bluuebunny/crossref_metadata_2025 huggingface dataset:
Suspensión condicional de la pena en procedimientos abreviados: ¿Derecho o abuso?
Authors: Zúñiga Brito Marieta de las Nubes , De la Vega Echeverría Edwin Daniel
Published: October 2023

Introducción. La suspensión condicional de la pena es una institución jurídica que permite a una persona condenada por un delito no cumplir la pena de prisión, siempre que cumpla con ciertas condiciones. En el Ecuador, esta figura está regulada por el artículo 74 del Código Orgánico Integral Penal (COIP). En el año 2016, la Corte Nacional de Justicia del Ecuador emitió la Resolución No. 02-2016, en la que resolvió que la suspensión condicional de la pena no es procedente en los casos resueltos mediante procedimiento abreviado. Esta resolución ha sido criticada por algunos sectores, que consideran que vulnera los derechos de las personas condenadas. Objetivo. El objetivo de este trabajo es analizar si la resolución de la Corte Nacional de Justicia vulnera los derechos de las personas condenadas por un delito mediante procedimiento abreviado. Metodología. Para el desarrollo de este trabajo se utilizó un método analítico-sintético, inductivo-deductivo con un enfoque cualitativo. Se realizó una revisión bibliográfica de la normativa y la jurisprudencia aplicable al tema. Resultados. El análisis de la normativa y la jurisprudencia aplicable al tema permite concluir que la resolución de la Corte Nacional de Justicia vulnera los derechos de las personas condenadas por un delito mediante procedimiento abreviado. La suspensión condicional de la pena es un derecho de las personas condenadas, reconocido por la Constitución y los instrumentos internacionales de derechos humanos. Conclusión. La resolución de la Corte Nacional de Justicia vulnera los derechos de las personas condenadas por un delito mediante procedimiento abreviado. Esta resolución debe ser revocada para garantizar el derecho a la reinserción social de estas personas. Área de estudio general: Derecho. Área de estudio específica: Derecho penal y procesal penal.
Aspek Hukum Sertipikat Elektronik Dalam Sistem Pendaftaran Tanah Di Indonesia
Authors: Arrizal Nizam Zakka , Ali Fauzi Muhammad
Published: October 2023

Land is a natural resource that is very important for human life, both directly and indirectly, directly such as being used as a place to live, to grow crops, to as an investment business. The importance of the function of the role of land requires strict regulations governing land use in order to avoid things that deviate. Land certificates are also required as proof of land ownership. Current technological developments make it easier for humans in all their activities, in the land sector now land certificates have undergone a change from what were originally in the form of physical documents to now electronic ones. This study discusses the legal aspects of electronic certificates in the land registration system in Indonesia. The method used is the normative juridical method, namely library law research which is carried out by examining library materials or mere secondary data. The results of the study show that Electronic Land Certificates are certificates issued in the form of electronic documents using an electronic system. The legal policy of mandatory electronic land certificates Land Registration in Indonesia is a regulation issued by the Ministry of ATR/Ka.BPN to improve services in the land sector in order to provide legal certainty and legal protection for owners.
PENDEKATAN DUALISTIK TERHADAP KASUS UJARAN KEBENCIAN BERDASARKAN PANCASILA
Authors: Eviningrum Sulistya
Published: October 2023

Abstract— The spread of hate speech is very dangerous for the life of the Indonesian state, so it must be seriously addressed through legal means. Law enforcement for the prohibition of hate speech must be oriented towards creating a just legal decision. The dominance of a monoistic approach in law enforcement against hate speech is criticized because it is very prone to abuse. A monoistic approach that emphasizes fulfilling the elements of the offense must be evaluated because the main subject being tested or tried in cases of hate speech is utterances or words. Utterances or words have an interpretation, therefore to ascertain whether the perpetrators of hate speech really intend or intentionally spread information that can cause hatred based on Ethnicity, Religion, Race and Intergroup (SARA), the perpetrator's mental attitude when conveying the message. The dualistic approach is important to clearly describe whether the elements of the offense are fulfilled and the perpetrator's actions can be legally justified. The dualistic approach in law enforcement against hate speech is more likely to present justice in accordance with the values ??contained in Pancasila.
Combination of Traditional Chinese and Western Medicine to Improve the Cure Rate of Elderly Patients with Severe Novel Coronavirus Infection
Authors: Rubing Duan , Dongping Rao , Qinxian Chen , Miner Hu , Jianghua Guo , L Liping
Published: October 2023

