bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression Profile of Sphingosine Kinase 1 Isoforms in Human Cancer Tissues and Cells: Importance and Clinical Relevance of the Neglected 1b-Isoform
Authors: Chen Hongjie , Haddadi Nahal , Zhu Xiaofeng , Hatoum Diana , Chen Size , Nassif Najah T. , Lin Yiguang , McGowan Eileen M.
Published: December 2022

Background.Overexpression of sphingosine kinase 1 (SphK1) is casually associated with many types of cancer, and inhibitors of SphK1 sensitize tumors to chemotherapy. SphK1 is expressed as two major isoforms, SphK1a and SphK1b. To date, no information has been reported on the SphK1 isoform expression profile and its clinical relevance. Objective. The objective is to examine the expression profile of the SphK1a and SPhK1b isoforms in human cancer and noncancer tissues and cell lines and explore their clinical relevance. Methods. We used PCR to qualitatively examine the expression profile of these two isoforms in breast, liver, and prostate cancer tissues plus paired adjacent tissues and in 11 cancer and normal cell lines (breast, cervical, bone, prostate, colon, brain, mesothelioma tumor and benign, and human kidney cells). Results. We found that SphK1a was ubiquitously expressed in all cancer cells and tissues tested; in contrast, SphK1b was only expressed in selective cell types in breast, prostate, and lung cancer. Conclusions. Our data suggest that SphK1a is important for generic SphK1/S1P functions, and SphK1b mediates specialized and/or unique pathways in a specific type of tissue and could be a biomarker for cancer. This discovery is important for future SphK1-related cancer research and may have clinical implications in drug development associated with SphK1-directed cancer treatment.
Feature Selection and Dwarf Mongoose Optimization Enabled Deep Learning for Heart Disease Detection
Authors: Balasubramaniam S. , Satheesh Kumar K. , Kavitha V. , Prasanth A. , Sivakumar T. A.
Published: December 2022

Heart disease causes major death across the entire globe. Hence, heart disease prediction is a vital part of medical data analysis. Recently, various data mining and machine learning practices have been utilized to detect heart disease. However, these techniques are inadequate for effectual heart disease prediction due to the deficient test data. In order to progress the efficacy of detection performance, this research introduces the hybrid feature selection method for selecting the best features. Moreover, the missed value from the input data is filled with the quantile normalization and missing data imputation method. In addition, the best features relevant to disease detection are selected through the proposed hybrid Congruence coefficient Kumar–Hassebrook similarity. In addition, heart disease is predicted using SqueezeNet, which is tuned by the dwarf mongoose optimization algorithm (DMOA) that adapts the feeding aspects of dwarf mongoose. Moreover, the experimental result reveals that the DMOA-SqueezeNet method attained a maximum accuracy of 0.925, sensitivity of 0.926, and specificity of 0.918.
Treatment with the Ferroptosis Inhibitor Ferrostatin-1 Attenuates Noise-Induced Hearing Loss by Suppressing Ferroptosis and Apoptosis
Authors: Ma Peng-Wei , Wang Wei-Long , Chen Jia-Wei , Yuan Hao , Lu Pei-Heng , Gao Wei , Ding Xue-Rui , Lun Yu-Qiang , Liang Rui , He Zu-Hong , Yang Qian , Lu Lian-Jun
Published: December 2022

Hair cell death induced by excessive reactive oxygen species (ROS) has been identified as the major pathogenesis of noise-induced hearing loss (NIHL). Recent studies have demonstrated that cisplatin- and neomycin-induced ototoxicity can be alleviated by ferroptosis inhibitors. However, whether ferroptosis inhibitors have a protective effect against NIHL remains unknown. We investigated the protective effect of the ferroptosis inhibitor ferrostatin-1 (Fer-1) on NIHL in vivo in CBA/J mice and investigated the protective effect of Fer-1 on tert-butyl hydroperoxide (TBHP)-induced hair cell damage in vitro in cochlear explants and HEI-OC1 cells. We observed ROS overload and lipid peroxidation, which led to outer hair cell (OHC) apoptosis and ferroptosis, in the mouse cochlea after noise exposure. The expression level of apoptosis-inducing factor mitochondria-associated 2 (AIFM2) was substantially increased following elevation of the expression of its upstream protein P53 after noise exposure. The ferroptosis inhibitor Fer-1was demonstrated to enter the inner ear after the systemic administration. Administration of Fer-1 significantly alleviated noise-induced auditory threshold elevation and reduced the loss of OHCs, inner hair cell (IHC) ribbon synapses, and auditory nerve fibers (ANFs) caused by noise. Mechanistically, Fer-1 significantly reduced noise- and TBHP-induced lipid peroxidation and iron accumulation in hair cells, alleviating ferroptosis in cochlear cells consequently. Furthermore, Fer-1 treatment decreased the levels of TfR1, P53, and AIFM2. These results suggest that Fer-1 exerted its protective effects by scavenging of ROS and inhibition of TfR1-mediated ferroptosis and P53-AIFM2 signaling pathway-mediated apoptosis. Our findings suggest that Fer-1 is a promising drug for treating NIHL because of its ability to inhibit noise-induced hair cell apoptosis and ferroptosis, opening new avenues for the treatment of NIHL.
Fluid Origin and Evolution of the Roc Blanc Silver Deposit (Jebilet Massif, Variscan Belt, Morocco): Constraints from Geology and Fluid Inclusions
Authors: El Arbaoui Amal , N’Diaye Ismaïla , Hajjar Zaineb , Wafik Amina , Boutaleb Abdelhak , Ilmen Said , Essaifi Abderrahim , Bouabdellah Mohammed
Published: December 2022

