bluuebunny/crossref_metadata_2025_split huggingface dataset:
Licorice extract inhibits the cGAS-STING pathway and protects against non-alcoholic steatohepatitis
Authors: Luo Wei , Xu Guang , Song Zheng , Mu Wenqing , Wen Jincai , Hui Siwen , Zhao Jia , Zhan Xiaoyan , Bai Zhaofang , Xiao Xiaohe 
Published: April 2023

Background: Inflammation and fibrosis are typical symptoms of non-alcoholic steatohepatitis (NASH), which is one of the most common chronic liver diseases. The cGAS-STING signaling pathway has been implicated in the progression of NASH, and targeting this pathway may represent a new therapeutic strategy. Licorice is a widely used herb with anti-inflammatory and liver-protective properties. In this study, we assessed the effect of licorice extract on the cGAS-STING pathway.Methods: Bone marrow-derived macrophages (BMDMs) were treated with licorice extract and then stimulated with HT-DNA, 2'3'-cGAMP, or other agonists to activate the cGAS-STING pathway. Quantitative real-time PCR and western blot were conducted to analyze whether licorice extract could affect the cGAS-STING pathway. Methionine and choline-deficient diet (MCD) was used to induce NASH in mice, which were treated with licorice extract (500 mg/kg) by gavage and/or c-176 (15 mg/kg) by intraperitoneal injection every 2 days. After 6 weeks of treatment, histological analysis of liver tissue was performed, along with measurements of plasma biochemical parameters.Results: Licorice extract inhibits cGAS-STING pathway activation. Mechanistically, it might function by inhibiting the oligomerization of STING. Treatment with licorice extract reduced inflammation and fibrosis in MCD diet-induced NASH mice models. Furthermore, we found that the therapeutic effect of combination treatment with licorice extract and C-176 (STING inhibitor) on the pathology and fibrosis of MCD diet-induced NASH models was similar to that of licorice extract or C-176 administered alone.Conclusion: Licorice extract can inhibit the cGAS-STING pathway and improve hepatic inflammation and fibrosis in NASH mice models. It strongly suggests that licorice extract may be a candidate therapeutic for NASH.
MEPIRAPIM-derived synthetic cannabinoids inhibit T-type calcium channels with divergent effects on seizures in rodent models of epilepsy
Authors: Harman Thomas , Udoh Michael , McElroy Dan L. , Anderson Lyndsey L. , Kevin Richard C. , Banister Samuel D. , Ametovski Adam , Markham Jack , Bladen Chris , Doohan Peter T. , Greba Quentin , Laprairie Robert B. , Snutch Terrance P. , McGregor Iain S. , Howland John G. , Arnold Jonathon C. 
Published: April 2023

Background: T-type Ca2+ channels (Cav3) represent emerging therapeutic targets for a range of neurological disorders, including epilepsy and pain. To aid the development and optimisation of new therapeutics, there is a need to identify novel chemical entities which act at these ion channels. A number of synthetic cannabinoid receptor agonists (SCRAs) have been found to exhibit activity at T-type channels, suggesting that cannabinoids may provide convenient chemical scaffolds on which to design novel Cav3 inhibitors. However, activity at cannabinoid type 1 (CB1) receptors can be problematic because of central and peripheral toxicities associated with potent SCRAs. The putative SCRA MEPIRAPIM and its analogues were recently identified as Cav3 inhibitors with only minimal activity at CB1 receptors, opening the possibility that this scaffold may be exploited to develop novel, selective Cav3 inhibitors. Here we present the pharmacological characterisation of SB2193 and SB2193F, two novel Cav3 inhibitors derived from MEPIRAPIM.Methods: The potency of SB2193 and SB2193F was evaluated in vitro using a fluorometric Ca2+ flux assay and confirmed using whole-cell patch-clamp electrophysiology. In silico docking to the cryo-EM structure of Cav3.1 was also performed to elucidate structural insights into T-type channel inhibition. Next, in vivo pharmacokinetic parameters in mouse brain and plasma were determined using liquid chromatography-mass spectroscopy. Finally, anticonvulsant activity was assayed in established genetic and electrically-induced rodent seizure models.Results: Both MEPIRAPIM derivatives produced potent inhibition of Cav3 channels and were brain penetrant, with SB2193 exhibiting a brain/plasma ratio of 2.7. SB2193 was further examined in mouse seizure models where it acutely protected against 6 Hz-induced seizures. However, SB2193 did not reduce spontaneous seizures in the Scn1a+/− mouse model of Dravet syndrome, nor absence seizures in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS). Surprisingly, SB2193 appeared to increase the incidence and duration of spike-and-wave discharges in GAERS animals over a 4 h recording period.Conclusion: These results show that MEPIRAPIM analogues provide novel chemical scaffolds to advance Cav3 inhibitors against certain seizure types.
Forehead monitoring of heart rate in neonatal intensive care
Authors: Stockwell S. J. , Kwok T. C. , Morgan S. P. , Sharkey D. , Hayes-Gill B. R. 
Published: April 2023