Objective: To study the curative effect of traditional Chinese and western medicine on novel coronavirus's (COVID-19) patients in Jiangmen Central Hospital. Methods: This study was a retrospective cohort study. A total of 582 cases of COVID-19 patients admitted to Jiangmen Central Hospital from January 2020 to March 31, 2023 were collected, and five indicators, such as cure rate, improvement rate, inefficiency rate, mortality rate and hospitalization time, were analyzed, and the curative effects and treatment days under different treatment methods were compared among the integrated traditional Chinese and western medicine group, the western medicine group and the Chinese medicine group. Results: There was no significant difference in the cure rate, improvement rate, inefficiency rate and mortality rate of ordinary patients of all ages and severe middle and light years (≤65 years old) after treatment with integrated traditional Chinese and western medicine, pure western medicine or pure Chinese medicine (P > 0.05). The cure rate and effective rate of severe elderly patients (> 65 years old) were significantly higher than that of pure western medicine group (P < 0.05) and the ineffective rate was significantly lower than that of western medicine group (P < 0.01). There was no significant difference in improvement rate and mortality (P > 0.05). Except severe young patients (≤40 years old), the treatment time of western medicine group was significantly shorter than that of traditional Chinese medicine group and traditional Chinese and western medicine treatment group (P < 0.05). Conclusion: The combination of traditional Chinese and western medicine can significantly improve the cure rate and effective rate of elderly patients and reduce the inefficiency of their treatment. Compared with Chinese medicine, western medicine has a better effect in shortening hospitalization time.
Towards a New Materialism in Psychedelic Studies
Authors: Oostveen Daan F.
Published: October 2023

We are currently living through a period of ‘psychedelic renaissance’, with an increased interest, both in clinical research and in society at large, in the use of psychedelic substances such as LSD, psylocybin, DMT and mescaline. This interest, however, has recently led to an increased influx of venture capital and a fast emerging psychedelic start-up ecosystem. In this article, I will discuss the metaphysical presuppositions of this psychedelic renaissance, and examine how these constitute the ‘pitfalls’ of a psychedelics ideology. I will argue in favour of a new materialism, by and large inspired by Deleuze and Guattari, as a more suitable metaphysical framework to understand psychedelics. New materialism implies both a monistic as well as a political framework, in which the challenges of cognitive capitalism vis-à-vis the psychedelic renaissance can be framed more accurately.
Psychedelic Crystals in Cinema: Opening Virtual Dimensions and Potential Healing
Authors: Biolchini Erica
Published: October 2023

This article proposes a different aesthetic state of Gilles Deleuze’s crystal-image defined as ‘psychedelic crystal’, a formation of the crystalline regime in light of the contemporary revival of scientific research exploring the healing potentialities of hallucinogenic drugs. The proposition of the psychedelic crystal occurs between Deleuze’s crystals of time, the therapeutic dimension of psychedelics, and Siegfried Kracauer’s concept of redemption (as salvation) through the cinematic medium. What lies in the middle of this encounter is a shared understanding of media – films as media; drugs as media – as holding a curative influence: to resume an affirmative potentiality for life and to restore a belief in the (physical and psychical) world. The film-philosophical dimension of the psychedelic crystal, developed specifically through an engagement with Jan Kounen’s Blueberry (2004) as case study, sees cinema with the potential to reanimate our mental and physical reality, especially when in relation to traumatically repressed, dissociated or repeated memory formations – thus looking at certain film aesthetics as a mind-revealing, mind-expanding and mind-healing technology which can be considered as intrinsically entangled with the current revival of therapeutic practices of psychoactive substances. As a proposition, the psychedelic crystal discloses a potential dimension of the psychedelic frontier of healing which transversally embraces the transdisciplinary gamut of film-philosophy, film theory and psychedelic research.
Tumour-associated macrophages: versatile players in the tumour microenvironment
Authors: Ji Zoey Zeyuan , Chan Max Kam-Kwan , Chan Alex Siu-Wing , Leung Kam-Tong , Jiang Xiaohua , To Ka-Fai , Wu Yi , Tang Patrick Ming-Kuen
Published: October 2023

Tumour-Associated Macrophages (TAMs) are one of the pivotal components of the tumour microenvironment. Their roles in the cancer immunity are complicated, both pro-tumour and anti-cancer activities are reported, including not only angiogenesis, extracellular matrix remodeling, immunosuppression, drug resistance but also phagocytosis and tumour regression. Interestingly, TAMs are highly dynamic and versatile in solid tumours. They show anti-cancer or pro-tumour activities, and interplay between the tumour microenvironment and cancer stem cells and under specific conditions. In addition to the classic M1/M2 phenotypes, a number of novel dedifferentiation phenomena of TAMs are discovered due to the advanced single-cell technology, e.g., macrophage-myofibroblast transition (MMT) and macrophage-neuron transition (MNT). More importantly, emerging information demonstrated the potential of TAMs on cancer immunotherapy, suggesting by the therapeutic efficiency of the checkpoint inhibitors and chimeric antigen receptor engineered cells based on macrophages. Here, we summarized the latest discoveries of TAMs from basic and translational research and discussed their clinical relevance and therapeutic potential for solid cancers.
Locomotor and respiratory muscle abnormalities in HFrEF and HFpEF
Authors: Mangner Norman , Winzer Ephraim B. , Linke Axel , Adams Volker
Published: October 2023

Heart failure (HF) is a chronic and progressive syndrome affecting worldwide billions of patients. Exercise intolerance and early fatigue are hallmarks of HF patients either with a reduced (HFrEF) or a preserved (HFpEF) ejection fraction. Alterations of the skeletal muscle contribute to exercise intolerance in HF. This review will provide a contemporary summary of the clinical and molecular alterations currently known to occur in the skeletal muscles of both HFrEF and HFpEF, and thereby differentiate the effects on locomotor and respiratory muscles, in particular the diaphragm. Moreover, current and future therapeutic options to address skeletal muscle weakness will be discussed focusing mainly on the effects of exercise training.
Multiple TLRs elicit alternative NLRP3 inflammasome activation in primary human monocytes independent of RIPK1 kinase activity
Authors: Unterberger Sarah , Mullen Lisa , Flint Melanie S. , Sacre Sandra
Published: October 2023