The Roc Blanc Pb-Zn-Ag-Au vein deposit is located in the NW of Marrakech, in the Central Jebilet massif. It is spatially related to Bramram-Tabouchennt-Bamega (BTB) granodioritic pluton (ca. 330 Ma) metamorphism aureole. The main veins hosted in black shales are oriented N-S to NNW-SSE. Pb-Zn-Ag-Au ore is associated with quartz, chlorite, sericite, and carbonate gangue minerals. Two major stages of ore deposition were distinguished. The preore stage (stage I) comprises two quartz-mineralised vein generations with Fe, As, Zn, and Cu ores (vg1 and vg2). The main ore stage (stage II) consists mainly on Ag, Au, Pb, Zn, Cu, and Sb ores, which is hosted by carbonaceous vein (vg3) and by two late quartz generations veins (vg4 and vg5 with a geodic quartz). Three types of fluid inclusions have been recognized in silver mineralisation bearing quartz veins according to petrographic investigations, microthermometry, and Raman spectroscopy studies: (i) liquid-rich H2O-N2-CH4±CO2-(salt) fluid inclusions (type 1), (ii) vapour-rich H2O-CO2-CH4-N2-(salt) fluid inclusions (type 2), and (iii) aqueous H2O-(salt) fluid inclusions (type 3). The interpretation of fluid inclusion data shows a mixing of two fluids that are metamorphic and surface to subsurface origin, trapped at boiling state. The first mineralised stage was deposited at

350
±
20
°
C

(this temperature of ore deposition was supported also by chlorite geothermometry) with salinity of 13.7 wt% NaCl equiv., while the deposition of the argentiferous stage, which consists of the main economic mineralisation of the Roc Blanc deposit, occurs during decreasing temperature at 150°C with a salinity of 12.1 wt% NaCl equiv. The all-mineralised ore was deposited at relatively low pressure, below ~1-1.1 kbar. So, fluid dilution and cooling are probably the main factor for silver deposition in the Roc Blanc polymetallic vein deposit. In addition, fluid inclusion studies reveal that the mineralising fluid corresponds to a mixture of metamorphic fluid (H2O-CH4-N2-CO2) with surface to subsurface aqueous gas-free fluids (H2O-salt, meteoric, or brine).
Pyogenic Liver Abscess: Contemporary Trends in a Tertiary Institute
Authors: Boaz Elad , Ben-Chetrit Eli , Bokhobza Yonathan , Yellinek Shlomo , Ben-Haim Menahem , Reissman Petachia , Dagan Amir
Published: December 2022

Background. Pyogenic liver abscess (PLA) is an uncommon but potentially life-threatening condition. In recent years, advances in diagnostics and management have led to early diagnosis and treatment and decreased mortality. We present recent data from a large series of patients with PLA and examine the trends in the management of PLA over a period of 50 years. Methods. The medical records of all patients admitted to the Shaare Zedek Medical Center, Israel, between January 2011 and December 2021 with a primary or secondary diagnosis of PLA were reviewed retrospectively. Results: Ninety-five patients with PLA were identified. Thirty-eight (40%) were female. The median patient age was 66 years (range 18–93). The diagnosis of PLA in all patients was confirmed with abdominal computed tomography (CT). In twenty patients (21.1%), PLA was not diagnosed by the initial abdominal US. Most abscesses were right-sided. Biliary tract origin was the most common underlying cause of PLA (n = 57, 60%), followed by cryptogenic etiology (n = 28, 30%). Escherichia coli, Klebsiella pneumoniae, and Streptococcus species were most commonly identified. The most common primary treatment modality was percutaneous drainage (PD), which was performed in 81 patients (85.3%). Fourteen patients (14.7%) were treated medically without intervention, and two patients (2.1%) were treated surgically following a failure of PD. Four patients died as a direct result of PLA. Conclusions. Patients diagnosed with PLA are older, the male predominance is less pronounced, and the offending pathogens are likely to originate from the biliary tract. This study questions the utility of abdominal US as the initial diagnostic imaging in patients with suspected PLA (versus CT) and demonstrates improved outcomes for patients with PLA over the years.
Phytosynthesis of TiO2 Nanoparticles Using E. crassipes Leaf Extracts, Their Photocatalytic Evaluation and Microbicide Effect
Authors: Velázquez-Hernández A. Monserrat , García-Rivas José Luis , Martínez-Gallegos Sonia , González-Juárez Julio César , Schabes-Retchkiman Pablo , Albiter Verónica
Published: December 2022