Heart rate is an extremely important physiological parameter to measure in critically unwell infants, as it is the main physiological marker that changes in response to a change in infant condition. Heart rate is routinely measured peripherally on a limb with a pulse oximeter. However, when infants are critically unwell, the blood supply to these peripheries is reduced in preference for central perfusion of vital organs such as the brain and heart. Measurement of heart rate with a reflection mode photoplethysmogram (PPG) sensor on the forehead could help minimise this problem and make it easier for other important medical equipment, such as cannulas, to be placed on the limbs. This study compares heart rates measured with a forehead-based PPG sensor against a wrist-based PPG sensor in 19 critically unwell infants in neonatal intensive care collecting 198 h of data. The two heart rates were compared using positive percentage agreement, Spearman’s correlation coefficient and Bland-Altman analysis. The forehead PPG sensor showed good agreement with the wrist-based PPG sensor with limits of agreement of 8.44 bpm, bias of −0.22 bpm; positive percentage agreement of 98.87%; and Spearman’s correlation coefficient of 0.9816. The analysis demonstrates that the forehead is a reliable alternative location for measuring vital signs using the PPG.
The bioenergetic “CK Clamp” technique detects substrate-specific changes in mitochondrial respiration and membrane potential during early VML injury pathology
Authors: McFaline-Figueroa Jennifer , Hunda Edward T. , Heo Junwon , Winders Elizabeth A. , Greising Sarah M. , Call Jarrod A. 
Published: April 2023

Volumetric muscle loss (VML) injuries are characterized by non-recoverable loss of tissue resulting in contractile and metabolic dysfunction. The characterization of metabolic dysfunction in volumetric muscle loss-injured muscle has been interpreted from permeabilized myofiber respiration experiments involving saturating ADP levels and non-physiologic ATP:ADP concentration ratios. The extent to which this testing condition obscures the analysis of mitochondrial (dys) function after volumetric muscle loss injury is unclear. An alternative approach is described that leverages the enzymatic reaction of creatine kinase and phosphocreatine to assess mitochondrial respiration and membrane potential at clamped physiologic ATP:ADP ratios, “CK Clamp.” The objective of this study was to validate the CK Clamp in volumetric muscle loss-injured muscle and to detect differences that may exist between volumetric muscle loss-injured and uninjured muscles at 1, 3, 5, 7, 10, and 14 days post-injury. Volumetric muscle loss-injured muscle maintains bioenergetic features of the CK Clamp approach, i.e., mitochondrial respiration rate (JO2) titters down and mitochondrial membrane potential is more polarized with increasing ATP:ADP ratios. Pyruvate/malate/succinate-supported JO2 was significantly less in volumetric muscle loss-injured muscle at all timepoints compared to uninjured controls (−26% to −84%, p &lt; 0.001) and electron conductance was less at day 1 (−60%), 5 (−52%), 7 (−35%), 10 (−59%), and 14 (−41%) (p &lt; 0.001). Palmitoyl-carnitine/malate-supported JO2 and electron conductance were less affected following volumetric muscle loss injury. volumetric muscle loss-injury also corresponded with a more polarized mitochondrial membrane potential across the clamped ATP:ADP ratios at day 1 and 10 (pyruvate and palmitoyl-carnitine, respectively) (+5%, p &lt; 0.001). This study supports previous characterizations of metabolic dysfunction and validates the CK Clamp as a tool to investigate bioenergetics in traumatically-injured muscle.
The lexical processing of Japanese collocations by Chinese Japanese-as-a-Foreign-Language learners: An experimental study by manipulating the presentation modality, semantic transparency, and translational congruency
Authors: Song Qichao , Fei Xiaodong , Matsumi Norio 
Published: April 2023