The canonical NOD-like receptor family pyrin domain containing 3 (NLRP3) pathway involves a priming step to induce pro-IL-1β followed by a secondary signal such as K+efflux to activate inflammasome formation. This then leads to the maturation of IL-1β and the formation of gasdermin D (GSDMD) pores that initiate pyroptosis and mediate IL-1β release. In contrast, primary human monocytes also engage an alternative pathway in response to toll-like receptor (TLR) 4 activation, without the need for a secondary signal. Data from a monocyte-like cell line suggest that the alternative pathway functions via the TLR adaptor protein TIR-domain-containing adapter-inducing interferon-β (TRIF), receptor-interacting protein kinase 1 (RIPK1), FAS-associated death domain (FADD) and caspase-8 upstream of NLRP3 activation, but in the absence of K+efflux or pyroptosis. Usage of the alternative pathway by other members of the TLR family that induce IL-1β but do not signal through TRIF, has yet to be explored in primary human monocytes. Furthermore, the mechanism by which IL-1β is released from monocytes remains unclear. Therefore, this study investigated if the alternative NLRP3 inflammasome pathway is initiated following activation of TLRs other than TLR4, and if GSDMD was necessary for the release of IL-1β. Monocytes were stimulated with ligands that activate TLR1/2, TLR2/6, TLR4 and TLR7 and/or TLR8 (using a dual ligand). Similar to TLR4, all of the TLRs investigated induced IL-1β release in a NLRP3 and caspase-1 dependent manner, indicating that TRIF may not be an essential upstream component of the alternative pathway. Furthermore, inhibition of RIPK1 kinase activity had no effect on IL-1β release. Although IL-1β was released independently of K+efflux and pyroptosis, it was significantly reduced by an inhibitor of GSDMD. Therefore, it is feasible that low level GSDMD pore formation may facilitate the release of IL-1β from the cell, but not be present in sufficient quantities to initiate pyroptosis. Together these data suggest that the alternative pathway operates independently of RIPK1 kinase activity, downstream of diverse TLRs including TLR4 in primary human monocytes and supports the potential for IL-1β release via GSDMD pores alongside other unconventional secretory pathways.
Modeling complement activation on human glomerular microvascular endothelial cells
Authors: Stevens Kes H. , Baas Laura M. , van der Velden Thea J. A. M. , Bouwmeester Romy N. , van Dillen Niels , Dorresteijn Eiske M. , van Zuilen Arjan D. , Wetzels Jack F. M. , Michels Marloes A. H. M. , van de Kar Nicole C. A. J. , van den Heuvel Lambertus P.
Published: October 2023

Introduction

Atypical hemolytic uremic syndrome (aHUS) is a rare kidney disease caused by dysregulation of the complement alternative pathway. The complement dysregulation specifically leads to damage to the glomerular endothelium. To further understand aHUS pathophysiology, we validated an ex vivo model for measuring complement deposition on both control and patient human glomerular microvascular endothelial cells (GMVECs).

Methods

Endothelial cells were incubated with human test sera and stained with an anti-C5b-9 antibody to visualize and quantify complement depositions on the cells with immunofluorescence microscopy.

Results

First, we showed that zymosan-activated sera resulted in increased endothelial C5b-9 depositions compared to normal human serum (NHS). The levels of C5b-9 depositions were similar between conditionally immortalized (ci)GMVECs and primary control GMVECs. The protocol with ciGMVECs was further validated and we additionally generated ciGMVECs from an aHUS patient. The increased C5b-9 deposition on control ciGMVECs by zymosan-activated serum could be dose-dependently inhibited by adding the C5 inhibitor eculizumab. Next, sera from five aHUS patients were tested on control ciGMVECs. Sera from acute disease phases of all patients showed increased endothelial C5b-9 deposition levels compared to NHS. The remission samples showed normalized C5b-9 depositions, whether remission was reached with or without complement blockage by eculizumab. We also monitored the glomerular endothelial complement deposition of an aHUS patient with a hybrid complement factor H (CFH)/CFH-related 1 gene during follow-up. This patient had already chronic kidney failure and an ongoing deterioration of kidney function despite absence of markers indicating an aHUS flare. Increased C5b-9 depositions on ciGMVECs were observed in all samples obtained throughout different diseases phases, except for the samples with eculizumab levels above target. We then tested the samples on the patient’s own ciGMVECs. The C5b-9 deposition pattern was comparable and these aHUS patient ciGMVECs also responded similar to NHS as control ciGMVECs.