In the present research work, the photocatalytic and microbicidal activities of titanium nanoparticles (TiO2 NPs) were evaluated. TiO2 NPs were obtained through the phytosynthesis process, using Eichhornia crassipes leaf extract. In order to determine whether particle size improves photocatalytic and microbicidal activities, the pH of the photosynthesized was modified to 12, 7, and 4. The TiO2 NPs modified were characterized by UV-Vis spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), and high-resolution transmission electron microscopy (HR-TEM) to reveal the crystalline and morphological nature of the phytosynthesized TiO2 NPs. UV-Vis analysis revealed that the wavelength for the TiO2 NPs was 327 nm, while FT-IR confirmed the presence of TiO2 NPs at peaks located between 536 and 532 cm-1. Finally, HR-TEM analysis showed that all nanoparticles had a TiO2 composition and a particle size ranging from 25 to 35 nm. For the photocatalytic and microbicidal tests, three concentrations of nanoparticles were used (100, 50, and 10 mg/L), and the results showed that TiO2 nanoparticles at a concentration of 10 mg·L-1 demonstrated excellent photocatalytic activity in photodegrading phenol [10 mg·L-1] up to 98.7%, while their microbicidal activity was more effective in contact with S. aureus than with E. coli, using a TiO2 NPs concentration of 100 mg·L-1.
Amentoflavone Exerts Anti-Neuroinflammatory Effects by Inhibiting TLR4/MyD88/NF-κB and Activating Nrf2/HO-1 Pathway in Lipopolysaccharide-Induced BV2 Microglia
Authors: Rong Shikuo , Yang Chunrong , Wang Feng , Wu Yiyang , Sun Kuishen , Sun Tao , Wu Zeyu
Published: December 2022

Background. Amentoflavone, a natural biflavone, exerts anti-inflammation, antioxidation, and antiapoptosis effects on many diseases. However, the mechanism of amentoflavone on neuroinflammation-related diseases has not been comprehensively examined clearly. Methods. BV2 microglial cells were treated with amentoflavone (10 μM), followed by lipopolysaccharide (LPS). Microglial activation and migration ability and the expression of proinflammatory cytokines and other signaling proteins were determined using immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay, and wound-healing assays. Results. Amentoflavone restored LPS-induced microglia activation, migration, and inflammation response which depends on regulating toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) pathway. In addition, amentoflavone also enhanced nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) levels in LPS-treated BV2 microglial cells. Conclusions. Amentoflavone ameliorated LPS-induced neuroinflammatory response and oxidative stress in BV2 microglia. These data provide new insight into the mechanism of amentoflavone in the treatment of neuroinflammation-related diseases. Therefore, amentoflavone may be a potential therapeutic option for neurological disorders.
Performance Evaluation of Deep Learning Algorithm Using High-End Media Processing Board in Real-Time Environment
Authors: Asif Muhammad , Rajab Tabarka , Hussain Samreen , Rashid Munaf , Wasi Sarwar , Ahmed Areeb , Kanwal Kehkashan
Published: December 2022

Image processing-based artificial intelligence algorithm is a critical task, and the implementation requires a careful examination for the selection of the algorithm and the processing unit. With the advancement of technology, researchers have developed many algorithms to achieve high accuracy at minimum processing requirements. On the other hand, cost-effective high-end graphical processing units (GPUs) are now available to handle complex processing tasks. However, the optimum configurations of the various deep learning algorithms implemented on GPUs are yet to be investigated. In this proposed work, we have tested a Convolution Neural Network (CNN) based on You Only Look Once (YOLO) variants on NVIDIA Jetson Xavier to identify compatibility between the GPU and the YOLO models. Furthermore, the performance of the YOLOv3, YOLOv3-tiny, YOLOv4, and YOLOv5s models is evaluated during the training using our PowerEdge Dell R740 Server. We have successfully demonstrated that YOLOV5s is a good benchmark for object detection, classification, and traffic congestion using the Jetson Xavier GPU board. The YOLOv5s achieved an average precision of 95.9% among all YOLO variants and the highest success rate achieved is 98.89.
Wind Velocity Field Simulation of the Large-Span Spatial Structure Based on the Wavelet Decomposition Method
Authors: Zhang Daming , Sun Fangjin , Xu Zhonghao
Published: December 2022

In this study, the wavelet decomposition method is combined with the vector AR model of the linear filter method to present a new method for simulating the fluctuating wind field of a large-span spatial structure. This method performs wavelet expansion on the autoregressive coefficients of the vector AR model in adequate space and adopts the least square method to estimate the autoregressive coefficients of the AR model. The implementation steps of this method are to simulate the wind field of large-span structures are given. The method is applied to the wind velocity field simulation of a large-span spatial structure, and the comparison between the simulation result and the target value and the comparison with the simulation result of the vector AR model are given. The results prove that the proposed method can reduce the information loss of wind velocity time-series analysis in the frequency domain, can accurately simulate the wind velocity time series of large-span spatial structures, and has high computational efficiency.
Visual Analysis of Multisource Heterogeneous Data Based on Improved DPCA Algorithm
Authors: Zhou Yun , Mengfei Wen , Youzhi He , Yun Cheng , Jinhui Lv , Yi Zuo
Published: December 2022

This paper proposes a multiview collaborative visual analysis system of network security based on a DPCA (clustering by fast search and find of density peaks) clustering algorithm called DPCANETVis, with network security analysis requirements for multisource heterogeneous data. Firstly, the system proposes an improved DPCA clustering algorithm based on the hierarchical relationship of mail sending and receiving to achieve the purpose of accurate classification. Secondly, a three-layer visual layout is designed to display relevant information such as data hierarchy, node relationship, behavior model, and other relevant information, by mixing a variety of interactive visual analysis methods such as tree diagram, word cloud, line diagram, subject river, and parallel coordinate. Lastly, based on the exploration of events, all suspicious nodes and their abnormal behaviors can be displayed in the system. Finally, the prototype system is used to analyze the network security log data set provided by the ChinaVis 2018, and the feasibility of the multilevel interactive visual analysis method for network security is verified through many experiments and discussions.
Pentraxin 3 Facilitates Shrimp-Allergic Responses in IgE-Activated Mast Cells
Authors: Du Jyun-Yi , Lai Hong-Yue , Hsiao Yu-Wei , Chi Jhih-Ying , Wang Ju-Ming
Published: December 2022

