar objects. In the isotropic case of a homogeneous distribution, we regain the Buchdahl limit $$2M/R \le 8/9$$

2
M
/
R
≤
8
/
9

. Our investigation shows a direct link between the maximum allowed compactness and pressure anisotropy vi-a-vis geometry of the associated 3-space.
Investigation on the New Physics effects of the vector leptoquark on semileptonic $$\bar{B}^*\rightarrow V \tau ^-\bar{\nu _{\tau }}$$ decays
Authors: Sheng Jin-Huan , Zhu Jie , Hu Quan-Yi 
Published: June 2021

AbstractIn recent years, the experimental results about the ratio of the branching ratios $$R_{D^{(*)}}$$

R

D

(

∗
)

and $$R_{K^{(*)}}$$

R

K

(

∗
)

, which are in the semileptonic $$b\rightarrow c l \bar{\nu }_{l}$$

b
→
c
l

ν

¯

l

and $$b\rightarrow s l^+l^-$$

b
→
s

l
+

l
-

decays, have been observed to deviate from the Standard Model prediction by $$1.4\sigma $$

1.4
σ

, $$2.5\sigma $$

2.5
σ

, $$2.4\sigma $$

2.4
σ

and $$2.2\sigma $$

2.2
σ

respectively. Motivated by these anomalies and by the abundant $$B^*$$

B
∗

data samples, we investigate possible New Physics effects of the vector leptoquark in the semileptonic decay $$\bar{B}^*_{u,d,s,c} \rightarrow V \tau ^-\bar{\nu }_{\tau }$$

B

¯

u
,
d
,
s
,
c

∗

→
V

τ
-

ν

¯

τ

($$V=D^*_{u,d,s},J/\psi $$

V
=

D

u
,
d
,
s

∗

,
J
/
ψ

). which is induced by $$b\rightarrow c \tau ^-\bar{\nu }_{\tau }$$

b
→
c

τ
-

ν

¯

τ

at the quark level. Using the best fit solutions for the new operator Wilson coefficients and the relevant form factors which are obtained in the light-front quark model, we find that (i) the contributions of the vector leptoquark to $$d{\varGamma }^{(L)}/dq^2(\bar{B}^*_{u,d,s,c} \rightarrow V \tau ^-\bar{\nu }_{\tau })$$

d

Γ

(
L
)

/
d

q
2

(

B

¯

u
,
d
,
s
,
c

∗

→
V

τ
-

ν

¯

τ

)

and $$R^{*(L)}_{V}(q^2)$$

R
V

∗
(
L
)

(

q
2

)

to be significant; (ii) the two best fit solutions in the vector leptoquark are indistinguishable from each other and give similar amounts of enhancements to these two observables; (iii) both two cases of the vector leptoquark give nearly same results as those of the Standard Model for $$A_{FB}^{\tau }(q^2)$$

A

FB

τ

(

q
2

)

, $$P_{\tau }(q^2)$$

P
τ

(

q
2

)

and $$F_{L}^{*V}(q^2)$$

F

L

∗
V

(

q
2

)

. We hope that the numerical results in this work will be tested in the future high energy experiments.
Anisotropic power-law inflation for a model of two scalar and two vector fields
Authors: Do Tuan Q. , Kao W. F. 
Published: June 2021

AbstractInspired by an interesting counterexample to the cosmic no-hair conjecture found in a supergravity-motivated model recently, we propose a multi-field extension, in which two scalar fields are allowed to non-minimally couple to two vector fields, respectively. This model is shown to admit an exact Bianchi type I power-law solution. Furthermore, stability analysis based on the dynamical system method is performed to show that this anisotropic solution is indeed stable and attractive if both scalar fields are canonical. Nevertheless, if one of the two scalar fields is phantom then the corresponding anisotropic power-law inflation turns unstable as expected.
Design Space Exploration of Matrix–Matrix Convolution Operation
Authors: Behera Piyalee , Deb Arighna 
Published: June 2021

Convolution is an important operation in neural networks which, in recent years, received significant attention from the researchers thanks to its ability to handle complex tasks such as image processing, computer vision in an efficient manner. In general, the convolution operation in neural networks considers two matrices as inputs: an image matrix representing an image and a kernel matrix required for necessary image processing operation and performs several multiplications and addition operations among the elements of image and kernel matrices. Realizing a circuit structure for matrix–matrix convolution is straightforward as each multiplication is realized by a multiplier, whereas an addition is carried out by an adder. However, the corresponding circuits result in large area, high power consumption and long delay because of the large number of multiplications and additions that are involved in the matrix–matrix convolution operations. While, the existing approaches focus on the accelerations of this computationally intensive tasks, they often do not guarantee minimality of area, power and delay. But we show that there exists design aspects through which the circuit structures for convolution operations can be realized with less area, power and delay. To do this, we consider the kernel definitions during the design of the circuit structures since the kernel matrices are often (pre)-determined based on the desired applications. Motivated by this, we first explore the design space of the convolution operation by introducing an alternative design scheme for realizing the respective operation between two matrices keeping the image processing/neural network applications in mind. Experimental evaluations confirm the potential benefits of the proposed design scheme and demonstrate that the reductions in the area and power by approximately [Formula: see text] and critical path delay by approximately [Formula: see text] can be achieved using the proposed design scheme. In addition, the FPGA implementations of the proposed scheme also show that the reductions of approximately [Formula: see text] and [Formula: see text] in the number of LUTs and in the number of pins, respectively, can be achieved. Compared to prior works, the proposed scheme allows higher parallelism with minimum LUT utilization.
Work-Related Risk Factors for Rotator Cuff Syndrome in a Prospective Study of Manufacturing and Healthcare Workers
Authors: Meyers Alysha R. , Wurzelbacher Steven J. , Krieg Edward F. , Ramsey Jessica G. , Crombie Kenneth , Christianson Annette L. , Luo Lian , Burt Susan 
Published: June 2021