Discussion

In conclusion, we demonstrate a robust and reliable model to adequately measure C5b-9-based complement deposition on human control and patient ciGMVECs. This model can be used to study the pathophysiological mechanisms of aHUS or other diseases associated with endothelial complement activation ex vivo.
CD8 T cell response and its released cytokine IFN-γ are necessary for lung alveolar epithelial repair during bacterial pneumonia
Authors: Zhang Xiaoying , Ali Mir , Pantuck Morgan Alexandra , Yang Xiaofeng , Lin Chih-Ru , Bahmed Karim , Kosmider Beata , Tian Ying
Published: October 2023

Introduction

Alveolar epithelial regeneration depends on the activity of resident quiescent progenitor cells. Alveolar epithelial type II (AT2) cells are known as the alveolar epithelial progenitor cells. They exit quiescent state, proliferate rapidly in response to injury and differentiate into alveolar epithelial type I (AT1) cells to regenerate the damaged alveolar epithelium. Although AT2 cell plasticity has been a very intense field of research, the role of CD8 T cell response and their released cytokine IFN-γ, in regulating AT2 cell plasticity and alveolar epithelial repair and regeneration after injury remains largely unknown.

Methods

We used flow cytometry to quantify the amount of CD8 T cells in mouse lungs after bacterial pneumonia caused by Streptococcus pneumoniae. To determine whether CD8 T cells and their released cytokine IFN-γ are necessary for AT2 cell activity during alveolar epithelial regeneration, we performed loss of function studies using anti-CD8 or anti-IFN-γ monoclonal antibody (mAb) treatment in vivo. We assessed the effects of CD8 T cells and cytokine IFN-γ on AT2 cell differentiation capacity using the AT2- CD8 T cell co-culture system in vitro.

Results

We detected a transient wave of accumulation of CD8 T cells in mouse lungs, which coincided with the burst of AT2 cell proliferation during alveolar epithelial repair and regeneration in mice following bacterial pneumonia caused by Streptococcus pneumoniae. Depletion of CD8 T cells or neutralization of cytokine IFN-γ using anti-CD8 or anti-IFN-γ monoclonal antibody significantly reduced AT2 cell proliferation and differentiation into AT1 cells in mice after bacterial pneumonia. Furthermore, co-culture of CD8 T cells or cytokine IFN-γ with AT2 cells promoted AT2-to-AT1 cell differentiation in both murine and human systems. Conversely, blockade of IFN-γ signaling abrogated the increase in AT2-to-AT1 cell differentiation in the AT2- CD8 T cell co-culture system.

Discussion

Our data demonstrate that CD8 T-cell response and cytokine IFN-γ are necessary for promoting AT2 cell activity during alveolar epithelial repair and regeneration after acute lung injury caused by bacterial pneumonia.
RIPK1 and RIPK3 inhibitors: potential weapons against inflammation to treat diabetic complications
Authors: Ke Dan , Zhang Zhen , Liu Jieting , Chen Peijian , Dai Yucen , Sun Xinhai , Chu Yanhui , Li Luxin
Published: October 2023

Diabetes mellitus is a metabolic disease that is characterized by chronic hyperglycemia due to a variety of etiological factors. Long-term metabolic stress induces harmful inflammation leading to chronic complications, mainly diabetic ophthalmopathy, diabetic cardiovascular complications and diabetic nephropathy. With diabetes complications being one of the leading causes of disability and death, the use of anti-inflammatories in combination therapy for diabetes is increasing. There has been increasing interest in targeting significant regulators of the inflammatory pathway, notably receptor-interacting serine/threonine-kinase-1 (RIPK1) and receptor-interacting serine/threonine-kinase-3 (RIPK3), as drug targets for managing inflammation in treating diabetes complications. In this review, we aim to provide an up-to-date summary of current research on the mechanism of action and drug development of RIPK1 and RIPK3, which are pivotal in chronic inflammation and immunity, in relation to diabetic complications which may be benefit for explicating the potential of selective RIPK1 and RIPK3 inhibitors as anti-inflammatory therapeutic agents for diabetic complications.
Chemokines, molecular drivers of thromboinflammation and immunothrombosis
Authors: Leberzammer Julian , von Hundelshausen Philipp
Published: October 2023

Blood clotting is a finely regulated process that is essential for hemostasis. However, when dysregulated or spontaneous, it promotes thrombotic disorders. The fact that these are triggered, accompanied and amplified by inflammation is reflected in the term thromboinflammation that includes chemokines. The role of chemokines in thrombosis is therefore illuminated from a cellular perspective, where endothelial cells, platelets, red blood cells, and leukocytes may be both the source and target of chemokines. Chemokine-dependent prothrombotic processes may thereby occur independently of chemokine receptors or be mediated by chemokine receptors, although the binding and activation of classical G protein-coupled receptors and their signaling pathways differ from those of atypical chemokine receptors, which do not function via cell activation and recruitment. Regardless of binding to their receptors, chemokines can induce thrombosis by forming platelet-activating immune complexes with heparin or other polyanions that are pathognomonic for HIT and VITT. In addition, chemokines can bind to NETs and alter their structure. They also change the electrical charge of the cell surface of platelets and interact with coagulation factors, thereby modulating the balance of fibrinolysis and coagulation. Moreover, CXCL12 activates CXCR4 on platelets independently of classical migratory chemokine activity and causes aggregation and thrombosis via the PI3Kβ and Btk signaling pathways. In contrast, typical chemokine-chemokine receptor interactions are involved in the processes that contribute to the adhesiveness of the endothelium in the initial phase of venous thrombosis, where neutrophils and monocytes subsequently accumulate in massive numbers. Later, the reorganization and resolution of a thrombus require coordinated cell migration and invasion of the thrombus, and, as such, indeed, chemokines recruit leukocytes to existing thrombi. Therefore, chemokines contribute in many independent ways to thrombosis.
An interpretable Alzheimer’s disease oligogenic risk score informed by neuroimaging biomarkers improves risk prediction and stratification
Authors: Suh Erica H. , Lee Garam , Jung Sang-Hyuk , Wen Zixuan , Bao Jingxuan , Nho Kwangsik , Huang Heng , Davatzikos Christos , Saykin Andrew J. , Thompson Paul M. , Shen Li , Kim Dokyoon ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: October 2023