Background. Since food avoidance is currently the only way to prevent allergic reactions to shrimp, a better understanding of molecular events in the induction and progression of allergy, including food allergy, is needed for developing strategies to inhibit allergic responses. Pentraxin 3 (PTX3) is rapidly produced directly from inflammatory or damaged tissues and is involved in acute immunoinflammatory responses. However, the role of PTX3 in the development of immediate IgE-mediated shrimp allergy remains unknown. Methods. Wild-type BALB/c mice were immunized intraperitoneally and were challenged with shrimp extract. Serum IgE and PTX3 levels were analyzed. RBL-2H3 cells were stimulated with either dinitrophenyl (DNP) or serum of shrimp-allergic mice, and markers of degranulation, proinflammatory mediators, and phosphorylation of signal proteins were analyzed. We further examined the effect of PTX3 in shrimp extract-induced allergic responses in vitro and in vivo. Results. Mice with shrimp allergy had increased PTX3 levels in the serum and small intestine compared with healthy mice. PTX3 augmented degranulation, the production of proinflammatory mediators, and activation of the Akt and MAPK signaling pathways in mast cells upon DNP stimulation. Furthermore, the expression of transcription factor CCAAT/enhancer-binding protein delta (CEBPD) was elevated in PTX3-mediated mast cell activation. Finally, the PTX3 inhibitor RI37 could attenuate PTX3-induced degranulation, proinflammatory mediator expression, and phosphorylation of the Akt and MAPK signaling. Conclusions. The results suggested that PTX3 can facilitate allergic responses. Our data provide new insight to demonstrate that PTX3 is a cause of allergic inflammation and that RI37 can serve as a therapeutic agent in shrimp allergy.
Association Between Diet and Fusobacterium nucleatum in the Feces of Healthy Adults: A Hospital-based Cross-sectional Study
Authors: Narii Nobuhiro , Zha Ling , Sobue Tomotaka , Kitamura Tetsuhisa , Shiba Satoshi , Mizutani Sayaka , Yamada Takuji , Yachida Shinichi
Published: December 2022

Fusobacterium nucleatum is involved in the development and progression of colorectal cancer. Although the gut microbiota is influenced by diet, studies on the association between diet and F. nucleatum are limited. We aimed to evaluate the association between various dietary factors and fecal F. nucleatum in healthy adults without a history of colorectal cancer or precancerous lesions. This was a cross-sectional study. Subjects who underwent total colonoscopy at the National Cancer Center Hospital (Tokyo, Japan) were included. Healthy subjects (n = 212) were divided into two groups according to the presence or absence of F. nucleatum in their feces which was calculated from data of whole-genome shotgun sequencing, with the group with F. nucleatum serving as cases and the group without F. nucleatum serving as controls. Multivariable logistic regression analysis adjusted potential confounders was conducted to estimate the associations between dietary intake and nutrients estimated by a validated food frequency questionnaire and the presence of F. nucleatum in the feces. There was a significant inverse association between dairy products and the presence of fecal F. nucleatum [high vs. low; OR, 0.41; 95% confidence interval, 0.17–0.95; Ptrend, 0.039]. These results may have important implications for colorectal cancer prevention through nutritional intervention.

Prevention Relevance:

F. nucleatum is well known as a colorectal cancer–associated bacterium. Dietary habits alter the composition and function of the intestinal microbiota. A high intake of dairy products in healthy adults may reduce F. nucleatum and prevent colorectal cancer.
Potential Effects of Age-Based Changes in Screening Guidelines on the Identification of Women at Risk for Developing Cervical Cancer
Authors: Piyathilake Chandrika J. , Badiga Suguna , Jolly Pauline E.
Published: December 2022

Current American Cancer Society guidelines estimated that screening starting at the age of 25 years with Pap and/or human papillomavirus (HPV) testing is sufficient to prevent cervical cancer. The effect of having HPV infections without Pap-based care until age 25 on the prevalence of higher grades of cervical intraepithelial neoplasia (≥CIN 2) and their determinants are largely unknown. The objectives of the study were to document the potential effects of age-based changes in screening guidelines on the identification of ≥CIN 2 and their determinants. The study included 1,584 women diagnosed with abnormal Pap and tested for HPVs and histologic diagnoses of cervical lesions. The association between demographic/lifestyle factors and HPV status and risk of being diagnosed with ≥CIN 2 among younger (21–<25 years) or older (≥25 year) women was tested using unconditional multiple logistic regression models. We observed that younger women who are not screened have a similar or higher risk of developing specific high-risk HPV genotype-associated ≥CIN 2 lesions compared with older women who are screened according to the current guidelines. In addition, younger women who reported live births, smoking, contraceptive use, and a higher number of sexual partners were significantly at higher risk of being diagnosed with ≥CIN 2. Targeted screening of younger women at risk for developing ≥CIN 2 will address the concern of overtreatment while providing the recommended care to those who require such care to prevent the development of cervical cancer.