IntroductionResearch on collocations has become an essential issue in L2 acquisition and cognitive psychology. Previous studies have mainly focused on phonographic languages such as English, Swedish, and German, and primarily discussed the effect of semantic transparency and translational congruency. However, these studies have lacked (1) an analysis of the interactions between presentation modalities (visual vs. auditory) and the semantic transparency and translational congruency, and (2) a discussion of an ideographic language, such as Chinese and Japanese.MethodsWe conducted an experiment with 36 Chinese Japanese-as-a-Foreign-Language learners to examine the processing of Japanese collocations. In the experiment, we manipulated the presentation modality, semantic transparency, and translational congruency during a lexical judgment task.ResultsData analysis using linear mixed-effects models revealed the following. (1) In both conditions of semantic transparency and translational congruency, the auditory presentation was associated with longer reaction times than the visual presentation. (2) In the visual presentation condition, neither semantic transparency nor translational congruency showed significant effects. (3) In the auditory presentation condition, the reaction time for collocations with high semantic transparency tended to be longer than that for collocations with medium semantic transparency and significantly longer than that for collocations with low semantic transparency. The reaction time for collocations with congruent translation was longer than that for collocations with incongruent translation.DiscussionThese results support the dual-route model of Japanese collocational processing by Chinese Japanese-as-a-Foreign-Language learners. Our findings suggest that whether the analytic or holistic processing dominates is closely related to the learners’ knowledge of Chinese and Japanese Kanji words and strongly influenced by the presentation modality, semantic transparency, and translational congruency.
Opioid use and opioid use disorder in mono and dual-system users of veteran affairs medical centers
Authors: Goulet Joseph , Cheng Yan , Becker William , Brandt Cynthia , Sandbrink Friedhelm , Workman Terri Elizabeth , Ma Phillip , Libin Alexander , Shara Nawar , Spevak Christopher , Kupersmith Joel , Zeng-Treitler Qing 
Published: April 2023

IntroductionEfforts to achieve opioid guideline concordant care may be undermined when patients access multiple opioid prescription sources. Limited data are available on the impact of dual-system sources of care on receipt of opioid medications.ObjectiveWe examined whether dual-system use was associated with increased rates of new opioid prescriptions, continued opioid prescriptions and diagnoses of opioid use disorder (OUD). We hypothesized that dual-system use would be associated with increased odds for each outcome.MethodsThis retrospective cohort study was conducted using Veterans Administration (VA) data from two facilities from 2015 to 2019, and included active patients, defined as Veterans who had at least one encounter in a calendar year (2015–2019). Dual-system use was defined as receipt of VA care as well as VA payment for community care (non-VA) services. Mono users were defined as those who only received VA services. There were 77,225 dual-system users, and 442,824 mono users. Outcomes were three binary measures: new opioid prescription, continued opioid prescription (i.e., received an additional opioid prescription), and OUD diagnosis (during the calendar year). We conducted a multivariate logistic regression accounting for the repeated observations on patient and intra-class correlations within patients.ResultsDual-system users were significantly younger than mono users, more likely to be women, and less likely to report white race. In adjusted models, dual-system users were significantly more likely to receive a new opioid prescription during the observation period [Odds ratio (OR) = 1.85, 95% confidence interval (CI) 1.76–1.93], continue prescriptions (OR = 1.24, CI 1.22–1.27), and to receive an OUD diagnosis (OR = 1.20, CI 1.14–1.27).DiscussionThe prevalence of opioid prescriptions has been declining in the US healthcare systems including VA, yet the prevalence of OUD has not been declining at the same rate. One potential problem is that detailed notes from non-VA visits are not immediately available to VA clinicians, and information about VA care is not readily available to non-VA sources. One implication of our findings is that better health system coordination is needed. Even though care was paid for by the VA and presumably closely monitored, dual-system users were more likely to have new and continued opioid prescriptions.
Impact of internal mammary artery perforator propeller flaps combined with radiotherapy in the treatment of large chest keloids: Our experience
Authors: Zhao Jianfang , Xie Kun , Qin Shangbin , He Rui , Jiang Shan , Qi Xin , Wen Bing 
Published: April 2023