Introduction

Stratification of Alzheimer’s disease (AD) patients into risk subgroups using Polygenic Risk Scores (PRS) presents novel opportunities for the development of clinical trials and disease-modifying therapies. However, the heterogeneous nature of AD continues to pose significant challenges for the clinical broadscale use of PRS. PRS remains unfit in demonstrating sufficient accuracy in risk prediction, particularly for individuals with mild cognitive impairment (MCI), and in allowing feasible interpretation of specific genes or SNPs contributing to disease risk. We propose adORS, a novel oligogenic risk score for AD, to better predict risk of disease by using an optimized list of relevant genetic risk factors.

Methods

Using whole genome sequencing data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort (n  =  1,545), we selected 20 genes that exhibited the strongest correlations with FDG-PET and AV45-PET, recognized neuroimaging biomarkers that detect functional brain changes in AD. This subset of genes was incorporated into adORS to assess, in comparison to PRS, the prediction accuracy of CN vs. AD classification and MCI conversion prediction, risk stratification of the ADNI cohort, and interpretability of the genetic information included in the scores.

Results

adORS improved AUC scores over PRS in both CN vs. AD classification and MCI conversion prediction. The oligogenic model also refined risk-based stratification, even without the assistance of APOE, thus reflecting the true prevalence rate of the ADNI cohort compared to PRS. Interpretation analysis shows that genes included in adORS, such as ATF6, EFCAB11, ING5, SIK3, and CD46, have been observed in similar neurodegenerative disorders and/or are supported by AD-related literature.

Discussion

Compared to conventional PRS, adORS may prove to be a more appropriate choice of differentiating patients into high or low genetic risk of AD in clinical studies or settings. Additionally, the ability to interpret specific genetic information allows the focus to be shifted from general relative risk based on a given population to the information that adORS can provide for a single individual, thus permitting the possibility of personalized treatments for AD.
Efficacy and safety of yoga for the management of chronic low back pain: an overview of systematic reviews
Authors: Zhang Xianshuai , Chang Tianying , Hu Wenlong , Shi Mingpeng , Chai Yating , Wang Siyi , Zhou Guohui , Han Mingze , Zhuang Minghui , Yu Jie , Yin He , Zhu Liguo , Zhao Changwei , Li Zhenhua , Liao Xing
Published: October 2023

Background

Yoga is a non-pharmacological conservative therapeutic modality that can be employed for the management of chronic low back pain (CLBP). In this overview, we have summarized and evaluated data from current systematic reviews (SRs) on the use of yoga for CLBP.

Methods

We comprehensively searched SRs on the use of yoga for CLBP in nine electronic databases from inception to September 2023. The methodological quality was evaluated using the Assessment of Multiple Systematic Review Scale-2 (AMSTAR-2). The reporting quality of the included SRs was evaluated using the Preferred Reporting Item for Systematic Review and Meta-Analysis-2020 (PRISMA-2020), and the quality of data was graded using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Two independent researchers performed the screening, data extraction, and quality assessment process of SRs.

Results

A total of 13 SRs were included. The results of the AMSTAR-2 indicated that the methodological quality of the included studies was relatively low. The PRISMA-2020 checklist evaluation results indicated that methodological limitations in reporting, especially regarding data processing and presentation, were the main weaknesses. The GRADE assessment indicated that 30 outcomes were rated moderate, 42 were rated low level, and 20 were rated very low level. Downgrading factors were mainly due to the limitations of the included studies.