Prevention Relevance:

This study documents the concerns of the age-based changes in screening guidelines on the identification of higher grades of cervical intraepithelial neoplasia and their determinants in women diagnosed with abnormal Pap smear and emphasize the need for targeted screening of younger women to prevent cervical cancer.
Intratumoral Gene Transfer of mRNAs Encoding IL12 in Combination with Decoy-Resistant IL18 Improves Local and Systemic Antitumor Immunity
Authors: Cirella Assunta , Bolaños Elixabet , Di Trani Claudia Augusta , de Andrea Carlos E. , Sánchez-Gregorio Sandra , Etxeberria Iñaki , Gonzalez-Gomariz Jose , Olivera Irene , Brocco Davide , Glez-Vaz Javier , Luri-Rey Carlos , Azpilikueta Arantza , Rodríguez Inmaculada , Fernandez-Sendín Myriam , Egea Josune , Eguren Iñaki , Sanmamed Miguel F. , Palencia Belen , Teijeira Alvaro , Berraondo Pedro , Melero Ignacio
Published: December 2022

IL12-based local gene therapy of cancer constitutes an active area of clinical research using plasmids, mRNAs, and viral vectors. To improve antitumor effects, we have experimentally tested the combination of mRNA constructs encoding IL12 and IL18. Moreover, we have used a form of IL18 [decoy-resistant IL18 (DR-18)] which has preserved bioactivity but does not bind to the IL18 binding protein decoy receptor. Both cytokines dramatically synergize to induce IFNγ release from mouse splenocytes, and, if systemically cotransferred to the liver, they mediate lethal toxicity. However, if given intratumorally to B16OVA tumor-bearing mice, the combination attains efficacy against the directly treated tumor and moderate tumor-delaying activity on distant noninjected lesions. Cotreatment was conducive to the presence of more activated CD8+ T cells in the treated and noninjected tumors. In keeping with these findings, the efficacy of treatment was contingent on the integrity of CD8+ T cells and cDC1 dendritic cells in the treated mice. Furthermore, efficacy of IL12 plus DR-18 local mRNA coinjection against distant concomitant tumors could be enhanced upon combination with anti–PD-1 mAb systemic treatment, thus defining a feasible synergistic immunotherapy strategy.
Frailty: Pathophysiology, Theoretical and Operational Definition(s), Impact, Prevalence, Management and Prevention, in an Increasingly Economically Developed and Ageing World
Authors: Doody Paul , Lord Janet M. , Greig Carolyn A. , Whittaker Anna C.
Published: December 2022

The world’s population is ageing, and most older adults experience a later life burdened with disease and disability. Frailty is a multidimensional and dynamic condition characterized by declines in reserve and function across multiple physiological systems, such that the ability to cope with every day or acute stressors becomes compromised. It is projected to become one of the most serious public health challenges economically developed societies will face in the coming century. This review provides a comprehensive overview of frailty, exploring its pathophysiology, theoretical and operational definition(s), impact, prevalence, management, and prevention, within the context of its emergence as a major public health challenge, in an increasingly economically developed and ageing world. Further, this review discusses the major limitations, deficiencies, and knowledge gaps presently within the field, and future research directions pertinent to the advancement of frailty research and the promotion of healthy longevity among the increasing global population of older adults.
Treatment of Congenital Hypothyroidism: Impact of Secular Changes in Levothyroxine Initial Dose on Early Growth
Authors: Niuro Laura , Danner Emmi , Viikari Liisa , Kero Jukka , Huopio Hanna , Jääskeläinen Jarmo , Niinikoski Harri
Published: December 2022

Introduction: Newborn screening of congenital hypothyroidism (CH) has enabled early treatment with levothyroxine (LT4), ensuring normal growth and development. The initial LT4 dose recommendation has increased over decades. We evaluated whether the increased LT4 dosing influenced thyroid-stimulating hormone (TSH) and thyroxine (fT4) concentrations, growth, or treatment-related symptoms. Methods: LT4 doses, TSH, fT4, anthropometrics, and treatment-related symptoms until age 2 years were evaluated in 172 Finnish CH patients born between 1980 and 2018. The patients were grouped according to birth decade: 1980s (n = 19, mean LT4 starting dose 6.8 μg/kg/day), 1990s (n = 50, 7.4 μg/kg/day), 2000s (n = 59, 9.7 μg/kg/day), and 2010s (n = 44, 10.8 μg/kg/day). Results: TSH concentrations were higher during the first 2 years of life in children born in the 1980s compared to children born later. TSH concentrations were often subnormal in children receiving higher LT4 doses (children born in the 2000s and 2010s). However, symptoms of overtreatment were uncommon. Linear or head growth showed no differences between the groups during the first 2 years of life. Although growth was within the normal spectrum, children in all groups were shorter than their target length at 2 years and their weight-for-length was above the mean through the first 2 years of life. Discussion: Current treatment practice with higher LT4 dose normalizes TSH rapidly without significant increase in side effects. However, irrespective of initial LT4 dose, children were shorter than expected at 2 years of age. Effects of different initial LT4 dose on cognitive development urges further investigation.
Leva militar y violencia en contra de la juventud en el Perú
Authors: Loayza-Javier Jerjes
Published: December 2022

(analytical)Compulsory military service in Peru has generated debates and controversies due to the violence with which it operates, both by forcing and mistreating and even torturing kidnapped youths. Only at the end of the 1990s would the cruelty with which it was operated be demonstrated, dismantling it inthe year 2000. The article seeks to identify said violence through the channeling that would operateduring the 1960s. Methodologically, a total of 28 interviews with men and women are applied between60 and 83 years old. As a hypothesis, the use of discrimination and authoritarianism to degrade the most popular sectors of the country is proposed. Thus, the installed demeaning biopolitical strategieswould persuade the population of the need for such levies, incurring in a legalized juvenile murder.
Keywords: Military training, violence, youth, discipline.
Integrin CD11b Contributes to Hypertension and Vascular Dysfunction Through Mediating Macrophage Adhesion and Migration
Authors: Lin Qiu-Yue , Bai Jie , Zhang Yun-Long , Li Hui-Hua
Published: December 2022

Background:

Leukocyte adhesion to endothelium is an early inflammatory response and is mainly controlled by the β2-integrins. However, the role of integrin CD11b/CD18 in the pathogenesis of hypertension and vascular dysfunction is unclear.