BackgroundKeloids are benign skin hyperplasias but have a tumor-like appearance. Clinical management of keloids remains challenging.AimsWe retrospectively evaluated the safety and efficacy of internal mammary artery perforator propeller flaps combined with timely radiotherapy in the treatment of large chest keloids.MethodsFrom June 2017 to May 2020, 25 patients with large chest keloids (average size 4.82 cm ± 2.53 cm × 9.04 cm ± 4.86 cm) who received both radiotherapy and internal mammary artery perforator flaps transplantation in our department were included. After surgical removal of the keloids, various propeller flaps based on the unilateral internal mammary artery were designed and applied to repair the defects. Timely and full-dose radiotherapy was performed for these patients after the operation.ResultsAfter keloid resection, the dimensions of the defect area were 3 cm–15 cm × 4 cm–25 cm, and the sizes of the flaps were 3 cm–16 cm × 4 cm–27 cm. For all 25 patients, the flaps survived, and the incisions healed in one stage. During the follow-up (median 18 months), no local recurrence was observed, and the itching and pain symptoms in the scar area were significantly relieved. Both physicians and patients were satisfied with the results.ConclusionsThe application of internal mammary artery perforator propeller flaps combined with radiotherapy in the treatment of chest keloids can effectively reduce the recurrence of keloids and relieve the related symptoms. It also has advantages including minimized donor site damage, short operation time and speedy postoperative recovery, suggesting its great clinical value.
Anti-Apoptotic Effect of Chrysophanol Isolated from Cassia tora Seed Extract on Blue-Light-Induced A2E-Loaded Human Retinal Pigment Epithelial Cells
Authors: Kim Su-Kang , Ban Ju-Yeon , Kang Hyungoo , Park Sang-il 
Published: April 2023

The seeds of Cassia tora (C. tora) species mainly contain anthraquinone, anthraquinone glycoside, and naphthalene derivatives. We investigated the anti-apoptotic effects of C. tora seed extract and its isolated compounds on blue-light-induced lipofuscin (A2E)-loaded human retinal pigment epithelial (RPE) cells. For analysis of the C. tora extract, high-performance liquid chromatography method was used. A2E-loaded human retinal pigment epithelial cells and blue light were used to create excessive photo-oxidation to induce cell death. Lactate dehydrogenase (LDH) assay was used to measure cell cytotoxicity, and the mRNA expression of genes involved in apoptosis was examined to evaluate the mechanism of cell death. C. tora extract, n-hexane fraction, and chrysophanol were found to inhibit apoptotic cell death. Additionally, C. tora extract, n-hexane fraction, and chrysophanol reduced the mRNA expression of genes involved in the apoptosis pathway. C. tora and chrysophanol were considered to inhibit apoptosis and oxidative stress response. The major component of C. tora has a protective effect against apoptosis. The ingredients of C. tora can be used as therapeutic substances or to prevent diseases caused by the excessive oxidation of A2E substances in the retina, such as in age-related macular degeneration.
In Situ Raman Analysis of Biofilm Exopolysaccharides Formed in Streptococcus mutans and Streptococcus sanguinis Commensal Cultures
Authors: Pezzotti Giuseppe , Ofuji Satomi , Imamura Hayata , Adachi Tetsuya , Yamamoto Toshiro , Kanamura Narisato , Ohgitani Eriko , Marin Elia , Zhu Wenliang , Mazda Osam , Togo Azusa , Kimura Satoshi , Iwata Tadahisa , Shiba Hideki , Ouhara Kazuhisa , Aoki Takashi , Kawai Toshihisa 
Published: April 2023

This study probed in vitro the mechanisms of competition/coexistence between Streptococcus sanguinis (known for being correlated with health in the oral cavity) and Streptococcus mutans (responsible for aciduric oral environment and formation of caries) by means of quantitative Raman spectroscopy and imaging. In situ Raman assessments of live bacterial culture/coculture focusing on biofilm exopolysaccharides supported the hypothesis that both species engaged in antagonistic interactions. Experiments of simultaneous colonization always resulted in coexistence, but they also revealed fundamental alterations of the biofilm with respect to their water-insoluble glucan structure. Raman spectra (collected at fixed time but different bacterial ratios) showed clear changes in chemical bonds in glucans, which pointed to an action by Streptococcus sanguinis to discontinue the impermeability of the biofilm constructed by Streptococcus mutans. The concurrent effects of glycosidic bond cleavage in water-insoluble α − 1,3–glucan and oxidation at various sites in glucans’ molecular chains supported the hypothesis that secretion of oxygen radicals was the main “chemical weapon” used by Streptococcus sanguinis in coculture.
Sweeping Surfaces according to Type-3 Bishop Frames in Euclidean 3-Space
Authors: Al-Jedani Awatif , Abdel-Baky Rashad A. 
Published: April 2023