Conclusion

Yoga appears to be an effective and safe non-pharmacological therapeutic modality for the Management of CLBP. Currently, it may exhibit better efficacy in improving pain and functional disability associated with CLBP. However, the methodological quality and quality of evidence for SRs/MAs in the included studies were generally low, and these results should be interpreted cautiously.
The behavioral and neural effects of parietal theta burst stimulation on the grasp network are stronger during a grasping task than at rest
Authors: Goldenkoff Elana R. , Deluisi Joseph A. , Destiny Danielle P. , Lee Taraz G. , Michon Katherine J. , Brissenden James A. , Taylor Stephan F. , Polk Thad A. , Vesia Michael
Published: October 2023

Repetitive transcranial magnetic stimulation (TMS) is widely used in neuroscience and clinical settings to modulate human cortical activity. The effects of TMS on neural activity depend on the excitability of specific neural populations at the time of stimulation. Accordingly, the brain state at the time of stimulation may influence the persistent effects of repetitive TMS on distal brain activity and associated behaviors. We applied intermittent theta burst stimulation (iTBS) to a region in the posterior parietal cortex (PPC) associated with grasp control to evaluate the interaction between stimulation and brain state. Across two experiments, we demonstrate the immediate responses of motor cortex activity and motor performance to state-dependent parietal stimulation. We randomly assigned 72 healthy adult participants to one of three TMS intervention groups, followed by electrophysiological measures with TMS and behavioral measures. Participants in the first group received iTBS to PPC while performing a grasping task concurrently. Participants in the second group received iTBS to PPC while in a task-free, resting state. A third group of participants received iTBS to a parietal region outside the cortical grasping network while performing a grasping task concurrently. We compared changes in motor cortical excitability and motor performance in the three stimulation groups within an hour of each intervention. We found that parietal stimulation during a behavioral manipulation that activates the cortical grasping network increased downstream motor cortical excitability and improved motor performance relative to stimulation during rest. We conclude that constraining the brain state with a behavioral task during brain stimulation has the potential to optimize plasticity induction in cortical circuit mechanisms that mediate movement processes.
Alterations of dynamic and static brain functional activities and integration in stroke patients
Authors: Guo Li , Zhao Zixuan , Yang Xu , Shi Weiyang , Wang Peng , Qin Dongdong , Wang Jiaojian , Yin Yong
Published: October 2023

Objective

The study aimed to investigate the comprehensive characteristics of brain functional activity and integration in patients with subcortical stroke using dynamic and static analysis methods and to examine whether alterations in brain functional activity and integration were associated with clinical symptoms of patients.

Methods

Dynamic amplitude of low-frequency fluctuation (dALFF), static amplitude of low-frequency fluctuation (sALFF), dynamic degree centrality (dDC), and static degree centrality (sDC) were calculated for 19 patients with right subcortical stroke, 16 patients with left subcortical stroke, and 25 healthy controls (HC). Furthermore, correlation analysis was performed to investigate the relationships between changes in brain functional measurements of patients and clinical variables.

Results

Group comparison results showed that significantly decreased dALFF in the left angular (ANG_L) and right inferior parietal gyrus (IPG_R), decreased sALFF in the left precuneus (PCUN_L), and decreased sDC in the left crus II of cerebellar hemisphere (CERCRU2_L) and IPG_R, while significantly increased sDC in the right lobule X of cerebellar hemisphere (CER10_R) were detected in patients with right subcortical stroke relative to HC. Patients with left subcortical stroke showed significantly decreased sALFF in the left precuneus (PCUN_L) but increased sDC in the right hippocampus (HIP_R) compared with HC. Additionally, the altered sDC values in the CER10_R of patients with right subcortical stroke and in the HIP_R of patients with left subcortical stroke were associated with the severity of stroke and lower extremities motor function. A correlation was also found between the altered sALFF values in the PCUN_L of patients with left subcortical stroke and lower extremities motor function.

Conclusion

These findings suggest that time-varying brain activity analysis may supply complementary information for static brain activity analysis. Dynamic and static brain functional activity and integration analysis may contribute to a more comprehensive understanding of the underlying neuropathology of dysfunction in stroke patients.
Bone marrow stromal cells reduce low-dose cytarabine-induced differentiation of acute myeloid leukemia
Authors: Smoljo Tomislav , Tomic Barbara , Lalic Hrvoje , Dembitz Vilma , Batinic Josip , Bedalov Antonio , Visnjic Dora
Published: October 2023

Low-dose cytarabine (LDAC) is a standard therapy for elderly acute myeloid leukemia (AML) patients unfit for intensive chemotherapy. While high doses of cytarabine induce cytotoxicity, the precise mechanism of action of LDAC in AML remains elusive. In vitro studies have demonstrated LDAC-induced differentiation; however, such differentiation is seldom observed in vivo. We hypothesize that this discrepancy may be attributed to the influence of bone marrow (BM) stromal cells on AML cells. Thus, this study aimed to investigate the impact of BM stromal cells on LDAC-induced differentiation of AML cell lines and primary samples. Our results demonstrate that the presence of MS-5 stromal cells prevented LDAC-induced cell cycle arrest, DNA damage signaling and differentiation of U937 and MOLM-13 cell lines. Although transcriptomic analysis revealed that the stroma reduces the expression of genes involved in cytokine signaling and oxidative stress, data obtained with pharmacological inhibitors and neutralizing antibodies did not support the role for CXCL12, TGF-β1 or reactive oxygen species. The presence of stromal cells reduces LDAC-induced differentiation in primary samples from AML-M4 and myelodysplastic syndrome/AML patients. In conclusion, our study demonstrates that BM stroma reduces differentiation of AML induced by LDAC. These findings provide insights into the limited occurrence of terminal differentiation observed in AML patients, and suggest a potential explanation for this observation.
The mechanisms of tanshinone in the treatment of tumors
Authors: Zhang Pengyu , Liu Wendi , Wang Yuan
Published: October 2023