Methods:

Hypertension was established by angiotensin II (490 ng/kg·per min) or deoxycorticosterone acetate salt. Hypertensive responses were studied in CD11b-deficient (CD11b
-/-
) mice, bone marrow transplanted and wild-type (WT) mice that were administered anti-CD11b neutralizing antibody or agonist leukadherin-1. Blood pressure was monitored with tail-cuff method and radiotelemetry. Blood and vascular inflammatory cells were assessed by flow cytometry. Aortic remodeling and function were examined using histology and aortic ring analysis. Cell adhesion and migration were evaluated in vitro. The relationship between circulating CD11b
+
immune cells and hypertension was analyzed in patients with hypertension.

Results:

We found that CD11b and CD18 expression as well as the CD45
+
CD11b
+
CD18
+
myeloid cells were highly increased in the aorta of angiotensin II-infused mice. Ablation or pharmacological inhibition of CD11b in mice significantly alleviated hypertension, aortic remodeling, superoxide generation, vascular dysfunction, and the infiltration of CD11b
+
macrophages through reducing macrophage adhesion and migration. These effects were confirmed in WT mice reconstituted with CD11b-deficient bone marrow cells. Conversely, angiotensin II-induced hypertensive response was exacerbated by CD11b agonist leukadherin-1. Notably, circulating CD45
+
CD11b
+
CD18
+
myeloid cells and the ligand levels in hypertensive patients were significantly higher than in normotensive controls.

Conclusions:

We demonstrated a critical significance of CD11b
+
myeloid cells in hypertension and vascular dysfunction. Targeting CD11b may represent a novel therapeutic option for hypertension.
Plasma sDPP4 (Soluble Dipeptidyl Peptidase-4) and Cognitive Impairment After Noncardioembolic Acute Ischemic Stroke
Authors: You Shoujiang , Bi Yucong , Miao Mengyuan , Bao Anran , Du Jigang , Xu Tan , Liu Chun-Feng , Zhang Yonghong , He Jiang , Cao Yongjun , Zhong Chongke
Published: December 2022

Background:

DPP4 (dipeptidyl peptidase-4) inhibitors have been proven to promote neuronal regeneration, reverse the development of cognitive deficits. However, the association of circulating soluble form (sDPP4 [soluble DPP4]) with poststroke cognitive impairment (PSCI) is unclear. We aimed to investigate the association between plasma sDPP4 levels and PSCI in patients with ischemic stroke.

Methods:

A total of 600 noncardioembolic stroke patients were included based on a preplanned ancillary study from the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). We used the Montreal Cognitive Assessment to evaluate cognitive function at 3 months follow-up after ischemic stroke. Binary logistic regression analyses were performed to investigate the association of plasma sDPP4 levels with subsequent PSCI. We further calculated integrated discrimination improvement and category-free net reclassification improvement to investigate the incremental prognostic effect of plasma sDPP4 beyond the basic model with conventional risk factors.

Results:

Plasma sDPP4 was inversely associated with PSCI after ischemic stroke, and the adjusted odds ratio (95% CI) for the highest versus lowest quartile of sDPP4 was 0.49 (0.29–0.81;
P
for trend=0.011). Each 1-SD increase of logarithm-transformed plasma sDPP4 concentration was associated with 17% (odds ratio, 0.83 [95% CI, 0.70–0.99]) lower risk of PSCI. Adding plasma sDPP4 to the basic model notably improved risk reclassification for PSCI, as shown by a category-free net reclassification improvement of 19.10% (95% CI, 2.52%–35.68%;
P
=0.03) and integrated discrimination improvement of 0.79% (95% CI, 0.13%–1.46%;
P
=0.02).

Conclusions:

Higher plasma sDPP4 levels were associated with decreased risk of cognitive impairment after noncardioembolic ischemic stroke.
Impact of Decompressive Craniectomy on Hemorrhagic Transformation in Malignant Ischemic Stroke in Mice
Authors: Borha Alin , Lebrun Florent , Touzé Emmanuel , Emery Evelyne , Vivien Denis , Gaberel Thomas
Published: December 2022

Background:

Endovascular thrombectomy has changed the management of ischemic stroke. The reperfusion can however lead to a hemorrhagic transformation (HT). Decompressive craniectomy (DC) is a surgical procedure used for malignant ischemic stroke. However, its efficacy was demonstrated before the era of endovascular thrombectomy trials. Here, we hypothesized that DC for ischemic stroke after thrombectomy could lead to a higher risk of HT. We thus evaluated this hypothesis in a mouse model of stroke induced by occlusion of the middle cerebral artery (MCAO) with or without mechanical reperfusion.

Methods:

Ninety mice subjected to MCAO were divided into 6 groups: permanent MCAO with or without DC; MCAO followed by a mechanical reperfusion with or without DC and MCAO with a mechanical reperfusion followed by r-tPA (recombinant tissue-type plasminogen activator)-induced reperfusion with or without DC. Mice were evaluated by magnetic resonance imaging 24 hours after the MCAO to assess ischemic lesion volumes, and the rate, type, and volume of HTs.