Objective This prospective study assessed the risk of developing rotator cuff syndrome (RCS) with separate or specific combinations of biomechanical exposures measures, controlling for individual confounders. Background Compared with other musculoskeletal disorders, rates of work-related shoulder musculoskeletal disorders have been declining more slowly. Method We conducted up to 2 years of individual, annual assessments of covariates, exposures, and health outcomes for 393 U.S. manufacturing and healthcare workers without RCS at baseline. Task-level biomechanical exposures assessed exposure to forceful exertions (level, exertion rates, duty cycles), vibration, and upper arm postures (flexion, abduction). Hazard ratios (HRs) were calculated with Cox proportional hazard models. Results We observed 39 incident RCS cases in 694 person-years (incidence rate = 5.62 per 100 person-years). Adjusting for confounders, we found increased risk of incident RCS associated with forceful hand exertions per minute for three upper arm posture tertiles: flexion ≥45° (≥28.2% time, HR = 1.11, CI [1.01, 1.22]), abduction ≥30° (11.9–21.2%-time, HR = 1.18, CI [1.04, 1.34]), and abduction >60° (≥4.8% time, HR = 1.16, CI [1.04, 1.29]). We failed to observe statistically significant effects for other interactions or any separate measures of biomechanical exposure. Conclusion This study highlights the importance of assessing combinations of exposure to forceful repetition and upper arm elevation when developing interventions for preventing RCS. Application Based on these results, interventions that reduce exposure to forceful repetition (i.e., lower force levels and/or slower exertion rates) may reduce the risk of RCS, especially when upper arm elevation cannot be avoided.
CGRP release in an experimental human trigeminal pain model
Authors: Frese Achim , Summ Oliver , Evers Stefan 
Published: June 2021

Background Migraine and trigemino-autonomic cephalalgia attacks are associated with an increase of α-calcitonin-gene related peptide levels in the ipsilateral jugular vein. It is however unknown whether trigeminal pain stimulation in healthy subjects without headache disorders also induces increase of calcitonin-gene related peptide levels. Findings We measured α-calcitonin-gene related peptide levels in eight healthy subjects after subcutaneous injection of capsaicin in the forehead and in the mandibular region and after injection of sodium chloride in the forehead. We observed a significant increase of α-calcitonin-gene related peptide level only after injection of capsaicin in the forehead (i.e. first trigeminal branch). We also observed trigemino-autonomic activation (lacrimation, rhinorrhea etc.) only after injection of capsaicin in the forehead. Conclusion Increase of α-calcitonin-gene related peptide levels do not only occur in primary headache attacks but also after experimental trigeminal pain of the first branch. This finding suggests that α-calcitonin-gene related peptide elevation is, at least an additional, unspecific effect of first trigeminal branch stimulation following pain activation and not a specific mechanism of idiopathic headache disorders.
Dysregulation of the peripheral glutamatergic system: A key player in migraine pathogenesis?
Authors: Benbow Tarique , Cairns Brian E 
Published: June 2021

Background Although the role of glutamate in migraine pathogenesis remains uncertain, there has been significant interest in the development of drug candidates that target glutamate receptors. Activation of trigeminovascular afferent fibers is now recognized as a crucial step to the onset of a migraine episode. New evidence suggests a dysfunction in peripheral glutamate regulation may play a role in this process. Objective To provide a narrative review of the role of peripheral glutamate dysfunction in migraine. Method A review of recent literature from neurobiological, pharmacological and genomic studies was conducted to support peripheral glutamate dysfunction as a potential element in migraine pathogenesis. Results Studies in rats suggest that elevated blood glutamate mechanically sensitizes trigeminal afferent fibers and stimulates the release of calcitonin-gene related peptide and other neuropeptides to promote and maintain neurogenic inflammation. These effects may be driven by upregulation of glutamate receptors, and modifications to reuptake and metabolic pathways of glutamate. Furthermore, genome wide association studies have found polymorphisms in glutamate receptor and transporter genes that are associated with migraine. Conclusion The role of peripheral glutamate signalling in the onset and maintenance of migraine is not completely elucidated and future studies are still needed to confirm its role in migraine pathogenesis.