Tanshinone is a lipophilic compound that is present in traditional Chinese medicine and is derived from the roots of Salvia miltiorrhiza (Danshen). It has been proven to be highly effective in combating tumors in various parts of the body, including liver carcinoma, gastric cancer, ovarian cancer, cervix carcinoma, breast cancer, colon cancer, and prostate cancer. Tanshinone can efficiently prevent the reproduction of cancerous cells, induce cell death, and inhibit the spread of cancerous cells, which are mainly involved in the PI3K/Akt signaling pathway, NF-κB pathway, Bcl-2 family, Caspase cascades, MicroRNA, MAPK signaling pathway, p21, STAT3 pathway, miR30b-P53-PTPN11/SHP2 axis, β-catenin, and Skp2. However, the properties and mechanisms of tanshinone’s anti-tumor effects remain unclear currently. Thus, this study aims to review the research progress on tumor prevention and mechanisms of tanshinone to gain new perspectives for further development and clinical application of tanshinone.
Time of day of exercise does not affect the beneficial effect of exercise on bone structure in older female rats
Authors: Cao Jay J. , Gregoire Brian R.
Published: October 2023

Background: Circadian clock genes are expressed in bone and biomarkers of bone resorption and formation exhibit diurnal patterns in animals and humans. Disruption of the diurnal rhythms may affect the balance of bone turnover and compromise the beneficial effects of exercise on bone.

Objective: This study investigated whether the time of day of exercise alters bone metabolism in a rodent model. We hypothesized that exercise during the active phase results in greater bone mass than exercise during the rest phase in older female rats.

Methods: Fifty-five, female 12-month-old Sprague Dawley rats were randomly assigned to four treatment groups (n = 13–14/group). Rats were subjected to no exercise or 2 h of involuntary exercise at 9 m/min and 5 days/wk for 15 weeks using motor-driven running wheels at Zeitgeber time (ZT) 4–6 (rest phase), 12–14 (early active phase), or 22–24 (late active phase). ZT 0 is defined as light on, the start of the rest phase. A red lamp was used at minimal intensity during the active, dark phase exercise period, i.e., ZT 12–14 and 22–24. Bone structure, body composition, and bone-related cytokines in serum and gene expression in bone were measured. Data were analyzed using one-way ANOVA followed by Tukey-Kramer post hoc contrasts.

Results: Exercise at different ZT did not affect body weight, fat mass, lean mass, the serum bone biomarkers, bone structural or mechanical parameters, or expression of circadian genes. Exercise pooled exercise data from different ZT were compared to the No-Exercise data (a priori contrast) increased serum IGF-1 and irisin concentrations, compared to No-Exercise. Exercise increased tibial bone volume/total volume (p = 0.01), connectivity density (p = 0.04), and decreased structural model index (p = 0.02). Exercise did not affect expression of circadian genes.

Conclusion: These data indicate that exercise is beneficial to bone structure and that the time of day of exercise does not alter the beneficial effect of exercise on bone in older female rats.
Prediction for blood lactate during exercise using an artificial intelligence—Enabled electrocardiogram: a feasibility study
Authors: Huang Shu-Chun , Lee Chen-Hung , Hsu Chih-Chin , Chang Sing-Ya , Chen Yu-An , Chiu Chien-Hung , Hsiao Ching-Chung , Su Hong-Ren
Published: October 2023

Introduction: The acquisition of blood lactate concentration (BLC) during exercise is beneficial for endurance training, yet a convenient method to measure it remains unavailable. BLC and electrocardiogram (ECG) both exhibit variations with changes in exercise intensity and duration. In this study, we hypothesized that BLC during exercise can be predicted using ECG data.

Methods: Thirty-one healthy participants underwent four cardiopulmonary exercise tests, including one incremental test and three constant work rate (CWR) tests at low, moderate, and high intensity. Venous blood samples were obtained immediately after each CWR test to measure BLC. A mathematical model was constructed using 31 trios of CWR tests, which utilized a residual network combined with long short-term memory to analyze every beat of lead II ECG waveform as 2D images. An artificial neural network was used to analyze variables such as the RR interval, age, sex, and body mass index.

Results: The standard deviation of the fitting error was 0.12 mmol/L for low and moderate intensities, and 0.19 mmol/L for high intensity. Weighting analysis demonstrated that ECG data, including every beat of ECG waveform and RR interval, contribute predominantly.