Results:

The ischemic volume was higher in the 2 groups without reperfusion than in the 4 groups with reperfusion independently of r-tPA treatment and DC. The distribution of HT types was different between the 6 groups. The HT volumes and HT scores was smaller in the 2 groups without reperfusion and in the reperfusion group without r-tPA and without DC. In mice having reperfusion, the mean HT score was higher in mice who had DC without r-tPA (HT score 5;
P
=0.048) or with r-tPA (HT score 8;
P
=0.02), than in mice without DC (HT score 1).

Conclusions:

DC for a malignant stroke, after reperfusion, corresponding to an endovascular thrombectomy failure, increases the risk of severe hemorrhagic transformations in a model of ischemic stroke in mice. This result support the need of clinical studies to evaluate the added value of DC at the era of endovascular thrombectomy.
Therapies Targeting Stroke Recovery
Authors: Richards Lorie G. , Cramer Steven C.
Published: December 2022

Stroke recovery therapeutics include many classes of intervention and numerous treatment targets. Stroke is a very heterogeneous disease. As such, stroke recovery therapeutics benefit from a personalized medicine approach that considers intersubject differences, such as in infarct location or stroke severity, when assigning treatment. Prediction of treatment responders can be improved by incorporating biological measures, such as neural injury and neural function, as the bedside behavioral phenotype has an incomplete relationship with the biological events underlying stroke recovery. Another ramification of high variability between patients is the need to examine effects of restorative therapies in relation to dose, time poststroke, and stroke severity in clinical trials. For example, enrollment across a wide time interval poststroke or in a population with a very broad range of deficits means high variance across patients in the biological state of the brain. The doses of rehabilitation therapy being studied are often low; it takes substantial practice to acquire a skill in the healthy brain; this is more, not less, pronounced after a stroke. Recognition and treatment of poststroke depression represents a major unmet need. These points are considered in the context of a review of recent advances in stroke recovery therapeutics.
Recalibrating the scope of scholarly publishing: A modest step in a vast decolonization process
Authors: Khanna Saurabh , Ball Jon , Alperin Juan Pablo , Willinsky John
Published: December 2022

By analyzing 25,671 journals largely absent from common journal counts, as well as Web of Science and Scopus, this study demonstrates that scholarly communication is more of a global endeavor than is commonly credited. These journals, employing the open-source publishing platform Open Journal Systems (OJS), have published 5.8 million items; they are in 136 countries, with 79.9% in the Global South and 84.2% following the OA diamond model (charging neither reader nor author). A substantial proportion of journals operate in more than one language (48.3%), with research published in 60 languages (led by English, Indonesian, Spanish, and Portuguese). The journals are distributed across the social sciences (45.9%), STEM (40.3%), and the humanities (13.8%). For all their geographic, linguistic, and disciplinary diversity, 1.2% are indexed in the Web of Science and 5.7% in Scopus. On the other hand, 1.0% are found in Cabell’s Predatory Reports, and 1.4% show up in Beall’s (2021) questionable list. This paper seeks to both contribute to and historically situate the expanded scale and diversity of scholarly publishing in the hope that this recognition may assist humankind in taking full advantage of what is increasingly a global research enterprise.
Picture-Perfect – The Perception and Applicability of Facsimiles in Museums
Authors: Tissen Liselore N.M. , van Veldhuizen Mané
Published: December 2022

Various types of digital and physical three-dimensional facsimile technologies (e.g., high-definition digital modelling and 3D printing) have entered the art world and have become increasingly important for research and presentation purposes. Yet, studies that go beyond the technical aspects of (3D) facsimile techniques, such as their significance for the conservation/restoration field and museum display, are scarce, especially in the case of easel paintings. Furthermore, studies that analyse the perception of these methods and, consequently, their impact on the authenticity of the original painting, do not exist to our knowledge. The aim of this research is twofold: firstly, it evaluates a viewer’s perception of various facsimiles; secondly, on the basis of this analysis, it aims to gain a better understanding and provide an overview of the applicability of (3D) facsimiles of artworks for presentation purposes and potential users (technical art historians, conservators, curators, material scientists and museum visitors). This research was executed by combining a literature review with quantitative and qualitative analyses of the data acquired through a) a questionnaire of 17 closed and open-ended questions and (b) an on-site session at the Mauritshuis museum (The Hague, The Netherlands). Based on analysis of the data collected through these activities, this paper attempts to provide an indication of the current attitude towards (3D) facsimile methods as well as to present some criteria of using these methods in a museum environment.
4. Presenting Conclusions from Assessed Evidence
Authors: Sutherland William J. , Amano Tatsuya , Boenisch Nicolas , Cheng Samantha H. , Christie Alec P. , Godfray Hugh Charles Jonathan , Grainger Matthew J. , McLean Angela R. , Morgan William H. , Ockendon Nancy , Randall Nicola , Sahlin Ullrika , White Thomas B.
Published: December 2022

Applying evidence builds on the conclusions of the assessment of the evidence. The aim of the chapter is to describe a range of ways of summarising and visualising different types of evidence so that it can be used in various decision-making processes. Evidence can also be presented as part of evidence capture sheets, argument maps, mind maps, theories of change, Bayesian networks or evidence restatements.
5. Improving the Reliability of Judgements
Authors: Wintle Bonnie C. , Mukherjee Nibedita , Hemming Victoria , Canessa Stefano , McBride Marissa
Published: December 2022