The aim of this work is to investigate sweeping surfaces and their local singularities due to type-3 Bishop frames in Euclidean 3-space, E3. A sweeping surface a is surface that is designed from a section curve positioned along a path, which acts as the vertebral column or spine curve, and it has symmetrical characteristics. In this work, we have specified a sweeping surface and have examined its geometry and singularity. Thereafter, we deduced the circumstances required for this surface to be a developable surface. In great detail, we concentrated on the fundamental discussion on whether the resulting developable surface is a cylindrical, cone or tangent surface. Meanwhile, examples are detailed to explain the applications of the notional outcomes.
Représentations féminines et masculines chez des patientes présentant un syndrome sec
Authors: Baudin Marianne 
Published: April 2023

Marianne Baudin, Representaciones femeninas y masculinas en las pacientes que presentan
un síndrome seco.
El síndrome seco es una patología autoinmune esencialmente femenina que interroga de manera directa la expresión de los deseos y los afectos (sequedad de lágrimas, secreciones salivales y vaginales).
El análisis de las representaciones femeninas y masculinas en el Rorschach y en el TAT de 36 pacientes muestra que todas estas mujeres se ven confrontadas a una herida, tanto del cuerpo real como del cuerpo fantasmático.
Ello, sea cual fuere la gravedad de la enfermedad, va a interrogar nuevamente el trabajo psíquico del complejo de castración, y las orientaciones libidinales, narcisísticas y objetales.
Las diferencias aparecen entre las pacientes de acuerdo a su edad : las de edad mas avanzada se tornan de manera privilegiada hacia el polo masculino, sobre el que se desplazan las descalificaciones castradoras ; las pacientes mâs jóvenes se mantienen en una búsqueda del doble narcisistico con el fin de atenuar el sufrimiento de su feminidad.

Palabras-clave : Sindrome seco, Representaciones femeninas y masculinas, Envejecimiento.
De l'attache à la tache. Grand-mère et petite fille : un lien singulier
Authors: Séchaud Évelyne 
Published: April 2023

Évelyne Séchaud, Del vínculo a la mancha. Abuela y nieta : un lazo singular.
A partir de una escena observada entre una abuela patenta y su nieta, se exponen algunos aspectos de la problemática femenina en su desarrollo pulsional y objetal. Por un lado, la representation de una mancha, viene a réunir en lo visual, lo anal y lo sexual de la sangre menstrual. Entre abuela y nieta circulan las representaciones enigmticas de la sexualidad femenina. Por otro lado, la lectura analitica del cuento de Charles Perrault, Caperucita roja, viene a apoyar la idea que, abuela y nieta, están unidas por el secreto de su amor hacia el mismo hombre, hijo de una y padre de la otra. Este lazo que las une, provee a la nieta un sostén dentro de su cambio de objeto inicial y un modelo identificatorio.

Palabras-clave : Abuela patema y nieta, Anal y sexual, Temporalidad femenina, Reciprocidad del lazo edípico en la línea paterna, Identificación.
La temporalité au féminin : une représentation paradoxale
Authors: Breucker Marie-Noëlle 
Published: April 2023

Marie-Nöelle Breucker, The temporality of femininity : a paradoxical representation.
When dealing with the articulation between temporality and femininity, the question of the origin of temporality arises, which contains a part of inescapable violence in the process of integrating the "infans". The conflictual nature of conscious, preconscious and unconscious representations of time attest to the paradoxical nature of its experience. But is there a temporal paradox of femininity ? This could be considered from two perspectives: the femininity of bisexuality and psychofemininity. Puberty gives us an example of the confrontation of cyclical time and the necessary inscription within the arrow of time. This specificity of femininity can be found as an evocation in fairytales and as a repetition in the transference that occurs during psychoanalytic treatment. This is how the inescapableness of the féminin superego and masochism, the immoderateness of narcisism and the unbearableness of anxiety and castration can be seen.

Key-words : Temporality, Femininity, Representation, Psychoanalytic treatment, Fairy tale.