Conclusion: By employing 2D convolution and artificial neural network-based methods, BLC during exercise can be accurately estimated non-invasively using ECG data, which has potential applications in exercise training.
Fine root decomposition in forest ecosystems: an ecological perspective
Authors: Saha Sudipta , Huang Lei , Khoso Muneer Ahmed , Wu Haibo , Han Donghui , Ma Xiao , Poudel Tika Ram , Li Bei , Zhu Meiru , Lan Qiurui , Sakib Nazmus , Wei Ruxiao , Islam Md. Zahirul , Zhang Peng , Shen Hailong
Published: October 2023

Fine root decomposition is a physio-biochemical activity that is critical to the global carbon cycle (C) in forest ecosystems. It is crucial to investigate the mechanisms and factors that control fine root decomposition in forest ecosystems to understand their system-level carbon balance. This process can be influenced by several abiotic (e.g., mean annual temperature, mean annual precipitation, site elevation, stand age, salinity, soil pH) and biotic (e.g., microorganism, substrate quality) variables. Comparing decomposition rates within sites reveals positive impacts of nitrogen and phosphorus concentrations and negative effects of lignin concentration. Nevertheless, estimating the actual fine root breakdown is difficult due to inadequate methods, anthropogenic activities, and the impact of climate change. Herein, we propose that how fine root substrate and soil physiochemical characteristics interact with soil microorganisms to influence fine root decomposition. This review summarized the elements that influence this process, as well as the research methods used to investigate it. There is also need to study the influence of annual and seasonal changes affecting fine root decomposition. This cumulative evidence will provide information on temporal and spatial dynamics of forest ecosystems, and will determine how logging and reforestation affect fine root decomposition.
Behavioral patterns in robotic collaborative assembly: comparing neurotypical and Autism Spectrum Disorder participants
Authors: Mondellini Marta , Prajod Pooja , Lavit Nicora Matteo , Chiappini Mattia , Micheletti Ettore , Storm Fabio Alexander , Vertechy Rocco , André Elisabeth , Malosio Matteo
Published: October 2023

Introduction

In Industry 4.0, collaborative tasks often involve operators working with collaborative robots (cobots) in shared workspaces. Many aspects of the operator's well-being within this environment still need in-depth research. Moreover, these aspects are expected to differ between neurotypical (NT) and Autism Spectrum Disorder (ASD) operators.

Methods

This study examines behavioral patterns in 16 participants (eight neurotypical, eight with high-functioning ASD) during an assembly task in an industry-like lab-based robotic collaborative cell, enabling the detection of potential risks to their well-being during industrial human-robot collaboration. Each participant worked on the task for five consecutive days, 3.5 h per day. During these sessions, six video clips of 10 min each were recorded for each participant. The videos were used to extract quantitative behavioral data using the NOVA annotation tool and analyzed qualitatively using an ad-hoc observational grid. Also, during the work sessions, the researchers took unstructured notes of the observed behaviors that were analyzed qualitatively.

Results

The two groups differ mainly regarding behavior (e.g., prioritizing the robot partner, gaze patterns, facial expressions, multi-tasking, and personal space), adaptation to the task over time, and the resulting overall performance.

Discussion

This result confirms that NT and ASD participants in a collaborative shared workspace have different needs and that the working experience should be tailored depending on the end-user's characteristics. The findings of this study represent a starting point for further efforts to promote well-being in the workplace. To the best of our knowledge, this is the first work comparing NT and ASD participants in a collaborative industrial scenario.
The study of movement skills in sports: toward an integrative approach
Authors: Loland Sigmund , Ettema Gertjan , Sandbakk Øyvind
Published: October 2023

The article commences with a fundamental objective: to comprehend movement skills in sports in a manner that can bridge the dualist gap between experiential qualities observed in practice and theoretical and mechanistic explanations. Drawing inspiration from Kuhn’s concept of scientific paradigms, practical examples from skiing research, and innovative insights into the integration of phenomenology and mechanistic explanation in cognitive science, we have outlined a three-step integrative approach. The first step entails the development of phenomenological descriptions of the primary experiential qualities inherent in the execution of the skills being investigated. In the second step, phenomenological descriptions play a pivotal role by setting constraints and delineating a space for the elaboration of multilevel mechanistic analyses. These analyses draw upon insights from various fields, encompassing biomechanics, motor control approaches, expertise studies, and cognitive science. The third step involves the systematization of findings and the formulation of sport-specific movement skills theories. We contend that such theories hold substantial significance as they serve as valuable supplements to skill studies conducted within rigid, nomological frameworks. Sport-specific theories include descriptions of first-person experiential qualities and can contribute to bridging the theory-practice gap effectively.
Challenges and opportunities for improvement in the management and financing system of Health Promotion Offices in Hungary
Authors: Horváth Krisztián , Túri Gergo , Kaposvári Csilla , Cseh Borbála , Dózsa Csaba László
Published: October 2023

Background

One hundred ten Health Promotion Offices (HPOs) have started operating in Hungary in response to public health challenges. Many of them have been active for almost 10 years, yet their operational experience has not been evaluated. The specific objectives of our study were: (1) to describe the current operational and funding system of HPOs, (2) to identify challenges related to the current management and funding practices, and (3) to formulate recommendations for improvement based on gathered experience and international experience.

Design

In order to gain a deeper insight into the operational experience of HPOs, an online survey was conducted with the professional or economic managers of HPOs. A scoping review was carried out to gather international experiences about best practices to formulate recommendations for improvement in developing the operational and financing scheme for HPOs.

Results

We found that current HPO network in Hungary faces three main challenges: a deficient management system, inflexible financing scheme, and unequal ability to purchase or provide services for the population.

Conclusions

Based on the survey complemented by international experiences, we propose the overhaul of the professional management system and switching toa combination of fixed and performance-based financing scheme for the HPOs in Hungary.