Judgements underpin all aspects of decision making, whether assessing the nature of the problem, interpreting evidence, or deciding upon the risks and benefits of different actions. Serious problems arise with conventional means of deriving judgements to inform decisions, such as confusing values and facts, listening to a single expert, or deploying processes prone to individual and group biases such as forced consensus. Thankfully there are methods that reduce the impact of such biases including processes such as the Delphi Technique and the IDEA protocol. This chapter outlines these methods to aid in eliciting better judgements in decision making.
6. Identifying Stakeholders and Collaborating with Communities
Authors: Best Marina , Irvine Robyn , Bako Longji , Citegetse Geoffroy , Field Alison , Roe Dilys , Rose David Rose , Spencer Jonathan
Published: December 2022

Working with communities, including local and Indigenous communities, is fundamental to most successful conservation practice. Key elements include determining the appropriate level of engagement, identifying the key stakeholders, identifying appropriate means of collaborating with different stakeholders, creating and maintaining trust, and collaborating to deliver the objectives.
7. Framing the Problem and Identifying Potential Solutions
Authors: Esmail Nafeesa , Green Rhys , Petrovan Silviu O. , Salafsky Nick , Taylor Nigel G. , Wilson Jeremy D.
Published: December 2022

The creation of effective policy and practice starts by framing the problem to be solved. This requires deciding what is important, identifying the current and potential future threats, diagnosing the actual cause of the problems, and identifying solutions, including innovating to create new ones when required. In this chapter we describe various techniques that can be used to frame the problem including horizon scanning, situation models and theory of change diagrams. These can be used to identify the analytical questions and specific assumptions that underpin the assessment of evidence and decision making.
8 Making Decisions for Policy and Practice
Authors: Cook Carly N. , Burgman Mark , Rumpff Libby , Thornton Ann
Published: December 2022

Having collaborated with the community to decide upon the objectives, identified the major threats to be addressed, considered the possible options and assessed the evidence, the next stage is to decide what to do. Many decisions can be decided easily, as either obvious or trivial, thus requiring no additional assessment of different stages of the process. The harder decisions then require assessing the likely consequences of options and determining the preferred trade off. There is a range of approaches for making each of these stages more rigorous, reducing the likelihood of making inefficient decisions. These approaches are described with an account of the situations under which is most appropriate to address the conservation problem.
13. Supplementary Material from Online Resources
Authors: Sutherland William J.
Published: December 2022

This chapter provides links to sources of evidence, to material that aids teaching evidence use, and to tools for delivering change. It also lists 1,100 collaborators in the Conservation Evidence project that underpins much of this book.
2. Public Investment and Low-carbon Transition in France
Authors: Hamdi-Cherif Meriem , Malliet Paul , Plane Mathieu , Reynes Frederic , Saraceno Francesco , Tourbah Alexandre
Published: December 2022

In Chapter 2, M. Hamdi-Cherif, P. Malliet, F. Reynes, M. Plane, F. Saraceno, and A. Tourbah argue that public investment in France has been on a downward trend since 2009, rebounding only in the wake of the COVID-19 crisis, with the objective of supporting global demand and spurring economic growth. The increase in investment, however, is less pronounced than during the global financial crisis. Orienting investment towards low-carbon capital within the framework of a long-term emission reduction goal, despite being unprecedented in history, is also insufficient, especially if its level is not maintained over the coming decades. The type of low-carbon transition strategy chosen—either relying more on technological progress or reaching a significant reduction in energy consumption (a Sobriety scenario)—will noticeably impact the composition and amount of investment needed to meet the targets.
3. Public Investment in Germany
Authors: Rietzler Katja , Watt Andrew
Published: December 2022

In Chapter 3, K. Rietzler and A. Watt emphasise that against the backdrop of an increasingly broad consensus that Germany has substantially underinvested in public goods for an extended period, the new Traffic Light Coalition Agreement sets out ambitious spending plans that go beyond the modernisation of Germany’s infrastructure and speeding up decarbonisation. At the same time, it has also committed to the debt brake and to avoiding tax hikes. Moreover, since the establishment of this new government, other fiscal challenges have arisen because of the war in Ukraine and a sharp rise in energy and food prices. By exploiting the scope of short-run flexibility (the debt brake is currently still suspended) and new off-budget measures, the government is seeking to square this circle by allowing greater investments in the face of competing demands. The national plan under the Recovery and Resilience Facility (RRF) complements national initiatives; but in Germany’s case, it is of limited macroeconomic relevance. The latest developments in RRF projects are sketched out in the chapter.
5. Current Challenges in the Spanish Energy Market
Authors: Villaverde José , Ibáñez Luzon Lucía , Balsalobre-Lorente Daniel , Maza Adolfo
Published: December 2022

Chapter 5 by J. Villaverde, L. Ibáñez Luzon, D. Balsalobre-Lorente, and A. Maza summarises the different public initiatives in the Spanish energy market in recent decades, always within the European Union framework. At the same time, it portrays the current turbulent situation, marked by the crisis unleashed by the COVID-19 pandemic and Russia’s invasion of Ukraine. The chapter reviews the historical evolution of the energy mix in Spain, with a focus on the effect that the different energy packages approved by the EC and their implementations have had on it. The chapter concentrates on the Spanish government’s policies and plans, within the guidelines set by the EU, especially Next GenerationEU and REPowerEU, in support of a green transition over the 2020–2030 period.